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    <YEAR>2024</YEAR>
    <VOL>16</VOL>
    <NO>2</NO>
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            <CONTENT>No Abstract</CONTENT>
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        <KEYWORD><KeyText>Editorial</KeyText></KEYWORD>
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    <REFRENCES>
        <REFRENCE>
            <REF>####</REF>
        </REFRENCE>
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</ARTICLE>

<ARTICLE>
    <TitleE>The Role of Biotechnology in Latest Therapeutic Approaches for Diabetes Mellitus</TitleE>
    <TitleF></TitleF>
    <TitleLang_ID>2</TitleLang_ID>
    <ABSTRACTS>

        <ABSTRACT>
            <Language_ID>2</Language_ID>
            <CONTENT>No Abstract</CONTENT>
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    <PAGES>
        <PAGE>
            <FPAGE>66</FPAGE>
            <TPAGE>67</TPAGE>
        </PAGE>
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    <AUTHORS>
        <AUTHOR>
<Name>Sepideh</Name>
<MidName></MidName>
<Family>Hajivalizadeh </Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Shahin</Name>
<MidName></MidName>
<Family>Akhondzadeh</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization></Organization>
</Organizations>
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<University></University>
</Universities>
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<Country></Country>
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<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR>
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    <KEYWORDS>
        <KEYWORD><KeyText>Artificial pancreas</KeyText></KEYWORD><KEYWORD><KeyText>Gastrointestinal microbiome</KeyText></KEYWORD><KEYWORD><KeyText>Glucose</KeyText></KEYWORD><KEYWORD><KeyText>Insulin</KeyText></KEYWORD><KEYWORD><KeyText>Monoclonal antibody</KeyText></KEYWORD><KEYWORD><KeyText>Stem cell transplantation</KeyText></KEYWORD><KEYWORD><KeyText>Tissue engineering </KeyText></KEYWORD><KEYWORD><KeyText>Treatment</KeyText></KEYWORD>
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    <REFRENCES>
        <REFRENCE>
            <REF>Elnashar M, Vaccarezza M, Al-Salami H. Cutting-edge biotechnological advancement in islet delivery using pancreatic and cellular approaches. Future Sci OA 2020 Nov 23;7(3):FSO660.##Reyes-Mart&#237;nez JE, Ruiz-Pacheco JA, Flores-Vald&#233;z MA, Elsawy MA, Vallejo-Cardona AA, Castillo-D&#237;az LA. Advanced hydrogels for treatment of diabetes. J Tissue Eng Regen Med 2019 Aug;13(8):1375-93.##Davies M, Dahl D, Heise T, Kiljanski J, Mathieu C. Introduction of biosimilar insulins in Europe. Diabet Med J Br Diabet Assoc 2017 Oct;34(10):1340-53.##Hanif N, Wu H, Xu P, Li Y, Bibi A, Zulfiqar A, et al. Proteomic changes to the updated discovery of engineered insulin and its analogs: pros and cons. Curr Issues Mol Biol 2022 Feb 11;44(2):867-88.##Rodr&#237;guez-Sarmiento DL, Le&#243;n-Vargas F, Garc&#237;a-Jaramillo M. Artificial pancreas systems: experiences from concept to commercialisation. Expert Rev Med Devices 2022 Nov;19(11):877-94.##Jarosinski MA, Dhayalan B, Rege N, Chatterjee D, Weiss MA. ‘Smart’ insulin-delivery technologies and intrinsic glucose-responsive insulin analogues. Diabetologia 2021 May;64(5):1016-29.##Madani S, Amanzadi M, Aghayan HR, Setudeh A, Rezaei N, Rouhifard M, et al. Investigating the safety and efficacy of hematopoietic and mesenchymal stem cell transplantation for treatment of T1DM: a systematic review and meta-analysis. Syst Rev 2022 May 2;11(1):82.##Khazaei M, Khazaei F, Niromand E, Ghanbari E. Tissue engineering approaches and generation of insulin-producing cells to treat type 1 diabetes. J Drug Target 2023 Jan;31(1):14-31.##Amer LD, Mahoney MJ, Bryant SJ. Tissue engineering approaches to cell-based type 1 diabetes therapy. Tissue Eng Part B Rev 2014 Oct 1;20(5):455-67.##Ashraf MT, Ahmed Rizvi SH, Kashif MAB, Shakeel Khan MK, Ahmed SH, Asghar MS. Efficacy of anti-CD3 monoclonal antibodies in delaying the progression of recent-onset type 1 diabetes mellitus: A systematic review, meta-analyses and meta-regression. Diabetes Obes Metab 2023 Nov;25(11):3377-89.##Zhang S, Deng F, Chen J, Chen F, Wu Z, Li L, et al. Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes: A systematic review. Front Cell Infect Microbiol 2022;12:1075201.##Akhondzadeh S. Hippocampal synaptic plasticity and cognition. J Clin Pharm Ther 1999;24(4):241-8.##Akhondzadeh S. The 5-HT hypothesis of schizophrenia. IDrugs 2001;4(3):295-300.##Akhondzadeh S, Ahmadi-Abhari SA, Assadi SM, Shabestari OL, Kashani AR, Farzanehgan ZM. Double-blind randomized controlled trial of baclofen vs. clonidine in the treatment of opiates withdrawal. J Clin Pharm Ther 2000; 25(5):347-53.##Kashani L, Eslatmanesh S, Saedi N, Niroomand N, Ebrahimi M, Hosseinian M, et al. Comparison of saffron versus fluoxetine in treatment of mild to moderate postpartum depression: a double-blind, randomized clinical trial. Pharmacopsychiatry 2017;50(2):64-8.##</REF>
        </REFRENCE>
    </REFRENCES>
</ARTICLE>

<ARTICLE>
    <TitleE>Factor VIII as a Novel Biomarker for Diagnosis, Prognosis, and Therapy Prediction in  Human Cancer and Other Disorders</TitleE>
    <TitleF></TitleF>
    <TitleLang_ID>2</TitleLang_ID>
    <ABSTRACTS>

        <ABSTRACT>
            <Language_ID>2</Language_ID>
            <CONTENT>&lt;p&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Coagulation factor VIII (FVIII) is an essential cofactor in the coagulation cascade, encoded by the &lt;em&gt;F8&lt;/em&gt; gene on the long arm of chromosome X (Xq28). FVIII is normally circulated in complex with Von Willebrand factor (VWF) and has relevant emerging extracoagulative functions. Dysregulation of FVIII is associated with tumor progression, and could be used as a novel biomarker for tumor screening and monitoring. In breast cancer, bladder cancer, colorectal carcinoma, esophageal carcinoma, hepatocellular carcinoma and lung cancer, &lt;em&gt;F8&lt;/em&gt; is regarded as an oncogene. In coronary heart disease, hemophilia A and liver disease, &lt;em&gt;F8&lt;/em&gt; dysregulation has been recognized as a potential biomarker for disease diagnosis and prognosis. However, the basis of these differential expression levels remains to be understood. In this review, which is a mixture of literature review and bioinformatics analysis we described the biological functions and characteristics of FVIII, and also its expression level in non-malignant disorders and various cancers.&lt;/span&gt;&lt;/p&gt;
</CONTENT>
        </ABSTRACT>
    </ABSTRACTS>
    <PAGES>
        <PAGE>
            <FPAGE>68</FPAGE>
            <TPAGE>80</TPAGE>
        </PAGE>
    </PAGES>
    <AUTHORS>
        <AUTHOR>
<Name>Sheyda</Name>
<MidName></MidName>
<Family>Khalilian </Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Student Research Committee, School of Medicine, Shahid Beheshti University of Medical SciencesDepartment of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical SciencesUSERN Office, Shahid Beheshti University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Student Research Committee, School of Medicine, Shahid Beheshti University of Medical SciencesDepartment of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical SciencesUSERN Office, Shahid Beheshti University of Medical Sciences</University>
</Universities>
<Countries>
<Country>IranIranIran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Zahra</Name>
<MidName></MidName>
<Family>Mohajer </Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Student Research Committee, School of Medicine, Shahid Beheshti University of Medical SciencesUSERN Office, Shahid Beheshti University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Student Research Committee, School of Medicine, Shahid Beheshti University of Medical SciencesUSERN Office, Shahid Beheshti University of Medical Sciences</University>
</Universities>
<Countries>
<Country>IranIran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Soudeh</Name>
<MidName></MidName>
<Family>Ghafouri-Fard</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization></Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country></Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR>
    </AUTHORS>
    <KEYWORDS>
        <KEYWORD><KeyText>Biomarkers</KeyText></KEYWORD><KEYWORD><KeyText>Cancer</KeyText></KEYWORD><KEYWORD><KeyText>Factor VIII</KeyText></KEYWORD><KEYWORD><KeyText>Prognosis</KeyText></KEYWORD>
    </KEYWORDS>
    <PDFFileName>60569.pdf</PDFFileName>
    <REFRENCES>
        <REFRENCE>
            <REF>Khalilian S, Motovali-Bashi M, Rezaie H. Factor VIII: Perspectives on immunogenicity and tolerogenic strategies for Hemophilia A patients. Int J Mol Cell Med 2020;9(1):33-50.##Rezaei H, Motovali-Bashi M, Khalilian S. Identification of Novel miRNAs in the F8 Gene Via Bioinformatics Tools. Iran J Biotechnol 2021 Apr;19(2):e2700.##Rezaei H, Motovali-Bashi M, Khalilian S. MicroRNA prediction in the FVIII gene locus: A step towards hemophilia A control. Gene Cell Tissue 2020;7:e103096.##Abdulqader AMR, Mohammed AI, Rachid S, Ghoraishizadeh P, Mahmood SN. Identification of the intron 22 and intron 1 inversions of the factor VIII gene in Iraqi Kurdish patients with hemophilia A. Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029619888293.##Nasirnejad Sola F, Morovvati S, Sabetghadam Moghadam M, Entezari M. Mutation detection and inhibitor risk in Iranian patients with Hemophilia A: Six novel mutations. Clin Case Rep 2020 Dec;8(12):2976-85.##Jalali-Qomi S, Motovali-Bashi M, Rezaei H, Khalilian S. Experimental validation of a predicted microRNA within human FVIII gene. Mol Biol Res Commun 2021 Jun;10(2):45-53.##Yamamoto K, de Waard V, Fearns C, Loskutoff DJ. Tissue distribution and regulation of murine von Willebrand factor gene expression in vivo. Blood 1998;92(8):2791-801.##Wion KL, Kelly D, Summerfield JA, Tuddenham EG, Lawn RM. Distribution of factor VIII mRNA and antigen in human liver and other tissues. Nature 1985;317(6039):726-9.##Do H, Healey JF, Waller EK, Lollar P. Expression of factor VIII by murine liver sinusoidal endothelial cells. J Biol Chem 1999;274(28):19587-92.##Hollestelle MJ, Thinnes T, Crain K, Stiko A, Kruijt JK, van Berkel TJ, et al. Tissue distribution of factor VIII gene expression in vivo–a closer look. Thromb Haemost 2001;86(09):855-61.##Walker GE, Merlin S, Zanolini D, Vandoni A, Volpe A, Gaidano G, et al. Factor VIII as a potential player in cancer pathophysiology. J Thromb Haemost 2022 Mar;20(3):648-60.##Rubio VEC, P&#233;rez-Segura P, Mu&#241;oz A, Farr&#233; AL, Ruiz LC, Lorente JA. High plasma levels of soluble P-Selectin and Factor VIII predict venous thromboembolism in non-small cell lung cancer patients: The Thrombo-Nsclc risk score. Thromb Res 2020;196:349-54.##Moik F, Posch F, Grilz E, Scheithauer W, Pabinger I, Prager G, et al. Haemostatic biomarkers for prognosis and prediction of therapy response in patients with metastatic colorectal cancer. Thromb Res 2020;187:9-17.##Folsom AR, Delaney JA, Lutsey PL, Zakai NA, Jenny NS, Polak JF, et al. Associations of factor VIIIc, D‐dimer, and plasmin–antiplasmin with incident cardiovascular disease and all‐cause mortality. Am J Hematol 2009;84(6):349-53.##Folsom AR, Wu KK, Rosamond WD, Sharrett AR, Chambless LE. Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 1997;96(4):1102-8.##Folsom AR, Rosamond WD, Shahar E, Cooper LS, Aleksic N, Nieto FJ, et al. Prospective study of markers of hemostatic function with risk of ischemic stroke. Circulation 1999;100(7):736-42.##Smith F, Lee A, Fowkes F, Price J, Rumley A, Lowe G. Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study. Arterioscler Thromb Vasc Biol 1997;17(11):3321-5.##Meade T, Cooper J, Stirling Y, Howarth D, Ruddock V, Miller G. Factor VIII, ABO blood group and the incidence of ischaemic heart disease. Br J Haematol 1994;88(3):601-7.##Kamphuisen PW, Eikenboom JC, Bertina RM. Elevated factor VIII levels and the risk of thrombosis. Arterioscler Thromb Vasc Biol 2001;21(5):731-8.##Raffield LM, Lu AT, Szeto MD, Little A, Grinde KE, Shaw J, et al. Coagulation factor VIII: Relationship to cardiovascular disease risk and whole genome sequence and epigenome‐wide analysis in African Americans. J Thromb Haemost 2020;18(6):1335-47.##Yap E, Timp J, Flinterman L, van Hylckama Vlieg A, Rosendaal F, Cannegieter S, et al. Elevated levels of factor VIII and subsequent risk of all‐cause mortality: results from the MEGA follow‐up study. J Thromb Haemost 2015;13(10):1833-42.##El‐Maarri O, Herbiniaux U, Graw J, Schr&#246;der J, Terzic A, Watzka M, et al. Analysis of mRNA in hemophilia A patients with undetectable mutations reveals normal splicing in the factor VIII gene. J Thromb Haemost 2005;3(2):332-9.##Johnsen JM, Fletcher SN, Huston H, Roberge S, Martin BK, Kircher M, et al. Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the my life, our future initiative. Blood Adv 2017;1(13):824-34.##Jankowska KI, McGill J, Pezeshkpoor B, Oldenburg J, Sauna ZE, Atreya CD. Further evidence that microRNAs can play a role in Hemophilia A disease manifestation: F8 gene downregulation by miR-19b-3p and miR-186-5p. Front Cell Dev Biol 2020;8:669.##Jankowska KI, McGill J, Pezeshkpoor B, Oldenburg J, Atreya CD, Sauna ZE. Clinical manifestation of hemophilia A in the absence of mutations in the F8 gene that encodes FVIII: role of microRNAs. Transfusion 2020;60(2):401-13.##Graw J, Brackmann H-H, Oldenburg J, Schneppenheim R, Spannagl M, Schwaab R. Haemophilia A: from mutation analysis to new therapies. Nat Rev Genet 2005;6(6):488-501.##Oldenburg J, Pezeshkpoor B, Pavlova A. Historical review on genetic analysis in hemophilia A. Semin Thromb Hemost 2014 Nov;40(8):895-902##Nienhuis AW, Nathwani AC, Davidoff AM. Gene therapy for hemophilia. Mol Ther 2017;25(5):1163-7.##Benson G, Auerswald G, Dolan G, Duffy A, Hermans C, Ljung R, et al. Diagnosis and care of patients with mild haemophilia: practical recommendations for clinical management. Blood Transfus 2018;16(6):535-44.##Sarachana T, Dahiya N, Simhadri VL, Pandey GS, Saini S, Guelcher C, et al. Small ncRNA expression-profiling of blood from hemophilia A patients identifies miR-1246 as a potential regulator of factor 8 gene. PLoS One 2015;10(7):e0132433.##Meng F. Hsa-miR-5581-3p and Hsa-miR-542-3p target the F8 gene in hemophilia A without F8 mutations. Mediterr J Hematol Infect Dis 2021;13(1):e2021041.##Mei B, Chen Y, Chen J, Pan CQ, Murphy JE. Expression of human coagulation factor VIII in a human hybrid cell line, HKB11. Mol Biotechnol 2006;34(2):165-78.##Hollestelle MJ, Geertzen HG, Straatsburg IH, van Gulik TM, van Mourik JA. Factor VIII expression in liver disease. Thromb Haemost 2004;91(02):267-75.##Colman RW. Hemostasis and thrombosis: basic principles and clinical practice: Lippincott Williams &amp; Wilkins; 2006. 1827 p.##Lenting PJ, Van Mourik JA, Mertens K. The life cycle of coagulation factor VIII in view of its structure and function. Blood 1998;92(11):3983-96.##Kaufman RJ, Pipe SW, Tagliavacca L, Swaroop M, Moussalli M. Biosynthesis, assembly and secretion of coagulation factor VIII. Blood Coagul Fibrinolysis 1997;8:S3-14.##Saenko EL, Ananyeva NM, Tuddenham EG, Kemball‐Cook G. Factor VIII–novel insights into form and function. Br J Haematol 2002;119(2):323-31.##Mandoj C, Pizzuti L, Sergi D, Sperduti I, Mazzotta M, Di Lauro L, et al. Observational study of coagulation activation in early breast cancer: development of a prognostic model based on data from the real world setting. J Transl Med 2018;16(1):129.##Khorana AA, Francis CW. Risk prediction of cancer-associated thrombosis: appraising the first decade and developing the future. Thromb Res 2018;164:S70-S6.##Zareba P, Duivenvoorden W, Pinthus JH. Thromboembolism in patients with bladder cancer: incidence, risk factors and prevention. Bladder Cancer 2018;4(2):139-47.##Walker GE, Merlin S, Zanolini D, Vandoni A, Volpe A, Gaidano G, et al. Factor VIII as a potential player in cancer pathophysiology. J Thromb Haemost 2022;20(3):648-60.##Gujam FJ, Going JJ, Mohammed Z, Orange C, Edwards J, McMillan DC. Immunohistochemical detection improves the prognostic value of lymphatic and blood vessel invasion in primary ductal breast cancer. BMC Cancer 2014;14(1):1-11.##Schellerer VS, Mueller-Bergh L, Merkel S, Zimmermann R, Weiss DR, Schildberg C, et al. Is coagulation factor VIII a useful marker for colorectal carcinoma? Int J Biol Markers2012 2012/ 01/01;27(1):20-6.##Byrne M, O’Donnell J, White B, Kennedy J, Reynolds J. Differential response of factor VIII and protein C expression following multimodal therapy for esophageal carcinoma. Journal of Clinical Oncology 2007;25(18_suppl):15106.##Zhuang M, Xin G, Wei Z, Li S, Xing Z, Ji C, et al. Dihydrodiosgenin inhibits endothelial cell-derived factor VIII and platelet-mediated hepatocellular carcinoma metastasis. Cancer Manag Res 2019;11:4871-82.##He Z, Chen H, Li G, Zhu H, Gao Y, Zhang L, et al. Diosgenin inhibits the migration of human breast cancer MDA-MB-231 cells by suppressing Vav2 activity. Phytomedicine 2014;21(6):871-6.##Hao-Peng Y, Lei Y, Jiang W-W, Qian L, Jun-Ping K, Bo-Yang Y. Diosgenin inhibits tumor necrosis factor-induced tissue factor activity and expression in THP-1 cells via down-regulation of the NF-κB, Akt, and MAPK signaling pathways. Chin J Nat Med 2013;11(6):608-15.##Ma H-D, Deng Y-R, Tian Z, Lian Z-X. Traditional Chinese medicine and immune regulation. Clin Rev Allergy Immunol 2013;44(3):229-41.##Zheng H, Wei Z, Xin G, Ji C, Wen L, Xia Q, et al. Preventive effect of a novel diosgenin derivative on arterial and venous thrombosis in vivo. Bioorg Med Chem Lett 2016;26(14):3364-9.##Wei Z, Xin G, Wang H, Zheng H, Ji C, Gu J, et al. The diosgenin prodrug nanoparticles with pH-responsive as a drug delivery system uniquely prevents thrombosis without increased bleeding risk. Nanomedicine 2018;14(3):673-84.##Liu X, Chen X, Yang J, Guo R. Association of ABO blood groups with von Willebrand factor, factor VIII and ADAMTS‑13 in patients with lung cancer. Oncol Lett 2017;14(3):3787-94.##Tas F, Kilic L, Serilmez M, Keskin S, Sen F, Duranyildiz D. Clinical and prognostic significance of coagulation assays in lung cancer. Respir Med 2013;107(3):451-7.##Guadagni F, Ferroni P, Basili S, Facciolo F, Carlini S, Crecco M, et al. Correlation between tumor necrosis factor-alpha and D-dimer levels in non-small cell lung cancer patients. Lung Cancer 2004;44(3):303-10.##Oleksowicz L, Bhagwati N, DeLeon-Fernandez M. Deficient activity of von Willebrand’s factor-cleaving protease in patients with disseminated malignancies. Cancer Res 1999;59(9):2244-50.##Gabazza EC, Taguchi O, Yamakami T, Machishi M, Ibata H, Suzuki S. Evaluating prethrombotic state in lung cancer using molecular markers. Chest 1993;103(1):196-200.##&#220;nsal E, Atalay F, Atikcan S, Yilmaz A. Prognostic signif https://pubmed.ncbi.nlm.nih.gov/14971870/icance of hemostatic parameters in patients with lung cancer. Respir Med 2004;98(2):93-8.##Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res 2019;47(W1):W556-W60.##Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, et al. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res 2017;77(21):e108-e10.##Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 2013;6(269):pl1.##Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, et al. COSMIC: the catalogue of somatic mutations in cancer. Nucleic Acids Res 2019;47(D1):D941-D7.##Birney E, Andrews TD, Bevan P, Caccamo M, Chen Y, Clarke L, et al. An overview of Ensembl. Genome research. 2004;14(5):925-8.##Wheeler DL, Church DM, Edgar R, Federhen S, Helmberg W, Madden TL, et al. Database resources of the National Center for Biotechnology Information: update. Nucleic Acids Res 2004;32(suppl_1):D35-D40.##Bamford S, Dawson E, Forbes S, Clements J, Pettett R, Dogan A, et al. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer 2004;91(2):355-8.##Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res 2016 Jul 8;44(W1):W90-7.##Goad KE, Gralnick HR. Coagulation disorders in cancer. Hematol Oncol  Clin North Am 1996;10(2):457-84.##Comerford C, Glavey S, Quinn J, O’Sullivan JM. The role of VWF/FVIII in thrombosis and cancer progression in multiple myeloma and other hematological malignancies. J Thromb Haemost 2022;20(8):1766-77.##P&#233;pin M, Kleinjan A, Hajage D, B&#252;ller H, Di Nisio M, Kamphuisen P, et al. ADAMTS‐13 and von Willebrand factor predict venous thromboembolism in patients with cancer. J Thromb Haemost 2016;14(2):306-15.##Terraube V, Marx I, Denis CV. Role of von Willebrand factor in tumor metastasis. Thromb Res 2007;120:S64-S70.##Yang X, Sun H-j, Li Z-r, Zhang H, Yang W-j, Ni B, et al. Gastric cancer-associated enhancement of von Willebrand factor is regulated by vascular endothelial growth factor and related to disease severity. BMC Cancer 2015;15(1):1-11.##Bannow BS, Recht M, N&#233;grier C, Hermans C, Berntorp E, Eichler H, et al. Factor VIII: Long-established role in haemophilia A and emerging evidence beyond haemostasis. Blood Rev 2019;35:43-50.##Noe DA. A mathematical model of coagulation factor VIII kinetics. Haemostasis 1996;26(6):289-303.##Fijnvandraat K, Peters M, Ten Cate JW. Inter‐individual variation in half‐life of infused recombinant factor VIII is related to pre‐infusion von Willebrand factor antigen levels. Br J Haematol 1995;91(2):474-6.##Jenkins PV, Rawley O, Smith OP, O&#39;Donnell JS. Elevated factor VIII levels and risk of venous thrombosis. British J Haematol 2012;157(6):653-63.##Risch L, Huber AR, Schmugge M. Diagnosis and treatment of heparin-induced thrombocytopenia in neonates and children. Thromb Res 2006;118(1):123-35.##Zakai N, Katz R, Jenny N, Psaty B, Reiner A, Schwartz S, 8, et al. Inflammation and hemostasis biomarkers and cardiovascular risk in the elderly: the Cardiovascular Health Study. J Thromb Haemost 2007;5(6):1128-35.##Rumley A, Lowe G, Sweetnam P, Yarnell J, Ford R. Factor VIII, von Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Heart Study. Br J Haematol 1999;105(1):110-6.##Conlan MG, Folsom AR, Finch A, Davis C, Sorlie P, Marcucci G, et al. Associations of factor VIII and von Willebrand factor with age, race, sex, and risk factors for atherosclerosis. Thromb Haemost 1993;70(09):380-5.##Lutsey P, Cushman M, Steffen L, Green D, Barr R, Herrington D, et al. Plasma hemostatic factors and endothelial markers in four racial/ethnic groups: the MESA study. J Thromb Haemost 2006;4(12):2629-35.##Roberts LN, Patel RK, Chitongo P, Bonner L, Arya R. African–Caribbean ethnicity is associated with a hypercoagulable state as measured by thrombin generation. Blood Coagul Fibrinolysis 2013;24(1):40-9.##Patel RK, Ford E, Thumpston J, Arya R. Risk factors for venous thrombosis in the black population. Thromb Haemost 2003;90(11):835-8.##Krek A, Gr&#252;n D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, et al. Combinatorial microRNA target predictions. Nat Genet 2005;37(5):495-500.##Grimson A, Farh KK-H, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 2007;27(1):91-105.##Calin GA, Liu C-G, Sevignani C, Ferracin M, Felli N, Dumitru CD, et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA 2004;101(32):11755-60.##Goff LA, Davila J, Swerdel MR, Moore JC, Cohen RI, Wu H, et al. Ago2 immunoprecipitation identifies predicted microRNAs in human embryonic stem cells and neural precursors. PloS One 2009;4(9):e7192.##Guerau-de-Arellano M, Alder H, Ozer HG, Lovett-Racke A, Racke MK. miRNA profiling for biomarker discovery in multiple sclerosis: from microarray to deep sequencing. J Neuroimmunol 2012; 248(1-2):32-9.##Yoon J-H, Srikantan S, Gorospe M. MS2-TRAP (MS2-tagged RNA affinity purification): tagging RNA to identify associated miRNAs. Methods 2012;58(2):81-7.##Ahmadi H, Ahmadi A, Azimzadeh-Jamalkandi S, Shoorehdeli MA, Salehzadeh-Yazdi A, Bidkhori G, et al. HomoTarget: a new algorithm for prediction of microRNA targets in Homo sapiens. Genomics 2013;101(2):94-100.##Zheng H, Fu R, Wang J-T, Liu Q, Chen H, Jiang S-W. Advances in the techniques for the prediction of microRNA targets. Int J Mol Sci 2013;14(4):8179-87.##Agarwal V, Bell GW, Nam J-W, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. Elife 2015;4:e05005.##Dusl M, Senderek J, M&#252;ller JS, Vogel JG, Pertl A, Stucka R, et al. A 3′-UTR mutation creates a microRNA target site in the GFPT1 gene of patients with congenital myasthenic syndrome. Hum Mol Genet 2015;24(12):3418-26.##Lagan&#224; A. Computational prediction of microRNA targets.  Adv Exp Med Biol 2015:887:231-52.##He B-S, Qu J, Chen M. Prediction of potential disease-associated microRNAs by composite network based inference. Sci Rep 2018;8(1):15813.##Wun T, White RH. Venous thromboembolism (VTE) in patients with cancer: epidemiology and risk factors. Cancer Invest 2009;27(sup1):63-74.##Lauw MN, van Doormaal FF, Middeldorp S, Buller HR. Cancer and venous thrombosis: current comprehensions and future perspectives. Semin Thromb Hemost 2013 Jul;39(5):507-14.##Altiay G, Ciftci A, Demir M, Kocak Z, Sut N, Tabakoglu E, et al. High plasma D-dimer level is associated with decreased survival in patients with lung cancer. Clinl Oncol (R Coll Radiol) 2007;19(7):494-8.##Oya M, Akiyama Y, Okuyama T, Ishikawa H. High preoperative plasma D-dimer level is associated with advanced tumor stage and short survival after curative resection in patients with colorectal cancer. Jpn J Clin Oncol 2001;31(8):388-94.##Sakurai M, Satoh T, Matsumoto K, Michikami H, Nakamura Y, Nakao S, et al. High pretreatment plasma D-dimer levels are associated with poor prognosis in patients with ovarian cancer independently of venous thromboembolism and tumor extension. Int J Gynecol Cancer 2015;25(4):593-8.##Marfia G, Navone SE, Fanizzi C, Tabano S, Pesenti C, Abdel Hadi L, et al. Prognostic value of preoperative von Willebrand factor plasma levels in patients with Glioblastoma. Cancer Med 2016;5(8):1783-90.##Yigit E, G&#246;n&#252;ll&#252; G, Y&#252;cel İ, Turgut M, Erdem D, &#199;akar B. Relation between hemostatic parameters and prognostic/predictive factors in breast cancer. Eur J Intern Med 2008;19(8):602-7.##Alevizopoulos A, Tyritzis S, Leotsakos I, Anastasopoulou I, Pournaras C, Kotsis P, et al. Role of coagulation factors in urological malignancy: a prospective, controlled study on prostate, renal and bladder cancer. Int J Urol 2017;24(2):130-6.##Falanga A, Russo L, Milesi V, Vignoli A. Mechanisms and risk factors of thrombosis in cancer. Crit Rev Oncol Hematol 2017;118:79-83.##Ingle PV, Samsudin SZ, Chan PQ, Ng MK, Heng LX, Yap SC, et al. Development and novel therapeutics in hepatocellular carcinoma: a review. Ther Clin Risk Manag 2016;12:445-55.##Yang Y, Sun X, Chi C, Liu Y, Lin C, Xie D, et al. Upregulation of long noncoding RNA LINC00152 promotes proliferation and metastasis of esophageal squamous cell carcinoma. Cancer Manag Res 2019;11:4643-54.##Llovet JM, Bustamante J, Castells A, Vilana R, Ayuso MDC, Sala M, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology 1999;29(1):62-7.##Chen X-P, Qiu F-Z, Wu Z-D, Zhang Z-W, Huang Z-Y, Chen Y-F, et al. Effects of location and extension of portal vein tumor thrombus on long-term outcomes of surgical treatment for hepatocellular carcinoma. Ann Surg Oncol 2006;13(7):940-6.##Minagawa M, Makuuchi M, Takayama T, Ohtomo K. Selection criteria for hepatectomy in patients with hepatocellular carcinoma and portal vein tumor thrombus. Ann Surg 2001;233(3):379.##</REF>
        </REFRENCE>
    </REFRENCES>
</ARTICLE>

<ARTICLE>
    <TitleE>The Protective Effect of Crocin on Rat Bone Marrow Mesenchymal Stem Cells Exposed  to Aluminum Chloride as an Endocrine Disruptor </TitleE>
    <TitleF></TitleF>
    <TitleLang_ID>2</TitleLang_ID>
    <ABSTRACTS>

        <ABSTRACT>
            <Language_ID>2</Language_ID>
            <CONTENT>&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Background:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; Mesenchymal Stem Cells (MSCs) have the ability to self-renew and proliferate which gives them healing properties in various tissues. Aluminium chloride (AlCl&lt;sub&gt;3&lt;/sub&gt;) is a chemical compound with harmful effects on health; oxidative stress caused by Aluminium has been reported previously. Crocin, a major component of &lt;em&gt;Crocus sativus &lt;/em&gt;(saffron), has antioxidant properties and has shown therapeutic potential. Researchers have been looking for ways to reduce the harmful effects of AlCl&lt;sub&gt;3&lt;/sub&gt;. &lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Methods:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; To investigate whether crocin can reduce AlCl&lt;sub&gt;3&lt;/sub&gt; cytotoxicity, rat Bone Marrow Mesenchymal Stem Cells (BM-MSCs) were isolated, cultured and divided into four experimental groups. The first group was the control, which was untreated cells. The second and third groups were treated with crocin (&lt;/span&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;50, 100, 250, 500 &lt;/span&gt;&lt;em&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;&amp;micro;M&lt;/span&gt;&lt;/em&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;) and AlCl&lt;sub&gt;3&lt;/sub&gt; (20, 25, 30 &lt;em&gt;mM&lt;/em&gt;) for 24 &lt;em&gt;hr&lt;/em&gt;. The fourth group was pre-treated with crocin (&lt;/span&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;250, 500 &lt;/span&gt;&lt;em&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;&amp;micro;M&lt;/span&gt;&lt;/em&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;) for 24 &lt;em&gt;hr&lt;/em&gt; and then treated with AlCl&lt;sub&gt;3&lt;/sub&gt; (20 &lt;em&gt;mM&lt;/em&gt;) overnight. Cytotoxicity was assessed using the MTT assay. Mineralization was evaluated by alizarin red staining. Sox-2 and E-cadherin expression were measured using real-time PCR.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Results:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; The results showed that AlCl&lt;sub&gt;3&lt;/sub&gt; caused cytotoxicity on BM-MSCs and decreased the mRNA expression of Sox-2 and E-cadherin, which are important for the maintenance of self-renewal and proliferation of BM-MSCs. In contrast, crocin protected the self-renewal characteristic of BM-MSCs by increasing Sox-2 expression and also preserved the proliferative effects on BM-MSCs by upregulating E-cadherin expression (***p&amp;le;0.001). &lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Conclusion:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; Overall, the study suggests that crocin can protect BM-MSCs from AlCl&lt;sub&gt;3&lt;/sub&gt;-induced cytotoxicity by upregulate Sox-2 expression and E-cadherin expression. This suggests that crocin may be a potential therapeutic agent for the treatment of AlCl&lt;sub&gt;3&lt;/sub&gt;-induced toxicity. &lt;/span&gt;&lt;/span&gt;&lt;/p&gt;
</CONTENT>
        </ABSTRACT>
    </ABSTRACTS>
    <PAGES>
        <PAGE>
            <FPAGE>81</FPAGE>
            <TPAGE>87</TPAGE>
        </PAGE>
    </PAGES>
    <AUTHORS>
        <AUTHOR>
<Name>Elaheh</Name>
<MidName></MidName>
<Family>Amini</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization></Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country></Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Zahra</Name>
<MidName></MidName>
<Family>Baharvand</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Azadeh</Name>
<MidName></MidName>
<Family>Niknejad</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Cellular &amp; Molecular Biology, Faculty of Biological Sciences, Kharazmi University</Organization>
</Organizations>
<Universities>
<University>Department of Cellular &amp; Molecular Biology, Faculty of Biological Sciences, Kharazmi University</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Yasaman</Name>
<MidName></MidName>
<Family>Tabari</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Cell and Molecular Biology, University of Science and Culture, Royan Institute, ACECR</Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Sahel</Name>
<MidName></MidName>
<Family>Shemshadi</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Cell and Developmental Biology, Julius-Maximilians-University</Organization>
</Organizations>
<Universities>
<University>Department of Cell and Developmental Biology, Julius-Maximilians-University</University>
</Universities>
<Countries>
<Country>Germany</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR>
    </AUTHORS>
    <KEYWORDS>
        <KEYWORD><KeyText>Aluminum chloride</KeyText></KEYWORD><KEYWORD><KeyText>Animals</KeyText></KEYWORD><KEYWORD><KeyText>Cadherins</KeyText></KEYWORD><KEYWORD><KeyText>Crocus</KeyText></KEYWORD><KEYWORD><KeyText>Oxidative stress</KeyText></KEYWORD><KEYWORD><KeyText>Rats</KeyText></KEYWORD>
    </KEYWORDS>
    <PDFFileName>60570.pdf</PDFFileName>
    <REFRENCES>
        <REFRENCE>
            <REF>Bellavia D, Dimarco E, Costa V, Carina V, Luca AD, Raimondi L, et al. Flavonoids in bone erosive diseases: perspectives in osteoporosis treatment. Trends Endocrinol Metab 2021 Feb;32(2):76-94.##Khorasany AR, Hosseinzadeh H. Therapeutic effects of saffron (Crocus sativus L.) in digestive disorders: a review. Iran J Basic Med Sci 2016 May;19(5):455-69.##Soelaiman IN, Das S, Shuid AN, Mo H, Mohamed N. Use of medicinal plants and natural products for treatment of osteoporosis and its complications. Evid Based Complement Alternat Med 2013:2013:764701.##Farkhondeh T, Samarghandian S, Yazdi HS, Samini F. The protective effects of crocin in the management of neurodegenerative diseases: a review. Am J Neurodegener Dis 2018 Feb 5;7(1):1-10.##Yorgun MA, Rashid K, Aslanidis A, Bresgen C, Dannhausen K, Langmann, T. Crocin, a plant-derived carotenoid, modulates microglial reactivity. Biochem Biophys Rep 2017 Oct 2:12:245-50.##Cao PC, Xiao WX, Yan YB, Zhao X, Liu S, Feng J, et al. Preventive effect of crocin on osteoporosis in an ovariectomized rat model. Evid Based Complement Alternat Med 2014:2014:825181.##Zaffar A, Leena S, Asha B, Sumedha Y, Pradyumna KM, Prashant S, et al. Crocin attenuates osteoclastogenesis and enhances bone health by skewing the immunoporotic “Treg-Th17” cell axis in post-menopausal osteoporotic mice model, Phytomedicine Plus 2022:2(3):100302.##Yang X, Huo F, Liu B, Liu J, Chen T, Li J, et al. Crocin inhibits oxidative stress and pro-inflammatory response of microglial cells associated with diabetic retinopathy through the activation of PI3K/Akt signaling pathway. J Mol Neurosci 2017 Apr;61(4):581-9.##Nicolopoulou-Stamati P, Hens L, Sasco AJ. Cosmetics as endocrine disruptors: are they a health risk?. Rev Endocr Metab Disord 2015 Dec;16(4):373-83.##Xu Y, Kaiyuan Y, Haoran W, Haiyang Z, Chongsheng B, Miao S, et al. Bone impairment caused by AlCl3 is associated with activation of the JNK apoptotic pathway mediated by oxidative stress. Food Chem Toxicol 2018 Jun;116(Pt B):307-14.##Yoon DS, Choi Y, Jang Y, Lee M, Choi WJ, Kim SH, et al. SIRT1 directly regulates SOX2 to maintain self‐renewal and multipotency in bone marrow‐derived mesenchymal stem cells. Stem Cells 2014 Dec;32(12):3219-31.##Rudiansyah M, El-Sehrawy AA, Ahmad I, Mergia Terefe E, Abdelbasset WK, Bokov DO, et al. Osteoporosis treatment by mesenchymal stromal/stem cells and their exosomes: Emphasis on signaling pathways and mechanisms. Life Sci 2022 Oct 1:306:120717.##Gall TM, Frampton AE. Gene of the month: E-cadherin (CDH1). J Clin Pathol 2013 Nov;66(11):928-32.##Soncin F, Ward CM. The function of e-cadherin in stem cell pluripotency and self-renewal. Genes (Basel) 2011 Feb 25;2(1):229-59.##Conacci-Sorrel, M, Simcha I, Ben-Yedidia T, Blechman J, Savagner P, Ben-Ze&#39;ev A. Autoregulation of E-cadherin expression by cadherin–cadherin interactions: the roles of β-catenin signaling, Slug, and MAPK. J Cell Biol 2003 Nov 24;163(4):847-57.##Seo E, Basu-Roy U, Zavadil J, Basilico C, Mansukhani A. Distinct functions of Sox2 control self-renewal and differentiation in the osteoblast lineage. Mol Cell Biol 2011 Nov;31(22):4593-608.##Baharara J, Amini E, Kerachian MA, Soltani M. The osteogenic differentiation stimulating activity of Sea cucumber methanolic crude extraction on rat bone marrow mesenchymal stem cells. Iran J Basic Med Sci 2014 Aug;17(8):626-31.##Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 2001 Dec;25(4):402-8.##Shi Y, Su J, Roberts AI, Shou P, Rabson AB, Ren G. How mesenchymal stem cells interact with tissue immune responses. Trends Immunol 2012 Mar;33(3):136-43.##Pino AM, Rosen CJ, Rodr&#237;guez JP. In osteoporosis, differentiation of mesenchymal stem cells (MSCs) improves bone marrow adipogenesis. Biol Res 2012;45(3):279-87.##Saud B, Malla R, Shrestha K. A review on the effect of plant extract on mesenchymal stem cell proliferation and differentiation. Stem Cells Int 2019 Jul 24:2019:7513404.##Perry JM, He XC, Sugimura R, Grindley JC, Haug JS, Ding S, et al. Cooperation between both Wnt/β-catenin and PTEN/PI3K/Akt signaling promotes primitive hematopoietic stem cell self-renewal and expansion. Genes Dev 2011 Sep 15;25(18):1928-42.##Manolagas SC. Wnt signaling and osteoporosis. Maturitas 2014;78(3):233-7.##Kolf CM, Cho E, Tuan RS. Mesenchymal stromal cells: biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther 2007;9(1):204.##Saraswati S, Bastakoty D, Young PP. Molecular and signaling pathways that modulate mesenchymal stem cell self-renewal. In: Stem Cells and Cancer Stem Cells Vol. 6. 2012.p.131-41.##Kamachi Y, Kondoh H. Sox proteins: regulators of cell fate specification and differentiation. Development 2013 Oct;140(20):4129-44.##Han SM, Han SH, Coh YR, Jang G, Chan Ra J, Kang SK, et al. Enhanced proliferation and differentiation of Oct4- and Sox2-overexpressing human adipose tissue mesenchymal stem cells. Exp Mol Med 2014 Jun 20;46(6):e101.##Rather MA, Thenmozhi AJ, Manivasagam T, Bharathi MD, Essa MM, Guillemin GJ. Neuroprotective role of Asiatic acid in aluminium chloride induced rat model of Alzheimer’s disease. Front Biosci (Schol Ed) 2018;10(2):262-75.##Sun X, Cao Z, Zhang Q, Liu S, Xu F, Che J, et al. Aluminum trichloride impairs bone and downregulates Wnt/β-catenin signaling pathway in young growing rats. Food Chem Toxicol 2015 Dec:86:154-62.##Cao Z, Fu Y, Sun X, Zhang Q, Xu F, Li Y. Aluminum trichloride inhibits osteoblastic differentiation through inactivation of Wnt/β-catenin signaling pathway in rat osteoblasts. Environ Toxicol Pharmacol 2016 Mar:42:198-204.##Adriana-Berenice PV, Alberto PB, del Pilar RGM, L&#243;pez-Marure R, Arellano-Galindo J, Guti&#233;rrez-Iglesias G.Toxic effect of titanium dioxide nanoparticles on human mesenchymal stem cells. Mol Cell Toxicol 2020;16:321-30.##Erceg S, Mateo EM, Zipancic I, Rodr&#237;guez Jim&#233;nez FJ, P&#233;rez Arag&#243; MA, Jim&#233;nez M, et al. Assessment of toxic effects of ochratoxin A in human embryonic stem cells. Toxins (Basel) 2019 Apr 10;11(4):217.##Denu RA, Hematti P. Effects of oxidative stress on mesenchymal stem cell biology. Oxid Med Cell Longev 2016;2016:2989076.##Amerizadeh F, Rezaei N, Rahmani F, Hassanian SM, Moradi‐Marjaneh R, Fiuji H, et al. Crocin synergistically enhances the antiproliferative activity of 5‐flurouracil through Wnt/PI3K pathway in a mouse model of colitis‐associated colorectal cancer. J Cell Biochem 2018 Dec;119(12):10250-61.##Mehri S, Abnous K, Mousavi SH, Shariaty VM, Hosseinzadeh H. Neuroprotective effect of crocin on acrylamide-induced cytotoxicity in PC12 cells. Cell Mol Neurobiol 2012 Mar;32(2):227-35.##Li B, Qin K, Wang B, Liu B, Yu W, Li Z, et al. Crocin promotes osteogenesis differentiation of bone marrow mesenchymal stem cells. In Vitro Cell Dev Biol Anim 2020;56(8):680-8.##</REF>
        </REFRENCE>
    </REFRENCES>
</ARTICLE>

<ARTICLE>
    <TitleE>The Protective Effect of N-acetylcysteine against Deltamethrin-Induced Hepatotoxicity  in Mice</TitleE>
    <TitleF></TitleF>
    <TitleLang_ID>2</TitleLang_ID>
    <ABSTRACTS>

        <ABSTRACT>
            <Language_ID>2</Language_ID>
            <CONTENT>&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Background:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; Exposure to pesticides is of concern to public health officials worldwide. Deltamethrin is a synthetic &lt;span style=&quot;color:black&quot;&gt;pyrethroid &lt;/span&gt;pesticide which is widely used in agriculture and veterinary medicine. Deltamethrin poisoning is always one of the concerns in medical centers&lt;/span&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; due to the &lt;/span&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;deltamethrin induced &lt;/span&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;hepatotoxicity.&lt;/span&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; This study evaluated the hepatoprotective effects of N-acetylcysteine (NAC) against deltamethrin induced hepatotoxicity in mice&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Methods:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; A total of 40 BALB/c male mice were randomly divided into four groups; the first group was used as a control (0.5 &lt;em&gt;ml&lt;/em&gt; normal saline); Groups 2-4 were treated with NAC [160 &lt;em&gt;mg/kg&lt;/em&gt; Body Weight (BW)], deltamethrin (50 &lt;em&gt;mg/kg&lt;/em&gt; BW), and NAC plus deltamethrin. At 1 and 24 &lt;em&gt;hr&lt;/em&gt; after treatment, the animals were sacrificed and blood and liver samples were obtained for analysis and the liver/body ration, hepatic enzymes as &lt;/span&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Aspartate aminotransferase (AST), Alanine Transaminase (ALT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH), Glutathione&lt;/span&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; (GSH) content and &lt;span style=&quot;background-color:white&quot;&gt;&lt;span style=&quot;color:black&quot;&gt;Reactive Oxygen Species&lt;/span&gt;&lt;/span&gt; (ROS) level were measured. For comparison between more than two experimental groups, one-way ANOVA following Tukey test was used by SPSS software.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Results:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; The deltamethrin significantly increased AST, ALT, ALP, and the level of ROS level at the end of 1 and 24 &lt;em&gt;hr&lt;/em&gt; after treatment; while the LDH level and GSH content were decreased. Mice in the deltamethrin treated group had a higher liver/body weight ratio than in other treated groups after 24 &lt;em&gt;hr&lt;/em&gt;. On the other hand, NAC in combination with deltamethrin significantly reduced the activities of AST, ALT, ALP, and increased GSH levels.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Conclusion:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; This study demonstrated that NAC has a hepatoprotective role against deltamethrin-induced toxicity.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;
</CONTENT>
        </ABSTRACT>
    </ABSTRACTS>
    <PAGES>
        <PAGE>
            <FPAGE>88</FPAGE>
            <TPAGE>94</TPAGE>
        </PAGE>
    </PAGES>
    <AUTHORS>
        <AUTHOR>
<Name>Ali</Name>
<MidName></MidName>
<Family>Ameri</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Student Research Committee, Faculty of Pharmacy, Hormozgan University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Student Research Committee, Faculty of Pharmacy, Hormozgan University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Alireza</Name>
<MidName></MidName>
<Family>Rahmati</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Student Research Committee, Faculty of Pharmacy, Hormozgan University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Student Research Committee, Faculty of Pharmacy, Hormozgan University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Shadi</Name>
<MidName></MidName>
<Family>Soroushfar </Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Student Research Committee, Faculty of Pharmacy, Hormozgan University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Student Research Committee, Faculty of Pharmacy, Hormozgan University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Mehdi</Name>
<MidName></MidName>
<Family>Lalehzari</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Trauma Research Center, Hormozgan University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Trauma Research Center, Hormozgan University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Tahereh</Name>
<MidName></MidName>
<Family>Dehghani</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Hamed</Name>
<MidName></MidName>
<Family>Haghi-Aminjan</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Jebreil</Name>
<MidName></MidName>
<Family>Shamseddin</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Mahmoud</Name>
<MidName></MidName>
<Family>Omidi</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hormozgan University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hormozgan University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR>
    </AUTHORS>
    <KEYWORDS>
        <KEYWORD><KeyText>Deltamethrin</KeyText></KEYWORD><KEYWORD><KeyText>Hepatoprotection</KeyText></KEYWORD><KEYWORD><KeyText>Liver</KeyText></KEYWORD><KEYWORD><KeyText>N-acetylcysteine</KeyText></KEYWORD><KEYWORD><KeyText>Pesticides</KeyText></KEYWORD>
    </KEYWORDS>
    <PDFFileName>60571.pdf</PDFFileName>
    <REFRENCES>
        <REFRENCE>
            <REF>Cunha FDS, Sousa NDC, Santos RFB, Meneses JO, do Couto MVS, de Almeida FTC, et al. Deltamethrin-induced nuclear erythrocyte alteration and damage to the gills and liver of Colossoma macropomum. Environ Sci Pollut Res Int 2018;25(15):15102-10.##Hołyńska-Iwan I, Szewczyk-Golec K. Pyrethroids: how they affect human and animal health? Medicina (Kaunas, Lithuania) 2020;56(11).##Parlato F, Buendia Palacios D, Ad&#227;o-Serrano M, Gon&#231;alves F, Carreiro C, Gouveia JL. A suicide attempt: deltamethrin intoxication. Eur J Case Rep Intern Med 2022;9(9):003573.##Hooven LA, Sherman KA, Butcher S, Giebultowicz JM. Does the clock make the poison? Circadian variation in response to pesticides. PloS One 2009;4(7):e6469.##Azmi MA, Naqvi SN, Azmi MA, Aslam M. Effect of pesticide residues on health and different enzyme levels in the blood of farm workers from Gadap (rural area) Karachi-Pakistan. Chemosphere 2006;64(10):1739-44.##Maroni M, Fanetti AC, Metruccio F. Risk assessment and management of occupational exposure to pesticides in agriculture. La Med Lav 2006;97(2):430-7.##Abhilash PC, Singh N. Pesticide use and application: an Indian scenario. J Hazard Mater 2009;165(1-3):1-12.##Mallick P, Moreau M, Song G, Efremenko AY, Pendse SN, Creek MR, et al. Development and application of a life-stage physiologically based pharmacokinetic (PBPK) model to the assessment of internal dose of pyrethroids in humans. Toxicol Sci 2020;173(1):86-99.##Rogliani P, Matera MG, Page C, Puxeddu E, Cazzola M, Calzetta L. Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine. Respir Rese 2019;20(1):104.##Zhang Q, Ju Y, Ma Y, Wang T. N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia: A randomized controlled trial. Medicine 2018;97(45):e13087.##Patriarca S, Furfaro AL, Domenicotti C, Odetti P, Cottalasso D, Marinari UM, et al. Supplementation with N-acetylcysteine and taurine failed to restore glutathione content in liver of streptozotocin-induced diabetics rats but protected from oxidative stress. Biochim Biophysica Acta 2005;1741(1-2):48-54.##de Andrade KQ, Moura FA, dos Santos JM, de Ara&#250;jo OR, de Farias Santos JC, Goulart MO. Oxidative stress and inflammation in hepatic diseases: therapeutic possibilities of N-acetylcysteine. Int J Mol Sci 2015;16(12):30269-308.##Otrubov&#225; O, Tureck&#253; L, Uličn&#225; O, Janega P, Luha J, Muchov&#225; J. Therapeutic effects of N-acetyl-L-cysteine on liver damage induced by long-term CCl4 administration. Gen Physiol Biophys 2018;37(1):23-31.##Oda SS, El-Maddawy Z. Protective effect of vitamin E and selenium combination on deltamethrin-induced reproductive toxicity in male rats. Exp Toxicol Pathol 2012;64(7-8):813-9.##Takasaki I, Oose K, Otaki Y, Ihara D, Fukuchi M, Tabuchi A, et al. Type II pyrethroid deltamethrin produces antidepressant-like effects in mice. Behav Brain Res 2013;257:182-8.##Corsetti G, Pasini E, Romano C, Calvani R, Picca A, Marzetti E, et al. Body weight loss and tissue wasting in late middle-aged mice on slightly imbalanced essential/non-essential amino acids diet. Front Med (Lausanne) 2018;5:136.##Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28(1):56-63.##Young DS. Effects of drugs on clinical laboratory tests. Ann Clin Biochem 1997;34 ( Pt 6):579-81.##Larsen T. Determination of lactate dehydrogenase (LDH) activity in milk by a fluorometric assay. J Dairy Res 2005;72(2):209-16.##Momtaz S, Baeeri M, Rahimifard M, Haghi-Aminjan H, Hassani S, Abdollahi M. Manipulation of molecular pathways and senescence hallmarks by natural compounds in fibroblast cells. J Cell Biochem 2019;120(4):6209-22.##Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem 1969;27(3):502-22.##Sulaiman S, Hussain M, Shad MN, Chiragh S. Hepatoprotective effect of prazosin is comparable To N-acetylcysteine in acetaminophen induced hepatotoxicity in mice. J Ayub Med Coll Abbottabad 2020;32(1):28-32.##More SS, Nugent J, Vartak AP, Nye SM, Vince R. Hepatoprotective effect of ψ-glutathione in a murine model of acetaminophen-induced liver toxicity. Chem Res Toxicol 2017;30(3):777-84.##Raza M, Ahmad M, Gado A, Al-Shabanah OA. A comparison of hepatoprotective activities of aminoguanidine and N-acetylcysteine in rat against the toxic damage induced by azathioprine. Comp Biochem Physiol C Toxicol Pharmacol 2003;134(4):451-6.##El-Yamany MF, Zaki ES, Shaltout SA, Saad MA. Bone marrow mononuclear cells boosts anti-cytogentical aberration effect of N-acetylcysteine and α-lipoic acid in rat&#39;s liver and bone marrow: implication of oxidative and inflammatory pathways. Toxicol Mech Methods 2021;31(6):437-49.##Sukumaran D, Usharani P, Paramjyothi GK, Subbalaxmi MVS, Sireesha K, Abid Ali M. A study to evaluate the hepatoprotective effect of N- acetylcysteine on anti tuberculosis drug induced hepatotoxicity and quality of life. Indian J Tuberc 2023;70(3):303-10.##Avizeh R, Najafzadeh H, Razijalali M, Shirali S. Evaluation of prophylactic and therapeutic effects of silymarin and N-acetylcysteine in acetaminophen-induced hepatotoxicity in cats. J Vet Pharmacol Ther 2010;33:95-9.##Kaya S, Yalcın T, Tektemur A, Kuloğlu T. N-Acetylcysteine may exert hepatoprotective effect by regulating meteorin-like levels in adriamycin-induced liver injury. Cell Stress Chaperones 2023.##Abdoli N, Azarmi Y, Eghbal MA. Protective effects of N-acetylcysteine against the statins cytotoxicity in freshly isolated rat hepatocytes. Adv Pharm Bull  2014;4(3):249-54.##Sathish P, Paramasivan V, Palani V, Sivanesan K. N-acetylcysteine attenuates dimethylnitrosamine induced oxidative stress in rats. Eur J Pharmacol 2011;654(2):181-6.##</REF>
        </REFRENCE>
    </REFRENCES>
</ARTICLE>

<ARTICLE>
    <TitleE>A Simple High Yield Technique for Isolation of Wharton&#39;s Jelly-derived Mesenchymal Stem Cell</TitleE>
    <TitleF></TitleF>
    <TitleLang_ID>2</TitleLang_ID>
    <ABSTRACTS>

        <ABSTRACT>
            <Language_ID>2</Language_ID>
            <CONTENT>&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Background:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; The isolation of Mesenchymal Stem Cells (MSCs) from various tissues is possible, with the umbilical cord emerging as a competitive alternative to bone marrow. In order to fulfill the demands of cell therapy, it is essential to generate stem cells on a clinical scale while minimizing time, cost, and contamination. Here is a simple and effective protocol for isolating MSC from Wharton&amp;#39;s Jelly (WJ-MSC) using the explant method with various supplements. &lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Methods:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; Utilizing the explant method, small fragments of Wharton&amp;#39;s jelly from the human umbilical cord were cultured in a flask. The multipotency of the isolated cells, were confirmed by their differentiation ability to osteocyte and adipocyte. Additionally, the immunophenotyping of WJ-MSCs showed positive expression of CD73, CD90, and CD105, while remaining negative for hematopoietic markers CD34 and CD45, meeting the criteria for WJ-MSC identification. Following that, to evaluate cells&amp;#39; proliferative capacity, various supplements, including basic Fibroblast Growth Factor (bFGF), Non-Essential amino acids (NEA), and L-Glutamine (L-Gln) were added to either alpha-Minimal Essential Medium (&amp;alpha;-MEM) or Dulbecco&amp;#39;s Modified Eagle&amp;#39;s Medium-F12 (DMEM-F12), as the basic culture media.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Results:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; WJ-MSCs isolated by the explant method were removed from the tissue after seven days and transferred to the culture medium. These cells differentiated into adipocyte and osteocyte lineages, expressing CD73, CD90, and CD105 positively and CD34 and CD45 negatively. The results revealed that addition of bFGF to &amp;alpha;-MEM or DMEM-F12 media significantly increased the proliferation of MSCs when compared to the control group. However, there were no significant differences observed when NEA or L-Gln were added.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Conclusion:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; Although bFGF considerably enhances cell proliferation, our study demonstrates that MSCs can grow and expand when properly prepared Wharton&amp;#39;s jelly tissues of the human umbilical cord.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;
</CONTENT>
        </ABSTRACT>
    </ABSTRACTS>
    <PAGES>
        <PAGE>
            <FPAGE>95</FPAGE>
            <TPAGE>103</TPAGE>
        </PAGE>
    </PAGES>
    <AUTHORS>
        <AUTHOR>
<Name>Bahare</Name>
<MidName></MidName>
<Family>Niknam</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Arezou</Name>
<MidName></MidName>
<Family>Azizsoltani </Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences </Organization>
</Organizations>
<Universities>
<University>Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences </University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Neda</Name>
<MidName></MidName>
<Family>Heidari</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Samaneh</Name>
<MidName></MidName>
<Family>Tokhanbigli</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for     Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for     Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Helia</Name>
<MidName></MidName>
<Family>Alavifard</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for     Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for     Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Mahsa</Name>
<MidName></MidName>
<Family>Haji Valili</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Davar</Name>
<MidName></MidName>
<Family>Amani</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Hamid</Name>
<MidName></MidName>
<Family>Asadzadeh Aghdaei</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Seyed Mahmoud</Name>
<MidName></MidName>
<Family>Hashemi </Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization></Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country></Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Kaveh</Name>
<MidName></MidName>
<Family>Baghaei</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization></Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country></Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR>
    </AUTHORS>
    <KEYWORDS>
        <KEYWORD><KeyText>Fibroblast growth factor 2</KeyText></KEYWORD><KEYWORD><KeyText>Mesenchymal stem cells</KeyText></KEYWORD><KEYWORD><KeyText>Umbilical cord</KeyText></KEYWORD>
    </KEYWORDS>
    <PDFFileName>60572.pdf</PDFFileName>
    <REFRENCES>
        <REFRENCE>
            <REF>Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 1974;17:331-340.##Mareschi K, Castiglia S, Sanavio F, Rustichelli D, Muraro M, Defedele D, et al. Immunoregulatory effects on T lymphocytes by human mesenchymal stromal cells isolated from bone marrow, amniotic fluid, and placenta. Exp Hematol 2016;44(2):138-150. e131.##Shi Y, Wang Y, Li Q, Liu K, Hou J, Shao C, et al. Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nat Rev Nephrol 2018;14(8):493-507.##Shu L, Niu C, Li R, Huang T, Wang Y, Huang M, et al. Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells (preprint). Stem Cell Res Ther 2020 Aug 18;11(1):361.##Meng F, Xu R, Wang S, Xu Z, Zhang C, Li Y, et al. Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19: a phase 1 clinical trial. Signal Transduct Target Ther 2020;5(1):172.##Liang J, Zhang H, Zhao C, Wang D, Ma X, Zhao S, et al. Effects of allogeneic mesenchymal stem cell transplantation in the treatment of liver cirrhosis caused by autoimmune diseases. Int J Rheum Dis 2017;20(9):1219-1226.##Wang L, Huang S, Li S, Li M, Shi J, Bai W, et al. Efficacy and safety of umbilical cord mesenchymal stem cell therapy for rheumatoid arthritis patients: a prospective phase I/II study. Drug Des Devel Ther 2019:4331-4340.##Bartolucci J, Verdugo FJ, Gonz&#225;lez PL, Larrea RE, Abarzua E, Goset C, et al. Safety and efficacy of the intravenous infusion of umbilical cord mesenchymal stem cells in patients with heart failure: a phase 1/2 randomized controlled trial (RIMECARD trial [randomized clinical trial of intravenous infusion umbilical cord mesenchymal stem cells on cardiopathy]). Circ Res 2017;121(10):1192-204.##Gao L, Zhang Y, Hu B, Liu J, Kong P, Lou S, et al. Phase II multicenter, randomized, double-blind controlled study of efficacy and safety of umbilical cord-derived mesenchymal stromal cells in the prophylaxis of chronic graft-versus-host disease after HLA-haploidentical stem-cell transplantation.  J Clin Oncol 2016 Aug 20;34(24):2843-50.##Friedenstein AJ, Gorskaja J, Kulagina N. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 1976;4(5):267-74.##Fraser JK, Wulur I, Alfonso Z, Hedrick MH. Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol 2006;24(4):150-4.##Perry BC, Zhou D, Wu X, Yang FC, Byers MA, Chu TM, et al. Collection, cryopreservation, and characterization of human dental pulp–derived mesenchymal stem cells for banking and clinical use. Tissue Eng Part C Methods 2008;14(2):149-56.##Cao C, Dong Y, Dong Y. [Study on culture and in vitro osteogenesis of blood-derived human mesenchymal stem cells]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2005 Aug;19(8):642-7. Chinese.##In&#39;t Anker PS, Scherjon SA, Kleijburg‐van der Keur C, de Groot‐Swings GM, Claas FH, Fibbe WE, et al. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 2004;22(7):1338-1345.##Ara&#250;jo AB, Salton GD, Furlan JM, Schneider N, Angeli MH, Laureano &#193;M, et al. Comparison of human mesenchymal stromal cells from four neonatal tissues: amniotic membrane, chorionic membrane, placental decidua and umbilical cord. Cytotherapy 2017;19(5):577-85.##Kalaszczynska I, Ferdyn K. Wharton’s jelly derived mesenchymal stem cells: future of regenerative medicine? Recent findings and clinical significance. Biomed Res Int 2015;2015.##Marino L, Castaldi MA, Rosamilio R, Ragni E, Vitolo R, Fulgione C, et al. Mesenchymal stem cells from the Wharton’s jelly of the human umbilical cord: biological properties and therapeutic potential. Int J Stem Cells 2019;12(2):218-226.##Li H, Ghazanfari R, Zacharaki D, Lim HC, Scheding S. Isolation and characterization of primary bone marrow mesenchymal stromal cells. Ann N Y Acad Sci 2016;1370(1):109-18.##Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells-current trends and future prospective. Bioscie Rep 2015;35(2):e00191.##Mazini L, Rochette L, Amine M, Malka G. Regenerative capacity of adipose derived stem cells (ADSCs), comparison with mesenchymal stem cells (MSCs). Int J Mol Sci 2019;20(10):2523.##Nancarrow-Lei R, Mafi P, Mafi R, Khan W. A systemic review of adult mesenchymal stem cell sources and their multilineage differentiation potential relevant to musculoskeletal tissue repair and regeneration. Curr Stem Cell Res Ther 2017;12(8):601-610.##Abbaszadeh H, Ghorbani F, Derakhshani M, Movassaghpour A, Yousefi M. Human umbilical cord mesenchymal stem cell‐derived extracellular vesicles: A novel therapeutic paradigm. J Cell Physiol 2020;235(2):706-17.##Mennan C, Wright K, Bhattacharjee A, Balain B, Richardson J, Roberts S. Isolation and characterisation of mesenchymal stem cells from different regions of the human umbilical cord. Biomed Res Int 2013;2013.##Gauthaman K, Fong CY, Suganya CA, Subramanian A, Biswas A, Choolani M, et al. Extra-embryonic human Wharton’s jelly stem cells do not induce tumorigenesis, unlike human embryonic stem cells. Reprod Biomed Online 2012;24(2):235-246##Deuse T, Stubbendorff M, Tang-Quan K, Phillips N, Kay MA, Eiermann T, et al. Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells. Cell Transplant 2011;20(5):655-67.##Zhou C, Yang B, Tian Y, Jiao H, Zheng W, Wang J, et al. Immunomodulatory effect of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells on lymphocytes. Cell Immunol 2011;272(1):33-8.##Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, et al. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+ CD25highFOXP3+ regulatory T cells. Stem Cells 2008;26(1):212-22.##Weiss ML, Anderson C, Medicetty S, Seshareddy KB, Weiss RJ, VanderWerff I, et al. Immune properties of human umbilical cord Wharton&#39;s jelly-derived cells. Stem Cells 2008;26(11):2865-74.##Fong CY, Chak LL, Biswas A, Tan JH, Gauthaman K, Chan WK, et al. Human Wharton’s jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev Rep 2011;7:1-16.##Barrett AN, Fong CY, Subramanian A. Liu W, Feng Y, Choolani M, et al. Human Wharton&#39;s jelly mesenchymal stem cells show unique gene expression compared with bone marrow mesenchymal stem cells using single-cell RNA-sequencing. Stem Cells Dev 2019;28(3):196-211.##Hass R, Kasper C, B&#246;hm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal 2011;9(1):1-14.##Baksh D, Yao R, Tuan RS. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells 2007;25(6):1384-392.##Can A, Karahuseyinoglu S. Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem Cells 2007;25(11):2886-95.##Majore I, Moretti P, Stahl F, Hass R, Kasper C. Growth and differentiation properties of mesenchymal stromal cell populations derived from whole human umbilical cord. Stem Cell Rev Rep 2011;7:17-31.##El Omar R, Beroud J, Stoltz JF, Menu P, Velot E, Decot V. Umbilical cord mesenchymal stem cells: the new gold standard for mesenchymal stem cell-based therapies? Tissue Eng Part B Rev 2014;20(5):523-44.##Hendijani F. Explant culture: An advantageous method for isolation of mesenchymal stem cells from human tissues. Cell Prolif 2017;50(2):e12334.##Saki N, Jalalifar MA, Soleimani M, Hajizamani S, Rahim F. Adverse effect of high glucose concentration on stem cell therapy. Int J Hematol Oncol Stem Cell Res 2013;7(3):34.##Stolzing A, Coleman N, Scutt A. Glucose-induced replicative senescence in mesenchymal stem cells. Rejuvenation Res 2006;9(1):31-5.##Chang TC, Hsu MF, Wu KK. High glucose induces bone marrow-derived mesenchymal stem cell senescence by upregulating autophagy. PloS One 2015;10(5):e0126537.##Tsai TL, Manner P, Li WJ. Regulation of mesenchymal stem cell chondrogenesis by glucose through protein kinase C/transforming growth factor signaling. Osteoarthritis Cartilage 2013;21(2):368-76.##Li YM, Schilling T, Benisch P, Zeck S, Meissner-Weigl J, Schneider D, et al. Effects of high glucose on mesenchymal stem cell proliferation and differentiation. Biochem Biophys Res Commun 2007;363(1):209-15.##Aguiari P, Leo S, Zavan B, Vindigni V, Rimessi A, Bianchi K, et al. High glucose induces adipogenic differentiation of muscle-derived stem cells. Proc Natl Acad Sci USA 2008;105(4):1226-31.##Choi KM, Seo YK, Yoon HH, Song KY, Kwon SY, Lee HS, et al. Effect of ascorbic acid on bone marrow-derived mesenchymal stem cell proliferation and differentiation. J Biosci Bioeng 2008;105(6):586-94.##Potdar PD, D’souza SB. Ascorbic acid induces in vitro proliferation of human subcutaneous adipose tissue derived mesenchymal stem cells with upregulation of embryonic stem cell pluripotency markers Oct4 and SOX 2. Human Cell 2010;23:152-5.##Kumar Mekala N, Raju Baadhe R, Rao Parcha S, Devi YP. Enhanced proliferation and osteogenic differentiation of human umbilical cord blood stem cells by L-ascorbic acid, in vitro. Curr Stem Cell Res Ther 2013;8(2):156-162.##Majumdar MK, Banks V, Peluso DP, Morris EA. Isolation, characterization, and chondrogenic potential of human bone marrow‐derived multipotential stromal cells. J Cell Physiol 2000;185(1):98-106.##Peister A, Mellad JA, Larson BL, Hall BM, Gibson LF, Prockop DJ. Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential. Blood 2004;103(5):1662-8.##Nekanti U, Rao VB, Bahirvani AG, Jan M, Totey S, Ta M. Long-term expansion and pluripotent marker array analysis of Wharton’s jelly-derived mesenchymal stem cells. Stem Cells Dev 2010;19(1):117-30.##Buyl K, Vanhaecke T, Desmae T, Lagneaux L, Rogiers V, Najar M, et al. Evaluation of a new standardized enzymatic isolation protocol for human umbilical cord-derived stem cells. Toxicol In Vitro 2015;29(6):1254-62.##Legzdina D, Romanauska A, Nikulshin S, Kozlovska T, Berzins U. Characterization of senescence of culture-expanded human adipose-derived mesenchymal stem cells. Int J Stem Cells 2016;9(1):124-36.##Crisostomo PR, Wang M, Wairiuko GM, Morrell ED, Terrell AM, Seshadri P, et al. High passage number of stem cells adversely affects stem cell activation and myocardial protection. Shock 2006;26(6):575-80.##Tonti GA, Mannello F. From bone marrow to therapeutic applications: different behaviour and genetic/epigenetic stability during mesenchymal stem cell expansion in autologous and foetal bovine sera? Int J Dev Biol 2002;52(8):1023-32.##Tesarova L, Jaresova K, Simara P, Koutna I. Umbilical cord-derived mesenchymal stem cells are able to use bFGF treatment and represent a superb tool for immunosuppressive clinical applications. Int J Mol Sci 2020;21(15):5366.##Nekanti U, Mohanty L, Venugopal P, Balasubramanian S, Totey S, Ta M. Optimization and scale-up of Wharton&#39;s jelly-derived mesenchymal stem cells for clinical applications. Stem Cell Res 2010;5(3):244-54.##von Bahr L, Sundberg B, L&#246;nnies L, Sander B, Karbach H, H&#228;gglund H, et al. Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy. Biol Blood Marrow Transplant 2012;18(4):557-64.##Luo L, Zhang Y, Chen H, Hu F, Wang X, Xing Z, et al. Effects and mechanisms of basic fibroblast growth factor on the proliferation and regenerative profiles of cryopreserved dental pulp stem cells. Cell Prol 2021;54(2):e12969.##Ramasamy R, Tong C, Yip W, Vellasamy S, Tan B, Seow HF. Basic fibroblast growth factor modulates cell cycle of human umbilical cord‐derived mesenchymal stem cells. Cell Prolif 2012;45(2):132-9.##Solchaga LA, Penick K, Porter JD, Goldberg VM, Caplan AI, Welter JF. FGF‐2 enhances the mitotic and chondrogenic potentials of human adult bone marrow‐derived mesenchymal stem cells. J Cell Physiol 2005;203(2):398-409.##Martin I, Muraglia A, Campanile G, Cancedda R, Quarto R. Fibroblast growth factor-2 supports ex vivo expansion and maintenance of osteogenic precursors from human bone marrow. Endocrinology 1997;138(10):4456-62.##Bianchi G, Banfi A, Mastrogiacomo M, Notaro R, Luzzatto L, Cancedda R, et al. Ex vivo enrichment of mesenchymal cell progenitors by fibroblast growth factor 2. Exp Cell Res 2003;287(1):98-105.##Tsutsumi S, Shimazu A, Miyazaki K, Pan H, Koike C, Yoshida E, et al. Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. Biochem Biophys Res Commun 2001;288(2):413-9.##van den Bos C, Mosca J, Winkles J, Kerrigan L, Burgess W, Marshak D. Human mesenchymal stem cells respond to fibroblast growth factors. Human Cell 1997;10(1):45-50.##Ng F, Boucher S, Koh S, Sastry KS, Chase L, Lakshmipathy U, et al. PDGF, TGF-β, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages. Blood 2008;112(2):295-307.##Jung S, Sen A, Rosenberg L, Behie LA. Identification of growth and attachment factors for the serum-free isolation and expansion of human mesenchymal stromal cells. Cytotherapy 2010;12(5):637-57.##Park J, Lee JH, Yoon BS, Jun EK, Lee G, Kim IY, et al. Additive effect of bFGF and selenium on expansion and paracrine action of human amniotic fluid-derived mesenchymal stem cells. Stem Cell Res Ther 2018;9:1-17.##Jung S, Panchalingam KM, Rosenberg L, Behie L. A. Ex vivo expansion of human mesenchymal stem cells in defined serum-free media. Stem Cells Int 2012;2012.##Fekete N, Rojewski MT, Lotfi R, Schrezenmeier H. Essential components for ex vivo proliferation of mesenchymal stromal cells. Tissue Eng Part C Methods 2014;20(2):129-39.##Fujimoto Y., Yokozeki T., Yokoyama A., Tabata Y. Basic fibroblast growth factor enhances proliferation and hepatocyte growth factor expression of feline mesenchymal stem cells. Regenerative therapy 2020;15:10-17.##Yoon JH, Roh EY, Shin S, Jung NH, Song EY, Chang JY, et al. Comparison of explant-derived and enzymatic digestion-derived MSCs and the growth factors from Wharton’s jelly. Biomed Res Int 2013;2013.##Mushahary D, Spittler A, Kasper C, Weber V, Charwat V. Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry A 2018;93(1):19-31.##</REF>
        </REFRENCE>
    </REFRENCES>
</ARTICLE>

<ARTICLE>
    <TitleE>Simple Determination of Bosentan in Plasma Samples by Reversed-Phase High-Performance Liquid Chromatography</TitleE>
    <TitleF></TitleF>
    <TitleLang_ID>2</TitleLang_ID>
    <ABSTRACTS>

        <ABSTRACT>
            <Language_ID>2</Language_ID>
            <CONTENT>&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:12pt&quot;&gt;&lt;span style=&quot;color:black&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Background:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; In order to measure the plasma levels of Losartan and Bosentan, a sensitive Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) technique was developed.&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:12pt&quot;&gt;&lt;span style=&quot;color:black&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Methods:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; To compare bioavailability, the Area Under the Curve (AUC), peak plasma concentration (Cmax), and time to Cmax (Tmax) were employed. The standard curve (150-2400 &lt;em&gt;ng/ml&lt;/em&gt;) was linear (R&lt;sup&gt;2&lt;/sup&gt;=0.999), relative errors were between 2.4 to 10.05% and the coefficient of variation (CV%) ranged from 1.52 to 10.88. A single dosage (test and reference) was used for the &lt;em&gt;in vivo&lt;/em&gt; investigation, which involved 16 healthy individuals.&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:12pt&quot;&gt;&lt;span style=&quot;color:black&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Results:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; The AUC0-48, AUC0-, Cmax, and Tmax of the test and reference had no statistically significant differences. The C&lt;sub&gt;max&lt;/sub&gt; and 95% confidence intervals of the ratio of C&lt;sub&gt;max&lt;/sub&gt; of the two formulations were 0.93-0.96 and 97.6-135%, respectively. &lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:12pt&quot;&gt;&lt;span style=&quot;color:black&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Conclusion:&lt;/span&gt;&lt;/strong&gt; &lt;span style=&quot;font-size:10.0pt&quot;&gt;Therefore, it was established that &lt;/span&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;generic Bosentan was equivalent to Bosentan from Actelion and that both medications could be regarded as equally effective in clinical settings. The blood level of Bosentan could be measured using this straightforward procedure in all hospital laboratories.&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;
</CONTENT>
        </ABSTRACT>
    </ABSTRACTS>
    <PAGES>
        <PAGE>
            <FPAGE>104</FPAGE>
            <TPAGE>110</TPAGE>
        </PAGE>
    </PAGES>
    <AUTHORS>
        <AUTHOR>
<Name>Zahra</Name>
<MidName></MidName>
<Family>Khalighi </Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Internal Medicine, School of Medicine, Shahid Mustafa Khomeini Hospital, Ilam University of Medical SciencesBiotechnology and Medicinal Plants Research Center, School of Medicine, Ilam University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Internal Medicine, School of Medicine, Shahid Mustafa Khomeini Hospital, Ilam University of Medical SciencesBiotechnology and Medicinal Plants Research Center, School of Medicine, Ilam University of Medical Sciences</University>
</Universities>
<Countries>
<Country>IranIran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Hori</Name>
<MidName></MidName>
<Family>Ghaneialvar</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Biotechnology and Medicinal Plants Research Center, School of Medicine, Ilam University of Medical SciencesDepartment of Clinical Biochemistry, School of Medicine, Ilam University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Biotechnology and Medicinal Plants Research Center, School of Medicine, Ilam University of Medical SciencesDepartment of Clinical Biochemistry, School of Medicine, Ilam University of Medical Sciences</University>
</Universities>
<Countries>
<Country>IranIran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Armin</Name>
<MidName></MidName>
<Family>Soltani</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Internal Medicine, School of Medicine, Shahid Mustafa Khomeini Hospital, Ilam University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Internal Medicine, School of Medicine, Shahid Mustafa Khomeini Hospital, Ilam University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Ali</Name>
<MidName></MidName>
<Family>Khorshidi</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Epidemiology and Biostatistics, School of Medicine, Ilam University of Medical Science</Organization>
</Organizations>
<Universities>
<University>Department of Epidemiology and Biostatistics, School of Medicine, Ilam University of Medical Science</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Elahe</Name>
<MidName></MidName>
<Family>Karimi</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization></Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country></Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Ardeshir</Name>
<MidName></MidName>
<Family>Moayeri</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Anatomy, School of Medicine, Ilam University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Anatomy, School of Medicine, Ilam University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Naser</Name>
<MidName></MidName>
<Family>Abbasi </Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Biotechnology and Medicinal Plants Research Center, School of Medicine, Ilam University of Medical SciencesDepartment of Pharmacology, School of Medicine, Ilam University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Biotechnology and Medicinal Plants Research Center, School of Medicine, Ilam University of Medical SciencesDepartment of Pharmacology, School of Medicine, Ilam University of Medical Sciences</University>
</Universities>
<Countries>
<Country>IranIran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Masoumeh</Name>
<MidName></MidName>
<Family>Tahmasebi</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Emergency Medicine, School of Medicine, Ilam University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Emergency Medicine, School of Medicine, Ilam University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Ali</Name>
<MidName></MidName>
<Family>Aidy</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization></Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country></Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR>
    </AUTHORS>
    <KEYWORDS>
        <KEYWORD><KeyText>Bioequivalence</KeyText></KEYWORD><KEYWORD><KeyText>Bosentan</KeyText></KEYWORD><KEYWORD><KeyText>High performance liquid chromatography</KeyText></KEYWORD><KEYWORD><KeyText>Losartan</KeyText></KEYWORD>
    </KEYWORDS>
    <PDFFileName>60573.pdf</PDFFileName>
    <REFRENCES>
        <REFRENCE>
            <REF>Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002;346(12):896-903.##Kiowski W, S&#252;tsch G, Hunziker P, M&#252;ller P, Kim J, Oechslin E, et al. Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure. Lancet (London, England). 1995;346(8977):732-6.##van Giersbergen PL, Halabi A, Dingemanse J. Single- and multiple-dose pharmacokinetics of Bosentan and its interaction with ketoconazole. Br J Clin Pharmacol 2002;53(6):589-95.##Parekh JM, Shah DK, Sanyal M, Yadav M, Shrivastav PS. Development of an SPE-LC-MS/MS method for simultaneous quantification of Bosentan and its active metabolite hydroxyBosentan in human plasma to support a bioequivalence study. J Pharm Biomed Anal 2012;70:462-70.##Atila A, Ozturk M, Kadioglu Y, Halici Z, Turkan D, Yayla M, et al. Development and validation of UFLC–MS/MS method for determination of Bosentan in rat plasma. J Pharm Biomed Anal 2014;97:33-8.##Bhavya Sri K, Mounika CH. Development and validation of uv-visible spectrophotometric method for analysis of Bosentan in spiked human plasma. International Journal of Current Pharmaceutical Research 2019;11(4):108-10.##Yokoyama Y, Tomatsuri M, Hayashi H, Hirai K, Ono Y, Yamada Y, et al. Simultaneous microdetermination of Bosentan, ambrisentan, sildenafil, and tadalafil in plasma using liquid chromatography/tandem mass spectrometry for pediatric patients with pulmonary arterial hypertension. J Pharm Biomed Anal 2014;89:227-32.##Qiu X, Zhao J, Wang Z, Xu Z, Xu RA. Simultaneous determination of Bosentan and glimepiride in human plasma by ultra performance liquid chromatography tandem mass spectrometry and its application to a pharmacokinetic study. J Pharm Biomed Anal   2014;95:207-12.##Li H, Zhang S, Tan B, Qiang Y, Li W, Chen S, et al. Investigation of Losartan Potassium as an eco-friendly corrosion inhibitor for copper in 0.5 M H2SO4. Journal of Molecular Liquids 2020;305(1):112789.##Qiang Y, Guo L, Li H, Lan X. Fabrication of environmentally friendly Losartan potassium film for corrosion inhibition of mild steel in HCl medium. Chemical Engineering Journal 2021;406:126863.##Zhao Z, Wang Q, Tsai EW, Qin XZ, Ip D. Identification of Losartan degradates in stressed tablets by LC-MS and LC-MS/MS. J Pharm Biomed Anal 1999;20(1-2):129-36.##Soldner A, Spahn-Langguth H, Mutschler E. HPLC assays to simultaneously determine the angiotensin-AT1 antagonist Losartan as well as its main and active metabolite EXP 3174 in biological material of humans and rats. J Pharm Biomed Anal 1998;16(5):863-73.##Selvadurai M, Meyyanathan SN. Sensitive and accurate estimation of Losartan potassium formulation by high-performance thin-layer chromatography. Pharm Methods 2011;2(2):95-8.##Iwasa T, Takano T, Hara K, Kamei T. Method for the simultaneous determination of Losartan and its major metabolite, EXP-3174, in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry. J Chromatogr B Biomed Sci Appl 1999;734(2):325-30.##Anandakumar K, Jambulingam M, Rmaesh J, Subarla SJ, Sangeetha P, Raja M. Development and validation of RP-HPLC method for the dissolution study of bosentan in bulk and in pharmaceutical dosage form. Current Journal of Applied Science and Technology 2018;18(2).##Weber C, Schmitt R, Birnboeck H, Hopfgartner G, van Marle SP, Peeters PAM, et al. Pharmacokinetics and pharmacodynamics of the endothelin-receptor antagonist bosentan in healthy human subjects. Clin Pharmacol Ther 1996;60(2):124-37.##Khan MA, Sinha S, Todkar M, Parashar V, Swamy Reddy K. Development and validation of a stability indicating analytical method for the related substances of Bosentan drug substance by HPLC. American Journal of Scientific and Industrial Research 2012;3(2):69-80.##Seth P. An in-vivo bioequivalence study of a new nifedipine extended release dosage form, ‘Opticaps’. Drug Development and Industrial Pharmacy 2008;20(9):1605-12.##Emami J, Varshosaz J, Falamarzian M, Tahvilian R. High performance liquid chromatographic determination, pharmacokinetic and comparative bioavailability studies of cisapride. J Pharm Biomed Anal 2003;33(3):513-20.##Bhadoriya A, Dasandi B, Parmar D, Shah PA, Shrivastav PS. Quantitation of tadalafil in human plasma using a sensitive and rapid LC-MS/MS method for a bioequivalence study. J Pharm Anal 2018;8(4):271-6.##Lausecker B, Hess B, Fischer G, Mueller M, Hopfgartner G. Simultaneous determination of Bosentan and its three major metabolites in various biological matrices and species using narrow bore liquid chromatography with ion spray tandem mass spectrometric detection. J Chromatogr B Biomed Sci Appl 2000;749(1):67-83.##Tanaka S, Uchida S, Hakamata A, Miyakawa S, Odagiri K, Inui N, et al. Simultaneous LC-MS analysis of plasma concentrations of sildenafil, tadalafil, bosentan, ambrisentan, and macitentan in patients with pulmonary arterial hypertension. Die Pharmazie 2020;75(6):236-9.##Markert C, Schweizer Y, Hellwig R, Wirsching T, Riedel KD, Burhenne J, et al. Clarithromycin substantially increases steady-state Bosentan exposure in healthy volunteers. Br J Clin Pharmacol 2014;77(1):141-8.##Al-Ghazawi M, Tutunji M, Aburuz S. Simultaneous determination of sildenafil and N-desmethyl sildenafil in human plasma by high-performance liquid chromatography method using electrochemical detection with application to a pharmacokinetic study. J Pharm Biomed Anal 2007;43(2):613-8.##Ma B, Shang X, Zhang Q, Li J, Liu Y, Cao X, et al. Rapid analysis of tadalafil in human blood plasma and seminal plasma by liquid chromatography/tandem mass spectrometry. J Pharm Biomed Anal 2013;77:149-57.##Nirogi R, Kandikere V, Komarneni P, Aleti R, Padala N, Kalaikadhiban I. LC-ESI-MS/MS method for quantification of ambrisentan in plasma and application to rat pharmacokinetic study. Biomed Chromatogr 2012;26(10):1150-6.##Enderle Y, Witt L, Wilkens H, Gr&#252;nig E, Haefeli WE, Burhenne J. Simultaneous quantification of endothelin receptor antagonists and phosphodiesterase 5 inhibitors currently used in pulmonary arterial hypertension. J Pharm Biomed Anal 2017;143:291-8.##Lavudu P, Rani AP, Chander AP, Bala sekaran C. Determination of bosentan in pharmaceutical dosage forms by high performance liquid chromatography. International Journal of Drug Delivery 2013;5(2):146-51.##Selvadurai Muralidharan, Kumar JR. Simple estimation of bosentan in tablet formulation by RP-HPLC.  American Journal of Analytical Chemistry 2012;3(11):715-8.##Ohtaka R, Maeda M, Iwagami T, Ueda T, Kimura Y, Imai K, et al. [Precision of internal standard method in HPLC analysis]. Yakugaku Zasshi 2003;123(5):349-55. Japanese.##Mannam RaYI. Estimation of bosentan monohydrate in male rabbit plasma by using RP-HPLC method. Journal of Applied Pharmaceutical Science 2017.##Atila A, Yilmaz B. Determination of bosentan in pharmaceutical preparations by linear sweep, square wave and differential pulse voltammetry methods. I ran J Pharm Res 2015;14(2):443-51.##Sajedi-Amin S, Asadpour-Zeynali K, Khoubnasabjafari M, Rashidi F, Jouyban A. Development and validation of ultrasound assisted and dispersive liquid-liquid microextractions combined with HPLC-UV method for determination of bosentan in human plasma and urine. Journal of the Brazilian Chemical Society 2017;28(5):868-77.##Jatczak M, Sidoryk K, Kossykowska M, Łuniewski W, Zagrodzka J, Lipiec-Abramska E. Development and validation of a UHPLC UV method for the in-process control of bosentan monohydrate synthesis. Chromatographia 2016;79(17):1131-41.##Dey S. Method development and estimation of Bosentan monohydrate in bulk and pharmaceutical dosage forms using UV-Visible Spectrophotometer. Journal of Pharmacy Research 2011;4(6):1713-5.##Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2014;27(9):911-39.##Bartlett JW, Frost C. Reliability, repeatability and reproducibility: analysis of measurement errors in continuous variables. Ultrasound Obstet Gynecol 2008;31(4):466-75.##Shammas HJ, Hoffer KJ. Repeatability and reproducibility of biometry and keratometry measurements using a noncontact optical low-coherence reflectometer and keratometer. Am J Ophthalmol 2012;153(1):55-61.e2.##Galderisi M, Henein M, D&#39;Hooge J, Sicari R, Badano L, Zamorano J, et al. Recommendations of the European Association of Echocardiography How to use echo-Doppler in clinical trials: Different modalities for different purposes. Eur J Echocardiogr 2011;12:339-53.##Watson PF, Petrie A. Method agreement analysis: a review of correct methodology. Theriogenology 2010;73(9):1167-79.##Karthikeyan K, Mahat MY, Chandrasekaran S, Gopal K, Franklin PX, Sivakumar BJ, et al. Bioanalytical method development, validation and quantification of dorsomorphin in rat plasma by LC-MS/MS. Biomed Chromatogr 2013;27(8):1018-26.##</REF>
        </REFRENCE>
    </REFRENCES>
</ARTICLE>

<ARTICLE>
    <TitleE>Poultry Gastrointestinal-derived Lactic Acid Bacteria (pGIT-d-LAB) Inhibit Multiple  Antibiotics Resistance Bacterial and Fungal Pathogens</TitleE>
    <TitleF></TitleF>
    <TitleLang_ID>2</TitleLang_ID>
    <ABSTRACTS>

        <ABSTRACT>
            <Language_ID>2</Language_ID>
            <CONTENT>&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Background:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; To develop a probiotic formulation for poultry feed, a few poultry gastrointestinal derived lactic acid bacteria (pGIT-d-LAB) were isolated from chicken intestinal specimens and &lt;em&gt;in vitro&lt;/em&gt; experiment was performed to evaluate their efficacy as potential probiotic candidate.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Methods:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; A total of 6 strains of LAB: &lt;em&gt;L&lt;/em&gt;&lt;em&gt;actobacillus brevis&lt;/em&gt; (&lt;em&gt;L. brevis&lt;/em&gt;)&lt;em&gt;,&lt;/em&gt; &lt;em&gt;L&lt;/em&gt;&lt;em&gt;actobacillus acidophilus &lt;/em&gt;(&lt;em&gt;L. acidophilus&lt;/em&gt;)&lt;em&gt;, Lactobacillus casei &lt;/em&gt;(&lt;em&gt;L. casei&lt;/em&gt;)&lt;em&gt;, Pediococci &lt;/em&gt;spp.&lt;em&gt;, Lactobacillus fermentum &lt;/em&gt;(&lt;em&gt;L. fermentum&lt;/em&gt;)&lt;em&gt; &lt;/em&gt;and&lt;em&gt; L&lt;/em&gt;&lt;em&gt;actobacillus plantarum &lt;/em&gt;(&lt;em&gt;L. plantarum&lt;/em&gt;)&lt;em&gt; &lt;/em&gt;were isolated and cultured for collection of Cell Free Supernatant (CFS). CFS collected was tested against pathogenic bacterial isolated from chicken feces as well as prevalent fungal pathogens, utilizing agar-well diffusion techniques. A preliminary investigation into the susceptibility of the pathogens to diverse antibiotics and antifungal drugs was conducted. Bacterial pathogens exhibiting resistance to a minimum of three classes of antibiotics were subsequently identified for pGIT-d-LAB CFS screening. &lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Results:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; The observed results revealed that the CFS derived from the isolates exhibited varying degrees of growth inhibition against different pathogens. Among the tested pGIT-d-LAB isolates, &lt;em&gt;L. acidophilus &lt;/em&gt;demonstrated the most prominent zone of inhibition, measuring 18 &lt;em&gt;mm&lt;/em&gt; against &lt;em&gt;Klebsiella pneumoniae&lt;/em&gt; ZTAC 1233. Notably, &lt;em&gt;Citrobacter diversus&lt;/em&gt; ZTAC 1255 showed resistance to all tested pGIT-d-LAB. Quantification of the metabolites produced was performed, and peak production levels was determined. &lt;em&gt;L.&lt;/em&gt;&lt;em&gt; acidophilus &lt;/em&gt;produced the highest amount of lactic acid (1.789&lt;em&gt;g/l&lt;/em&gt;), &lt;em&gt;Pediococci &lt;/em&gt;spp. produced the highest amount of diacetyl and H&lt;sub&gt;2&lt;/sub&gt;0&lt;sub&gt;2&lt;/sub&gt; (1.918&lt;em&gt;g/l&lt;/em&gt;) (0.0025&lt;em&gt;g/l&lt;/em&gt;) at 48&lt;em&gt; hr&lt;/em&gt; peak values respectively. &lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Conclusion:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; The test isolates are potential probiotic candidates for controlling pathogens in poultry. &lt;/span&gt;&lt;/span&gt;&lt;/p&gt;
</CONTENT>
        </ABSTRACT>
    </ABSTRACTS>
    <PAGES>
        <PAGE>
            <FPAGE>111</FPAGE>
            <TPAGE>119</TPAGE>
        </PAGE>
    </PAGES>
    <AUTHORS>
        <AUTHOR>
<Name>Bolanle</Name>
<MidName></MidName>
<Family>Adeniyi</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization></Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country></Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Abimbola</Name>
<MidName></MidName>
<Family>Adesuyi </Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Ibadan</Organization>
</Organizations>
<Universities>
<University>Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Ibadan</University>
</Universities>
<Countries>
<Country>Nigeria</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Funmilola</Name>
<MidName></MidName>
<Family>Ayeni </Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Ibadan</Organization>
</Organizations>
<Universities>
<University>Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Ibadan</University>
</Universities>
<Countries>
<Country>Nigeria</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Temitope</Name>
<MidName></MidName>
<Family>Ogunbanwo </Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Microbiology, Faculty of Science, University of Ibadan</Organization>
</Organizations>
<Universities>
<University>Department of Microbiology, Faculty of Science, University of Ibadan</University>
</Universities>
<Countries>
<Country>Nigeria</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Taiwo</Name>
<MidName></MidName>
<Family>Agidigbi</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Ibadan</Organization>
</Organizations>
<Universities>
<University>Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Ibadan</University>
</Universities>
<Countries>
<Country>Nigeria</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR>
    </AUTHORS>
    <KEYWORDS>
        <KEYWORD><KeyText>Antibacterial agents</KeyText></KEYWORD><KEYWORD><KeyText>Chickens</KeyText></KEYWORD><KEYWORD><KeyText>Lactic acid</KeyText></KEYWORD><KEYWORD><KeyText>Poultry</KeyText></KEYWORD><KEYWORD><KeyText>Probiotics</KeyText></KEYWORD>
    </KEYWORDS>
    <PDFFileName>60574.pdf</PDFFileName>
    <REFRENCES>
        <REFRENCE>
            <REF>Wang Y, Wu J, Lv M, Shao Z, Hungwe M, Wang J, et al. Metabolism characteristics of lactic acid Bacteria and the expanding applications in food industry. Front Bioeng Biotechnol 2021;9:612285.##Guo XH, Kim JM, Nam HM, Park SY, Kim JM. Screening lactic acid bacteria from swine origins for multistrain probiotics based on In vitro functional properties. Anaerobe 2010;16(4):321-6.##Al-Surrayai T, Al-Khalaifah H, Al-Mansour H, Kishk M, Al-Mutairi A, Sultan H, Al-Saleem H. Evaluation of the lactic acid bacteria based formulated probiotic product for poultry. Front Anim Sci 2022;3:1026958.##Tavakoli M, Hamidi-Esfahani Z, Hejazi MA, Azizi MH, Abbasi S. Characterization of probiotic abilities of lactobacilli isolated from Iranian koozeh traditional cheese. Polish J Food Nutrition Sci 2017;67(1):1.##Dvorožň&#225;kov&#225; E, Buckov&#225; B, Hurn&#237;kov&#225; Z, Revajov&#225; V, Laukov&#225; A. Effect of probiotic bacteria on phagocytosis and respiratory burst activity of blood polymorphonuclear leukocytes (PMNL) in mice infected with Trichinella spiralis. Vet Parasitol 2016;231:69-76.##Adeniyi BA, Ayeni FA, Ogunbanwo ST. Antagonistic activities of   lactic acid bacteria isolated from fermented diary food against organisms implicated in urinary tract infection. Biotechnology 2006;5(2):183-8.##Biswas A, Dev K, Tyagi PK, Mandal A. The effect of multi strain probiotics as feed additives on performance, immunity, expression of nutrient transporter genes and gut morphometry in broiler chickens. Anim Bioscience 2022;35(1):64-74.##Toshimitsu T, Mochizuki J, Ikegami S, Itou H. Identification of a Lactobacillus plantarum strain that ameliorates chronic inflammation and metabolic disorders in obese and type 2 diabetic mice. J Dairy Sci 2016;99(2):933-46.##Bamidele A, Adeniyi A. Evaluation of organic acids, anti-salmonella activities of lactic acid bacteria isolated from Nigerian grown salad vegetables. British Biotechnology Journal 2016;11(1):1-10.##Wang Y, Don, Z, Song D, Zhou H, Wang W, Miao H. Effects of microencapsulated probiotics and prebiotics on growth performance, antioxidative abilities, immune functions, and caecal microflora in broiler chickens. Food Agric Immunol 2018;29(1):859-69.##Yaqoob MU, Wang G, Wang M. An updated review on probiotics as an alternative of antibiotics in poultry. Anim Biosci 2022;35(8):1109-20.##Reuben RC, Roy PC, Sarkar SL, Alam RU, Jahid IK. Isolation, characterization, and assessment of lactic acid bacteria toward their selection as poultry probiotics. BMC Microbiolol 2019;19(1):253.##Adetoye A, Pinloche E, Adeniyi BA, Ayeni FA. Characterization and anti-Salmonella activities of lactic acid bacteria isolated from cattle feaces. BMC Microbiol 2018;18(1):96.##Liu A, Xu R, Zhang S, Wang Y, Hu B, Ao X, et al. Antifungal mechanisms and application of lactic acid bacteria in bakery products: A review. Front Microbiol 2022;13:924398.##Ahlberg SH, Joutsjoki V, Korhonen HJ. Potential of lactic acid bacteria in aflatoxin risk mitigation. Int J Food Microbiol 2015;207:87-102.##Coda R, Cassone A, Rizzello CG, Nionelli L, Cardinali G, Gobbetti M. Antifungal activity of Wickerhamomyces anomalus and Lactobacillus plantarum during sourdough fermentation: identification of novel compounds and long-term effect during storage of wheat bread. Appl Environ Microbiol 2011;77(10):3484-92.##Mokoena MP, Omatola CA, Olaniran AO. Applications of lactic acid bacteria and their bacteriocins against food spoilage Microorganisms and foodborne pathogens. Molecules 2021;26(22):7055.##L&#243;pez P, Spano G. Editorial: Industrial and health applications of lactic acid bacteria and their metabolites, volume II. Front. Microbiol 2023;14:1242253.##Del Coco VF, Sparo MD, Sidoti A, Sant&#237;n M, Basualdo JA, C&#243;rdoba MA. Effects of Enterococcus faecalis CECT 7121 on Cryptosporidium parvum infection in mice. Parasitol Res 2016 Aug;115(8):3239-44.##Simons A, Alhanout K, Duval RE. Bacteriocins, antimicrobial peptides from bacterial origin: overview of their biology and their impact against multidrug-resistant bacteria. Microorganisms 2020;8(5):639.##Hern&#225;ndez-Gonz&#225;lez JC, Mart&#237;nez-Tapia A, Lazcano-Hern&#225;ndez G, Garc&#237;a-P&#233;rez BE, Castrej&#243;n-Jim&#233;nez NS. Bacteriocins from lactic acid bacteria. A powerful alternative as antimicrobials, probiotics, and immunomodulators in veterinary medicine. Animals (Basel) 2021;11(4):979.##Zheng J, G&#228;nzle MG Lin XB, Ruan L, Sun M. Diversity and dynamics of bacteriocins from human microbiome. Environ Microbiol 2014;17(6):2133-43.##Mokoena MP. Lactic acid bacteria and their bacteriocins: classification, biosynthesis and applications against uropathogens: A mini-review. Molecules 2017:22(8):1255.##Ahlberg SH, Joutsjoki V, Korhonen HJ. Potential of lactic acid bacteria in aflatoxin risk mitigation. Int J Food Microbiol 2015;207:87-102.##Cizeikiene D, Juodeikiene G, Paskevicius A, Bartkiene E. Antimicrobial activity of lactic acid bacteria against pathogenic and spoilage microorganism isolated from food and their control in wheat bread. Food Control 2013;31(2):539-45.##Ebrahimi M, Sadeghi A, Mortazavi SA. The use of cyclic dipeptide producing LAB with potent anti-aflatoxigenic capability to improve techno-functional properties of clean-label bread. Ann. Microbiol 2020;70:24.##Jin J, Nguyen TTH, Humayun S, Park S, Oh H, Lim S. Characteristics of sourdough bread fermented with Pediococcus pentosaceus and Saccharomyces cerevisiae and its bio-preservative effect against Aspergillus flavus. Food Chem 2012;345:128787.##Moradi M, Guimar&#227;es JT, Sahin S. Current applications of exopolysaccharides from lactic acid bacteria in the development of food active edible packaging. Curr Opin Food Sci 2021;40:33-9.##Cong L, Chen C, Mao S, Han Z, Zhu Z, Li Y. Intestinal bacteria, a powerful weapon for fungal infections treatment. Front Cell Infect Microbiol 2023;13:1187831.##Ceresa C, Rinaldi M, Chiono V, Carmagnola I, Allegrone G, Fracchia L. Lipopeptides from Bacillus subtilis AC7 inhibit adhesion and biofilm formation of Candida albicans on silicone. Antonie Van Leeuwenhoek 2016;109(10):1375-88.##Rusu E, Enache G, Cursaru R, Alexescu A, Radu R, Onila O, et al. Prebiotics and probiotics in atopic dermatitis (Review). Exp Therapeu Med 2019;18(2):926-31.##Steiner NC, Lorentz A. Probiotic potential of Lactobacillus species in allergic rhinitis. Int Arch Allergy Immunol 2021;182(9):807-18.##Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev 2004;(2):CD003048.##Collado MC, Meriluoto J, Salminen S. Role of commercial probiotic strains against human pathogen adhesion to intestinal mucus. Lett Appl Microbiol 2007;45(4):454-60.##Brenner DM, Moeller MJ, Chey WD, Schoenfeld PS. The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Am J Gastroenterol 2009;104(4):1033-49.##Fujimori S, Tatsuguchi A, Gudis K, Kishida T, Mitsui K, Ehara A. High dose probiotic and prebiotic cotherapy for remission induction of active Crohn’s disease. J Gastroenterol Hepatol 2007;22(8):1199-204.##Furrie E, Macfarlane S, Kennedy A, Cummings JH, Walsh SV, O’Neil DA. Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 2005;54(2): 242-9.##Shen YL, Zhang LQ, Yang Y, Yin BC, Ye BC, Zhou Y. Advances in role and mechanism of lactic acid bacteria in treating obesity. Food Bioeng 2022;1(8):101-15.##Teng Y, Wang Y, Tian Y, Chen Y, Guan W, Piao C, et al. Lactobacillus plantarum LP104 ameliorates hyperlipidemia induced by AMPK pathways in C57BL/6N mice fed high‐fat diet. J Func Foods 2020;64:103665.##JoVE Science Education Database, Microbiology. Serial Dilutions and Plating: Microbial Enumeration. JoVE, Cambridge, MA, (2023).##Nugroho ADW, Kleerebezem M, Bachmann H. A novel method for long-term analysis of lactic acid and ammonium production in non-growing Lactococcus lactis reveals pre-culture and strain dependence. Front Bioeng Biotechnol 2020 Oct 8;8:580090.##Seki M, Iida K, Saito M, Nakayama H, Yoshida S. Hydrogen peroxide production in Streptococcus pyogenes: involvement of lactate oxidase and coupling with aerobic utilization of lactate. J Bacteriol. 2004 Apr;186(7):2046-51.##Rosca I, Petrovici AR, Brebu M, Stoica I, Minea B, Marangoci N. An original method for producing acetaldehyde and diacetyl by yeast fermentation. Braz J Microbiol 2016;47(4):949-54.##Hayden DH, Karla AV, and Lixin Z. A review of antimicrobial resistance in poultry farming within low-resource settings. Animals (Basel) 2020;10(8):1264.##Przemysław R, Michał M, Hanna B, Sebastian N, Jarosław W, Danuta W, et al. Prevalence and characterization of antimicrobial resistance genes and class 1 and 2 integrons in multi-resistant E. coli isolated from poultry production. Scientifc Reps 2022;12(1):6062.##R&#246;nnqvist D, Forsgren-Brusk U, Husmark U, Grahn-H&#229;kansson E. Lactobacillus fermentum Ess-1 with unique growth inhibition of vulvo-vaginal candidiasis pathogens. J Med Microbiol 2007;56(Pt 11):1500-4.##</REF>
        </REFRENCE>
    </REFRENCES>
</ARTICLE>

<ARTICLE>
    <TitleE>Investigating the Effects of HMGB1 Overexpression on Colorectal Cancer Cell Migration via Oncolytic Herpes simplex Virus Type 1 (oHSV-1)</TitleE>
    <TitleF></TitleF>
    <TitleLang_ID>2</TitleLang_ID>
    <ABSTRACTS>

        <ABSTRACT>
            <Language_ID>2</Language_ID>
            <CONTENT>&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Background:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; Colorectal Cancer (CRC) represents a significant global health challenge, and its progression, resistance to therapy, and metastasis are strongly influenced by the tumor microenvironment, including factors like hypoxia. This study explores the impact of High Mobility Group Box 1 (HMGB1) overexpression on CRC cell migration, while identifying potential genes associated with this process. &lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Methods:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; To explore this, we developed oncolytic virotherapy, resulting in HSV-HMGB1, an oncolytic &lt;em&gt;Herpes simplex&lt;/em&gt; virus that expresses HMGB1. HMGB1 is known its role in cancer progression, particularly in the context of cancer cell migration. &lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Results:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; Contrary to expectations, our scratch assays indicated that HSV-HMGB1 did not significantly induce migration in CRC cells, suggesting that HMGB1 might not directly contribute to this process. Employing microarray analysis, we investigated gene expression changes linked to CRC cell migration, leading to construction of a Protein-Protein Interaction (PPI) network. This network revealed the presence of hub proteins, including as NDRG1, LGALS1, and ANGPTL4, which are recognized for their roles in cancer cell migration. The differential expression of these genes under hypoxic conditions was further validated using quantitative RT-PCR, aligning with the findings from our microarray data.&amp;nbsp; &lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Conclusion:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; Our findings emphasize the complex regulation of CRC cell migration, and provides valuable insights into potential molecular mechanisms and pathways. These findings have implications for further research into cancer progression and the development of therapeutic strategies.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;
</CONTENT>
        </ABSTRACT>
    </ABSTRACTS>
    <PAGES>
        <PAGE>
            <FPAGE>120</FPAGE>
            <TPAGE>129</TPAGE>
        </PAGE>
    </PAGES>
    <AUTHORS>
        <AUTHOR>
<Name>Sara</Name>
<MidName></MidName>
<Family>Shayan</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Molecular Virology, Pasteur Institute of Iran</Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Arash</Name>
<MidName></MidName>
<Family>Arashkia</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Molecular Virology, Pasteur Institute of Iran</Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Golnaz</Name>
<MidName></MidName>
<Family>Bahramali</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Hepatitis and AIDS and Blood Borne Diseases, Pasteur Institute of Iran</Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Kayhan</Name>
<MidName></MidName>
<Family>Azadmanesh</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization></Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country></Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR>
    </AUTHORS>
    <KEYWORDS>
        <KEYWORD><KeyText>Colorectal neoplasms</KeyText></KEYWORD><KEYWORD><KeyText>Galectin 1</KeyText></KEYWORD><KEYWORD><KeyText>HMGB1 protein</KeyText></KEYWORD><KEYWORD><KeyText>Oncolytic virotherapy</KeyText></KEYWORD><KEYWORD><KeyText>Simplex virus</KeyText></KEYWORD><KEYWORD><KeyText>Tumor microenvironment</KeyText></KEYWORD>
    </KEYWORDS>
    <PDFFileName>60575.pdf</PDFFileName>
    <REFRENCES>
        <REFRENCE>
            <REF>Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol 2019;14(2):89-103.##Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin 2023;73(3):233-54.##Li Y, Zhao L, Li XF. Hypoxia and the tumor microenvironment. Technol Cancer Res Treat 2021;20:15330338211036304.##Roy S, Kumaravel S, Sharma A, Duran CL, Bayless KJ, Chakraborty S. Hypoxic tumor microenvironment: Implications for cancer therapy. Exp Biol Med (Maywood) 2020;245(13):1073-86.##Mi Y, Mu L, Huang K, Hu Y, Yan C, Zhao H, et al. Hypoxic colorectal cancer cells promote metastasis of normoxic cancer cells depending on IL-8/p65 signaling pathway. Cell Death Dis 2020;11(7):610.##Höckel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst  2001;93(4):266-76.##Muz B, de la Puente P, Azab F, Azab AK. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckl) 2015;3:83-92.##Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov 2015;14(9):642-62.##Friedman GK, Haas MC, Kelly VM, Markert JM, Gillespie GY, Cassady KA. Hypoxia moderates γ(1)34.5-deleted Herpes simplex virus oncolytic activity in human glioma xenoline primary cultures. Transl Oncol 2012;5(3):200-7.##Shayan S, Arashkia A, Azadmanesh K. Modifying oncolytic virotherapy to overcome the barrier of the hypoxic tumor microenvironment. Where do we stand? Cancer Cell Int 2022;22(1):370.##Reinblatt M, Pin RH, Federoff HJ, Fong Y. Utilizing tumor hypoxia to enhance oncolytic viral therapy in colorectal metastases. Ann Surg 2004;239(6):892-9; discussion 9-902.##Post DE, Van Meir EG. A novel hypoxia-inducible factor (HIF) activated oncolytic adenovirus for cancer therapy. Oncogene 2003;22(14):2065-72.##Shayan S, Arashkia A, Bahramali G, Abdoli A, Nosrati MSS, Azadmanesh K. Cell type-specific response of colon cancer tumor cell lines to oncolytic HSV-1 virotherapy in hypoxia. Cancer Cell Int 2022;22(1):164.##Štros M, Polansk&#225; E, Štruncov&#225; S, Posp&#237;šilov&#225; Š. HMGB1 and HMGB2 proteins up-regulate cellular expression of human topoisomerase IIα. Nucleic Acids Res 2009;37(7):2070-86.##Mandke P, Vasquez KM. Interactions of high mobility group box protein 1 (HMGB1) with nucleic acids: Implications in DNA repair and immune responses. DNA Repair (Amst) 2019;83:102701.##Gao X, Zhou S, Qin Z, Li D, Zhu Y, Ma D. Upregulation of HMGB1 in tumor-associated macrophages induced by tumor cell-derived lactate further promotes colorectal cancer progression. J Transl Med 2023;21(1):53.##Liu WL, Li CY, Cheng WC, Chang CY, Chen YH, Lu CY, et al. High mobility group box 1 promotes lung cancer cell migration and motility via regulation of dynamin-related protein 1. Int J Mol Sci 2021;22(7).##Zhang J, Kou Y-B, Zhu J-S, Chen W-X, Li S. Knockdown of HMGB1 inhibits growth and invasion of gastric cancer cells through the NF-κB pathway in vitro and in vivo. Int J Oncol 2014;44(4):1268-76.##Guimbellot JS, Erickson SW, Mehta T, Wen H, Page GP, Sorscher EJ, et al. Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis. BMC Med Genomics 2009;2(1):15.##Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015;43(7):e47-e.##Benjamini Y, Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society Series B (Methodological) 1995;57(1):289-300.##Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, et al. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 2011;39(Database issue):D561-8.##Smoot ME, Ono K, Ruscheinski J, Wang P-L, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 2011;27(3):431-2.##Chen S-J, Liao D-L, Chen C-H, Wang T-Y, Chen K-C. Construction and analysis of protein-protein interaction network of heroin use disorder. Sci Rep 2019;9(1):4980.##Soofi A, Taghizadeh M, Tabatabaei SM, Rezaei Tavirani M, Shakib H, Namaki S, et al. Centrality analysis of protein-protein interaction networks and molecular docking prioritize potential drug-targets in type 1 diabetes. Iran J Pharm Res 2020;19(4):121-34.##Li CY, Cai JH, Tsai JJP, Wang CCN. Identification of hub genes associated with development of head and neck squamous cell carcinoma by integrated bioinformatics analysis. Front Oncol 2020;10:681.##Chin C-H, Chen S-H, Wu H-H, Ho C-W, Ko M-T, Lin C-Y. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol 2014;8(Suppl 4):S11.##Carbon S, Ireland A, Mungall CJ, Shu S, Marshall B, Lewis S, et al. AmiGO: online access to ontology and annotation data. Bioinformatics 2009;25(2):288-9.##Kanehisa M, Araki M, Goto S, Hattori M, Hirakawa M, Itoh M, et al. KEGG for linking genomes to life and the environment. Nucleic Acids Res 2008;36(Database issue):D480-4.##Bakhashab S, Lary S, Ahmed F, Schulten HJ, Bashir A, Ahmed FW, et al. Reference genes for expression studies in hypoxia and hyperglycemia models in human umbilical vein endothelial cells. G3 (Bethesda) 2014;4(11):2159-65.##Chowdhury P, Dey P, Ghosh S, Sarma A, Ghosh U. Reduction of metastatic potential by inhibiting EGFR/Akt/p38/ERK signaling pathway and epithelial-mesenchymal transition after carbon ion exposure is potentiated by PARP-1 inhibition in non-small-cell lung cancer. BMC Cancer 2019;19(1):829.##Rodr&#237;guez MI, Peralta-Leal A, O&#39;Valle F, Rodriguez-Vargas JM, Gonzalez-Flores A, Majuelos-Melguizo J, et al. PARP-1 regulates metastatic melanoma through modulation of vimentin-induced malignant transformation. PLOS Genet 2013;9(6):e1003531.##Swindall AF, Stanley JA, Yang ES. PARP-1: Friend or foe of DNA damage and repair in tumorigenesis? Cancers (Basel) 2013;5(3):943-58.##Zhang Y, Yang X, Liu S, Zhuang Z, Wei M, Deng X, et al. Comprehensive analysis of potential prognostic values of ANGPTLs in colorectal cancer. Genes (Basel) 2022;13(12):2215.##Jia H-T, Shao Y-F, Zhou X-I, Yang G, Huang L, Aikemu B, et al. PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway. Front Oncol 2023 Feb 2:13:1026561.##Wu Y, Liu M, Li Z, Wu XB, Wang Y, Wang Y, et al. LYAR promotes colorectal cancer cell mobility by activating galectin-1 expression. Oncotarget 2015;6(32):32890-901.##Santulli G. Angiopoietin-like proteins: a comprehensive look. Front Endocrinol (Lausanne) 2014;5:4.##Cai Y-C, Yang H, Wang K-F, Chen T-H, Jiang W-Q, Shi Y-X. ANGPTL4 overexpression inhibits tumor cell adhesion and migration and predicts favorable prognosis of triple-negative breast cancer. BMC Cancer 2020;20(1):878.##Hefni E, Menon D, Ma T, Asiedu EB, Sultan A, Meiller T, et al. Angiopoietin-like 4 induces head and neck squamous cell carcinoma cell migration through the NRP1/ABL1/PXN pathway. Cellular Signal 2023;108:110697.##Zhao J, Liu J, Wu N, Zhang H, Zhang S, Li L, et al. ANGPTL4 overexpression is associated with progression and poor prognosis in breast cancer. Oncol Lett 2020;20(3):2499-505.##Liu J, Shao Y, He Y, Ning K, Cui X, Liu F, et al. MORC2 promotes development of an aggressive colorectal cancer phenotype through inhibition of NDRG1. Cancer Sci 2019;110(1):135-46.##Joshi V, Lakhani SR, McCart Reed AE. NDRG1 in cancer: A suppressor, promoter, or both? Cancers (Basel) 2022;14(23):5739.##Shi W, Xue C, Su XZ, Lu F. The roles of galectins in parasitic infections. Acta Trop 2018;177:97-104.##Peng KY, Jiang SS, Lee YW, Tsai FY, Chang CC, Chen LT, et al. Stromal galectin-1 promotes colorectal cancer cancer-initiating cell features and disease dissemination through SOX9 and β-Catenin: Development of niche-based biomarkers. Front Oncol 2021;11:716055.##</REF>
        </REFRENCE>
    </REFRENCES>
</ARTICLE>

<ARTICLE>
    <TitleE>CYP21A2 Gene Analysis in Southern Iranian CAH Patients and a Brief Review of the  Mutation Spectrum</TitleE>
    <TitleF></TitleF>
    <TitleLang_ID>2</TitleLang_ID>
    <ABSTRACTS>

        <ABSTRACT>
            <Language_ID>2</Language_ID>
            <CONTENT>&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Background:&lt;/span&gt;&lt;/strong&gt;&lt;em&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; CYP21A2&lt;/span&gt;&lt;/em&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; gene mutations are responsible for more than 95% of Congenital Adrenal Hyperplasia&lt;/span&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; (CAH)&lt;/span&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; disorders with&lt;/span&gt; &lt;span style=&quot;font-size:10.0pt&quot;&gt;autosomal recessive inheritance. Most of these pathogenic mutations originate from the &lt;em&gt;CYP21A1P&lt;/em&gt;, a neighboring pseudogene with 98% homology, due to unequal crossing over or gene conversion events. Mutation identification of the gene could be beneficial for accurate diagnosis and outcome prediction. &lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Methods:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; Twelve unrelated patients with CAH diagnosis&lt;/span&gt; &lt;span style=&quot;font-size:10.0pt&quot;&gt;were recruited for genetic counseling. To ensure distinct amplification of the &lt;em&gt;CYP21A2&lt;/em&gt; gene rather than its pseudogene, the complete sequence of the gene was amplified through two overlapping fragments by specific primers. The entire sequences were screened by direct Sanger sequencing using new sequencing primers. &lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

&lt;p style=&quot;text-align:justify&quot;&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Results&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;: Only two pathogenic point mutations were identified. The c.293-13C&amp;gt;G, also known as In2G, and the c.955C&amp;gt;T mutations were found in 37.5 and 33.3% of alleles, respectively. One patient showed homozygous gene deletion. &lt;/span&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;We also reviewed recent reports on &lt;em&gt;CYP21A2&lt;/em&gt; gene mutations in Iran.&lt;/span&gt; &lt;/span&gt;&lt;/p&gt;

&lt;p&gt;&lt;span style=&quot;font-size:11pt&quot;&gt;&lt;strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt;Conclusion:&lt;/span&gt;&lt;/strong&gt;&lt;span style=&quot;font-size:10.0pt&quot;&gt; Evaluating the ethnicity-specific gene mutation data is significant for populations with diverse ethnic groups including the Iranian population. Although several common mutations have been reported as causative mutations among CAH patients, identifying only two common point mutations in Fars province would help prioritize exon sequencing and reduce the cost and time of genotyping.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;
</CONTENT>
        </ABSTRACT>
    </ABSTRACTS>
    <PAGES>
        <PAGE>
            <FPAGE>130</FPAGE>
            <TPAGE>135</TPAGE>
        </PAGE>
    </PAGES>
    <AUTHORS>
        <AUTHOR>
<Name>Danial</Name>
<MidName></MidName>
<Family>Zangene</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Ali</Name>
<MidName></MidName>
<Family>Moravvej</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Neonatal Research Center, Shiraz University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Neonatal Research Center, Shiraz University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Homa</Name>
<MidName></MidName>
<Family>Ilkhanipoor</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Pediatric Endocrinology, School of Medicine, Shiraz University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Pediatric Endocrinology, School of Medicine, Shiraz University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Anis </Name>
<MidName></MidName>
<Family>Amirhakimi</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Pediatric Endocrinology, School of Medicine, Shiraz University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Pediatric Endocrinology, School of Medicine, Shiraz University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Zhila</Name>
<MidName></MidName>
<Family>Afshar</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization>Department of Pediatric Endocrinology, School of Medicine, Shiraz University of Medical Sciences</Organization>
</Organizations>
<Universities>
<University>Department of Pediatric Endocrinology, School of Medicine, Shiraz University of Medical Sciences</University>
</Universities>
<Countries>
<Country>Iran</Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR><AUTHOR>
<Name>Mona</Name>
<MidName></MidName>
<Family>Entezam</Family>
<NameE></NameE>
<MidNameE></MidNameE>
<FamilyE></FamilyE>
<Organizations>
<Organization></Organization>
</Organizations>
<Universities>
<University></University>
</Universities>
<Countries>
<Country></Country>
</Countries>
<EMAILS>
<Email></Email>
</EMAILS>
</AUTHOR>
    </AUTHORS>
    <KEYWORDS>
        <KEYWORD><KeyText>Adrenal hyperplasia</KeyText></KEYWORD><KEYWORD><KeyText>Congenital</KeyText></KEYWORD><KEYWORD><KeyText>Genotyping techniques</KeyText></KEYWORD><KEYWORD><KeyText>Mutation</KeyText></KEYWORD>
    </KEYWORDS>
    <PDFFileName>60576.pdf</PDFFileName>
    <REFRENCES>
        <REFRENCE>
            <REF>Carvalho B, Marques CJ, Santos-Silva R, Fontoura M, Carvalho D, Carvalho F. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: An update on genetic analysis of CYP21A2 gene. Exp Clin Endocrinol Diabetes 2021 Jul;129(7):477-81.##Kanczkowski W, Sue M, Bornstein SR. The adrenal gland microenvironment in health, disease and during regeneration. Hormones (Athens) 2017;16(3):251-65.##Espinosa Reyes TM, Collazo Mesa T, Lantigua Cruz PA, Agramonte Machado A, Dom&#237;nguez Alonso E, Falhammar H. Molecular diagnosis of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. BMC Endocr Disord. 2020;20(1):165.##Turcu AF, Auchus RJ. The next 150 years of congenital adrenal hyperplasia. J Steroid Biochem Mol Biol Sep 1;153:63-71.##Dumić M. [Congenital adrenal hyperplasia due to 21-hydroxylase enzyme deficiency]. Lijec Vjesn 1996 Mar:118 Suppl 1:13-6. Croatian.##Held PK, Bird IM, Heather NL. Newborn screening for congenital adrenal hyperplasia: Review of factors affecting screening accuracy. Int J Neonatal Screen 2020;6(3):67.##Miller WL. Congenital adrenal hyperplasia: Time to replace 17OHP with 21-deoxycortisol. Horm Res Paediatr 2019;91(6):416-20.##Baumgartner-Parzer S, Witsch-Baumgartner M, Hoeppner W. EMQN best practice guidelines for molecular genetic testing and reporting of 21-hydroxylase deficiency. Eur J Hum Genet 2020;28(10):1341-67.##Xu Z, Chen W, Merke DP, McDonnell NB. Comprehensive mutation analysis of the CYP21A2 gene: An efficient multistep approach to the molecular diagnosis of congenital adrenal hyperplasia. J Mol Diagn 2013 Nov;15(6):745-53.##Gitelman SE, Bristow J, Miller WL. Mechanism and consequences of the duplication of the human C4/P450c21/gene X locus. Mol Cell Biol 1992;12(5):2124-34.##Yang Z, Mendoza AR, Welch TR, Zipf WB, Yung Yu C. Modular variations of the human major histocompatibility complex class III genes for serine/threonine kinase RP, complement component C4, steroid 21-hydroxylase CYP21, and tenascin TNX (the RCCX module): A mechanism for gene deletions and disease associat. J Biol Chem 1999;274(17):12147-56.##Lee HH. The chimeric CYP21P/CYP21 gene and 21-hydroxylase deficiency. J Hum Genet 2004;49(2):65-72.##Higashi Y, Yoshioka H, Yamane M, Gotoht O, Fujm-Kuriyama Y. Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: A pseudogene and a genuine gene. Proc Natl Acad Sci USA 1986 May;83(9):2841-5.##Falhammar H, Nordenstr&#246;m A. Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome. Endocrine 2015 Sep;50(1):32-50.##Ghizzoni L, Cappa M, Chrousos G, Loche S, Maghnie M. Molecular Genetics of 21-Hydroxylase Deficiency. Vol. 20, Endocr Dev. Basel, Karger. 2011. P. 80-7.##Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An endocrine society* clinical practice guideline. J Clin Endocrinol Metab 2018 Nov 1;103(11):4043-88.##Lee HH, Lee YJ, Lin CY. PCR-based detection of the CYP21 deletion and TNXA/TNXB hybrid in the RCCX module. Genomics 2004 May 1;83(5):944-50.##Choi Y, Sims GE, Murphy S, Miller JR, Chan AP. Predicting the functional effect of amino acid substitutions and indels. PLoS One 2012 Oct 8;7(10):e46688.##Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods 2010 Apr;7(4):248-9.##Vakili R, Baradaran-Heravi A, Barid-Fatehi B, Gholamin M, Ghaemi N, Abbaszadegan MR. Molecular analysis of the CYP21 gene and prenatal diagnosis in families with 21-hydroxylase deficiency in Northeastern Iran. Horm Res 2005 Apr;63(3):119-24.##Ramazani A, Kahrizi K, Razaghiazar M, Mahdieh N, Koppens P. The frequency of eight common point mutations in CYP21 gene in Iranian patients with congenital adrenal hyperplasia. IBJ 2008;12(1): 49-53.##Rabbani B, Akbari MT, Mahdieh N, Zaridust E, Ashtiani MTH, Lee HH, et al. Homozygous complete deletion of CYP21A2 causes a simple virilizing phenotype in an Azeri child. Asian Biomedicine 2011 Dec;5(6):889-92.##Rabbani B, Mahdieh N, Ashtiani MTH, Larijani B, Akbari MT, New M, et al. Mutation analysis of the CYP21A2 gene in the Iranian population. Genet Test Mol Biomarkers 2012 Feb 1;16(2):82-90.##Forouzanfar K, Seifi M, Hashemi-Gorji F, Karimi N, Estiar MA, Karimoei M, et al. Mutation analysis of the CYP21A2 gene in congenital adrenal hyperplasia. Cell Mol Biol 2015;61(4):51-5.##Kolahdouz M, Hashemipour M, Khanahmad H, Rabbani B, Salehi M, Rabbani A, et al. Mutation detection of CYP21A2 gene in nonclassical congenital adrenal hyperplasia patients with premature pubarche. Adv Biomed Res 2016;5(1):33.##Kollahi NA, Rohani F, Baghbani-Arani F, Shojaei A. Complex alleles of cyp21a2 are the most frequent causes of congenital adrenal hyperplasia in Iranian population. Iran J Pediatr 2019 Dec 1;29(6).##Soveizi M, Mahdieh N, Setoodeh A, Sayarifard F, Abbasi F, Bose HS, et al. P.Gln318X and p.Val281Leu as the Major Variants of CYP21A2 Gene in Children with Idiopathic Premature Pubarche. Int J Endocrinol 2020;2020:4329791.##Claahsen - van der Grinten HL, Speiser PW, Ahmed SF, Arlt W, Auchus RJ, Falhammar H, et al. Congenital adrenal hyperplasia-current insights in pathophysiology, diagnostics, and management. Endocr Rev 2022 Jan 12;43(1):91-159.##Narasimhan ML, Khattab A. Genetics of congenital adrenal hyperplasia and genotype-phenotype correlation. Fertil Steril 2019;111(1):24-9.##Witchel SF, Azziz R. Nonclassic congenital adrenal hyperplasia. Int J Pediatr Endocrinol 2010;2010:625105.##Higashi Y, Tanaet A, Inoue H, Hiromasa T, Fujii-Kuriyama Y. Aberrant splicing and missense mutations cause steroid 21-hydroxylase [P-450(C21)] deficiency in humans: Possible gene conversion products. Proc Natl Acad Sci USA 1988 Oct;85(20):7486-90.##Lee HH, Chang SF, Tsai FJ, Tsai LP, Lin CY. Mutation of IVS2-12A/C&gt;G in combination with 707-714delGAGACTAC in the CYP21 gene is caused by deletion of the C4-CYP21 repeat module with steroid 21-hydroxylase deficiency. J Clin Endocrinol Metab 2003 Jun;88(6):2726-9.##Riedl S, R&#246;hl FW, Bonfig W, Br&#228;mswig J, Richter-Unruh A, Fricke-Otto S, et al. Genotype/phenotype correlations in 538 congenital adrenal hyperplasia patients from Germany and Austria: Discordances in milder genotypes and in screened versus prescreening patients. Endocr Connect 2019;8(2):86-94.##Tajima T, Fujieda K, Fujii-Kuriyama Y. de novo mutation causes steroid 21-hydroxylase deficiency in one family of HLA-identical affected and unaffected siblings. J Clin Endocrinol Metab 1993 Jul;77(1):86-9.##Ezquieta B, Cueva E, Oyarz&#225;bal M, Oliver A, Varela JM, Jariego C. Gene conversion (655G splicing mutation) and the founder effect (Gln318Stop) contribute to the most frequent severe point mutations in congenital adrenal hyperplasia (21-hydroxylase deficiency) in the Spanish population. Clin Genet 2002 Aug;62(2):181-8.##Globerman H, Amor M, Parker KL, New MI, White PC. Nonsense mutation causing steroid 21-hydroxylase deficiency. J Clin Invest 1988;82(1):139-44.##Kleinle S, Lang R, Fischer GF, Vierhapper H, Waldhauser F, F&#246;dinger M, et al. Duplications of the functional CYP21A2 gene are primarily restricted to Q318X alleles: Evidence for a founder effect. J Clin Endocrinol Metab 2009;94(10):3954-8.##Prado MJ, de Castro SM, Kopacek C, de Mello MP, Rispoli T, Grandi T, et al. Development of CYP21A2 Genotyping Assay for the Diagnosis of Congenital Adrenal Hyperplasia. Mol Diagn Ther 2017;21(6):663-75.##Saadat M, Ansari-Lari M, Farhud DD. Consanguineous marriage in Iran. Ann Hum Biol 2004;31(2):263-9.##Koohiyan M, Azadegan-Dehkordi F, Koohian F, Hashemzadeh-Chaleshtori M. Genetics of hearing loss in north Iran population: An update of spectrum and frequency of GJB2 mutations J Audiol Otol 2019 Oct;23(4):175-180.##</REF>
        </REFRENCE>
    </REFRENCES>
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