Iranian Journal of Basic Medical Sciences最新文献

{"title":"Royal jelly induces ROS-mediated apoptosis in acute lymphoblastic leukemia (ALL)-derived Nalm-6 cells: Shedding light on novel therapeutic approaches for ALL.","authors":"Somayeh Yazdanparast, Davood Bashash, Amirsalar Nikkhah Bahrami, Mohammad Ghorbani, Mehrdad Izadirad, Mehdi Bakhtiyaridovvombaygi, Seyede Zahra Hasanpour, Ahmad Gharehbaghian","doi":"10.22038/IJBMS.2024.76261.16498","DOIUrl":"10.22038/IJBMS.2024.76261.16498","url":null,"abstract":"<p><strong>Objectives: </strong>Until recently, a conventional chemotherapy regimen for Acute lymphoblastic leukemia (ALL) is considered an efficient therapeutic method in children. However, suboptimal long-term survival rates in adults, disease relapse, and drug-induced toxicities require novel therapeutic agents for ALL treatments. Today, natural products with pharmacological benefits play a significant role in treating different cancers. Among the most valued natural products, honey bees' royal jelly (RJ) is one of the most appreciated which has revealed anti-tumor activity against different human cancers. This study aimed to evaluate anti-leukemic properties and the molecular mechanisms of RJ cytotoxicity on ALL-derived Nalm-6 cells.</p><p><strong>Materials and methods: </strong>The metabolic activity was measured by MTT assay. Apoptosis, cell distribution in the cell cycle, and intracellular reactive oxygen species (ROS) level were investigated using flow cytometry analysis. Moreover, quantitative real-time PCR (qRT-PCR) was performed to scrutinize the expression of various regulatory genes.</p><p><strong>Results: </strong>RJ significantly decreased the viability of Nalm-6 cells but had no cytotoxic effect on normal cells. In addition, RJ induced ROS-mediated apoptosis by up-regulating pro-apoptotic genes while decreasing anti-apoptotic gene expression. The results outlined that ROS-dependent up-regulation of FOXO4 and Sirt1 inhibits the cells' transition to the S phase of the cell cycle through p21 up-regulation. The qRT-PCR analysis of autophagy-related gene expression also demonstrated that RJ induced BECN1 mediated autophagy in Naml-6 cells.</p><p><strong>Conclusion: </strong>Taken together, this study showed that RJ can be utilized as a potent natural substance to induce ALL cells' programmed cell death. However, further studies are required to examine this compound's pharmaceutical application.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 7","pages":"801-812"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of methylene blue for the prevention and treatment of COVID-19: A narrative review.","authors":"Elaheh Emadi, Daryoush Hamidi Alamdari, Davood Attaran, Soroush Attaran","doi":"10.22038/IJBMS.2024.71871.15617","DOIUrl":"10.22038/IJBMS.2024.71871.15617","url":null,"abstract":"<p><p>The newest virus from the SARS family of viruses called acute syndrome-coronavirus-2 (SARS-CoV-2), which causes COVID-19 disease, was identified in China at the end of 2019. In March 2020, after it spread to 29 additional countries, it was declared a pandemic by the World Health Organization (WHO). SARS-CoV-2 infection mainly starts through the respiratory tract and causes a wide spectrum of symptoms from asymptomatic infections to acute respiratory distress syndrome with multi-organ failure and vasoplegic shock. Among the many immunomodulatory and antiviral drugs that have been studied for the treatment of COVID-19, methylene blue (MB) may play an influential role. This article reviews the history of MB applications, the antiviral effects of MB against SARS-CoV-2, and the results of <i>in vivo</i> and <i>in vitro</i> studies of the use of MB in COVID-19. Based on studies, MB can simultaneously affect most of the host's harmful responses caused by SARS-CoV-2 infection due to its multiple properties, including anti-hypoxemia, anti-oxidant, immune system modulator, and antiviral. The use of MB is associated with a reduction in the possibility of getting infection, and mortality, and can be used as a safe, effective, cheap, and available treatment option with minimal side effects for the clinical management of COVID-19.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 7","pages":"780-792"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of crocin on the enhancement of <i>in vitro</i> neurogenesis: Involvement of Notch and CREB/BDNF signaling pathways.","authors":"Shayan Vafaei, Vida Mirzaie, Masoumeh Baghalishahi, Elahe Mousanejad, Seyed Noureddin Nematollahi-Mahani","doi":"10.22038/IJBMS.2024.76308.16513","DOIUrl":"10.22038/IJBMS.2024.76308.16513","url":null,"abstract":"<p><strong>Objectives: </strong>Adult neurogenesis, the process of generating new neurons, continues throughout life. Unfortunately, this process is insufficient in pathological conditions and needs to be promoted. Crocin, the active component of saffron, affects neurogenesis <i>in vivo</i> and <i>in vitro</i>. We aimed to investigate the enhancing effects of crocin on the neurogenesis of adipose-derived mesenchymal stem cells in the presence of retinoic acid, as well as the molecular pathways involved.</p><p><strong>Materials and methods: </strong>Differentiation capacities and stemness potential of harvested ADSCs were evaluated by differentiating into osteocytes and adipocytes, and expression of mesenchymal CD markers by flow cytometry. The optimum dose of crocin was assessed with an MTT assay. Crocin, retinoic acid, CREB/BDNF, and Notch inhibitors and their combination were added to the culture medium. Jag1, Hes1, Notch, and BDNF gene expression were analyzed by RT-PCR on days 7, 14, and 21, while CREB, DCX, SOX2, and NeuN expression were analyzed by immunofluorescence.</p><p><strong>Results: </strong>Expression of mesenchymal CD markers as well as adipogenic and osteogenic differentiation confirmed the origin and properties of ADSCs. The optimal dose of crocin was 1 mM. Crocin significantly (<i>P</i><0.05) increased, while inhibitors (DATP&Naphthol) significantly (<i>P</i><0.05) decreased Jag1, Hes1, Notch, and BDNF expression. Immunofluorescent assessments showed that expression of DCX, BDNF, NeuN, and Sox2 proteins increased significantly (<i>P</i><0.05) after crocin administration and decreased significantly (<i>P</i><0.05) after inhibitor administration.</p><p><strong>Conclusion: </strong>Crocin can be used as an enhancer for neural differentiation of MSCs <i>in vitro</i> in the presence of retinoic acid. The mechanism is proposed through Notch and CREB/BDNF signaling pathways.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 7","pages":"914-922"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An <i>in situ</i> forming gelatin-based hydrogel loaded with soluble amniotic membrane promotes full-thickness wound regeneration in rats.","authors":"Mohammad Azimi-Alamouty, Mohammad Amin Habibi, Amin Ebrahimi Sadrabadi, Zahra Jamalpoor","doi":"10.22038/IJBMS.2024.74290.16140","DOIUrl":"10.22038/IJBMS.2024.74290.16140","url":null,"abstract":"<p><strong>Objectives: </strong>Early effective treatment and appropriate coverage are vital for full-thickness wounds. Amnion membrane-derived products have recently emerged in tissue engineering. However, the optimal concentration, carrier for controlled release, and handling have remained challenges. This study aims to develop and optimize an <i>in situ</i> forming, amniotic-based hydrogel for wound healing.</p><p><strong>Materials and methods: </strong>Here, a composite matrix was fabricated with gelatin hydrogel modified with methacrylate functional group conjugated (GelMA) and keratose (wt.1%), loaded with mesenchymal stem cells (MSCs, 1×10⁵ cell/ml) and optimized soluble amniotic membrane (SAM, 0.5 mg/ml). The physicochemical properties of the final subject were evaluated <i>in vitro</i> and <i>in vivo</i> environments.</p><p><strong>Results: </strong>The results of the <i>in vitro</i> assay demonstrated that conjugation of the methacryloyl group with gelatin resulted in the formation of GelMA hydrogel (26.7±1.2 kPa) with higher mechanical stability. Modification of GelMA with a glycosaminoglycan sulfate (Keratose) increased controlled delivery of SAM (47.3% vs. 84.3%). Metabolic activity (93%) and proliferation (21.2 ± 1.5 µg/ml) of MSCs encapsulated in hydrogel improved by incorporation of SAM (0.5 mg/ml). Furthermore, the migration of fibroblasts was facilitated in the scratched assay by SAM (0.5 mg/ml)/MSCs (1×10⁵ cell/ml) conditioned medium. The GelMA hydrogel groupes revealed regeneration of full-thickness skin defects in rats after 3 weeks due to the high angiogenesis (6.3 ± 0.3), cell migration, and epithelialization.</p><p><strong>Conclusion: </strong>The results indicated in situ forming and tunable GelMA hydrogels containing SAM and MSCs could be used as efficient substrates for full-thickness wound regeneration.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 8","pages":"1005-1014"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442638","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":"Comprehensive and updated review on anti-oxidant effects of <i>Nigella sativa</i> and its constituent, thymoquinone, in various disorders.","authors":"Mohammad Reza Aslani, Saeideh Saadat, Mohammad Hossein Boskabady","doi":"10.22038/IJBMS.2024.75985.16453","DOIUrl":"10.22038/IJBMS.2024.75985.16453","url":null,"abstract":"<p><p>Several pharmacological effects were described for <i>Nigella sativa</i> (<i>N. sativa</i>) seed and it has been used traditionally to treat various diseases. In this review article, the updated and comprehensive anti-oxidant effects of <i>N. sativa</i> and its main constituent, thymoquinone (TQ), on various disorders are described. The relevant articles were retrieved through PubMed, Science Direct, and Scopus up to December 31, 2023. Various extracts and essential oils of <i>N. sativa</i> showed anti-oxidant effects on cardiovascular, endocrine, gastrointestinal and liver, neurologic, respiratory, and urogenital diseases by decreasing and increasing various oxidant and anti-oxidant marketers, respectively. The main constituent of the plant, TQ, also showed similar anti-oxidant effects as the plant itself. The anti-oxidant effects of different extracts and essential oils of <i>N. sativa</i> were demonstrated in various studies which were perhaps due to the main constituent of the plant, TQ. The findings of this review article suggest the possible therapeutic effect of <i>N. sativa</i> and TQ in oxidative stress disorders.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 8","pages":"923-951"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442639","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 lupeol and flutamide on experimentally-induced polycystic ovary syndrome in mice.","authors":"Ali Rezaei-Golmisheh, Rajabali Sadrkhanlou, Abbas Ahmadi, Hassan Malekinejad","doi":"10.22038/IJBMS.2024.77602.16783","DOIUrl":"10.22038/IJBMS.2024.77602.16783","url":null,"abstract":"<p><strong>Objectives: </strong>Polycystic ovary syndrome (PCOS) is one of the main causes of infertility in women. This study was conducted to uncover the effects of lupeol as an anti-androgenic triterpene on experimentally-induced PCOS in mice.</p><p><strong>Materials and methods: </strong>Eighty immature female mice were divided into 4 groups: Control (C), PCOS (P), Lupeol (L), and Flutamide (F). PCOS was induced in test groups by injection of Dehydroepiandrosterone (60 mg/kg/day, IP) for twenty days. Following the PCOS induction, the two groups of L and F were treated with lupeol (40 mg/kg/day) and/or flutamide (10 mg/kg/day) respectively and the two groups of C and P received sesame oil (0.1 ml/mouse/day) for 15 days. After the treatment period, ten animals in each group were selected for collecting blood and ovary samples. <i>In vitro</i> fertilization assessment was carried out on 10 remaining mice in each group. The hormonal assays and oxidative stress biomarker determination were performed on serum and tissue samples. Moreover, histopathological analyses were conducted on the ovaries.</p><p><strong>Results: </strong>PCOS-elevated concentration of LH and Testosterone was significantly (<i>P</i><0.05) lowered in lupeol and flutamide-received animals. Lupeol and flutamide both reduced PCOS-induced fibrosis and the number of atretic follicles. Both compounds declined the PCOS-increased lipid peroxidation and protein oxidation in serum and the ovaries. Lupeol increased the PCOS-reduced fertility rate and decreased the number of arrested embryos by 12%.</p><p><strong>Conclusion: </strong>These findings indicate that lupeol could be a novel compound in the treatment of PCOS as it reduced PCOS-induced structural and also functional disorders.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 8","pages":"1067-1076"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442642","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":"Renoprotective effect of <i>Limonium duriusculum</i> (de Girard) Kuntze via modulation of oxidative stress/ UPR markers and inflammation during cyclosporine-induced nephrotoxicity in rats.","authors":"Azzedine Redouane-Salah, Ameddah Souad, Wafa Kerkatou, Kamil Wojnicki, Adrian M Ramos, Alberto Ortiz, Bozena Kaminska, Ahmed Menad","doi":"10.22038/IJBMS.2024.77052.16661","DOIUrl":"10.22038/IJBMS.2024.77052.16661","url":null,"abstract":"<p><strong>Objectives: </strong>The present study aimed to explore the mechanisms underlying the potency of the renoprotective effect of the EtOAc fraction of <i>Limonium duriusculum</i> (EALD) (Plumbaginaceae) against cyclosporine A (CsA), in comparison to vitamin E (Vit. E).</p><p><strong>Materials and methods: </strong>In the <i>in-vivo</i> experiment, a model of CsA-induced nephrotoxicity was established by dosing male Wistar rats with 25 mg/kg, for 14 days. The protective effect of EALD was investigated through pretreatment of rats with a dose of 200 mg/kg for 14 days, compared to the oral administration of Vit. E at 100 mg/kg. Renal function and markers of oxidative stress were then assessed. Furthermore, a complementary <i>in-vitro</i> study was carried out to evaluate CsA-induced endoplasmic reticulum stress (ERS) and inflammation on cell culture (3T3 cells and MCT cells) using western blot and quantitative RT-PCR..</p><p><strong>Results: </strong>Pretreatment of rats with EALD significantly attenuated the elevated levels of renal dysfunction markers (BUN, creatinine) and suppressed malondialdehyde (MDA) levels; It also significantly regulated the changes in superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxydase (GPx), and glutathione S-transferase (GST) levels as compared to Vit. E, demonstrating a more effective recovery in renal tissues. Treatment of cells with CsA was linked to the expression of ERS and inflammatory markers activating transcription factor (ATF4), inositol-requiring enzyme 1α (IRE1α), binding immunoglobulin protein (BiP), and monocyte chemoattractant protein-1 (MCP1). In contrast, pretreatment of cells with EALD resulted in a significant decrease in both ERS and inflammatory markers.</p><p><strong>Conclusion: </strong>These findings indicate the renoprotective potential of <i>L. duriusculum</i>, as it demonstrated the ability to ameliorate CsA-induced renal dysfunction through its distinctive antioxidant properties.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"27 8","pages":"1023-1032"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442676","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":"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":"27 2","pages":"203-213"},"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":"27 2","pages":"170-179"},"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":"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":"27 4","pages":"509-517"},"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}