Daihan Xie, Lixin Xie, Chao Fang, Zhefei Du, Zhenyu Cao, Chunxia Su, Yu Huo
{"title":"New advances of nanozymes for the diagnosis and treatment of digestive system diseases (Review).","authors":"Daihan Xie, Lixin Xie, Chao Fang, Zhefei Du, Zhenyu Cao, Chunxia Su, Yu Huo","doi":"10.3892/ijmm.2025.5617","DOIUrl":"10.3892/ijmm.2025.5617","url":null,"abstract":"<p><p>Despite the significant progress that has been made in the diagnosis and treatment of digestive system diseases, these conditions continue to pose a serious public health concern worldwide. There is an ongoing need for strategies that are precise, efficient and minimally invasive. Nanozymes, engineered nanomaterials that exhibit catalytic functions, have attracted considerable interest in this context. However, clinical application of nanozymes remains limited primarily due to their diversity, targetability, biocompatibility and early‑stage clinical translation. The present review presented a comprehensive analysis of nanozymes in digestive system diseases. The main enzyme‑like activities of nanozymes are summarized to guide further material selection and characteristic exploration. Preclinical applications are highlighted with mechanisms and theranostic effects discussed alongside their potential limitations. Emerging combination therapies, including photodynamic therapy, sonodynamic therapy and biotherapy, are reviewed. Finally, the current challenges of nanozymes and possible future developments are discussed.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953286","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":"[Expression of Concern] Novel insights into the role of HSP90 in cytoprotection of H2S against chemical hypoxia‑induced injury in H9c2 cardiac myocytes.","authors":"Zhanli Yang, Chuntao Yang, Liangcan Xiao, Xinxue Liao, Aiping Lan, Xiuyu Wang, Ruixian Guo, Peixi Chen, Chengheng Hu, Jianqiang Feng","doi":"10.3892/ijmm.2025.5618","DOIUrl":"10.3892/ijmm.2025.5618","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the photos shown in Fig. 5B and D were apparently matching images, such that data which were intended to have shown the results of differently performed mitochondrial protection experiments appeared to have been derived from the same original source. The authors were contacted by the Editorial Office to offer an explanation for the apparent anomaly in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 28: 397‑403, 2011; DOI: 10.3892/ijmm.2011.682].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953338","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}
Guangjie Zhang, Qindong Liang, Yongfang Wu, Yingshuang Wang
{"title":"Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review).","authors":"Guangjie Zhang, Qindong Liang, Yongfang Wu, Yingshuang Wang","doi":"10.3892/ijmm.2025.5626","DOIUrl":"10.3892/ijmm.2025.5626","url":null,"abstract":"<p><p>Traditional cancer research generally utilizes commercial immortalized cancer cell lines cultivated in two‑dimensional (2D) culture systems. However, as cell‑cell/cell‑matrix interactions and the microenvironment cannot be explored <i>in vivo</i>, 2D cell culture models inadequately replicate the phenotype and physiology of original tissues. Therefore, three‑dimensional (3D) cell culture technologies, such as organoids, which present potential for mimicking the features of primary solid tumors <i>in vivo</i>, may be useful in cancer research. By embedding them into special medium, cancer cell lines can be propagated to form tumor organoids. Notably, cells in tumor organoids are different from their original 2D counterparts. During organoid or spheroid formation, crucial aspects including cancer biology, transcriptome, proteome, signal pathways and drug sensitivity, undergo alterations. The present review summarizes the disparities between 2D cancer cells culture and 3D tumor organoids or spheroids with the aim to guide researchers in selecting optimal models for scientific investigations.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000559","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":"MicroRNA‑885‑5p regulates cell cycle progression in liver cancer cells.","authors":"Chaiyaboot Ariyachet, Archittapon Nokkeaw, Pisit Tangkijvanich","doi":"10.3892/ijmm.2025.5608","DOIUrl":"10.3892/ijmm.2025.5608","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are small non‑coding RNAs that regulate gene expression by targeting messenger RNAs for translational repression or degradation. Dysregulation of miRNAs has been implicated in liver cancer development, including hepatocellular carcinoma (HCC). The present study identified miR‑885‑5p as a novel tumor-suppressor miRNA in liver cancer. Analysis of miRNA expression profiles from The Cancer Genome Atlas Program and Gene Expression Omnibus databases demonstrated a consistent downregulation of miR‑885‑5p in HCC tissues. Overexpression of miR‑885‑5p via lentiviral transduction significantly suppressed liver cancer cell proliferation, supporting its tumor‑suppressive role. To investigate the underlying mechanism, transcriptomic profiling of miR‑885‑5p‑overexpressing liver cancer cells was performed. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses highlighted the cell cycle as the most significantly affected pathway. Specifically, miR‑885‑5p downregulated key G<sub>1</sub>/S transition‑promoting genes, including <i>CDK6</i>, E2F Transcription Factor 2 and Origin Recognition Complex Subunit 1 (<i>ORC1</i>), in liver cancer cells. To examine if miR‑885‑5p regulates the G1/S transition, a bromodeoxyuridine labeling assay and cell cycle analysis were performed. Corroborating the transcriptomic data, liver cancer cells with overexpressed miR‑885‑5p exhibited reduced bromodeoxyuridine incorporation and G<sub>1</sub> phase arrest. To gain further mechanistic insights, bioinformatics tools were used to predict gene targets of miR‑885‑5p in the G<sub>1</sub>/S transition. Dual luciferase assays were conducted, which identified the direct interaction of miR‑885‑5p with the 3' untranslated regions of <i>CDK6</i> and <i>ORC1</i> messenger RNAs. Given its inhibitory effect on the G<sub>1</sub>/S transition, the therapeutic potential of miR‑885‑5p was assessed. miR‑885‑5p overexpression sensitized liver cancer cells to the CDK4/6 inhibitors palbociclib, ribociclib and abemaciclib. The present findings collectively demonstrated that miR‑885‑5p induces cell cycle arrest and enhances CDK4/6 inhibitor sensitivity in liver cancer, suggesting its potential as a therapeutic target.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845874","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}
Jin-Long Chen, Fang Chen, Ting-Ting Zhang, Nai-Fu Liu
{"title":"[Expression of Concern] Suppression of SIK1 by miR‑141 in human ovarian cancer cell lines and tissues.","authors":"Jin-Long Chen, Fang Chen, Ting-Ting Zhang, Nai-Fu Liu","doi":"10.3892/ijmm.2025.5627","DOIUrl":"10.3892/ijmm.2025.5627","url":null,"abstract":"<p><p>Following the publication of this paper, for the western blots shown in Fig. 1A, where the expression levels of salt‑inducible kinase 1 were detected in ovarian cancer tissues, it was drawn to the Editor's attention by a concerned reader that the β‑actin loading controls for patients 4, 6 and 7 were strikingly similar in appearance. Moreover, several of the protein bands in this figure were strikingly similar to data which subsequently appeared in another paper written by different authors at different research institutes that was published in the journal <i>Experimental and Therapeutic Medicine</i>, although this paper has since been retracted. The authors were contacted by the Editorial Office to offer an explanation for this apparent anomaly in the presentation of the data in this paper, although up to this time, no response from the authors has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 37: 1601‑1610, 2016; DOI: 10.3892/ijmm.2016.2553].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000565","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":"Role of the gut-brain axis in neurological diseases: Molecular connections and therapeutic implications (Review).","authors":"Hongjuan Zhang, Jia Luan, Ling He, Xianfang Pan, Hujun Zhang, Yujie Li, Haiyan Li","doi":"10.3892/ijmm.2025.5633","DOIUrl":"10.3892/ijmm.2025.5633","url":null,"abstract":"<p><p>The gut-brain axis, a bidirectional communication system involving the central nervous system, enteric nervous system and gastrointestinal tract, plays a pivotal role in neurological health and disease. The present review synthesizes current evidence on its anatomical foundations, functional mechanisms and the role of gut microbiota in neurological diseases. It is explored how dysregulation of the gut-brain axis contributes to neurodegenerative, neuroinflammatory, neurodevelopmental, cerebrovascular and epileptic disorders through molecular mechanisms including neuroinflammation, neurotransmitter modulation, oxidative stress, and blood-brain barrier changes. Furthermore, therapeutic strategies targeting this axis, such as dietary interventions, probiotics, pharmacological approaches and emerging therapies were evaluated. The present review highlights the potential for developing biomarkers and personalized medicine approaches based on gut-brain axis components, while acknowledging translational challenges. However, significant heterogeneity in probiotic strains, FMT protocols, and patient microbiota baselines limits immediate translation. Future trials must address these variables through standardized designs and multi-omics biomarker integration.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040190","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":"Baicalin mitigates polycystic ovary syndrome‑associated non‑alcoholic fatty liver disease by inhibiting the AR/SREBP1 axis.","authors":"Bi-Hui Jin, Han Xu, Zi-Yan Zhang, Yu-Hang Fan, Chun-Yan Jiang, Shao-Long Qi, Chen-Yu Xiao, Xiao-Hua Fu, Ling-Bo Qian","doi":"10.3892/ijmm.2025.5630","DOIUrl":"10.3892/ijmm.2025.5630","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a common endocrine disorder frequently associated with metabolic disturbances, such as non‑alcoholic fatty liver disease (NAFLD), driven by hyperandrogenism‑induced lipogenesis. Baicalin (BA), a flavonoid derived from <i>Scutellaria baicalensis</i>, exhibits therapeutic potential in the treatment of PCOS; however, the specific mechanisms against PCOS‑associated NAFLD remain unclear. In the present study, a PCOS mouse model was established via subcutaneous implantation of dihydrotestosterone. Model validation confirmed irregular estrous cycles, ovarian histopathological abnormalities and altered serum hormone levels. Treatment with BA markedly alleviated NAFLD‑associated metabolic abnormalities, including central obesity, dyslipidemia and hepatic steatosis. Moreover, liver transcriptomics indicated that BA modulated lipid metabolism primarily through sterol regulatory element‑binding protein 1 (SREBP1)‑mediated lipogenesis. Results of western blot analysis confirmed that BA suppressed hepatic protein expression of SREBP1 and its downstream lipogenic enzymes, fatty acid synthase and acetyl‑CoA carboxylase, indicating inhibition of hepatic lipogenesis. As androgen receptor (AR) functions as an upstream transcriptional regulator of SREBP1, network pharmacological analysis highlighted AR as a potential target of BA. Molecular docking predicted the BA‑AR binding site, guiding purification of truncated AR protein for isothermal titration calorimetry (ITC). Subsequently ITC was used to confirm the specific BA‑AR binding affinity. Luciferase reporter assays in MDA‑kb2 cells demonstrated that BA inhibited AR transcriptional activity. Collectively, the results of the present study indicated that BA ameliorates PCOS‑associated NAFLD through targeting the AR/SREBP1 axis, highlighting its potential as a therapeutic strategy for managing lipid metabolism disorders in PCOS.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040164","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":"Innovative strategies to enhance MSCs efficacy in acute kidney injury (Review).","authors":"Yuanxia Zou, Jian Dai, Jingyuan Fu, Honglian Wang, Meng Yang, Jiraporn Kantapan, Li Wang, Nathupakorn Dechsupa","doi":"10.3892/ijmm.2025.5620","DOIUrl":"10.3892/ijmm.2025.5620","url":null,"abstract":"<p><p>Acute kidney injury (AKI) remains a significant clinical challenge, characterized by rapid kidney dysfunction with potential progression to chronic kidney disease. Mesenchymal stem cells (MSCs) offer promising therapeutic potential due to their regenerative, immunomodulatory and anti‑inflammatory capabilities. Despite these advantages, clinical translation is hampered by low MSCs retention, limited cell survival and suboptimal secretion of therapeutic factors in injured renal tissues. Recent research efforts have introduced innovative strategies to optimize MSCs effectiveness, including various preconditioning approaches (hypoxia, chemical/drug‑based and biological cytokines), advanced three‑dimensional cell culture methods (hydrogels and spheroids), genetic modification techniques and improved delivery routes. The present review summarizes current advancements, underlying mechanisms and therapeutic outcomes associated with these novel strategies to enhance MSCs efficacy in AKI, highlighting their clinical potential and guiding future translational research directions.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000562","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":"Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review).","authors":"Jinzhou Xu, Zhiyu Xia, Shaogang Wang, Qidong Xia","doi":"10.3892/ijmm.2025.5612","DOIUrl":"10.3892/ijmm.2025.5612","url":null,"abstract":"<p><p>Oncolytic viruses (OV) are an emerging form of immunotherapy that utilize naturally occurring or engineered viruses to specifically infect and lyse tumor cells. They achieve tumor treatment through direct tumor cell killing or by inducing immunogenic cell death to enhance immune responses. However, the efficacy of OV has been suboptimal in clinical trials. This review comprehensively examines mechanisms of resistance to OV through three interconnected dimensions: The characteristics of tumors and tumor cells, factors related to stromal cells and the extracellular matrix (ECM) and the host immune status. Potential solutions targeting these mechanisms are also proposed. For instance, OV typically achieve tumor selectivity through tumor‑specific receptors or specific promoters. However, due to inter‑ and intratumoral heterogeneity, the lack of such specific receptors or promoters in tumor cells can lead to off‑target effects of OV, resulting in treatment resistance. The ECM in the tumor microenvironment, such as hyaluronic acid, may also impede viral transport. Additionally, the clearance of OV by immune cells can contribute to suboptimal therapeutic outcomes of OV treatment. Consequently, investigating predictive biomarkers of OV efficacy, utilizing ECM‑degrading enzymes and combining with immune checkpoint inhibitors represents a promising strategy to augment the therapeutic effects of OV. Synthesizing current evidence, it is anticipated that future investigations will optimize the therapeutic effects of OV treatment and bring better immunotherapeutic outcomes for cancer patients.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953372","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":"Application of nanobody‑based CAR‑T in tumor immunotherapy (Review).","authors":"Hongjing Liu, Xueping Liu, Xuyan Zhou, Siliang Duan, Xin Huang, Hongxin Fei, Yali Kou","doi":"10.3892/ijmm.2025.5628","DOIUrl":"10.3892/ijmm.2025.5628","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cell therapy is a type of cellular immunotherapy showing promising clinical effectiveness and high precision. CAR‑T cells express membrane receptors with high specificity, which enable them to identify certain target antigens generated by cancerous cells. The three primary structural elements of the CAR are the extracellular domain, transmembrane domain and cytoplasmic domain. Nanobodies are a type of antibody fragment derived from the variable domains of camelid heavy chain antibodies (VHH), which are the antigen‑specific binding domains. They have high clinical applicability due to their tiny size, excellent target affinity, adaptable functions and guaranteed stability. Structurally pre‑designed nanobodies were transduced in primary T lymphocytes, forming CAR‑T cells and these have been demonstrated to have inhibitory effects on hematologic malignancy or solid tumor cells/tissues both <i>in vivo</i> and <i>in vitro</i>. At present, a number of novel nanobody‑based modalities can include a single nanobody, a bi‑valent nanobody and multivalent nanobody CAR‑T cells with bispecific and multispecific characteristics, showing promising therapeutic efficacy that is similar to CAR‑T cells modulated with a single‑chain variable fragment. Intriguingly, CAR‑T cells targeting the B‑cell maturation antigen modified using an anti‑B‑cell maturation antigen single nanobody or bivalent nanobody have been shown to exhibit clinical efficacy comparable to scFv‑modulated CAR‑T cells. The application of nanobodies in CAR‑T therapy has been well established from laboratory‑based evidence to clinical application and they have great potential for developing advanced CAR‑T cells for more complex employment.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"56 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000554","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}