Journal of Molecular Histology最新文献

{"title":"BRCC3 promotes progression and immune evasion in non-small cell lung cancer through regulation of PD-L1 and B7-H3","authors":"Kai Liu,&nbsp;Qun Shen,&nbsp;Chaochao Wei,&nbsp;Chong Meng,&nbsp;Anyan Zhou,&nbsp;Lirong Liu,&nbsp;Yongxing Chen","doi":"10.1007/s10735-026-10880-6","DOIUrl":"10.1007/s10735-026-10880-6","url":null,"abstract":"<div><p>While elevated levels of the deubiquitinating enzyme BRCC3 have been documented in a range of cancers, its capacity to influence immune checkpoint expression or enable tumor immune evasion in non-small cell lung cancer (NSCLC) remains uncharacterized. BRCC3 expression and clinical relevance were assessed using TIMER2, UALCAN, and Kaplan-Meier Plotter databases, and validated in NSCLC tissues and cell lines. Functional impacts were evaluated through proliferation, migration, invasion, and syngeneic tumor models. CD8+ T cell cytotoxicity and cytokine secretion were measured in co-culture systems. Protein interactions and ubiquitination of PD-L1/B7-H3 were analyzed by co-immunoprecipitation and western blot. Rescue experiments with PD-L1 or B7-H3 overexpression were performed. BRCC3 upregulation correlated with advanced NSCLC, nodal spread, and worse survival. BRCC3 knockdown suppressed malignant phenotypes and tumor growth, and shifted the immune response toward a proinflammatory phenotype, accompanied by enhanced CD8 + T cell killing. Mechanistically, BRCC3 directly interacted with PD-L1 and B7-H3, enhancing their protein levels via deubiquitination. Overexpression of either PD-L1 or B7-H3 partially restored tumor growth and attenuated T cell activation induced by BRCC3 silencing. BRCC3 drives immune escape in NSCLC by deubiquitination-mediated upregulation of PD-L1 and B7-H3, thereby dampening anti-tumor immunity. Targeting BRCC3 may represent a potential therapeutic strategy to overcome resistance to current immunotherapies.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374140","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":"Zingerone supplementation stimulates germ cell proliferation, inhibits apoptosis and modulates autophagy and ferroptosis in the mice testis","authors":"Miti Jerang,&nbsp;Guruswami Gurusubramanian,&nbsp;Vikas Kumar Roy","doi":"10.1007/s10735-026-10881-5","DOIUrl":"10.1007/s10735-026-10881-5","url":null,"abstract":"<div><p>The aim of this study was to evaluate the effects of zingerone supplementation on testicular spermatogenesis by analyzing germ cell proliferation, cell survival, and antioxidant status in the testis of mice. Zingerone was administered orally in three doses: 10, 25, and 50 mg/kg for 35 days. An in vitro study was also performed on the testicular explants treated with 5 and 25 mg/mL dose of zingerone. The present study revealed that zingerone treatment significantly increased the sperm concentration and cell proliferation. Furthermore, the expression of active caspase-3, transferrin receptor, GPx4 and the levels of MDA and SOD were found to be decreasing, while the levels of catalase and the expression of Bcl-2, LAMP2, AR, ER-β were significantly increasing in the zingerone treated group. Thus, these findings suggest that zingerone supplementation might promote spermatogenesis by stimulating germ cell proliferation, cell survival, and, inhibiting apoptosis and oxidative stress. Furthermore, modulation of autophagy and ferroptosis might be involved in the recycling of cellular component due to elevated proliferation and survival of cell in the mice testis. However, further investigation would be required to unravel the zingerone mediated exact role of autophagy and ferroptosis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366274","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 protective role of vitamin E against omeprazole-induced liver alterations in male wistar rats (Rattus norvegicus)","authors":"Zozan Abdullah Ibrahim,&nbsp;Intissar Numman Waheed,&nbsp;Yahya Ahmed Mohammed","doi":"10.1007/s10735-026-10872-6","DOIUrl":"10.1007/s10735-026-10872-6","url":null,"abstract":"<div><p>Due to the limited information available regarding the effect of Omeprazole (OM) on rats’ liver function. This study aimed to elucidate the impact on liver morphology, hepatic enzymes, liver weight, and electrolytes in male Wistar rats. Fifty rats were randomly allocated into five groups (n = 10): control, OM (5 mg/kg/day), OM + Vit. E (5 mg/kg/day each), Vit. E alone (5 mg/kg/day each), and a recovery group (5 mg/kg/day each), for 28 days. Biochemical analysis evaluated hepatic enzymes (ALP, AST, ALT) and serum electrolytes. Histological examination of hepatic tissues was performed using H&amp;E, PAS, and Masson’s Trichrome staining. OM significantly increased ALP (177.56 U/L), AST (145.2 U/L), and ALT (47.8 U/L) compared with controls (<i>P</i> ≤ 0.05). Co-administration of Vit E effectively attenuated these elevations, while the recovery group demonstrated only partial normalization. OM also significantly reduced liver weight, altered liver shape, and disrupted Cl⁻, Ca²⁺, and K⁺ homeostasis, though Na⁺ levels remained unaffected. On a histological basis, blood vessels and sinusoids were dilated with blood. around the central vein, increased collagen deposition, and decreased glycogen granules in hepatocytes were observed; OM induced notable parenchymal changes, whereas Vit. E preserved near-normal hepatic architecture. The hepatic somatic index showed no significant variation across groups (<i>P</i> &gt; 0.05). The liver was harmed by omeprazole, and vitamin E prevented the effects.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366324","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":"Vitamin D3 promotes regression of endometrial implants comparable to buserelin in a rat model of endometriosis","authors":"Ayşe Köylü,&nbsp;Suna Ömeroğlu,&nbsp;Saadet Özen Akarca Dizakar,&nbsp;Mürşide Ayşe Demirel,&nbsp;Zeynep Yığman,&nbsp;Tuncay Peker","doi":"10.1007/s10735-026-10879-z","DOIUrl":"10.1007/s10735-026-10879-z","url":null,"abstract":"<div><p>Buserelin, a gonadotropin-releasing hormone agonist, reduces gonadotropin and estrogen levels and is commonly used to alleviate the symptoms of endometriosis. Vitamin D3 has been reported to exhibit anti-inflammatory and pro-apoptotic properties, which may contribute to the regression of endometrial lesions. We aimed to investigate the effects of vitamin D3 on the regression and recurrence prevention of endometrial implant sites through the induction of apoptosis comparable to buserelin acetate in an experimental rat endometriosis model. Endometrial implant size and adhesion scores were evaluated following treatment. Microscopic analyses were performed using hematoxylin–eosin-stained preparations. Apoptotic activity was assessed by TUNEL assay, along with the expression of Bcl-2 and Bax antibodies. Untreated rats exhibited larger implant volumes, severe glandular and stromal alterations, and pronounced inflammatory infiltration. In contrast, vitamin D3 and buserelin treatments reduced implant size and adhesion scores. The vitamin D3–treated group demonstrated a high density of TUNEL-positive cells. Increased expression of Bcl-2 protein was found in untreated groups whereas, increased expression of Bax protein was found in both treated groups. In conclusion, vitamin D₃ may have contributed to the regression of endometrial implants, possibly through mechanisms involving apoptotic pathways. Further studies are needed to clarify its role and to evaluate its potential clinical relevance.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358844","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":"Stigmasterol glucoside attenuates RANKL-induced osteoclastogenesis and bone resorption by suppressing MAPK and STAT3 signaling pathways: an integrative pharmacological study","authors":"Yiwei Jiang,&nbsp;Zhiyu Jin,&nbsp;Kui Guo,&nbsp;Maihuan Wang,&nbsp;Zhen Cao","doi":"10.1007/s10735-026-10877-1","DOIUrl":"10.1007/s10735-026-10877-1","url":null,"abstract":"<div><p>Osteoporosis is a metabolic bone disease characterized by excessive osteoclast-mediated bone resorption. Stigmasterol glucoside (SG), a glycosylated phytosterol with enhanced hydrophilicity, has shown potential anti-inflammatory activities, but its role in bone metabolism remains largely unexplored. This study aimed to investigate the effects and underlying mechanisms of SG on osteoclastogenesis. An integrative pharmacological strategy was employed, combining network pharmacology and molecular docking to predict potential targets. These predictions were validated using primary bone marrow-derived macrophages (BMMs). Osteoclast differentiation and function were assessed via TRAcP staining, F-actin ring immunofluorescence, and bone resorption pit assays. Molecular mechanisms were elucidated using RT-qPCR, Western blotting, and luciferase reporter assays. Network pharmacology and molecular docking identified MAPK and STAT3 signaling axes as the core targets of SG, with high binding affinities for MAP2K1, JAK2, and STAT3. In vitro experiments demonstrated that SG dose-dependently inhibited RANKL-induced osteoclast differentiation and bone resorptive activity without cytotoxicity. At the molecular level, SG suppressed the expression and transcriptional activity of the master regulators NFATc1 and c-Fos, leading to the downregulation of essential functional markers. Further mechanistic investigations revealed that these inhibitory effects were driven by the attenuation of early-stage phosphorylation in the MAPK (p38, JNK, and ERK) and STAT3 signaling axes. SG effectively suppresses osteoclastogenesis and resorptive function by simultaneously intercepting the MAPK and STAT3/NFATc1 signaling axes. These findings provide experimental evidence that SG is a promising natural pharmacological candidate for the treatment of osteoporosis and bone loss-related disorders.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343653","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":"Downregulation of fibroblast growth factor 7 impairs endometrial receptivity and decidualisation via extracellular signal-regulated kinase and C-Jun N-Terminal kinase pathways, contributing to recurrent spontaneous abortion","authors":"Yaqian Lu,&nbsp;Ruiqing Tong,&nbsp;Nan Wang,&nbsp;Weiqin Zhou,&nbsp;Fei Xia,&nbsp;Yanyu Zhong","doi":"10.1007/s10735-026-10842-y","DOIUrl":"10.1007/s10735-026-10842-y","url":null,"abstract":"<div><p>Recurrent spontaneous abortion (RSA) presents a significant reproductive hurdle, impacting 2–5% of women globally. Despite identification of various aetiological factors, approximately half of all cases remain unexplained. In this study, we delve into the critical role of fibroblast growth factor 7 (FGF7) in RSA, particularly in the realm of impaired endometrial receptivity. Leveraging bioinformatic analyses and experimental approaches involving decidual tissues, as well as human endometrial stromal cells (HESCs) and Ishikawa cells culture, we probe into the regulatory patterns of FGF7 and its impact on essential cellular processes pivotal for endometrial function. Our results reveal a correlation between FGF7 downregulation (decreased by approximately 50%, <i>p</i> &lt; 0.05) and disruptions in HESC proliferation and apoptosis, pivotal aspects of RSA pathogenesis. Notably, we delineate the disruptions in decidualisation processes crucial for successful implantation and pregnancy maintenance under FGF7 suppression. These insights deepen our comprehension of the molecular dynamics underlying impaired endometrial receptivity in RSA, potentially guiding the development of targeted therapies. Our study underscores the therapeutic potential of FGF7 modulation, backed by evidence from related studies on its benefits in tissue regeneration and oxidative stress mitigation.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343670","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":"miR-524-5p suppresses cervical cancer progression through targeting the LRP6/Wnt/β-catenin axis","authors":"Min Yuan,&nbsp;Jialin Li,&nbsp;Yingying Huang,&nbsp;Yufei Liang","doi":"10.1007/s10735-026-10855-7","DOIUrl":"10.1007/s10735-026-10855-7","url":null,"abstract":"<div><p>As a leading gynecological malignancy worldwide, cervical cancer represents a major threat to female health. Further research is essential to elucidate its pathogenic mechanisms and develop effective therapeutic interventions. The objective is to examine the correlation between miR-524-5p and both the diagnostic and prognostic aspects of cervical cancer, while also elucidating its underlying mechanisms. Quantitative detection of miR-524-5p and LRP6 levels were performed via RT-qPCR, ELISA and Western blot. The diagnostic and prognostic potential of serum miR-524-5p in cervical cancer was assessed using ROC, Kaplan–Meier curves, and multivariate Cox regression. Bioinformatic analysis coupled with dual-luciferase reporter assays validated the direct targeting of LRP6 by miR-524-5p. The CCK-8 and Transwell assays were employed to assess the biological behavior of cervical cancer cells. Serum miR-524-5p was downregulated in cervical cancer compared to normal controls, and it had higher diagnostic value and worse survival outcome. LRP6 was identified as a direct target of miR-524-5p and demonstrated negative regulation by it. The upregulation of miR-524-5p was found to exert a marked inhibitory effect on the proliferative capacity of CaSki and HeLa cells, as well as their migratory and invasive potential. Additionally, the Wnt/β-catenin pathway was inhibited. However, co-transfection of miR-524-5p and LRP6 overexpression partially reversed the repressive effect of miR-524-5p mimic on cell biological functions. miR-524-5p demonstrates predictive potential for early detection and prognosis in cervical cancer. Functionally, it affects the Wnt/β-catenin pathway by directly targeting LRP6, thereby inhibiting malignant cell behavior.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343712","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":"Ceramide-PKCζ signaling axis mediates burn-enhanced ectopic calcification during Achilles tendon healing","authors":"Ye Ding,&nbsp;Xin Jiang,&nbsp;Xiangming Ye","doi":"10.1007/s10735-026-10878-0","DOIUrl":"10.1007/s10735-026-10878-0","url":null,"abstract":"<div><p>Burn injury frequently leads to heterotopic ossification (HO) during tendon healing, but the underlying molecular mechanisms remain poorly understood. This study investigated the role of the ceramide–protein kinase C zeta (PKCζ) signaling axis in burn-enhanced ectopic calcification during Achilles tendon healing and evaluated the therapeutic potential of PKCζ inhibition. A combined burn injury and Achilles tendon puncture model was established in C57BL/6 mice, with sham control, tendon puncture, and burn combined tendon puncture groups. Micro-computed tomography analysis revealed significantly increased bone volume at the calcaneal insertion site in burn-injured animals. Both total PKCζ and phosphorylated PKCζ expression were markedly elevated in the burn combined injury group. In vitro, C2-ceramide treatment significantly enhanced PKCζ activation and promoted osteogenic differentiation of Achilles tendon stem cells, as evidenced by increased alkaline phosphatase activity, calcium deposition, and upregulation of runt-related transcription factor 2 and osteopontin expression. Co-treatment with 2-acetyl-1,3-cyclopentanedione (ACPD), an atypical PKC (aPKC) inhibitor, effectively blocked ceramide-induced PKCζ activation and osteogenic differentiation. In vivo administration of the aPKC inhibitor significantly reduced ectopic calcification (bone volume on micro-CT) and decreased expression of PKCζ and osteogenic markers. These findings suggest that burn injury enhances ectopic calcification during Achilles tendon healing through activation of the ceramide–PKCζ signaling pathway, promoting aberrant osteogenic differentiation of tendon stem cells. Atypical PKC inhibition represents a potential therapeutic strategy for preventing burn-associated ectopic calcification.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343661","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":"Alpha-2-macroglobulin attenuates glucocorticoid-induced osteonecrosis of the femoral head by enhancing osteogenesis and antioxidant defense via the Akt/Nrf2 signaling pathway","authors":"Qingjian He,&nbsp;Xin Zheng,&nbsp;Boyun Huang,&nbsp;Xianjie Xie,&nbsp;Manying Lin,&nbsp;Pengcheng Lin,&nbsp;He Chen,&nbsp;Jinghui Li","doi":"10.1007/s10735-026-10861-9","DOIUrl":"10.1007/s10735-026-10861-9","url":null,"abstract":"<div><p>Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is featured by oxidative stress and impaired bone regeneration. Alpha-2-Macroglobulin (α-2 M) was reported to possess cytoprotective and anti-inflammatory properties, and have shown its role in alleviating GIONFH. nuclear factor erythroid 2-related factor 2 (Nrf2) was proved to mediate oxidative stress in GIONFH. We aimed to investigate whether α-2 M attenuates GIONFH by exerting a dual osteogenic and antioxidant effect through the Akt/Nrf2 signaling pathway. We induced GIONFH model in rats and injected α-2 M and Nrf2 inhibitor subsequently. Micro-CT and histology revealed that α-2 M treatment prevented methylprednisolone (MPS)-induced bone loss, preserving trabecular structure and reducing empty lacunae. α-2 M reversed the MPS-mediated suppression of Akt-Nrf2 pathway, upregulating the expression of heme oxygenase-1 (HO-1) and osteogenic markers. The Nrf2 inhibitor ML385 negated these benefits, confirming that α-2 M mitigates GIONFH by upregulating osteogenesis and reducing oxidative stress through the Akt/Nrf2 axis. The results demonstrated that α-2 M is a promising target for managing GIONFH.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343618","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":"Targeting metabolic reprogramming in HPV-associated oral squamous cell carcinoma: current advances, challenges, and clinical prospects","authors":"Anjali Kumari,&nbsp;Vivek Shit,&nbsp;Mohammad Sajid,&nbsp;Mausumi Bharadwaj","doi":"10.1007/s10735-026-10863-7","DOIUrl":"10.1007/s10735-026-10863-7","url":null,"abstract":"<div><p>Human papillomavirus (HPV)-associated oral squamous cell carcinoma (OSCC) is increasingly investigated as a potentially distinct subset of head and neck cancers with unique molecular features. In contrast to HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), which demonstrates a well-established favorable prognosis, the prognostic significance of HPV in OSCC remains inconsistent and continues to be actively investigated. HPV oncoproteins E6 and E7 are known to induce metabolic rewiring in HPV-driven cancers and are suggested to play a similar role in OSCC, influencing glycolysis, mitochondrial function, and nutrient utilization to support tumor proliferation, survival, and immune evasion. This metabolic reprogramming also contributes to therapeutic resistance, potentially reducing the efficacy of chemoradiation and immunotherapy in subsets of patients. This review synthesizes current evidence from molecular, metabolic, preclinical, and translational studies examining HPV-driven metabolic alterations, incorporating recent findings from both OSCC and broader HPV-associated head and neck cancer (HNSCC) models. It evaluates therapeutic strategies targeting glycolysis, mitochondrial metabolism, metabolic regulators, and drug repurposing approaches. Emerging studies suggest that glycolytic inhibition, mitochondrial modulation, and repurposed agents such as metformin and dichloroacetate (DCA) may suppress tumor growth and enhance therapeutic sensitivity in HPV-positive models. Metabolic crosstalk between tumor cells, stromal components, and immune infiltrates highlights the potential of metabolic targeting to influence both cancer cell survival and antitumor immunity. However, several challenges remain, including tumor metabolic heterogeneity, systemic toxicity of metabolic inhibitors, lack of predictive biomarkers, translational gaps between preclinical models and clinical outcomes, and limited HPV-positive OSCC-specific clinical data. Targeting metabolic reprogramming, therefore, may represent a promising, though still evolving, therapeutic strategy. Advancing this approach may require a biomarker-guided patient stratification and rational combination strategies. Overall, this review provides an integrated overview of HPV-driven metabolic alterations and current therapeutic progress while emphasizing the need for clinically grounded and mechanistically informed translational research.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343637","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}