Iranian Journal of Basic Medical Sciences最新文献

{"title":"Lysyl oxidase-like 2 promotes the survival, migration, and ferroptosis of endometrial cancer cells by activating the phosphoinositide 3-kinase/protein kinase B pathway.","authors":"Jiashi Gu, Huanmei Sun, Juan Shao, Hu Zhang, Zhanpeng Zhu, Dongqin Ma, Yingchun Duan","doi":"10.22038/ijbms.2024.79933.17317","DOIUrl":"10.22038/ijbms.2024.79933.17317","url":null,"abstract":"<p><strong>Objectives: </strong>LOXL2, known as Lysyl oxidase-like 2, is classified as a lysyl oxidase (LOX) family member. However, its role and mechanism in endometrial cancer (EC) are unknown. Therefore, we aimed to investigate the potential role and mechanism of LOXL2 in EC.</p><p><strong>Materials and methods: </strong>The levels of LOXL2 expression in EC tissues and normal adjacent tissues were evaluated by immunohistochemically (IHC) labeling. Following the dye application, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell methodologies were executed to evaluate the effects of LOXL2 inhibition and up-regulation on the growth, programmed cell death, migration, and susceptibility to iron-dependent cell death of EC. Moreover, protein analysis through Western blotting and gene expression analysis using Real-time quantitative PCR (RT-qPCR) was employed to measure the levels of pertinent biomarkers.</p><p><strong>Results: </strong>LOXL2 is highly expressed in both EC tissues and serum in vivo. Silencing LOXL2 reduced EC cell proliferation and migration while increasing apoptosis <i>in vitro</i>. LOXL2 silencing increased the ferroptosis-related proteins Solute Carrier Family 7 Member 11 (SLC7A11) and Ferritin Heavy Chain 1 (FTH1) while decreasing Glutathione Peroxidase 4 (GPX4) (both, <i>P<</i>0.001). Additionally, LOXL2 silencing reduced the p-PI3K and p-Akt protein expression, while LOXL2 overexpression (OE-LOXL2) elevated the p-PI3K and p-Akt protein expression (both, <i>P<</i>0.001). Additionally, LOXL2 silencing increases SLC7A11 and FTH1 while decreasing GPX4 (both <i>P<</i>0.001). LOXL2 overexpression has the opposite effect. However, the LY294002 inhibitor restores SLC7A11 and FTH1 expression while decreasing GPX4 (<i>P<</i>0.001).</p><p><strong>Conclusion: </strong>Our research demonstrated that LOXL2 might protect EC via phosphorylation by activating the PI3K/AKT pathway.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 1","pages":"72-79"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059073","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":"Sulforaphane alleviates membranous nephropathy by inhibiting oxidative stress-associated podocyte pyroptosis.","authors":"Daoyuan Lv, Laping Chu, Yuan Du, Chunqing Li, Neng Bao, Yuqing Su, Gang Wang, Yanlie Zheng, Yafen Yu","doi":"10.22038/ijbms.2024.78960.17083","DOIUrl":"10.22038/ijbms.2024.78960.17083","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the natural product sulforaphane (SFN) in protection of membranous nephropathy (MN) by inhibiting oxidative stress-associated podocyte pyroptosis.</p><p><strong>Materials and methods: </strong>A passive Heymann nephritis (PHN) model was established and treated with SFN. Clinical manifestations were examined by testing 24-hr urine protein, albumin, total cholesterol, triglyceride, high-density and low-density lipoprotein levels. Podocyte injury was observed through glomerular ultrastructure and the expression of podocin and desmin. Intrarenal oxidative stress was evaluated through assessment of oxidative markers, including malondialdehyde, 8-isoprostane, and 8-hydroxydeoxyguanosine, and the activities of anti-oxidant enzymes, including total superoxide dismutase, catalase, and γ-glutamylcysteine synthetase. Podocyte and intrarenal pyroptosis were investigated by observing the localization of the GSDMD N-terminus (GSDMD(N)) in podocytes; the expression of pyroptosis signaling pathway, including GSDMD, NF-κB p65, p-NF-κB p65 (Ser536), NLRP3, ASC, caspase-1, IL-1β, and IL-18; and pyroptosis encounter Nrf2 in the glomeruli and kidney.</p><p><strong>Results: </strong>SFN has a protective effect on MN, as reflected by alleviation of nephrotic syndrome, amelioration of podocyte foot process fusion, increased expression and normalization of podocin, and decreased expression of desmin in the glomeruli. Mechanistically, SFN relieved intrarenal oxidative stress, as indicated by decreased renal malondialdehyde, 8-isoprostane, and 8-hydroxydeoxyguanosine and increased activity of total superoxide dismutase, catalase, and γ-glutamylcysteine synthetase. SFN also inhibited podocyte and intrarenal pyroptosis, as revealed by decreased colocalization of GSDMD (N) with synaptopodin and ZO-1, decreased expression of pyroptosis signaling pathway, and increased expression of Nrf2 in the glomeruli and kidney.</p><p><strong>Conclusion: </strong>SFN could alleviate MN by inhibiting oxidative stress-associated podocyte pyroptosis.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 2","pages":"237-244"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028713","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":"Evaluating ginkgetin from <i>Ginkgo biloba</i> as a novel agent for sleep promotion through molecular docking and <i>in vivo</i> studies.","authors":"Mir Behrad Aghazadeh Ghadim, Ebrahim Salimi-Sabour, Alireza Shahriari, Mahdi Niazi, Farideh Bahrami","doi":"10.22038/ijbms.2025.82718.17878","DOIUrl":"https://doi.org/10.22038/ijbms.2025.82718.17878","url":null,"abstract":"<p><strong>Objectives: </strong>Sleep impacts the well-being and quality of life of millions. Given conventional pharmacotherapy's limitations and side effects, the quest for adequate and proper sleep promotion is imperative. This study aims to identify a suitable and effective compound for sleep by examining qualified herbal compounds in the PubChem database using <i>in silico</i> methods. Ultimately, the extracted compound (ginkgetin, a bioactive flavonoid from <i>Ginkgo biloba</i>) through molecular docking by considering the GABAA receptors will be evaluated through the <i>in vivo</i> method in an animal model to serve as proof for the findings from the molecular docking process.</p><p><strong>Materials and methods: </strong>Utilizing a comprehensive approach, this research employed molecular docking to screen 2299 phytochemicals for their affinity towards the GABAA receptor, focusing on the GABA, benzodiazepine, and steroid-binding sites. Ginkgetin emerged as a top candidate due to its high binding affinity. Subsequent <i>in vivo</i> electrophysiological assessments in rats treated with <i>G. biloba</i> extract containing ginkgetin evaluated alterations in sleep architecture, REM, and NREM sleep phases.</p><p><strong>Results: </strong>Molecular docking identified ginkgetin as possessing the highest binding affinity among the screened phytochemicals. <i>In vivo</i> studies corroborated these findings, demonstrating that rats treated with <i>Ginkgo biloba</i> extract significantly enhanced REM and NREM sleep compared to controls.</p><p><strong>Conclusion: </strong>Ginkgetin, derived from <i>G. biloba</i>, shows promising potential as a novel therapeutic agent for sleep disorders, supported by its strong affinity to key receptor sites and its efficacy in modulating sleep architecture <i>in vivo</i>. These findings contribute to the expanding evidence base for the therapeutic use of <i>G. biloba</i> in sleep promotion and underscore the need for further research to elucidate the mechanisms and clinical applicability of ginkgetin in sleep disorder treatment.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 6","pages":"746-754"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023825","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":"Can resisted swimming exercise substitute for the protective effects of estrogen on cardiometabolic risk factors in obese postmenopausal rat model?","authors":"Sara Shirazpour, Mohammad Khaksari, Abbas Ali Gaini, Hamideh Bashiri, Kayvan Khoramipour, Forouzan Rafie","doi":"10.22038/ijbms.2025.82005.17745","DOIUrl":"https://doi.org/10.22038/ijbms.2025.82005.17745","url":null,"abstract":"<p><strong>Objectives: </strong>Following our previous studies on the anti-obesity and cardioprotective effects of 17-beta estradiol (E2), this study was designed to determine the effects of Resisted swimming (RSW) training and E2 (alone and in combination) on cardiometabolic risk factors in an obese postmenopausal rat model.</p><p><strong>Materials and methods: </strong>Female ovariectomized rats (OVX) were given a standard diet (SD) or a 60% high-fat diet (HFD) for 16 weeks and were divided into two groups: SD and HFD. The rats were divided into ten groups to assess the effects of 8 weeks of E2 (1 mg/kg, IP) administration and RSW (5 days a week) on cardiometabolic risk factors. Parameters including body weight, BMI, visceral fat, blood glucose (BG), and cardiac oxidative stress were assessed 72 hr after the last swimming session.</p><p><strong>Results: </strong>HFD increased body weight, BMI, visceral fat, and BG levels in OVX rats. Additionally, it negatively affected the lipid profile and cardiac oxidative stress, but both E2 and RSW reduced these parameters in HFD-fed OVX rats. Although RSW and E2 equally prevented these changes, swimming was more effective than estrogen in increasing HDL levels in the SD group. The combination of E2 and RSW had a more significant effect on modulating glucose, TAC, TG, and HDL indices than the individual treatments.</p><p><strong>Conclusion: </strong>Overall, RSW ameliorates cardiometabolic risk factors in postmenopausal conditions caused by obesity, probably by modulating cardiac oxidative stress. It is also an effective non-pharmacological treatment for E2 substitution.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 6","pages":"718-727"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995788","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":"Ivermectin decreases inflammation and imiquimod-induced psoriasis-like skin lesions in rat via targeting TLR4/p65 NF-κB.","authors":"Tayebeh Noori, Antoni Sureda, Samira Shirooie","doi":"10.22038/ijbms.2025.83254.18008","DOIUrl":"https://doi.org/10.22038/ijbms.2025.83254.18008","url":null,"abstract":"<p><strong>Objectives: </strong>Psoriasis is a chronic skin disease that usually manifests as white and silver spots on the skin. Because of its anti-inflammatory properties, we investigated the effects of ivermectin (IVM) on imiquimod (IMQ)-induced psoriasis in rats.</p><p><strong>Materials and methods: </strong>Fifteen rats were assigned to 3 different groups (n=5 per group): the control group received normal water and food; the psoriasis group, in which psoriasis was induced by topical application of IMQ (1 mg per rat), and treatment group where rats were treated daily with topical IVM-gel (1%) from day 3 to 7. The Psoriasis Area Severity Index (PASI) Score for the entire treatment period was used to assess erythema, silver scale, and skin thickness on the dorsal region of rats, and the spleen-to-body weight index on day 7 was examined. Moreover, histological assessment of skin tissues was performed using fluorescence immunostaining and hematoxylin-eosin (H&E) staining.</p><p><strong>Results: </strong>The severity of lesions in the ivermectin group was reduced compared to the IMQ group, with a significant decrease in the average PASI scores. The results of fluorescence immunostaining showed that topical administration of IVM-gel reduced inflammation by decreasing Toll-like receptor 4 (TLR4) levels and p65 nuclear factor kappa-B (NF-κB). Furthermore, findings from H&E staining revealed that IVM-gel decreased dermal fibrosis, epidermal thickness, and infiltration of inflammatory cells caused by IMQ.</p><p><strong>Conclusion: </strong>Based on the obtained results, it can be concluded that IVM-gel can effectively reduce psoriasis lesions due to its therapeutic properties, such as anti-inflammatory effects via targeting TLR4/p65 NF-κB.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 6","pages":"808-814"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996262","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":"<i>In vitro</i> and <i>in vivo</i> evaluation of photo-induced antileishmanial activity of indocyanine green-loaded nanomicelles.","authors":"Shirin Jalili, Jafar Mosafer, Seyed Amin Mousavi Nezhad, Ameneh Sazgarnia, Mohammad Ali Mohaghegh, Mehdi Hoseini","doi":"10.22038/ijbms.2025.82333.17807","DOIUrl":"10.22038/ijbms.2025.82333.17807","url":null,"abstract":"<p><strong>Objectives: </strong>Due to its low toxicity and high absorbance in the range of 650 to 900 nm, indocyanine green (ICG) has garnered significant attention for its applications in photodynamic therapy (PDT) and photothermal therapy (PTT). However, its tendency to aggregate in aqueous environments limits its efficacy in both <i>in vitro</i> and <i>in vivo</i> applications. Encapsulating ICG in a biocompatible nanomicelle can improve its aqueous stability and photophysical properties. The present study investigated the synergistic effect of ICG-loaded nanomicelles upon irradiation by an 808-nm laser on <i>Leishmania major</i> (<i>L. major</i>) parasites.</p><p><strong>Materials and methods: </strong>Initially, a nanomicelle comprised ICG was synthesized and characterized. Then, the temperature increase during irradiation and promastigote viability were evaluated <i>in vitro</i>. Subsequently, the prepared samples' <i>in vitro</i> dark toxicity and phototoxicity were assessed via the MTS assay. Finally, the <i>in vivo</i> antileishmanial efficacy of the ICG-loaded nanomicelles formulation was investigated in BALB/c mice.</p><p><strong>Results: </strong>The absorbance of ICG-loaded nanomicelles at 808 nm was more than 2 times greater than Free-ICG. Also, the prepared formulation exhibited a mean diameter of ~25 nm and a zeta potential of -2.3 ± 1 mV. The combination of ICG-loaded nanomicelles and 808 nm laser with a power density of 2.5 W cm^-2 led to a significant reduction in the survival rate of promastigotes and lesion size of infected mice compared to control groups.</p><p><strong>Conclusion: </strong>The PDT/PTT mediated by ICG-loaded nanomicelles can be considered a promising and efficient therapeutic method for <i>L. major</i>, as it is inexpensive, safe, and easy to implement.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"498-505"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448797","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":"Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathway.","authors":"Huan-Qi Zhang, Dao-Ming Zhang, Zhi-Zhen Huang, Jing Cheng, Chong Zhang, Neng-Ming Lin, Yangling Li","doi":"10.22038/ijbms.2025.82513.17836","DOIUrl":"10.22038/ijbms.2025.82513.17836","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) presents a significant challenge in oncology due to its highly aggressive nature and inherent resistance to conventional therapeutic interventions. Vortioxetine, a novel antidepressant, exhibits anticancer abilities and can traverse the blood-brain barrier. In this study, the antitumor effect and mechanism of vortioxetine on GBM cells were investigated. Cell proliferation in GBM cells was assessed using the CCK8 and colony formation assays. Flow cytometry, western blot, and wound healing assay were used to study the mechanisms of vortioxetine. mCherry-GFP-LC3B and confocal microscopy were used to evaluate autophagic activity. RNA sequencing uses the capabilities of high-throughput sequencing methods to provide insight into the transcriptome of cells. Vortioxetine significantly inhibited the proliferation of GBM cells by inducing G1/G0 phase cell cycle arrest. Meanwhile, it also reduced the migratory capabilities of GBM cells. Furthermore, it promoted apoptotic cell death in GBM cells. In addition, it promoted autophagy in GBM cells, and autophagy inhibitors markedly enhanced its antiproliferative activities. Vortioxetine could down-regulate the expressions of PI3K and Akt, which were related to the occurrence and development of GBM. Our findings support the potential of vortioxetine as a novel therapeutic agent for GBM treatment. Vortioxetine exhibits anti-GBM activity via the PI3K-Akt signaling pathway. Meanwhile, our findings reveal autophagy inhibitors as an effective sensitizer for vortioxetine, offering new strategies for treating GBM.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 4","pages":"401-408"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449049","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":"COTI-2 suppresses the malignancy of bladder cancer by inducing apoptosis via the AMPK-mTOR signaling pathway.","authors":"Yuancai Zheng, Keqi Wang, Chenyu Wu, Yuying Qin, Yihan Sun, Xinyu Lu, Yupeng Xu, Gonghui Li","doi":"10.22038/ijbms.2024.80284.17378","DOIUrl":"10.22038/ijbms.2024.80284.17378","url":null,"abstract":"<p><strong>Objectives: </strong>COTI-2, an innovative oral homocysteine, has shown promising antitumor results on multiple types of cancer. However, its effects in treating bladder cancer (BCa) and the underlying molecular mechanisms have not been elucidated. The present study aimed to explore the antitumor effects of COTI-2 on BCa and the potential mechanisms.</p><p><strong>Materials and methods: </strong>BCa cell lines, including the 5637 and T24 cell lines, were treated with COTI-2 at concentrations of 0.5 and 1 μM, respectively. Cell Counting Kit (CCK)-8 assay, colony formation assay, apoptosis assay, and transwell migration and invasion assay were conducted to evaluate the antitumor effects of COTI-2 on BCa cells. Western blotting, H&E, immunohistochemical staining, and immunofluorescence analysis were performed to investigate the underlying mechanisms. Moreover, a xenograft model in nude mice using T24 cells was generated to determine the antitumor activities of COTI-2 <i>in vivo</i>.</p><p><strong>Results: </strong>COTI-2 highly inhibited the proliferation of BCa cell lines, including 5637 and T24 cells, and induced their apoptosis. Moreover, it efficiently suppressed the migration and invasion of BCa cells. Additionally, the subcutaneous xenograft model in nude mice showed that COTI-2 treatment inhibited the tumor growth of BCa by inducing its apoptosis in vivo. We also found that COTI-2 promoted apoptosis in BCa cells, presumably through activating the AMPK/mTOR pathway.</p><p><strong>Conclusion: </strong>Our data suggest that COTI-2 effectively reduces the malignancy of BCa, probably by inducing apoptosis via the AMPK/mTOR signaling pathway. These data highlight the potential of COTI-2 as a therapeutic agent for the treatment of BCa.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 3","pages":"240-246"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188764","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 exerts protective effects against valproic acid-induced testicular damage through modulating the JAK1/STAT-3/IL-6 signaling pathway in rats.","authors":"Eda Dokumacioglu, Hatice Iskender, Kubra Asena Terim Kapakin, İSmail Bolat, Behzat Mokhtare, Ali Dogan Omur, Armagan Hayirli","doi":"10.22038/ijbms.2024.76948.16659","DOIUrl":"10.22038/ijbms.2024.76948.16659","url":null,"abstract":"<p><strong>Objectives: </strong>This experiment was carried out to investigate the protective effects of curcumin (CUR) on testicular damage induced by the valproic acid (VPA) administration.</p><p><strong>Materials and methods: </strong>Male Wistar-Albino rats (n=28, 250-300 g) were randomly divided into four groups: Control (1 ml saline, oral), VPA (500 mg/kg, IP), CUR (200 mg/kg, oral), or VPA+CUR (500 mg/kg, VPA, IP plus 200 mg/kg CUR, oral). The treatments were applied for 14 days. Serum testosterone and testis [Janus kinases1 (JAK1), signal transducers and activators of transcription-3 (STAT-3), interleukin-6 (IL-6), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-18 (IL-18), and nuclear factor (NF)-κB)] samples were collected for biochemical analyses. Semen samples were subjected to microscopy for spermatological parameters. Testis tissue was also analyzed for histopathological and immunohistochemical methods.</p><p><strong>Results: </strong>The VPA administration caused a 37% decrease in serum testosterone concentration and 5.32, 9.51, 2.44, and 3.68-fold increases in testicular tissue JAK1, STAT-3, IL-6, and MDA levels, respectively. There were also 50, 52, and 72% reductions in sperm motility, sperm viability, and the mean testicular biopsy score, respectively, accompanied by considerable degenerative changes and necrosis in seminiferous tubules in the VPA group. There is also an immune-positive reaction for IL-18 and NF-κB in only Leydig cells.</p><p><strong>Conclusion: </strong>The CUR treatment may be beneficial in restoring testicular damage through antiinflammatory and anti-oxidant potential.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":"28 2","pages":"230-236"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028801","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 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}