International journal of molecular medicine最新文献

Following the publication of the above article, an interested reader drew to the authors' attention that, concerning the Von Kossa staining experiments shown in Fig. 5E on p. 2002, the 'NC' and 'OvercircRNA‑0079201+miR‑140‑3p mimic' data panels appeared to contain an overlapping section of data, such that data which were intended to show the results of different experiments had apparently been derived from the same original source. In addition, it was also noted that the COL10A1 western blots featured in Fig. 5D were strikingly similar to blots that had appeared in an article in Journal of Cellular and Molecular Medicine by the same research group. In their response, the authors confirmed that the only figure part requiring correction was the 'NC' von Kossa staining panel in Fig. 5E; concerning the COL10A1 western blot in Fig. 5D, after re‑examining the original experimental records and source files, they could confirm that this panel was derived from experiments conducted specifically for the above article. The revised version of Fig. 5, now showing the correct data for the 'NC' data panel in Fig. 5E, is shown on the next page. The authors can 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 International Journal of Molecular Medicine 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 46: 1993‑2006, 2020; DOI: 10.3892/ijmm.2020.4737].

Follistatin‑like protein 1 (FSTL1), a secreted glycoprotein, serves a key role in regulating various biological processes. The present review explores the molecular mechanisms through which FSTL1 influences inflammation, cellular senescence and tumour progression. As a multifunctional protein with both autocrine and paracrine properties, FSTL1 regulates cell survival, proliferation, differentiation and migration, while also modulating immune responses. Evidence indicates that FSTL1 exerts context‑dependent regulatory effects on pathological conditions by modulating signalling pathways, such as TGF‑β, NF‑κB and MAPK. Furthermore, increased FSTL1 expression has been found in the inflammatory synovial tissues of patients with osteoarthritis and it contributes to nucleus pulposus cell inflammation. In conclusion, the distinctive structural features and widespread expression of FSTL1 position it as a key target for understanding the mechanisms underlying inflammation, senescence and tumourigenesis, providing potential options for novel diagnostic and therapeutic strategies for these conditions.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, concerning the immunofluorescence images shown in Fig. 2C on p. 855, the 'Blank/E‑cadherin' and 'TGF‑β2‑SIS3/E‑cadherin' data panels appeared to show the same data, albeit with different intensities of staining. In addition, in Fig. 3B on p. 856, the GAPDH blots shown for the '7 days' and '28 days' experiment gels were strikingly similar in appearance, in spite of different experiments being reported. After having asked the authors to explain the apparent anomalies in these figures, they realized that they had been assembled erroneously. Corrected versions of Figs. 2 and 3, now showing the correct data for the 'TGF‑β2‑SIS3/E‑cadherin' experiment in Fig. 2C and the GAPDH western blots for the '28 days' experiment in Fig. 3B, are shown opposite and on the next page. The errors made in assembling Figs. 2 and 3 did not grossly affect either the results or the conclusions reported in this paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to present this; moreover, the Editor and the authors apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 851‑860, 2018; DOI: 10.3892/ijmm.2018.3662].

Following the publication of the above article, an interested reader drew to the authors' attention that, concerning the Transwell migration assay images shown in Fig. 6 on p. 287, the data panels for figure parts 6E (the DMSO experiment) and 6G (the pcDNA3.1+DMSO experiment) contained strikingly similar data, albeit with different sizing of the images, suggesting that these data had been derived from the same original source. Upon investigating this figure, the authors realized that this figure had inadvertently been assembled incorrectly: The data panel for the DMSO group in the HTR‑8/SVneo cell migration assay (Fig. 6E) had been duplicated from the correctly displayed pcDNA3.1+DMSO group panel. The revised version of Fig. 6, now showing the correct data panel for Fig. 6E, is shown on the next page. The authors confirm that the error 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 International Journal of Molecular Medicine 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 44: 281-290, 2019; DOI: 10.3892/ijmm.2019.4175].

Sepsis is a life‑threatening clinical syndrome characterized by a dysregulated host immune response to infection, with its pathogenesis closely linked to the aberrant activation and dysfunction of various immune cells. The kidney is among the most vulnerable organs in sepsis. The development of acute kidney injury (AKI) in sepsis, referred to as sepsis‑associated AKI (SA‑AKI), is often associated with significantly increased mortality. Despite its clinical impact, specific and effective therapies for SA‑AKI remain scarce. Increasing evidence highlights that complex intrarenal inflammatory processes, primarily driven by diverse immune cell populations, are central to the onset and progression of SA‑AKI. The present review provides a comprehensive analysis of the roles of both innate and adaptive immune cells, such as macrophages, neutrophils, dendritic cells, natural killer cells, natural killer T (NKT) cells, B cells and T cells, in SA‑AKI and explores potential therapeutic strategies, offering a theoretical foundation and insights for the development of more effective prevention and treatment approaches.

Diabetic kidney disease (DKD) is a microvascular complication of diabetes, characterized by region‑specific metabolic reprogramming that disrupts kidney function and markedly impairs patient prognosis. By enabling in situ visualization and analysis of metabolite distribution within kidney tissue, spatial metabolomics offers a unique advantage in detecting spatial heterogeneity in metabolic alterations, which is inaccessible through conventional metabolomics. This approach not only enhances the understanding of DKD pathophysiology but also provides a solid foundation for the development of precision nephrology strategies informed by spatial metabolite data. The present review discusses the fundamental workflows and spatial resolution capabilities of spatial metabolomics, summarizing the key metabolites involved in regional metabolic disruptions in multiple DKD animal models. Moreover, it highlights notable metabolites, including glucose, succinate, phosphatidylserine, lysophosphatidylglycerol, phosphatidylglycerol, sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, taurine, glutamate, L‑carnitine, choline, adenosine monophosphate and guanosine monophosphate. The continued advancement of imaging technologies and data analysis methodologies is expected to further refine the spatial resolution and precision of spatial metabolomics, thereby facilitating its broader application in clinical practice.

Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive cognitive decline and whose pathology is closely linked to cellular autophagy dysfunction. Autophagy is a key process involved in cell clearance. Impaired autophagy can drive neuronal damage and death related to AD pathology. Therefore, targeting autophagy dysfunction has emerged as a promising therapeutic strategy. Exercise, as a non‑pharmaceutical and low‑cost intervention method, can enhance autophagy activity and alleviate AD symptoms. However, the mechanism by which it regulates autophagy in AD remains unclear. The present review summarizes evidence that exercise acts as an effective early intervention. Exercise activates key cellular signaling pathways (mammalian target of rapamycin, sirtuin 1 and adiponectin receptor 1) and regulates microRNAs (small non‑coding RNAs) and irisin (a muscle hormone) to restore normal autophagy. The present review also explores the use of exercise combined with natural products for potential synergistic therapeutic effects. This review provides insights into developing new AD prevention and management strategies by detailing how exercise corrects AD‑related autophagy dysfunction.

The tumor microenvironment (TME) in oral squamous cell carcinoma (OSCC) represents a dynamic and heterogeneous ecosystem in which non-immune stromal cells play important roles in tumor progression, invasion and therapeutic resistance. Among these, cancer-associated fibroblasts (CAFs), derived mainly from normal oral fibroblasts under the influence of tumor-derived cytokines such as transforming growth factor β (TGF-β), angiopoietin-like 3 and platelet-derived growth factor-BB, are the most abundant. CAFs exhibit a myofibroblastic phenotype characterized by α-smooth muscle actin, fibroblast activation protein and integrin α6 expression and their presence correlates with aggressive tumor behavior and poor prognosis. Functionally, CAFs contribute to the 'reverse Warburg effect', remodeling of the extracellular matrix via matrix metalloproteinases and lysyl oxidase, promotion of angiogenesis and immunosuppression through cytokines such as TGF-β, interleukin (IL) 6 and IL-10. Programmed death-ligand 1 (PD-L1), a key immune checkpoint molecule, suppresses T-cell activation by binding programmed death-1 (PD-1) on lymphocytes while also exerting intrinsic oncogenic functions, including enhancement of epithelial-mesenchymal transition, proliferation and resistance to radiotherapy and chemotherapy. PD-L1-enriched extracellular vesicles released by CAFs and tumor cells further propagate immune evasion and metastasis. Although PD-1/PD-L1 blockade with pembrolizumab or nivolumab has improved outcomes in advanced OSCC, variability in PD-L1 expression and intratumoral heterogeneity challenge predictive accuracy. The present review integrated stromal and immune perspectives, emphasizing the dual oncogenic and immunomodulatory roles of CAFs and PD-L1 in shaping the OSCC TME and identifying future therapeutic opportunities targeting both compartments.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disorder characterized by unexplained fibrosis and limited therapeutic options, highlighting the urgent need for innovative treatments. Hyaluronic acid (HA), which is upregulated in IPF and correlates with disease severity, plays an undefined role in its pathogenesis. Hyaluronic acid synthase 2 (HAS2), a key enzyme in HA production, has an unclear function in IPF progression, particularly regarding its involvement in macrophage polarization. Understanding this mechanism is essential for identifying novel therapeutic targets and developing effective drugs for IPF. The present study investigated the roles of HAS2 and HA in IPF and identified potential therapeutic agents. Transcriptomic analysis revealed HAS2 as a critical IPF‑associated gene in patient samples, bleomycin (BLM)‑induced mouse models, and transforming growth factor β1 (TGF‑β1)‑induced myofibroblasts. Single‑cell RNA sequencing further confirmed the fibroblast‑specific upregulation of HAS2 in fibrotic lungs. Experimental validation showed elevated HAS2 expression and HA accumulation in fibrosis models. HA facilitated macrophage M2 polarization and TGF‑β1 secretion through CD44‑dependent STAT6 activation, with CD44 inhibition blocking this effect. Knockdown of HAS2 in fibroblasts decreased HA release and impaired their ability to promote M2 polarization, suggesting that fibroblast‑derived HA drives this process. High‑throughput virtual screening, coupled with absorption, distribution, metabolism and excretion (ADME) profiling, identified orcinol glucoside (OG) as a potential HAS2 inhibitor, which was validated through surface plasmon resonance, cellular thermal shift assays, and molecular dynamics simulations. OG suppressed HA synthesis in TGF‑β1‑induced and HAS2‑overexpressing myofibroblasts in a dose‑dependent manner, inhibiting M2 polarization induction. In vivo, OG reduced collagen deposition, HA, and TGF‑β1 levels in BLM‑induced fibrotic mice. These findings established HAS2 as a central pathogenic factor in IPF and suggested OG as a promising therapeutic candidate, providing a novel approach for IPF treatment by targeting HA synthesis and macrophage polarization.

G protein‑coupled receptor 124 (GPR124) and peroxisome proliferator‑activated receptor γ (PPARγ) constitute two mechanistically distinct signaling molecules that exhibit functional convergence through their opposing regulation of the canonical Wnt/β‑catenin pathway, thereby establishing a critical regulatory network governing inflammatory homeostasis and tissue repair responses. The present comprehensive review elucidates the molecular architecture and pathophysiological significance of the GPR124‑Wnt‑PPARγ regulatory axis, with particular emphasis on its therapeutic implications in chronic inflammatory diseases. GPR124, originally identified as an adhesion G protein‑coupled receptor essential for central nervous system angiogenesis and blood‑brain barrier integrity, functions as a context‑dependent co‑activator of Wnt7a/Wnt7b signaling. By contrast, PPARγ, a ligand‑activated nuclear receptor and master regulator of metabolism and inflammation, exerts potent antagonistic effects on Wnt/β‑catenin signaling through direct β‑catenin degradation mechanisms. The opposing regulation of Wnt signaling by these two receptors establishes a molecular framework that critically influences disease progression in atherosclerosis, diabetic complications, neuroinflammation and cancer‑associated inflammation, with its function being fine‑tuned by tissue‑specific expression patterns and diverse mechanisms. Understanding the GPR124‑Wnt‑PPARγ axis provides novel therapeutic opportunities for combination targeting strategies in chronic inflammatory conditions, where the balance between pro‑angiogenic Wnt activation and anti‑inflammatory PPARγ signaling determines disease outcomes. The present review examines the molecular architecture of GPR124‑PPARγ crosstalk, analyzes pathophysiological implications across multiple organ systems, and evaluates emerging therapeutic strategies for targeting this regulatory network in chronic inflammatory diseases.