Iranian Journal of Basic Medical Sciences最新文献

{"title":"Synthesis and evaluation of gene delivery vectors based on PEI-modified metal-organic framework (MOF) nanoparticles.","authors":"Somayeh Khosrojerdi, Leila Gholami, Majid Khazaei, Alireza Hashemzadeh, Majid Darroudi, Reza Kazemi Oskuee","doi":"10.22038/IJBMS.2023.71892.15644","DOIUrl":"10.22038/IJBMS.2023.71892.15644","url":null,"abstract":"<p><strong>Objectives: </strong>Zirconium-based metal-organic frameworks (MOFs) nanostructures, due to their capability of easy surface modification, are considered interesting structures for delivery. In the present study, the surfaces of UIO-66 and NH2-UIO-66 MOFs were modified by polyethyleneimine (PEI) 10000 Da, and their efficiency for plasmid delivery was evaluated.</p><p><strong>Materials and methods: </strong>Two different approaches, were employed to prepare surface-modified nanoparticles. The physicochemical characteristics of the resulting nanoparticles, as well as their transfection efficiency and cytotoxicity, were investigated on the A549 cell line.</p><p><strong>Results: </strong>The sizes of DNA/nanocarriers for PEI-modified UIO-66 (PEI-UIO-66) were between 212-291 nm and 267-321 nm for PEI 6-bromohexanoic acid linked UIO-66 (PEI-HEX-UIO-66). The zeta potential of all was positive with the ranges of +16 to +20 mV and +23 to +26 mV for PEI-UIO-66 and PEI-HEX-UIO-66, respectively. Cellular assay results showed that the PEI linking method had a higher rate of gene transfection efficiency with minimal cytotoxicity than the wet impregnation method. The difference between transfection of modified nanoparticles compared to the PEI 10 kDa was not significant but the PEI-HEX-UIO-66 showed less cytotoxicity.</p><p><strong>Conclusion: </strong>The present study suggested that the post-synthetic modification of MOFs with PEI 10000 Da through EDC/NHS+6-bromohexanoic acid reaction can be considered as an effective approach for modifying MOFs' structure in order to obtain nanoparticles with better biological function in the gene delivery process.</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/PMC10790290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485552","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":"Polyherbal extract improves glycometabolic control in alloxan-induced diabetic rats <i>via</i> down-regulating the MAPK/JNK pathway, modulating Nrf-2/Keap-1 expression, and stimulating insulin signaling.","authors":"Bilal Aslam, Asif Hussain, Muhammad Naeem Faisal, Shaneel Kousar, Alishbah Roobi, Muhammad Rehan Sajid, Aneela Gul","doi":"10.22038/IJBMS.2023.72553.15780","DOIUrl":"10.22038/IJBMS.2023.72553.15780","url":null,"abstract":"<p><strong>Objectives: </strong>This study focused on the evaluation of antioxidant and antidiabetic activities of polyherbal extract (PHE), containing <i>Cassia absus</i> (L.), <i>Gymnema sylvestre</i> (R. Br.), <i>Nigella sativa</i> (L.), and <i>Piper nigrum</i> (L.), in alloxan-induced diabetes model.</p><p><strong>Materials and methods: </strong><i>In vitro</i>, HPLC characterization, DPPH scavenging assay, and α-amylase inhibition test were conducted. <i>In vivo</i>, acute oral toxicity of PHE was assessed. Alloxan-induced diabetic Wistar rats (n=6) were orally treated with PHE (200, 400, and 600 mg/kg/day) and glibenclamide (GLB; 10 mg/kg/day) for six consecutive weeks. Then, biochemical biomarkers, oxidative stress parameters, histopathological examination, and mRNA expression levels (RT-qPCR) were determined.</p><p><strong>Results: </strong>The presence of polyphenols in PHE was confirmed in correlation to marked DPPH scavenging (IC₅₀: 1.60 mg/ml) and α-amylase inhibition (IC₅₀: 0.82 mg/ml). PHE demonstrated no toxicity in rats up to a dose of 2000 mg/kg. In diabetic rats, PHE dose-dependently ameliorated the serum levels of glucose, insulin, glycated hemoglobin A1c (HbA1c), leptin, and glucokinase (GCK). Also, PHE substantially alleviated serum inflammatory markers (TNF-α and CRP) and oxidative stress indicators (MDA, SOD, and CAT) in pancreatic tissues. PHE, particularly at 600 mg/kg, attenuated cellular oxidative stress <i>via</i> modulating the mRNA expression levels of genes regulating MAPK/JNK (Mapk-8, Traf-4, and Traf-6) and Nrf-2/Keap-1 pathways and promoted insulin signaling through up-regulating insulin signaling cascade (Pdx-1, Ins-1, and Ins-2), as compared to GLB. Furthermore, histopathological findings supported the aforementioned results.</p><p><strong>Conclusion: </strong>Our study suggests that polyherbal extract has promising antioxidant and antidiabetic activities by modulating the MAPK/JNK, Nrf-2/Keap-1, and insulin signaling pathways.</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/PMC10790299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485611","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":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/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":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/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":"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":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/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":"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":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/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":"Andrographolide demonstrates anti-proliferative activity in oral cancer by promoting apoptosis, the programmed cell death process.","authors":"Gauri Mansinh Kumbhar, Amol Dilip Jadhav, Supriya Kheur, Ladke Vaibhav Sunil","doi":"10.22038/ijbms.2024.76691.16599","DOIUrl":"10.22038/ijbms.2024.76691.16599","url":null,"abstract":"<p><strong>Objectives: </strong>Andrographolide has been studied on different types of human cancer cells, but very few studies have been conducted on oral cancer. The study aimed to evaluate the anticancer potential of Andrographolide on an oral cancer cell line (KB) through <i>in-silico</i> network analysis and <i>in vitro</i> assays.</p><p><strong>Materials and methods: </strong>The <i>in-silico</i> analysis involved the determination of drug-likeness prediction, prediction of common targets between oral cancer and andrographolide, Protein-Protein Interactions (PPI), hub genes, top 10 associated pathways by Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway, gene ontology (GO), and molecular docking experiments. <i>In vitro</i> assays comprised MTT assay, apoptosis assay, cell cycle analysis, intracellular reactive oxygen species (ROS) measurement, mitochondrial membrane potential (MMP), anti-migration activity, and gene expressions using polymerase chain reaction (PCR).</p><p><strong>Results: </strong>Fifteen common genes were obtained and were seen to be involved in cellular proliferation, regulation of apoptosis, migration of cells, regulation of MAPK cascade, and regulation of cell cycle. The most common genes involved in the top 10 pathways were MAPK1, MAPK8, MAPK14, and IL6 which were seen to be associated with the MAPK signaling pathway which may be the key pathway through which andrographolide may aid in treating oral cancer. <i>In vitro</i> assays showed anti-proliferative properties, late apoptosis, and anti-migratory properties.</p><p><strong>Conclusion: </strong>According to the results obtained, andrographolide has shown anticancer properties and has the potential to be used as a chemotherapeutic drug. The <i>in-silico</i> approach used in the present study can aid as a model for future research in developing efficient cancer treatments.</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/PMC11366947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125694","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":"MicroRNA miR-188-5p enhances SUMO2/3 conjugation by targeting SENP3 and alleviates focal cerebral ischemia/reperfusion injury in rats.","authors":"","doi":"10.22038/ijbms.2024.76165.16485","DOIUrl":"10.22038/ijbms.2024.76165.16485","url":null,"abstract":"<p><strong>Objectives: </strong>Expression of miR-188-5p changes upon experiencing cerebral I/R injury. SENP3 is a predicted target of miR-188-5p. The study aimed to examine the potential mechanism underlying the miR-188-5p mediated enhancement of SUMO2/3 conjugation via targeting SENP3 and alleviation against cerebral I/R injury.</p><p><strong>Materials and methods: </strong>Focal cerebral I/R was established in Sprague-Dawley rats using the MCAO model. The expression of miR-188-5p was modulated through intracerebroventricular (ICV) administration of its mimics or inhibitors. The expression of miR-188-5p, SENP3, and SUMO2/3 was detected using RT-qPCR or western blot analysis. Dual luciferase reporter assays were conducted to demonstrate the targeting effect of miR-188-5p on SENP3 in N2a cells. HE staining and TUNEL staining were performed to evaluate neurocellular morphological changes and detect neurocellular apoptosis, respectively. The extent of neurological deficits was evaluated using mNSS. TTC staining was used to evaluate the infarct area.</p><p><strong>Results: </strong>In the cerebral ischemic penumbra, the expression of miR-188-5p declined and SENP3 levels increased following I/R. Dual luciferase reporter assays confirmed that miR-188-5p directly acted on SENP3 in N2a cells. As a self-protective mechanism, SUMO2/3 conjugation increased after reperfusion. After ICV administration of miR-188-5p inhibitor, the expression of miR-188-5p was down-regulated, the expression of SENP3 was up-regulated, the SUMO2/3 conjugation decreased, and cerebral I/R injury was exacerbated. However, ICV administration of small hairpin RNA targeting SENP3 partially reversed the effects of the miR-188-5p inhibitor.</p><p><strong>Conclusion: </strong>MiR-188-5p mitigated cerebral I/R injury by down-regulating SENP3 expression and consequently enhancing SUMO2/3 conjugation in rats.</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/PMC11366937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125703","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":"Antiarrhythmic potentials of irisin in ischemia/reperfusion injury of diabetic rats through modulating mitochondria-endoplasmic reticulum interaction and inhibiting pyroptosis.","authors":"Xiaona Zhang Zhang, Kai Jing, Wei Ma, Jin Wang","doi":"10.22038/ijbms.2024.78069.16878","DOIUrl":"10.22038/ijbms.2024.78069.16878","url":null,"abstract":"<p><strong>Objectives: </strong>Myocardial arrhythmia is a major complication of ischemia-reperfusion (I/R) injury in patients with diabetes. Irisin has significant cardioprotective effects, while its role in the pathophysiology of I/R injury-induced myocardial arrhythmia in the presence of diabetes is not well identified. Here, we aimed to investigate the potential antiarrhythmic impacts and mechanisms (mitochondrial biogenesis, endoplasmic reticulum (ER) stress, and pyroptosis) by which irisin reduces I/R injury-induced myocardial arrhythmia in diabetic rats.</p><p><strong>Materials and methods: </strong>Thirty high-fat diet-induced diabetic rats were subjected to I/R injury and myocardial arrhythmia. Irisin (0.5 μg/kg/day) was injected intraperitoneally before induction of I/R injury. Electrocardiography was used to measure the incidence and severity of ventricular arrhythmias. ELISA and western blotting analyses were employed to quantify the expression of mitochondrial biogenesis, ER stress, and pyroptosis-related proteins in ischemic myocardium.</p><p><strong>Results: </strong>Irisin treatment in diabetic rats significantly decreased the lactate dehydrogenase level and the number and severity of arrhythmia induced by I/R injury. Irisin up-regulated the expression of mitochondrial biogenesis-related proteins while down-regulating the expression of ER stress and pyroptosis-related proteins. Furthermore, the inhibition of mitochondrial quality control by mdivi-1 significantly abolished the cardioprotective effect of irisin.</p><p><strong>Conclusion: </strong>Our findings suggest that irisin reduced myocardial arrhythmia induced by I/R injury in diabetic rats by modulating the interaction of mitochondrial biogenesis and ER stress proteins and inhibiting the pyroptosis pathway. These findings provide a promising strategy for managing myocardial arrhythmia in diabetic patients, but supplementary studies are needed to confirm the clinical efficacy of irisin in these patients.</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/PMC11459340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390502","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":"C-71980262, a novel small molecule against human papilloma virus-16 E6 (HPV-16 E6) with anticancer potency against cervical cancer: A computational guided <i>in vitro</i> approach.","authors":"Ashish Kumar","doi":"10.22038/ijbms.2024.78090.16882","DOIUrl":"10.22038/ijbms.2024.78090.16882","url":null,"abstract":"<p><strong>Objectives: </strong>Human papillomavirus-16 E6 (HPV-16 E6) forms a heterodimer complex to up-regulate the degradation of tumor suppressor protein p53 to promote cervical cancer. This study aims to identify a novel small molecule against E6 with anticancer efficacy against HPV-16, a prime high-risk serotype inducer for cervical cancer.</p><p><strong>Materials and methods: </strong>Autodock-vina-based high-throughput virtual screening and atomistic molecular dynamic simulations were used for identification of targeted lead molecules. HPV-16 infected SiHa and CaSki cell lines were used to validate the lead compound in vitro. Proliferation of cancer cells was analyzed by MTT assay and flow cytometry was used to analyze target inhibition, apoptosis, and p53.</p><p><strong>Results: </strong>High throughput virtual screening and molecular dynamic simulation identified C-71980262 as a lead candidate that could bind HPV-E6. Atomistic molecular dynamic simulation of E6 bound C-71980262 for 200 ns showed that the predicted ligand binding was stable with minimal energy expenditure, proposing the viability and veracity of the assessed molecule. C-71980262 inhibited the proliferation of SiHa and CaSki cells with GI50 values of 355.70 nM and 505.90 nM, respectively. The compound reduced HPV-16 E6 while inducing early and late-phase apoptosis in these cells. Treatment with C-71980262 increased the p53-positive populations in SiHa and CaSki cells.</p><p><strong>Conclusion: </strong>C-71980262 was identified as a novel lead molecule that could inhibit the HPV-16 E6 and increase p53 in cervical cancer cells. Further in vitro and in vivo validation is warranted to consolidate and corroborate this lead compound against HPV-induced cancer progression.</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/PMC11459339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390525","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}