Research in Iran: Hopes and Disappointments 2 2 In the September 15, 2016 issue of Science, Dr. Richard Stone wrote a report regarding selling theses and research articles in Iran. There are noteworthy points in this report which truly disturb the Iranian scientific community, but the present report is not the whole truth about the Iranian scientific community. Iran’s scientific infrastructure was destroyed in the eight-year imposed war by Saddam Hossein in a way that production of Iranian scientific articles in the Web of Sciences, which was twice Turkey’s scientific articles before the Islamic Revolution, decreased to one-tenth of Turkey’s scientific articles after the imposed war. Luckily, with creation of scientific infrastructure in the country’s universities in a 25-year period after the war, Iranian scientific production increased noticeably in such a way that in 2011 Iran had the greatest impetus in scientific production and also in industry, for example in production of drugs, we succeeded in producing 90% of country’s needed drugs 1, 2. We succeeded in training enough physicians, dentists, and specialized physicians so that even small Iranian cities have neurosurgeons and orthopedic surgeons. Unfortunately, two problems arose in continuation of this policy: 1. Many private universities and on-line public universities began training students without logical policies especially postgraduate students without appropriate scientific infrastructure, qualified professors, and qualified students; 2. Western economic sanctions which began in 2011, although the economy was the primary focus, also targeted the Iranian scientific infrastructure. For example, university and researcher access to ISI journals via the digital library was terminated or purchase of research material such as laboratory kits for research and educational objectives encountered serious problems. Researchers and the society of Iranian scientists believe this act has not been scientific and fair. We must accept that the above mentioned two factors delivered injuries to the body of higher education. On the other hand, one must confess that at international levels, credible Iranian scientific universities move forward in education and research with power as evidenced by acceptance of Iranian medical graduates with high scores on the USMLE. Many weak scientific journals which daily appear like mushrooms in many Southeast Asian countries and even European countries have disrupted the correct international scientific environment. The Iranian scientific society is hopeful. The Joint Comprehensive Plan of Action (JCPOA) and the vision of Dr. Rouhani’s cabinet will increase the Iranian scientific society’s endurance and will put a stop to present worries. Along the same lines, vision of the Iranian Ministry of Health and Medical Education in research evaluation of universities, in the past three years, has returned from quantity to quality. Many, in place of number of articles, put emphasis on article quality. Also, for improvement of medical university research infrastructures, a national granting body at the Health Ministry, titled NIMAD, was created which financially supports large national projects. In addition, ten large comprehensive research laboratories opened in the past three years. More than ten large cohort studies and thirty national disease registries have begun operating across the country. We are hopeful that in the next few years, exit of these large studies will result in research quality improvement in the country’s medical universities. 1 1 Shahin Akhondzadeh Psychiatric Research Center, Roozbeh Hospital, South Kargar Street Psychiatric Research Center, Roozbeh Hospital, South Kargar Street Iran Editorial 250.pdf Akhondzadeh S. US editors and reviewers can no longer handle submissions by authors employed by the government of Iran: Is it fair and logical? Avicenna J Med Biotechnol 2013;5(4):203.##Akhondzadeh S. Iranian science shows world's fastest growth: ranks 17th in science production in 2012. Avicenna J Med Biotechnol 2013;5(3):139.##

The Effects of Berberine and Palmatine on Efflux Pumps Inhibition with Different Gene Patterns in Pseudomonas aeruginosa Isolated from Burn Infections 2 2 Background: Related Multidrug Resistance (MDR) to efﬂux pumps is a signiﬁcant problem in treating infections caused by Pseudomonas aeruginosa (P. aeruginosa). Plant compounds have been identified as Pump Inhibitors (EPIs). In the current study, the potential effect of Berberine and Palmatine as EPIs were investigated on efflux pump inhibition through focusing on different gene patterns in P. aeruginosa isolated from burn infections. Methods: All isolates were collected and identified using the standard biochemical tests. Antimicrobial sensitivity was performed based on disk agar diffusion method for 12 antibiotics. MIC-MBC tests were also performed based on the broth microdilution method to detect synergistic relationship between ciprofloxacin, Berberine and Palmatine. Detection of mexA, mexB, mexC, mexD, mexE, mexF and mexX was conducted by PCR assay. Fisher's Exact test and Logistic Regression were used as statistical tools. Results: A total of 60 P. aeruginosa isolates were collected. The highest and lowest levels of resistance were found to be respectively against clindamycin and tigecycline. Comparing the MIC with MBC distribution, it was found that Berberine and Palmatine lower the MIC-MBC level of ciprofloxacin. The PCR results indicated that the highest frequency is about MexAB-OprM operon. The statistical analysis among different gene patterns of efflux pumps showed that there were no significant relationships between the effectiveness of Berberine and Palmatine (p>0.05). Conclusion: It can be speculated that Berberine and Palmatine both act as EPIs and can be used as auxiliary treatments with the purpose of increasing the effect of available antibiotics as well as decreasing the emergence of MDR bacteria. The efficiency of these combinations should be studied further under in vivo conditions to have a more comprehensive conclusion regarding this issue. 2 7 Seyed Sadjjad Aghayan Department of Basic Sciences, Islamic Azad University, Damghan Branch Department of Basic Sciences, Islamic Azad University, Damghan Branch Iran Hamidreza Kalalian Mogadam Faculty of Medicine, Shahroud University of Medical Sciences Faculty of Medicine, Shahroud University of Medical Sciences Iran Mozhgan Fazli Faculty of Medicine, Shahroud University of Medical Sciences Faculty of Medicine, Shahroud University of Medical Sciences Iran Davood Darban-Sarokhalil Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences Iran Seyed Sajjad Khoramrooz Medicinal Plants Research Center, Yasuj University of Medical Sciences Medicinal Plants Research Center, Yasuj University of Medical Sciences Iran Fereshteh Jabalameli Department of Microbiology Faculty of Medicine, Tehran University of Medical Sciences Department of Microbiology Faculty of Medicine, Tehran University of Medical Sciences Iran Somayeh Yaslianifard Department of Microbiology, Faculty of Medicine, Alborz University of Medical Sciences Department of Microbiology, Faculty of Medicine, Alborz University of Medical Sciences Iran Mehdi Mirzaii Faculty of Medicine, Shahroud University of Medical Sciences Faculty of Medicine, Shahroud University of Medical Sciences Iran BerberinePalmatinePseudomonas aeruginosa 259.pdf Qader AR, Muhamad JA. Nosocomial infection in Sulaimani burn Hospital, Iraq. Ann Burns Fire Disasters 2010;23(4):177-181.##Soares de Macedo JL, Santos JB. Nosocomial infections in a Brazilian Burn Unit. Burns 2006;32(4):477-481.##Church D, Elsayed S, Reid O, Winston B, Lindsay R. Burn wound infections. Clin Microbiol Rev 2006;19(2):403-434.##Poole K. Efflux-mediated multiresistance in gram-negative bacteria. Clin Microbiol Infect 2004;10(1):12-26.##Pearson JP, Van Delden C, Iglewski BH. Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals. J Bacteriol 1999;181(4):1203-1210.##Piddock LJ. Multidrug-resistance efflux pumps - not just for resistance. Nat Rev Microbiol 2006;4(8):629-636.##Misra R, Bavro VN. Assembly and transport mechanism of tripartite drug efflux systems. Biochim Biophys Acta 2009;1794(5):817-825.##Poole K, Srikumar R. Multidrug efflux in Pseudomonas aeruginosa: components, mechanisms and clinical significance. Curr Top Med Chem 2001;1(1):59-71.##Strateva T, Yordanov D. Pseudomonas aeruginosa-a phenomenon of bacterial resistance. J Med Microbiol 2009;58(Pt 9):1133-1148.##Llanes C, Hocquet D, Vogne C, Benali-Baitich D, Neuwirth C, Plésiat P. Clinical strains of Pseudomonas aeruginosa overproducing MexAB-OprM and MexXY efflux pumps simultaneously. Antimicrob Agents Chemother 2004;48(5):1797-1802.##Zechini B, Versace I. Inhibitors of multidrug resistant efflux systems in bacteria. Recent Pat Antiinfect Drug Discov 2009;4(1):37-50.##Lewis K, Ausubel FM. Prospects for plant-derived antibacterials. Nat Biotechnol 2006;24(12):1504-1507.##Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother Res 2008;22(8):999-1012.##Dkhil MA. Role of berberine in ameliorating Schistosoma mansoni-induced hepatic injury in mice. Biol Res 2014;47:8.##Xiao CW, Ji QA, Wei Q, Liu Y, Bao GL. Antifungal activity of berberine hydrochloride and palmatine hydrochloride against Microsporum canis-induced dermatitis in rabbits and underlying mechanism. BMC Complement Altern Med 2015;15:177.##Cech NB, Junio HA, Ackermann LW, Kavanaugh JS, Horswill AR. Quorum quenching and antimicrobial activity of goldenseal (Hydrastis canadensis) against methicillin-resistant Staphylococcus aureus (MRSA). Planta Med 2012;78(14):1556-1561.##Stermitz FR, Lorenz P, Tawara JN, Zenewicz LA, Lewis K. Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpine, a multidrug pump inhibitor. Proc Natl Acad USA 2000;97(4):1433-1437.##Ettefagh KA, Burns JT, Junio HA, Kaatz GW, Cech NB. Goldenseal (Hydrastis canadensis L.) extracts synergistically enhance the antibacterial activity of berberine via efflux pump inhibition. Planta Med 2011;77(8):835-840.##Mahon CR, Lehman DC, Manuselis G. Textbook of Diagnostic Microbiology. 4th ed. Philadelphia: Saunders; 2011. 1395 p.##Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement. CLSI document M100- S22. Wayne, PA: Clinical and Laboratory Standard Institute; 2012. 230 p.##Kalantar E, Torabi V, Salimizand H, Soheili F, Beiranvand S, Soltan Dallal MM. First survey of Metallo-β-Lactamase producers in clinical isolates of Pseudomonas aeruginosa from a referral burn center in Kurdistan Province. Jundishapur J Nat Pharm Prod 2012;7(1):23-26.##Biswal I, Arora BS, Kasana D, Neetushree. Incidence of multidrug resistant pseudomonas aeruginosa isolated from burn patients and environment of teaching institution. J Clin Diagn Res 2014;8(5):Dc26-29.##Arabestani MR, Rajabpour M, Yousefi Mashouf R, Alikhani MY, Mousavi SM. Expression of efflux pump MexAB-OprM and OprD of Pseudomonas aeruginosa strains isolated from clinical samples using qRT-PCR. 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Antimicrob Agents Chemother 2002;46(10):3133-3141.##Jian-ling J, Guo-qiang H, Zhen M, Pei-ji G. Antibacterial mechanisms of berberine and reasons for little resistance. Chin Herb Med 2010;3(1):27-35.##

The Role of M2000 as an Anti-inflammatory Agent in Toll-Like Receptor 2/microRNA-155 Pathway 2 2 Background: M2000 is a newly designed and safe Non-Steroidal Anti-Inflammatory Drug (NSAID). The aim of this study was to assess the effects of M2000 on expression levels of Suppressor of Cytokine Signaling-1 (SOCS-1) and Src Homology-2 domain-containing inositol-5’-phosphatase 1 (SHIP1) proteins via Toll-Like Receptor (TLR) 2/microRNA-155 pathway. Methods: HEK293 TLR2 cell line and Peripheral Blood Mononuclear Cells (PBMCs) were treated by different concentrations of M2000 in MTT assay. RNA was extracted by miRNeasy Mini kit. Then, cDNA was synthesized and the expression levels of SOCS1, SHIP1 and miRNA155 were evaluated by Quantitative Real time PCR. Results: Our results showed that M2000 significantly increased the expression levels of SOCS1 and SHIP-1 in Lipopolysachride (LPS)-treated and non-treated cells. Moreover, M2000 decreased expression level of miR-155 in LPS treated PBMCs. Conclusion: M2000 can be used as NSAID in LPS induced inflammation and decrease inflammatory cytokines production by targeting SOCS1, SHIP1 and miR-155 in autoimmune and inflammatory diseases. 8 12 Fatemeh Pourgholi Hematology and Oncology Research Center, Tabriz University of Medical SciencesImmunology Research Center, Tabriz University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences Hematology and Oncology Research Center, Tabriz University of Medical SciencesImmunology Research Center, Tabriz University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences IranIranIran Mahsa Hajivalili Hematology and Oncology Research Center, Tabriz University of Medical SciencesImmunology Research Center, Tabriz University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences Hematology and Oncology Research Center, Tabriz University of Medical SciencesImmunology Research Center, Tabriz University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences IranIranIran Rasoul Razavi Department of Hematology and Blood Banking, Tarbiat Modares University Department of Hematology and Blood Banking, Tarbiat Modares University Iran Shadi Esmaeili Department of Hematology and Blood Banking, Tarbiat Modares University Department of Hematology and Blood Banking, Tarbiat Modares University Iran Behzad Baradaran Immunology Research Center, Tabriz University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences Immunology Research Center, Tabriz University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences IranIran Ali Akbar Movasaghpour Hematology and Oncology Research Center, Tabriz University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences Hematology and Oncology Research Center, Tabriz University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences IranIran Sanam Sadreddini Immunology Research Center, Tabriz University of Medical Sciences Immunology Research Center, Tabriz University of Medical Sciences Iran Hamidreza Goodarzynejad Basic and Clinical Research Department, Tehran Heart Center Basic and Clinical Research Department, Tehran Heart Center Iran Abbas Mirshafiey Department of Immunology, Faculty of Public Health, Tehran University of Medical Sciences Department of Immunology, Faculty of Public Health, Tehran University of Medical Sciences Iran Mehdi Yousefi Immunology Research Center, Tabriz University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences Immunology Research Center, Tabriz University of Medical SciencesDepartment of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences IranIran MicroRNAsSHIP1SOCS1 260.pdf Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal anti-inflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci 2013;16(5):821-847.##Whelton A. Renal and related cardiovascular effects of conventional and COX-2-specific NSAIDs and non-NSAID analgesics. Am J Ther 2000;7(2):63-74.##Bauerová K, Nosál'ová V, Mihalová D, Navarová J. Contribution to safe anti-inflammatory therapy with indomethacin. Cent Eur J Public Health 2004;12 Suppl:S8-10.##Afraei S, Azizi G, Zargar SJ, Sedaghat R, Mirshafiey A. New therapeutic approach by G2013 in experimental model of multiple sclerosis. Acta Neurol Belg 2015;115(3):259-266.##Mirshafiey A, Cuzzocrea S, Rehm BH, Matsuo H. M2000: a revolution in pharmacology. Med Sci Monit 2005;11(8):PI53-63.##Mirshafiey A, Matsuo H, Nakane S, Rehm BH, Koh CS, Miyoshi S. Novel immunosuppressive therapy by M2000 in experimental multiple sclerosis. Immunopharmacol Immunotoxicol 2005;27(2):255-265.##Huang QQ, Pope RM. The role of toll-like receptors in rheumatoid arthritis. Curr Rheumatol Rep 2009;11(5):357-364.##Kimura A, Naka T, Muta T, Takeuchi O, Akira S, Kawase I, et al. Suppressor of cytokine signaling-1 selectively inhibits LPS-induced IL-6 production by regulating JAK-STAT. Proc Natl Acad Sci USA 2005;102(47):17089-17094.##Chen Y, Liu W, Sun T, Huang Y, Wang Y, Deb DK, et al. 1,25-Dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting MicroRNA-155–SOCS1 in macrophages. J Immunol 2013;190(7):3687-3695.##Parsa KV, Ganesan LP, Rajaram MV, Gavrilin MA, Balagopal A, Mohapatra NP, et al. Macrophage pro-inflammatory response to Francisella novicida infection is regulated by SHIP. PLoS Pathog 2006;2(7):e71-e71.##Handal B, Enlow R, Lara D, Bailey M, Vega F, Hu P, et al. Investigating the expression of oncogenic and tumor suppressive microRNA in DLBCL. J Assoc Genet Technol 2013;39(1):14-20.##Martinez-Nunez RT, Louafi F, Friedmann PS, Sanchez-Elsner T. 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MicroRNA-155 as a proinflammatory regulator via SHIP-1 down-regulation in acute gouty arthritis. Arthritis Res Ther 2014;16(2):R88.##Pauley KM, Cha S, Chan EK. MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun 2009;32(3-4):189-194.##Nakagawa R, Naka T, Tsutsui H, Fujimoto M, Kimura A, Abe T, et al. SOCS-1 participates in negative regulation of LPS responses. Immunity 2002;17(5):677-687.##Strassheim D, Kim JY, Park JS, Mitra S, Abraham E. Involvement of SHIP in TLR2-induced neutrophil activation and acute lung injury. J Immunol 2005;174(12):8064-8071.##Guha M, Mackman N. The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. J Biol Chem 2002;277(35):32124-32132.##Fattahi MJ, Abdollahi M, Agha Mohammadi A, Rastkari N, Khorasani R, Ahmadi H, et al. Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug. 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Induction of Epigenetic Alteration by CPUK02, An Ent- kaurenoid Derivative of Stevioside 2 2 Background: Dietary polyphenols, such as those found in green tea and red wine, are linked to antitumor activity. They are known to influence many signaling pathways epigenetically within the human body. In this regard, CPUK02 (15-Oxosteviol benzyl ester) is a new ent-kaurenoid derivative of stevioside and exhibits strong anti-cancer activity in vitro and in vivo. Nowadays, the role of epigenetics in cancer has been the subject of intensive study and DNA methylation targeting represents a relevant strategy for cancer treatment. There are no reports regarding the effects of CPUK02 on epigenetic alterations in colorectal cancer cell line. This study was an attempt to compare CPUK02 with 5-AZA as DNMT inhibitor agent and evaluate whether it can induce its anti-cancer effects via altering the level of DNMT3b mRNA, MGMT and SFRP2 methylation pattern in HCT 116 cell line. Methods: To evaluate DNMT3b expression, DNMT3B mRNA levels in HCT116 CRC cell line were quantified by real-time reverse-transcriptase Polymerase Chain Reaction (PCR) assay after 24 hr of incubation time with CPUK02 and 5-AZA. In addition, the methylation patterns of 2 CpG islands in this cell line were examined by methylation-specific PCR methods. Results: CPUK02 surprisingly, decreased the DNMT3b mRNA level. The average expression levels of DNMT3b in HCT116 treated with CPUK02 and 5-AZA relative to the GAPDH expression level in control were 0.16 and 0.5%, respectively. Furthermore, CPUK02 could decrease the methylated allele of MGMT and SFRP2 genes in HCT 116 after 24 hr. Conclusion: In this study, positive correlation was found between mRNA expression of DNMT3b and gene promoter hypermethylation after treatment with CPUK02 and 5-AZA. Our data confirmed that CPUK02 like 5-AZA exhibits demethylating properties. 13 18 Pooneh Mokarram Gasteroenterohepatology Research Center, Nemazee Hospital, Faculty of Medicine, Shiraz University of Medical SciencesDepartment of Biochemistry, Faculty of Medicine, Shiraz University of Medical Sciences Gasteroenterohepatology Research Center, Nemazee Hospital, Faculty of Medicine, Shiraz University of Medical SciencesDepartment of Biochemistry, Faculty of Medicine, Shiraz University of Medical Sciences IranIran Zeinab Mohammadi Department of Biochemistry, Faculty of Medicine, Shiraz University of Medical Sciences Department of Biochemistry, Faculty of Medicine, Shiraz University of Medical Sciences Iran Saeid Khazayel Department of Biochemistry, Faculty of Medicine, Shiraz University of Medical Sciences Department of Biochemistry, Faculty of Medicine, Shiraz University of Medical Sciences Iran Zhang Dayong Drug Research Institute, China Pharmaceutical University Drug Research Institute, China Pharmaceutical University China 5-AZAColorectal neoplasmDNMTEpigeneticMethylation 261.pdf American Cancer Society [Internet]. 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Overexpression of Recombinant Human Teriparatide, rhPTH (1-34) in Escherichia coli: An Innovative Gene Fusion Approach 2 2 Background: Parathyroid hormone is an 84-amino acid peptide secreted by the parathyroid glands. Its physiological role is maintenance of normal serum calcium level and bone remodeling. Biological activity of this hormone is related to N-terminal 1-34 amino acids. The recombinant form of hormone (1-34) has been approved for treatment of osteoporosis from 2002. In this study, a novel fusion partner has been developed for preparation of high yield recombinant 1-34 amino acids of hPTH. Methods: Novel nucleotide cassette designed encoding a chimeric fusion protein comprising of a fusion partner consisting of a His-tag in N-terminal, 53 amino acids belong to Escherichia coli (E. coli) β-galactosidase (LacZ) gene, a linker sequence for increasing of expression and protection of target peptide structure from fusion tag effect, an Enteropeptidase cleavage site, rhPTH (1-34) gene fragment. Optimized fusion gene was synthesized and ligated into pET-28a vector under control of T7 promoter, and then transformed in E. coli (DH5α) cells. Positive clones containing this gene were double digested with NcoI and-BamHI and also approved by sequencing. Gene overexpression was observed in SDS-PAGE after induction with 0.2 mM IPTG. Confirmation of gene expression was performed by western blotting using anti-His-tag antibody conjugated with peroxidase. Results: By this fusion gene design approach, we achieved a high level expression of the rhPTH, where it represented at least 43.7% of the total protein as determined by SDS-PAGE and confirmed by western blotting. Conclusion: In addition to high level expression of the designed gene in this work, specific amino acid sequence of bacterial β-galactosidase was selected as major part of carrier tag for protection of this hormone as important step of recombinant rhPTH with relevant isoelectronic point (pI). This innovation resulted in recombinant production of hPTH very well and the gene construct could be applied as a pattern for similar recombinant peptides where recombinant protein degradation is a critical issue. 19 22 Nahid Bakhtiari Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST) Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST) Iran Zahra Amini Bayat Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST) Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST) Iran Sepideh Sagharidouz Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST) Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST) Iran Mohsen Vaez Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST) Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST) Iran CloningEscherichia coliExpressionRecombinantTeriparatide 262.pdf Diaz R, El-Hajj Fuleihan G, Brouwn E. Parathyroid Hor-mone and Polyhormones: Production and Export. In: Fray J (Ed) Handbook of Physiology. USA, New York: Oxford University; 1999. p. 607-622.##Elaine WY, Neer RM, Lee H, Wyland JJ, Amanda V, Davis MC, et al. Time-dependent changes in skeletal response to teriparatide: Escalating vs. constant dose teriparatide (PTH 1–34) in osteoporotic women. Bone 2011;48(4):713-719.##Larijani B, Alimadadi A. Recombinant Parathormone and osteoporosis a review article. Tehran Univ Med J 2010;68(9):497-507.##Tregear GW, Van Rietschoten J, Greene E, Keutmann HT, Niall HD, Reit B, et al. Bovine parathyroid hormone: minimum chain length of synthetic peptide required for biological activity. Endocrinol 1973;93(6):1349-1353.##Morelle G, Mayer H. Increased synthesis of human parathyroid hormone in Escherichia coli through alterations of the 5′ untranslated region. Biochim Biophys Acta (BBA)-Gene Structure and Expression 1988;950(3):459-462.##Xiu Z, Li M, Zhou S, Dou H, Zhou H, Chen C. 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Anti-Quorum Sensing Activity of Substances Isolated from Wild Berry Associated Bacteria 2 2 Background: Quorum Sensing (QS) is a mechanism used by bacteria to determine their physiological activities and coordinate gene expression based on cell to cell signaling. Many bacterial physiological functions are under the regulation of quorum sensing such as virulence, luminescence, motility, sporulation and biofilm formation. The aim of the present study was to isolate and characterize Quorum Sensing Inhibitory (QSI) substances from epiphytic bacteria residing on wild berries surfaces. Methods: Fifty nine bacterial isolates out of 600 screened bacteria were successfully isolated. These bacteria were obtained from berry surfaces of different plants in the wild forests of Ajloun-Jordan. Screening for QSI activity using Chromobacterium violaceum ATCC 12472 monitor strain, resulted in isolating 6 isolates exhibiting QSI activity only, 11 isolates with QSI and antibacterial activity, and 42 isolates with antibacterial activity only. Three potential isolates S 130, S 153, and S 664, were gram positive rods and spore formers, catalase positive and oxidase negative. These were chosen for further testing and characterization. Results: Different solvent extraction of the QSI substances based on polarity indicated that the activity of S 130 was in the butanol extract, S 153 activity in both chloroform and butanol; and for S 664, the activity was detected in the hexane extract. The chloroform extract of S 153 and hexane extract of S 664 were proteinaceous in nature while QSI substances of the butanol extract of S 130 and S 153 were non-proteinaceous. All the tested QSI substances showed a marked thermal stability when subjected at several time intervals to 70oC, with the highest stability observed for the butanol extract of S 153. Assessing the QSI substances using violacein quantification assay revealed varying degrees of activity depending upon the extracting solvent, type of the producer bacteria and the concentration of the substances. Conclusion: This study highlighted the potential of untapped reservoirs in nature to be used as a source of unique metabolite that may be further developed for therapy. The potential QSI substances included in this study are just one aspect to be further analyzed for use as biopharmaceutical agents. 23 30 Suha M. Abudoleh Faculty of Pharmacy, Isra University Faculty of Pharmacy, Isra University Jordan Adel M. Mahasneh Department of Biological Sciences, Faculty of Science, The University of Jordan Department of Biological Sciences, Faculty of Science, The University of Jordan Jordan Quorum sensingChromobacterium violaceum 263.pdf Albuqerque P, Nicola AM, Nieves E, Paes HC, Williamson PR, Silva-Pereira I, et al. Quorum sensing-mediated, cell density-dependent regulation of growth and virulence in Cryptococcus neoformians. MBio 2013;5(1):e00986-13.##Lu HD, Spiegel AC, Hurley A, Perez LJ, Maisel K, Ensign LM, et al. Modulating Vibrio cholera quorum-sensing-controlled communication using autoinducer-loaded nanoparticles. Nano lett 2015;15(4):2235-2241.##Zhou M, Guo Z, Yang Y, Duan Q, Zhang Q, Yao F, et al. Flagellin F4 fimbriae have opposite effects on biofilm formation and quorum sensing in F4ac+ enterotoxigenic Escherichia coli. Vet Microbiol 2014;168(1):148-153.##Dusane DH, Matkar P, Venugopalan VP, Kumar AR, Zinjarde SS. Cross-species induction of antimicrobial compounds, biosurfactants and quorum-sensing inhibitors in tropical marine epibiotic bacteria by pathogens and biofouling microorganisms. Curr Microbiol 2011;62(3):974-980.##Musthafa KS, Saroja V, Pandian SK, Ravi AV. Antipathogenic potential of marine Bacillus sp. SS4 on N-acyl-homoserine-lactone-mediated virulence factors production in Pseudomonas aeruginosa (PAO1). J Biosci 2011;36(1):55-67.##van Kessel JC, Rutherford ST, Cong JP, Quinodoz S, Healy J, Bassler BL. Quorum sensing regulates the osmotic stress response in Vibrio harveyi. J Bacteriol 2015;197(1):73-80.##Lv J, Wang Y, Zhong C, Li Y, Hao W, Zhu J. The microbial attachment potential and quorum sensing measurement of aerobic granular activate sludge and flocculent activated sludge. Bioresour Technol 2014;151:291-296.##Khmel IA, Belik AS, Zaitseva YV, Danilova NN. Quorum sensing and communication in bacteria. Moscow Univ Biol Sci Bull 2008;63(1):25-31.##Abudoleh SM, Mahasneh AM. Quorum sensing inhibitors from epiphytic bacteria isolated from wild berries. In: Mendez-Vilas A, editor. Microbes in Applied Research: Current Advances and Challenges. Singapore: World Scientific Publishing Co; 2012. p. 561-566.##Nithya C, Aravindraja C, Pandian SK. Bacillus pumilus of Palk Bay origin inhibits quorum-sensing-mediated virulence factors in Gram-negative bacteria. Res Microbiol 2010;161(4):293-304.##González JE, Keshavan ND. Messing with bacterial quorum sensing. Microbiol Mol Biol Rev 2006;70(4):859-875.##Packiavathy IA, Agilandeswari P, Mustafa KS, Pandian SK, Ravi AV. Antibiofilm and quorum sensing inhibitory potential of Cuminum cyminum and its secondary metabolite methyl eugenol against Gram negative bacterial pathogens. Food Res Int 2012;45(1):85-92.##Alvarez MV, Moreira MR, Ponce A. Antiquorum sensing and antimicrobial activity of natural agents with potential use in food. J Food Saf 2012;32:379-387.##Truchado P, López-Gálvez F, Gil MI, Tomás-Barberán FA, Allende A. Quorum sensing inhibitory and antimicrobial activities of honeys and the relationship with individual phenolics. Food Chem 2009;115(4):1337-1344.##Vikram A, Jayaprakasha GK, Jesudhasan PR, Pillai SD, Patil BS. Suppression of bacterial cell-cell signaling, biofilm formation and type III secretion system by citrus flavonoids. J Appl Microbiol 2010;109(2):515-527.##Choo JH, Rukayadi Y, Hwang JK. Inhibition of bacterial quorum sensing by vanilla extract. Lett Appl Microbiol 2006;42(6):637-641.##Cotar AI. Quorum sensing inhibitors as anti-pathogenic drugs in the fight against Pseudomonas aeruginosa infections. Clin Microbiol 2013;2:1-2.##Alasil SM, Omar R, Ismail S, Yusof MY. Inhibition of quorum sensing-controlled virulence factors and biofilm formation in Pseudomonas aeruginosa by culture extract from novel bacterial species of Paenibacillus using a Rat model of chronic lung infection. Int J Bacteriol 2015;2015:671562.##Guo Y, Huang E, Yuan C, Zhang L, Yousef AE. Isolation of a Paenibacillus sp. strain and structural elucidation of its broad-spectrum lipopeptide antibiotic. Appl Environ Microbiol 2012;78:3156-3165.##McLean RJ, Pierson LS 3rd, Fuqua C. A simple screening protocol for the identification of quorum signal antagonists. J Microbiol Methods 2004;58(3):351-360.##Kanagasabhapthy M, Yamazaki G, Ishida A, Sasaki H, Nagata S. Presence of quorum-sensing inhibitors-like compounds from bacteria isolated from the brown alga Colpomenia sinusoa. Lett Appl Microbiol 2009;49(5):573-579.##McLean R, Bryant S, Vattem D, Givskov M, Rasmussen T, Balaban N. Detection in vitro of quorum-sensing molecules and their inhibitors. In: Balaban N, editor. The Control of Biofilm Infections by Signal Manipulation. USA: Springer; p. 39-50.##Lamberte LS, Cabera EC, Rivera WL. Activity of the ethanolic extract of propolis (EEP) as a potential inhibitor of quorum sensing-mediated pigment production in Chromobacterium violaceium and virulence factor production in Pseudomonas aeruginosa. Philipp Agric Sci 2011;94(1):14-22.##Nithya C, Begum MF, Pandian SK. Marine bacterial isolates inhibit biofilm formation and disrupt mature biofilms of Pseudomonas aerugionsa PA01. Appl Microbiol Biotechnol 2010;88:341-358.##Wilson GS, Raftos DA, Corrigan SL, Nair SV. Diversity and antimicrobial activities of surface-attached marine bacteria from Sydney Harbour, Australia. Microbiol Res 2010;165(4):300-311.##Chopra I, Hodgson J, Metcale B, Poste G. The search for antimicrobial agents effective against bacteria resistant to multiple antibiotics. Antimicrob Agents Chemother 1997;41(3):497-503.##Maeda T, García-Contreras R, Pu M, Sheng L, Garcia LR, Tomás M, et al. Quorum quenching quandary: resistance to antivirulence compounds. ISME J 2012;6(3):493-501.##Saga T, Yamaguchi K. 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Isolation and Identification of Phyllospheric Bacteria Possessing Antimicrobial Activity from Astragalus obtusifolius, Prosopis juliflora, Xanthium strumarium and Hippocrepis unisiliqousa 2 2 Background: The widespread utilization of antimicrobial compounds has caused emergence of resistant microorganisms in the world. Hence, the research to probe the products with antimicrobial features has led to finding natural habitats and discovering new pharmaceutical products. Methods: In this study, an attempt was made to explore the niche of novel habitat to isolate pyllospheric bacteria from the above ground parts (stems and leaves) of Astragalus obtusifolius, Prosopis juliflora, Xanthium strumarium, and Hippocrepis unisiliqousa to evaluate their antimicrobial features. The inhibitory effects of these strains on the growth of two fungi (Aspergillus niger, Aspergillus fumigatus), two yeasts (Saccharomyces cerevisiae, Candida albicans) and six bacteria (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Salmonella typhi, Streptococcus pyogenes) were tested. Results: In total, 113 bacterial strains were isolated. Twenty five bacterial strains (B-1 to B-25) indicated promising antimicrobial (antibacterial and antifungal) activities against aforementioned pathogens. The identification of the bacterial strains was ascertained by morphological, physiological, biochemical tests and two strains with the strongest antimicrobial activities were further characterized based on 16s rRNA sequencing. These two strains were identified as Bacillus amyloliquefaciens. Conclusion: Our results provide evidence that phyllospheric microorganisms are capable of producing some compounds with antimicrobial properties. 31 37 Zohreh Mazinani Drug Design and Bioinformatics Unit, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran Drug Design and Bioinformatics Unit, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran Iran Marzieh Zamani Drug Design and Bioinformatics Unit, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran Drug Design and Bioinformatics Unit, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran Iran Soroush Sardari Drug Design and Bioinformatics Unit, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran Drug Design and Bioinformatics Unit, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran Iran Antibacterial agents16s rRNABacillus amyloliquefaciens 264.pdf Mukhtar I, Mushtaq S, Ali A, Khokhar I. 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Chilling and cultivar type affect the diversity of bacterial endophytes colonizing sweet pepper (Capsicum anuum L.). Can J Microbiol 2006;52(2):1036-1045.##Stapleton AE, Simmons SJ. Plant control of phyllosphere diversity: genotype interactions with ultraviolet- B radiation. In: Bailey MJ, Lilley AK, Timms-Wilson PTN, Spencer-Phillips PTN. Microbial Ecology of the Aerial Plant Surface. Wallingford, UK: CABI International; 2006. p. 223-238.##Ryan RP, Germaine K, Franks A, Ryan DJ, Dowling DN. Bacterial endophytes: recent developments and applications. FEMS Microbiol Lett 2008;278(4):1-9.##Dudeja SS, Giri R, Saini R, Suneja-Madan P, Kothe E. Interaction of endophytic microbes with legumes. J Basic Microbiol 2012;52(2):248-260.##Haroun NE, Elamin SE, Mahgoub BM, Elssidig MA, Mohammed EH. Leaf blight: A new disease of Xanthium strumarium L. caused by Curvularia lunata and Drechslera spicifera in Sudan. 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Association of ATP-Binding Cassette Transporter A1 (ABCA1)-565 C/T Gene Polymorphism with Hypoalphalipoproteinemia and Serum Lipids, IL-6 and CRP Levels 2 2 Background: ATP-binding cassette transporter A1 (ABCA1) is a membrane integral protein which plays a vital role in High Density Lipoprotein (HDL) metabolism and exerts a protective effect against Hypoalphalipoproteinemia (HA) by mediation of rate-limiting step in HDL biogenesis. In addition, this protein possesses anti-inflammatory effects by inhibiting the production of some inflammatory cytokines in macrophages. This study investigated the association of ABCA1-565 C/T gene polymorphism with HA and serum lipids, IL-6 and CRP levels. Methods: A population which consisted of 101 HA and 95 normal subjects were genotyped for ABCA1-565C/T polymorphism by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The serum concentrations of lipids, IL-6 and high sensitive-CRP (hs-CRP) were measured by the relevant methods. Results: The frequency of T allele was significantly higher in the HA group than the controls (31.7 vs. 19.5%, p=0.002). Thus, carriers of the T allele (CT and TT genotypes) had a higher risk for HA (p=0.016, OR=2.04, 95% CI=1.14-3.63). T allele carriers demonstrated decreased HDL-C and increased triglyceride, IL-6 and CRP levels than those with the CC genotype.   Conclusion: This study suggests that the-565 C/T polymorphism of ABCA1 gene is associated with an increased risk of HA, decreased HDL-C and increased TG, IL-6 and CRP. 38 43 Mohammad Mahdi Babashamsi Department of Biochemistry, Faculty of Medicine, Babol University of Medical Sciences Department of Biochemistry, Faculty of Medicine, Babol University of Medical Sciences Iran Sohrab Halalkhor Department of Biochemistry, Faculty of Medicine, Babol University of Medical Sciences Department of Biochemistry, Faculty of Medicine, Babol University of Medical Sciences Iran Hamid Moradi Firouzjah Department of Molecular and Cell biology, Faculty of Basic Sciences, University of Mazandaran Department of Molecular and Cell biology, Faculty of Basic Sciences, University of Mazandaran Iran Hadi Parsian Department of Biochemistry, Faculty of Medicine, Babol University of Medical Sciences Department of Biochemistry, Faculty of Medicine, Babol University of Medical Sciences Iran Seyed Farzad Jalali Department of Cardiology, Faculty of Medicine, Babol University of Medical Sciences Department of Cardiology, Faculty of Medicine, Babol University of Medical Sciences Iran Mohammad Babashamsi Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran -565 C/T polymorphismABCA1CRPHypoalphalipoproteinemiaIL-6Lipids 265.pdf Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001;285(19):2486-2497.##Liu Y, Tang C. Regulation of ABCA1 functions by signaling pathways. Biochim Biophys Acta 2012;1821(3):522-529.##Oram JF. Molecular basis of cholesterol homeostasis: lessons from Tangier disease and ABCA1. Trends Mol Med 2002;8(4):168-173.##Alharbi KK, Khan IA, Al-Daghri NM, Munshi A, Sharma V, Mohammed AK, et al. ABCA1 C69T gene polymorphism and risk of type 2 diabetes mellitus in a Saudi population. J Biosciences 2013;38(5):893-897.##McGrowder D, Riley C, Morrison EYSA, Gordon L. The role of high-density lipoproteins in reducing the risk of vascular diseases, neurogenerative disorders, and cancer. Cholesterol 2010;2011:496925.##Pisciotta L, Hamilton-Craig I, Tarugi P, Bellocchio A, Fasano T, Alessandrini P, et al. Familial HDL deficiency due to ABCA1 gene mutations with or without other genetic lipoprotein disorders. Atherosclerosis 2004;172(2):309-320.##Rejeb J, Omezzine A, Rebhi L, Boumaiza I, Kchock K, Belkahla R, et al. Associations between common poly-morphisms of adenosine triphosphate-binding cassette transporter A1 and coronary artery disease in a Tunisian population. Arch Cardiovascular Diseases 2010;103(10):530-537.##Brunham LR, Kruit JK, Pape TD, Timmins JM, Reuwer AQ, Vasanji Z, et al. β-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment. Nat Med 2007;13(3):340-347.##Yin K, Liao DF, Tang CK. ATP-binding membrane cassette transporter A1 (ABCA1): a possible link be-tween inflammation and reverse cholesterol transport. Mol Med 2010;16(9-10):438-449.##Oram JF, Lawn RM. ABCA1. The gatekeeper for eliminating excess tissue cholesterol. J Lipid Res 2001;42(8):1173-1179.##Hansson GK, Robertson AK, Söderberg-Nauclér C. Inflammation and atherosclerosis. Annu Rev Pathol 2006;1:297-329.##Tang C, Liu Y, Kessler PS, Vaughan AM, Oram JF. The macrophage cholesterol exporter ABCA1 functions as an anti-inflammatory receptor. J Biol Chem 2009;284(47):32336-32343.##Francisco G, Hernández C, Simó R. Serum markers of vascular inflammation in dyslipemia. Clin Chim Acta 2006;369(1):1-16.##Benton JL, Ding J, Tsai MY, Shea S, Rotter JI, Burke GL, et al. Associations between two common poly-morphisms in the ABCA1 gene and subclinical atherosclerosis: Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2007;193(2):352-360.##Castaño-Jameson M, Guevara M, Flores A, Medina I, Ayala B, Aguilar M, et al. Association between ABCA1 R230C polymorphism and biochemical parameters in subjects with metabolic syndrome (641.7). The FASEB J 2014;28(1 Suppl):641-647.##Daimon M, Kido T, Baba M, Oizumi T, Jimbu Y, Kameda W, et al. Association of the ABCA1 gene polymorphisms with type 2 DM in a Japanese population. Biochem Biophys Res Commun 2005;329(1):205-210.##Kyriakou T, Hodgkinson C, Pontefract DE, Iyengar S, Howell WM, Wong YK, et al. Genotypic effect of the -565C>T polymorphism in the ABCA1 gene promoter on ABCA1 expression and severity of atherosclerosis. Arterioscler Thromb Vasc Biol 2005;25(2):418-423.##Lutucuta S, Ballantyne CM, Elghannam H, Gotto AM Jr, Marian AJ. Novel polymorphisms in promoter region of ATP binding cassette transporter gene and plasma lipids, severity, progression, and regression of coronary atherosclerosis and response to therapy. Circ Res 2001;88(9):969-973.##Halalkhor S, Mesbah-Namin SA, Daneshpour MS, Hedayati M, Azizi F. Association of ATP-binding cassette transporter-A1 polymorphism with apolipoprotein AI level in Tehranian population. J Genet 2011;90(1):129-132.##Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16(3):1215.##Jensen MK, Pai JK, Mukamal KJ, Overvad K, Rimm EB. Common genetic variation in the ATP-binding cassette transporter A1, plasma lipids, and risk of coronary heart disease. Atherosclerosis 2007;195(1):e172-180.##Takagi S, Iwai N, Miyazaki S, Nonogi H, Goto Y. Relationship between ABCA1 genetic variation and HDL cholesterol level in subjects with ischemic heart diseases in Japanese. Thromb Haemost 2002;88(2):369-370.##Liu SL, Guo ZG, Lai WY, Tu Y, Chen JT. [Distribution of-477C/T single nucleotide polymorphism in the promoter region of ABCA1 gene and its significance for plasma lipids levels in normal Chinese Han population]. Di Yi Jun Yi Da Xue Bao 2004;24(6):650-652.##Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol 2015;15(2):104-116.##Liu M, Chung S, Shelness GS, Parks JS. Hepatic ABCA1 and VLDL triglyceride production. Biochim Biophys Acta 2012;1821(5):770-777.##Chung S, Gebre AK, Seo J, Shelness GS, Parks JS. 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In Vitro Activity of Linezolid in Combination with Photodynamic Inactivation Against Staphylococcus aureus Biofilms 2 2 Background: Biofilm infections are a major challenge in medical practice. Bacteria that live in a biofilm phenotype are more resistant to both antimicrobial therapy and host immune responses compared to their planktonic counterparts. So, there is need for new therapeutic strategies to combat these infections. A promising approach [known as Photodynamic Inactivation (PDI)] to kill bacteria growing as biofilms uses light in combination with a photosensitizer to induce a phototoxic reaction which produces reactive oxygen species that can destroy lipids and proteins causing cell death. PDI does not always guarantee full success, so, combination of PDI with antibiotics may give increased efficiency. This study aimed to determine if PDI was effective in the eradication of Staphylococcus aureus (S. aureus) biofilms in combination with linezolid. Methods: The susceptibility of biofilm cultures of three S. aureus strains to Methylene Blue (MB) and Toluidine Blue O (TBO)-mediated PDI was determined alone and in combination with linezolid. Results: Bactericidal activity (≥3 log10 reduction in viable cell count) was not achieved with MB/TBO-PDI or antibiotic treatment alone. When antibiotic treatment was combined with TBO-PDI, a greater reduction in viable count than antibiotic alone was observed for two strains. Conclusion: This study showed that although TBO-PDI did not have good bactericidal activity against S. aureus biofilms; it increased the antimicrobial activity of linezolid against these bacteria. 44 48 Nasim Kashef Department of Microbiology, Faculty of Biology, College of Science, University of Tehran Department of Microbiology, Faculty of Biology, College of Science, University of Tehran Iran Mahboobeh Akbarizare Department of Microbiology, Faculty of Biology, College of Science, University of Tehran Department of Microbiology, Faculty of Biology, College of Science, University of Tehran Iran Mohammad Reza Razzaghi Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences Iran Antibiotic therapyBiofilmPhotodynamic inactivationStaphylococcus aureus 266.pdf Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol 2004;2(2):95-108.##Bryers JD. Medical biofilms. Biotechnol Bioeng 2008;100(1):1-18.##El-Azizi M, Rao S, Kanchanapoom T, Khardori N. In vitro activity of vancomycin, quinupristin/dalfopristin, and linezoid against intact and disrupted biofilms of staphylococci. Ann Clin Microbio Antimicrob 2005;4:2.##Mah TF, O'Toole GA. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol 2001;9(1):34-39.##Kim PY, Kim YS, Koo IG, Jung JC, Kim GJ, Choi MY, et al. Bacterial inactivation of wound infection in a human skin model by liquid-phase discharge plasma. PLoS ONE 2011;6(8):e24104.##Wainwright M, Crossley KB. Photosensitizing agents-circumventing resistance down biofilms: a review. Int Biodeter Biodegrad 2004;53:119-126.##Jori G. Photodynamic therapy of microbial infections: state of the art and perspectives. J Environ Pathol Toxicol Oncol 2006;25(1-2):505-519.##Beirão S, Fernandes S, Coelho J, Faustino MA, Tomé JP, Neves MG, et al. Photodynamic inactivation of bacterial and yeast biofilms with a cationic porphyrin. Photochem Photobiol 2014;90(6):1387-1396.##Gad F, Zahra T, Hasan T, Hamblin MR. Effects of growth phase and extracellular slime on photodynamic inactivation of gram-positive pathogenic bacteria. Antimicrob Agents Chemother 2004;48(6):2173-2178.##Lin HY, Chen CT, Huang CT. Use of merocyanine 540 for photodynamic inactivation of Staphylococcus aureus planktonic and biofilm cells. Appl Environ Microbiol 2004;70(11):6453-6458.##Kashef N, Karami S, Djavid GE. Phototoxic effect of hypericin alone and in combination with acetylcysteine on Staphylococcus aureus biofilms. Photodiagnosis Photodyn Ther 2015;12(2):186-192.##Chibebe Junior J, Fuchs BB, Sabino CP, Junqueira JC, Jorge AO, Ribeiro MS, et al. Photodynamic and antibiotic therapy impair the pathogenesis of Enterococcus faecium in a whole animal insect model. PLoS One 2013;8(2):e55926.##Barra F, Roscetto E, Soriano AA, Vollaro A, Postiglione I, Pierantoni GM, et al. Photodynamic and antibiotic therapy in combination to fight biofilms and resistant surface bacterial infections. Int J Mol Sci 2015;16(9):20417-20430.##Cassidy CM, Donnelly RF, Elborn JS, Magee ND, Tunney MM. Photodynamic Antimicrobial Chemotherapy (PACT) in combination with antibiotics for treatment of Burkholderia cepacia complex infection. J Photochem Photobiol B 2012;106:95-100.##Dastgheyb SS, Eckmann DM, Composto RJ, Hickok NJ. Photo-activated porphyrin in combination with antibiotics: therapies against Staphylococci. J Photochem Photobiol B 2013;129:27-35.##Swaney SM, Aoki H, Ganoza MC, Shinbarger DL. The oxazolidinone linezolid inhibits intiation of protein synthesis in bacteria. Antimicrob Agents Chemother 1998;42(12):3251-3255.##Sharma M, Visai L, Bragheri F, Cristiani I, Gupta PK, Speziale P. Toluidine blue-mediated photodynamic effects on staphylococcal biofilms. Antimicrob Agents Chemother 2008;52(1):299-305.##Clinical and Laboratory Standards Institute publications. Methods for determining bactericidal activity of antimicrobial agents; Approved Guideline. Pennsylvania: Wayne, PA; 1999. 7 p.##Vilela SF, Junqueira JC, Barbosa JO, Majewski M, Munin E, Jorge AO. Photodynamic inactivation of Staphylococcus aureus and Escherichia coli biofilms by malachite green and phenothiazine dyes: an in vitro study. Arch Oral Biol 2012;57(6):704-710.##Izano EA, Amarante MA, Kher WB, Kaplan JB. Differential roles of poly-N-acetylglucosamine surface polysaccharide and extracellular DNA in Staphylococcus aureus and Staphylococcus epidermidis biofilms. Appl Environ Microbiol 2008;47(2):470-476.##Li X, Guo H, Tian Q, Zheng G, Hu Y, Fu Y, et al. Effects of 5-aminolevulinic acid-mediated photodynamic therapy on antibiotic-resistant staphylococcal biofilm: an in vitro study. J Surg Res 2013;184(2):1013-1021.##Grinholc M, Rapacka-Zdonczyk A, Rybak B, Szabados F, Bielawski KP. Multiresistant strains are as susceptible to photodynamic inactivation as their naïve counterparts: protoporphyrin IX-mediated photoinactivation reveals differences between methicillin-resistant and methicillin-sensitive Staphylococcus aureus strains. Photomed Laser Surg 2014;32(3):121-129.##Park JH, Ahn MY, Kim YC, Kim SA, Moon YH, Ahn SG, et al. In vitro and in vivo antimicrobial effect of photodynamic therapy using a highly pure chlorin e6 against Staphylococcus aureus Xen29. Biol Pharm Bull 2012;35(4):509-514.##Di Poto A, Sbarra MS, Provenza G, Visai L, Speziale P. The effect of photodynamic treatment combined with antibiotic action or host defense mechanisms on Staphylococcus aureus biofilms. 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