Journal of Molecular Histology最新文献

{"title":"Ferroptosis induction by curcumin through regulating the expression of glutathione peroxidase 4 in papillary thyroid carcinoma","authors":"Li Ren,&nbsp;Haofeng Ding,&nbsp;Yun Sun,&nbsp;Shenzhen Zhou,&nbsp;Tongtong Li,&nbsp;Jingyi Xia,&nbsp;Zhigao Zhu,&nbsp;Mohan Geng,&nbsp;Bo Zhu,&nbsp;Congli Zhang","doi":"10.1007/s10735-026-10922-z","DOIUrl":"10.1007/s10735-026-10922-z","url":null,"abstract":"<div><p>To clarify the role of glutathione peroxidase 4 (GPX4)-mediated ferroptosis in curcumin-treated papillary thyroid carcinoma (PTC) cells and explore the underlying mechanisms. GPX4 expression and clinical relevance were analysed in 54 PTC tissues by immunohistochemistry. B-CPAP cells were used to assess proliferation, migration, apoptosis and cell cycle after curcumin treatment. Ferroptosis was evaluated by detecting malondialdehyde (MDA), reactive oxygen species (ROS), Fe²⁺ and glutathione (GSH) levels, with ferrostatin 1 (Fer-1) and agonists (RSL3) used for validation. Molecular docking and Western blot were performed to analyse GPX4 interaction and expression. A nude mouse xenograft model was established to evaluate in vivo effects. Elevated GPX4 expression correlated with poor prognosis in PTC, including increased lymph node and distant metastasis and reduced progression-free survival. In vitro studies showed that curcumin downregulated GPX4 and induced ferroptotic features, including increased MDA and ROS, elevated Fe²⁺ and decreased GSH. These changes were accompanied by inhibited proliferation and migration, as well as G2/M arrest. Importantly, the ferroptosis inhibitor Fer-1 reversed curcumin-induced cell death and partially restored migration, confirming ferroptosis as the primary anticancer mechanism. Molecular docking analysis suggested a possible interaction between curcumin and the GPX4 protein at the Gln-55 and Pro-155 residues; however, this prediction was not experimentally validated in the present study. Importantly, GPX4 overexpression partially rescued curcumin-induced loss of cell viability and lipid peroxidation, supporting a functional role for GPX4 in curcumin-induced ferroptosis. In vivo experiments showed that curcumin significantly suppressed tumour growth in the xenograft model without observable organ toxicity and reduced GPX4 expression in tumour tissues. This study shows that curcumin inhibits PTC progression via GPX4-mediated ferroptosis; GPX4 overexpression partially reversed these effects, supporting its functional role. These findings identify curcumin as a promising therapeutic agent for PTC treatment and suggest GPX4 as a potential therapeutic target.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667986","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":"Morphometric and immunohistochemical characterization of Rodlet cells in the kidney and liver of Gymnotus carapo","authors":"Eduen Gross,&nbsp;Gabriela Olea,&nbsp;Sabrina Méndez Galarza,&nbsp;Franco González,&nbsp;Claucia Aparecida Honorato,&nbsp;Carolina Flores Quintana","doi":"10.1007/s10735-026-10927-8","DOIUrl":"10.1007/s10735-026-10927-8","url":null,"abstract":"<div><p>Freshwater ecosystems are increasingly exposed to environmental stressors capable of inducing physiological and immunological alterations in aquatic organisms. In this context, fish are widely recognized as valuable bioindicators because they reflect environmental changes at tissue and cellular levels. The present study aimed to characterize the morphology, morphometry, and NF-κB immunoreactivity of Rodlet cells (RCs) in the kidney and liver of the Neotropical teleost <i>Gymnotus carapo</i>. A total of 32 specimens collected from natural lentic environments (n = 14) and commercial holding facilities (n = 18) were examined using histological, histochemical (Periodic acid–Schiff, PAS), morphometric, and immunohistochemical techniques. RCs were identified in both organs and were classified into the four classical differentiation stages (granular, transitional, mature, and secretory), exhibiting the characteristic morphological features previously described for this cell type. Morphometric analysis demonstrated a progressive increase in cell length across the morphologically defined differentiation stages. Immunohistochemistry revealed NF-κB immunoreactivity in RCs located individually within the renal and hepatic parenchyma, associated with hematopoietic tissue and melanomacrophage centers, and occasionally within blood vessels. Immunoreactivity was detected in both the cytoplasm and the nucleus of RCs, consistent with the presence of NF-κB in these cells. Although the present study did not evaluate environmental contaminants or experimentally induced inflammatory conditions, the combined histological, morphometric, and immunohistochemical findings provide baseline evidence suggesting that RCs participate in immune-related processes and may represent potential histological biomarkers for future environmental monitoring studies. Nevertheless, this hypothesis requires further validation through controlled experimental approaches evaluating environmental stressors and inflammatory responses.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667977","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":"Integrated UPLC-MS/MS profiling and network pharmacology-based analysis of the anti-hyperglycemic potential of Baihu Jia Renshen Decoction combined with Sanghuangporus vaninii extract in mice","authors":"Jia Zhang,&nbsp;Ying Chen,&nbsp;Yanfa Lin,&nbsp;Zifeng Huang,&nbsp;Xiaodong Ge,&nbsp;Bin Liu,&nbsp;Zirui Huang","doi":"10.1007/s10735-026-10921-0","DOIUrl":"10.1007/s10735-026-10921-0","url":null,"abstract":"<div><p>Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder requiring multi-target therapeutic strategies. Traditional Chinese medicine offers potential multi-component interventions, yet the material basis and molecular mechanisms of novel formulations often remain incompletely defined. This study developed an integrated formula (FSV) combining a modified Baihu Jia Renshen Decoction with Sanghuangporus vaninii extract and explored its anti-hyperglycemic potential using chemical profiling, network pharmacology, in vitro α-glucosidase inhibition, and an STZ/HSHFD-induced hyperglycemic mouse model. A total of 2,413 database-matched features were annotated, most of which should be regarded as putative rather than standard-confirmed identifications. Mangiferin and several flavonoids were retained as plant/fungus-compatible candidate constituents, whereas implausible xenobiotic matches were excluded from biological interpretation. Network pharmacology predicted the involvement of inflammation- and insulin-resistance-related targets, including TNF, AKT1, IL6, NFKB1, and MAPK3 (also known as ERK1), whereas ALB was treated as a high-connectivity carrier protein rather than a direct druggable mediator. FSV inhibited α-glucosidase in vitro and was associated with improvements in hyperglycemia, insulin-sensitivity indices, dyslipidemia, and tissue morphology in the mouse model. These phenotypic findings are presented as experimental support accompanying the pathway predictions, while direct pathway validation is left for future mechanistic studies. Overall, the results provide a preliminary basis for further chemical validation and mechanistic investigation of FSV in diabetes-related metabolic dysfunction.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148628494","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":"Syntaxin-4, a key exocytosis mediating protein, shows heterogeneous expression in insulin-positive cells of human donors with new-onset and longer duration of type 1 diabetes: comparison with non-diabetic autoantibody-positive and -negative donors","authors":"Joshua Potman,&nbsp;Kevin Xueying Sun,&nbsp;Kaaj Pala,&nbsp;Lars Krogvold,&nbsp;Knut Dahl-Jørgensen,&nbsp;Shiva Reddy","doi":"10.1007/s10735-026-10901-4","DOIUrl":"10.1007/s10735-026-10901-4","url":null,"abstract":"<div><p>Syntaxin-4, a beta cell plasma membrane-anchored protein, attaches to beta cell granules with two spatially-located nearby proteins, facilitating the fusion of beta cell-docked granules to the plasma membrane, followed by exocytotic release of insulin and remaining granule contents. During type 1 diabetes (T1D) and its preceding phase, it is unclear whether syntaxin-4 levels decline in residual beta cells, thereby contributing to impaired insulin release. The level of syntaxin-4 in insulin-positive regions of islets was determined following immunofluorescence staining of human pancreatic sections, with co-immunofluorescence staining for insulin and for glucagon by immunoperoxidase. Random islets from non-diabetic autoantibody-negative (Group 1; <i>n</i> = 7), non-diabetic autoantibody-positive (Group 2; <i>n</i> = 6), new-onset T1D (Group 3; <i>n</i> = 4) and long-term T1D (Group 4; <i>n</i> = 10) donors were quantified for syntaxin-4 levels. In groups 1 and 2, inter-islet staining intensities for syntaxin-4, although variable across individual donors, were similar overall between the groups, with lower intensities in group 3. In group 4, 3 donors with 0.58–1.5 years of T1D showed mean intensities comparable to groups 1 and 2, whereas donors with 4–7 years of T1D showed declining intensities. In general, the average syntaxin-4 intensities in the two diabetic groups were lower than those in the non-diabetic groups. The expression of syntaxin-4 in insulin-positive islet cells showed marked differences in intensity among most diabetic donors and autoantibody-positive and -negative non-diabetic donors. In some long-term diabetic donors, syntaxin-4 was also present in insulin- and glucagon-negative cells. During protracted T1D, reduced syntaxin-4 in islets may impair insulin release.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-026-10901-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148614762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of long-term use of very low-carbohydrate Ketogenic diet on the thyroid gland and adipose tissue of adult male albino rats (biochemical and histological study)","authors":"Randa Ahmed Ibrahim,&nbsp;Nehal Mohammed Elwaddah,&nbsp;Neven Makram Aziz,&nbsp;Jermeen Emad Yousef,&nbsp;Seham Abd El-Raouf Abd El-Aleem,&nbsp;Entesar Ali Saber","doi":"10.1007/s10735-026-10907-y","DOIUrl":"10.1007/s10735-026-10907-y","url":null,"abstract":"<div><p>Ketogenic diet (KD) therapy is a high-fat, low-carbohydrate, low-protein diet with a macronutrient ratio of 89% fat, 10% protein, and 1% carbohydrates. This causes the body's primary energy source to shift to lipids. Improved glycemic control, weight loss, and the treatment of metabolic and cardiovascular diseases are among the therapeutic advantages of this metabolic shift. Therefore, this study was designed to detect if the prolonged intake of KD has beneficial or hazardous effects on the thyroid gland and adipose tissue by using 20 adult male albino rats divided into two groups. Both groups received 30 gm of food every day for 60 days: a standard diet for the control group and KD for the ketogenic group. Blood samples were taken for measurement of lipid profile and thyroid hormones. Body weight, body mass index (BMI), and food intake with atherogenic index were also measured. Tissue samples from the thyroid gland and adipose tissue were also taken for histological analysis using Hematoxylin and Eosin (H&amp;E), Sudan black, Masson Trichrome, PAS, and immunohistochemical staining (caspase 3 and calcitonin antibodies). The results of the present study showed that the long-term use of the KD diet produced a significantly lower body weight, BMI, and food intake, with an atherogenic serum lipid profile and increased TSH levels. Additionally, it produced histological changes in the thyroid and adipose tissues with increased caspase-3 expression and a greater number of calcitonin-positive cells. In conclusion, this study highlights the adverse effects of the KD on thyroid and adipose tissues, evidenced by reduced serum T3 and T4, elevated TSH, follicular cell disruption, and adipose tissue alterations like reduced lipid droplet size and increased vascularization. The results could be alarming for the health hazards of chronic KD consumption in humans without medical supervision.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148615142","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":"Prophylactic administration of silica nanoparticles loaded with amifostine prevents cisplatin-induced nephrotoxicity in rats","authors":"Rehab A. Mohamed,&nbsp;Nadia A. Mohamed,&nbsp;Dawoud F. Habib,&nbsp;Noha E. Ibrahim,&nbsp;Zakaria El-Khayat,&nbsp;Amal M. El-Feky,&nbsp;Enayat Emara,&nbsp;Wagdy K. B. Khalil,&nbsp;Amani F. H. Noureldeen","doi":"10.1007/s10735-026-10910-3","DOIUrl":"10.1007/s10735-026-10910-3","url":null,"abstract":"<div><p>Drug-induced nephrotoxicity is a major limitation in chemotherapy, particularly with cisplatin, necessitating effective renal-protective strategies. Amifostine, a thiol-based prophylactic agent, has potential to mitigate such toxicity. This study demonstrates a prophylactic nephroprotective strategy where SiNPs@AMF was administered prior to and during cisplatin treatment and development of novel nano-emulsified formulation to potentially overcome the limitations of free amifostine, such as its short half-life and systemic side effects. Hollow silica nanoparticles loaded with amifostine were prepared via ultrasonication and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. Fifty male Wistar rats were randomly assigned to five groups: normal control, nano-emulsion control (SiNPs), nephrotoxic (cisplatin), amifostine nano-emulsion (SiNPs@AMF), and combined treatment (SiNPs@AMF + cisplatin). Cisplatin-induced nephrotoxicity was established by intraperitoneal injections (20 mg/kg, twice day after day). Serum inflammatory and extracellular matrix biomarkers (HA, MMP-9, NF-κB, MCP-1) were quantified by ELISA.urea, creatinine by spectrophotometer. Renal microRNA (miR-29a, miR-193a) and podocyte markers (podocin, nephrin) were evaluated using quantitative real-time PCR. P53 expression was assessed via immunohistochemistry. Cisplatin markedly increased serum urea, creatinine, HA, MMP-9, NF-κB, and MCP-1, downregulated miR-29a, podocin, and nephrin, and upregulated miR-193a, accompanied by elevated P53 immunoreactivity. Treatment with SiNPs@AMF significantly attenuated inflammatory and extracellular matrix disruptions, restored miR-29a, podocin, and nephrin expression, reduced miR-193a overexpression, and decreased P53 staining. Silica nano-emulsified amifostine effectively mitigates cisplatin-induced nephrotoxicity by suppressing inflammation, preserving extracellular matrix integrity, and restoring renal microRNA balance. These findings support the therapeutic potential of nano-formulated thiol compounds as a targeted strategy to prevent chemotherapy-associated renal injury.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148614764","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":"LncRNA MNX1-AS1 drives the progression of non-small cell lung cancer and serves as a ceRNA to target COMMD8 by sponging miR-218-5p","authors":"Gao-Feng Liu,&nbsp;Li Zhou,&nbsp;Yu-Bo Zhao,&nbsp;Jia-Hong Tang,&nbsp;Qing-Yuan Li,&nbsp;Xiao-Yong Ding,&nbsp;Xiao-Zhen Zhang,&nbsp;Su-Juan Cui,&nbsp;Yong Zhang,&nbsp;Zhen-Wei Sun","doi":"10.1007/s10735-026-10891-3","DOIUrl":"10.1007/s10735-026-10891-3","url":null,"abstract":"<div><p>The role and mechanistic action of MNX1-AS1 in non-small cell lung cancer (NSCLC) remain unclear. This study aimed to investigate the function of MNX1-AS1 in the progression of NSCLC. A total of 40 paired tumor and adjacent lung tissue samples from patients with NSCLC were collected to investigate the expression of MNX1-AS1. H1299 and HCC827 cells were transfected with sh-MNX1-AS1, shRNA-NC, miR-218-5p mimic, mimic-NC, pcDNA3.1-COMMD8, or empty vector (pcDNA3.1). The expression of MNX1-AS1, miR-218-5p, and COMMD8 was detected using quantitative real-time PCR (qRT-PCR). Cell proliferation was evaluated using CCK-8 assays, while cell migration and invasion were evaluated using Transwell assays. Dual-luciferase reporter and RNA pull-down assays were performed to validate the targeting interactions between MNX1-AS1 and miR-218-5p, as well as between COMMD8 and miR-218-5p. In vivo, a nude mouse model was established: tumor volume and weight were measured after four weeks. Gene expression in tumor tissue was quantified using qRT-PCR, and Ki-67 expression was evaluated using immunohistochemistry. MNX1-AS1 expression was significantly upregulated in NSCLC tissues (<i>P</i> &lt; 0.05) and was correlated with poor prognosis in NSCLC patients. MNX1-AS1 knockdown markedly suppressed the viability, migration, and invasion of H1299 and HCC827 cells (<i>P</i> &lt; 0.05). Mechanistically, MNX1-AS1 acted as a molecular sponge for miR-218-5p, thereby relieving miR-218-5p-mediated repression of its direct target COMMD8 (<i>P</i> &lt; 0.05). Functional rescue experiments revealed that miR-218-5p silencing or COMMD8 overexpression partially reversed the inhibitory effects of MNX1-AS1 knockdown on the cell viability, migration, and invasion of H1299 and HCC827 cells. In vivo, sh-MNX1-AS1 significantly reduced tumor volume and weight (<i>P</i> &lt; 0.05). Moreover, the expression of MNX1-AS1, COMMD8, and Ki-67 were downregulated, while the expression of miR-218-5p was upregulated in sh-MNX1-AS1 tumor tissues (<i>P</i> &lt; 0.05). MNX1-AS1 promotes the progression of NSCLC by modulating the miR-218-5p/COMMD8 axis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-026-10891-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148614807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOX9 knockdown alleviates Aβ1‑42‑induced neuroinflammation by regulating microglial polarization via inactivation of the ASK1/JNK signaling pathway","authors":"Minghui Zheng,&nbsp;Bingxu Hou,&nbsp;Ruxue Ma,&nbsp;Kaidi Wang,&nbsp;Junzhi Xia,&nbsp;Zheng Tan","doi":"10.1007/s10735-026-10913-0","DOIUrl":"10.1007/s10735-026-10913-0","url":null,"abstract":"<div><p>Neuroinflammation driven by microglial polarization imbalance plays a key role in Aβ-induced neuronal injury, a core pathological feature of Alzheimer’s disease (AD). The transcription factor SOX9 has been linked to AD progression, but its mechanism remains unclear. SOX9 expression was measured in peripheral blood mononuclear cells from 24 patients with AD and 24 age-matched healthy controls and correlated with Montreal Cognitive Assessment scores. An Aβ1-42-stimulated BV-2 cell model was used to investigate the effects of SOX9 and apoptosis signal-regulating kinase 1 (ASK1) on microglial polarization. Neuronal injury was evaluated in a BV-2/SH-SY5Y co-culture system. The transcriptional regulation of ASK1 by SOX9 was examined using dual-luciferase reporter and chromatin immunoprecipitation assays. ASK1 overexpression and the ASK1 inhibitor GS-4997 were used for mechanistic validation. SOX9 expression was increased in peripheral blood mononuclear cells from patients with AD and was negatively correlated with cognitive function. SOX9 was also upregulated in Aβ1-42-stimulated BV-2 cells. SOX9 overexpression enhanced M1-associated inflammatory markers and reduced M2-associated markers, whereas SOX9 knockdown produced the opposite effects. In the co-culture system, SOX9 knockdown increased SH-SY5Y cell viability, reduced LDH release and apoptosis, increased Bcl-2 expression, and decreased Bax and cleaved caspase-3 expression. SOX9 bound to the ASK1 promoter and promoted ASK1 transcription. SOX9 silencing suppressed ASK1, JNK, and p38 phosphorylation, while ASK1 overexpression reversed the effects of SOX9 knockdown on microglial polarization and neuronal injury. Consistently, GS-4997 blocked the pro-inflammatory and neurotoxic effects induced by SOX9 overexpression. SOX9 exacerbates AD neuroinflammation by promoting microglial M1 polarization via the ASK1/JNK signaling axis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148614896","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":"Celastrol attenuates synovial inflammation and experimental arthritis by modulating PTGS2-associated ferroptosis resistance in fibroblast-like synoviocytes","authors":"Yunke Guo,&nbsp;Hao Tang,&nbsp;Zulayat Ablikim,&nbsp;Lirong Deng,&nbsp;Ting Wang,&nbsp;Mengjiang Tian","doi":"10.1007/s10735-026-10917-w","DOIUrl":"10.1007/s10735-026-10917-w","url":null,"abstract":"<div><p>Rheumatoid arthritis (RA) is characterized by persistent synovial inflammation and aggressive activation of fibroblast-like synoviocytes (FLS). Celastrol has recognized anti-inflammatory activity, but its mechanism in RA remains incompletely defined. This study investigated whether the anti-arthritic effect of celastrol is associated, at least in part, with a PTGS2-associated ferroptosis-resistance pathway in FLS. Potential targets of celastrol in RA were identified through integrated bioinformatic analyses. Collagen-induced arthritis (CIA) rats and primary FLS were used to evaluate the effects of celastrol in vivo and in vitro. Joint pathology, inflammatory mediator expression, oxidative stress, iron accumulation, lipid peroxidation, and ferroptosis-related proteins were assessed. Loss- and gain-of-function experiments were performed to examine the functional role of PTGS2. Bioinformatic screening identified PTGS2 as a candidate functional mediator linking celastrol to RA. In CIA rats, celastrol reduced paw swelling, arthritis severity, synovial hyperplasia, inflammatory cell infiltration, and cartilage and bone destruction. In FLS, celastrol suppressed cell proliferation and migration and decreased the expression of pro-inflammatory cytokines. Mechanistically, the combined changes in intracellular iron, lipid peroxidation, mitochondrial function, and ferroptosis-related proteins supported attenuation of a ferroptosis-resistant phenotype after celastrol treatment. PTGS2 expression was markedly elevated in RA models and was downregulated by celastrol. PTGS2 overexpression attenuated the anti-inflammatory effects of celastrol and reversed several ferroptosis-associated changes, supporting a functional role for PTGS2 in this process. Celastrol alleviates synovial inflammation and experimental arthritis, at least in part, in association with PTGS2 modulation and attenuation of a ferroptosis-resistant phenotype in FLS. To our knowledge, these findings provide experimental evidence linking celastrol, PTGS2-associated regulation, and ferroptosis resistance in RA models.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148614897","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":"Electroacupuncture confers neuroprotection against ischemic stroke via the DNA methylation–RhoGDIα axis","authors":"Xiaoli Min,&nbsp;Qing Zhao,&nbsp;Xiaohong Zhao,&nbsp;Ying Shi,&nbsp;Quanming Chen,&nbsp;Xuhui Li,&nbsp;Jiayi Hu,&nbsp;Yong Zeng,&nbsp;Feifei Shang","doi":"10.1007/s10735-026-10904-1","DOIUrl":"10.1007/s10735-026-10904-1","url":null,"abstract":"<div><p>Electroacupuncture (EA) has emerged as a promising alternative therapy for ischemic brain injury, yet its underlying molecular mechanisms remain incompletely understood. This study investigated the neuroprotective effects and epigenetic mechanisms of EA in a mouse model of ischemic stroke. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in mice. EA was applied at Baihui (GV20) and left Zusanli (ST36) acupoints following surgery. Neurological deficits were assessed, infarct volume was measured by TTC staining, and neuronal damage was evaluated by Nissl staining. RhoGDIα protein expression was determined by Western blot. Global DNA methylation was quantified by ELISA, and promoter-specific methylation of RhoGDIα was examined by quantitative methylation-specific PCR (MSP), and mRNA expression of candidate DNA methyltransferases (DNMTs) and demethylases (TETs) was measured by qPCR. EA alleviated MCAO-induced brain injury, as reflected by improved neurological scores, reduced infarct volume, and attenuated neuronal loss. RhoGDIα expression was downregulated after MCAO and restored by EA treatment. Pharmacological inhibition of RhoGDIα abolished the neuroprotective effects of EA, underscoring its essential role in EA-mediated protection. Mechanistically, MCAO induced hypermethylation of the RhoGDIα promoter, which was reversed by EA, leading to restoration of RhoGDIα expression. Furthermore, co-administration of the DNA methylation inhibitor 5-Azacytidine synergistically enhanced the neuroprotective efficacy of EA. Our findings demonstrate that EA ameliorates ischemic brain injury in association with epigenetic regulation of RhoGDIα via promoter demethylation. This study identifies RhoGDIα as a key mediator of EA-induced neuroprotection and suggests that the DNA methylation–RhoGDIα axis may represent a promising therapeutic target for ischemic stroke.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148614808","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}