Iranian Journal of Basic Medical Sciences最新文献

{"title":"Cited2 inhibited hypoxia-induced proliferation and migration of PASMCs via the TGF-β1/Cited2/PPARγ pathway.","authors":"Hong-Juan Wang, Lan Ma, Qin Yu","doi":"10.22038/IJBMS.2023.74455.16178","DOIUrl":"10.22038/IJBMS.2023.74455.16178","url":null,"abstract":"<p><strong>Objectives: </strong>Proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) contribute to hypoxia-induced pulmonary hypertension (HPH). The transcription factor Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (Cited2) has been implicated in the control of tumor cells and mesenchymal stem cell (MSC) and cardiomyocyte growth or migration. Whether Cited2 is involved in the proliferation and migration of PASMCs and the underlying mechanisms deserve to be explored.</p><p><strong>Materials and methods: </strong>Cited2 expression was detected in rat PASMCs under hypoxia conditions and HPH rat models. The effect of Cited2 on the proliferation and migration of PASMC was detected by overexpression or knockdown of the Cited2 gene. After PAMSCs were treated with recombinant TGF-β1 and the lentivirus vector overexpressing Cited2, expression of peroxisome proliferator-activated receptor gamma (PPARγ) was examined by western blotting.</p><p><strong>Results: </strong>We revealed that hypoxia down-regulated the expression of Cited2 in PASMCs and rat pulmonary arteries. Cited2 overexpression inhibited the proliferation and migration of PASMCs under hypoxia, while Cited2 knockdown induced the proliferation and migration of PASMCs. Cited2 inhibits the negative regulation of the TGF-β1 pathway on PPARγ to inhibit the proliferation and migration of PASMCs.</p><p><strong>Conclusion: </strong>These findings suggest that increased Cited2 expression contributes to the inhibition of PASMCs proliferation and migration by regulating TGF-β1-mediated target gene expression in HPH and provides a new target for molecular therapy of HPH.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10897560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990050","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":"Dexmedetomidine protects against sepsis-induced lung injury through autophagy and Smad2/3 signaling pathway.","authors":"Zhanli Liu, Jiqing Xu, Yanqiu Zhao, Yanbin Wan, Rui Guo, Canling Long, Jia Liu, Xinhuang Yao, Wenchao Yin","doi":"10.22038/IJBMS.2023.73479.15964","DOIUrl":"10.22038/IJBMS.2023.73479.15964","url":null,"abstract":"<p><strong>Objectives: </strong>Dexmedetomidine (Dex) is a potent α2-adrenergic receptor(α2-AR) agonist that has been shown to protect against sepsis-induced lung injury, however, the underlying mechanisms of this protection are not fully understood. Autophagy and the Smad2/3 signaling pathway play important roles in sepsis-induced lung injury, but the relationship between Dex and Smad2/3 is not clear. This study aimed to investigate the role of autophagy and the Smad2/3 signaling pathway in Dex-mediated treatment of sepsis-induced lung injury. Sepsis was performed using cecal ligation and puncture (CLP) in C57BL/6J mice.</p><p><strong>Materials and methods: </strong>Mice were randomly assigned to four groups (n=6 per group): sham, CLP, CLP-Dex, and CLP-Dex-YOH, Yohimbine hydrochloride (YOH) is an α2-AR blocker. The cecum was carefully separated to avoid blood vessel damage and was identified and punctured twice with an 18-gauge needle. The pathological changes, inflammatory factor levels, oxidative stress, autophagy, Smad2/3 signaling pathway-related protein levels in lung tissues, and the activity of superoxide dismutase (SOD) and malonaldehyde (MDA) in the serum were measured.</p><p><strong>Results: </strong>CLP-induced lung injury was reflected by increased levels of inflammatory cytokines, apoptosis, and oxidative stress, along with an increase in the expression of autophagy and Smad2/3 signaling pathway-related proteins. Dex could reverse these changes and confer a protective effect on the lung during sepsis. However, the administration of YOH significantly reduced the positive effects of Dex in mice with sepsis.</p><p><strong>Conclusion: </strong>Dex exerts its beneficial effects against sepsis-induced lung injury through the regulation of autophagy and the Smad2/3 signaling pathway.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10897556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990052","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":"Propolis and its therapeutic effects on renal diseases: A review.","authors":"Fatemeh Salami, Reza Mohebbati, Sara Hosseinian, Samira Shahraki, Hossein Hossienzadeh, Abolfazl Khajavi Rad","doi":"10.22038/IJBMS.2024.73081.15880","DOIUrl":"10.22038/IJBMS.2024.73081.15880","url":null,"abstract":"<p><p>Propolis is produced by bees using a mixture of bees wax and saliva. It contains several bioactive compounds that mainly induce anti-oxidant and anti-inflammatory effects. In this review, we aimed to investigate the effects of propolis on kidney diseases. We used \"Kidney\", \"Disease\", \"Propolis\", \"Renal\", \"Constituent\", \"Mechanism\", \"Infection\", and other related keywords as the main keywords to search for works published before July 2023 in Google scholar, Scopus, and Pubmed databases. The search terms were selected according to Medical Subject Headings (MeSH). This review showed that propolis affects renal disorders with inflammatory and oxidative etiology due to its bioactive compounds, mainly flavonoids and polyphenols. There have been few studies on the effects of propolis on kidney diseases; nevertheless, the available studies are integrated in this review. Overall, propolis appears to be effective against several renal diseases through influencing mechanisms such as apoptosis, oxidative balance, and inflammation.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10897566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990058","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":"Metformin improves memory via AMPK/mTOR-dependent route in a rat model of Alzheimer's disease.","authors":"Reza Ale Mahmoud Mehraban, Parvin Babaei, Kambiz Rohampour, Adele Jafari, Zoleikha Golipoor","doi":"10.22038/IJBMS.2023.73075.15879","DOIUrl":"10.22038/IJBMS.2023.73075.15879","url":null,"abstract":"<p><strong>Objectives: </strong>Metformin, as an insulin sensitizer, is a familiar antidiabetic drug. Increasing evidence points to metformin's protective effects against Alzheimer's disease (AD). However, the mechanism is not well understood. The present study evaluated whether inhibiting AMPK and activating mTOR could stop metformin from improving memory in rats with streptozotocin (STZ) -induced Alzheimer's disease.</p><p><strong>Materials and methods: </strong>Twelve-week-old Wistar rats, were injected 3 mg/kg STZ intracerebroventricularly on days 1 and 3 to develop the animal model. Metformin was applied orally at 100 mg/kg (17 days). Forty-five min before the retrieval phase, dorsomorphin (DM; AMPK inhibitor, 2 M) and MHY (mTOR activator, 0.1 M) were administered. Morris Water Maze (MWM) and shuttle box were utilized to measure spatial and passive avoidance memory, respectively. Congo red staining was used to identify cortical amyloid deposition.</p><p><strong>Results: </strong>The findings exhibited a considerable enhancement in spatial learning and memory in the metformin treatment group (<i>P</i>≤0.05). Injection of DM and MHY alone could not significantly change MWM and passive avoidance. Additionally, co-administration of DM and MHY increased escape latency (<i>P</i>≤0.001) and reduced the total time spent in the target quadrant (TTS) (<i>P</i>≤0.05) compared to the STZ+MET group during retrieval of MWM. Also, co-injection of DM and MHY increased step-through latency (STL) and decreased time spent in the dark compartment (TDC) compared to the STZ+MET group (<i>P</i>≤0.001).</p><p><strong>Conclusion: </strong>Metformin appears to have a therapeutic impact by activating AMPK and inactivating mTOR. As a result, it could be used as an Alzheimer's treatment strategy.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706741","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":"Melatonin enhanced the cardioprotective effects of HTK solution on Langendorff-perfused mouse hearts subjected to ischemia/reperfusion.","authors":"Mingchu Sun, Zihui Zhang, Yue Yin, Lu Yu, Wenhua Jiang, Chan Zhang, Chunhu Gu, Heng Ma, Yishi Wang","doi":"10.22038/IJBMS.2023.74152.16109","DOIUrl":"10.22038/IJBMS.2023.74152.16109","url":null,"abstract":"<p><strong>Objectives: </strong>Cardiac arrest is a crucial procedure in various cardiac surgeries, during which the heart is subjected to an ischemic state. The occurrence of ischemia/reperfusion (I/R) injury is inevitable due to aortic blockage and opening. The Histidine-tryptophan-ketoglutarate (HTK) solution is commonly used as an organ protection liquid to mitigate cardiac injury during cardiac surgery. Despite its widespread use, there is significant potential for improving its protective efficacy.</p><p><strong>Materials and methods: </strong>The cardioprotective effect of HTK solution with and without melatonin was evaluated using the isolated Langendorff-perfused mouse heart model. The isolated C57bL/6 mouse hearts were randomly divided into four groups: control, I/R, HTK solution treatment before reperfusion (HTK+I/R), and HTK solution combined with melatonin before reperfusion (HTK+M+I/R). Cardiac function and myocardial injury markers were then measured. AMP-activated protein kinase α2 (AMPKα2) KO mice were used to investigate the underlying mechanism.</p><p><strong>Results: </strong>In our study, we found that melatonin significantly improved the protective effects of HTK solution in an isolated Langendorff-perfused mouse model, mechanistically by reducing mitochondrial damage, improving energy metabolism, inhibiting cardiomyocyte apoptosis, and reducing myocardial infarction size. We also observed that the HTK solution alone was ineffective in inhibiting ER stress, but when melatonin was added, there was a significant reduction in ER stress. Furthermore, melatonin was found to alleviate carbonyl stress during cardiac I/R. Interestingly, our results showed that the cardioprotective properties of melatonin were dependent on AMPKα2.</p><p><strong>Conclusion: </strong>The findings presented in this study offer a valuable empirical foundation for the development of perioperative cardioprotective strategies.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139706772","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":"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":null,"pages":null},"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}

{"title":"Resveratrol treatment ameliorates hepatic damage via the TGF-β/SMAD signaling pathway in a phenobarbital/CCl₄-induced hepatic fibrosis model.","authors":"Merve Aykaç, Eda Balkan, Semin Gedi Kli, Nurinnisa Öztürk","doi":"10.22038/IJBMS.2024.75737.16398","DOIUrl":"10.22038/IJBMS.2024.75737.16398","url":null,"abstract":"<p><strong>Objectives: </strong>Liver fibrosis is a wound healing response characterized by excessive accumulation of extracellular matrix proteins. This study aimed to investigate the effects of resveratrol treatment on the TGF-β/SMAD signaling pathway and related biochemical parameters, apoptosis, and liver regeneration phenobarbital-CCl₄ induced hepatic fibrosis rat model.</p><p><strong>Materials and methods: </strong>This model was created through phenobarbital and CCl₄ (0.2-0.35 ml/kg). Resveratrol (1 mg/kg/day) was administered to the fibrosis and control groups. Immunohistochemical staining was performed to evaluate αSMA, TGF-β1, and PCNA in liver tissue. The TUNEL method and Masson's Trichome staining were used to determine apoptosis and collagen accumulation. AST, ALP, ALT, total protein, and total bilirubin levels were measured to determine biochemical status. SMAD2, SMAD3, SMAD4, and SMAD7 expression levels were measured to determine TGF-β1 related hepatic fibrosis.</p><p><strong>Results: </strong>The SMAD2, SMAD3, and SMAD4 mRNA expression levels were increased and the SMAD7 mRNA expression level was decreased in the fibrosis control group. The SMAD7 mRNA expression level was higher in the phenobarbital-CCl₄ induced resveratrol treated group. Increased biochemical parameters indicating hepatic damage, increased number of apoptotic cells, and collagen accumulation surrounding the central vein were observed in the fibrosis group compared with the other groups. It was concluded that administration of resveratrol ameliorates the adverse effects of hepatic fibrosis by regulating biochemical parameters, controlling TGF-β1/SMAD signaling, enhancing tissue regeneration, and reducing apoptosis in liver cells.</p><p><strong>Conclusion: </strong>Resveratrol can be a beneficial option for the prevention of liver damage in a phenobarbital-CCl₄ induced hepatic fibrosis.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758771","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":null,"pages":null},"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":null,"pages":null},"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}

{"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^R, Rif^R, 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^R, Rif^R, 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^R, Rif^R, 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":null,"pages":null},"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}