Folia histochemica et cytobiologica最新文献

{"title":"Silencing GJB2 attenuates IL-1β-induced chondrocyte injury by activating Nrf2/HO-1 signaling and preserving mitochondrial function.","authors":"Hongyi Pan, Lianguo Wu","doi":"10.5603/fhc.111194","DOIUrl":"https://doi.org/10.5603/fhc.111194","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondrial oxidative stress is a key driver of inflammation-induced chondrocyte dysfunction and cartilage degeneration. However, the molecular regulators linking inflammatory signaling to mitochondrial impairment in chondrocytes remain incompletely understood.</p><p><strong>Material and methods: </strong>Public transcriptomic datasets were analyzed using differential expression analysis, weighted gene co-expression network analysis (WGCNA), and screening for oxidative stress-related genes to identify osteoarthritis (OA)-associated hub genes. An IL-1β-induced CHON-001 chondrocyte injury model was established, and the GJB2 gene, which encodes connexin 26, was silenced using siRNA. Cell viability, oxidative stress, apoptosis, Nrf2/HO-1 signaling, and mitochondrial membrane potential were evaluated.</p><p><strong>Results: </strong>Integrated bioinformatics analysis of multiple GEO datasets identified GJB2 as a key oxidative stress-related hub gene. IL-1β stimulation significantly increased GJB2 expression and induced oxidative stress, apoptosis, and mitochondrial dysfunction. GJB2 knockdown reduced reactive oxygen species (ROS) accumulation, attenuated inflammatory responses, inhibited apoptosis, restored Nrf2 nuclear translocation and HO-1 expression, and preserved mitochondrial membrane potential.</p><p><strong>Conclusions: </strong>GJB2 promotes inflammation-associated oxidative injury and mitochondrial dysfunction in chondrocytes. Silencing GJB2 activates the Nrf2/HO-1 antioxidant pathway and confers cytoprotective effects, identifying GJB2 as a critical regulator and highlighting connexin-mediated redox signaling as a potential therapeutic target for cartilage degeneration.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879428","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":"TSSC3 as a potential biomarker in osteosarcoma: implications for angiogenesis.","authors":"Hanzhen Feng, Wenmang Xu, Qiang Feng, Xiaolong Wei, Meijin Huang, Ziran Gao","doi":"10.5603/fhc.112768","DOIUrl":"https://doi.org/10.5603/fhc.112768","url":null,"abstract":"<p><strong>Introduction: </strong>. Osteosarcoma (OS) is a highly vascularized malignant tumor whose growth and metastasis depend on angiogenesis. Tumor-suppressing STF cDNA 3 (TSSC3) has been identified as a tumor suppressor in OS, but its role and underlying mechanisms in regulating angiogenesis remain unclear.</p><p><strong>Materials and: </strong>METHODS: . Immunohistochemistry was used to assess the expression of TSSC3, VEGF-A, and CD31 in OS tissues. OS cells that stably overexpressed TSSC3 were established via lentiviral transduction, and conditioned medium from these cells was used to culture human umbilical vein endothelial cells (HUVECs). The proliferation, migration, and tube formation of HUVECs were evaluated using CCK-8, wound healing, Transwell, and tube formation assays. qRT-PCR and Western blotting were conducted to assess VEGFA mRNA and VEGF-A protein levels in TSSC3-overexpressing cells. A xenograft model in nude mice was used to evaluate angiogenesis in vivo, and changes in the Src/ERK pathway were examined by Western blotting.</p><p><strong>Results: </strong>. TSSC3 was downregulated, and VEGF-A was upregulated in OS tissues, both of which were associated with prognosis. Conditioned medium from the TSSC3-overexpressing cells significantly inhibited HUVEC proliferation, migration, and tube formation. In vivo, TSSC3 overexpression led to reduced tumor weight, VEGF-A expression, and microvessel density. Moreover, TSSC3 suppressed VEGF-A synthesis and secretion in a Src/ERK-dependent manner.</p><p><strong>Conclusions: </strong>. TSSC3 inhibits angiogenesis in OS by downregulating VEGF-A via the Src/ERK pathway, providing a theoretical and experimental basis for anti-angiogenic therapies targeting TSSC3.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863980","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":"Molecular mechanism by which dichotomitin inhibits growth and metastasis of gastric cancer MKN-45 cells via the EGFR/ROS signaling pathway.","authors":"Zhao Ning, Quan Quan, Xi-Chun Huang, Jun-Hao Li, Zhe Liu, Cheng-Hao Jin","doi":"10.5603/fhc.113717","DOIUrl":"https://doi.org/10.5603/fhc.113717","url":null,"abstract":"<p><strong>Introduction: </strong>Dichotomitin (DC), an isoflavone from Belamcanda chinensis, has anti-inflammatory and antioxidant properties, but its role in gastric cancer (GC) remains unexplored. This study aimed to elucidate the mechanisms by which DC modulates GC cell proliferation, apoptosis, and migration.</p><p><strong>Materials and methods: </strong>. MKN-45 cells were used for in vitro studies, and xenograft tumor models were established using BALB/c nude mice for in vivo evaluation. Bioinformatics analysis predicted core targets. CCK-8, flow cytometry, wound healing, Transwell, and fluorescence microscopy assays were performed to assess proliferation, cell-cycle distribution, apoptosis, migration, and ROS levels. Expression of proteins in the EGFR/MAPK, EGFR/AKT, and AKT/GSK-3β/β-catenin pathways was determined by Western blotting.</p><p><strong>Results: </strong>. In vitro, DC significantly inhibited GC cell proliferation and induced morphological changes. DC induced cell cycle arrest in the G0/G1 phase and promoted mitochondria-dependent apoptosis by modulating EGFR/MAPK signaling, while inhibiting migration through the AKT/GSK-3β/β-catenin pathway. Mechanistically, DC inhibited EGFR activation and elevated ROS levels. The EGFR agonist NSC228155 reversed these effects, confirming dependence on EGFR-ROS signaling. In vivo, DC dose‑dependently inhibited tumor growth, with medium/high doses outperforming 5‑fluorouracil. Histological examination of major organs showed no significant abnormalities, confirming low toxicity at therapeutic doses.</p><p><strong>Conclusions: </strong>. DC inhibited proliferation, induced cell cycle arrest and apoptosis, and suppressed migration in GC cells by modulating EGFR-related ROS-dependent signaling pathways.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817721","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":"Tectochrysin suppresses the profibrotic phenotype of human keloid fibroblasts and is associated with reduced nuclear p65 accumulation.","authors":"Lin Ma, Wei Zheng, Weibo Song, Aijing Ma, Qianqian Zhang, Lei Gao, Hongyu Wang","doi":"10.5603/fhc.111687","DOIUrl":"10.5603/fhc.111687","url":null,"abstract":"<p><strong>Introduction: </strong>Keloids are fibroproliferative scars characterized by persistent fibroblast activation and excessive extracellular matrix deposition. Tectochrysin is a natural flavone with anti-inflammatory and anti-oxidative activities, but its effects on keloid fibroblasts remain unclear.</p><p><strong>Material and methods: </strong>Human keloid fibroblasts (HKFs) and human skin fibroblasts (HSFs) were exposed to tectochrysin. Cell viability was assessed by CCK-8. HKF apoptosis, intracellular reactive oxygen species (ROS), wound closure, vimentin immunofluorescence, profibrotic protein expression, and nuclear/cytoplasmic p65 distribution were evaluated. TGF-β1-stimulated HSFs were used as a controllable profibrotic activation model.</p><p><strong>Results: </strong>Tectochrysin preferentially decreased HKF viability at 5 and 10 μg/mL while exerting weaker effects on HSFs, and significantly increased HKF apoptosis. It reduced intracellular ROS, delayed wound closure, altered vimentin-positive cytoskeletal organization in adherent HKFs, and decreased α-smooth-muscle-actin, collagen I, and fibronectin expression in HKFs. Tectochrysin also attenuated TGF-β1-induced upregulation of these markers in HSFs. Nuclear p65 abundance was reduced, whereas cytoplasmic p65 changed only modestly.</p><p><strong>Conclusions: </strong>Tectochrysin suppresses the profibrotic phenotype of keloid fibroblasts and is associated with reduced nuclear p65 accumulation, supporting further evaluation as a candidate anti-keloid agent.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"140-149"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360242","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":"Ginsenoside Rg3 inhibits Ang II-induced cardiac fibrosis via the GLP-1 receptor signaling pathway.","authors":"Jie Zhao, Zheng Yan, Chaokun Guan, Dongsheng Li, Xisheng Yan, Xiao Li, Yanglin Li, Xing Liu, Shifan Tang","doi":"10.5603/fhc.106697","DOIUrl":"10.5603/fhc.106697","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiac fibrosis is a major pathological feature of multiple cardiovascular diseases and an important risk factor for heart failure. Ginsenoside Rg3 (Rg3), a natural triterpenoid saponin extracted from Panax ginseng, has been shown to exert cardioprotective effects. In this study, we assessed the effects of Rg3 on angiotensin II (Ang II)-induced cardiac fibrosis in both cellular and animal models and investigated the underlying mechanisms.</p><p><strong>Material and methods: </strong>For the cellular experiments, primary mouse cardiac fibroblasts (CFs) were treated with Ang II (1 μM) and Rg3 (25, 50, or 100 μM) for 24 h to assess the effects of Rg3 on cardiac fibrosis in vitro. The glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin-3 (9-39) (1 μM) was used to validate the role of GLP-1R signaling in the anti-fibrotic effects of Rg3 in vitro. A CCK-8 assay was performed to assess cell viability. For the animal experiments, male C57BL/6J mice were divided into 4 groups (6 mice per group): Sham, Ang II, Ang II + Rg3 (50 mg/kg), and Ang II + Rg3 (100 mg/kg). Collagen deposition in mouse cardiac tissues was assessed by picrosirius red staining. The expression of fibrosis-related proteins (MMP-2, MMP-9, α-SMA, collagen I, collagen III, and fibronectin), GLP-1R, phosphorylated Smad2/3, total Smad2/3, RhoA, and ROCK2 in CFs and mouse cardiac tissues was examined by RT-qPCR, western blotting, and immunofluorescence staining.</p><p><strong>Results: </strong>Rg3 treatment reversed the Ang II-induced upregulation of MMP-2, MMP-9, α-SMA, collagen I, collagen III, p-Smad2/3, RhoA, and ROCK2 and the downregulation of GLP-1R in CFs. Exendin-3 (9-39) antagonized the effects of Rg3 on the expression of fibrosis-related proteins, GLP-1R, p-Smad2/3, RhoA, and ROCK2 in CFs. Furthermore, Rg3 administration suppressed collagen deposition, reduced the expression of MMP-2, MMP-9, α-SMA, collagen I, collagen III, p-Smad2/3, RhoA, and ROCK2, and increased GLP-1R levels in the cardiac tissues of Ang II-infused mice.</p><p><strong>Conclusions: </strong>Rg3 exerts an anti-fibrotic effect in cardiac fibrosis models by inhibiting activation of the RhoA/ROCK and Smad2/3 pathways through upregulation of GLP-1R.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"60-74"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503452","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":"Lactucin inhibits growth and induces apoptosis in gastric cancer cells by targeting MAPK signaling.","authors":"Dan Wei, Peng-Li Wang, Jing Jiang","doi":"10.5603/fhc.110087","DOIUrl":"10.5603/fhc.110087","url":null,"abstract":"<p><strong>Introduction: </strong>Lactucin, a sesquiterpene lactone isolated from chicory (Cichorium intybus L.), demonstrates broad-spectrum anticancer activity across multiple malignancies, yet its mechanistic role in gastric cancer (GC) remains unexplored. This study aimed to elucidate the potential mechanism by which lactucin modulates GC cell proliferation and apoptosis.</p><p><strong>Material and methods: </strong>NUGC-3 and MKN-1 cells were used for in vitro studies, and xenograft tumor models were established using BALB/c nude mice for animal studies. To assess cell proliferation, cell cycle distribution, and apoptosis, CCK-8 assay and flow cytometry analyses were conducted, while cell morphology was examined under an inverted microscope. Levels of proteins associated with cell cycle, apoptosis, and mitogen-activated protein kinase (MAPK) signaling were determined by Western blotting.</p><p><strong>Results: </strong>In vitro, lactucin significantly attenuated GC cell proliferation and induced alterations in their morphology. Lactucin induced cell cycle arrest in the G0/G1 phase by reducing protein levels of cyclins (cyclin B1 and cyclin D1) and cyclin-dependent kinases (CDKs), including CDK2 and CDK4. Moreover, lactucin promoted GC cell apoptosis in a dose-dependent manner by downregulating Bcl-2, upregulating Bax, and increasing cleavage of caspase-3 and PARP. In vivo, lactucin inhibited tumor growth and decreased Ki67 expression levels in xenograft tumors.</p><p><strong>Conclusions: </strong>Lactucin inhibited proliferation, induced cell cycle arrest and apoptosis in GC cells by inactivating the MAPK/p38 pathway.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"89-98"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948135","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":"Exosomal Lnc-DLK1-35 reprograms microglia into a pro-tumorigenic phenotype via a non-canonical cytokine signature to promote glioblastoma progression and chemoresistance.","authors":"Dan Li, Yufeng Li, Zhuo Wang, Xuan Zheng, Yang Wang, Jianxiong Guo, Jingwu Li, Yongliang Liu, Yuhui Li","doi":"10.5603/fhc.109684","DOIUrl":"10.5603/fhc.109684","url":null,"abstract":"<p><strong>Introduction: </strong>Temozolomide (TMZ) resistance in glioblastoma (GBM) involves dynamic crosstalk of cancer cells with tumor-associated microglia, but the role of exosomal long non-coding RNAs (lncRNAs) remains poorly defined.</p><p><strong>Material and methods: </strong>We isolated exosomes from TMZ-sensitive (U251) and TMZ-resistant (U251TR) GBM cells. Lnc-DLK1-35 expression was modulated by overexpression/knockdown and validated by RT-qPCR. Exosome internalization by microglia (HMC3 cells) was tracked via PKH67 labeling. Microglial polarization was assessed by studying morphology, marker expression (CD16/CD32/iNOS/Arg-1/CD206/CD163), and cytokine secretion (ELISA: IL-6, TNF-α, TGF-β, IL-10, CXCL13). Functional impact on GBM cells by indirect co-culture with IL4-activated HMC3 cells was examined using CCK-8 and Transwell assays.</p><p><strong>Results: </strong>Lnc-DLK1-35 was enriched in U251TR cells and their exosomes. GBM exosomes delivered Lnc-DLK1-35 to microglia, inducing a unique GBM-educated phenotype: amoeboid morphology, elevated type 1 macrophage (M1) markers (CD16, iNOS) but suppressed immunoregulatory factors (IL-10, CXCL13). This reprogramming required exosomal transfer. In addition, indirect co-culture with IL4-activated HMC3 cells enhanced GBM malignancy, reduced TMZ sensitivity and promoted migration and invasion.</p><p><strong>Conclusions: </strong>Exosomal Lnc-DLK1-35 reprograms cultured microglia cells into a pro-tumorigenic state via a non-canonical cytokine signature, driving TMZ resistance and invasion. Targeting this axis disrupts microglia-GBM communication, revealing a novel therapeutic strategy.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"48-59"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431732","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":"Expression of BDNF-TrkB-AKT1 pathway components and apoptosis-related factors across yak brain regions at low and high altitudes.","authors":"Qian Zhang, Yan Cui, Junfeng He, Yangyang Pan, Meng Wang, Hongliang Jin","doi":"10.5603/fhc.110409","DOIUrl":"10.5603/fhc.110409","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigated the expression of brain-derived neurotrophic factor (BDNF) signaling components (BDNF-TrkB-AKT1) and apoptosis-related factors (Bcl-2 and Bax) in yak brain regions at different altitudes.</p><p><strong>Material and methods: </strong>The cerebral cortex, cerebellum, hippocampus, thalamus, and medulla oblongata were collected from 3-year-old yaks living at low and high altitudes. The relative mRNA expression of BDNF, TrkB, AKT1, Bcl-2, and Bax was assessed by qRT-PCR. Protein abundance and cellular localization of BDNF, TrkB, AKT1, Bcl-2, and Bax were evaluated by Western blotting and immunohistochemistry, with immunoreactivity quantified by optical density analysis.</p><p><strong>Results: </strong>Within each altitude group, BDNF, TrkB, AKT1, and Bcl-2 mRNA expression and the corresponding protein levels (BDNF, TrkB, AKT1, and Bcl-2) were significantly higher in the cerebral cortex and hippocampus than in the cerebellum, thalamus, and medulla oblongata (P < 0.05). In contrast, Bax mRNA and Bax protein levels did not differ significantly among the five regions. Compared with low-altitude yaks, high-altitude yaks showed significantly higher BDNF, TrkB, AKT1, and Bcl-2 mRNA expression and higher BDNF, TrkB, AKT1, and Bcl-2 protein levels in brain tissues (P < 0.05), whereas Bax protein expression did not differ between altitude groups. Immunohistochemistry revealed immunoreactivity for BDNF, TrkB, AKT1, Bcl-2, and Bax in both altitude groups, with prominent labeling in cortical pyramidal neurons and across the pyramidal cell layer in the hippocampal CA region. Immunoreactivity was also detected in large neurons of the thalamus and medulla oblongata. In the cerebellum, labeling was strongest in Purkinje cells, with weaker signals in the granule cell layer and molecular layer.</p><p><strong>Conclusions: </strong>BDNF-TrkB-AKT1 pathway components and Bcl-2 showed relatively higher expression in the cerebral cortex and hippocampus within each altitude group, whereas Bax expression did not vary across regions. These patterns are consistent with an association between BDNF-TrkB-AKT1 signaling and increased Bcl-2 expression without a corresponding increase in Bax, which may support neuronal adaptation in the cerebral cortex and hippocampus. Elevated expression of BDNF, TrkB, AKT1, and Bcl-2 at high altitude suggests enhanced adaptation to hypoxia in high-altitude yaks; the underlying mechanisms require further investigation.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"39-47"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431735","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":"MOTS-c primes adrenal cortex metabolism without directly driving steroidogenesis.","authors":"Malgorzata Blatkiewicz, Kacper Kaminski, Marta Sobalska-Kwapis, Marta Szyszka, Anna Olechnowicz, Karol Jopek, Marcin Rucinski","doi":"10.5603/fhc.110668","DOIUrl":"10.5603/fhc.110668","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c), a 16-amino acid mitochondrial-derived peptide, regulates cellular metabolism through AMPK and mTOR signaling and exerts protective effects across multiple endocrine tissues. However, its role in adrenal physiology remains unexplored. We hypothesized that MOTS-c establishes \"steroidogenic readiness\" by priming metabolic pathways rather than directly activating hormone synthesis.</p><p><strong>Material and methods: </strong>Adult male Wistar rats (n = 16) received continuous MOTS-c (0.1 μmol/24 h) or saline via subcutaneous micro-osmotic pumps for 24 hours. Adrenal tissues were analyzed using qRT-PCR, immunohistochemistry, ELISA, and RNA-sequencing.</p><p><strong>Results: </strong>MOTS-c showed significantly higher expression in ZF/ZR vs. ZG. MOTS-c treatment did not alter classical steroidogenic genes or circulating corticosterone and aldosterone levels. RNA-seq identified 39 differentially expressed genes, notably upregulation of purinergic receptor P2ry4 (4.3-fold, P < 0.05) - a novel MOTS-C target enhancing calcium signaling. Additional changes included upregulation of Apoc4 and downregulation of stress markers Bag3 and Smurf2, mitochondrial carrier Slc25a30, and peroxisomal factor Pex11a. Gene Set Enrichment Analysis revealed inhibition of cAMP response, mitophagy, and histone deacetylation pathways, alongside activation of cell proliferation, indicating metabolic reprogramming without steroidogenic activation.</p><p><strong>Conclusions: </strong>MOTS-c functions as a metabolic conductor that primes adrenocortical cells for enhanced steroidogenic responsiveness without stimulating basal hormone synthesis. By upregulating calcium signaling, modulating lipid metabolism, downregulating stress-response proteins, and inhibiting mitophagy, MOTS-c establishes a preparatory metabolic state optimized for subsequent ACTH or stress stimulation. These findings reveal a novel preparatory mechanism in adrenal physiology and identify MOTS-c as a potential therapeutic target for HPA axis disorders requiring enhanced adrenal reserve capacity without basal hypercortisolemia.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"26-38"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431749","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":"CRISPR-mediated MLH1 disruption suppresses endometrial cancer growth via genomic instability induction and Wnt/β-catenin pathway inhibition.","authors":"Baoling Xing, Xiaoying Zhang, Li Shen, Xinpeng Zhang","doi":"10.5603/fhc.111186","DOIUrl":"10.5603/fhc.111186","url":null,"abstract":"<p><strong>Introduction: </strong>MutL homolog 1 (MLH1) loss is a defining molecular feature of endometrial cancer (EC) and a principal driver of microsatellite instability (MSI). Ishikawa cells harbor intrinsic MLH1 promoter hypermethylation, resulting in reduced but not abolished MLH1 expression and placing these cells in a vulnerable, partially compromised mismatch repair state. This study explores the effects of MLH1 knockdown (MLH1-KD) on MSI, cellular functions, signaling pathways, and tumor growth in Ishikawa EC cells.</p><p><strong>Material and methods: </strong>Using CRISPR/Cas9, we created an MLH1-KD Ishikawa EC cell line, validated through Sanger sequencing, qRT-PCR, western blotting, comet assays, and γ-H2AX analysis. Functional assays assessed proliferation, migration, and cell cycle progression and apoptosis. RNA sequencing identified global transcriptomic changes, and Wnt/β-catenin pathway activity was measured by a dual-luciferase reporter assay. A xenograft model evaluated tumor growth in vivo.</p><p><strong>Results: </strong>MLH1-KD cells showed MSI-H characteristics, increased DNA damage, and downregulation of key EC-related genes. Functionally, MLH1-KD led to significant reductions in cell proliferation and migration, which was accompanied by cell cycle arrest and a marked increase in apoptosis. RNA sequencing revealed profound alterations in the Wnt signaling pathway. Crucially, this was confirmed by a dual-luciferase reporter assay, which showed a significant inhibition of Wnt/β-catenin signaling activity. In vivo, MLH1-KD significantly decreased tumor weight and size in nude mice.</p><p><strong>Conclusions: </strong>In EC cells with pre-existing MLH1 promoter methylation, MLH1-KD leads to MSI-H, enhances genomic instability, disrupts Wnt signaling, impairs cellular functions, and inhibits tumor growth, highlighting Wnt signaling and MSI-H as potential therapeutic targets in EC.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":" ","pages":"75-87"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607562","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}