Pasteur Institute of Iran Iranian Biomedical Journal 2008-823X 30 3 2026 04 01 Resveratrol in Combination Therapy: Mechanisms and Limitations of Resveratrol in Cancer, Regeneration, and Chronic Disease 97 124 740687 10.61882/ibj.5210 EN Effat Noori Department of Medical Biotechnology, Faculty of Medicine, Shahed University, Tehran, Iran 0000-0002-8196-1967 Ramazan Rezaei Department of Immunology, Faculty of Medicine, Shahed University, Tehran, Iran 0000-0002-4504-7238 Samira Valiyari Department of Medical Biotechnology, Faculty of Medicine, Shahed University, Tehran, Iran Mahmood Rekabgardan Department of Regenerative Medicine, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 0000-0002-0670-8021 Parvin Mohammadi Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran 0000-0002-4724-8113 Fatemeh Soleymani Department of Medical Biotechnology, Faculty of Medicine, Shahed University, Tehran, Iran 0009-0003-7081-2899 Elham Sharif Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 0000-0001-5559-2048 Zohreh Jafari Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 0000-0002-1532-576X Delsuz Rezaee Department of Genetic and Molecular Medicine, School of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran 0000-0001-9547-3211 Fatemeh Hajighasemi Department of Immunology, Faculty of Medicine, Shahed University, Tehran, Iran; 0000-0003-0145-4621 Forough Shams* Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 0000-0001-5862-2679 Journal Article 2026 08 25 Resveratrol (RSV), a nonflavonoid polyphenol phytoalexin, has considerable therapeutic potential for managing chronic and acute diseases due to its anti-inflammatory, anti-cancer, antimicrobial, and antioxidant properties. It can help protect cells from free radical damage and modulate signaling pathways in the body to promote overall health. RSV can also facilitate the therapeutic effects of mesenchymal stem cells by increasing their self-renewal, survival, anti-aging effects, and lineage commitment. However, the natural form of RSV has limitations, such as poor intestinal absorption and low bioavailability. This review focuses on the potential of RSV to explore its effects and mechanisms of action in cancer, regenerative medicine, and chronic disease. It also discusses how RSV can protect normal tissue against genomic instability and presents findings from combination therapies involving RSV and nanoparticle-based agents. Overall, this review highlights the latest developments regarding RSV as a promising compound, emphasizing the potential to overcome its limitations.

https://ibj.pasteur.ac.ir/article_740687_7270e4c01c129862910cdeea71f74b2d.pdf

Pasteur Institute of Iran Iranian Biomedical Journal 2008-823X 30 3 2026 04 01 Global Perspectives on Rabies Prevention and Control: A Decade of World Rabies Day Themes and Progress toward Elimination (2016–2025) 125 131 740688 10.61882/ibj.5398 EN Ashkan Alamdary Research and Development Department, Production and Research Complex, Pasteur Institute of Iran, Karaj, Iran; 0000-0001-7776-8809 Mehdi Ajorloo Biological Products and Blood Safety Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Alireza Gholami Research and Development Department, Production and Research Complex, Pasteur Institute of Iran, Karaj, Iran; 0000-0003-0706-2821 Journal Article 2026 08 25 Rabies is a fatal zoonotic disease, responsible for approximately 59,000 human deaths annually; the majority occur in developing regions of Asia and Africa. This review explores worldwide efforts to prevent and control rabies during 2016–2025, using the evolving themes of World Rabies Day (WRD) as a framework. The research objective is to assess epidemiological trends, intervention strategies, challenges, and innovations related to the World Health Organization's target of zero human rabies deaths by 2030. The findings highlight a significant reduction in global rabies occurrence, with mass vaccination campaigns for dogs achieving 70% coverage in Guinea and a 95% decrease in human cases in Latin America. However, gaps in surveillance, vaccine shortages, and poor public education persist. Low-cost intradermal prophylaxis, monoclonal antibodies, and AI-driven surveillance systems are promising approaches but remain constrained by socioeconomic inequalities and insufficient investment. Achieving “Zero by 30” requires stronger collaboration, equitable resource distribution, and sustained community mobilization.

https://ibj.pasteur.ac.ir/article_740688_3c80206ff30b62c56c2d46268b9f4fcc.pdf

Pasteur Institute of Iran Iranian Biomedical Journal 2008-823X 30 3 2026 04 01 Therapeutic Effects of Vernonia amygdalina on Oxidative Stress and Histopathological Damage in Pancreatic Toxicity Induced by 1,2-dimethylhydrazine in Wistar Rats 132 140 740689 10.61882/ibj.5354 EN Augustine Okpiabhele Department of Biochemistry, Faculty of Natural and Applied Sciences, Michael and Cecilia Ibru University, Ughelli, Delta State, Nigeria; 0000-0002-2552-2732 Osahon Abu Department of Biochemistry, Faculty of Life Sciences, University of Benin, Benin City, Edo State, Nigeria 0000-0002-8007-2199 Ambrose Akpovona Department of Biochemistry, Faculty of Natural and Applied Sciences, Michael and Cecilia Ibru University, Ughelli, Delta State, Nigeria; 0000-0003-1255-9250 Journal Article 2026 08 25 Background: 1,2-Dimethylhydrazine (DMH) induces pancreatic oxidative stress via reactive oxygen species overproduction and antioxidant depletion. Given the rich phytochemical and antioxidant properties of Vernonia amygdalina, this study investigated its therapeutic effects in inhibiting oxidative stress and histopathological damage induced by DMH in Wistar rats. Methods: Adult male Wistar rats were divided into different groups and exposed to DMH via the intraperitoneal route. Animals received oral administration of V. amygdalina ethanol extract at low (200 mg/kg) and high (400 mg/kg) doses, both before and after DMH exposure. The pancreatic tissues were then subjected to biochemical analysis and histopathological examination using standardized protocols. Results: The administration of V. amygdalina significantly attenuated body weight loss in both the pre- and post-treatment groups. Furthermore, it significantly improved (p < 0.05) the levels of total protein, amylase, nitric oxide, catalase, superoxide dismutase, malondialdehyde, glutathione peroxidase, glutathione (GSH), and glutathione reductase and reduced GSH percentages compared to the DMH group. The pancreatic tissues from DMH-induced rats treated with V. amygdalina showed a significant reduction (p < 0.05) in organ weight compared to the DMH group. Histological studies revealed the protective and regenerative effects of V. amygdalina on pancreatic tissues. Conclusion: This study indicates that V. amygdalina can effectively suppress irregularities in pancreatic function and oxidative stress induced by DMH toxicity due to its antioxidant properties. This observation implies that V. amygdalina holds promise as a novel therapeutic strategy for improving DMH systemic toxicity in animal models and could serve as a benchmark for future clinical trials.

https://ibj.pasteur.ac.ir/article_740689_32c10ba02271a387c00ccd8599db944b.pdf

Pasteur Institute of Iran Iranian Biomedical Journal 2008-823X 30 3 2026 04 01 Antidepressant Effects of L-Arginine and Its Role in Brain Energy Metabolism 141 152 740690 10.61882/ibj.5314 EN Temuri Mantashashvili Department of Biology, Ivane Javakhishvili Tbilisi State University, 11th Building, University Street, 0186, Tbilisi, Georgia 0000-0002-9738-1027 Luka Nakaidze Department of Biology, Ivane Javakhishvili Tbilisi State University, 11th Building, University Street, 0186, Tbilisi, Georgia 0009-0004-9396-397X Mariam Shengelia Department of Biology, Ivane Javakhishvili Tbilisi State University, 11th Building, University Street, 0186, Tbilisi, Georgia 0009-0001-1276-5030 Nana Koshoridze Department of Biology, Ivane Javakhishvili Tbilisi State University, 11th Building, University Street, 0186, Tbilisi, Georgia 0000-0002-6856-174X Journal Article 2026 08 25 Background: Mitochondrial dysfunction and impaired cellular energy metabolism are increasingly recognized as key contributing factors in depression. This study evaluated the amino acid L-arginine as a potential agent for behavioral rescue and bioenergetic restoration using a corticosterone-induced rat model of depression. Methods: Male rats were randomly assigned to four groups (n = 10): control (DMSO intraperitoneally [i.p.] + water oral gavage), corticosterone-induced depression (20 mg/kg, i.p. for 14 days), L-arginine treatment (150 mg/kg, oral gavage for 14 days), and fluoxetine (10 mg/kg, oral gavage for 14 days). To ensure handling equivalence, all oral administrations were performed via gavage (1.0 mL/100 g). Behavioral rescue was assessed via open field, forced swim (FST), and tail suspension (TST) tests. Hippocampal energy metabolism and PI3K/Akt/mTOR pathway activation were analyzed. Results: L-arginine significantly improved the hippocampal bioenergetic profile, demonstrating efficacy comparable to the positive control fluoxetine. It led to a significant reduction in immobility time during FST and TST, alongside restoring glycolysis, the tricarboxylic acid cycle, and mitochondrial respiratory chain activities. Concurrently, L-arginine enhanced the activation state of the PI3K/Akt/mTOR signaling pathway (phosphorylated Akt/Akt and p-mTOR/mTOR ratios) and improved the functional state of the mitochondrial permeability transition pore. These metabolic and signaling improvements strongly correlated with the rescue of depressive-like behaviors. Conclusion: Our findings demonstrate that L-arginine possesses potent antidepressant-like potential, mediated through bioenergetic restoration and signaling pathway modulation. By activating key metabolic processes in the hippocampus, L-arginine effectively restores impaired cellular energy homeostasis, suggesting its promise as a metabolic modulator for alleviating neurobiological disturbances associated with depressive conditions.

https://ibj.pasteur.ac.ir/article_740690_9427afcb5941c8b2c4899253b0c9bf8f.pdf

Pasteur Institute of Iran Iranian Biomedical Journal 2008-823X 30 3 2026 04 01 Molecular Characterization of Multi-Drug Resistant Histamine-Producing Gram-Negative Bacteria Isolated from Fermented Prosopis africana Seeds (okpee) in Nigeria 153 164 740691 10.61882/ibj.5259 EN Cyril Adonu Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Enugu State University of Science and Technology, Enugu State, Nigeria 0000-0002-3486-8137 Sunday Urama Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Enugu State University of Science and Technology, Enugu State, Nigeria 0009-0002-3691-5897 Abugu Felix Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Enugu State University of Science and Technology, Enugu State, Nigeria 0009-0000-3593-6667 Eze Victor Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Enugu State University of Science and Technology, Enugu State, Nigeria 0009-0002-6866-8931 Treasure Ujam Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Enugu State University of Science and Technology, Enugu State, Nigeria 0000-0002-8523-3086 Gospel OKpara Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Enugu State University of Science and Technology, Enugu State, Nigeria 0009-0007-8987-2428 Hannah Okorie Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Enugu State University of Science and Technology, Enugu State, Nigeria 0000-0003-4477-3972 Eucharia Imanyika Department of Medical Microbiology, College of Medicine, Enugu State University of Science and Technology, Enugu State, Nigeria 0000-0002-8611-8952 Journal Article 2026 08 25 Background: Fermented Prosopis africana seeds (okpee) are naturally protein-rich but exude odors that attract houseflies. These flies can carry contaminants, including pathogens and histamine-producing bacteria. Bacterial histamine in food can cause illnesses and pseudo-hypersensitivity reactions. This study investigated multidrug-resistant, histamine-producing Gram-negative bacteria (GNB) isolated from okpee sold in Enugu Ezike, Nigeria. Methods: Histamine content of the mesquite seed samples was determined using high-performance liquid chromatography. Bacteriological isolates from randomly sampled okpee were identified by 16S rRNA gene sequencing. Antibiotic susceptibility of the isolated bacteria was assessed using the Kirby-Bauer disk agar diffusion method. The isolates were also screened for resistant plasmids and virulence genes (Stx2 and toxA). Results: Histamine levels of the fermented samples averaged 1.0 × 10-4-6.2 × 10-1 mg/kg. Of 240 samples of okpee screened, 25 (10.5%) were contaminated with histamine-producing GNB, including Pseudomonas spp., Escherichia coli, E. fergusonii, and Shigella flexneri. All the isolated histamine-producing bacteria were resistant to amoxicillin, erythromycin, ampicillin, and cefuroxime, with more than 50% exhibiting resistance to the other antibiotics tested. The test isolates were found to harbor multiple resistant plasmids (size: 0.5 kbp-10 kbp) and virulence factor genes Stx2 and toxA. Conclusion: This study observed a high prevalence of bacterial contaminants capable of producing histamine in okpee sold in Enugu Ezike, Nigeria. The isolates were multidrug-resistant and harbored virulent genes, posing a serious public health risk. Therefore, strengthening hygiene practices during the production and handling of okpee is necessary to prevent contamination and ensure product safety.

https://ibj.pasteur.ac.ir/article_740691_5538a53a9677d7a0ad0569abbadfb646.pdf

Pasteur Institute of Iran Iranian Biomedical Journal 2008-823X 30 3 2026 04 01 Antiviral Potential of Lipopeptide Biosurfactant Isolated from Acinetobacter junii B6 165 173 740692 10.61882/ibj.5241 EN Amir Mohammad Bagheri Herbal and Traditional Medicines Research Center, Institute of Pharmaceutical Sciences, Kerman University of Medical Sciences, Kerman, Iran 0000-0002-7375-4888 Hamid Forootanfar Pharmaceutical Sciences and Cosmetic Products Research Center, Institute of Pharmaceutical Sciences, Kerman University of Medical Sciences, Kerman, Iran 0000-0001-5049-7674 Gholamreza Dehghannoudeh Department of Pharmaceutics, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran 0000-0003-1420-2650 Mohammad Amin Raeisi Estabragh Department of Pharmaceutics, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran 0000-0001-5992-1654 Ibrahim M. Banat School of Biomedical Sciences, Faculty of Life & Health Sciences, Ulster University, Coleraine BT52 1SA, N. Ireland, UK 0000-0001-8964-2840 Hosnieh Sokhandan Influenza and Respiratory Viruses Department, Pasteur Institute of Iran, Tehran, Iran 0009-0003-1750-2090 Hadiseh Shokouhi Influenza and Respiratory Viruses Department, Pasteur Institute of Iran, Tehran, Iran; 7Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 0000-0002-4325-6554 Mandana Ohadi Pharmaceutics Research Center, Institute of Pharmaceutical Sciences, Kerman University of Medical Sciences, Kerman, Iran 0000-0001-7251-3751 Parvaneh Mehrbod* Influenza and Respiratory Viruses Department, Pasteur Institute of Iran, Tehran, Iran Journal Article 2026 08 25 Background: Influenza A virus (IAV) is a global health concern, increasing the exploration of alternative therapeutics. Biosurfactants (BSs) are biodegradable, non-toxic biomolecules with favorable biological activities. Acinetobacter junii B6, known for utilizing crude oil as a carbon and energy source, produces BSs. This study evaluated the antiviral potential of the lipopeptide biosurfactant (LPB) against H1N1/A/PR8/34 infection. Methods: A. junii B6 LPB was extracted and characterized in our previous study. The 50% cytotoxic concentration and non-cytotoxic concentration (NCTC), defined as the concentration with no toxicity on cells, were determined by the MTT assay on MDCK cells. The NCTC was exposed to the cells in the presence of PR8 (100 TCID50) under simultaneous, pre- and post-exposure combination treatments for 1 h. After 48 h of incubation, the hemagglutination and MTT assays assessed viral propagation and cell protection, respectively. Amantadine and oseltamivir served as antiviral control drugs. Results: The extracted LPB caused a 1 log2 reduction in pre- and post-exposure treatments, whereas amantadine and oseltamivir reduced viral titers by more than 1 log2. Cell protection was favorable in all combination treatments except for LPB co-treatment. LPB extract showed limited but notable anti-IAV activity, alongside cell protection. Conclusion: While LPB is less potent than amantadine and oseltamivir, its non-toxic and environmentally friendly nature warrants further study. As surfactants act on the lipid envelope, viral proteins, and nucleocapsid proteins, LPB could be potentially used as an adjuvant with other antiviral agents to control the prevalence of viral diseases and improve therapeutic outcomes.

https://ibj.pasteur.ac.ir/article_740692_1231e8515d1877a015ad2222fb5734a7.pdf

Pasteur Institute of Iran Iranian Biomedical Journal 2008-823X 30 3 2026 04 01 Clonal Diversity and Genetic Landscape of mecC-Positive S. aureus in Human Samples from Iran: First Report of CC/ST423/t742 174 187 740693 10.61882/ibj.5161 EN Mehdi Goudarzi Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 0000-0001-6720-9341 Sima Sadat Seyedjavadi Department of Mycology, Pasteur Institute of Iran, Tehran, Iran 0000-0002-5896-5636 Mozhgan Raigani Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran 0000-0003-4764-0606 Zahra Salehi Department of Mycology, Pasteur Institute of Iran, Tehran, Iran 0000-0002-4913-6211 Masoud Dadashi Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran 0000-0002-4800-2078 Mohammad Javad Nasiri Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 0000-0002-3279-0671 Journal Article 2026 08 25 Background: The emergence of mecC-carrying Staphylococcus aureus strains is a serious concern in public health. Our study investigated the clonal diversity, genetic characteristics, antimicrobial resistance, virulence determinants, biofilm-forming ability, and molecular epidemiology of mecC-positive Staphylococcus aureus isolates obtained from hospitalized patients in Iran. Methods: We analyzed 45 mecC-carrying S. aureus strains isolated from 1,590 S. aureus samples collected from different clinical sources. The characterization included antimicrobial susceptibility tests, assessment of biofilm formation, spa typing, multilocus sequence typing (MLST), and PCR analysis to detect resistance, biofilm-related, and virulence genes. Results: Our results showed that 17.8%, 17.8%, and 64.4% of the isolates were classified as weak, intermediate, and strong biofilm producers, respectively. The prevalence of the ant(4΄)-Ia and tet(M) was found in 80% and 73.3% of the isolates, respectively. MLST revealed that the 45 isolates belonged to four clonal complexes: CC8 (44.4%), CC130 (24.5%), CC121 (17.8%), and CC425 (13.3%). The majority of S. aureus isolates belonged to the CC8/ST239 lineage (44.4%). Also, tst-positive strains belonged to CC121/ST599/t5930 (17.8%) and CC8/ST239/t037 (11.1%), while eta-positive isolates belonged to CC/ST130/t843 (15.6%). Fusidic acid-resistant S. aureus isolates primarily belonged to CC8/ST239/t037 lineage (11.1%), followed by CC8/ST239/t7688 (6.7%), both carrying the fusB gene. Vancomycin-intermediate S. aureus strains were classified into CC/ST599/t5930 (6.7%) and CC/ST130/t843 (4.4%) clones. Conclusion: This study highlights the need for close and continuous monitoring of the genetic diversity and characteristics of the mecC-carrying S. aureus strains. Besides, urgent measures are required to prevent the transmission of these strains and to effectively treat associated infections.

https://ibj.pasteur.ac.ir/article_740693_f20c4f10ddd52ef71654dedc7683b846.pdf

Pasteur Institute of Iran Iranian Biomedical Journal 2008-823X 30 3 2026 04 01 Whole-Exome Sequencing Identified a Novel Mutation in an Iranian Patient with Epidermolysis Bullosa 188 192 740694 10.61882/ibj.5232 EN Reza Mirfakhraie Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 0000-0003-1709-8975 Solmaz Hassani Fard Katiraei Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 0009-0008-4691-0997 Mina Mirnezami Department of Dermatology, School of Medicine, Arak University of Medical Sciences, Arak, Iran 0000-0001-9423-004X Sahar Bayat Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, Iran 0000-0002-2066-183X Mohsen Soosanabadi Department of Medical Genetics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran 0000-0002-9359-9782 Ali Kookhaei Department of Dermatology, School of Medicine, Arak University of Medical Sciences, Arak, Iran 0009-0001-0901-4041 Milad Gholami Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, Iran 0000-0002-7201-8301 Journal Article 2026 08 25 Background: Epidermolysis bullosa (EB) is a rare, genetically heterogeneous disorder characterized by skin fragility. EB is categorized into four types: simplex, junctional, dystrophic, and Kindler syndromes. The condition is caused by mutations in several genes that are important for skin integrity and dermal-epidermal adhesion. In the present study, we recruited a patient with EB from an Iranian pedigree for genetic evaluation. Methods: Whole-exome sequencing (WES) and bioinformatics analysis were performed using genomic DNA from the patient with EB. The potential variant was confirmed by Sanger sequencing. Results: We identified a novel likely pathogenic variant in exon 3 of the COL17A1 gene: c.82dup (p.Thr28Asnfs15). The patient’s parents were heterozygous carriers of this mutation. In silico structural prediction suggested that this variant could cause premature termination of COL17A1. This variant is associated with intermediate junctional EB-4 (JEB4). Conclusion: This study highlights that WES enhances our understanding of genetic diagnosis, and it contributes to the expanded mutational spectrum of the COL17A1 gene associated with JEB.

https://ibj.pasteur.ac.ir/article_740694_a6eecfc83f7acc3a8316ed458f72d914.pdf