Tissue & cell最新文献

{"title":"Rotenone-driven DNA hypermethylation of the miR-6991–3p promoter induces death of mouse brain organoids","authors":"Zeyu Cui ,&nbsp;Xin Liu ,&nbsp;Xijin Gao ,&nbsp;Zhihua Yu ,&nbsp;Weidong Pan ,&nbsp;Te Liu","doi":"10.1016/j.tice.2025.102831","DOIUrl":"10.1016/j.tice.2025.102831","url":null,"abstract":"<div><div>Rotenone has potential chemical toxicity in the nervous system of both insects and mammals, but its deep molecular biological mechanisms have not been clarified. Here, the epigenetic regulatory mechanism underlying the toxicity of rotenone was studied using murine brain organoids (mBOs). Transmission electron microscopy indicated that rotenone destroyed mBOs’mitochondrial structure. RRBS-Seq showed that some promoter regions from the DLK1-DIO3 imprinted microRNA clusters were hypomethylated. But, rotenone stimulated hypermethylation significantly on the promoter DNA of miR-6991–3p. MiR-6991–3p in the rotenone-treated mBOs had the greatest decreased miRNA expression compared with the control. Meanwhile, luciferase report assay indicated that miR-6991–3p induced a decrease in luciferase activity via binding to specific sites on the 3′UTR of DEDD2 gene. To overexpression of miR-6991–3p attenuated mBO proliferated inhibition and cell death, accumulation for lipid peroxidation products significantly by rotenone inducing. Subsequently, results of cell staining and molecular biology experiment revealed that overexpression for miR-6991–3p significantly weakened expression levels of death-related genes (DEDD2, caspase-8, caspase-3, and caspase-1), but significantly elevated expression levels of cell proliferation-related genes (Ki67 and BCL2) in rotenone treated mBOs group. Here, we reveal a novel epigenetic mechanism of rotenone-induced neuronal death, in which rotenone induced promoter DNA hypermethylation of miR-6991–3p in the <em>DLK1</em>-<em>DIO3</em> imprinted cluster. This caused miR-6991–3p transcriptional activity to be downregulated, which subsequently significantly increased the expression of its target gene, <em>DEDD2</em>, ultimately leading to neural organoid cell death.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"Article 102831"},"PeriodicalIF":2.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of mesenchymal stem cells on repair of injured endometrium in mice","authors":"Yang Wang ,&nbsp;Yuanxi Zhao ,&nbsp;Yuanke Liu ,&nbsp;Jingjing Wang ,&nbsp;Fang Liu","doi":"10.1016/j.tice.2025.102827","DOIUrl":"10.1016/j.tice.2025.102827","url":null,"abstract":"<div><div>Endometrial damage severely affects women's reproductive health and function. Although various treatments are available, their efficacy remains generally unsatisfactory. Mesenchymal stem cells (MSCs) possess multidirectional differentiation abilities and immunoregulation. To evaluate whether direct MSC transplantation into the uterine cavity enhances endometrial thickness, an animal model with thin endometrium was developed by administering ethanol into the uterine cavity. Our study aimed to observe and compare repair effects about three types of MSCs on endometrial injury, including menstrual blood-derived MSCs (MenSCs), bone marrow MSCs (BMSCs), and umbilical cord-derived mesenchymal stem cells (UC-MSCs). HE and Masson staining were used to assess endometrial morphology and fibrosis in the third estrous period post-operation. Immunohistochemistry and western blot were utilized to detect the expression of marker proteins in endometrial tissue. Endometrial thickness and protein expression in the MSC transplantation groups showed a notable improvement compared to the control group, though still below normal levels. Among MSC transplantation groups, no statistical difference was observed between MenSC and BMSC groups in endometrial thickness or ItgαVβ3 expression, but MenSCs showed higher levels than UC-MSCs, with statistical significance. CK18 and Vimentin expression in the MenSC and BMSC groups were similarly higher than UC-MSCs, with no significant difference. VEGF expression indicated that MenSCs outperformed both BMSCs and UC-MSCs. In conclusion, all three types of MSCs improved endometrial thickness and regeneration when transplanted into the injured endometrium. MenSCs demonstrated the greatest potential in promoting endometrial regeneration and improving receptivity, suggesting a promising new approach for treating endometrial injury.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"Article 102827"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gegen Qinlian Decoction improves Alzheimer’s disease through TLR4/NF-κB/NLRP3 pathway","authors":"Bin Zhang,&nbsp;Liudan Chen,&nbsp;Mengru Kang,&nbsp;Liang Ai,&nbsp;Yangu Tao","doi":"10.1016/j.tice.2025.102818","DOIUrl":"10.1016/j.tice.2025.102818","url":null,"abstract":"<div><h3>Objective</h3><div>Alzheimer’s disease (AD) is a neurodegenerative disease that leads to dementia, but effective treatments are lacking. This study aims to evaluate the therapeutic effects of Gegen Qinlian Decoction (GGQLD) on AD and investigate the underlying mechanisms.</div></div><div><h3>Methods</h3><div>Using network pharmacology and bioinformatics, we identified 376 active ingredients of GGQLD and 427 drug targets. Among these, 7 potential targets (CASP1, MKI67, NFKB1, TLR4, NLRP3, IL1B, and AKT1) were identified as intersecting targets of both GGQLD and AD. Functional enrichment analysis revealed that GGQLD regulates pyroptosis-related pathways. In vivo, GGQLD was administered to AD rat models to assess its effects on spatial learning, memory, and brain tissue injury.</div></div><div><h3>Results</h3><div>GGQLD significantly reduced latency time by 40 % and increased platform crossings by 60 % in AD rats, demonstrating improved spatial learning and memory abilities. It also reduced hippocampal tissue damage and abnormal Aβ deposition. Mechanistically, GGQLD downregulated pyroptosis-related targets (TLR4, NF-κB, NLRP3, IL-1β, and Caspase-1), which were significantly upregulated in AD. ROC analysis demonstrated strong diagnostic significance for these genes, with AUC values exceeding 0.70. Functional enrichment and KEGG analysis further indicated that GGQLD exerts its therapeutic effects through multiple pathways, particularly the NOD-like receptor pathway, Necroptosis, and NF-kappa B pathway.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that GGQLD improves spatial learning, reduces brain tissue damage, and alleviates inflammation in AD through the regulation of pyroptosis-related pathways, providing evidence for its potential as a therapeutic agent for AD.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"Article 102818"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nintedanib abrogates patient vitreous-induced Akt activation and tube formation of human retinal microvascular endothelial cells","authors":"Qiang Li ,&nbsp;Xiaoping Zhou ,&nbsp;Yanhui Yang ,&nbsp;Qing Zhang ,&nbsp;Zhiyuan Li ,&nbsp;Haote Han ,&nbsp;Fang Yuan ,&nbsp;Hongwei Deng ,&nbsp;Hetian Lei ,&nbsp;Yajian Duan","doi":"10.1016/j.tice.2025.102817","DOIUrl":"10.1016/j.tice.2025.102817","url":null,"abstract":"<div><div>Growth factors and cytokines in the vitreous are critical drivers of proliferative diabetic retinopathy (PDR), a condition in which many patients exhibit resistance to current therapies. PDR is characterized by the formation of fibrovascular membranes on the vitreous side of the retina, which, if untreated, can lead to retinal detachment. Nintedanib, a clinically approved drug for idiopathic pulmonary fibrosis, targets multiple tyrosine kinases, including vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), and fibroblast growth factor receptors (FGFRs). In this study, we demonstrate that nintedanib effectively inhibits PDR vitreous-induced signaling molecules—namely, phosphorylation of VEGFR2, Akt, and Erk1/2—as well as cellular responses, including proliferation, migration, and tube formation in primary human retinal microvascular endothelial cells, at a non-toxic concentration of 1 μM. These findings suggest that nintedanib holds potential as a novel therapeutic option for the treatment of PDR.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102817"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melamine-induced adrenal structural and functional alterations and the contribution of morin to the adrenal repair in Wistar rats","authors":"Alshaymaa M. Abdelmenem ,&nbsp;Ezat A. Mersal ,&nbsp;Ahmed A. Morsi ,&nbsp;Marwa Omar Abdel All ,&nbsp;Ghaiath Hussein ,&nbsp;Khalid Elfaki Ibrahim ,&nbsp;Mohamed S. Salim","doi":"10.1016/j.tice.2025.102826","DOIUrl":"10.1016/j.tice.2025.102826","url":null,"abstract":"<div><div>Melamine is a prevalent environmental toxicant associated with well-established toxicity on several organs. The adrenal gland is a highly dynamic organ that makes it susceptible to chemicals’ toxicity. The current work investigated the adrenal histo-biochemical alterations caused by melamine exposure in rats and explored whether morin has protective potential against such adrenal toxicity. The experiment utilized 32 adult male Wistar rats randomly divided into control, morin, melamine, and melamine/morin groups. Adrenal toxicity was induced by melamine (126 mg/kg/d). Morin was used in a dose of 50 mg/kg/d. All treatments were given via oral gavage for 4 weeks. The adrenal oxidative stress markers, serum corticosterone (CORT), adrenocorticotrophic hormone (ACTH), and the mRNA expression of the steroidogenic genes; StAR (Steroidogenic acute regulatory protein), P450scc (Cholesterol side-chain cleavage enzyme), and11β-HSD1 (11β-Hydroxysteroid dehydrogenase type 1) were evaluated. Also, histological and immunohistochemical examinations of the paraffin-processed adrenal sections were performed. Melamine decreased adrenal tissue superoxide dismutase (SOD) and catalase (CAT) activities, increased adrenal malondialdehyde (MDA) levels, decreased serum CORT and increased ACTH levels, and suppressed the adrenal cortical expression of genes involved in steroidogenesis. Moreover, the inducible nitric oxide synthase (iNOS) and cysteine-aspartic acid protease-3 (caspase-3) expression were upregulated as indicated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Besides, melamine caused remarkable adrenal histopathological changes. However, morin administration greatly repaired the adrenal injury and restored the adrenal function. Morin maintained the adrenal histoarchitecture and protected against melamine-provoked adrenal toxicity by downregulating the inflammation and the adrenal apoptotic processes and relieving the oxidative stress burden.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"Article 102826"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of granulocyte colony-stimulating factor against tramadol-induced cerebellar neurotoxicity","authors":"Ghalia Mahfouz Attia ,&nbsp;Lashin S. Ali ,&nbsp;Mamdouh Eldesoqui ,&nbsp;Wael M. Elsaed ,&nbsp;Sally Abdallah Mostafa ,&nbsp;Emad A. Albadawi ,&nbsp;Rasha Ahmed Elmansy ,&nbsp;Yasir Hassan Elhassan ,&nbsp;Mohamed Berika ,&nbsp;Abdelnaser A. Badawy ,&nbsp;Mohammad El-Nabalaway ,&nbsp;Amal Fahmy Dawood ,&nbsp;Hanan Said Seleem","doi":"10.1016/j.tice.2025.102832","DOIUrl":"10.1016/j.tice.2025.102832","url":null,"abstract":"<div><h3>Background</h3><div>Tramadol (TRM) is a centrally acting synthetic opioid and serotonin/norepinephrine reuptake inhibitor. Despite being a potent painkiller, long-term use can induce permanent neurotoxicity. Granulocyte colony-stimulating factor (G-CSF) is a cytokine that helps to mobilize stem cells and facilitate their integration over injured neurons.</div></div><div><h3>Aim</h3><div>This work aims to study the histopathological, biochemical, and molecular alterations in the cerebellar cortex induced by TRM in comparison to the postulated protective effect of G-CSF versus TRM withdrawal.</div></div><div><h3>Methods</h3><div>32 adult male albino rats were equally divided into four groups: control, TRM, TRM+G-CSF-treated, and TRM withdrawal groups. The TRM group received a daily dose of 80 mg/kg body weight orally via gastric tube for 12 weeks. The TRM+G-CSF-treated group received subcutaneous injections of 100 μg/kg body weight of G-CSF for seven consecutive days, then TRM from the 8th day. The TRM withdrawal group received TRM for 12 weeks; then, the rats were left without TRM administration for a further 12 weeks. The structural, biochemical, and molecular changes of the cerebellum were measured.</div></div><div><h3>Results</h3><div>The study revealed that TRM not only induced cerebellar atrophy but also triggered microgliosis, neuroinflammation, and apoptotic indicators, all while suppressing autophagy. However, G-CSF and TRM withdrawal reversed these alterations with superiority to G-CSF.</div></div><div><h3>Conclusion</h3><div>The current investigation shows that G-CSF may improve behavioral, neurochemical, immunohistochemical, and molecular metrics in the rat cerebellum after tramadol-induced injury. G-CSF exhibits a superior protective effect compared to tramadol withdrawal. This is achieved through its antioxidant, anti-apoptotic, and autophagic enhancement properties, as well as its ability to reduce cerebellar gliosis.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102832"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular morphometry of the neoplastic microenvironment and its association with the immunoexpression of interleukin-4","authors":"Caio Rodrigues Maia ,&nbsp;Maria Sara Maia de Queiroz ,&nbsp;Carlos Augusto Galvão Barboza ,&nbsp;Sérgio Adriane Bezerra de Moura ,&nbsp;Keila Martha Amorim Barroso ,&nbsp;Pedro Paulo de Andrade Santos","doi":"10.1016/j.tice.2025.102816","DOIUrl":"10.1016/j.tice.2025.102816","url":null,"abstract":"<div><div>The objective of this research is to perform a cellular morphometric analysis, identify nuclear malignant keratinocyte irregularities, compare the immunoexpression of interleukin-4 (IL-4) and investigate neoplastic invasion depth in Lower Lip Squamous Cell Carcinoma (LLSCC) and Oral Tongue Squamous Cell Carcinoma (OTSCC) cases. A total of 60 cases were analyzed (30 on the lower lip and 30 on the oral tongue). Concerning the cellular morphometry analysis, 16 malignant keratinocytes from each case were analyzed. IL-4 immunoexpression was analyzed in the parenchyma and stroma of the investigated lesions, in both deep and superficial fields, employing an image analysis software. ANOVA and Spearman’s correlation statistical tests were applied. Total IL-4 immunoexpression was higher in LLSCC cases in all analyzed fields (<em>p</em>: 0.007); Positive correlation between the cellular perimeter of malignant keratinocytes in the superficial fields and lesion invasion depth was observed (<em>p</em>: 0.009), as well as between the total cellular area and neoplastic invasion depth (<em>p</em>: 0.038). A negative correlation, on the other hand, was observed between superficial lesion parenchyma IL-4 immunoexpression and nuclear perimeter in superficial fields (<em>p</em>: 0.007), as well as between total deep stroma IL-4 immunoexpression and neoplastic invasion depth (<em>p</em>: 0.008). These findings suggest that SCC displaying greater neoplastic invasion depth exhibit greater nuclear and cellular morphology alterations, albeit reducing IL-4 expression, potentially due to loss of the differentiated cell phenotype.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"Article 102816"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NEK kinases in cell cycle regulation, DNA damage response, and cancer progression","authors":"Joy T. Folahan,&nbsp;Nektarios Barabutis","doi":"10.1016/j.tice.2025.102811","DOIUrl":"10.1016/j.tice.2025.102811","url":null,"abstract":"<div><div>The NIMA-related kinase (NEK) family of serine/threonine kinases is essential for the regulation of cell cycle progression, mitotic spindle assembly, and genomic stability. In this review, we explore the structural and functional diversity of NEK kinases, highlighting their roles in both canonical and non-canonical cellular processes. We examine recent preclinical findings on NEK inhibition, showcasing promising results for NEK-targeted therapies, particularly in cancer types characterized by high NEK expression. We discussed the therapeutic potential of targeting NEKs as modulators of cell cycle and DDR pathways, with a focus on identifying strategies to exploit NEK activity for enhanced treatment efficacy. Future research directions are proposed to further elucidate NEK-mediated mechanisms and to develop selective inhibitors that target NEK-related pathways.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"94 ","pages":"Article 102811"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrodin promotes ferroptosis in CRC cells by inhibiting SKP2 to reduce NCOA4 ubiquitination","authors":"Qiao Zhang ,&nbsp;Zhijie Xu ,&nbsp;Wanying Liu ,&nbsp;Zhidong Cheng ,&nbsp;Yating Ding ,&nbsp;Yafeng Xie ,&nbsp;Shengyu Yan","doi":"10.1016/j.tice.2025.102793","DOIUrl":"10.1016/j.tice.2025.102793","url":null,"abstract":"<div><h3>Background</h3><div>Gastrodin, an important component of traditional Chinese medicine, is gaining interest because of its anti-tumor effects. Ferroptosis is a new mode of cell death, which has emerged as a promising target for colorectal cancer (CRC) treatment. This research investigates the action mechanism of gastrodin on the process of CRC by inducing ferroptosis.</div></div><div><h3>Methods</h3><div>The mRNA and protein levels were measured via qRT-PCR and western blot. Cell viability was assessed by CCK-8 assay. The cell proliferation was examined using colony formation assay. Live-Dead cell staining was evaluated by Calcein-AM/PI staining. The effect of ferroptosis was evaluated by detecting the levels of reactive oxygen species (ROS), intracellular total iron, ferrous iron (Fe^2 +), malondialdehyde (MDA), glutathione (GSH) by kits, as well as the expressions of subunit solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), ferritin light chain (FTL) and acyl-CoA synthetase long chain family member 4 (ACSL4) by western blot. Co-immunoprecipitation (Co-IP) assay was applied to analyze the binding relationship between S-phase kinase-associated protein 2 (SKP2) and nuclear receptor coactivator 4 (NCOA4).</div></div><div><h3>Results</h3><div>Gastrodin could induce ferroptosis in CRC cells. SKP2 ameliorated gastrodin induced ferroptosis in CRC cells. Besides, SKP2 mediated NCOA4 degradation by ubiquitination. SKP2 was involved in ferroptosis of CRC cells by regulating NCOA4. Gastrodin induced ferroptosis in CRC cells via SKP2/NCOA4 axis.</div></div><div><h3>Conclusion</h3><div>Gastrodin repressed SKP2 expression, deactivated NCOA4 ubiquitination thus elevated NCOA4 expression, and promoted ferroptosis in CRC cells.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"Article 102793"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise induced irisin mitigates hepatitis in anabolic-androgenic steroids treated rats via modulation of PGC-1-α/PPARγ/Nrf2 and NRF2/NF-κB/TLR4 signaling","authors":"Gamal A. Salem ,&nbsp;Mohamed Aref ,&nbsp;Nanees F. El-Malkey ,&nbsp;Haifa A. Alqahtani ,&nbsp;Noha ali abd-almotaleb ,&nbsp;Mohamed A. Nassan ,&nbsp;Hadeel Elsherbiny","doi":"10.1016/j.tice.2025.102829","DOIUrl":"10.1016/j.tice.2025.102829","url":null,"abstract":"<div><div>Irisin, a myokine released during exercise, has been shown to exert protective effects against metabolic and inflammatory disorders. Its role in mitigating hepatic damage induced by anabolic-androgenic steroids (AAS) remains largely unexplored. This study was conducted to examine the effects of exercise on irisin level and its capability to prevent hepatotoxicity caused by anabolic androgenic steroids (AAS) in rat model. The fifty-two male rats were divided into four groups: control, AAS treated (15 mg/kg/day S.C/8 W), exercised, and exercised- AAS treated. The following procedures were carried out: liver function tests, serum irisin, tissue inflammatory and oxidative stress markers, macro and micromorphological evaluation, and the examination of nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor-gamma (PPARγ) and its coactivator-1α (PGC1α) by immunohistochemistry. The liver tissue's expression of nuclear factor kappa B (NF-κB), Toll-like receptor-4 (TLR4), and Nrf2 mRNA was also assessed. After administering AAS to animals, aerobic exercise was found to significantly improve liver function tests, inflammation, and oxidative stress, reduce liver weight, improve morphological and histological changes, and improve the hepatic injury score. Furthermore, there was a notable rise in serum irisin, hepatic PPARγ, PGC1α, and Nrf2 immune-expressions and Nrf2 mRNA expression, while NF-κB and TLR4 mRNA expressions were significantly decreased. In conclusion, the irisin/PGC1α/PPARγ/Nrf2 and Nrf2/NF-κB/TLR4 signaling pathways may be modulated by aerobic exercise, which also reduces the liver's oxidative stress and inflammatory reactions to AAS treatment.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"Article 102829"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}