Tissue & cell最新文献

{"title":"Altered lung inflammation and expression of endoplasmic reticulum stress markers in male mice aged-asthma model.","authors":"Farshad Armin, Hamdollah Panahpour, Ramin Salimnejad, Hakimeh Saadati, Ali Abedi, Mohammad Reza Aslani","doi":"10.1016/j.tice.2025.102938","DOIUrl":"https://doi.org/10.1016/j.tice.2025.102938","url":null,"abstract":"<p><p>Although there is a strong correlation between aging and asthma pathophysiology, the underlying mechanism has not been fully elucidated. The endoplasmic reticulum (ER) has been demonstrated to be a crucial intracellular organelle involved in the pathogenesis of numerous diseases. The aim of the current study was to investigate ER stress markers in the lung tissue of aged ovalbumin (OVA)-sensitized mice. Male BALB/C mice were randomly divided into the following four groups (10 in each): 1) control, 2) OVA-sensitized (OVA), 3) D-galactose-induced aging (D-gal), and 4) OVA-sensitized associated with D-galactose-induced aging (OVA+D-gal). Total WBCs and differential cells were counted using the bronchoalveolar lavage (BAL) fluid. Lung tissue was analyzed for ER stress markers (ATF4, ATF6, GRP78, CHOP, and XBP1) through Real Time-PCR technique as well as histopathological assessment. The data indicated a significant increase in both total WBCs and differential cells within the OVA, D-gal, and OVA+D-gal groups when compared to the control group, particularly evident in the OVA+D-gal group. Also, the results showed that the increased expression of ER stress markers (ATF4, ATF6, GRP78, CHOP, and XBP1) was significantly higher in the OVA, D-gal, and OVA+D-gal groups than in the control group. Interestingly, the increased expression of CHOP, ATF4, and XBP1 was observed in the OVA+D-gal group more than in other groups. In aged OVA-sensitized mice, the findings revealed a maladaptive ER stress response in their lung tissue, characterized by elevated levels of CHOP, ATF4, and XBP1 expression.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"102938"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050074","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 ameliorates cardiac injury induced by nandrolone decanoate through downregulation of osteopontin and mTOR expressions.","authors":"Mohamed Aref, Wesam Mr Ashour, Nanees F El-Malkey, Haifa A Alqahtani, Mohamed A Nassan, Noha Ali Abd-Almotaleb, Gamal A Salem","doi":"10.1016/j.tice.2025.102932","DOIUrl":"https://doi.org/10.1016/j.tice.2025.102932","url":null,"abstract":"<p><p>Nandrolone-decanoate (NA), a synthetic anabolic steroid, negatively impacts cardiac function. While exercise is known to benefit cardiovascular health, its effects on individuals misusing anabolic steroids require further study. Osteopontin (OPN) and mammalian target of rapamycin (m-TOR) are crucial in inflammation-related cardiovascular diseases and can be influenced by exercise, though results are inconclusive. This study aims to examine how exercise affects NA's cardiac adverse effects and the potential role of OPN and m-TOR. The study involved 52 male rats divided into four groups: control, exercise-only, NA-treated (15 mg/kg/day S.C for 8 W), and combined exercise and NA treatment. Researchers measured blood pressure, heart rate (HR), serum cardiac enzymes, CRP, IL-1B, IL-6, Brain Natriuretic Peptide (BNP) and conducted macro and micromorphological assessments. Additionally, immunohistochemical analysis of cardiac OPN and mTOR was performed. The NA-treated group showed significant increases in blood pressure, HR, weight, and cardiac enzymes compared to the control group. Exercise significantly improved these parameters in the combined exercise and NA treatment group, except for blood pressure. All groups exhibited an increase in cardiac weight relative to the control. The NA-treated group displayed marked hyaline degeneration and necrosis in cardiac tissues, with increased cell diameter and excess collagen deposition, which was less severe in the combined exercise (EX) and NA treatment group. NA treatment significantly elevated inflammatory mediators and the area percentage of OPN and m-TOR expression. These markers were significantly reduced in the combined exercise and NA treatment group. BNP was remarkably raised in EX+NA group compared to all other groups. Exercise mitigated NA-induced cardiac damage by reducing inflammation, possibly through the downregulation of cardiac OPN and m-TOR expression.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"102932"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033183","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":"Impacts of type 1 diabetes mellitus on male fertility and embryo quality in superovulated mice.","authors":"Begum Alyürük, Yusufhan Yazir, Zeynep Ece Utkan Korun, Özcan Budak, Ender Yalçinkaya Kalyan, Kamil Can Kiliç","doi":"10.1016/j.tice.2025.102941","DOIUrl":"https://doi.org/10.1016/j.tice.2025.102941","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to compare embryo quality, sperm morphology, motility, and fertilization obtained from male mice with type 1 diabetes mellitus (T1DM) induced by streptozotocin (STZ) in control and diabetic mice undergoing in vitro fertilization (IVF).</p><p><strong>Methods: </strong>CD-1 male mice were divided into control and DM groups, with an i.p. injection of 100 mg/kg STZ to induce T1DM. One month later, the mice were euthanized to investigate the effects of STZ-induced T1DM on the reproductive system. Sperms were obtained from the epididymis and vas deferens. The morphology and motility of the cells were evaluated. Follicle development was stimulated by controlled ovarian stimulation, and oocytes were collected by extracting oviducts and ovaries from female mice housed under controlled environmental conditions with ad libitum access. Both groups underwent IVF with fertilized zygotes followed up until the third day before embryo quality was compared.</p><p><strong>Results: </strong>Female mice bred with diabetic males exhibited significantly lower fertilization rates than the controls (p < 0.05). Sperm from diabetic mice displayed abnormalities in shape and movement, with reduced motility and fertilization. Embryos from male diabetic mice exhibited a higher incidence of developmental arrest during early embryogenesis. Although no significant differences in oocyte quality were observed, embryos from diabetic mice exhibited higher growth rates. These findings highlighted the T1DM's detrimental effects on sperm morphology, motility, fertilization, and early embryonic development, thus contributing to our understanding of reproductive complications.</p><p><strong>Conclusion: </strong>In conclusion, our findings demonstrated that T1DM significantly impaired sperm morphology, motility, and fertilization capacity, leading to reduced embryo quality and increased developmental arrest. These results highlight the detrimental impact of DM on male reproductive potential and underscore the importance of glycemic control in optimizing outcomes in assisted reproductive techniques such as IVF.</p>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"95 ","pages":"102941"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033184","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":"The modulation of SHED-induced macrophage polarization and plasticity through paracrine mediators","authors":"Azadeh Mohammad-Hasani ,&nbsp;Saeed Mohammadi ,&nbsp;Mohsen Saeidi ,&nbsp;Ali Fallah ,&nbsp;Ayyoob Khosravi","doi":"10.1016/j.tice.2025.103038","DOIUrl":"10.1016/j.tice.2025.103038","url":null,"abstract":"<div><div>Although the effect of stem cells from human exfoliated deciduous teeth (SHED) on macrophage polarization and plasticity has been studied in recent years, its mechanism needs to be elucidated. Here, we aimed to investigate how SHED-MSCs cross-talk with THP-1 cell-derived macrophages in a co-culture system. SHED- MSCs were indirectly co-cultured with polarized M0 and M1 macrophages using the six-well transwell culture system, and their effects on macrophage plasticity, surface molecule expression, cytokine secretion, oxidative stress indexes, and gene expression were evaluated. Using flow cytometry, we confirmed macrophage polarization and observed a significant shift toward the M2 phenotype (CD206) following co-culture with SHED-MSCs. Cytokine analysis revealed increased levels of anti-inflammatory factors (TGFB2, IL-10) and reduced pro-inflammatory cytokines (TNF-α, IL-12). Importantly, SHED-MSCs modulated the oxidative state of macrophages, significantly reducing Nitric oxide (NO) and Malondialdehyde (MDA) levels while enhancing antioxidant markers including Total antioxidant capacity (TAC), Superoxide dismutase (SOD), and Catalase (CAT). Gene expression analysis further supported this regulatory effect, with upregulation of <em>ARG1</em> (<em>Arginase 1</em> gene) and downregulation of <em>IL-6R</em> (<em>Interleukin 6 receptor</em> gene) in treated macrophages. our findings show that SHED-MSCs exert potent paracrine effects that not only reprogram inflammatory macrophages toward a reparative phenotype but also restore redox homeostasis. These results highlight the potential of SHED-MSCs as a therapeutic cell source for the treatment of inflammation- and oxidative stress–related diseases.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 103038"},"PeriodicalIF":2.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580245","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":"Pooled umbilical cord-derived MSCs retain key phenotypic and immunomodulatory properties – A path toward consistent manufacturing","authors":"Urban Švajger ,&nbsp;Kaja Zajc ,&nbsp;Ana Bajc Česnik ,&nbsp;Katrina Hartman","doi":"10.1016/j.tice.2025.103036","DOIUrl":"10.1016/j.tice.2025.103036","url":null,"abstract":"<div><div>Mesenchymal stromal stem cells (MSCs) represent a promising cell therapy tool, by merit of their regenerative and unique immunomodulatory properties. However, their clinical utility is often hindered by batch-to-batch variability, which is the result of several factors, particularly those of donor heterogeneity and differences in manufacturing. To address this issue, we developed a protocol for pooling umbilical cord-derived MSCs (UC-MSCs) from multiple donors that demonstrates comparable characteristics across pooled and single donor MSCs. We see this as a basis to generate a more homogenous and scalable cell products in the future, allowing for low passage manufacture, termed equipotent MSCs (EQ-MSCs). We characterized EQ-MSCs in comparison to UC-MSCs through extensive phenotypic analysis and by functional and immunological assessment. We demonstrate that EQ-MSCs retain the characteristic phenotypic features of single donor MSCs, with stable expression across multiple passages. Morphological evaluation of mixed donor cultures showed no significant alterations in cellular shape or growth patterns. The analysis of multilineage differentiation capacity demonstrated equivalent adipogenic, osteogenic, and chondrogenic potential, to single donor UC-MSCs. Strong colony forming ability of EQ-MSCs, indicative of preserved clonogenic potential, was also demonstrated. In terms of function, EQ-MSCs expressed key inhibitory molecules, including PD-L1, PD-L2, B7-H3, and adhesion molecule ICAM-1, with further upregulation upon IFN-γ priming, suggesting their capacity for enhanced immunomodulatory profile in response to an inflammatory environment. Functional co-culture assays with human PBMCs revealed a dose-dependent suppression of T cell proliferation, where EQ-MSCs showed comparable immunomodulatory activity to UC-MSCs. Our results support the pooling strategy of UC-MSCs as a viable strategy toward increasing product homogeneity, while at the same time maintaining key biological features.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 103036"},"PeriodicalIF":2.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144570605","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":"The small GTP-binding Ras-like protein DIRAS2 promotes cell proliferation in oral leukoplakia via the RAF/MEK/MAPK pathway","authors":"Jing Li ,&nbsp;Zitong Tian ,&nbsp;Wenjing Li ,&nbsp;Min Wang ,&nbsp;Xiaofei Tang ,&nbsp;Min Zhang","doi":"10.1016/j.tice.2025.103037","DOIUrl":"10.1016/j.tice.2025.103037","url":null,"abstract":"<div><h3>Background</h3><div>The small GTP-binding Ras-like protein DIRAS2 may function as tumor suppressors in some tumors. However, a precise relation of DIRAS2 to precancerous lesions and their progression into cancer remains uncharted. <em>Methods.</em> DIRAS2 expression was detected in human oral leukoplakia (OLK) tissues and normal epithelial tissues. Using the Crispr/Cas9 and Cre-LoxP technology, homozygous knockout DIRAS2^flox/flox mice were produced, and crossed to K14-Cre mice in which the Cre recombinase specifically expressed in the epithelium. Epithelium specific DIRAS2 conditional knockout mice were generated. 4NQO-induced mouse model of DIRAS2 conditional knockout mice and control mice was used to explore the impact of epithelium specific deletion of DIRAS2 on the progression of tongue precancerous lesions and underlining mechanism was investigated. <em>Results and Conclusion.</em> The expression of DIRAS2 was abnormally higher in human OLK tissues than that in normal mucosa tissues. DIRAS2 conditional knockout in epithelium could inhibit the progression of tongue precancerous lesions in mice induced by 4NQO within the period analyzed. Besides, cell proliferation was decreased and the MAPK signaling cascade proteins were down-regulated expressed in both DIRAS2 knockdown human dysplastic oral keratinocyte cells and the tongue precancerous tissues of DIRAS2 conditional-knockout mice compared with the control, respectively. In summary, DIRAS2 may promote cell proliferation of OLK via the RAF/MEK/MAPK pathway.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 103037"},"PeriodicalIF":2.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587534","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":"Inhibition of pyroptosis by belnacasan: A potential strategy for mitigating acute lung injury and multiple organ dysfunction","authors":"Arzu Güneş ,&nbsp;Duygu Gürsoy Gürgen ,&nbsp;Arife Ahsen Kaplan ,&nbsp;İlknur Keskin","doi":"10.1016/j.tice.2025.103034","DOIUrl":"10.1016/j.tice.2025.103034","url":null,"abstract":"<div><h3>Introduction</h3><div>Acute lung injury (ALI) caused by infections and trauma poses a significant public health concern. The activation of caspase-1 triggers the expression of interleukin-1 beta (IL-1β), leading to pyroptosis. Targeting pyroptosis may offer therapeutic benefits in ALI. This study evaluates the therapeutic potential of belnacasan (Bel), a caspase-1 inhibitor, in reducing pyroptosis and mitigating multi-organ failure in a murine ALI model induced by lipopolysaccharide (LPS).</div></div><div><h3>Methods</h3><div>Thirty BALB/c mice were divided into five groups (n = 6): control, LPS, LPS+Bel, Bel, and DMSO. The LPS group received 5 mg/kg LPS, while the LPS+Bel group was treated with 50 mg/kg belnacasan one hour post-LPS. Histopathological, immunohistochemical, and ultrastructural analyses were conducted on lung tissues. Organ damage was assessed through histopathological evaluation and biochemical markers, including ALT/AST for livers and BUN/creatinine for kidneys. Inflammation was evaluated through C-reactive protein (CRP) levels. IL-1β levels in bronchoalveolar lavage fluid (BALF) were measured using ELISA, and alveolar macrophages were analysed via confocal microscopy.</div></div><div><h3>Results</h3><div>The findings suggest that belnacasan treatment may reduce multiple organ dysfunction by inhibiting pyroptosis and preserving tissue morphology. The CRP, ALT, AST, BUN, and creatinine levels corroborate the histopathological results. Immunofluorescence and ELISA findings indicate that belnacasan treatment can inhibit IL-1β and reduce both pyroptotic and non-pyroptotic alveolar macrophages in BALF. Transmission electron microscopy (TEM) analyses revealed that belnacasan preserved the integrity of the blood-air barrier.</div></div><div><h3>Conclusions</h3><div>Belnacasan inhibits pyroptosis, reduces inflammation, and preserves organ morphology in ALI. These findings underscore its potential as a therapeutic agent for preventing multiple organ dysfunction in ALI.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 103034"},"PeriodicalIF":2.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580244","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":"Maintaining high levels of HIF-1α protects osteoarthritis cartilage by activating autophagy","authors":"Xiaolei Chen ,&nbsp;Gangning Feng ,&nbsp;Lufei Shao ,&nbsp;Xue Lin ,&nbsp;Xiaoxin He ,&nbsp;Yong Yang ,&nbsp;Xin Zhao ,&nbsp;Jiangbo Yan ,&nbsp;Long Ma ,&nbsp;Yong Zhou ,&nbsp;Kuanmin Tian ,&nbsp;Hui Wang ,&nbsp;Zhibin Lan ,&nbsp;Zhidong Lu ,&nbsp;Di Xue ,&nbsp;Qunhua Jin","doi":"10.1016/j.tice.2025.103027","DOIUrl":"10.1016/j.tice.2025.103027","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and subchondral bone remodeling, with hypoxia-inducible factor-1α (HIF-1α) playing a pivotal role in chondrocyte survival under hypoxic and inflammatory conditions. This study investigated the protective mechanisms of HIF-1α in OA by examining its effects on autophagy and oxidative stress in both human OA cartilage samples and murine models. Proteomic and immunohistochemical analyses revealed elevated HIF-1α expression alongside reduced autophagy markers Microtubule-Associated Protein 1 Light Chain 3(LC3) and increased cartilage damage indicators Matrix Metalloproteinase 13(MMP13), decreased Type 2 Collagen (COL2) in OA-affected tissues. In vitro experiments demonstrated that HIF-1α inhibition exacerbated oxidative stress Reactive Oxygen Species (ROS) and impaired autophagy, while HIF-1α activation (via DMOG) enhanced autophagy and reduced ROS, thereby preserving chondrocyte function. In vivo, DMOG treatment in a destabilized medial meniscus (DMM) mouse model attenuated cartilage degradation, suppressed MMP13, and restored COL2 expression. Furthermore, HIF-1α upregulation correlated with reduced β-catenin and HIF-2α levels, suggesting its role in mitigating subchondral bone sclerosis. These findings highlight that maintaining high HIF-1α levels protects OA cartilage by enhancing autophagy and inhibiting oxidative stress, offering a potential therapeutic strategy for OA management.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 103027"},"PeriodicalIF":2.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580243","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":"Human placental extract (HPE) counteracts diabetic brain neurodegeneration by targeting PI3K/mTOR/GSK3β signaling and modulates hippocampal apoptosis and regeneration","authors":"Shreen Matar ,&nbsp;Rehab A. Gomaa ,&nbsp;Amina Essawy ,&nbsp;Abeer El Wakil","doi":"10.1016/j.tice.2025.103033","DOIUrl":"10.1016/j.tice.2025.103033","url":null,"abstract":"<div><h3>Objective</h3><div>Diabetes mellitus (DM) is closely associated with neurodegeneration, predominantly through impaired insulin signaling and inflammation-driven neuronal cell death. This study aimed to evaluate the neuroprotective effects of human placental extract (HPE) on hippocampal integrity and neurogenesis in a streptozotocin (STZ)-induced diabetic rat model.</div></div><div><h3>Methods</h3><div>Male rats were randomly assigned into four groups: control, HPE, STZ, and STZ + HPE. Apoptosis was assessed via flow cytometry using Annexin V-FITC/PI staining, while ELISA measured hippocampal levels of PI3K, mTOR, and GSK3β. Histological and ultrastructural changes were analyzed using toluidine blue staining and transmission electron microscopy (TEM), and immunohistochemical markers GFAP, Ki67, and caspase-3 were used to evaluate astrocyte activation, cell proliferation, and neuronal apoptosis, respectively.</div></div><div><h3>Results</h3><div>STZ significantly increased early and late apoptotic cells (4.30 ± 0.15 % and 16.21 ± 0.08 %) and necrosis (3.28 ± 0.58 %) while reducing viable cells to 76.05 ± 0.84 %, compared to controls (93.16 ± 0.29 %). HPE treatment of diabetic rats significantly reversed these changes (<em>p</em> &lt; 0.001). Moreover, STZ downregulated PI3K (31.46 ± 2.25 pg/mg) and mTOR (1.59 ± 0.10 ng/mg), while upregulating GSK3β (3.65 ± 0.12 ng/mg). HPE treatment restored PI3K (41.28 ± 2.49 pg/mg), mTOR (2.24 ± 0.15 ng/mg), and reduced GSK3β (2.74 ± 0.28 ng/mg).</div><div>Histologically, STZ caused degeneration of pyramidal neurons, irregular nuclear membranes, and cytoplasmic vacuolation in the CA3 region, which were ameliorated by HPE. GFAP immunoreactivity, markedly declined in diabetic rats, was augmented following HPE treatment, indicating attenuation of reactive astrogliosis. Additionally, HPE restored Ki67-positive proliferative cells in the CA3 region, reversing the diabetes-induced decline in hippocampal neurogenesis. Caspase-3 immunostaining showed elevated apoptosis in STZ rats, which was significantly reduced by HPE, restoring levels comparable to those of controls and confirming its anti-apoptotic effect.</div></div><div><h3>Conclusions</h3><div>HPE significantly mitigates STZ-induced hippocampal damage by restoring insulin signaling (PI3K/mTOR/GSK3β pathway), suppressing apoptosis and inflammation, and promoting neurogenesis. The combined effects on both caspase-3-mediated apoptosis and Ki67-driven proliferation highlight HPE's dual role in neuroprotection and regeneration. These findings support the therapeutic potential of HPE in managing diabetes-associated neurodegenerative changes.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 103033"},"PeriodicalIF":2.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534225","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":"Mechanisms of Complanatoside A against extracellular matrix accumulation, inflammation and proliferation of mesangial cells in diabetic nephropathy through network pharmacology and experimental validation","authors":"Weiyu Han ,&nbsp;Zhewen Deng ,&nbsp;Jiaqi Li,&nbsp;Beiting Ma,&nbsp;Zhengxin Lu,&nbsp;Yimu Zhang,&nbsp;Chaoxing Ren,&nbsp;Bo Ma","doi":"10.1016/j.tice.2025.103031","DOIUrl":"10.1016/j.tice.2025.103031","url":null,"abstract":"<div><div>Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide, underscoring the urgent need to explore effective strategies for its prevention and control. Accumulating evidence indicates that inhibition of abnormal mesangial cells (MCs) proliferation, particularly during the early stages of DN, represents a critical therapeutic strategy for attenuating the progression of DN. Complanatoside A (CA), a major flavonoid derived from <em>Semen Astragali Complanati</em>, has demonstrated significant reno-protective properties. In this study, diabetic mouse models and high-glucose (HG)-induced mouse mesangial cell models were established to investigate the reno-protective mechanisms of CA. Furthermore, network pharmacology was employed to predict molecular targets and signaling pathways. Histopathological analysis revealed that CA alleviated key renal pathological changes, including glomerular interstitial fibrosis, thickening of the glomerular basement membrane, mesangial matrix expansion, glomerulosclerosis, and fibrillar collagen deposition. Furthermore, CA inhibited HG-induced mesangial extracellular matrix (ECM) accumulation, inflammatory responses, and cellular proliferation. Through network pharmacology, eight core genes (TNF-α, AKT1, HSP90AA1, MMP9, PPARG, SRC, PTGS2, and MMP2) were identified as critical targets of CA in DN and were primarily associated with inflammatory responses and ECM deposition. Molecular docking analysis confirmed that CA exhibited high binding affinity for these inflammation- and ECM-related genes. This study demonstrated that CA effectively mitigated renal injury in DN by suppressing inflammatory pathways and ECM deposition, thus providing novel insights into its therapeutic potential. These findings offer new perspectives for the development of traditional Chinese medicine-based interventions for the treatment of DN.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"96 ","pages":"Article 103031"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144557366","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}