{"title":"Effects of different pre-conditioning exercise on leptin synthesis and its downstream signalling pathway in T2DM rats.","authors":"Sen Lin, Yuzhi Hu, Shuqiao Ding, Yazhe Hu","doi":"10.22038/ijbms.2024.77774.16828","DOIUrl":"10.22038/ijbms.2024.77774.16828","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the effects of pre-conditioning exercise on body lipid metabolism, leptin secretion, and the downstream pathways at the early stage of type 2 diabetes mellitus (T2DM).</p><p><strong>Materials and methods: </strong>The T2DM model was established using an 8-week high-sugar, high-fat diet combined. The T2DM model was established using an 8-week high-sugar, high-fat diet combined with streptozocin (STZ) injection. Two exercise interventions, high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) were performed during the model-building process. One week following the STZ injection, rats were euthanized. Blood, gastrocnemius muscle, and epididymal fat pad were collected. Plasma leptin content was measured by ELISA. The expression of leptin-mRNA in epididymal adipose tissue was measured using RT-qPCR, and its protein expression was detected by a western blot. Leptin, leptin-R, and AMPK (AMP-activated protein kinase) - ACC (Acetyl-CoA carboxylase) expression in gastrocnemius muscle was also detected by western blot. Free fatty acids (FFA) and triglycerides (TG) contents in gastrocnemius muscle were measured using a biochemical assay.</p><p><strong>Results: </strong>In the HIIT group, glucose tolerance and leptin receptor expression increased, as did the expression and phosphorylation of AMPK protein. At the early stage of T2DM, it increased significantly in the gastrocnemius muscle in the MICT group.</p><p><strong>Conclusion: </strong>At the early stage of T2DM, pre-conditioning exercise in the form of HIIT was found to inhibit the leptin-mRNA expression in adipose tissue, suppress leptin synthesis, up-regulate AMPK-ACC signaling pathway, and promote lipid decomposition in skeletal muscle tissue. Pre-conditioning of MICT led to the accumulation of FFA and TG in skeletal muscle, likely due to exercise adaptation rather than ectopic deposition of lipids.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 1","pages":"31-37"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058952","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":"Infiltration of innate and adoptive lymphoid cells in 4T1 and MC4-L2 breast cancer models.","authors":"Reihane Rasooli Tehrani, Hossein Asgarian-Omran, Saeid Taghiloo, Reza Valadan, Soheil Azizi, Abolghasem Ajami","doi":"10.22038/ijbms.2024.80535.17434","DOIUrl":"10.22038/ijbms.2024.80535.17434","url":null,"abstract":"<p><strong>Objectives: </strong>Innate lymphoid cells (ILCs) are tissue-resident lymphocytes that have vital roles in activating further immune responses. However, due to their tumor-induced diversity, we decided to examine ILCs, T cells, and the associated cytokines in mouse models of breast cancer.</p><p><strong>Materials and methods: </strong>4T1 and MC4-L2 cells were used to induce triple-negative and hormone-receptor-positive breast cancer, respectively. Tumor tissue was resected at early and late stages of tumor growth and used for further analysis. Total RNA was extracted and used in Real-Time PCR to analyze the expression of IFN-γ, IL-4, IL-10, IL-13, and IL-22. Tumor tissue was digested and used in a flow cytometric assay. H&E staining was used to examine the pathology of tumor progression.</p><p><strong>Results: </strong>Both tumor models showed a notable increase in T-cell frequency at the early stage of tumor growth. However, as the tumors progressed, the frequency of T cells significantly decreased, while the ILC component exhibited a significant increase in tumor progression. Gene analysis indicated a significant increase in the inflammatory to anti-inflammatory cytokine ratio during tumor progression in the tumor model. In contrast, this ratio was considerably reduced in advanced MC4-L2 tumors. Both tumor models showed the development of invasive breast carcinoma and lung metastasis in advanced tumors.</p><p><strong>Conclusion: </strong>Our study highlighted the expansion of ILCs during tumor progression in two distinct breast cancer models with different immunogenicity. These findings suggest that ILCs may actively modulate the tumor microenvironment during the advanced stage of tumor growth.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 1","pages":"63-71"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059072","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}
Mohammad Ghasemi Narimani, Fatemeh Kalalinia, Somayeh Marouzi, Sara Gheshlaghi, Zahra Salmasi, Maryam Hashemi
{"title":"Nanoformulation innovations: Revolutionizing precision in migraine therapy.","authors":"Mohammad Ghasemi Narimani, Fatemeh Kalalinia, Somayeh Marouzi, Sara Gheshlaghi, Zahra Salmasi, Maryam Hashemi","doi":"10.22038/ijbms.2024.79824.17290","DOIUrl":"10.22038/ijbms.2024.79824.17290","url":null,"abstract":"<p><strong>Objectives: </strong>Migraine, a serious neurological disease that affects millions of people worldwide, is one of the most considerable burdens on the healthcare system and has significant economic implications. Even though various treatment methods are available, including medication, lifestyle changes, and behavioral therapy, many migraine sufferers do not receive adequate relief or experience intolerable side effects. Hence, the present review aims to evaluate the nanoformulation regarding migraine therapy.</p><p><strong>Materials and methods: </strong>Between 2005 and 2024, specific keywords were used to search several databases, such as Pubmed, Google Scholar, and Scopus.</p><p><strong>Results: </strong>The nanoformulation field is an increasing field within nanotechnology that offers new solutions for treating migraine, including improving drug delivery, increasing therapeutic efficacy, and minimizing side effects. By combining nanoscale materials with therapeutic agents, nanoformulations can enhance bioavailability, sustain drug release, deliver targeted drugs, and penetrate the Blood-Brain Barrier (BBB) more efficiently. Nanoformulation has the potential to be a useful tool for migraine therapy. However, several challenges still need to be overcome, such as the BBB penetration, safety and biocompatibility of the product, manufacturing, and scalability reproducibility to pass regulatory approval and affordability. To overcome these challenges, research efforts should be focused on developing innovative techniques to penetrate the BBB, target specific migraine pathways, incorporate personalized medicine approaches, and develop nanotechnology-based diagnostics.</p><p><strong>Conclusion: </strong>A nanotechnology-based approach aims to revolutionize migraine therapy, improving patient outcomes and living standards by offering personalized and precise treatments.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 1","pages":"16-30"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059074","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":"Role of VDAC1 in hepatocyte apoptosis during acute liver injury in rats induced by obstructive jaundice.","authors":"Jinshan Liu, Jinlong Hu, Hongyu Xu, Liang Yan, Jiaming Yao, Baoqiang Cao","doi":"10.22038/ijbms.2024.78454.16962","DOIUrl":"10.22038/ijbms.2024.78454.16962","url":null,"abstract":"<p><strong>Objectives: </strong>Exploring the role of VDAC1 in hepatocyte apoptosis during acute liver injury induced by obstructive jaundice.</p><p><strong>Materials and methods: </strong>Animal and cell models were established to investigate possible mechanisms during acute liver injury induced by OJ. Blood was collected for liver function assessment. H&E and TEM were employed to observe pathological changes in the liver tissues. Flow cytometry was used to measure the hepatocyte apoptosis. The mitochondrial MPTP assay was employed to assess the mitochondrial function of hepatocytes. IHC, western blot, and qRT-PCR were employed to determine the expression levels of VDAC1. Then, VDAC-siRNA was used to establish a knockdown model. Flow cytometry was used again to measure hepatocyte apoptosis following VDAC1 knockdown.</p><p><strong>Results: </strong>The serum of rats in the OJ group exhibited a significant increase in liver function. Irregular tissue structure and mitochondrial morphology were observed in the liver tissues of OJ rats. A significant increase in mitochondrial permeability in hepatocytes. The expression levels of VDAC1 were significantly increased in the liver tissue of OJ rats. They were also significantly increased in the hepatocytes, primarily within mitochondrial membranes, determined by western blot <i>in vivo</i> and <i>in vitro</i>. Significant increases in the rates of hepatocyte apoptosis, particularly early apoptosis, were observed in the OJ groups. However, there was a reverse in the rates of hepatocyte apoptosis after knockdown regulation of VDAC1 only within the cells of the OJ group.</p><p><strong>Conclusion: </strong>The up-regulation of VDAC in liver injury caused by obstructive jaundice may lead to increased early apoptosis of hepatocytes.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 1","pages":"87-97"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059077","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}
Sara Mostafalou, Fatemeh Moafi-Madani, Maryam Baeeri, Mahban Rahimifard, Hamed Haghi-Aminjan
{"title":"Azelaic acid reduces arsenic-induced toxicity and inflammation in the rat islets of langerhans.","authors":"Sara Mostafalou, Fatemeh Moafi-Madani, Maryam Baeeri, Mahban Rahimifard, Hamed Haghi-Aminjan","doi":"10.22038/ijbms.2025.84651.18311","DOIUrl":"https://doi.org/10.22038/ijbms.2025.84651.18311","url":null,"abstract":"<p><strong>Objectives: </strong>Arsenic is classified as a toxic metal that is naturally found in the Earth's crust, and long-term exposure to it can result in chronic human disorders like cancer and diabetes. Azelaic acid (AZA), a natural dicarboxylic acid, has been reported to have anti-oxidant and anti-inflammatory effects; hence, it may protect against the metabolic toxicity of arsenic. This study aimed to investigate whether AZA could ameliorate sodium arsenite (SA) toxicity toward rat islets of Langerhans.</p><p><strong>Materials and methods: </strong>Pancreatic Islets of Langerhans isolated from adult male Wistar rats were divided into four groups of 10: control, SA, AZA, and SA plus AZA. Twenty-four hours after incubation, cell viability, cell death pathways, reactive oxygen species (ROS), inflammatory factor gene expression, and insulin secretion were evaluated.</p><p><strong>Results: </strong>SA dose-dependently decreased cell viability, increased apoptosis, ROS generation, expression of inflammatory mediators (NF-κB, IL-1β, and TNF-α), and insulin secretion. AZA was able to ameliorate all these changes significantly.</p><p><strong>Conclusion: </strong>Our results indicate that SA can potentially disrupt cellular homeostasis and function in the islets of Langerhans and can increase the risk of metabolic diseases such as diabetes. On the other hand, AZA protected islets of Langerhans against the toxic effects of SA, seemingly due to its anti-apoptotic, anti-inflammatory, and anti-oxidant properties, indicating that AZA may have the potential to run intracellular mechanisms beneficial for coping with the metabolic toxicity of arsenic.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 6","pages":"784-789"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009519","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":"Investigation of the molecular and cellular effects of Shilajit on 5-fluorouracil (5-FU)-induced nephrotoxicity in rats.","authors":"Mehmet Ezer, Melek Öztürkler, Kezban Yıldız-Dalgınlı, Emine Atakişi, Hatice Beşeren-Havadar, Onur Atakişi","doi":"10.22038/ijbms.2025.80989.17525","DOIUrl":"10.22038/ijbms.2025.80989.17525","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the protective effects of shilajit on 5-fluorouracil (5-FU)-induced nephrotoxicity in a rat model.</p><p><strong>Materials and methods: </strong>Twenty male Sprague Dawley rats were divided into four groups: Control, 5-FU, shilajit, and 5-FU + shilajit. 5-FU was administered intraperitoneally at 200 mg/kg, while shilajit was given orally at 200 mg/kg. Kidney tissues were analyzed for oxidative stress markers, protein expression (SIRT2, SIRT3, β-catenin, E-cadherin, and caspase-3), and histopathological changes.</p><p><strong>Results: </strong>5-FU significantly increased oxidative stress parameters and kidney damage markers. Shilajit co-administration with 5-FU reduced oxidative stress and increased anti-oxidant status and SIRT2, SIRT3, and cell adhesion protein expression. Histopathological evaluation showed reduced renal damage in the shilajit + 5-FU group compared to the 5-FU group.</p><p><strong>Conclusion: </strong>Shilajit exhibited significant protective effects against 5-FU-induced nephrotoxicity, improving oxidative parameters, protein expression, and kidney histopathology. Further studies are needed to elucidate its molecular mechanism and therapeutic potential.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 5","pages":"565-574"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642474","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":"Sinapic acid attenuated nephrotoxicity against Cyclophosphamide in mice model: A histochemical, immunohistochemical and histopathological evaluation.","authors":"Saeed Raoof, Shiva Rezaei, Mehryar Zargari, Mansoureh Mirzaei, Seyed Jalal Hosseinimehr, Abbasali Karimpour Malekshah, Fereshteh Talebpour Amiri","doi":"10.22038/ijbms.2025.83903.18155","DOIUrl":"10.22038/ijbms.2025.83903.18155","url":null,"abstract":"<p><strong>Objectives: </strong>Cyclophosphamide (CP) is a chemotherapeutic drug used to treat various tumors. It causes nephrotoxicity by producing reactive oxygen species. Sinapic acid (SA) exhibits anti-oxidant, antiapoptotic, and anti-inflammatory activities at low doses as a phenylpropanoid. This study aimed to investigate the protective effects of SA on SP-induced renal injury.</p><p><strong>Materials and methods: </strong>Forty-eight BALB/c mice were randomly divided into control, SA (for seven consecutive days, with two doses of 5 and 10 mg/kg), CP (single dose, 200 mg/kg), and CP + SA (5 and 10 mg/kg). On the 10th day of the study, mice were examined by renal function markers (Urea and Creatinine), oxidative stress markers (MDA and GSH), histopathological, and immunohistochemical assays (caspase-3 and NF-kB kidney).</p><p><strong>Results: </strong>MDA levels increased and GSH levels decreased significantly in CP-treated mice. In addition, the histopathological structure of the kidney tissue in CP-treated mice showed significantly severe kidney tissue damage associated with increased urea and creatinine. The administration of SA in CP-treated mice significantly reduced serum urea and creatinine concentrations. In addition, the immunohistochemical staining of caspase- 3 and NF-kB decreased significantly in the CP + SA group compared to CP-treated mice.</p><p><strong>Conclusion: </strong>Overall, our study suggests that sinapic acid, a substance with antioxidant, antiapoptotic, and anti-inflammatory properties, can be used as a complementary therapy to protect nephrotoxicity against CP.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 5","pages":"655-661"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642478","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}
Mahboobeh Ghasemzadeh Rahbardar, Mohammad Ehsan Taghavizadeh Yazdi, Sima Beigoli, Hamideh Amin, Mohammad Hossein Boskabady
{"title":"Exploring the role of curcumin, nanocurcumin, and a PPAR agonist in preventing paraquat-induced systemic inflammation and oxidative stress in rats.","authors":"Mahboobeh Ghasemzadeh Rahbardar, Mohammad Ehsan Taghavizadeh Yazdi, Sima Beigoli, Hamideh Amin, Mohammad Hossein Boskabady","doi":"10.22038/ijbms.2025.82057.17753","DOIUrl":"10.22038/ijbms.2025.82057.17753","url":null,"abstract":"<p><strong>Objectives: </strong>We investigated the effects of curcumin, nanocurcumin, and pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) activator, on the systemic inflammation and oxidative stress induced by inhaled paraquat (PQ).</p><p><strong>Materials and methods: </strong>The experimental design included male Wistar rats divided into nine groups. Animals of the control group (Ctrl) were exposed to saline and those of other groups to 54 mg/m<sup>3</sup> PQ aerosols 8 times on alternate days. PQ exposing groups were treated with saline (PQ group), curcumin (30 mg/kg, Cu), nanocurcumin (2 and 8 mg/kg, NC-L, and NC-H), pioglitazone (5 mg/kg, Pio), Pio+ Cu-L, Pio + NC-L, and dexamethasone (0.03 mg/kg, Dexa). Pio was administered intraperitoneally and other treating agents by gavage for 16 days during the PQ exposure period. Total and differential white blood cell (WBC) counts, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), thiol, interleukin (IL)-10, and tumor necrosis factor-alpha (TNF-α) levels were measured.</p><p><strong>Results: </strong>The inhalation of PQ increased total WBC, differential WBC, MDA, IL-10, and TNF-α blood levels. It also decreased blood levels of CAT, SOD, and thiol. The treatment groups (Cu, NC-L, NC-H, Pio+Cu, Pio+NC-L, Pio, and Dexa) ameliorated PQ-induced alterations. Furthermore, the improvements in most parameters in the Pio+Cu and NC-L-treated group were more significant than the results of the three substances individually.</p><p><strong>Conclusion: </strong>The amelioration of systemic inflammation and oxidative stress caused by inhaled PQ by Cu, NC, and Pio were shown. Furthermore, the findings indicated a synergistic effect between Pio with Cu and NC, suggesting the involvement of PPARγ-mediated mechanisms in the effects of curcumin.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 7","pages":"852-859"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698504","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}
Xiaogang Zhang, Mengqing Shi, Zhongying Xing, Jie Su, Yuying Gu, Zhongping Ning
{"title":"Schisandrin B regulates the SIRT1/PI3K/Akt signaling pathway to ameliorate Ang II-infused cardiac fibrosis.","authors":"Xiaogang Zhang, Mengqing Shi, Zhongying Xing, Jie Su, Yuying Gu, Zhongping Ning","doi":"10.22038/ijbms.2025.83918.18160","DOIUrl":"10.22038/ijbms.2025.83918.18160","url":null,"abstract":"<p><strong>Objectives: </strong>Schisandrin B (SchB), extracted from <i>Schisandra chinensis</i>, has antimicrobial and anti-inflammatory effects. The study aimed to investigate SchB's possible defense against angiotensin II (Ang II)-infused cardiac fibrosis and its molecular processes.</p><p><strong>Materials and methods: </strong>An equivalent volume of saline or Ang II (2.0 mg/kg/day, HY-13948, MedChemExpress) was administered subcutaneously to male C57BL/6 mice aged between 8 and 10 weeks. SchB (30 mg/kg/day, HY-N0089, MedChemExpress) was given via intraperitoneal injection two hours before Ang II infusion for 28 days. Comprehensive morphological, histological, and biochemical analyses were conducted. We evaluated the mRNA and protein expression levels using western blot and RT-qPCR techniques.</p><p><strong>Results: </strong>SchB treatment improves heart disease in Ang II-induced mice. SchB markedly lowered serum levels of cardiac fibrosis-related markers, including cTnI, cTnT, ANP, and BNP. In addition, SchB elevated sirtuin 1 (SIRT1) expression while reducing α-SMA, TGF-β1, collagen I, collagen III, and CTGF <i>in vivo</i>. Furthermore, SchB inhibited the migration of Ang II-infused rat cardiac fibroblasts. SchB increased SIRT1 expression while decreasing TGF-β1, α-SMA, collagen I, and collagen III, whereas EX-527, an inhibitor of SIRT1, recovered their activities <i>in vitro</i>. Furthermore, SchB elevated SIRT1 expression while lowering the expressions of p-PI3K (p85, Tyr458) and p-Akt (Ser473) proteins.</p><p><strong>Conclusion: </strong>Our results suggest that SchB regulates the SIRT1/PI3K/Akt pathway to prevent Ang II-infused cardiac fibrosis.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 7","pages":"946-954"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698517","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}
Yong Liu, Xinyu Liu, Shuang Li, Tianshuang Xu, Yang Lu, Tao Wang, Hui Yuan
{"title":"Spermine: A prospective treatment for high glucose-induced myocardial fibrosis in db/db mice.","authors":"Yong Liu, Xinyu Liu, Shuang Li, Tianshuang Xu, Yang Lu, Tao Wang, Hui Yuan","doi":"10.22038/ijbms.2025.83464.18060","DOIUrl":"10.22038/ijbms.2025.83464.18060","url":null,"abstract":"<p><strong>Objectives: </strong>This study explored the molecular mechanism by which exogenous spermine attenuates diabetic cardiomyopathy (DCM)-induced myocardial fibrosis.</p><p><strong>Materials and methods: </strong>db/db mice and primary neonatal mouse cardiac fibroblasts were used to conduct <i>in vivo</i> and <i>in vitro</i> experiments. The levels of total cholesterol (TC), triglycerides (TG), creatine kinase isoenzyme (CK-MB), troponin I (cTnI), and lactate dehydrogenase (LDH) were measured. Heart function and collagen deposition were assessed using echocardiographic analysis, Masson staining, and Sirius red staining. Cell proliferation and migration were analyzed using EdU and transwell assays. Relevant protein expression was evaluated by immunohistochemistry and western blot.</p><p><strong>Results: </strong>After 12 weeks, the mice in the type 2 diabetes (T2D) group exhibited increased blood glucose, TG, TC, and serum myocardial marker enzyme levels. Ejection fraction (EF) and left ventricular fractional shortening left ventricular fractional shortening (FS) decreased, while LVIDs and LVIDd increased. Significant collagen fiber deposition and increased HW/TL ratio, SSAT, α-SMA, TGF-β1, and Collagen-I/III expression was observed in myocardial tissue. Conversely, ODC expression was down-regulated. In the T2D + spermine (SP) group, these trends were reversed. <i>In vitro</i>, high glucose conditions led to increased proliferation of cardiac fibroblasts. SSAT, α-SMA, TGF-β1, Collagen-I/III, MMP-2, MMP-9, p-Smad-2, TβRI, and TβRII were up-regulated, while ornithine decarboxylase (ODC) expression was down-regulated. Interestingly, these changes were reversed in the HG + SP group.</p><p><strong>Conclusion: </strong>Our findings demonstrate that SP reduces collagen synthesis and secretion by inhibiting the TGF-β1/Smads signaling pathway. These results provide new insights into potential therapeutic approaches for DCM.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 7","pages":"907-915"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698518","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}