Leila Arabi, Ali Roohbakhsh, Bizhan Malaekeh-Nikouei, Bibi Sedigheh Fazly Bazzaz
{"title":"Joining COPE: Opportunities and benefits for the Iranian Journal of Basic Medical Sciences.","authors":"Leila Arabi, Ali Roohbakhsh, Bizhan Malaekeh-Nikouei, Bibi Sedigheh Fazly Bazzaz","doi":"10.22038/ijbms.2023.76381.16530","DOIUrl":"10.22038/ijbms.2023.76381.16530","url":null,"abstract":"","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 1","pages":"1-2"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10722480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Voluntary exercise improves pulmonary inflammation through NF-κB and Nrf2 in type 2 diabetic male rats.","authors":"Seyed Zanyar Athari, Fariba Mirzaei Bavil, Rana Keyhanmanesh, Hajie Lotfi, Yousef Sajed, Aref Delkhosh, Fariba Ghiasi","doi":"10.22038/IJBMS.2023.70416.15307","DOIUrl":"10.22038/IJBMS.2023.70416.15307","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the effects of voluntary exercise as an anti-inflammatory intervention on the pulmonary levels of inflammatory cytokines in type 2 diabetic male rats.</p><p><strong>Materials and methods: </strong>Twenty-eight male Wistar rats were divided into four groups (n=7), including control (Col), diabetic (Dia), voluntary exercise (Exe), and diabetic with voluntary exercise (Dia+Exe). Diabetes was induced by a high-fat diet (4 weeks) and intraperitoneal injection of streptozotocin (35 mg/kg), and animals did training on the running wheel for 10 weeks as voluntary exercise. Finally, the rats were euthanized and the lung tissues were sampled for the evaluation of the levels of pulmonary interleukin (IL)-10, IL-11, and TNF-α using ELISA, and the protein levels of Nrf-2 and NF-κB using western blotting and tissue histopathological analysis.</p><p><strong>Results: </strong>Diabetes reduced the IL-10, IL-11, and Nrf2 levels (<i>P</i><0.001 to P<0.01) and increased the levels of TNF-α and NF-κB compared to the Col group (<i>P</i><0.001). Lung tissue levels of IL-10, IL-11, and Nrf2 in the Dia+Exe group enhanced compared to the Dia group (<i>P</i><0.001 to <i>P</i><0.05), however; the TNF-α and NF-κB levels decreased (<i>P</i><0.001). The level of pulmonary Nrf2 in the Dia+Exe group was lower than that of the Exe group while the NF-κB level increased (<i>P</i><0.001). Moreover, diabetes caused histopathological changes in lung tissue which improved with exercise in the Dia+Exe group.</p><p><strong>Conclusion: </strong>These findings showed that voluntary exercise could improve diabetes-induced pulmonary complications by ameliorating inflammatory conditions.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 1","pages":"74-80"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10722479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sibel Çiğdem Tuncer, Cihan Gur, Sefa Kucukler, Serkan Ali Akarsu, Fatih Mehmet Kandemir
{"title":"Effects of zingerone on rat induced testicular toxicity by sodium arsenite via oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, and autophagy pathways.","authors":"Sibel Çiğdem Tuncer, Cihan Gur, Sefa Kucukler, Serkan Ali Akarsu, Fatih Mehmet Kandemir","doi":"10.22038/IJBMS.2024.73342.15934","DOIUrl":"https://doi.org/10.22038/IJBMS.2024.73342.15934","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate the effects of zingerone (ZNG) treatment on testicular toxicity in rats induced by sodium arsenite (SA).</p><p><strong>Materials and methods: </strong>In the study, five groups were formed (n=7) and the experimental groups were designated as follows; Vehicle group, ZNG group, SA group, SA+ZNG 25 group, and SA+ZNG 50 group. While SA was administered orally to rats at 10 mg/kg/bw, ZNG was given to rats orally at 25 and 50 mg/kg/bw doses for 14 days.</p><p><strong>Results: </strong>As a result of the presented study, an increase was observed in the MDA contents of the testicular tissue of the rats administered SA, while significant decreases were observed in GSH levels, SOD, CAT, and GPx activities. The mRNA transcript levels of the pro-inflammatory genes NF-κB, TNF-α, IL-1β, and IL-6 were triggered after SA administration. Additionally, SA administration caused inflammation by increasing RAGE, NLRP3, and JAK-2/STAT3 gene expression. Moreover, endoplasmic reticulum (ER) stress occurred in the testicular tissues of SA-treated rats and thus ATF-6, PERK, IRE1, and GRP78 genes were up-regulated. SA caused apoptosis by up-regulating Bax and Caspase-3 expressions and inhibiting Bcl-2 expression in testicles. SA caused histological irregularities in the testicles, resulting in decreased sperm quality.</p><p><strong>Conclusion: </strong>ZNG treatment reduced SA-induced oxidative stress, ER stress, inflammation, apoptosis, and histological irregularities in the testicles while increasing sperm quality. As a result, it was observed that ZNG could alleviate the toxicity caused by SA in the testicles.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 5","pages":"603-610"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of electroacupuncture combined with sulforaphane in the treatment of sarcopenia in SAMP8 mice.","authors":"Fei Guo, Linlin Fu, Zhenchan Lu","doi":"10.22038/IJBMS.2024.71345.15509","DOIUrl":"https://doi.org/10.22038/IJBMS.2024.71345.15509","url":null,"abstract":"<p><strong>Objectives: </strong>Skeletal muscles mitochondrial dysfunction is the main cause of sarcopenia. Both electroacupuncture (EA) and sulforaphane (SFN) have been shown to improve oxidative stress and inflammation levels to maintain mitochondrial function, but the effects and mechanisms of their combination on sarcopenia are unclear. This study aimed to investigate the regulatory effects of EA combined with SFN on sarcopenia.</p><p><strong>Materials and methods: </strong>SAMP8 mice were used and intervened with EA or SFN, respectively, and Masson and HE staining were used to observe pathological changes in skeletal muscle tissue. Transmission electron microscopy was used to detect tissue mitochondrial changes. TUNEL staining was used to assess apoptosis. The biochemical and molecular content was tested by ELISA, western blot, and qRT-PCR.</p><p><strong>Results: </strong>The results showed that oxidative stress, apoptosis, and IL-6, TNF-α, Atrogin-1, and MuRF1 levels in skeletal muscles cells were suppressed and mitochondrial damage was repaired after EA or SFN intervention. In addition, we found that the above changes were associated with the activation of the AMPK/Sirt1/PGC-1α pathway in skeletal muscle tissues, and the promotion effect of combined EA and SFN intervention was more significant.</p><p><strong>Conclusion: </strong>In conclusion, this study found that EA combined with SFN mediated the repair of mitochondrial damage through activation of the AMPK/Sirt1/PGC-1α pathway, thereby alleviating skeletal muscles morphology and function in sarcopenia. This study combines EA with SFN, which not only broadens the use of electroacupuncture and SFN but also provides a scientific experimental basis for the treatment of sarcopenia.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 5","pages":"560-566"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preventive effects of quercetin against inflammation and apoptosis in cyclophosphamide-induced testicular damage.","authors":"Duygu Uzun-Goren, Yesim Hulya Uz","doi":"10.22038/IJBMS.2024.74458.16177","DOIUrl":"https://doi.org/10.22038/IJBMS.2024.74458.16177","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to investigate the effects of quercetin (QRC) against cyclophosphamide (CP)-induced testicular damage and how it interacts with apoptotic and inflammatory signaling pathways.</p><p><strong>Materials and methods: </strong>Forty male Wistar rats were randomly divided into four groups, 10 in each group; Control group (corn oil, intragastrically, 14 days), QRC group (100 mg/kg QRC, dissolved in corn oil, 14 days), CP group (200 mg/kg CP, intraperitoneally, single dose on the 7th day), and CP+QRC group (100 mg/kg QRC, intragastrically, 14 days and 200 mg/kg CP, intraperitoneally, single dose on the 7th day). Animals were sacrificed one day after the last QRC application and the effects of quercetin were evaluated by histological, morphometrical, and hormonal parameters. Also, nuclear factor kappa B (NFkB), nuclear factor erythroid 2 related factor 2 (Nrf2), Bcl-2 associated X protein (Bax), and B-cell lymphoma-2 (Bcl-2) immunoreactivities were evaluated immunohistochemically.</p><p><strong>Results: </strong>CP increased the testicular weight/body weight ratio, significantly decreasing body weights and testicular weights. All hormone levels were also reduced significantly. Morphometrically, seminiferous tubules diameter and germinal epithelial thickness decreased, while a significant increase was determined in interstitial field width in addition to histological damage. Furthermore, immunohistochemical findings also indicated that NFkB and Bax immunoreactivity were increased in the CP group, whereas significant decrease was seen in Nrf2 and Bcl-2 immunoreactivity. Apoptotic cell and tubule index were reduced in CP. QRC ensured improvement in all findings.</p><p><strong>Conclusion: </strong>Data showed us, that QRC may have preventive effects in CP-induced testicular damage by acting on NFkB, Nrf2, Bax, and Bcl-2 pathways.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 5","pages":"647-656"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Underlying anti-cancer mechanisms of histone deacetylase (HDAC) inhibitors in tamoxifen-resistant breast cancer cells.","authors":"Lingyan Wang, Yukai Xu, Chunhui Gao","doi":"10.22038/IJBMS.2024.76157.16478","DOIUrl":"https://doi.org/10.22038/IJBMS.2024.76157.16478","url":null,"abstract":"<p><strong>Objectives: </strong>Breast cancer is an important women's malignancy with high cancer-related deaths worldwide. Drug resistance lowers the treatment efficacy in this malignancy. This study aimed to explore the underlying mechanisms of histone deacetylase (HDAC) inhibitor trichostatin A (TSA) to overcome resistance to tamoxifen in breast cancer cells.</p><p><strong>Materials and methods: </strong>Tamoxifen-resistance in MCF-7 breast cancer cells was simulated. MTT assay was used to detect the cytotoxic effects of HDAC inhibitor and PI3K inhibitor on the cancer cells. Trans-well assay was applied to evaluate the invasion and migration of the treated cancer cells. Flow cytometer assay was also applied to evaluate cell cycle phases in the treated cancer cells. Finally, expression of vascular endothelial growth factor (VEGF), E-cadherin, Vimentin, phosphorylated phosphatidylinositol kinase (p-PI3k), phosphorylated protein kinase B (p-AKT), and phosphorylated mammalian target protein of rapamycin (p-mTOR) was evaluated by western blotting.</p><p><strong>Results: </strong>The obtained results indicated that HDAC inhibitor treatments significantly decreased viability, migration, and invasion in the cancer cells. Furthermore, the frequency of the treated cancer cells significantly increased in the S phase as well as significantly decreasing in the G2/M phase of the cell cycle. Moreover, HDAC inhibitor modified levels of VEGF, E-cadherin, Vimentin, p-PI3k, p-AKT, and p-mTOR proteins. However, HDAC inhibitor combined with PI3K inhibitor exerts more profound effects on the cancer cells as compared to HDAC inhibitor monotherapy.</p><p><strong>Conclusion: </strong>HDAC inhibitors inhibited the survival of breast cancer drug-resistant cells, invasion, migration, and angiogenesis by inhibiting the PI3k/Akt/mTOR signaling pathway.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 6","pages":"775-779"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11024407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Significance of genotypes and resistance status of <i>Mycobacterium tuberculosis</i> strains in gene expression of apoptosis cell death and inflammatory pathways in A549 lung epithelial cell line.","authors":"Rouhollah Abdolhamidi, Setareh Haghighat, Arfa Moshiri, Abolfazl Fateh, Seyed Davar Siadat","doi":"10.22038/IJBMS.2024.75195.16303","DOIUrl":"10.22038/IJBMS.2024.75195.16303","url":null,"abstract":"<p><strong>Objectives: </strong>Tuberculosis (TB) has been a major health issue throughout history. As part of TB infection, host-<i>Mycobacterium tuberculos</i>is (Mtb) interactions are important. Through immune pathology and cell death control processes, Mtb infection facilitates intracellular growth. The relationship between apoptosis and inflammation in Mtb infection remains unclear. In this study, the levels of related apoptosis and inflammatory genes were assessed in A549 cells infected with a variety of Mtb strains.</p><p><strong>Materials and methods: </strong>Mtb isolates with different phenotypes (sensitive, INH<sup>R</sup>, Rif<sup>R</sup>, MDR, and XDR) were collected from the Pasteur Institute of Iran, during this study. Whole genome sequencing was previously performed on all strains, and the Beijing genotype was selected as sensitive. Also, for other resistant strains, the New-1 genotype was available and isolated for genotype comparison. A549 lung carcinoma cells were also grown and infected with selected Mtb strains. Genes involved in inflammation and apoptosis were detected using reverse transcription-PCR (RT-PCR).</p><p><strong>Results: </strong>All sensitive strains and resistant strains were found to significantly up-regulate anti-apoptotic (<i>bcl2</i> and <i>rb1</i>), chemokine (<i>IL-8</i> and <i>MCP-1</i>), and pro-inflammatory cytokine (<i>TNF-</i><i>α</i> and <i>IFN-</i><i>γ</i>) expression, while significant down-regulation was observed after 24 and 48 hr of infection in anti-inflammatory genes (IL-10) and pro-apoptotic genes (bad and bax). Besides resistance strains, Mtb genotypes also affected gene expression. The Beijing genotype (sensitive isolate) influences inflammatory and apoptotic genes more sharply than the New-1 genotype (INH<sup>R</sup>, Rif<sup>R</sup>, MDR, and XDR).</p><p><strong>Conclusion: </strong>Gene expression differences related to apoptosis and inflammation examined in the current study may be attributed to genotypes rather than resistance status since the expression of most genes has been observed to be lower in resistant strains (INH<sup>R</sup>, Rif<sup>R</sup>, MDR, and XDR belonging to the New-1 genotype) compared to sensitive strains (Beijing genotype).</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 7","pages":"825-831"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Curcumin and saroglitazar attenuate diet-induced nonalcoholic steatohepatitis by activating the Nrf2 pathway and suppressing ERK1/2 signaling.","authors":"Reza Afarin, Negar Dinarvand, Hossein Azizi Dariuni, Ghazal Orak, Bahar Jaberian Asl, Reza Azizi, Azam Khedri","doi":"10.22038/IJBMS.2024.75293.16320","DOIUrl":"10.22038/IJBMS.2024.75293.16320","url":null,"abstract":"<p><strong>Objectives: </strong>Non-alcoholic fatty liver disease (NAFLD) is a chronic steatohepatitis disorder. If left untreated, it can progress to hepatocellular carcinoma. Several studies have shown that saroglitazar, a PPARα/γ dual agonist, and curcumin (the principal constituent of turmeric) may be effective in the treatment of NAFLD. This research aimed to study the pharmacological mechanism of these compounds in rats with NAFLD.</p><p><strong>Materials and methods: </strong>NAFLD was induced in male Wistar rats (aged 6-8 weeks) by feeding them a high-fat diet (HFD) for 6 weeks. Subsequently, the rats were divided into four groups, with Group 1 continuing on HFD, while groups 2, 3, and 4 received HFD supplemented with saroglitazar, curcumin, and both saroglitazar and curcumin, respectively. We evaluated the expression of Nrf2, ERK1/2, NOX1,2,4, antioxidant enzymes, PPARα, γ, and genes regulating lipid metabolism in the liver. Histopathology of liver tissue was also examined. Furthermore, we analyzed serum levels of lipid profiles and hepatic enzymes.</p><p><strong>Results: </strong>Rats with NAFLD that received treatment involving saroglitazar and curcumin showed a significant decrease in the expression of ERK1/2, SREBP1, PPARγ, pro-inflammatory cytokines, NOXs, and ROS levels. Additionally, the levels of Nrf2, PPARα, and antioxidant enzymes showed a significant increase. The serum levels of lipid profiles and hepatic enzymes also decreased significantly after drug treatment.</p><p><strong>Conclusion: </strong>Our results confirm that both saroglitazar and curcumin ameliorate NAFLD by regulating the Nrf2 and ERK1/2 signaling pathways. These findings suggest that curcumin could serve as a suitable substitute for saroglitazar, although they appear to have a synergistic effect.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 8","pages":"1015-1022"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of bioactive extract nanoparticles on pulp stem cell behavior relevant to dental care using chemical composition of gelatin-Arabian gum nano polymer.","authors":"Xiaoni Tan, Moli Zhang, BiBo Tu","doi":"10.22038/IJBMS.2024.76467.16548","DOIUrl":"10.22038/IJBMS.2024.76467.16548","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate the impact of bioactive plant extracts on the proliferation and migration of dental pulp stem cells (DPSCs) and their potential implications for dental care, focusing on the nurse-caring aspect.</p><p><strong>Materials and methods: </strong>TDPSCs were cultured on gelatin polymer scaffolds mimicking the extracellular matrix (ECM) environment. Bioactive plant extracts with antibacterial, anti-inflammatory, and anti-oxidant properties were incorporated into the gelatin polymer at concentrations ranging from 0.1% to 2.0%. Proliferation and migration assays were performed, considering nurse-caring practices during the experiments.</p><p><strong>Results: </strong>Treatment with specific bioactive plant extracts significantly enhanced DPSC proliferation, showing a 2.5-fold increase compared to the control groups. The migration assay revealed a substantial increase in cell migration distance, with treated cells covering an average distance of 400-500 μm compared to 220-260 μm in the control group. Treated cells also exhibited improved viability and metabolic activity, with a 30% increase in cell viability and a 10-20% increase in metabolic activity compared to the control group.</p><p><strong>Conclusion: </strong>This study demonstrates that bioactive plant extracts have the potential to enhance DPSC proliferation, migration, viability, and metabolic activity. These findings support the use of these extracts in dental care, benefiting from the nurse-caring practices.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 8","pages":"975-984"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Hu, Yang Wang, Ying Chen, ChuanYing Li, Yun Long, Cheng Wu
{"title":"Co-administration of 1,25-dihydroxyvitamin D3 and infliximab improves colitis in mice by modulating Treg differentiation.","authors":"Yan Hu, Yang Wang, Ying Chen, ChuanYing Li, Yun Long, Cheng Wu","doi":"10.22038/IJBMS.2024.74640.16209","DOIUrl":"10.22038/IJBMS.2024.74640.16209","url":null,"abstract":"<p><strong>Objectives: </strong>The combination of TNF-α inhibitors and vitamin D in colitis remains to be elucidated. In the present study, we revealed the benefit of infliximab (IFX) and vitamin D in a mouse model of Ulcerative colitis (UC).</p><p><strong>Materials and methods: </strong>A dextran sulfate sodium-induced colitis model was used. The therapeutic effect of the combination was evaluated by symptom and histopathology analysis. The synergistic mechanism was explored by detecting the regulatory effect of the combined therapy on Regulatory T cell (Treg) differentiation.</p><p><strong>Results: </strong>IFX and 1,25-dihydroxyvitamin D3 (VitD3) synergistically prevented the development of colitis by improving clinical signs, pathological and hematological manifestation, and inhibiting intestinal inflammation (decreasing TNF-α, IL-1β, and IL-6). Co-administration of IFX (2.5 mg/kg) with VitD3 or IFX (5.0 mg/kg) with VitD3 was more effective than administration of IFX (2.5 mg/kg, 5.0 mg/kg). There was no difference in therapeutic effect between IFX (5.0 mg/kg) and VitD3+ IFX (2.5 mg/kg) groups or between the VitD3+IFX (5.0 mg/kg) and VitD3+ Azathioprine (AZA) groups. VitD3 or combination therapy showed more powerful regulation of splenetic Treg differentiation and IL-10 production than IFX alone. Moreover, VitD3 alone or in combination induced higher levels of Foxp3 and IL-10 than IFX in colon tissue. In ulcerative colitis patients, serum VitD3 levels positively correlated with Treg levels.</p><p><strong>Conclusion: </strong>VitD3 and IFX synergistically inhibit colitis based on their powerful regulation of Treg differentiation. VitD3 combined with IFX is an alternative therapy for patients who are intolerant to standard doses of IFX or combination of IFX and AZA.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 9","pages":"1172-1179"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}