Research in Molecular Medicine

en Aptamers as Targeting Agents: Revolutionizing the Delivery of Plant Bioactive Compounds for Cancer Treatment داروسازی Pharmacology review review <div style="text-align: justify;">Cancer represents a significant public health challenge, being one of the leading causes of illness and death globally. The urgent need for innovative, effective, and less toxic therapeutic strategies is paramount. Natural products, particularly plant bioactive compounds, have shown notable anticancer properties but face challenges, such as poor solubility and low bioavailability. This review explores the innovative role of aptamers in enhancing the delivery of these compounds. Aptamers, with their unique properties, offer a promising solution to the challenges faced by natural compounds, facilitating targeted drug delivery and improving therapeutic outcomes. By leveraging the specificity and binding affinity of aptamers, we can revolutionize the delivery of plant bioactive compounds, ultimately advancing cancer treatment and improving patient care. The integration of nanotechnology further enhances the potential of aptamer-guided delivery systems, marking a significant advancement in cancer therapy.</div>   Aptamer, plant bioactive compound, cancer, nanoparticle 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1086-1&slc_lang=en&sid=1 Leila Asadian leilaasadian@ymail.com 100319475328460013505 100319475328460013505 No Assistant Professor of Emergency Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Narges Hedayati Hedayatin931@mums.ac.ir 100319475328460013506 100319475328460013506 No Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Seyed Mohammad Amin Jafari r.yazdian@mazums.ac.ir 100319475328460013507 100319475328460013507 No School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Rezvan Yazdian-Robati yazdianr921@gmail.com 100319475328460013508 100319475328460013508 Yes Pharmaceutical Sciences Research Center, Institute of Herbal Medicines and Metabolic Disorders, Mazandaran University of Medical Sciences, Sari, Iran

en Expression of CD39 and CD73 Ectonucleotidases in Interferon--Treated Human Wharton's Jelly Mesenchymal Stem Cells ايمونولوژي Immunology پژوهشي Research Background: Mesenchymal stem cells (MSCs) exhibit substantial immunomodulatory properties. Interferon gamma (IFN-γ) exposure has been shown to enhance the immunoregulatory capacity of MSCs. This study aimed to evaluate the expression levels of ectonucleotidases CD39 and CD73, which generate adenosine, a potent immunosuppressant, in Wharton's Jelly-mesenchymal stem cells (WJ-MSCs) cultured in the presence or absence of IFN-g. Methods: MSCs isolated from human umbilical cord Wharton's jelly were cultured and propagated. Phenotypic characterization of the isolated cells was performed using flow cytometry to assess the expression of characteristic surface markers. The cultured MSCs were then treated with IFN-g. After 24 hours of treatment, the expression levels of CD39 and CD73 genes were quantified in both IFN-g-treated and untreated cells using real-time quantitative polymerase chain reaction. Results: Exposure to IFN-γ resulted in a significant upregulation of CD39 gene expression compared with untreated cells, while no statistically significant difference was observed in CD73 expression between IFN-γ-treated and untreated groups. Conclusion: The findings suggest that CD39 upregulation may serve as a molecular integrator of inflammatory cytokine-mediated licensing of MSCs, contributing to their immunoregulatory capacity possibly through modulation of the expression of downstream target genes; however, further studies are required to indicate the inflammatory and immunosuppressive effects associated with CD39 induction.   Mesenchymal stem cells, Interferon gamma, Adenosine, CD39, CD73, Immunomodulation 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-829-5&slc_lang=en&sid=1 Leila Pirdel leilapirdel@yahoo.com 100319475328460013526 100319475328460013526 Yes Department of Medicine, Ard.C., Islamic Azad University, Ardabil, Iran. Manijeh Pirdel pirdelm@yahoo.com 100319475328460013527 100319475328460013527 No Department of Midwifery, As.C., Islamic Azad University, Astara, Iran.

en Protective Effects of Laser-Irradiated Streptococcus pneumoniae: A Novel Vaccine Candidate ميکروبيولوژي Microbiology پژوهشي Research <div style="text-align: justify;">Streptococcus pneumoniae (S. pneumoniae) is a significant cause of community-acquired pneumonia worldwide. Pneumococcal vaccines can prevent severe disease; however, their high cost, limited serotype coverage, and variable effectiveness across populations underscore the need for alternative vaccine strategies. Laser irradiation has been proposed as a novel approach to attenuate bacterial virulence while preserving immunogenicity. Clinical isolates of S. pneumoniae were irradiated using low‑energy laser irradiation at wavelengths of 660 nm, 820 nm, and 915 nm to prepare an inactivated bacterial vaccine. Sterility testing confirmed complete bacterial inactivation. BALB/c mice were immunized three times at two-week intervals and were then challenged with wild-type S. pneumoniae. A commercial pneumococcal vaccine served as a positive control. Antibody responses (immunoglobulin M [IgM], IgG, and IgA) were measured, and survival was monitored for 21 days post-challenge. Irradiation at 915 nm was the most effective for bacterial inactivation. Mice immunized with the 915 nm-inactivated vaccine showed significantly higher levels of IgM, IgG, and IgA compared to the unvaccinated group. Following bacterial challenge, all mice in this group survived, whereas 40% of mice immunized with the commercial vaccine died within 21 days after challenge. Low-energy laser irradiation at 915 nm effectively inactivated S. pneumoniae while retaining its immunogenic properties. Immunization with this preparation elicited robust antibody responses and provided complete protection in mice, suggesting that it may serve as a novel pneumococcal vaccine candidate.</div> Pneumococcal vaccine, Laser, Immunization, Antibody. 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1388-2&slc_lang=en&sid=1 Nabeel Khudhair Hassoon nabelalmoswi@gmail.com 100319475328460013520 100319475328460013520 No Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran. Mohammad Rabbani Khorasgani m.rabbani@biol.ui.ac.ir 100319475328460013521 100319475328460013521 Yes Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran. Ihsan F. Rostum nouralihasn@yahoo.com 100319475328460013522 100319475328460013522 No College of Cosmetic & Laser Techniques, Cordoba Private University, Al- Najaf Al- Ashraf - Iraq. Babak Beikzadeh b.beikzadeh@bio.ui.ac.ir 100319475328460013523 100319475328460013523 No Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.

en Prediction of Physicochemical Properties, Antioxidant Activity, and Transmembrane Helices of Alpha and Beta Globin Chains of Hemoglobin بيولوژي Biology پژوهشي Research <div style="text-align: justify;">Background: This study aimed to predict the physicochemical properties, antioxidant activity, and potential penetration of alpha helices of the alpha- and beta-globin chains of human hemoglobin in membranes of red blood cells (RBCs). Methods: The physicochemical properties of hemoglobin's alpha- and beta-globin chains were predicted using the ProtScale tool. Antioxidant activity was predicted using AnOxPePred, and transmembrane regions were identified using TMHMM‑2.0. Statistical analysis was conducted using the Kolmogorov-Smirnov test and Pearson correlation in SPSS software (version 27). Results: Based on the prediction results, a significant direct correlation was observed between hydrophobicity and membrane‑anchoring tendency for both alpha globin (r = 0.494, P < 0.001) and beta-globin (r = 0.869, P < 0.001) chains. The highest free radical scavenging (FRS) score in the alpha globin chain was associated with the sequence WGKVGAHAGEYGAEALERMF (residues 14-33), while the highest FRS in the beta-globin chain was linked to the sequence VLVCVLAHHFGKEFTPPV (residues 113-126). Alpha globin chains showed a higher tendency to penetrate the inner layer of the cell membrane of red blood cells (RBCs) than beta-globin chains. Discussion: The study predicted that high FRS scores are located on the outer surface of alpha- and beta-globin chains, particularly at loop structures and junctions. Alpha globin chains are more likely to penetrate the cell membrane. Conclusion: Regions with higher FRS scores are more exposed to the cytoplasm, which contains more free radicals.</div> Hemoglobin, Antioxidant, Transmembrane Alpha Helices, Antioxidant Activity, Physicochemical Properties 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1369-2&slc_lang=en&sid=1 Roohallah Yousefi r.yosefi@modares.ac.ir 100319475328460013509 100319475328460013509 No Department of Biochemistry, Faculty of biology of Tarbiat Modares University, Tehran, Iran Seyed Hossein khaleghinejad hosseinkhaleghi89@yahoo.com 100319475328460013510 100319475328460013510 Yes Department of Bioinformatics and Applied Biotechnology, Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran. Dariush Gholami d.gholami@ausmt.ac.ir 100319475328460013511 100319475328460013511 No Department of Bioinformatics and Applied Biotechnology, Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol, Iran Sadegh Hasannia hasannia@modares.ac.ir 100319475328460013512 100319475328460013512 No Department of Biochemistry, Faculty of biology of Tarbiat Modares University, Tehran, Iran.

en Narrative Review of β-Lactam Resistance in Key Bacterial Pathogens: Efficacy and Innovations in Combination Therapies باکتری شناسی پزشکی Medical bacteriology review review <div style="text-align: justify;">Background: β-Lactam antibiotics (BLIs) are essential for treating bacterial infections, but resistance is increasing due to β-lactamases, altered penicillin-binding proteins (PBPs), and reduced permeability in pathogens, such as E. coli, K. pneumoniae, P. aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), A. baumannii, N. gonorrhoeae, and vancomycin-resistant Enterococcus faecium. BLIs aim to restore the effectiveness of these antibiotics, but non-enzymatic resistance remains a challenge. Methods: This narrative review searched databases including PubMed, Scopus, Web of Science, and Google Scholar for articles published between 2020 and 2025. Key search terms included "beta-lactam resistance" and "clustered regularly interspaced short palindromic repeats (CRISPR)-mediated antimicrobial resistance." Out of approximately 1,200 articles, 88 peer-reviewed studies were selected, focusing on resistance mechanisms, prevalence, and innovative therapies for selected pathogens. Results: E. coli and K. pneumoniae exhibit high prevalence rates of extended-spectrum β-lactamases, with Cefotaximase‑Munich (CTX-M) found in 72.5% of cases and carbapenemase blaKPC-2 in 66% of K. pneumoniae. Methicillin-resistant Staphylococcus aureus (MRSA) relies on the mecA gene (30% prevalence in burn infections), while A. baumannii shows a prevalence of blaOXA-23 at 68.9%, and N. gonorrhoeae has blaTEM-1 in 86.88% of cases. The combination of ceftazidime and avibactam reduces mortality in carbapenem-resistant K. pneumoniae (CRKP) infections by 52%, with additional synergy observed when combined with aztreonam (89% effectiveness). Phage therapy and CRISPR/Cas9 have shown effectiveness in targeting multidrug-resistant (MDR) strains and restoring susceptibility. Conclusion: Managing β-lactam resistance effectively requires a deep understanding of pathogen-specific mechanisms. While β-lactamase inhibitors (BLIs), such as ceftazidime/avibactam, are useful, their effectiveness is limited by efflux pumps and modifications to penicillin-binding proteins (PBPs). Bacteriophage therapy has proven highly effective in significantly reducing multidrug-resistant (MDR) A. baumannii in vivo, and CRISPR/Cas9 can precisely target resistance genes such as blaKPC to restore antibiotic sensitivity. Additionally, nanocarrier systems improve drug delivery by overcoming challenges like efflux and biofilm formation. This review synthesizes advancements made since 2020, highlighting innovative strategies involving phage therapy, CRISPR, and nanocarriers, while addressing critical research gaps in understudied pathogens, paving the way for precision antimicrobial therapies. Background: β-Lactam antibiotics (BLIs) are essential for treating bacterial infections, but resistance is increasing due to β-lactamases, altered penicillin-binding proteins (PBPs), and reduced permeability in pathogens, such as E. coli, K. pneumoniae, P. aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), A. baumannii, N. gonorrhoeae, and vancomycin-resistant Enterococcus faecium. BLIs aim to restore the effectiveness of these antibiotics, but non-enzymatic resistance remains a challenge. Methods: This narrative review searched databases including PubMed, Scopus, Web of Science, and Google Scholar for articles published between 2020 and 2025. Key search terms included "beta-lactam resistance" and "clustered regularly interspaced short palindromic repeats (CRISPR)-mediated antimicrobial resistance." Out of approximately 1,200 articles, 88 peer-reviewed studies were selected, focusing on resistance mechanisms, prevalence, and innovative therapies for selected pathogens. Results: E. coli and K. pneumoniae exhibit high prevalence rates of extended-spectrum β-lactamases, with Cefotaximase‑Munich (CTX-M) found in 72.5% of cases and carbapenemase blaKPC-2 in 66% of K. pneumoniae. Methicillin-resistant Staphylococcus aureus (MRSA) relies on the mecA gene (30% prevalence in burn infections), while A. baumannii shows a prevalence of blaOXA-23 at 68.9%, and N. gonorrhoeae has blaTEM-1 in 86.88% of cases. The combination of ceftazidime and avibactam reduces mortality in carbapenem-resistant K. pneumoniae (CRKP) infections by 52%, with additional synergy observed when combined with aztreonam (89% effectiveness). Phage therapy and CRISPR/Cas9 have shown effectiveness in targeting multidrug-resistant (MDR) strains and restoring susceptibility. Conclusion: Managing β-lactam resistance effectively requires a deep understanding of pathogen-specific mechanisms. While β-lactamase inhibitors (BLIs), such as ceftazidime/avibactam, are useful, their effectiveness is limited by efflux pumps and modifications to penicillin-binding proteins (PBPs). Bacteriophage therapy has proven highly effective in significantly reducing multidrug-resistant (MDR) A. baumannii in vivo, and CRISPR/Cas9 can precisely target resistance genes such as blaKPC to restore antibiotic sensitivity. Additionally, nanocarrier systems improve drug delivery by overcoming challenges like efflux and biofilm formation. This review synthesizes advancements made since 2020, highlighting innovative strategies involving phage therapy, CRISPR, and nanocarriers, while addressing critical research gaps in understudied pathogens, paving the way for precision antimicrobial therapies.</div> Beta-Lactam, Klebsiella pneumonia, CRISPR/Cas9, β-Lactamase inhibitors 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1365-4&slc_lang=en&sid=1 Rouzbeh Sojoudi Masuleh rouzbehs77@gmail.com 100319475328460013498 100319475328460013498 No Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Zahra Salimian Rizi zahra.salimian2001@gmail.com 100319475328460013499 100319475328460013499 No Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Ali Rashidi iamalirashidi2020@gmail.com 100319475328460013500 100319475328460013500 No Department of Microbiology, Razi Vaccine and Serum Research Institute, Karaj, Iran Amir Hossein Salek Khalili amirhsk81@gmail.com 100319475328460013501 100319475328460013501 No Department of Medical Bacteriology, School of Medicine, Shahed University, Tehran, Iran. Seyedeh Zahra Mohsenzadeh Mohsenzademahyaa@gmail.com 100319475328460013502 100319475328460013502 No Medical Laboratory Science, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Ghazale Aghaei Ghazaleh.aghaee8080@gmail.com 100319475328460013503 100319475328460013503 No Department of Microbiology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran. Mohammad Karimbakhsh mohammadkarimbakhsh1@gmail.com 100319475328460013504 100319475328460013504 Yes Department of Bacteriology, Pasteur institute of Iran, Tehran, Iran.

en Cytotoxic Effects of Dimethylamino Parthenolide on the Rheumatoid Arthritis Fibroblast-Like Synoviocytes Cell Line ايمونولوژي Immunology گزارش کوتاه Short Communication <div style="text-align: justify;">Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which fibroblast-like synoviocytes (FLS) play a critical role in its pathogenesis. Due to the significant side effects associated with conventional treatments and the lack of response to the therapy in some patients, researchers are investigating novel therapeutic approaches that offer improved efficacy and a more favorable safety profile. This study aimed to investigate the cytotoxic activity of dimethylamino parthenolide (DMAPT) on the rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) cell line. Methods: For this purpose, the RA-FLS cell line, previously generated in our unpublished studies, was treated with varying concentrations of DMAPT (0-160 μM) for 24 and 48 hours. Cell viability was assessed using the MTT assay. The half-maximal inhibitory concentration (IC₅₀) values were derived from dose-response curves fitted using GraphPad Prism software (version). Results: Our results demonstrated that DMAPT exerts cytotoxic effects on the RA-FLS cell line, leading to a significant reduction in cell viability. This cytotoxic effect is dose-dependent, such that cell viability decreased with increasing dose. The half-maximal inhibitory concentration (IC ₅₀) values of DMAPT for rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were 51.02 μM at 24 hours and 45.8 μM at 48 hours. Conclusion: Our results demonstrated that DMAPT exerts cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS).</div> Dimethylamino Parthenolide, DMAPT, Rheumatoid Arthritis, RAFLS, FLS, Fibroblast-Like Synoviocytes 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1465-1&slc_lang=en&sid=1 Sara Sadeqi Sadeqisara390@yahoo.com 100319475328460013513 100319475328460013513 No Department of Immunology and Microbiology, Sari Medical School, Mazandaran University of Medical Sciences, Sari, Iran Zahra Yazdani zahrayazdanikachooi1391@gmail.com 100319475328460013514 100319475328460013514 No Department of Immunology and Microbiology, Sari Medical School, Mazandaran University of Medical Sciences, Sari, Iran Parisa Zafari pzafari.70@gmail.com 100319475328460013515 100319475328460013515 No Department of Immunology, School of Medicine, Hamedan University of Medical Sciences, Hamedan, Iran. Salman Ghafari salmanghafari@gmail.com 100319475328460013516 100319475328460013516 No Orthopedic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Alireza Rafiei rafiei1710@gmail.com 100319475328460013517 100319475328460013517 Yes Department of Immunology and Microbiology, Sari Medical School, Mazandaran University of Medical Sciences, Sari, Iran.