Molecular medicine reports最新文献

{"title":"Lactylation and exercise: A molecular link to disease alleviation (Review).","authors":"Jian Wang, Lei Wu","doi":"10.3892/mmr.2026.14035","DOIUrl":"10.3892/mmr.2026.14035","url":null,"abstract":"<p><p>Regular physical activity improves physical capacity and overall health by enhancing cardiopulmonary function and muscle strength, reducing stress, and improving psychological well‑being and quality of life. Despite these known benefits, the molecular mechanisms that underlie these effects remain incompletely understood. Lactylation, a modification wherein lactate molecules form ester bonds with proteins, induces functional changes in these proteins. Evidence indicates that exercise can regulate lactylation, which, in turn, affects intracellular signaling pathways and metabolic processes. This modulation plays a role in promoting health and facilitating disease alleviation. The present review offers an extensive review of the mechanisms through which exercise influences lactylation and discusses the potential clinical applications of lactylation in the prevention and treatment of exercise‑related diseases.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"34 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical‑immune feedback regulation in distraction osteogenesis: From mechanotransduction to immune microenvironment remodeling (Review).","authors":"Xian Wang, Yuetong Wang, Shixi He, Cheng Ma, Zhengzhong He, Xuanping Huang","doi":"10.3892/mmr.2026.14038","DOIUrl":"https://doi.org/10.3892/mmr.2026.14038","url":null,"abstract":"<p><p>Distraction osteogenesis (DO) is a well‑established regenerative technique in which controlled tensile forces stimulate <i>de novo</i> bone formation between gradually separated bone segments. Although traditionally interpreted as a mechanically driven process, accumulating evidence indicates that successful DO depends on the coordinated regulation of mechanotransduction, immune microenvironment remodeling, angiogenesis, osteogenesis and subsequent bone remodeling. The present review summarizes current advances in the biological mechanisms of DO and proposes an integrative mechanical‑immune feedback framework to explain how mechanical cues and immune responses interact throughout the regenerative process. During the latency phase, osteotomy‑induced sterile injury initiates hematoma formation, inflammatory cell recruitment and early cytokine release, thereby establishing a preparatory microenvironment for tissue repair. During the distraction phase, various mechanical parameters, such as rate, rhythm, frequency and local tissue stiffness, are sensed by mechanosensitive structures, including integrin‑focal adhesion complexes, primary cilia, mechanosensitive ion channels and cytoskeleton‑associated nuclear signaling systems. These signals in turn activate downstream signaling pathways, including MAPK, Wnt/β‑catenin, bone morphogenetic protein‑Smad, Akt/mTOR/NF‑κB and Ras homolog family member A/Yes‑associated protein/transcriptional co‑activator with PDZ‑binding motif, which collectively promote osteogenic differentiation, matrix deposition and vascular remodeling. In parallel, mechanical stimulation can reshape the local immune milieu by regulating macrophage polarization, cytokine balance, osteoclast‑osteoblast coupling and angiogenesis‑osteogenesis interactions. During consolidation, immune‑mediated remodeling, extracellular matrix maturation and coordinated bone formation and resorption contribute to mineralization and structural integration of the regenerate. Based on these phase‑specific events, DO can be conceptualized as a dynamic process involving mechanical input, mechanotransduction, immune modulation, vascularized osteogenesis and remodeling feedback. This mechanical‑immune perspective provides a structured basis for understanding heterogeneity in DO outcomes across anatomical sites, age groups and pathological conditions, which may inform future optimization of distraction protocols, biomarker‑guided monitoring and targeted immunomodulatory strategies.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"34 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota in patients receiving dialysis: Mechanisms, complications and the road to personalized microbiome‑based care (Review).","authors":"Chenxia Jin, Yanping Wang","doi":"10.3892/mmr.2026.14044","DOIUrl":"https://doi.org/10.3892/mmr.2026.14044","url":null,"abstract":"<p><p>Gut dysbiosis is increasingly recognized as a potential contributor to poor outcomes in patients receiving dialysis, yet its mechanistic complexity and therapeutic implications remain incompletely understood in clinical practice. The uremic environment, dietary restrictions, polypharmacy and dialysis modality‑specific factors collectively reshape the gut microbial ecology, promoting the overproduction of deleterious metabolites such as indoxyl sulfate, p‑cresyl sulfate and trimethylamine N‑oxide while depleting protective short‑chain fatty acids. These alterations compromise intestinal barrier integrity, fuel systemic inflammation through endotoxemia and NOD‑like receptor family pyrin domain containing 3 inflammasome activation and have been associated with cardiovascular disease, immune dysfunction, peritonitis, protein‑energy wasting and cognitive impairment. Although probiotic, prebiotic, synbiotic and dietary interventions show promise, heterogeneous responses across trials underscore the inadequacy of one‑size‑fits‑all strategies. Multi‑omics profiling has revealed substantial interindividual variability in microbial composition and metabolic capacity, providing a rationale for personalized approaches. The present review synthesizes current evidence on the mechanisms underlying dysbiosis and complications in patients receiving dialysis and proposes a roadmap toward personalized microbiome‑based care to improve clinical outcomes.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"34 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ΔNp63α‑mediated regulation of tumor‑associated genes and pathways in hepatocellular carcinoma progression.","authors":"Xiaowen Lin, Anghui Peng, Min Zhang, Xinyang Yu","doi":"10.3892/mmr.2026.14040","DOIUrl":"https://doi.org/10.3892/mmr.2026.14040","url":null,"abstract":"<p><p>ΔNp63α is key in cellular development and epithelial tumors; however, its role in hepatocellular carcinoma (HCC) remains unclear. In the present study, the oncogenic role and molecular functions of ΔNp63α in HCC were investigated. Analysis of The Cancer Genome Atlas revealed an association between p63 expression and patient survival. ΔNp63α overexpression in SNU387 cells notably enhanced cell proliferation and migration, supporting its role in promoting aggressive HCC phenotypes. Transcriptome analysis revealed extensive ΔNp63α‑associated transcriptional changes, with differentially expressed genes enriched in tumor‑associated processes, including 'Wnt signaling pathway', 'Notch signaling pathway', 'cell adhesion molecules' and 'extracellular matrix organization'. Chromatin immunoprecipitation sequencing revealed widespread ΔNp63α binding in promoter‑proximal and ‑distal regulatory regions, suggesting potential involvement in transcriptional regulation through both proximal and distal genomic elements. ΔNp63α upregulation was also associated with increased CCCTC‑binding factor (CTCF) occupancy near the promoters of tumor‑associated genes and these gained CTCF sites were enriched for p63 motifs. Collectively, the present findings identified ΔNp63α as an oncogenic regulator of HCC and suggest that it may regulate tumor‑associated gene programs through coordinated proximal and distal chromatin regulatory mechanisms.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"34 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycyrrhizic acid attenuates corneal inflammation and pathological angiogenesis through FAK/PI3K/AKT signaling.","authors":"Jinjin Yu, Huiheng Qu, Yinming Fang, Weicheng Xu, Nannan Ding, Jie Ji, Nan Wang, Wei Shi","doi":"10.3892/mmr.2026.14046","DOIUrl":"https://doi.org/10.3892/mmr.2026.14046","url":null,"abstract":"<p><p>Corneal alkali burns lead to severe inflammation and corneal neovascularization (CNV), both of which are major causes of visual impairment. The suppression of inflammation, promotion of epithelial repair and inhibition of CNV formation are promising therapeutic strategies for restoring corneal transparency. This study investigated the effects and underlying mechanisms of glycyrrhizic acid (GA) on inflammation, epithelial wound healing and CNV in a murine model of alkali burn. GA markedly alleviated corneal opacity, enhanced epithelial wound closure and reduced CNV formation in alkali‑burned mice. Mechanistically, GA markedly downregulated tumor necrosis factor‑α, interleukin (IL)‑6, IL‑17 and vascular endothelial growth factor A (VEGF‑A) expression in injured corneas. In human umbilical vein endothelial cells, GA attenuated VEGF‑A‑induced proliferation and angiogenic activity. In human corneal epithelial cells, GA activated the focal adhesion kinase (FAK)/PI3K/AKT signaling pathway, upregulated Bcl‑2 and cyclin D1 expression and suppressed Bax and caspase‑3 expression, thereby promoting cell proliferation and reducing apoptosis. Overall, GA exerts protective effects against alkali burn‑induced corneal injury by suppressing inflammation and neovascularization while promoting epithelial repair through activation of the FAK/PI3K/AKT signaling pathway.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"34 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Retracted] (‑)‑Epicatechin protects against myocardial ischemia‑induced cardiac injury via activation of the PTEN/PI3K/AKT pathway.","authors":"Jia-Wen Li, Xiao-Yun Wang, Xin Zhang, Lei Gao, Li-Feng Wang, Xin-Hua Yin","doi":"10.3892/mmr.2026.14036","DOIUrl":"10.3892/mmr.2026.14036","url":null,"abstract":"<p><p>Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the control GAPDH western blot data featured in Fig. 4A on p. 8305 had already appeared previously in an article in the journal <i>Cellular Physiology and Biochemistry</i> in a different experimental context written by different authors (albeit one of the research institutes was held in common between the papers). In addition, after assessing the data in this paper independently in the Editorial Office, it also came to light that two pairs of data panels featured respectively in Fig. 2A (showing H&E‑stained histological sections) and Fig. 2B (showing the results of TUNEL assays) contained overlapping sections of data where different experimental conditions were reported, suggesting that these data panels were derived from the same original sources. Owing to the fact that the contentious data in the above article had already been published prior to its submission to <i>Molecular Medicine Reports</i>, the Editor has decided that this paper should be retracted from the Journal. Upon contacting the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 8300‑8308, 2018; DOI: 10.3892/mmr.2018.8870].</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"34 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress in synergistic multimechanism of nanomaterial-mediated neuroinflammatory therapy (Review).","authors":"Heng Wang, Pei Yang, Wantao Liu","doi":"10.3892/mmr.2026.14037","DOIUrl":"https://doi.org/10.3892/mmr.2026.14037","url":null,"abstract":"<p><p>Neuroinflammation treatment faces notable challenges such as low blood‑brain barrier (BBB) penetration, poor targeting and systemic toxicity, limiting traditional therapies due to inefficient drug delivery and bioavailability. Nanomaterials have innovatively reshaped this paradigm through multiple mechanisms. The present review elaborates core strategies in immunocyte phenotype regulation, oxidative stress intervention and targeted delivery, focusing on modulating microglia transition from pro‑inflammatory to repair states, constructing systems for reactive oxygen species regulation and developing biomimetic carriers for BBB penetration and lesion targeting. The present review highlights technical bottlenecks in long‑term biosafety evaluation, cross‑organ metabolic mechanism analysis and clinical translation standardization.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"34 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piezo1 knockdown alleviates high‑altitude cerebral edema by improving brain microvascular endothelial cell tight junctions via blocking the calcium influx‑mediated Calpain‑1 activity.","authors":"Taijian Cao, Zhicheng Xiang, Yangyang Zhao, Drolma Gomchok, Haifeng Ma, Shiwang Li, Dahai Cao, Chunqing Yang, Qiang Zhang","doi":"10.3892/mmr.2026.14042","DOIUrl":"https://doi.org/10.3892/mmr.2026.14042","url":null,"abstract":"<p><p>High‑altitude cerebral edema (HACE) is a life‑threatening complication of acute high‑altitude exposure, but effective treatment strategies remain limited. The influence of Piezo1 on the tight junctions of brain microvascular endothelial cells in HACE was examined to identify novel therapeutic interventions against HACE. A mouse model of HACE was established through exposure to a simulated high‑altitude hypobaric hypoxia environment. Brain water content, Evans Blue staining, magnetic resonance imaging, hematoxylin and eosin staining, FITC‑Dextran leakage assay and transmission electron microscopy were utilized to evaluate the impact of Piezo1 on HACE. A cell model of HACE was created by subjecting bEnd.3 cells to high fluid shear stress (HFSS) and hypoxic conditions. The effects of Piezo1 and Calpain‑1 on tight junction protein expression were assessed via western blot analysis. Mice with HACE exhibited increased brain water content, disrupted blood‑brain barrier integrity, enhanced microvascular permeability, hippocampal and cortical damage and reduced expression of VE‑cadherin, occludin, claudin‑5 and ZO‑1 proteins, alongside elevated Piezo1 and Calpain‑1 activity in brain microvascular endothelial cells. Silencing of Piezo1 alleviated these HACE symptoms. bEnd.3 cells subjected to HFSS and hypoxia showed increased intracellular Ca²⁺, along with heightened Calpain‑1 protein expression and activity, while levels of VE‑cadherin, occludin, claudin‑5 and ZO‑1 proteins were diminished. Both Piezo1 silencing and Calpain‑1 inhibition reversed these <i>in vitro</i> changes. Notably, Piezo1 silencing reduced Calpain‑1 activity without significantly altering Calpain‑1 protein levels. Piezo1 silencing may ameliorate HACE by enhancing tight junctions in brain microvascular endothelial cells through the suppression of calcium influx‑mediated Calpain‑1 activity. Thus, targeting Piezo1 expression may represent a promising therapeutic approach for HACE.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"34 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigallocatechin gallate and thermal cycling‑stimulation synergistically promote apoptosis in A549 cells via endoplasmic reticulum stress‑induced calcium ion dysregulation and oxidative stress.","authors":"Fang-Tzu Hsu, Hsu-Hsiang Liu, Yi Kung, Chieh-Jou Lin, Chih-Yu Chao","doi":"10.3892/mmr.2026.14043","DOIUrl":"https://doi.org/10.3892/mmr.2026.14043","url":null,"abstract":"<p><p>Non‑small cell lung cancer (NSCLC), as the predominant subtype of lung cancer, presents a considerable clinical challenge due to its high rates of recurrence and the significant adverse effects associated with conventional therapeutic modalities. In response to these challenges, the present study has explored the combined anticancer effects of epigallocatechin gallate (EGCG) together with thermal cycling‑stimulation (TCS). The findings obtained demonstrated that the combination of EGCG and TCS led to a synergistic decrease in the viability of A549 and NCI‑H460 NSCLC cells, whereas IMR‑90 normal lung fibroblasts exhibited minimal cytotoxic effects. Further investigations revealed that EGCG could mitigate the TCS‑induced upregulation of the heat shock proteins (HSPs) HSP70 and HSP105, whereas the expression levels of proteasome subunits were concurrently decreased. These alterations were accompanied by the disruption of proteostasis, and also by the activation of endoplasmic reticulum (ER) stress‑associated pathways. Furthermore, pharmacological inhibition studies suggested a mutual interplay between inositol 1,4,5‑trisphosphate receptor‑mediated ER Ca2+ release and an excessive production of reactive oxygen species, ultimately causing the cells to undergo mitochondrial apoptosis. In summary, the present study has shown that the combined treatment of EGCG and TCS reduces the required dosage of EGCG, while also attenuating TCS‑induced heat shock responses. Consequently, the present study offers a novel and promising <i>in vitro</i> proof‑of‑concept strategy for treating NSCLC.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"34 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the landscape of targeted therapies for renal cell carcinoma in the era of precision medicine (Review).","authors":"Hongguo Cui, Jingheng Song, Peisen Yang, Zhengchao Zhang, Yuanyuan Liu, Gang Zhang, Aimin Tian, Jizhong Che, Yangyang Liu, Hui Sun, Yankai Xu","doi":"10.3892/mmr.2026.14041","DOIUrl":"https://doi.org/10.3892/mmr.2026.14041","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy characterized by dysregulation of angiogenic signaling, immune evasion and epigenetic remodeling. Advances in molecular profiling have redefined RCC as a pathway‑driven disease, enabling the development of targeted therapies and immune checkpoint inhibitors (ICIs) that have notably improved clinical outcomes. The present review evaluated current evidence on the molecular basis and therapeutic landscape of RCC, with emphasis on von Hippel‑Lindau‑hypoxia‑inducible factor signaling, chromatin remodeling alterations and immune regulatory pathways. The present review summarizes pivotal phase III clinical trials evaluating VEGF‑targeted tyrosine kinase inhibitors, mechanistic target of rapamycin inhibitors, immune checkpoint inhibitors and combination regimens, including nivolumab plus ipilimumab, pembrolizumab + axitinib and lenvatinib + pembrolizumab. Emerging biomarkers, including International Metastatic Renal Cell Carcinoma Database Consortium risk stratification, programmed death‑ligand 1 expression and chromatin remodeling gene alterations (polybromo 1/BRG1‑associated factor 180, BRCA1‑associated protein 1 and SET domain containing 2), are discussed in the context of their clinical utility and limitations. Despite marked progress, durable predictive biomarkers and optimal treatment sequencing strategies remain unresolved. Resistance to therapy emerges through adaptive angiogenic signaling, immune escape and metabolic reprogramming, underscoring the need for integrated multi‑omics approaches and rational combination strategies. By integrating molecular biology with clinical trial evidence, the present review provides a structured framework for understanding therapeutic decision‑making in RCC and highlights future directions toward biomarker‑guided precision oncology.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"34 6","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}