International Journal Of Molecular Medicine[JOURNAL]
Sun
200 papers
Exercise and fluoxetine in Alzheimer's disease: Molecular mechanisms of synergistic and antagonistic effects (Review).
Wu M, Li Y
Int J Mol Med · 2026 Sep · PMID 42396669 · Full text
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid‑β deposition, tau pathology, synaptic dysfunction, neuronal loss and neuroinflammation. Regular physical activity is a key non...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid‑β deposition, tau pathology, synaptic dysfunction, neuronal loss and neuroinflammation. Regular physical activity is a key non‑pharmacological strategy that can ameliorate cognitive impairment and multiple AD‑related pathological features across experimental models by improving mitochondrial function and quality control, strengthening antioxidant defenses, suppressing neuroinflammation and supporting synaptic plasticity. These effects are closely linked to enhanced neurotrophic signaling and cerebrovascular regulation, both of which contribute to resilience against AD‑associated cognitive decline. Fluoxetine, a selective serotonin reuptake inhibitor widely prescribed for depression, has also shown potential benefits in AD models, including modulation of mitochondrial and redox homeostasis, inflammatory signaling and neuroplasticity. The present review integrates evidence on the convergent and divergent molecular targets of exercise and fluoxetine within core AD pathways, highlighting scenarios in which combined interventions may produce synergistic effects, as well as conditions that could lead to antagonistic effects. By mapping shared nodes and potential points of interference, the present review aims to clarify mechanistic hypotheses and inform the design of optimized, clinically translatable strategies that integrate lifestyle and pharmacological approaches for AD.
[Corrigendum] Arginine ADP‑ribosyltransferase 1 promotes angiogenesis in colorectal cancer via the PI3K/Akt pathway.
Yang L, Xiao M, Li X … +2 more , Tang Y, Wang YL
Int J Mol Med · 2026 Sep · PMID 42396667 · Full text
Following the publication of the above paper, it has been drawn to the Editor's attention by a concerned reader that, regarding the cell migration assay data shown in Fig. 3A on p. 738, data panels 'a' and 'c' for the 'C...
Following the publication of the above paper, it has been drawn to the Editor's attention by a concerned reader that, regarding the cell migration assay data shown in Fig. 3A on p. 738, data panels 'a' and 'c' for the 'Co‑cultured for 12 h' experiments (lower row of panels) exhibited overlapping sections, such that these data panels, which were intended to show the results of differently performed experiments, had apparently been derived from the same original source. Moreover, the 'Co‑cultured for 6 h'/'d' panel (on the top row) was also found to share overlapping data with the 'Co‑cultured for 12 h'/'b' panel on the lower row. In addition, it was noted that various of the β‑actin control blots shown in Figs. 1B and 6A on p. 737 and p. 740, respectively, were strikingly similar, where different experimental conditions were reported, suggesting that either or both of these figures may have been assembled incorrectly. Upon examining their original data, the authors have realized that data in these figures were inadvertently assembled incorrectly. Certain of the images for the 6 h and 12 h time points were inadvertently misused during figure compilation due to a folder selection error; specifically, the data erroneously shown in the 'Co‑cultured for 6 h'/'d' panel and in the 'Co‑cultured for 12 h'/'a' panel have been replaced with the correct data. Concerning the re‑use of the β‑actin control blots, those in Fig. 6 were included in error; the revised versions of Figs. 4 and 6 are shown on the next page. The authors confirm that the errors associated with these figures did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 37: 734‑742, 2016; DOI: 10.3892/ijmm.2016.2473].
Oral‑gut axis in systemic disease: A barrier‑metabolism‑immunity three‑dimensional regulatory model (Review).
Li Q, Cheng M, Li W … +3 more , Wang X, Liu X, Yan Y
Int J Mol Med · 2026 Sep · PMID 42396665 · Full text
The oral‑gut axis is an interorgan regulatory network connecting the two core microbial niches in the human body. It sustains systemic homeostasis through bidirectional microbial translocation, metabolite signaling and i...
The oral‑gut axis is an interorgan regulatory network connecting the two core microbial niches in the human body. It sustains systemic homeostasis through bidirectional microbial translocation, metabolite signaling and immune crosstalk. The present review presented a novel barrier‑metabolism‑immunity three‑dimensional regulatory framework that clarifies the core mechanisms of oral‑gut axis dysregulation: Bidirectional translocation of oral and gut microbiota disrupts microbial homeostasis; key metabolites, including short‑chain fatty acids and trimethylamine N‑oxide, mediate interorgan signaling; immune cell migration and barrier damage collectively constitute the pathological basis, which drives multisystem disorders through secondary axes. The present study classified oral‑gut axis imbalance into three quantifiable subtypes: Barrier‑dominant, metabolism‑dominant and immunity‑dominant, each linked to distinct diseases such as inflammatory bowel disease, type 2 diabetes mellitus and rheumatoid arthritis. Accordingly, a stratified, personalized intervention strategy was proposed. Current challenges include difficulties in causal verification, substantial interindividual variability in intervention efficacy and limited tools for real‑time interorgan tracking. Future research will benefit from microbiota gene editing, multi‑omics integration and in vivo imaging to advance mechanistic understanding and clinical translation. This three‑dimensional model provides a standardized theoretical foundation and practical guidance for the diagnosis and treatment of oral‑gut axis‑related diseases.
Endothelial dysfunction: A central mechanism linking autosomal dominant polycystic kidney disease and intracranial aneurysms (Review).
Xu X, Xu R, Zhang L
Int J Mol Med · 2026 Sep · PMID 42396661 · Full text
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder and is characterized by the progressive development of multiple bilateral renal cysts and the deterioration of renal func...
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder and is characterized by the progressive development of multiple bilateral renal cysts and the deterioration of renal function. Patients with ADPKD also have a substantially elevated risk of diverse systemic vascular complications such as intracranial aneurysm (IA), a serious life‑threatening condition. IA occurs much more frequently in patients with ADPKD than in the general population, and IA rupture can lead to subarachnoid hemorrhage, a major cause of mortality and long‑term disability. Although clinical evidence supports an association between ADPKD and IA, the exact nature of the molecular and pathological connections between these conditions remains unclear, making it difficult to develop effective preventive and therapeutic strategies. Advances in vascular biology have led to the view that endothelial dysfunction is a pivotal event in the pathogenesis of multiple vascular diseases. Consequently, there is increasing attention on the role of endothelial dysfunction in mediating the relationship between ADPKD and IA. The present review first summarizes the physiological functions and structural characteristics of endothelial cells, and then focuses on the pathological effects of endothelial dysfunction in ADPKD and IA. Additionally, the review describes therapeutic strategies that aim to restore endothelial function, with a focus on the use of early screening and precision treatment, to improve the prognosis of patients with ADPKD complicated by IA.
ABCG2 transporter: Structural and functional associations with gout (Review).
Asif MA, Zulfiqar Z, Mustafa BE … +7 more , Nazir U, Sun J, Wang Z, Cui Y, Hao S, Boshuai L, Shi Y
Int J Mol Med · 2026 Sep · PMID 42396658 · Full text
ATP‑binding cassette sub‑family G member 2 (ABCG2) is a key regulator of urate homeostasis, and its dysfunction is a major genetic risk factor for hyperuricemia and gout in humans and animals. Initially, ABCG2 was known...
ATP‑binding cassette sub‑family G member 2 (ABCG2) is a key regulator of urate homeostasis, and its dysfunction is a major genetic risk factor for hyperuricemia and gout in humans and animals. Initially, ABCG2 was known for its role in multidrug resistance. ABCG2 has since been identified as a high‑capacity urate efflux pump, located at the apical membranes of renal proximal tubules, intestinal enterocytes and hepatic canaliculi. The present review covers the molecular structure, physiological functions and pathophysiological effects of ABCG2, with particular focus on the common Q141K (rs2231142) loss‑of‑function variant. The Q141K variant impairs protein stability and trafficking, reducing urate transport and increasing the risk of gout and cardiorenal comorbidities. The present review explores the central role of ABCG2 within the urate transportome, highlighting its contrasting and cooperative interactions with reabsorptive and secretory transporters, as well as its regulation by novel mechanisms, including the gut microbiome and microbial metabolites. These observations have significant clinical implications for pharmacogenomic approaches, as Q141K variant carriers exhibit a reduced response to uricosuric drugs. The present review also highlights emerging treatments that go beyond standard urate‑lowering therapies, including ABCG2 activators, microbiome modulators and gene‑editing techniques, offering a potential shift toward personalized gout prevention and treatment. Understanding the multifaceted role of ABCG2 is essential for developing targeted strategies to address the root cause of impaired urate excretion.
Research progress on the chemical and pharmacological effects of (Review).
Mao J, Du X, Zeng D … +2 more , Luo X, Li Y
Int J Mol Med · 2026 Sep · PMID 42396655 · Full text
(family ) has a long‑standing history of cultivation in South Asia. The medicinal value of has attracted extensive attention due to its potential efficacy in the intervention of nervous system diseases, anti‑arrhythmia,...
(family ) has a long‑standing history of cultivation in South Asia. The medicinal value of has attracted extensive attention due to its potential efficacy in the intervention of nervous system diseases, anti‑arrhythmia, analgesia, anti‑inflammation and antitumor fields. However, research on its pharmacological effects are predominantly limited to experiments, and a systematic pharmacological exploration of different extracts and monomer compounds from is lacking. Additionally, notable safety risks exist both before and after the processing of , thus its clinical application and toxicity mechanisms require further in‑depth analysis. The present review comprehensively evaluated the latest research progress on the traditional medicinal history, chemical composition analysis and pharmacological activity of , and aimed to provide a systematic theoretical reference for the follow‑up basic research of and its industrial application in the pharmaceutical field.
[Corrigendum] Effect of SDF‑1/CXCR4 axis on the migration of transplanted bone mesenchymal stem cells mobilized by erythropoietin toward lesion sites following spinal cord injury.
Li J, Guo W, Xiong M … +6 more , Han H, Chen J, Mao D, Tang B, Yu H, Zeng Y
Int J Mol Med · 2026 Sep · PMID 42396654 · Full text
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, regarding the experiments showing the localization of fluorescently‑labeled cells transplanted into the injured...
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, regarding the experiments showing the localization of fluorescently‑labeled cells transplanted into the injured spinal cord in Fig. 4 on p. 1210, the fluorescence images shown in Fig. 4A and 4B contained an overlapping section, such that data which were intended to have shown the results of differently performed experiments appeared to have been derived from the same original source. Upon contacting the authors about these issues, they have realized that images featured in Fig. 4 of this article were inadvertently assembled incorrectly. The revised version of Fig. 4, now featuring data from a repeated experiment, is shown below [note that the original GFP‑conjugated green secondary antibody was replaced with Alexa Fluor 594 (Cy3) red fluorescent secondary antibody, and the description has been revised in the figure legend accordingly]. The authors wish to emphasize that the error made in assembling the data in this figure did not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of for granting them this opportunity to publish a Corrigendum, and apologize to both the Editor and the readership for any inconvenience caused. [International Journal of Molecular Medicine 36: 1205‑1214, 2015; DOI: 10.3892/ijmm.2015.2344].
enhances the malignant phenotype of glioma cells and exerts immunomodulatory effects through feedback crosstalk with exonic circRNA and interferon‑induced .
Wen X, Gu X, Yan X … +7 more , Chen N, Zhou L, Li H, Hoffman AR, Li W, Hu JF, Cui J
Int J Mol Med · 2026 Sep · PMID 42396652 · Full text
Gliomas comprise a group of common primary brain tumors with a high degree of malignancy and a poor prognosis. There are currently no targeted therapeutics for glioma in clinical practice. The present study revealed a no...
Gliomas comprise a group of common primary brain tumors with a high degree of malignancy and a poor prognosis. There are currently no targeted therapeutics for glioma in clinical practice. The present study revealed a novel crosstalk circuitry mechanism that contributes to the overexpression of Friend leukemia virus integration 1 () in glioma. , a member of the ETS transcription factor family, was upregulated in glioma and its expression was associated with malignant phenotype and poor prognosis of the disease. Notably, aberrant expression in glioma was regulated by its exonic circRNA FECR1 through a positive feedback mechanism. knockdown suppresses tumor phenotypes of glioma cells. Using RNA‑seq and Co‑IP assays, the present study identified interferon‑stimulated gene 15 (), a paracrine factor known to reprogram the tumor immunosuppressive microenvironment, as a new molecular target of in glioma. coordinated with ISG15 to suppress immune function, including the secretion of the cytokines perforin, IFN‑γ, TNF‑α and IL2 from T cells, as well as perforin from γδ T cells. Mechanistically, bound to the promoter regulatory elements, where it activates the gene by orchestrating an active intrachromosomal spatial loop with characteristic DNA hypomethylation and histone H3K9 and H3K27 acetylation. As a downstream target, also participated in a positive feedback loop with by enhancing its stability from ubiquitination‑induced degradation. Thus, targeting this feedback circuitry may provide a novel strategy to develop therapeutics for gliomas.
Role of ZEB1 in angiogenesis and therapeutic potential (Review).
Ren R, Yan C, Xiang Y … +3 more , Jin L, Cheng F, Zhang L
Int J Mol Med · 2026 Sep · PMID 42396647 · Full text
Zinc finger E‑box binding homeobox 1 (ZEB1), a key transcription factor governing epithelial‑mesenchymal transition, plays indispensable roles in embryonic development, neural differentiation and a wide range of patholog...
Zinc finger E‑box binding homeobox 1 (ZEB1), a key transcription factor governing epithelial‑mesenchymal transition, plays indispensable roles in embryonic development, neural differentiation and a wide range of pathological processes. Emerging evidence has revealed that ZEB1 exerts multifaceted and context‑dependent functions in angiogenesis. Under physiological conditions, ZEB1 contributes to the regulation of vascular development and endothelial homeostasis, whereas in pathological settings it promotes aberrant neovascularization through diverse molecular mechanisms. In the present review, the structural characteristics, biological functions and regulatory mechanisms of ZEB1 were systematically summarized, with a particular focus on recent advances regarding its roles in both physiological and pathological angiogenesis. Furthermore, the therapeutic potential of targeting ZEB1 in vascular diseases was discussed and future research directions that may facilitate the development of novel strategies for the prevention and treatment of angiogenesis‑related disorders were highlighted.
[Corrigendum] Crocin exerts anti‑inflammatory and anti‑catabolic effects on rat intervertebral discs by suppressing the activation of JNK.
Li K, Li Y, Ma Z … +1 more , Zhao J
Int J Mol Med · 2026 Sep · PMID 42396646 · Full text
Following the publication of the above paper, a concerned reader has drawn to the Editor's attention that, regarding the immunohistochemical images shown in Fig. 6A and B on p. 1297, the 'Control' and 'LPS+Crocin' panels...
Following the publication of the above paper, a concerned reader has drawn to the Editor's attention that, regarding the immunohistochemical images shown in Fig. 6A and B on p. 1297, the 'Control' and 'LPS+Crocin' panels in Fig. 6A showed an overlapping section, such that these data, which were intended to show the results of differently performed experiments, had apparently been derived from the same original source. In addition, the 'LPS+Crocin' panel in Fig. 6B contained data that subsequently reappeared in a paper published by the same research group in the journal . The authors were contacted by the Editorial Office to offer an explanation for these apparent anomalies in the presentation of the data in this paper, and the placement of the wrongly identified images in the figure was caused by errors that occurred during the process of copying the multiple images from the microscope system to the computer. The corrected version of Fig. 6, now showing the correct images for the 'Control' and 'LPS+Crocin' data panels in Fig. 6A, and the 'LPS' and 'LPS+Crocin' data panels in Fig. 6B (both the NBT‑ and DAPI‑stained images), is shown on the next page. The authors confirm that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 36: 1291‑1299, 2015; DOI: 10.3892/ijmm.2015.2359].
Neuropilin‑1: Emerging roles in nerve‑vessel‑bone coupling during fracture repair (Review).
Zhang K, Li T, Liu H … +12 more , Ti H, Zhang Z, Yuan Z, Wu J, Yan X, Luo Z, Hu H, Yao X, Shi S, Wu X, Yuan FL, Chen X
Int J Mol Med · 2026 Sep · PMID 42396644 · Full text
Fracture healing is a sophisticated biological process orchestrated by the spatiotemporal coordination of neural, vascular and skeletal systems to sustain reparative homeostasis. However, this regulatory network is often...
Fracture healing is a sophisticated biological process orchestrated by the spatiotemporal coordination of neural, vascular and skeletal systems to sustain reparative homeostasis. However, this regulatory network is often disrupted in pathological conditions, such as osteoporosis, diabetes and aging, leading to impaired outcomes, such as delayed fracture healing and nonunion. Synthesizing available multidisciplinary evidence suggests that neuropilin‑1 (NRP1), a transmembrane glycoprotein with pleiotropic functions, may serve as a potential mediator integrating multisystemic signals and participating in nerve‑vessel‑bone crosstalk during fracture repair. Endowed with distinctive structural domains, NRP1 selectively binds diverse ligands and has been observed to localize preferentially in active bone repair zones and critical cellular populations. There, it exhibits preliminary biological potential to assist in coordinating angiogenesis, modulating the function of bone‑repair cells, and guiding nerve fibers. In systemic metabolic disorders or in localized, extreme inflammatory microenvironments, dysregulation of NRP1‑mediated signaling may be associated with clinical complications, such as delayed fracture healing and nonunion. Therefore, a more in‑depth exploration of the nerve‑vessel‑bone crosstalk and pathological networks potentially governed by NRP1 may provide preliminary mechanistic insight into the imbalances in bone repair. The present review summarizes the current understanding of the possible roles of NRP1 in physiological fracture healing and organizes reported specific dysregulation patterns across systemic high‑risk diseases and distinct inflammatory osteolytic states. Finally, the present review discusses the translational potential of NRP1 as a candidate therapeutic target for delayed healing, explicitly highlighting current translational opportunities and significant preclinical barriers, in an aim to provide a preliminary theoretical framework for developing NRP1‑targeted therapies for nonunion.
TRPV1‑mediated central sensitisation: Core mechanisms of migraine chronification and novel targeted therapeutic strategies (Review).
Zhang M, Pu Y, Zhang Y … +5 more , Hu J, Li S, Tang H, Fang B, Bai X
Int J Mol Med · 2026 Sep · PMID 42396643 · Full text
Migraines are highly prevalent and disabling neurological disorders. Central sensitisation constitutes the core pathophysiological basis for its recurrent and chronic nature. Transient receptor potential vanilloid 1 (TRP...
Migraines are highly prevalent and disabling neurological disorders. Central sensitisation constitutes the core pathophysiological basis for its recurrent and chronic nature. Transient receptor potential vanilloid 1 (TRPV1), a key molecule in pain signalling, is not only involved in peripheral nociception, but is also highly expressed in central pain‑processing regions. TRPV1 directly contributes to the initiation and maintenance of central sensitisation, positioning it as a promising therapeutic target for migraine management. The present review systematically summarised the biological characteristics of TRPV1 and its associations with central sensitisation and migraines. The molecular mechanisms through which TRPV1 mediates central sensitisation are elaborated upon, including the regulation of neurotransmitter release, activation of glial cells, involvement in inflammatory responses and modulation of synaptic plasticity. Furthermore, the research progress and clinical challenges of TRPV1‑targeted strategies are discussed, including antagonists, agonists and genetic regulation. Lastly, the present study proposes future research directions at both basic and clinical levels, providing a novel molecular perspective on migraine pathogenesis and establishing a theoretical foundation for the development of targeted clinical therapies.
Neutrophil extracellular traps in thrombosis of hematologic malignancies: Underlying mechanisms and therapeutic opportunities (Review).
Lv K, Ma Z, Chen Q … +4 more , Su Y, Ma J, Wang C, Yu L
Int J Mol Med · 2026 Aug · PMID 42359710 · Full text
Patients with cancer, particularly those diagnosed with hematological malignancies, exhibit thrombus incidence rates that exceed those observed in the general population by a substantial margin, and this elevated risk is...
Patients with cancer, particularly those diagnosed with hematological malignancies, exhibit thrombus incidence rates that exceed those observed in the general population by a substantial margin, and this elevated risk is associated with worse clinical outcomes. Neutrophil extracellular traps (NETs), which are web‑like structures released by neutrophils as part of their innate immune repertoire, drive coagulation and vascular occlusion by supplying a physical scaffold, recruiting procoagulant factors, and cleaving tissue factor pathway inhibitors. In hematological malignancies, emerging evidence points to NET overproduction and dysregulation as key drivers of thrombosis, representing a previously underappreciated mechanistic axis. The present review focuses on the molecular mechanisms by which NETs promote thrombosis, specifically on thrombosis associated with hematological malignancies (such as myeloproliferative neoplasm, acute myeloid leukemia, Hodgkin lymphoma, multiple myeloma and acute lymphoblastic leukemia), and also explores the clinical translation potential of NET‑related therapies. The present study offers a potential basis for refining current approaches to coagulation risk reduction in patients with hematological malignancies.
Mitochondria‑endoplasmic reticulum contact site nexus: Molecular integration, disease pathogenesis and therapeutic opportunities (Review).
Liu Y, Che X, Wei W … +2 more , Teng C, Li H
Int J Mol Med · 2026 Aug · PMID 42359697 · Full text
Mitochondria‑endoplasmic reticulum contact sites (MERCs) are dynamic, nanoscale membrane domains that serve as crucial signaling hubs for inter‑organellar communication. These specialized interfaces are maintained by a c...
Mitochondria‑endoplasmic reticulum contact sites (MERCs) are dynamic, nanoscale membrane domains that serve as crucial signaling hubs for inter‑organellar communication. These specialized interfaces are maintained by a complex network composed of tethering, promoter, and disruptor proteins and coordinate a wide range of cellular processes, such as calcium and zinc ion homeostasis, lipid biosynthesis and transfer, redox signaling, mitochondrial dynamics (fission, fusion and mitophagy), autophagy, apoptosis, inflammation and cellular senescence. Accordingly, the structural and functional integrity of MERCs is vital for cellular adaptation and survival. Nevertheless, MERC plasticity is often impaired in various human pathologies. Alterations in MERC composition, abundance, or function are regarded as pathogenic mechanisms in neurodegenerative diseases, metabolic disorders, cardiovascular conditions, cancer and orthopedic diseases. Common manifestations of MERC dysfunction include disrupted ion signaling, bioenergetic failure, excessive oxidative stress, and impaired organelle quality control. Therefore, targeted modulation of MERCs represents a promising therapeutic avenue. However, translating this potential into clinical practice faces considerable challenges. This is because MERC function is dynamic, context‑dependent and dualistic; both excessive and deficient coupling can drive pathology. Future progress hinges on deciphering the precise regulatory codes that govern MERC assembly, developing tools for real‑time, high‑resolution in vivo analysis, and designing innovative, cell‑type‑specific interventions that normalize rather than simply inhibit or enhance MERC function. A multidisciplinary approach integrating spatial proteomics, super‑resolution imaging, and advanced disease modeling is warranted for unlocking the full diagnostic and therapeutic potential of these organelle contact sites.
Metabolic messengers from the gut to the joint: Toward precision management of osteoarthritis (Review).
Zhang R, Zhang L, Wang Y … +2 more , Kang X, Zheng J
Int J Mol Med · 2026 Aug · PMID 42359688 · Full text
Osteoarthritis has evolved from a mechanical concept to a metabolic whole‑organ disease driven by systemic inflammation. The 'gut‑joint axis' represents a 'biological highway' where intestinal dysbiosis permits the trans...
Osteoarthritis has evolved from a mechanical concept to a metabolic whole‑organ disease driven by systemic inflammation. The 'gut‑joint axis' represents a 'biological highway' where intestinal dysbiosis permits the translocation of microbial metabolites into synovial joints. This review focuses on three pivotal metabolite classes with opposing roles: Short‑chain fatty acids (SCFAs), which function as anti‑inflammatory guardians; trimethylamine N‑oxide (TMAO), which acts as a pro‑inflammatory aggressor; and bile acids (BAs), which serve as complex regulators that balance homeostasis and catabolism. This review further proposes a novel 'metabolite homeostasis imbalance' theoretical framework, which posits that osteoarthritis pathogenesis is driven by the disruption of the dynamic equilibrium between protective (SCFAs), destructive (TMAO) and context‑dependent regulatory (BAs) microbial metabolites. This integrative 'metabolite homeostasis imbalance' model deconstructs the 'biological highway' metaphor into a three‑tier mechanistic schema encompassing intestinal barrier integrity, systemic metabolite trafficking and tissue‑specific effector functions in the joint microenvironment, thereby providing a unifying conceptual foundation bridging scattered single‑metabolite research and mechanism‑targeted precision OA management. Additionally, the potential of sports medicine interventions, including exercise and probiotics, to modulate this axis is evaluated. This synthesis provides a comprehensive theoretical basis for novel clinical strategies targeting gut‑derived metabolic networks to preserve joint health and mitigate disease progression.
MTA2: Decoding pathogenic mechanisms, clinical implications and therapeutic frontiers across disease landscapes (Review).
Xie H, Chen L, Gou J … +6 more , Long X, Yang Y, Hu H, Wu P, Yan Q, Wu Y
Int J Mol Med · 2026 Aug · PMID 42359685 · Full text
Metastasis‑associated protein 2 (MTA2), a crucial member of the metastasis‑associated family of transcriptional regulators, serves as a core component of the Mi‑2/nucleosome remodeling and deacetylase complex. It contrib...
Metastasis‑associated protein 2 (MTA2), a crucial member of the metastasis‑associated family of transcriptional regulators, serves as a core component of the Mi‑2/nucleosome remodeling and deacetylase complex. It contributes to diverse human diseases through epigenetic regulation and integration of multiple signaling pathways. This paper systematically reviews the molecular and structural properties of MTA2 and investigates its functional mechanisms in both oncological and non‑oncological contexts, focusing on breast cancer, gastric cancer and hepatocellular carcinoma, emphasizing its biological roles in cancer metastasis, drug resistance and tumor microenvironment remodeling. Building on existing research, the review highlights the clinical significance of MTA2 as a potential diagnostic marker and therapeutic target in cancer and discusses targeted intervention strategies aimed at the MTA2‑related regulatory network. Finally, the development of highly specific inhibitors targeting MTA2 and the establishment of rapid MTA2 detection techniques for real‑time intraoperative margin assessment will fully unlock the clinical potential of MTA2.
Recombinant myonectin ameliorates sepsis‑induced cardiomyopathy by alleviating mitochondrial dysfunction via the AdipoR1/AMPK pathway.
Li P, Chen R, Zhang H … +4 more , Li L, Luo H, Du B, Yang P
Int J Mol Med · 2026 Aug · PMID 42359680 · Full text
Sepsis‑induced cardiomyopathy (SIC) is a common complication of sepsis and is associated with a high mortality rate; however, effective therapies remain lacking. Mitochondrial dysfunction is a key pathogenic mechanism. M...
Sepsis‑induced cardiomyopathy (SIC) is a common complication of sepsis and is associated with a high mortality rate; however, effective therapies remain lacking. Mitochondrial dysfunction is a key pathogenic mechanism. Myonectin, also known as C1q tumor necrosis factor‑related protein 15, is a novel member of the C1q/TNF‑related protein family. It has been demonstrated to exert cardioprotective effects by suppressing inflammatory response, inhibiting apoptosis and attenuating cardiac fibrosis. Despite these known functions, whether myonectin protects against SIC remains unclear. The present study aimed to investigate the protective potential of recombinant myonectin (rMyonectin) against SIC. Lipopolysaccharide (LPS)‑induced and cecal ligation and puncture‑induced SIC models were established in C57BL/6J mice, and LPS‑stimulated neonatal mouse cardiomyocytes (NMCMs) were used for validation. Mice and NMCMs were pretreated with rMyonectin prior to the respective challenge. The results showed that rMyonectin improved cardiac function, attenuated myocardial injury, inhibited apoptosis and preserved the integrity of myocardial mitochondria in SIC mice. Furthermore, rMyonectin inhibited LPS‑induced apoptosis in cardiomyocytes. It concurrently promoted mitochondrial biogenesis, maintained mitochondrial dynamics and stabilized mitochondrial membrane potential, thereby improving mitochondrial function and enhancing ATP production. Importantly, these protective effects were abolished by either adiponectin receptor 1 (AdipoR1) knockdown or AMP‑activated protein kinase (AMPK) inhibition. These findings suggest that rMyonectin protects against SIC by alleviating mitochondrial dysfunction via the AdipoR1/AMPK pathway, highlighting its promise as a protective agent.
Myokines in exercise‑mediated bone homeostasis: Molecular signaling mechanisms and therapeutic implications for bone disorders (Review).
Tian B, Chen X, Zheng J … +1 more , Kang X
Int J Mol Med · 2026 Aug · PMID 42359679 · Full text
Skeletal muscle functions as an endocrine organ, secreting myokines that mediate interorgan communication with bone. Exercise‑induced myokines regulate bone homeostasis by orchestrating osteoblast differentiation, osteoc...
Skeletal muscle functions as an endocrine organ, secreting myokines that mediate interorgan communication with bone. Exercise‑induced myokines regulate bone homeostasis by orchestrating osteoblast differentiation, osteoclastogenesis, and osteocyte mechano‑sensing through key signaling pathways, including the Wnt/β‑catenin, mitogen‑activated protein kinase, phosphatidylinositol‑3‑kinase/AKT, nuclear factor kappa B and transforming growth factor‑beta/bone morphogenetic protein pathways. The present review provides a critical synthesis of the current evidence and proposes a conceptual framework for the tripartite muscle‑bone‑immune axis, which has not been systematically integrated into previous reviews. Emerging evidence highlights a tripartite muscle‑bone immune axis, wherein myokines modulate immune cells within the bone niche, with dysregulation contributing to age‑related osteoporosis and sarcopenia. Methodological innovations such as multi‑omics, single cell and spatial transcriptomics, organ‑on‑a‑chip platforms, and artificial intelligence are accelerating discovery. The present review synthesizes current knowledge on myokine mediated muscle‑bone crosstalk and evaluates the therapeutic implications for bone disorders.
Skeletal muscle‑derived extracellular vesicles in multi‑organ degenerative disease: Mechanisms and therapeutic delivery perspectives (Review).
Wei X, Guo C, Zhang W … +5 more , Wang G, Li W, Gao B, Gao B, Zhang L
Int J Mol Med · 2026 Sep · PMID 42359675 · Full text
Multi‑organ degenerative diseases are age-associated or chronic disorders marked by progressive tissue deterioration, impaired repair and functional decline, with representative conditions including sarcopenia, osteoporo...
Multi‑organ degenerative diseases are age-associated or chronic disorders marked by progressive tissue deterioration, impaired repair and functional decline, with representative conditions including sarcopenia, osteoporosis, osteoarthritis, neurodegenerative or ischemia‑associated neurological disorders, heart failure, chronic kidney disease and diabetes‑associated tissue dysfunction. Their frequent coexistence in aging populations limits the effectiveness of therapeutic strategies directed at a single organ or pathway. Extracellular vesicles (EVs) are lipid bilayer‑enclosed particles that shuttle proteins, lipids, metabolites and regulatory RNAs between cells and tissue. As a highly metabolic and secretory tissue, skeletal muscle releases skeletal muscle‑derived EVs (SkM‑EVs) that may carry muscle‑enriched microRNAs, together with other regulatory cargo molecules involved in local tissue remodeling and systemic signaling. SkM‑EVs have therefore been proposed as mediators of muscle‑centered cross‑organ communication and potential delivery vehicles for molecular intervention, although therapeutic evidence remains largely preclinical. The present review examines the biological functions of SkM‑EVs, their regulation by exercise, aging and metabolic stress and their potential involvement in multi‑organ degenerative diseases. The present study aimed to discuss engineering strategies for SkM‑EVs, including cargo loading, surface modification and targeted delivery, with particular attention to controversies, methodological limitations, quality control requirements and barriers to clinical translation.
Molecular mechanism of hydromorphone preconditioning in cerebral ischemia/reperfusion‑induced inflammatory injury.
Yao J, Huang Z, Li S … +2 more , Lun M, Fan J
Int J Mol Med · 2026 Aug · PMID 42318970 · Full text
The present study explored the protective mechanism of hydromorphone (HM) preconditioning in cerebral ischemia/reperfusion injury (CIRI). An animal model of CIRI was established by middle cerebral artery occlusion/reperf...
The present study explored the protective mechanism of hydromorphone (HM) preconditioning in cerebral ischemia/reperfusion injury (CIRI). An animal model of CIRI was established by middle cerebral artery occlusion/reperfusion in male C57BL/6J mice. An I/R cell model was induced by oxygen‑glucose deprivation/reperfusion. Brain tissue injury and cell injury were evaluated by hematoxylin and eosin staining, 2,3,5‑triphenyltetrazolium chloride staining, lactate dehydrogenase testing and a Cell Counting Kit‑8 assay. Nod‑like receptor protein 3 (NLRP3)‑positive expression and caspase‑1 activity were assessed by immunostaining and caspase‑1 activity assays, respectively. Reverse transcription‑quantitative PCR or western blotting were used to quantify the expression levels of microRNA (miR)‑195‑5p, RNA‑binding motif protein 15 (RBM15) and upstream stimulatory factor 2 (USF2). RNA immunoprecipitation (RIP) and dual‑luciferase assays verified the binding between miR‑195‑5p and RBM15, followed by RIP analysis of N6‑methyladenosine (m6A) enrichment on USF2 and quantitative analysis of m6A content. The binding of RBM15 and insulin‑like growth factor 2 mRNA‑binding protein 3 (IGF2BP3) to the USF2 m6A site was analyzed by a dual‑luciferase assay. HM preconditioning inhibited NLRP3‑mediated pyroptosis, alleviated neurological deficits, and reduced inflammatory injury in brain tissue. Mechanistically, hydromorphone (HM) preconditioning targeted RBM15 and reduced IGF2BP3‑mediated m6A modification by upregulating miR‑195‑5p expression, thus decreasing USF2 expression, reducing the enrichment of USF2 on the NLRP3 promoter, and inhibiting NLRP3‑mediated pyroptosis. In conclusion, HM preconditioning may repress NLRP3‑mediated pyroptosis and alleviate CIRI via the effects of miR‑195‑5p/RBM15/USF2.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe