New Biomarkers in Early Diagnosis of Acute Kidney Injury in Children 2 2 Acute Kidney Injury (AKI) is a common condition with a high risk of mortality and morbidity, so, early diagnosis and management of AKI is very important in clinical practice. Despite significant progress in the management of AKI, it still carries high morbidity and mortality. BUN and serum creatinine are not very sensitive nor specific for the diagnosis of AKI because they are affected by many renal and non-renal factors that are independent of kidney injury or kidney function and change significantly only after significant kidney injury and with a substantial time delay. Detection of biomarkers of AKI made predominantly by the injured kidney tissue are essential for the early diagnosis of AKI. An ideal biomarker should be one that could be easily measured, with no interference with other biologic variables, and be able to clarify early phases of kidney damage. The most common biomarkers studied are Neutrophil Gelatinase-Associated Lipocalin (NGAL), Interleukin-18 (IL-18), Kidney Injury Molecule-1 (KIM-1), Cystatin-C, L type Fatty Acid-Binding Protein (L-FABP), N-Acetyl- β-D Glucosaminidase (NAG), netrin-1, vanin-1, and Monocyte Chemoattractant Protein-1 (MCP-1) and calprotectin. 264 269 Behnaz Bazargani Pediatric Chronic Kidney Disease Research Center, Department of Pediatric Nephrology, Children Medical Center Hospital, Tehran University of Medical Sciences Pediatric Chronic Kidney Disease Research Center, Department of Pediatric Nephrology, Children Medical Center Hospital, Tehran University of Medical Sciences Iran Mastaneh Moghtaderi Acute kidney injuryBiomarkerCalprotectinCystatin CInterleukin-18KIM-1NGAL 60513.pdf Stevens LA, Lafayette RA, Perrone RD, et al. Laboratory evaluation of kidney function. In: Schrier, RW., editor. Diseases of the Kidney and Urinary Tract Vol 1-3. 8th ed. 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Antibodies Produced Toward Recombinant RBD and Nucleocapsid Neutralize SARS-COV-2 2 2 Background: The highly contagious SARS-COV-2 virus spread rapidly from China and formed a global pandemic. The virus has infected over 509 million people worldwide and killed about 6.32 million up to date. Up on invasion, the Receptor Binding Domain (RBD) of Spike protein plays a crucial role in the entry of the virus into the host cell. The virus N protein is another protein that has a critical role for genome packaging. Methods: As bioinformatics approaches, the cassette design, codon adaptation, and protein stability were investigated in this study. Synthetic genes of RBD and N were cloned separately in pET28a + expression vector. They were transferred into Escherichia coli (E. coli) BL21 DE3 host cell, and expression of recombinant proteins was induced with IPTG. The recombinant proteins were purified by column chromatography and approved by Western blotting. Animal immunization was performed with each of the recombinant proteins individually and in combination of the two. The antibody titer of the blood serum from control and immunized mice groups was determined by ELISA technique. Finally, the anti-spike neutralization test was performed. Results: The expression and purification of RBD protein were monitored on SDS-PAGE, two bands of about 28 and 45 kDa for RBD and N appeared on gel distinctly, which were further validated by Western blotting. According to ELISA results, related antibodies were traced to a dilution of 1/64000 in immunized sera. The neutralization test exhibited produced antibodies' potency to bind the virus proteins. Using SPSS software, statistical analysis was performed by Duncan's test and T-test. Conclusion: According to the present study, recombinant proteins, either RBD alone or in combination with N adequately stimulated the immune response, and the raised antibodies could neutralize the virus in in vitro test. 270 277 Amir Rezaei Department of Biology, Shahed University Department of Biology, Shahed University Iran Shahram Nazarian Hossein Samiei Abianeh Department of Biology, Imam Hussein University Department of Biology, Imam Hussein University Iran Emad Kordbacheh Department of Biology, Imam Hussein University Department of Biology, Imam Hussein University Iran Zahra Alizadeh Department of Biology, Shahed University Department of Biology, Shahed University Iran Seyed Latif Mousavi Gargari CoronavirusNucleocapsidRecombinant vaccinesSARS-CoV-2Spike glycoprotein 60514.pdf Kahn JS, McIntosh K. History and recent advances in coronavirus discovery. Pediatr Infect Dis J 2005;24(11 Suppl):S223-7, discussion S6.##Mahase E. 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A Panel of Circulating microRNAs as a Potential Biomarker for the Early Detection of Gastric Cancer 2 2 Background: The high mortality rate of Gastric Cancer (GC) is a consequence of delayed diagnosis. The early diagnosis of GC could increase the five-year survival rate among patients. We aimed to find a panel of microRNAs (miRNA) for the detection of GC in the early stages. Methods: In this case-control study, we selected consistently upregulated miRNAs from the results of 12 high-throughput miRNA profiling studies in GC. In the profiling phase, the differential expressions of 13 candidate miRNAs were analyzed by quantitative reverse-transcription PCR (qRT-PCR) in two pooled RNA samples prepared from the plasma of eight GC patients and eight matched controls. In the validation phase, significantly upregulated miRNAs from the profiling phase were further evaluated in the plasma samples of 97 patients with stage I-IV gastric adenocarcinoma and 100 healthy controls. Results: In the profiling phase, six miRNAs (miR-18a, 21, 25, 92a, 125b and 221) were significantly upregulated in the GC patients compared to the controls (p<0.05). However, in the validation phase, only significant up-regulation of miR-18a, 21 and 125b was confirmed (p<0.05). A panel of miR-18a/21/125b was able to detect GC patients with stage I-IV from the controls (p<0.001; AUC=0.92, sensitivity=86%; specificity=85%). In addition, the panel could distinguish the early-stage GC (I+II) from the control group with an AUC of 0.83, a sensitivity of 83%, and a specificity of 75%. Conclusion: A panel of circulating miR18a/21/125b could be suggested as a potential biomarker for the early detection of GC. 278 286 Kioomars Saliminejad Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical SciencesReproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences IranIran Habibollah Mahmoodzadeh Department of Surgery, Cancer Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences Department of Surgery, Cancer Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences Iran Shahrzad Soleymani Fard Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences Iran Marjan Yaghmaei Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences Iran Hamid Reza Khorram Khorshid Genetics Research Center, University of Social Welfare and Rehabilitation Sciences Iran Seyed Asadollah Mousavi Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences Iran Mohammad Vaezi Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences Iran Seyed Hamidollah Ghaffari BiomarkerCirculating microRNADetectionGastric cancerGene expression 60515.pdf Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. 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Bioactive Materials Derived from Menstrual Blood Stem Cells Enhance the Quality of In Vitro Bovine Embryos 2 2 Backgrounds: The aim of this study was to determine whether the addition of bioactive materials derived from Menstrual Blood Stem Cells (MenSCs) to the oocyte maturation medium may improve the quality of bovine embryos in vitro. Methods: MenSCs were collected from 6 healthy women (between 26 and 36 years old) and after 3 days of culture, their bioactive materials were frozen. The bovine Cumulus-Oocyte-Complexes (COCs) were aspirated from ovarian slaughterhouse and the oocytes with more than three layers of cumulus cells were cultured in vitro in media supplemented with (treatment) and without (control) 10% MenSCs’ bioactive materials. After IVM/IVF, the presumptive zygotes were cultured for 8 days. Results: The blastocyst rate on day 8 in treatment group was higher than control (40.2±1.9 vs. 23±4.2.3, p=0.001). The ratio of Trophectoderm (TE) and Inner Cell Mass (ICM) (ICM/TE) cells was also greater in treatment group compared to control (30.3±2 vs. 14.9±1; p=0.001). The re-expansion of vitrified blastocysts, 24 hours after warming, in treatment group was higher than control (93.3±2.5 vs. 66.2±8.8; p=0.01). The expression of some genes related to pluripotency and implantation (OCT4, CDX2, and IFNT) were increased in treatment group compared to control (p<0/05). Conclusion: In conclusion, the addition of MenSCs’ bioactive materials during in vitro maturation of bovine oocytes could improve the quantity and quality of bovine IVP embryos. Also, the expression of some genes associated with pluripotency and implantation in the blastocyst would be increased. 287 293 Mohammad Sobhan Amini Department of Animal Science, Science and Research Branch, Islamic Azad UniversityReproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Department of Animal Science, Science and Research Branch, Islamic Azad University IranIran Mohammad Mehdi Naderi Abolfazl Shirazi Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Mehdi Aminafshar Department of Animal Science, Science and Research Branch, Islamic Azad University Department of Animal Science, Science and Research Branch, Islamic Azad University Iran Sara Borjian Boroujeni Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Mostafa Pournourali Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Ali Malekpour Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran BovineEmbryoIn vitro productionIVMMenstrual blood stem cells 60516.pdf Moore SG, Hasler JF. A 100-Year Review: Reproductive technologies in dairy science. J Dairy Sci 2017;100(12):10314-31.##Nejat-Dehkordi S, Ahmadi E, Shirazi A, Nazari H, Shams-Esfandabadi N. Embryo co-culture with bovine amniotic membrane stem cells can enhance the cryo-survival of IVF-derived bovine blastocysts comparable with co-culture with bovine oviduct epithelial cells. Zygote 2021;29(2):102-7.##Shadmanesh A, Nazari H, Shirazi A, Ahmadi E, Shams-Esfandabadi N. Human amniotic membrane stem cells' conditioned medium has better support for in-vitro production of bovine embryos than FBS. Reprod Domest Anim 2022;57(2):173-84.##Sena-Netto SB, Sprícigo JFW, Leme LO, Guimarães ALS, Caixeta FMC, Dode MAN, et al. The replacement of fetal bovine serum with bovine serum albumin during oocyte maturation and embryo culture does not improve blastocyst quality after slow freezing cryopreservation. Biopreserv Biobank 2020;18(3):171-9.##Holm P, Callesen H. In vivo versus in vitro produced bovine ova: similarities and differences relevant for practical application. Reprod Nutr Dev 1998;38(6):579-94.##Thompson JG. Comparison between in vivo derived and in vitro produced pre-elongation embryos from domestic ruminants. Reprod Fertil Dev 1997;9(3):341-54.##Richter KS. The importance of growth factors for preimplantation embryo development and in vitro culture. Curr Opin Obstet Gynecol 2008;20(3):292-304.##Meng X, Ichim TE, Zhong J, Rogers A, Yin Z, Jackson J, et al. Endometrial regenerative cells: a novel stem cell population. J Transl Med 2007;5:57.##Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA 2004;292(1):81-5.##Gang EJ, Bosnakovski D, Figueiredo CA, Visser JW, Perlingeiro RC. SSEA-4 identifies mesenchymal; stem cells from bone marrow. Blood 2007;109(4):1743-51.##Greco SJ, Liu K, Rameshwar P. Functional similarities among genes regulated by OCT4 in human mesenchymal and embryonic stem cells. Stem Cells 2007;25(12):3143-54.##Yao S, Chen S, Clark J, Hao E, Beattie GM, Hayek A, et al. Long-term self-renewal and directed differentiation of human embryonic stem cells in chemically defined conditions. Proc Natl Acad Sci USA 2006;103(18):6907-12.##Khoury M, Alcayaga-Miranda F, Illanes SE, Figueroa FE. The promising potential of menstrual stem cells for antenatal diagnosis and cell therapy. Front Immunol 2014; 5:205.##Liu Y, Niu R, Li W, Lin J, Stamm C, Steinhoff G, Ma N. Therapeutic potential of menstrual blood-derived endometrial stem cells in cardiac diseases. Cell Mol Life Sci 2019;76(9):1681-95.##Wu X, Luo Y, Chen J, Pan R, Xiang B, Du X, et al. Transplantation of human menstrual blood progenitor cells improves hyperglycemia by promoting endogenous progenitor differentiation in type 1 diabetic mice. Stem Cells Dev 2014;23(11):1245-57.##Farahavar A, Shirazi A, Kohram H, Zareh Shahneh A, Sarvari A, Naderi MM, et al. Culture of ovine IVM/IVF zygotes in isolated mouse oviduct: effect of basal medium. Avicenna J Med Biotechnol 2013;5(2):133-7.##Jeong YJ, Choi HW, Shin HS, Cui XS, Kim NH, Gerton GL, et al. Optimization of real time RT-PCR methods for the analysis of gene expression in mouse eggs and preimplantation embryos. Mol Reprod Dev 2005;71(3):284-9.##Bevers MM, Dieleman SJ, Vandeb Hurk R. Regulation and modulation of oocyte maturation in the bovine. Theriogenology 1997;47(1):13-22.##Wan Y, Li D, Deng M, Liu Z, Liu L, Wang F. Comprehensive transcriptome analysis of mRNA expression patterns of early embryo development in goat under hypoxic and normoxic conditions. Biology (Basel) 2021;10(5):381.##Van Soom A, Yuan YQ, Peelman LJ, de Matos DG, Dewulf J, Laevens H, et al. 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Evaluation of PLGA-Encapsulated Recombinant GroEL of S. typhi immune Responses Against Enterohaemorrhagic and Enteropathogenic Escherichia coli 2 2 Background: Heat Shock Proteins (HSPs) elicit humoral and cellular immune responses. Due to their high sequence homology, they can be developed as a new immunogen for cross prophylactic and vaccination effects against infectious agents such as Enteropathogenic and Enterohemorrhagic Escherichia coli (EPEC and EHEC). This study aimed to evaluate the immunogenicity and cross-protective efficacy of rGroEL of Salmonella typhi (S. typhi) encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles against EPEC and EHEC. Methods: Recombinant GroEL was expressed in Escherichia coli (E. coli) and purified using Ni-NTA affinity chromatography. The protein was encapsulated in PLGA by the double emulsion method, and the nanoparticles were characterized physicochemically. BALB/c mice were immunized, and the efficacy of the protein to elicit immune responses was assessed. Results: Over-expression in E. coli led to corresponding 64.5 kDa protein bands in Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis (SDS-PAGE). Non-ag-gregated nanoparticles had a spherical shape with a mean diameter of 194.3±3 nm and encapsulation efficiency of 89.5±2.5%. Antibody isotyping revealed that GroEL immunization induced both IgG1 and IgG2a antibodies. Moreover, immunization of the mice with recombinant GroEL protein conferred 80 and 60% protection against lethal infections by EPEC and EHEC, respectively. Furthermore, organ burden studies revealed a significant reduction in infection in the immunized mice compared to the non-immunized ones. Passive immunization with anti-GroEL sera also protected 50% of the mice against the lethal doses of EHEC and EPEC strains. Conclusion: The findings indicated that immunization of the mice with recombinant GroEL of S. typhi elicited cross-protection against other bacterial infections. This represented the immense potential of GroEL to be developed as a single vaccine against multiple pathogens 294 302 Milad Parvane Biology Research Center, Faculty of Basic Sciences, Imam Hossein University Biology Research Center, Faculty of Basic Sciences, Imam Hossein University Iran Shahram Nazarian Emad Kordbacheh Biology Research Center, Faculty of Basic Sciences, Imam Hossein University Biology Research Center, Faculty of Basic Sciences, Imam Hossein University Iran Javad Fathi Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical SciencesStudent Research Committee, School of Medicine, Shiraz University of Medical Sciences Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical SciencesStudent Research Committee, School of Medicine, Shiraz University of Medical Sciences IranIran Mohamad Ebrahim Minae Mohammad Reza Ramezani Biology Research Center, Faculty of Basic Sciences, Imam Hossein University Biology Research Center, Faculty of Basic Sciences, Imam Hossein University Iran Heat-shock proteinsImmunogenicityNanoparticlesSalmonella typhiVaccines 60517.pdf Rojas-Lopez M, Monterio R, Pizza M, Desvaux M, Rosini R. Intestinal pathogenic Escherichia coli: Insights for vaccine development. Front Microbiol 2018;9:440.##Felegary A, Nazarian S, Kordbacheh E, Fathi J, Minae ME. An approach to chimeric subunit immunogen provides efficient protection against toxicity, type III and type v secretion systems of Shigella. Int Immunopharmacol 2021;100:108132.##Fathi J, Kordbacheh E, Hadi N, Nazarian S. An in silico design, expression and purification of a chimeric protein as an immunogen candidate consisting of IpaD, StxB, and TolC proteins from Shigella spp. Avicenna J Med Biotechnol 2022;14(3):247-58.##Gohar A, Abdeltawab NF, Fahmy A, Amin MA. Development of safe, effective and immunogenic vaccine candidate for diarrheagenic Escherichia coli main pathotypes in a mouse model. BMC Res Notes 2016;9(1):90.##Vansofla AN, Nazarian S, Kordbache E, Fathi J. An IgG/IgY sandwich-ELISA for the detection of heat-labile enterotoxin B subunit of enterotoxigenic Escherichia coli. Gene Reports 2021;23(9):101099.##Fathi J, Ebrahimi F, Nazarian S, Tarverdizade Y. Purification of Shiga-like toxin from Escherichia coli O157: H7 by a simple method. J Applied Biotechnol Rep 2017;4(4):707-11.##Taheri M, Nazarian S, Ebrahimi F, Bakhshi M, Fathi J. Immunogenic evaluation of recombinant chimeric protein containing EspA-Stx2b-Intimin against E. coli O157 H7. Sci J Kurdistan Univ Med Sci 2018;22(6):49-62.##Kordbacheh E, Nazarian S, Hajizade A, Farhang A. Entrapment of HETS recombinant protein onto PLGA and alginate NPs improves the immunogenicity of the protein against E. coli O157: H7. Mol Immunol 2019;114:612-9.##Rahimi Z, Malekzadegan Y, Bahador A, Azimzadeh M, Haghighi MA. Phylogenetic study, distribution of virulence genes and antibiotic resistance profiles of Escherichia coli isolated from Bushehr coastal water. Gene Reports 2022;26:101473.##García A, Fox JG. A one health perspective for defining and deciphering Escherichia coli pathogenic potential in multiple hosts. Comp Med 2021;71(1):3-45.##Fathi J, Ebrahimi F, Nazarian S, Hajizade A, Malekzadegan Y, Abdi A. Production of egg yolk antibody (IgY) against shiga-like toxin (stx) and evaluation of its prophylaxis potency in mice. Microb Pathog 2020;145:104199.##Kordbacheh E, Nazarian S, Hajizadeh A, Fasihi-Ramandi M, Fathi J. Recombinant HcpA-EspA-Tir-Stx2B chimeric protein induces immunity against attachment and toxicity of Escherichia coli O157: H7. Microb Pathog 2019;129:176-82.##Theri M, Nazarian S, Ebrahimi F, Bakhshi M, Fathi J. [Immunization evaluation of type III secretion system recombinant antigens and Shiga like toxin binding subunit of E. coli O157: H7]. J Babol Univ Med Sci 2018;20(7):47-54. Persian.##O'Neil PT, Machen AJ, Deatherage BC, Trecazzi C, Tischer A, Machha VR, et al. The chaperonin GroEL: a versatile tool for applied biotechnology platforms. 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Comparative Antioxidant and Anti-gout Activities of Citrullus colocynthis loaded Fruit Silver nanoparticles with its Ethanolic extract 2 2 Background: The biological synthesis of silver nanoparticles (AgNPs) using plant materials is a rapidly developing method with several alternative medical applications. This comparative study of ethanolic fruit extract of Citrullus colocynthis (C. colocynthis) (EFECC) and synthesized silver nanoparticles (CC-AgNPs) were carried out for antioxidants and anti-gout arthritic activities. Methods: The AgNPs were synthesized using C. colocynthis fruit and its characterization was done by UV-visible spectroscopy, TEM, XRD and FT-IR. The 90% ethanol was used for extract preparation. Antioxidant activity was analyzed by DPPH and the Hydrogen Peroxide (H2O2) method. In vitro anti-arthritic activity was tested by xanthine oxidase inhibition, protein denaturation and HRBC membrane stabilization assay. Results: The synthesized CC-AgNPs were confirmed by UV-vis spectroscopy and TEM images displayed spherical shapes with 10-45 nm size range. Furthermore, the functional groups and crystalline structure of CC-AgNPs were determined by FT-IR and XRD analysis. The biosynthesized CC-AgNPs exhibited an excellent free radical scavenging ability than EFECC. In anti-arthritic activity, the CC-AgNPs showed effective inhibition of xanthine oxidase production, protein denaturation, and damaged RBC membranes compared to EFECC. Conclusion: The antioxidant activities and in vitro anti-arthritic assays revealed that CC-AgNPs are better anti-gout agents than EFECC. This research suggested that biosynthesized silver nanoparticles from C. colocynthis fruit are an important target in the field of anti-gout drug discovery. 303 309 Suganya Karunakaran Department of Biotechnology, Dr. MGR Educational & Research Institute, deemed to be University, Maduravoyal Department of Biotechnology, Dr. MGR Educational & Research Institute, deemed to be University, Maduravoyal India Rajeswary Hari Citrullus colocynthisMetal nanoparticlesSilverSpectrophotometryUltravioletXanthine oxidase 60518.pdf Petchi RR, Vijaya C, Parasuraman S. Anti-arthritic activity of ethanolic extract of Tridax procumbens (Linn.) in Sprague Dawley rats. Pharmacognosy Res 2013;5(2):113-7.##Alamgeer, Uttra AM, Hasan UH. Anti-arthritic activity of aqueous-methanolic extract and various fractions of Berberis orthobotrys Bien ex Aitch. BMC Complement Altern Med 2017;17(1):371.##Laev SS, Salakhutdinov NF. Anti-arthritic agents: progress and potential. Bioorg Med Chem 2015;23(13):3059-80.##Kamel KM, Gad AM, Mansour SM, Safar MM, Fawzy HM. Novel anti-arthritic mechanisms of Polydatin in complete Freund’s adjuvant-induced arthritis in rats: involvement of IL-6, STAT-3, IL-17, and NF-кB. Inflammation 2018;41(5):1974-86.##Arya V, Gupta VK, Kaur R. A review on plants having anti-arthritic potential. Int J Pharm Sci Rev Res 2011;7(2):131-6.##Choudhary M, Kumar V, Malhotra H, Singh S. Medicinal plants with potential anti-arthritic activity. J Intercult Ethnopharmacol 2015;4(2):147-79.##El-Seedi HR, El-Shabasy RM, Khalifa SA, Saeed A, Shah A, Shah R, et al. Metal nanoparticles fabricated by green chemistry using natural extracts: Biosynthesis, mechanisms, and applications. RSC Adv. 2019;9(42):24539-59.##Sadeghi B, Gholamhoseinpoor F. A study on the stability and green synthesis of silver nanoparticles using Ziziphora tenuior (Zt) extract at room temperature. Spectrochim Acta A Mol Biomol Spectrosc 2015;134:310-5.##Vijayaraj R, Kumar KN, Mani P, Senthil J, Kumar GD, Jayaseelan T. Green synthesis of silver nanoparticles from ethanolic seed extract of Acranythes aspera (Linn.) and its anti-inflammatory activities. Int J Pharm Ther 2016;7:42-8.##Baraka A, Dickson S, Gobara M, El-Sayyad GS, Zorainy M, Awaad MI, et al. Synthesis of silver nanoparticles using natural pigments extracted from Alfalfa leaves and its use for antimicrobial activity. Chem Pap 2017;71(11):2271-81.##Chouaibi M, Rigane K, Ferrari G. Extraction of Citrullus colocynthis L. seed oil by supercritical carbon dioxide process using response surface methodology (RSM) and artificial neural network (ANN) approaches. Industrial Crops and Products 2020;158:113002.##Perveen S, Ashfaq H, Ambreen S, Ashfaq I, Kanwal Z, Tayyeb A. Methanolic extract of Citrullus colocynthis suppresses growth and proliferation of breast cancer cells through regulation of cell cycle. Saudi J Biolol Sci 2021;28(1):879-86.##Kapoor M, Kaur N, Sharma C, Kaur G, Kaur R, Batra K, et al. Citrullus colocynthis an important plant in Indian traditional system of medicine. Pharmacogn Rev 2020;14(27):22-7.##Hussain AI, Rathore HA, Sattar MZ, Chatha SA, Sarker SD, Gilani AH. Citrullus colocynthis (L.) Schrad (bitter apple fruit): A review of its phytochemistry, pharmacology, traditional uses and nutritional potential. J Ethnopharmacol 2014 8;155(1):54-66.##Satyavani K, Gurudeeban S, Ramanathan T, Balasubramanian T. Biomedical potential of silver nanoparticles synthesized from calli cells of Citrullus colocynthis (L.) Schrad. J Nanobiotechnology 2011;9:43.##Sandhiya V, Thirunavukkarasu P, Gomathy B, Sridhar M, Rajeshkumar S, Ravi M, et al. Agnp-Hp synthesized using red marine algae Halymenia pseudofloresii and its pharmacological activities. Annals of the Romanian Society for Cell Biology 2021;25(6):19433-50.##Rifaath M, Kavitha S, Vishnupriya V, Selvaraj J, Gayathri R. An in vitro analysis on the antioxidant and antigout activity of ethanolic leaf extract of Mentha Piperita Linn. NVEO-NATURAL VOLATILES & ESSENTIAL OILS Journal| NVEO 2021;11:6378-86.##Chaithanya MV, Maheswari TU, Rajeshkumar S. Anti-inflammatory and antioxidant activity of lycopene, raspberry, green tea herbal formulation mediated silver nanoparticle. J Indian Acad Oral Med Radiol 2021;33(4):397-400.##Suganya K, Hari R, Chokkalinagam P, Baskaran P, Maheswaran S, Singh M, et al. Anti-gout arthritic activities of ethanolic and zinc oxide nanoparticle extracts of Citrullus colocynthis-An In vitro and Insilico studies. Annals of the Romanian Society for Cell Biology 2021;25(3):8020-33.##Mohanty AS, Jena BS. Innate catalytic and free radical scavenging activities of silver nanoparticles synthesized using Dillenia indica bark extract. J Colloid Interface Sci 2017;496:513-21.##Kharat SN, Mendhulkar VD. Synthesis, characterization and studies on antioxidant activity of silver nanoparticles using Elephantopus scaber leaf extract. Mater Sci Eng C Mater Biol Appl 2016;62:719-24.##Vilas V, Philip D, Mathew J. Essential oil mediated synthesis of silver nanocrystals for environmental, anti-microbial and antioxidant applications. Mater Sci Eng C Mater Biol Appl 2016;61:429-36.##Kalpana VN, Payel C, Rajeswari VD. Lagenaria siceraria aided green synthesis of ZnO NPs: anti-dandruff, anti-microbial and anti-arthritic activity. Res J Chemistry Environment 2017;21(11):14-9.##Palani T, Shobha K, Thirunavukkarasu P, Hari R. In vitro and in silico antigout arthritic activities of ethanolic and aqueous stem extracts of Cissus quadrangularis-A TLR2 and TLR4 receptor approach. J Applied Pharmaceutical Science 2018;8(9):015-22.##Viswanathan S, Palaniyandi T, Shanmugam R, Tharani M, Rajendran BK, et al. Biomedical potential of silver nanoparticles capped with active ingredients of Hypnea valentiae, red algae species. Particulate Science and Technology 2022;40(6):686-96.##Salari S, Bahabadi SE, Samzadeh-Kermani A, Yosefzaei F. In-vitro evaluation of antioxidant and antibacterial potential of green synthesized silver nanoparticles using Prosopis farcta fruit extract. Iran J Pharm Res 2019;18(1):430-5.##Govindappa M, Hemashekhar B, Arthikala MK, Rai VR, Ramachandra YL. Characterization, antibacterial, antioxidant, antidiabetic, anti-inflammatory and antityrosinase activity of green synthesized silver nanoparticles using Calophyllum tomentosum leaves extract. Results in Physics 2018;9:400-8.##Ramaswamy M, Solaimuthu C, Duraikannu S. Antiarthritic activity of synthesized silver nanoparticles from aqueous extract of Moringa concanensis Nimmo leaves against FCA induced rheumatic arthritis in rats. Drug Delivery Therapeutics 2019;9(3):66-75.##Hosseinikhah SM, Barani M, Rahdar A, Madry H, Arshad R, Mohammadzadeh V, et al. Nanomaterials for the diagnosis and treatment of inflammatory arthritis. Int J Mol Sci 2021;22(6):3092.##Zhang S, Wu L, Cao J, Wang K, Ge Y, Ma W, et al. Effect of magnetic nanoparticles size on rheumatoid arthritis targeting and photothermal therapy. Colloids Surf B Biointerfaces 2018;170:224-32.##Gautam RK, Sharma S, Sharma K, Gupta G. Evaluation of antiarthritic activity of butanol fraction of Punica granatum Linn. Rind extract against Freund’s complete adjuvant-induced arthritis in rats. J Environ Pathol Toxicol Oncol 2018;37(1):53-62.##Kiyani MM, Sohail MF, Shahnaz G, Rehman H, Akhtar MF, Nawaz I, et al. Evaluation of turmeric nanoparticles as anti-gout agent: modernization of a traditional drug. Medicina (Kaunas) 2019;55(1):10.##Biswal B. Standardization protocol development of hydroalcoholic extract of fruits of Citrullus Colocynthis against anti-arthritic activity. International Journal of Green Pharmacy (IJGP) 2016 Mar 5;10(1).##Mani A, Vasanthi C, Gopal V, Chellathai D. Role of phyto-stabilised silver nanoparticles in suppressing adjuvant induced arthritis in rats. Int Immunopharmacol 2016;41:17-23.##

Association between PTCH1 and RAD54B Single-Nucleotide Polymorphisms and Non-syndromic Orofacial Clefts in the Northeast Population of Iran 2 2 Background: Non-Syndromic Cleft Lip with or without cleft Palate (NSCL/P) is a common developmental disorder of the head and neck with a multifactorial etiology. The current study aimed to evaluate the potential association of PTCH1 (rs10512248) and RAD54B (rs12681366) polymorphisms with NSCL/P in the Northeast Iranian population. Methods: In the present study, blood samples were taken from 122 subjects with NSCL/P and 161 healthy controls. Polymerase Chain Reaction (PCR) followed by Restriction Fragment Length Polymorphism (RFLP) were used to conduct genotyping of single-nucleotide polymorphisms. Results: Although differences were observed between cases and controls in rs10512248 and rs12681366, our data did not support a significant association of these polymorphisms with NSCL/P in our population. Conclusion: Our findings suggest that polymorphisms of rs10512248 and rs12681366 may not be potential risk factors for NSCL/P in the Northeast Iranian population due to the multifactorial and multiethnicity characteristics of some genes. 310 316 Reza Morvaridi Farimani Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences Department of Orthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences Iran Mohsen Azimi-Nezhad Non-Communicable Diseases Research Center, Neyshabur University of Medical SciencesUMR, INSERM U 1122, IGE-PCV, Interaction Géne-Environment Enpathophysiologie Cardiovasculaire, Université De Lorraine Non-Communicable Diseases Research Center, Neyshabur University of Medical SciencesUMR, INSERM U 1122, IGE-PCV, Interaction Géne-Environment Enpathophysiologie Cardiovasculaire, Université De Lorraine IranFrance Hamid Reza Khorram Khorshid Genetics Research Center, University of Social Welfare and Rehabilitation Sciences Genetics Research Center, University of Social Welfare and Rehabilitation Sciences Iran Asghar Ebadifar Dentofacial Deformities Research Center Research Institute of Dental Sciences, Faculty of Dentistry, Shahid Beheshti University of Medical Sciences Dentofacial Deformities Research Center Research Institute of Dental Sciences, Faculty of Dentistry, Shahid Beheshti University of Medical Sciences Iran Saba Tohidkhah Tehran University of Medical Sciences Tehran University of Medical Sciences Iran Zahra Jafarian Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences Iran Koorosh Kamali Department of Public Health, Faculty of Public Health, Zanjan University of Medical Sciences Department of Public Health, Faculty of Public Health, Zanjan University of Medical Sciences Iran Zeinab Nazari Non-Communicable Diseases Research Center, Neyshabur University of Medical Sciences Non-Communicable Diseases Research Center, Neyshabur University of Medical Sciences Iran Reza Ebrahimzadeh-Vesal Pardis Genetic Laboratory Iran Cleft lipCleft palatePolymorphismPTCH1RAD54B 60519.pdf Mangold E, Ludwig KU, Nöthen MM. Breakthroughs in the genetics of orofacial clefting. Trends Mol Med 2011;17(12):725-33.##Machado RA, Martelli-Junior H, Reis SRdA, Küchler EC, Scariot R, das Neves LT, et al. Identification of novel variants in cleft palate-associated genes in Brazilian patients with non-syndromic cleft palate only. Front Cell Dev Biol 2021;9:638522.##Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC. Cleft lip and palate. Lancet 2009;374(9703):1773-85.##van Rooij IA, Ludwig KU, Welzenbach J, Ishorst N, Thonissen M, Galesloot TE, et al. Non-syndromic cleft lip with or without cleft palate: genome-wide association study in europeans identifies a suggestive risk locus at 16p12. 1 and supports SH3PXD2A as a clefting susceptibility gene. Genes 2019;10(12):1023.##Auerkari EI, Bilynov Y, Yuniastuti M, Listyowati L, Sulistyani LD. Association of a polymorphism in the gene encoding methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) 1958G> A with orofacial cleft. Pesqui Bras Odontopediatria Clin Integr 2021;21:e5896.##Murthy J, Bhaskar L. Current concepts in genetics of nonsyndromic clefts. Indian J Plast Surg 2009;42(1):68-81.##Saber K, Amir Mansour S, Mozafar K, Farid N. Incidence of cleft lip and palate in Iran. A meta-analysis. Saudi Med J 2011;32:390-3.##Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet 2011;12(3):167-78.##Indencleef K, Roosenboom J, Hoskens H, White JD, Shriver MD, Richmond S, et al. Six NSCL/P loci show associations with normal-range craniofacial variation. Front Genet 2018;9:502.##Reynolds K, Zhang S, Sun B, Garland MA, Ji Y, Zhou CJ. Genetics and signaling mechanisms of orofacial clefts. Birth Defects Res 2020;112(19):1588-634.##Butali A, Mossey PA, Adeyemo WL, Eshete MA, Gowans LJ, Busch TD, et al. Genomic analyses in African populations identify novel risk loci for cleft palate. Hum Mol Genet 2019;28(6):1038-51.##Carter TC, Molloy AM, Pangilinan F, Troendle JF, Kirke PN, Conley MR, et al. Testing reported associations of genetic risk factors for oral clefts in a large Irish study population. Birth Defects Res A Clin Mol Teratol 2010;88(2):84-93.##Liu X, Yang S, Meng L, Chen C, Hui X, Jiang Y, et al. Association between PTCH1 and RAD54B single‐nucleotide polymorphisms and non‐syndromic orofacial clefts in a northern Chinese population. J Gene Med 2018;20(12):e3055.##Yu Y, Zuo X, He M, Gao J, Fu Y, Qin C, et al. Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity. Nat Commun 2017;8:14364.##Juriloff DM, Harris MJ, Mager DL, Gagnier L. Epigenetic mechanism causes Wnt9b deficiency and nonsyndromic cleft lip and palate in the A/WySn mouse strain. Birth Defects Res A Clin Mol Teratol 2014;100(10):772-88.##Riley BM, Mansilla MA, Ma J, Daack-Hirsch S, Maher BS, Raffensperger LM, et al. Impaired FGF signaling contributes to cleft lip and palate. Proc Natl Acad Sci USA 2007;104(11):4512-7.##Metzis V, Courtney AD, Kerr MC, Ferguson C, Rondón Galeano MC, Parton RG, et al. Patched1 is required in neural crest cells for the prevention of orofacial clefts. Hum Mol Genet 2013;22(24):5026-35.##Larsen AK, Mikkelsen DB, Hertz JM, Bygum A. Manifestations of Gorlin-Goltz syndrome. Dan Med J 2014;61(5):A4829.##Muzio LL. Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis 2008;3:32.##Nagai Y, Yamamoto Y, Yasuhara T, Hata K, Nishikawa T, Tanaka T, et al. High RAD54B expression: an independent predictor of postoperative distant recurrence in colorectal cancer patients. Oncotarget 2015;6(25):21064-73.##Qiao W, Huang P, Wang X, Meng L. Susceptibility to DNA damage caused by abrogation of Rad54 homolog B: A putative mechanism for chemically induced cleft palate. Toxicology 2021;456:152772.##Wang R, Li Y, Chen Y, Wang L, Wu Q, Guo Y, et al. Inhibition of RAD54B suppresses proliferation and promotes apoptosis in hepatoma cells. Oncol Rep 2018;40(3):1233-42.##Rivero ER, Neves AC, Silva-Valenzuela MG, Sousa SO, Nunes FD. Simple salting-out method for DNA extraction from formalin-fixed, paraffin-embedded tissues. Pathol Res Pract 2006;202(7):523-9.##Elahi MM, Jackson IT, Elahi O, Khan AH, Mubarak F, Tariq GB, et al. Epidemiology of cleft lip and cleft palate in Pakistan. Plast Reconstr Surg 2004;113(6):1548-55.##Rafighdoost H, Hashemi M, Danesh H, Bizhani F, Bahari G, Taheri M. Association of single nucleotide polymorphisms in AXIN2, BMP4, and IRF6 with Non-Syndromic Cleft Lip with or without Cleft Palate in a sample of the southeast Iranian population. J Appl Oral Sci 2017;25:650-6.##Soghani B, Ebadifar A, Khorshid HRK, Kamali K, Hamedi R, Moghadam FA. The study of association between reduced folate carrier 1 (RFC1) polymorphism and non-syndromic cleft lip/palate in Iranian population. BioImpacts 2017;7(4):263-8.##Ebadifar A, Ameli N, Khorramkhorshid HR, Zeinabadi MS, Kamali K, Khoshbakht T. Incidence assessment of MTHFR C677T and A1298C polymorphisms in Iranian non-syndromic cleft lip and/or palate patients. J Dent Res Dent Clin Dent Prospects 2015;9(2):101-4.##Rafighdoost H, Hashemi M, Narouei A, Eskanadri-Nasab E, Dashti-Khadivaki G, Taheri M. Association between CDH1 and MSX1 gene polymorphisms and the risk of nonsyndromic cleft lip and/or cleft palate in a southeast Iranian population. Cleft Palate Craniofac J 2013;50(5):98-104.##Rafiqdoost Z, Rafiqdoost A, Rafiqdoost H, Hashemi M, Khayatzadeh J, Eskandari-Nasab E. Investigation of FGF1 and FGFR gene polymorphisms in a group of Iranian patients with nonsyndromic cleft lip with or without cleft palate. Int J Pediatr Otorhinolaryngol 2014;78(5):731-6.##Rafighdoost F, Rafighdoost A, Rafighdoost H, Rigi-Ladez M-A, Hashemi M, Eskandari-Nasab E. The 19-bp deletion polymorphism of dihydrofolate reductase (DHFR) and nonsyndromic cleft lip with or without cleft palate: evidence for a protective role. J Appl Oral Sci 2015;23:272-8.##Cui D, Li L, Lou H, Sun H, Ngai S, Shao G, et al. The ribosomal protein S26 regulates p53 activity in response to DNA damage. Oncogene 2014;33(17):2225-35.##Sham PC, Purcell SM. Statistical power and significance testing in large-scale genetic studies. Nat Rev Genet 2014;15(5):335-46.##Yasuhara T, Suzuki T, Katsura M, Miyagawa K. Rad54B serves as a scaffold in the DNA damage response that limits checkpoint strength. Nat Commun 2014;5:5426.##Feng S, Liu J, Hailiang L, Wen J, Zhao Y, Li X, et al. Amplification of RAD54B promotes progression of hepatocellular carcinoma via activating the Wnt/β-catenin signaling. Transl Oncol 2021;14(8):101124.##Hiramoto T, Nakanishi T, Sumiyoshi T, Fukuda T, Matsuura S, Tauchi H, et al. Mutations of a novel human RAD54 homologue, RAD54B, in primary cancer. 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Effects of Poly-N-isopropylacrylamide Microgels Containing Antibiofilm Substances on Pseudomonas aeruginosa Isolated from Chronic Wounds 2 2 Background: Biofilm formation helps Pseudomonas &lrm;aeruginosa (P. &lrm;aeruginosa) survive in various environments. Microgels can be effective in treatment of bacterial infections. The major aim of this study was to investigate effects of poly-N-isopropyl-acrylamide microgels (PNIPAM) on P. aeruginosa. Methods: Totally&lrm;, &lrm;100 P. aeruginosa strains were isolated from chronic wound infections&lrm;. Quantitative assessments of biofilm formation and antibiotic susceptibility were carried out. Furthermore, algD, lasR, and PA2714 genes were amplified to investigate gene frequencies and expression rates. Results: Significant decreases were seen in lasR expression in EDTA-treated samples&lrm;. Significant decreases were observed in expression of algD and lasR treated with xylitol. Decreased &lrm;expression of PA2714 was seen in samples treated with xylitol with no significance.  Conclusion: The PNIPAM containing xylitol &lrm;or EDTA could penetrate biofilms of P. aeruginosa and significantly decrease expression of lasR and algD. This can be a novel strategy in the management of chronic wounds. 317 320 Akram Etemadinia Department of Pathobiology, School of Public Health, Tehran University of Medical Science Department of Pathobiology, School of Public Health, Tehran University of Medical Science Iran Amir Seyfoori Department of Biomaterials and Tissue Engineering, Breast Cancer Research Center, Motamed Cancer Institute, ACECR Iran Abbas Rahimi Foroushani Department of Pathobiology, School of Public Health, Tehran University of Medical Science Department of Pathobiology, School of Public Health, Tehran University of Medical Science Iran Ramin Mazaheri Nezhad Fard Department of Pathobiology, School of Public Health, Tehran University of Medical ScienceFood Microbiology Research Center, Tehran University of Medical Science Department of Pathobiology, School of Public Health, Tehran University of Medical ScienceFood Microbiology Research Center, Tehran University of Medical Science IranIran Ronak Bakhtiari BiofilmsMicrogelsPseudomonas aeruginosaReal-time PCR 60520.pdf Aibuedefe EO, Udogadi NS, Hakeem SO. Characterisation of the prevailing multidrug Pseudomonas aeruginosa strains from surgical wound using 16S rRNA sequencing technique. Malays J Med Sci 2021;28(4):37-49.##Elahi Y, Nowroozi J, Fard RM. Isolation and characterization of bacteriophages from wastewater sources on Enterococcus spp. isolated from clinical samples. Iran J Microbiol 2021;13(5):671.##Seyfoori A, Sarfarazijami S, Seyyed Ebrahimi S. pH-responsive carbon nanotube-based hybrid nanogels as the smart anticancer drug carrier. Artif Cells Nanomed Biotechnol 2019;47(1):1437-43.##Mirzaie A, Peirovi N, Akbarzadeh I, Moghtaderi M, Heidari F, Yeganeh FE, et al. Preparation and optimization of ciprofloxacin encapsulated niosomes: A new approach for enhanced antibacterial activity, biofilm inhibition and reduced antibiotic resistance in ciprofloxacin-resistant methicillin-resistance Staphylococcus aureus. Bioorg Chem 2020;103:104231.##Fathollahipour S, Abouei Mehrizi A, Ghaee A, Koosha M. Electrospinning of PVA/chitosan nanocomposite nanofibers containing gelatin nanoparticles as a dual drug delivery system. J Biomed Mater Res A 2015;103(12):3852-62.##Basseri H, Bakhtiyari R, Hashemi SJ, Baniardelani M, Shahraki H, Hosainpour L. Antibacterial/antifungal activity of extracted chitosan from American cockroach (Dictyoptera: Blattidae) and German cockroach (Blattodea: Blattellidae). J Med Entomol 2019;56(5):1208-14.##Rahim K, Saleha S, Basit A, Zhu X, Ahmed I, Huo L, et al. Pseudomonas aeruginosa as a powerful biofilm producer and positive action of amikacin against isolates from chronic wounds. Jundishapur J Microbiol 2017;10(10):e57564.##Metcalf D, Bowler P, Parsons D. Wound biofilm and therapeutic strategies. Microbial biofilms-importance and applications Rijeka: InTech. 2016;13(2):145-53.##Rofooei A, Zare Karizi S, Honarmand Jahromi S. Evaluation of antibiotic resistance profile and biofilm forming potential of Pseudomonas aeruginosa clinical isolates. J Anim Environ 2018;10(3):483-8.##Ammons MC, Ward LS, Dowd S, James GA. Combined treatment of Pseudomonas aeruginosa biofilm with lactoferrin and xylitol inhibits the ability of bacteria to respond to damage resulting from lactoferrin iron chelation. Int J Antimicrob Agents 2011;37(4):316-23.##

Mitochondrial Transfer from Menstrual Blood Stromal/Stem Cells Promotes Survival of Cardiomyocytes Following Myocardial Infarction 2 2 Dear editor, Recently, Mitochondrial Transfer (MT) from stem cells to injured cells has been proposed as a novel therapeutic strategy that could restore the bioenergetics requirement of damaged tissues 1. This organelle is essential for cellular homeostasis, cell survival, cell growth, cell death induction, calcium storage, cell signaling, and energy supply, especially in energy-demanding cells like cardiomyocytes 2,3. Mitochondrial dysfunction is contributed to a majority of pathologic conditions like Myocardial Infarction (MI) and cardiomyopathies 4. Mitochondrial impairment results in reduction of Adenosine Triphosphate (ATP) production, induces the generation of intracellular Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS), and activates the caspase cleavage pathway 5. It has been confirmed that Mesenchymal Stem Cells (MSCs) could transport mitochondria to a range of cells including endothelial cells and cardiomyocytes 6. It appears that healthy mitochondrial donation by MSCs is a unique phenomenon that leads to replacement of dysfunctional mitochondria in injured cells. It has been designated that the transfer of even a small number of Multipotent Mesenchymal Stem Cells (MMSC)-derived mitochondria resulted in enhanced oxidative phosphorylation and promotion of cell proliferation in the recipient damaged cells 7. Although mitochondrial transmission from various sources of stem cells like Bone Marrow Mesenchymal Stem Cell (BM-MSCs), induced Pluripotent Stem Cells (iPSCs), and Dental Pulp Derived Mesenchymal Stem Cell (DP-MSCs) has been stated, there is no report about MT from menstrual blood Stromal/Stem Cells (MenSCs). Recently we have perceived that, transepicardial MenSCs administration could improve cardiac function, prevent metaplastic development, and promote survival of cardiomyocytes following MI conceivably by transfer of their mitochondria to preserved cardiomyocytes and endothelial cells. We tracked the injected MenSCs 28 days’ post-transplantation by anti-human mitochondrial antibody in MI site in rat model and demonstrated successfully transferred human mitochondria from MenSCs into the targeted cells. Researchers have showed that mitochondrial dysfunction plays critical role in the loss of cardiomyocytes during MI 8. Although exact mechanisms of MT have not been clarified yet, it has indicated that the local microenvironment of injured tissue releases physiological signals that trigger MT 9. For instance, mitochondrial DNA (mtDNA) released by damaged cells is engulfed by MSCs and that later, prompts the cytoprotective function of MSCs and boosts mitochondrial biogenesis 10. Furthermore, ROS and RNS can also stimulate mitochondrial donation 11. It is assumed that, transmission of mitochondria derived from MenSCs may lead to maintenance of cellular homeostasis, preservation of aerobic respiration, reduction the level of ROS, prevention of cell death, and upregulation of cardio-protective cytokines in the cardiomyocytes 12. Mitochondria in MSCs like MenSCs is in dormant state due to lesser energy demands. However upon differentiation, increase in levels of respiratory enzymes, greater oxygen consumption rate, augmented levels of intracellular ATP, increase in mtDNA copy number and mRNA levels may occur 13,14. Interestingly, it has been indicated that the MT phenomenon from MSCs not only results in protection of injured targeted cells, but also, it can lead to more MSCs survival due to decreasing their partially depolarized and dysfunctional mitochondria 15. Researchers indicated that transmission of mitochondria from BM-MSCs to cardiomyocytes can inhibit apoptosis and reprogrammed differentiated cardiomyocytes to progenitor-like cells 16. Furthermore, iPSC-MSCs directly protects cardiomyocytes against induced cardiomyopathy through bioenergetic preservation by functional MT 17. Also MT from MSCs to endothelial cell rescued the injured endothelial cell by reducing apoptosis and promoting proliferation 18. Meanwhile, some resident cells in injured site could transfer mitochondria to injured cells; we believe that only endogenous transfer is transient and cannot inhibit progressive injuries following MI. Our studies have shown that; administration of MenSCs post-MI modifies the metabolism and restores the functionality of heart, and also protect myocardium from further subsequent injuries mainly with donation of their healthy mitochondria to cardiomyocytes and endothelial cells. It is likely that the donor mitochondria fuse with mitochondria in the recipient cell, and restore bioenergetic requirements; or the recipient cell removes its injured mitochondria and gets the donated healthy mitochondria 19. Researchers revealed that human mitochondrial DNA from MSCs could be found in mice 28 days after MSC administration. However, MSC nuclear DNA was not detected 3 days post administration and suggesting that the long-term therapeutic effects of MSCs administration may be related to MT 15. So, the stem cell-based mitochondria transfer approach from MenSCs can be considered as a newly effective therapeutic strategy to treat cardiomyopathies. 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