Reports of Biochemistry and Molecular Biology最新文献

{"title":"Betulinic Acid Attenuates Methotrexate Nephrotoxicity by Reducing Oxidative Stress and The Expression of TLR4/NF-Κb Signaling Pathway.","authors":"Mehrnoush Matin, Mohammad Javad Khodayar, Esrafil Mansouri, Yasin Etehadi, Mehrnoosh Moosavi","doi":"10.66224/rbmb.14.2.271","DOIUrl":"https://doi.org/10.66224/rbmb.14.2.271","url":null,"abstract":"<p><strong>Background: </strong>Methotrexate (MTX) is a medication widely used in the treatment of various conditions, including cancer. One potential side effect of MTX is nephrotoxicity. The purpose of the present study was to evaluate the effects of betulinic acid (BA) on MTX-induced nephrotoxicity in mice through the TLR4/NF-κB signaling pathway.</p><p><strong>Methods: </strong>Four groups- control, BA 25 mg/kg, MTX 20 mg/kg, and BA+MTX- were considered for seven days to evaluate the effect of BA on MTX nephrotoxicity. Factors such as blood urea nitrogen (BUN), serum creatinine, antioxidant enzymes, oxidative stress markers, and pro-inflammatory cytokines were investigated. Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) expression levels were measured using Western blot analysis.</p><p><strong>Results: </strong>BUN and creatinine serum levels were significantly reduced in the BA-treated group compared to the MTX group. Furthermore, BA administration inhibited the activation of the TLR4/NF-κB signaling pathway, resulting in reduced expression of TLR4 and NF-κB. This decreased the release of pro-inflammatory cytokines linked to kidney inflammation, such as interleukin-1β and tumor necrosis factor-alpha. Moreover, BA exhibited notable antioxidant properties by enhancing the activity of enzymes like catalase, superoxide dismutase, and glutathione peroxidase. This antioxidant effect was evident by decreasing the levels of oxidative stress markers, as measured by the lipid peroxidation assay, and increasing the total thiol level.</p><p><strong>Conclusions: </strong>These findings suggest that BA can ameliorate MTX-induced nephrotoxicity by reducing oxidative stress and enhancing the antioxidant defense system. It effectively reduces renal damage, inflammation, and oxidative stress. Our results demonstrate that BA's anti-inflammatory and antioxidant qualities could protect the kidneys from MTX's nephrotoxic effects.</p>","PeriodicalId":45319,"journal":{"name":"Reports of Biochemistry and Molecular Biology","volume":"14 2","pages":"271-281"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered DNA Methylation Patterns in <i>IFI44L</i> and <i>FOXP3</i> Genes in Patients with Rheumatoid Arthritis: A Case-Control Study.","authors":"Delnya Gholami, Zahra Ourang, Mohammad Saatchi, Esmat Rigi Yousefabadi, Emran Esmaeilzadeh, Maassoumeh Akhlaghi, Hoda Kavosi, Hamid Reza Khorram Khorshid","doi":"10.66224/rbmb.14.2.314","DOIUrl":"https://doi.org/10.66224/rbmb.14.2.314","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic modifications, particularly DNA methylation, are implicated in the pathogenesis of rheumatoid arthritis (RA). This study assessed the diagnostic utility of FOXP3, TET2, and IFI44L methylation in peripheral blood and examined their associations with inflammatory markers.</p><p><strong>Methods: </strong>We enrolled 100 patients with RA and 105 healthy controls. Clinical and laboratory data were recorded. DNA methylation at FOXP3, TET2, and IFI44L levels were quantified using MethyQESD (dual enzymatic digestion followed by real-time PCR). Group differences were analyzed with non-parametric tests; diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis.</p><p><strong>Results: </strong>FOXP3 promoter methylation levels were significantly in RA than in controls (P = 0.026), whereas IFI44L methylation levels were significantly lower in RA (P< 0.0001) and showed strong diagnostic performance (AUC 0.811; P< 0.001). No significant difference in TET2 methylation was observed between groups. In RA patients, FOXP3 and TET2 methylation levels were positively correlated with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), while IFI44L methylation was negatively correlated.</p><p><strong>Conclusions: </strong>IFI44L methylation levels in peripheral blood may serve as a promising potential diagnostic biomarker for RA. The associations of FOXP3, TET2, and IFI44L methylation levels with CRP and ESR suggest potential roles in RA-related inflammatory processes.</p>","PeriodicalId":45319,"journal":{"name":"Reports of Biochemistry and Molecular Biology","volume":"14 2","pages":"314-325"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13723346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149325783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role and Mechanism of NCAPD2 In Regulating the P53 Signaling Pathway to Mediate the Proliferation and Invasion of Pancreatic Cancer Cells.","authors":"Fuhua Li, Aili Cui, Linyuan Feng","doi":"10.66224/rbmb.14.2.223","DOIUrl":"https://doi.org/10.66224/rbmb.14.2.223","url":null,"abstract":"<p><strong>Background: </strong>The relationship between non-structural maintenance of chromosomes condensin I complex subunit D2 (NCAPD2) and pancreatic cancer (PC) has never been explored, but NCAPD2 has been confirmed to play a role in a variety of tumors. This study aimed to study the anti-cancer effect of NCAPD2 in pancreatic cancer PaTu8988 cells in vitro and its mechanism.</p><p><strong>Methods: </strong>NCAPD2 expression level within PC and the survival rate of patients was analyzed by making use the public database for bioinformatics analysis. Western blotting served to detect the expression level and knockdown level of NCAPD2 mRNA within PC. Cell Counting Kit-8 (CCK-8), colony formation, wound healing assays and Transwell assays were employed to examine the proliferation inhibition which induced by NCAPD2 knockdown. Furthermore, Western blotting was applied to analyze the influence of NCAPD2 knockdown on the p53 signaling pathway.</p><p><strong>Results: </strong>NCAPD2 was upregulated in PC cells lines PaTu8988T and tissues and was involved in poor prognosis (P < 0.05). Down-regulation of NCAPD2 expression can effectively inhibited the proliferation, migration, and invasion processes of PC cells. Additionally, the expression levels of p53, phosphorylated p53 (p-p53), and p21 proteins were markedly reduced following NCAPD2 knockdown (P < 0.05).</p><p><strong>Conclusions: </strong>NCAPD2 is highly expressed in PC and has poor prognosis. Its regulatory function in PC progression may be mediated through modulation of the p53 signaling pathway, thereby influencing, proliferation, apoptosis, and invasion in PaTu8988T cells.</p>","PeriodicalId":45319,"journal":{"name":"Reports of Biochemistry and Molecular Biology","volume":"14 2","pages":"223-234"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13723344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149325787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of <i>UCP2</i> G (-866) A Polymorphism, but not <i>NAT2</i> G (590) A, with Presbycusis Susceptibility in an Iranian Population.","authors":"Faezeh Karimnia, Omid Jazayeri, Mohammad Karimian, Eisa Jorjani","doi":"10.66224/rbmb.14.2.206","DOIUrl":"https://doi.org/10.66224/rbmb.14.2.206","url":null,"abstract":"<p><strong>Background: </strong>Presbycusis, or age-related hearing loss, is a common sensory disorder in older adults. Oxidative stress is a major pathogenic mechanism, and polymorphisms in genes regulating detoxification and reactive oxygen species (ROS) balance, such as <i>NAT2</i> and <i>UCP2</i>, may influence disease susceptibility.</p><p><strong>Methods: </strong>We conducted a case-control study including 120 male presbycusis patients (mean age 65.1 years) and 120 age-matched healthy controls (mean age 63.4 years). Genotyping of the <i>NAT2</i> 590G>A (rs1799930) and <i>UCP2</i> G (-866) A (rs659366) polymorphisms was performed using PCR-RFLP. Statistical analyses included odds ratios (ORs) with 95% confidence intervals (CIs), logistic regression, and Hardy-Weinberg equilibrium testing. Bioinformatics tools (including the UCSC Genome Browser, ORegAnno, and CpG island analysis) were used to predict the functional effects of variants.</p><p><strong>Results: </strong>No significant association was observed between <i>NAT2</i> 590G>A and presbycusis risk (OR = 1.22, 95% CI = 0.84-1.79, p = 0.289). In contrast, the UCP2 G(-866)A polymorphism showed a strong association: the AA genotype (OR = 3.20, 95% CI = 1.22-8.41, p = 0.018), A allele (OR = 1.68, 95% CI = 1.14-2.47, p = 0.008), and dominant GA+AA vs. GG model (OR = 1.84, 95% CI = 1.10-3.08, p = 0.02). Bioinformatics analysis indicated that the polymorphism may alter CpG islands in the promoter region and may could affect transcription factor binding and gene expression.</p><p><strong>Conclusions: </strong>Our findings suggest that the <i>UCP2</i> G (-866) A polymorphism, but not <i>NAT2</i> 590G>A polymorphism, contributes to presbycusis susceptibility in the studied Iranian population. This variant could serve as a potential biomarker for the genetic risk assessment of presbycusis.</p>","PeriodicalId":45319,"journal":{"name":"Reports of Biochemistry and Molecular Biology","volume":"14 2","pages":"206-214"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methamphetamine-Induced Oxidative Stress and Inflammatory Markers as Indicators of Blood-Brain Barrier Disruption.","authors":"Mushtaq Talib Abood, Mustafa Taha Mohammed","doi":"10.66224/rbmb.14.2.171","DOIUrl":"https://doi.org/10.66224/rbmb.14.2.171","url":null,"abstract":"<p><strong>Background: </strong>Methamphetamine (METH) abuse has been linked to neurotoxicity, oxidative stress, and dysfunction of the blood-brain barrier (BBB), potentially leading to cognitive impairments. This study aimed to evaluate the association between METH use, oxidative stress biomarkers, inflammation (NF-κB), endothelial permeability (MLCK), and memory impairment.</p><p><strong>Methods: </strong>A total of 150 male participants, aged 18-50 years, were recruited, including 75 METH users and 75 age-matched healthy controls. Serum levels of myosin light chain kinase (MLCK, NCBI Gene ID: 4638), nuclear factor kappa B (NF-κB, NCBI Gene ID: 4790), total oxidant status (TOS), total antioxidant capacity (TAC), catalase activity (CAT), and oxidative stress index (OSI) were measured. Receiver operating characteristic (ROC) curves and logistic regression were used to analyze biomarker sensitivity and risk association.</p><p><strong>Results: </strong>MLCK and NF-kB were significantly elevated in METH users compared to controls (p< 0.001*). TOS and OSI were higher, while TAC and CAT were lower in METH users (p< 0.001*). ROC analysis revealed MLCK (AUC = 0.978) and NF-kB (AUC = 0.959) as sensitive biomarkers for BBB dysfunction. Logistic regression indicated increased odds of memory impairment with elevated MLCK (OR = 1.246) and NF-kB (OR = 1.452), though these associations were not statistically significant (p > 0.05).</p><p><strong>Conclusions: </strong>Chronic METH use is associated with oxidative stress, inflammation, and increased BBB permeability, implicating MLCK and NF-kB as potential biomarkers for neurovascular damage and cognitive decline. Larger studies are warranted to confirm these associations.</p>","PeriodicalId":45319,"journal":{"name":"Reports of Biochemistry and Molecular Biology","volume":"14 2","pages":"171-180"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Oral Squamous Cell Carcinoma Risk Associated with <i>MLH1</i> rs63749795 Polymorphism in the Dominant Genetic Model.","authors":"Razieh Zare, Mohammad Javad Mokhtari, Mohammad Javad Fattahi, Nazanin Mohammadi, Bijan Khademi","doi":"10.66224/rbmb.14.2.215","DOIUrl":"https://doi.org/10.66224/rbmb.14.2.215","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) represents the predominant form of cancer affecting the oral cavity, accounting for more than 90% of all oral malignancies. Despite advancements in treatment, the five-year survival rate has remains relatively unchanged, primarily due to late-stage diagnosis. This study aimed to evaluate the genetic variation in <i>MutL homolog 1</i> (<i>MLH1</i>) (rs63749795) in patients with OSCC.</p><p><strong>Methods: </strong>A cross-sectional case-control study was performed, including a total of 102 patients diagnosed with OSCC and 100 healthy individuals serving as controls. Genotyping of the <i>MLH1</i> rs63749795 polymorphism was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction (TP-ARMS-PCR) method, followed by agarose gel electrophoresis.</p><p><strong>Results: </strong>The predominant genotype observed in both OSCC patients and healthy controls was the CT genotype, with respective frequencies of 45.1% and 55%. The least frequent genotype in both groups was TT, with frequencies of 12.7% in patients and 17% in controls. Most patients were in tumor grade 1 (70.96%) and tumor stage III (35.8%). Among the patients, 53.3% showed lymph node involvement. No statistically significant associations were observed between clinicopathological features and genotypes (P>0.05). The allele frequencies of MLH1 rs63749795 did not differ significantly between patients and controls. However, the rs63749795 polymorphism was associated with reduced OSCC susceptibility under the dominant genetic model (OR = 0.53, 95% CI = 0.29-0.96, P = 0.03 for CT+TT vs. CC genotype).</p><p><strong>Conclusions: </strong>The <i>MLH1</i> rs63749795 polymorphism may be associated with reduced susceptibility to OSCC under the dominant genetic model; however, although further studies involving larger populations are needed.</p>","PeriodicalId":45319,"journal":{"name":"Reports of Biochemistry and Molecular Biology","volume":"14 2","pages":"215-222"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-apoptotic, Anti-inflammatory, Anti-ulcer Effect of Silver Green Synthesis of <i>Boesenbergia Rotunda</i> Rhizome.","authors":"Tola Abdulsattar Faraj","doi":"10.66224/rbmb.14.2.191","DOIUrl":"https://doi.org/10.66224/rbmb.14.2.191","url":null,"abstract":"<p><strong>Background: </strong>Silver nanoparticles (SNPs) synthesized using the aqueous rhizome extract of Boesenbergia rotunda exhibit a wide range of biological activities and have traditionally been used in treating various ailments. The present study aimed to evaluate the gastroprotective effects of biosynthesized SNPs against ethanol-induced acute gastric mucosal injury in rats.</p><p><strong>Methods: </strong>SNPs were synthesized and characterized using X-ray diffraction (XRD), UV-Vis spectroscopy, and transmission electron microscopy (TEM).</p><p><strong>Results: </strong>Alleviated ethanol-induced gastric lesions, as evidenced by a reduced ulcer index. Ethanol-induced gastric damage was associated with decreased mucus production, lowered gastric pH, and increased ulcerated areas, edema, and inflammatory cell infiltration in the submucosa. Administration of SNPs markedly increased the activities of superoxide dismutase (SOD) and catalase (CAT), and elevated prostaglandin E2 (PGE2) levels, while significantly reducing malondialdehyde (MDA) concentrations in gastric tissue homogenates. SNPs also prevented oxidative stress by inhibiting lipid peroxidation. Furthermore, SNP treatment enhanced periodic acid-Schiff (PAS) staining of the gastric mucosa, upregulated HSP-70 protein expression, and downregulated Bax protein levels. SNPs also modulated inflammatory cytokines by increasing IL-10 and reducing TNF-α and IL-6 levels. Acute toxicity testing at a high dose (500 mg/kg) showed no toxicological symptoms in rats.</p><p><strong>Conclusions: </strong>The present study demonstrates that Boesenbergia rotunda-derived silver nanoparticles exert significant gastroprotective effects, likely due to their antioxidant properties, stimulation of gastric secretions, enhancement of endogenous antioxidant enzymes (SOD, CAT, PGE2), suppression of lipid peroxidation, upregulation of HSP-70, downregulation of Bax, and modulation of inflammatory cytokines.</p>","PeriodicalId":45319,"journal":{"name":"Reports of Biochemistry and Molecular Biology","volume":"14 2","pages":"191-205"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effect of Naringenin on Cisplatin-Induced Liver Toxicity via Suppressing Inflammation and Oxidative Stress in Mice.","authors":"Mohammad Heidari-Kahkesh, Layasadat Khorsandi, Atefeh Ashtari, Mohammad Javad Khodayar, Darioush Bijan Nejad","doi":"10.66224/rbmb.14.2.292","DOIUrl":"https://doi.org/10.66224/rbmb.14.2.292","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin (Cis) is a chemotherapeutic drug recognized for its hepatotoxic effects and its potential to trigger oxidative stress. This research aimed to evaluate the protective function of naringenin (NG) in mitigating Cis-induced liver toxicity by examining the inflammatory pathways and oxidative stress in mice.</p><p><strong>Methods: </strong>Adult male mice were given 50 mg/kg NG for two weeks, without Cis or with 10 mg/kg Cis on the 10th day. Histological analysis and biochemical indicators, including AST (Aspartate aminotransferase), ALT (Alanine aminotransferase), and ALP (Alkaline phosphatase), were measured to evaluate liver toxicity. The protein levels of Nrf2 (Nuclear factor erythroid 2-related factor 2) and NF-κB (nuclear factor-kappa B), two main inflammation-related biomarkers, were measured to assess inflammation within the liver tissue. Oxidative stress biomarkers, including CAT (Catalase), GSH (Glutathione), SOD (Superoxide dismutase), and MDA (Malondialdehyde), were also evaluated.</p><p><strong>Results: </strong>Pretreatment with NG improved histological changes and decreased AST, ALT, and ALP levels, indicating the attenuating impact of NG against liver toxicity induced by Cis. NG reduced inflammation of the liver tissue by decreasing Nrf2 protein levels and elevating the levels of NF-κB protein in the Cis-intoxicated mice. NG could also suppress oxidative stress in the liver tissue of the Cis-treated mice via decreasing MDA contents and enhancing CAT, SOD, and GSH levels.</p><p><strong>Conclusions: </strong>The findings indicated that NG exerts a protective action against Cis-induced hepatotoxicity by reducing histological alterations, inflammation, and oxidative stress.</p>","PeriodicalId":45319,"journal":{"name":"Reports of Biochemistry and Molecular Biology","volume":"14 2","pages":"292-300"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent Fasting Attenuates Adriamycin-induced Hepatoxicity in Rats: Possible Role for Nrf2/HO-1 and LC3/Sirt1 Pathways.","authors":"Abdelaziz Mohamed Hussein, Fathy Hamada Elsaid, Wessam El-Sayed, Elsayed Abdelfatah Eid, Omar Abd-Alhakem Ammar, Abdelnaser Badway, Gamal Othman, Shorouk Elsaeed Mohammed Elmorshdy","doi":"10.66224/rbmb.14.2.235","DOIUrl":"https://doi.org/10.66224/rbmb.14.2.235","url":null,"abstract":"<p><strong>Background: </strong>The current study was designed to examine, whether intermittent fasting can ameliorate the liver damage induced by adriamycin (ADR) in rats, as well as its possible underlying mechanisms.</p><p><strong>Methods: </strong>Forty male Sprague Dawley rats were allocated into 4 equal groups, control, fasting, ADR and ADR+ Fasting groups. At the end of the experiment (eight weeks after ADR administration), blood samples were collected for the measurement of ALT, AST, and albumin, and liver tissues were harvested for biochemical analyses of oxidative stress markers (AMD, GSH and Catalase). Real-time PCR was performed for NRF2 and HO-1, as well as histopathological examination and immunostaining for caspase-3, LC3, and Sirt-1 expression.</p><p><strong>Results: </strong>Administration of ADR caused significant elevation in liver enzymes (ALT, AST), lipid peroxidation (MDA), histopathological damage score and caspase-3 in liver tissues (p< 0.05) with a notable decrease in GSH, catalase, Nrf2, HO-1, LC3, and Sirt-1 genes expression (p< 0.05). Conversely, the application of intermittent fasting (IF) to ADR-treated rats caused significant attenuation of the raised liver enzymes (ALT, AST), lipid peroxidation (MDA), histopathological damage score and caspase-3 in liver tissues and significant improvement in the attenuated GSH, catalase, Nrf2, HO-1, Lc3 and Sirt-1 gene expression (p< 0.05).</p><p><strong>Conclusions: </strong>Intermittent fasting could potentially offer protection against ADR-induced hepatotoxicity in rats by reducing oxidative stress and apoptosis and modifying the expression of Nrf2/HO-1, LC3, and Sirt-1.</p>","PeriodicalId":45319,"journal":{"name":"Reports of Biochemistry and Molecular Biology","volume":"14 2","pages":"235-249"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Immune Tolerance and Insulin Secretion of Mesenchymal Stem Cell-Derived Insulin-Producing cells via Interferon-γ and Tumor Necrosis Factor-α Priming.","authors":"Mohga Mohamed Al-Issawi, Mahmoud Mohamed Gabr, Sherry Mohamed Khater, Abdel-Aziz Fatouh Abdel-Aziz","doi":"10.66224/rbmb.14.2.155","DOIUrl":"https://doi.org/10.66224/rbmb.14.2.155","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) have the potential to treat type 1 diabetes mellitus (T1DM) by differentiating into insulin-producing cells (IPCs). However, various immunological factors were limiting the therapeutic efficacy of transplanted MSC-derived IPCs. Preconditioning MSCs with proinflammatory cytokines was proven to enhance their immunosuppressive capabilities. Yet, it remains unclear how cytokine stimulation influences the immunoregulatory features of theses differentiated IPCs. Therefore, we aimed to investigate the potential role of tumor necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ)-primed MSC-derived IPCs in inducing and regulating immunological tolerance.</p><p><strong>Methods: </strong>MSCs were isolated from human adipose tissue (hAT-MSCs) and differentiated into IPCs. Subsequently, the cells were assigned into five groups as follows: the control (hAT-MSCs) group, the differentiated (IPCs) group, the differentiated cells primed with IFN-γ (IPCs+ IFN-γ group), the differentiated cells primed with TNF-α (IPCs+ TNF-α group), the differentiated cells primed with both cytokines (IPCs+ Mix group). Flow cytometry, reverse transcription polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA) were employed to detect the expression of immunomodulators, insulin/c-peptide, and pancreatic gene expression.</p><p><strong>Results: </strong>The results indicated that IPCs treated with both cytokines exhibited the highest expression of insulin/c-peptide and pancreatic genes, as well as the immune checkpoints programmed death ligand 1 (PD-L1) and kynurenine (KYN), which are immunosuppressants. Furthermore, IFN-γ priming also enhanced the expression of the immunological regulators: human leukocyte antigen class 1 (HLA-ABC) and class 2 (HLA-DR).</p><p><strong>Conclusions: </strong>Preconditioning IPCs with IFN-γ/TNF-α enhances their immunomodulatory profile through checkpoint molecules and insulin secretion, suggesting a novel immunological strategy for treating T1DM.</p>","PeriodicalId":45319,"journal":{"name":"Reports of Biochemistry and Molecular Biology","volume":"14 2","pages":"155-170"},"PeriodicalIF":1.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13723347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149325785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}