Journal of Molecular Histology最新文献

{"title":"S100 signaling in hair follicle biology: emerging mechanistic insights and therapeutic opportunities","authors":"Dongfan Wei,&nbsp;Hongwei Jia,&nbsp;Lin Shang,&nbsp;Di Zhang,&nbsp;Fenglin Zhuo","doi":"10.1007/s10735-026-10928-7","DOIUrl":"10.1007/s10735-026-10928-7","url":null,"abstract":"<div><p>S100 proteins are a conserved family of calcium-binding proteins that regulate diverse cellular processes across multiple tissues, with particularly important roles in skin biology. In the hair follicle (HF), different S100 members are expressed in epithelial, mesenchymal, and immune compartments, where they have been linked to keratinocyte differentiation, hair cycle regulation, redox balance, and local immune control. This Review summarizes current evidence on the distribution and function of S100 proteins in HF biology and hair disease. We focus on how individual S100 isoforms contribute to intracellular calcium sensing, extracellular alarmin activity, epithelial–mesenchymal communication, and inflammatory signaling within the HF microenvironment. Studies in human skin, cultured HF-related cells, and animal models indicate that S100 proteins can influence pathways relevant to HF regeneration and pathology, including Wnt/β-catenin, NF-κB, MAPK, and oxidative stress-related signaling. However, the field remains fragmented, and many proposed functions are still inferred from expression patterns rather than direct biochemical or genetic evidence. Clarifying the cellular sources, downstream targets, and context-specific actions of S100 proteins will be essential for understanding their roles in HF physiology and disease.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719586","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":"Unraveling the neuroprotective and anti-seizure potential of Calendula officinalis L. extracts in PTZ-induced experimental epilepsy in rats","authors":"Abdelaziz M. Hussein,&nbsp;Ahmed F. Abouelnaga,&nbsp;Somaya Saad,&nbsp;Marwa Abass,&nbsp;Nedaa A. Kiwan,&nbsp;Sally Shaaban,&nbsp;Amal F. Soliman,&nbsp;Khalid Sarhan,&nbsp;Mennatullah A. M. Hussein,&nbsp;Abdelnaser A. Badawy,&nbsp;Walaa Obydah","doi":"10.1007/s10735-026-10925-w","DOIUrl":"10.1007/s10735-026-10925-w","url":null,"abstract":"<div><p>To examine the potential neuroprotective and anti-seizure effects of <i>Calendula officinalis</i> L. extracts (COE) in PTZ-induced seizures in rats as well as its effects on hippocampal electrophysiological alterations and signaling pathways implicated in epileptogenesis. A recording electrode was stereotaxically inserted in the CA1 hippocampus area of 36 male rats. Rats were randomly allocated into 3 equal groups (i) sham group, (ii) PTZ group (50 mg/kg i.p in 0.2 mL on alternate days for 2 weeks) and (iii) COE group (200 mg/Kg COE orally in 1.0 ml saline daily for 2 weeks with PTZ injection). COE considerably reduced the Racine score and lengthened the latency to the first seizure. In comparison to the PTZ and sham groups, we observed a large increase in delta and theta waves and a significant decrease in gamma waves with high amplitude sharp spikes in the electrophysiological recordings of the COE group. Also, we found a significant decrease in MDA and HO-1 expression, an increase in GSH and catalase and Nrf2 expression in the COE group compared to the PTZ group (<i>p</i> &lt; 0.01). In addition, the COE group showed a significant rise in BDNF and Hsp70 expression and decrease in caspase-3 expression compared to the PTZ group (<i>p</i> &lt; 0.001). COE exhibited neuroprotective and anti-seizures actions in PTZ-induced kindled rats. Resetting the electrophysiological rhythm from hippocampal CA1 gamma waves, reducing oxidative stress, upregulating the antioxidant Nrf2/HO-1 pathway and neuroprotective proteins (Hsp70 and BDNF), and downregulating apoptotic proteins (caspase-3) could be potential mechanisms.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p> Administration of PTZ in rats results in an increased the production of ROS in hippocampus of the brain with upregulation of caspase-3 and downregulation of HO-1, Nrf2, BDNF and Hsp70 leading to enhanced neuronal firing and epileptic seizure. On the other hand, COE treatment with PTZ injection prevents epileptic seizure and reduces the neuronal firing via reduction of ROS production, downregulation of caspase-3 and upregulation of antioxidant genes (Nrf2/HO1), BDNF and Hsp70. Red arrows indicate the effect of PTZ administration alone, while blue arrows indicate the effect of COE administration with PTZ. ROS= reactive oxygen species, Nrf2 = nuclear erythroid related factor, HO-1 = heme oxygenase-1, BDNF= brain derived neurotrophic factor, Hsp70 = heat shock protein 70. COE= <i>calendula officinalis</i> L. extract. ↑ = increase, ↓ = decrease</p></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719827","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":"Guanxinshu attenuates atherosclerosis by suppressing Galectin-3-mediated NLRP3 inflammasome activation","authors":"Ruonan Wei,&nbsp;Zhongyi Zhu,&nbsp;Chunchun Zhao,&nbsp;Kefang Zuo,&nbsp;Luyang Jia,&nbsp;Andong Zhang,&nbsp;Bin Huang,&nbsp;Gucheng Zhou,&nbsp;Min Xiao","doi":"10.1007/s10735-026-10908-x","DOIUrl":"10.1007/s10735-026-10908-x","url":null,"abstract":"<div><p>Atherosclerosis (AS) is a chronic inflammatory vascular disease strongly associated with the activation of the NLRP3 inflammasome. Studies have shown that Galectin-3 (Gal-3) promotes NOD-like receptor family pyrin domain-containing 3 (NLRP3) activation. To investigate whether Guanxinshu (GXS) alleviates AS by modulating Gal-3/NLRP3 inflammasome-associated signaling. ApoE^−/− mice fed a high-fat diet for 12 weeks were used to establish an AS model. Mice were divided into five groups: control, model, low-dose GXS (12.5 g/kg/day), high-dose GXS (25 g/kg/day), and simvastatin. Treatments were administered via oral gavage for 5 consecutive weeks. Human coronary artery endothelial cells (HCAECs) were treated with oxidized LDL (ox-LDL) to establish an injury model, followed by intervention with GXS-containing serum or the Gal-3 inhibitor TD139. Oil Red O staining, HE staining, immunohistochemistry, Western blotting, ELISA, immunofluorescence, co-immunoprecipitation, and molecular docking were used for comprehensive assessment. GXS significantly reduced aortic plaque area and lipid levels; it decreased IL-6, IL-18, and TNF-α levels in both serum and aorta. GXS suppressed the expression of Gal-3, NLRP3, ASC, caspase-1, and IL-1β proteins, and reduced Gal-3/NLRP3 co-localization. In vitro, GXS-containing serum improved HCAECs viability, reduced inflammatory cytokines, disrupted the interaction between Gal-3 and NLRP3, and reduced ox-LDL-induced NLRP3 inflammasome-associated protein expression, with effects comparable to TD139. Molecular docking predicted potential binding between representative candidate components of GXS and Gal-3, as well as potential binding affinity between Gal-3 and NLRP3 proteins. This study demonstrates for the first time that GXS mitigates vascular inflammation and slows AS progression by modulating Gal-3/NLRP3 inflammasome-associated signaling and reducing NLRP3 inflammasome-associated protein expression.</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 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148699629","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":"MAGEA1 drives tumor progression via activation of the AKT pathway and correlates with elevated radiosensitivity in lung adenocarcinoma","authors":"Fang Meng,&nbsp;Qi Zhu,&nbsp;Shiqiang Zhang","doi":"10.1007/s10735-026-10931-y","DOIUrl":"10.1007/s10735-026-10931-y","url":null,"abstract":"<div><p>Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Identifying novel molecular mechanisms underlying its progression and treatment resistance is crucial. MAGEA1, a cancer-testis antigen, exhibits oncogenic functions in multiple solid tumors; however, its expression profile and precise role in NSCLC remain poorly defined. MAGEA1 expression in NSCLC versus normal tissue was analyzed via TCGA bioinformatics, and differential expression was orthogonally validated by RT-qPCR and Western blot in normal lung epithelial and lung adenocarcinoma cell lines. Cellular proliferation, migration, and invasion were assessed by CCK-8 and Transwell assays. Apoptosis and radiosensitivity were evaluated using flow cytometry, colony formation, immunofluorescence, and comet assays. In vivo tumor growth and metastasis was examined in subcutaneous and lung metastasis mouse models. Downstream pathways were explored via RNA-seq. MAGEA1 was significantly upregulated in NSCLC tissues. Its overexpression promoted lung adenocarcinoma cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and in vivo tumor growth and metastasis, whereas MAGEA1 knockdown reversed these effects. Moreover, MAGEA1 overexpression increased irradiation-induced DNA damage and apoptosis and decreased clonogenic survival, indicating increased radiosensitivity. Mechanistically, MAGEA1 exerted its oncogenic effects primarily through activation of the AKT pathway. This study demonstrates that MAGEA1 drives lung adenocarcinoma progression by activating the PI3K/AKT pathway and correlates with elevated radiosensitivity, highlighting its potential as a therapeutic target in lung adenocarcinoma.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700340","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":"NAT10-mediated ac4C acetylation of PKM2 promotes papillary thyroid carcinoma through regulating glycolysis","authors":"Guobin Qiu,&nbsp;Yinghuan Cen,&nbsp;Yuan Li,&nbsp;Jiaan Ye,&nbsp;Sufen Li,&nbsp;Xin Li","doi":"10.1007/s10735-026-10924-x","DOIUrl":"10.1007/s10735-026-10924-x","url":null,"abstract":"<div><p>Papillary thyroid carcinoma (PTC) represents the most common histological variant among differentiated thyroid cancers. N4-acetylcytidine (ac⁴C) is a modified nucleoside in mRNA, which is essential for the regulation of mRNA stability. N-acetyltransferase (NAT)10 is an enzyme responsible for ac⁴C modification, acting as an “ac⁴C writer.” This study aimed to investigate the role of NAT10 in PTC and the underlying mechanisms involved. A total of forty-eight patients with PTC were recruited, and a nude mouse model was developed. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression levels of NAT10 and pyruvate kinase (PK) M2. Cell viability was evaluated using the cell counting kit-8 (CCK-8), while proliferation was determined through colony formation assay. Glycolysis indicators were measured using commercially available kits. Bioinformatics analysis was used to screen the target genes of NAT10. The interaction between NAT10 and PKM2 was analyzed via RNA immunoprecipitation (RIP) and dual luciferase reporter assays. NAT10 was increased in PTC tissues and cells. NAT10 inhibition suppressed cell proliferation and glycolysis in PTC cells and restrained tumor growth and tissue malignancy in xenograft tumor mice. Mechanistically, PKM2 has been identified as a downstream regulatory target influenced by NAT10-mediated ac⁴C acetylation. Additionally, rescue experiments indicated that the overexpression of PKM2 enhanced both cell viability and glycolysis activity in PTC cells. NAT10-mediated ac⁴C acetylation of PKM2 exacerbated the progression of PTC by promoting glycolysis, which might provide a new insight for PTC therapy.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148699630","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":"Stage-dependent expression and nuclear localization of EZH2 in endometrial carcinogenesis: evidence from cell lines and human tissues","authors":"Oya Korkmaz,&nbsp;Işıl Aydemir,&nbsp;Elgin Turkoz Uluer,&nbsp;Muzaffer Sancı,&nbsp;Gulden Diniz,&nbsp;Sevil Sayhan,&nbsp;Sevinç İnan","doi":"10.1007/s10735-026-10930-z","DOIUrl":"10.1007/s10735-026-10930-z","url":null,"abstract":"<div><p>Enhancer of zeste homolog 2 (EZH2) is a key epigenetic regulator implicated in tumor progression; however, its expression pattern and subcellular localization across different stages of endometrial carcinogenesis remain incompletely characterized. This study evaluated EZH2 expression in two biologically distinct endometrial carcinoma cell lines (Ishikawa and MFE-319) and in archived human endometrial tissues representing proliferative and secretory endometrium, hyperplasia, and Type I and Type II endometrial carcinomas. Histopathological evaluation was performed using hematoxylin and eosin staining. EZH2 expression was assessed by immunocytochemistry and Western blot analysis in the cell lines and by immunohistochemistry in tissue specimens, while apoptosis was evaluated by TUNEL assay in tissue samples. MFE-319 cells demonstrated significantly higher EZH2 expression than Ishikawa cells (H-score: 352.9 ± 78.9 vs. 137.6 ± 31.5, <i>p</i> &lt; 0.0001), and Western blot analysis confirmed the same direction of change. Among tissue specimens, the highest EZH2 immunoreactivity was observed in Type II endometrial carcinoma (366.0 ± 63.7), with significantly higher expression than proliferative endometrium (231.5 ± 59.3), secretory endometrium (190.5 ± 52.4), and hyperplasia without atypia (261.0 ± 56.9), whereas no significant differences were detected among several intermediate histopathological groups. Nuclear localization of EZH2 became more prominent in atypical hyperplasia and carcinoma tissues. Apoptotic indices were significantly higher in both Type I and Type II carcinomas than in normal endometrium and hyperplasia groups, representing an association with increased EZH2 expression rather than evidence of a direct mechanistic relationship. These findings demonstrate that EZH2 expression differs across histopathological categories of endometrial lesions, with the highest expression observed in Type II endometrial carcinoma. The observed predominance of nuclear EZH2 in atypical hyperplasia and carcinoma further supports its association with aggressive tumor biology, although additional functional and clinicopathological studies are required to establish its clinical and biological significance.</p><h3>Graphical abstract</h3><p>Overview of EZH2 expression across different endometrial tissue groups and endometrial carcinoma cell lines. Increased EZH2 expression was observed in endometrial carcinoma tissues and MFE-319 cells compared with normal endometrium, hyperplasia, and Ishikawa cells, and was associated with an aggressive disease phenotype and increased apoptosis.</p><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":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683006","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":"Quercetin and hesperidin attenuate cyclophosphamide-induced renal injury in rats","authors":"Şemsi Gül Yılmaz Kocaman,&nbsp;Serkan Yılmaz,&nbsp;Aslı Uçar","doi":"10.1007/s10735-026-10933-w","DOIUrl":"10.1007/s10735-026-10933-w","url":null,"abstract":"<div><p>Cyclophosphamide (CP) is an effective chemotherapeutic agent whose clinical use is limited by nephrotoxicity associated with oxidative stress and inflammation. This study investigated the potential nephroprotective effects of quercetin (QUE) and hesperidin (HSP) against CP-induced renal injury in rats. Thirty-six male Wistar albino rats were randomly assigned to six groups (<i>n </i>= 6): Control, QUE, HSP, CP, QUE + CP, and HSP + CP. QUE and HSP were administered orally at a dose of 100 mg/kg/day for 15 days. CP (200 mg/kg) was administered intraperitoneally on the final day to induce nephrotoxicity. Renal function was assessed using serum biochemical parameters (urea, uric acid, creatinine, blood urea nitrogen [BUN], albumin, and total protein), oxidative stress was evaluated by measuring renal antioxidant enzyme activities (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], and glutathione S-transferase [GST]) together with malondialdehyde (MDA) levels, and histopathological alterations were examined using hematoxylin–eosin staining. CP administration significantly increased serum urea, uric acid, creatinine, blood urea nitrogen, and total protein levels (all <i>p</i> &lt; 0.05). It also increased renal MDA levels (<i>p</i> &lt; 0.001) while reducing SOD (<i>p</i> &lt; 0.05), CAT (<i>p</i> &lt; 0.05), GPx (<i>p</i> &lt; 0.001), and GST (<i>p</i> &lt; 0.001) activities, accompanied by marked histopathological damage characterized by glomerular degeneration, tubular injury, hemorrhage, and inflammatory cell infiltration. Pretreatment with QUE or HSP significantly attenuated these alterations (all <i>p</i> &lt; 0.05). Both flavonoids improved renal biochemical parameters, restored antioxidant defense mechanisms, reduced MDA levels, and ameliorated histopathological alterations compared with the CP group. Although QUE showed numerically greater improvements across several outcomes, direct statistical superiority over HSP was not demonstrated. QUE and HSP exert protective effects against CP-induced nephrotoxicity by reducing oxidative damage and preserving renal tissue integrity. These findings suggest that flavonoid-based adjunctive interventions may represent a promising strategy for reducing chemotherapy-associated renal injury and warrant further mechanistic and translational investigation.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683013","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":"Arginase 1 as a candidate immune-metabolic biomarker in lumbar disc herniation: integrated bioinformatics, experimental validation, and clinical evidence","authors":"Qifeng Yao,&nbsp;Wei Shang,&nbsp;Mengdi Hu,&nbsp;Xue Wei,&nbsp;Wenjing Chang","doi":"10.1007/s10735-026-10932-x","DOIUrl":"10.1007/s10735-026-10932-x","url":null,"abstract":"<div><p>This study aimed to identify a candidate immune-related biomarker for lumbar disc herniation (LDH) and examine the functional relevance of ARG1 in intervertebral disc degeneration. Bioinformatics analysis was performed using the GSE146904 transcriptomic dataset to identify differentially expressed genes (DEGs) and determine the core target. A puncture-induced rat disc degeneration model was then established, followed by in vivo ARG1 gain- and loss-of-function interventions. In vitro assays were used to evaluate the effects of ARG1 on chondrocyte biological behavior, extracellular matrix metabolism, inflammatory responses, and arginine metabolism. In addition, 57 patients with LDH and 68 healthy controls were retrospectively enrolled to assess the diagnostic value of serum ARG1. After multidimensional screening of the high-effect candidate DEGs, ARG1 was the only gene that met the prespecified immune-process, immune-pathway, and skeletal-system annotation criteria and was therefore prioritized for experimental validation. ARG1 was expressed at a low level in degenerated intervertebral disc tissues. ARG1 up-regulation attenuated puncture-induced disc injury and pain sensitization, promoted chondrocyte proliferation, inhibited apoptosis, increased SOX9 and COL2A1 expression, and reduced MMP13 and ADAMTS5 expression. Clinical testing showed that serum ARG1 levels were reduced in patients with LDH and were negatively correlated with Pfirrmann grade and VAS pain score. The area under the curve of serum ARG1 for distinguishing patients with LDH from healthy controls was 0.818. ARG1 was associated with attenuation of puncture-induced disc injury and early degenerative changes and may serve as a candidate auxiliary serum biomarker for LDH assessment and a potential target for future studies of immune-metabolic regulation.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682952","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 role of the HB-EGF-regulated EGFR-mitophagy axis in maintaining cartilage homeostasis and osteoarthritis","authors":"JunHua Wang,&nbsp;ChiShou Mo,&nbsp;Qiang Wang,&nbsp;Jia Qin,&nbsp;Yong Li,&nbsp;WuXun Peng","doi":"10.1007/s10735-026-10916-x","DOIUrl":"10.1007/s10735-026-10916-x","url":null,"abstract":"<div><p>This study investigates the mechanism by which heparin-binding epidermal growth factor (HB-EGF) maintains cartilage homeostasis in osteoarthritis (OA) through the epidermal growth factor receptor (EGFR)–mitochondrial autophagy axis. Given the challenges in OA treatment and the critical role of impaired mitochondrial autophagy in disease progression, this research first identified key regulators using transcriptomic data from human OA cartilage and GEO databases. An in vitro OA model was established via IL-1β induction in chondrocytes, through which HB-EGF was found to reverse the IL-1β-induced metabolic imbalance by downregulating catabolic markers (Mmp13, Adamts5) and upregulating anabolic markers (Acan, Col2a1). Further analysis revealed that HB-EGF enhanced mitophagy, as indicated by increased levels of Pink1, Parkin, and Lc3-II alongside decreased P62. These protective effects were attenuated by the mitophagy inhibitor Mdivi-1, confirming the dependence on this pathway. In conclusion, HB-EGF activates EGFR signaling to promote PINK1/ PARKIN-mediated mitophagy, which facilitates the clearance of damaged mitochondria and improves mitochondrial function, thereby restoring chondrocyte metabolic balance and delaying OA progression, suggesting the EGFR–mitophagy axis as a potential therapeutic target for OA.</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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668022","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":"Olive leaf extract attenuates acrylamide-induced reproductive toxicity through reduced oxidative DNA damage and apoptosis associated with 8-OHdG and Caspase-3 in rats","authors":"Nevzat Saat,&nbsp;Emrah Hicazi Aksu,&nbsp;Musa Tatar,&nbsp;Buse Öztürk,&nbsp;Kıymet Kübra Tüfekçi","doi":"10.1007/s10735-026-10923-y","DOIUrl":"10.1007/s10735-026-10923-y","url":null,"abstract":"<div><p>Acrylamide (ACR) is a toxic compound formed during high-temperature processing of carbohydrate-rich foods and is known to exert reproductive toxicity through oxidative stress and apoptosis. Olive leaf extract (OLE) possesses potent antioxidant and anti-inflammatory properties, primarily attributable to its polyphenolic constituents, particularly oleuropein. This study aimed to investigate the protective effects of OLE against ACR-induced reproductive toxicity in male and female rats. Forty female and forty male Sprague-Dawley rats were randomly assigned to four groups (n = 10 per sex per group): control, ACR (5 mg/kg/day), OLE (250 mg/kg/day), and ACR + OLE, administered by oral gavage for 21 days. Body weight, estrous cycle characteristics, spermatological parameters (motility, viability, morphology, and density), histopathological alterations in ovary, uterus, and testis, and immunohistochemical expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and Caspase-3 were evaluated. ACR exposure significantly reduced sperm motility and increased the percentages of dead and morphologically abnormal spermatozoa compared with the control group, whereas sperm density was unaffected. Histopathological examination revealed pronounced degenerative changes in ovarian, uterine, and testicular tissues in the ACR group, including vascular disruption, epithelial degeneration, and extensive vacuolization. ACR significantly increased 8-OHdG and Caspase-3 expression in reproductive tissues (<i>p</i> &lt; 0.01), indicating enhanced oxidative DNA damage and apoptosis. Co-administration of OLE markedly ameliorated these adverse effects, though testicular Caspase-3 levels were only partially restored, suggesting a tissue-specific limitation of the protective effect at the dose employed. These findings indicate that OLE exerts a significant cytoprotective effect through its antioxidant and anti-apoptotic properties, with the extent of protection varying across tissue types. Further studies incorporating a broader range of parameters and exposure conditions are needed to establish more robust evidence for the protective potential of OLE.</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":"148667999","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}