International Journal Of Molecular Medicine[JOURNAL]
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200 papers
Endothelial UNC5B regulates blood‑retinal barrier homeostasis.
Yao Y, Wang S, Li J … +4 more , Jin Q, Chen Z, Jiang Q, Li K
Int J Mol Med · 2026 Apr · PMID 41789631 · Full text
The blood‑retinal barrier (BRB), a critical component of the retinal neurovascular unit (NVU), is essential for maintaining retinal homeostasis. Dysfunction of the BRB contributes to vascular leakage, neuronal degenerati...
The blood‑retinal barrier (BRB), a critical component of the retinal neurovascular unit (NVU), is essential for maintaining retinal homeostasis. Dysfunction of the BRB contributes to vascular leakage, neuronal degeneration and gliosis, which are the core pathological hallmarks of diabetic retinopathy (DR) and retinal vein occlusion (RVO). Despite the importance of the BRB, the molecular mechanisms underlying the preservation of BRB integrity under pathological conditions remain unclear. The present study identified the endothelial receptor unc‑5 netrin receptor B (UNC5B) as a critical regulator of BRB and NVU homeostasis and a potential therapeutic target for neurovascular protection. Analysis of a public Gene Expression Omnibus single‑cell transcriptomic dataset, cell and animal models, and clinical samples revealed reduced UNC5B expression in the aqueous humor of patients and in the retinas of DR and RVO models. , endothelial knockdown of UNC5B increased apoptosis (assessed by PI/calcein‑AM staining), impaired barrier function (evaluated by BSA uptake and permeability of cell monolayer) and reduced pericyte recruitment, whereas UNC5B knockdown in pericytes had no detectable effects on pericyte proliferation, apoptosis or migration. , endothelial‑specific UNC5B deficiency markedly exacerbated retinal vascular leakage and structural damage in the DR model, as evidenced by Evans blue leakage, Periodic acid‑Schiff staining and immunofluorescence analyses. Furthermore, UNC5B knockdown abolished the protective effects of high‑dose netrin‑1 administration in DR mice. Endothelial UNC5B modulation, including knockdown and overexpression, affected not only the vascular integrity but also the neural components within the NVU, as evidenced by altered retinal ganglion cell degeneration and glial activation in the DR model, assessed using NeuN, β‑III tubulin and vimentin staining. In the RVO model, endothelial UNC5B deficiency aggravated retinal edema and thinning, as revealed by retinal imaging. Mechanistically, transcriptomic and protein analyses revealed that UNC5B downregulation was associated with increased extracellular matrix protein deposition and reduced Hippo pathway activity. Collectively, these findings established UNC5B as a key mediator of BRB and NVU stability, and highlighted its therapeutic potential in maintaining vascular integrity and protecting neural elements in retinal vascular diseases.
DUSP26: Unveiling a critical molecular mediator and therapeutic target in developmental dysplasia of the hip‑associated secondary osteoarthritis.
Wang E, Zhang H, Wu D … +2 more , Ali S, Ji X
Int J Mol Med · 2026 Apr · PMID 41789628 · Full text
Secondary osteoarthritis, a degenerative joint disease, is often precipitated by well‑characterized etiological factors, with developmental dysplasia of the hip (DDH) emerging as a leading contributor. Despite its clinic...
Secondary osteoarthritis, a degenerative joint disease, is often precipitated by well‑characterized etiological factors, with developmental dysplasia of the hip (DDH) emerging as a leading contributor. Despite its clinical importance, the intricate molecular and cellular cascades triggered by the biomechanical perturbations associated with DDH remain poorly understood. In the present study, a swaddling‑induced rat model of DDH was successfully developed, which recapitulated key pathological features including acetabular labral tears and cartilage degeneration. Through comprehensive mRNA‑sequencing analysis of acetabular cartilage samples from rats with DDH, a notable upregulation of dual‑specificity phosphatase 26 (DUSP26) was identified, a protein with previously unreported roles in joint homeostasis. Subsequently, in an inflammatory microenvironment induced by interleukin (IL)‑1β, adenovirus‑mediated overexpression of DUSP26 demonstrated marked chondroprotective effects. Specifically, this intervention led to a significant increase in the expression of type II collagen, a hallmark of healthy chondrocytes, while concurrently reducing the levels of catabolic markers such as type I collagen, TNF‑α and IL‑6. Reciprocally, adenovirus‑delivered short hairpin RNA‑mediated DUSP26 silencing exacerbated cartilage degradation, validating its protective function. Employing mass spectrometry‑based proteomics combined with genetic and pharmacological approaches, the underlying mechanism was elucidated: DUSP26 overexpression exerted its chondroprotective effects by dephosphorylating and inactivating histone deacetylase (HDAC)1, HDAC2 and HDAC8, thereby maintaining chondrocyte integrity. Collectively, the findings of the present study underscore DUSP26 as a promising therapeutic target for DDH‑associated osteoarthritis, offering novel mechanistic insights and laying the groundwork for the development of targeted interventions to mitigate secondary joint degeneration.
Bumetanide‑blocked SLC12A2 exerts a protective effect in experimental diabetic retinopathy.
Zhang Y, Wang X, Xie Q … +6 more , Huang Y, Huang D, Liu Z, Xu T, Ni M, Yang H
Int J Mol Med · 2026 Apr · PMID 41789623 · Full text
Diabetic retinopathy (DR) is a common microvascular complication that leads to vision loss in patients with diabetes. The SLC12A2/SLC12A4 inhibitor, bumetanide, has been reported to alleviate hypoxia‑induced retinopathy....
Diabetic retinopathy (DR) is a common microvascular complication that leads to vision loss in patients with diabetes. The SLC12A2/SLC12A4 inhibitor, bumetanide, has been reported to alleviate hypoxia‑induced retinopathy. It was hypothesized that it may exert the same effect in DR. DR cell types and SLC12A2/SLC12A4 expression at the cell level were analyzed using single cell RNA‑sequencing (scRNA‑seq) data. Next, cell [high glucose (HG) stimulation] and animal (mice injected with streptozotocin) DR models were constructed. The protective effects and possible mechanisms of bumetanide and SLC12A2 were investigated through a series of experiments, including Cell Counting Kit‑8, TUNEL, Transwell, tube formation, ELISA, immunofluorescence staining, western blot and reverse transcription‑quantitative PCR assays. Bumetanide reduced HG‑induced cell apoptosis by suppressing the expression of SLC12A2 and SLC12A4. Second, scRNA‑seq analysis revealed that SLC12A2 was predominantly expressed in endothelial cells, which are the main targets of hyperglycemic damage. Endothelial cell‑related markers were involved in angiogenesis and adhesion molecule‑related pathways. Third, in HG‑stimulated cells, SLC12A2 knockdown efficiently reduced the inflammatory response and angiogenesis, while maintaining endothelial barrier integrity. This protective process involved reduced release of inflammatory factors (IL‑1β and IL‑6) and growth factors (vascular endothelial growth factor), suppression of adhesion molecule expression (VCAM1, ICAM1, E‑Selectin and P‑Selectin), activation of tight junction protein (ZO‑1), and decreased matrix metalloproteinases (MMP2 and MMP9). Furthermore, SLC12A2 deficiency ameliorated DR progression in streptozotocin‑induced diabetic mice by improving retinal thickness and pathological changes. The present study elucidates the crucial role of bumetanide in DR treatment and suggests that targeting SLC12A2 may represent a novel therapeutic strategy for the prevention of DR.
Peroxisome proliferator‑activated receptor α regulates acesulfame‑K‑induced NAFLD via hepatic PLCβ: Foe and friend.
Lin PY, Xie JR, Qian TC … +12 more , Wang SS, Yu SY, Shi WB, Wang Y, Cen LZ, Zhu QJ, Zheng YY, Gao H, Fang R, Xia ZX, Liu AM, Xu L
Int J Mol Med · 2026 Apr · PMID 41789618 · Full text
Food additive acesulfame‑K (AK), a non‑nutritive sweetener, is widely used as a low‑calorie sugar substitute to reduce energy intake. However, its potential impact on nonalcoholic fatty liver disease (NAFLD) and the invo...
Food additive acesulfame‑K (AK), a non‑nutritive sweetener, is widely used as a low‑calorie sugar substitute to reduce energy intake. However, its potential impact on nonalcoholic fatty liver disease (NAFLD) and the involvement of peroxisome proliferator‑activated receptor α (PPARα) remain unclear. In the present study, male wild‑type (WT) and PPARα‑null (KO) mice fed a 60% high‑fat diet were treated with AK (2 mg/ml) in drinking water for 12 weeks to evaluate the effects of chronic AK exposure on NAFLD progression and the role of PPARα. PPARα inhibition and activation strategies were further applied in and models to validate the key findings. AK supplementation markedly increased hepatic lipid accumulation and impaired glucose tolerance through activation of phospholipase C beta (PLCβ) in hepatic sweet taste receptor (STR) signaling in the WT mice, but not in the KO mice. Consistently, PLCβ activation was observed in AK‑induced lipid accumulation in Hepa1‑6 and Huh‑7 cells and was abolished by PPARα knockdown or inhibition. Pharmacological activation of PPARα mitigated AK‑induced NAFLD progression by suppressing PLCβ activation in STR signaling. These findings demonstrated that chronic AK intake exacerbates NAFLD progression via PLCβ activation in hepatic STR signaling and that PLCβ activation depends on physiological PPARα activity. Pharmacological PPARα activation exerts a protective effect, highlighting the dual roles of PPARα in regulating AK‑associated NAFLD risk.
miRNA‑378a‑5p attenuates the development of abdominal aortic aneurysm via ABLIM1‑MKL1 signaling pathways.
Wang J, Zou Y, Wang Y … +8 more , Yang Z, Liu D, Su X, Song H, Xu K, Yan C, Liu D, Han Y
Int J Mol Med · 2026 Apr · PMID 41716026 · Full text
Abdominal aortic aneurysm (AAA) is a fatal cardiovascular disease with no effective drug treatment currently available. The aberrant expression levels of microRNAs (miRNAs or miRs) contribute to AAA pathogenesis. In the...
Abdominal aortic aneurysm (AAA) is a fatal cardiovascular disease with no effective drug treatment currently available. The aberrant expression levels of microRNAs (miRNAs or miRs) contribute to AAA pathogenesis. In the present study, miRNA microarray analysis was performed to screen for differentially expressed miRNAs in the aortas of AAA mice compared with those in control mice, and to clarify the role and mechanism of miRNA‑378a‑5p (miR‑378a‑5p) in the AAA development. A comprehensive miRNA microarray analysis was conducted to screen for differentially expressed miRNAs in the aortas of AAA mice and control mice. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to detect the expression levels of miR‑378a‑5p in the serum and aortas of patients with AAA and mice. To clarify the role of miR‑378a‑5p in the AAA development , miR‑378a‑5p antagomir and angomir were administered to ApoE‑/‑ mice using tail venous injection, followed by Angiotensin II (Ang II) infusion. Next, the role of miR‑378a‑5p in the phenotypic switching and migration of vascular smooth muscle cells (VSMCs) was examined and . Mechanistically, the targets of miR‑378a‑5p were identified by bioinformatics analysis, luciferase assay, RT‑qPCR and western blotting. Co‑immunoprecipitation assay combined with mass spectrometry were carried out for excavating potential downstream effectors. The expression of miR‑378a‑5p was decreased in the serum and aortas of patients with AAA (aortic dissection) and mice, and tumor necrosis factor‑α‑treated VSMCs. , the antagomir‑378a‑5p aggravated AAA formation, as evidenced by a larger maximal aortic diameter and greater medial elastin degradation than in control mice. miR‑378a‑5p angomir had the opposite effect. , miR‑378a‑5p overexpression significantly promoted the contraction ability and suppressed the migration of VSMCs, whereas miR‑378a‑5p knockdown inhibited the contraction ability and increased the migration of VSMCs. Mechanistically, it was identified that miR‑378a‑5p played a protective role in AAA development by regulating actin‑binding LIM protein 1 (ABLIM1)‑megakaryoblastic leukemia 1 (MKL1) pathway. miR‑378a‑5p exerts protective effects against AAA by maintaining VSMCs homeostasis via the ABLIM1‑MKL1 pathway. Therefore, targeting miR‑378a‑5p may be an attractive therapeutic strategy for AAA treatment.
The role and mechanism of IL‑35 in myasthenia gravis (Review).
Mao J, Zhang LM, Zhu YL … +2 more , Gao SJ, Liu MW
Int J Mol Med · 2026 Apr · PMID 41716022 · Full text
Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by impaired neuromuscular junction transmission, leading to fluctuating muscle weakness and fatigue. This condition is driven primarily by autoantibod...
Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by impaired neuromuscular junction transmission, leading to fluctuating muscle weakness and fatigue. This condition is driven primarily by autoantibodies targeting the acetylcholine receptor at the neuromuscular junction. These antibodies are predominantly generated through a T‑cell‑dependent pathway, initiating immunomodulatory responses via complement activation. Cytokines and inflammatory mediators also play pivotal roles in the pathogenesis of MG. Recently, increasing attention has been given to the involvement of cytokines in autoimmune diseases. Interleukin‑35 (IL‑35), an immunoregulatory cytokine, is critical in various inflammatory and autoimmune conditions. It modulates immune responses by promoting Treg proliferation, enhancing their immunosuppressive functions, inhibiting Th17 cell differentiation, and reducing proinflammatory cytokine levels. IL‑35 is thus pivotal in the onset and progression of MG. The present review outlines the key functions of IL‑35 in MG pathogenesis and the impact of IL‑35 on the treatment and prognosis of myasthenia gravis, explores its therapeutic potential, and assesses its prognostic value, offering insights into its mechanisms and implications for treatment.
Metabolic hubs in reproduction: The regulatory network of lipid droplets in gamete and embryo physiology (Review).
Pan L, Wen Z, Jin Y
Int J Mol Med · 2026 Apr · PMID 41716021 · Full text
Lipid droplets (LDs) are dynamic organelles that extend beyond lipid storage to regulate diverse aspects of reproductive physiology. In both mammals and , LDs support gamete maturation, fertilization, embryogenesis and s...
Lipid droplets (LDs) are dynamic organelles that extend beyond lipid storage to regulate diverse aspects of reproductive physiology. In both mammals and , LDs support gamete maturation, fertilization, embryogenesis and steroidogenesis by modulating lipid mobilization, signaling pathways, protein quality control and hormone production. The present review highlights the roles of LDs in oocytes, sperm, Sertoli and granulosa cells, embryonic stem cells and early embryos. Key regulatory molecules, including perilipins, adipose triglyceride lipase, Hormone‑Sensitive Lipase (HSL), Diacylglycerol O‑acyltransferases and seipin, as well as lipophagy, are discussed in the context of reproductive cell function. demonstrates conserved genetic pathways linking LD metabolism with gamete quality and embryonic viability. The present review aimed to discuss emerging technologies such as lipidomics, high‑resolution imaging, Clustered Regularly Interspaced Short Palindromic Repeats screening and single‑cell sequencing that enable deeper investigation into LD dynamics. Finally, the present review aimed to examine how LD dysfunction contributes to reproductive disorders including infertility, polycystic ovary syndrome and metabolic syndrome. Understanding LD biology offers promising avenues for improving reproductive health and gamete and embryonic developmental potential.
Microglia‑mediated neuroinflammation in intracerebral hemorrhage: Pathological mechanisms and implications for therapeutic development (Review).
Fan X, Pu C, Zhong L … +6 more , Wang O, Zhao B, Liao D, Bai X, Chen G, Yang G
Int J Mol Med · 2026 Apr · PMID 41716017 · Full text
Intracerebral hemorrhage (ICH), a life‑threatening subtype of stroke accounting for 10‑15% of global stroke cases, is characterized by high disability and mortality rates, imposing a heavy socioeconomic burden worldwide....
Intracerebral hemorrhage (ICH), a life‑threatening subtype of stroke accounting for 10‑15% of global stroke cases, is characterized by high disability and mortality rates, imposing a heavy socioeconomic burden worldwide. Despite its clinical importance, no effective therapeutic interventions exist for this condition. As the resident immune cells of the central nervous system, microglia play a pivotal role in the pathophysiology of ICH. These cells can be activated to adopt either anti‑inflammatory or pro‑inflammatory phenotypes. Following ICH, pro‑inflammatory mediators derived from microglia act as key drivers of neuroinflammation, thereby exacerbating secondary brain injury. By contrast, promoting the phenotypic shift of microglia toward an anti‑inflammatory state has been shown to mitigate an inflammatory response and facilitate neurological recovery. In the present study, existing evidence was reviewed to propose that post‑ICH brain injury and repair are orchestrated not by isolated cells, but by a highly dynamic neuroimmune network centered on microglia. Elucidating the spatiotemporal dynamics and key communicative nodes within this network represents a critical frontier. Moving beyond the classical M1/M2 dichotomy to target this network contextually offers a promising and precise therapeutic aim for future investigations.
Dysregulated post‑translational modifications in granulosa cells drive ovarian dysfunction and potential infertility applications (Review).
Zhong Y, Zou Y, Yang Z … +3 more , Wang J, Pan Z, Feng J
Int J Mol Med · 2026 Apr · PMID 41716015 · Full text
Ovarian granulosa cells (GCs), as key components of follicles, orchestrate follicular development and ovarian maturation through bidirectional communication with oocytes and through hormone synthesis. Their dysfunction s...
Ovarian granulosa cells (GCs), as key components of follicles, orchestrate follicular development and ovarian maturation through bidirectional communication with oocytes and through hormone synthesis. Their dysfunction substantially contributes to female infertility. Post‑translational modifications (PTMs) carry out pivotal roles in the regulation of ovarian physiology and pathology by modulating GC proliferation, differentiation, apoptosis and steroid hormone secretion. The present review seeks to summarize the current advances in canonical PTMs such as phosphorylation, methylation, acetylation and ubiquitination, as well as novel protein modifications such as SUMOylation and lactylation, particularly focusing on their roles in the proliferation, differentiation and apoptosis of GCs at the molecular level. Moreover, the present review explores how aberrant PTMs impair GC function, leading to follicular developmental disorders, and proposes that targeting PTM‑regulated signaling in GCs may provide novel therapeutic strategies for ovarian dysfunction. Collectively, the present review aims to provide insights into elucidating the etiology of infertility, and establishing a theoretical foundation for the development of PTM‑targeted reproductive interventions.
[Corrigendum] Hsa_circularRNA_0079201 suppresses chondrocyte proliferation and endochondral ossification by regulating the microRNA‑140‑3p/SMAD2 signaling pathway in idiopathic short stature.
Liu X, Yan C, Deng X … +1 more , Jia J
Int J Mol Med · 2026 Apr · PMID 41685591 · Full text
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‑1...
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 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].
Targeting the gut‑bone axis through exercise: A novel approach to osteoporosis prevention and treatment (Review).
Wu J, Zhang S, Wu J … +7 more , Luan Y, Yao X, Xu B, Wang Y, Sheng Y, Xue Y, Ren Y
Int J Mol Med · 2026 Apr · PMID 41685587 · Full text
Osteoporosis is a metabolic bone disease marked by decreased bone mineral density and deterioration of bone microarchitecture. Its development involves complex interactions between genetic factors, nutrition, hormones an...
Osteoporosis is a metabolic bone disease marked by decreased bone mineral density and deterioration of bone microarchitecture. Its development involves complex interactions between genetic factors, nutrition, hormones and lifestyle factors. As the global population is aging, osteoporosis has become a public health concern. Although drug treatments such as bisphosphonates and hormone replacement therapy are available, these options are limited by high costs and adverse side effects, highlighting the need for alternative approaches. The gut microbiota is a regulator of bone metabolism through its metabolites, effects on immune function and role in maintaining intestinal barrier integrity, endocrine signaling and nutrient absorption. Exercise, beyond its role in promoting bone strength through mechanical loading, enhances calcium absorption, thereby modulating gut microbiota composition. Within this context, exercise‑based strategies may provide a promising avenue for both osteoporosis prevention and treatment by targeting the gut‑bone axis, however, the underlying molecular mechanisms remain incompletely understood and additional clinical evidence is required. The present review summarizes how exercise‑induced changes in gut microbiota may influence bone health, also discussing the relevance of these to the management of osteoporosis.
Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review).
Cascardi E, Della Mura M, Sgarro N … +9 more , Minei S, Cazzato G, Maiorano E, Lo Muzio L, Bizzoca ME, Vieira E Silva FF, Lo Muzio E, Dioguardi M, Ballini A
Int J Mol Med · 2026 Apr · PMID 41685581 · Full text
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 therapeut...
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.
[Corrigendum] Silencing of Rac1 modifies lung cancer cell migration, invasion and actin cytoskeleton rearrangements and enhances chemosensitivity to antitumor drugs.
Chen QY, Xu LQ, Jiao DM … +7 more , Yao QH, Wang YY, Hu HZ, Wu YQ, Song J, Yan J, Wu LJ
Int J Mol Med · 2026 Apr · PMID 41685580 · Full text
Following the publication of this paper, it was drawn to the Editor's attention by an interested reader that, for the Transwell migration and invasion assay experiments shown in Fig. 3A and 3C respectively on p. 772, one...
Following the publication of this paper, it was drawn to the Editor's attention by an interested reader that, for the Transwell migration and invasion assay experiments shown in Fig. 3A and 3C respectively on p. 772, one and two pairs of data panels respectively were overlapping, such that data which were intended to show the results of differently performed experiments had apparently been derived from the same original sources. In addition, in Fig. 1 on p. 771, the same data panel had apparently been included to show the results of (C) strong cytoplasmic Rac1 expression and (E) weak cytoplasmic Rac1 expression in lung squamous cell carcinoma tissues. Upon contacting the authors about these issues, they realized that certain of the data had inadvertently been included in Figs. 1 and 3 incorrectly. The revised versions of Figs. 1 and 3, now featuring the correct data for weak cytoplasmic expression in Fig. 1E and the correct data panels for the 801D‑shRNA control and 801D‑NSC23766 experiments in Fig. 3A and C respectively, are shown opposite and on the next page. The authors wish to emphasize that the errors made in assembling the data in this pair of figures 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 28: 769‑776, 2011; DOI: 10.3892/ijmm.2011.775].
and hyperglycemia fuel gastric cancer glycolysis: Mechanisms and targeted intervention (Review).
Liu Y, Wang F, Deng Y … +10 more , Hu Y, Shu F, Yu J, Gou G, Wen M, Luo C, Lu X, Du Q, Xu J, Xie R
Int J Mol Med · 2026 Apr · PMID 41685579 · Full text
() is a Gram‑negative bacterial pathogen, and infection with this pathogen is a primary risk factor for gastric cancer (GC), often inducing chronic gastritis, which further increases the risk of cancer. Glycolysis carrie...
() is a Gram‑negative bacterial pathogen, and infection with this pathogen is a primary risk factor for gastric cancer (GC), often inducing chronic gastritis, which further increases the risk of cancer. Glycolysis carries out a key role in GC metabolism, serving as the primary energy pathway for cancer cells, particularly under hypoxic conditions. Enhanced glycolysis allows GC cells to sustain high proliferation rates and produce lactic acid, creating an acidic tumor microenvironment that promotes tumor progression. Understanding the mechanisms of ‑driven glycolysis may provide new insights into GC pathogenesis and reveal novel therapeutic targets. The present review addresses advances in glycolysis research in GC, summarizing its characteristics, identifying key mediators involved in metabolic reprogramming and exploring potential molecular mechanisms to recommend new targets for therapy.
Orcinol glucoside ameliorates pulmonary fibrosis by suppressing hyaluronic acid synthesis and macrophage M2 polarization via targeting hyaluronic acid synthase 2.
Li C, Tang X, Luo X … +7 more , Lai X, Yang J, Xu Z, Muhetaer G, Xie Y, Huang X, Li H
Int J Mol Med · 2026 Apr · PMID 41685577 · Full text
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 (...
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. , 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.
Post‑translational modifications in diabetic kidney disease (Review).
He M, Wang Z, Miao Z … +6 more , Zhao Y, Wei L, Zhang L, Yin R, Wang Y, Yang L
Int J Mol Med · 2026 Apr · PMID 41685570 · Full text
Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease, with increasing global prevalence, resulting in a notable increase in the risk of kidney failure and cardiovascular events. Post‑translational...
Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease, with increasing global prevalence, resulting in a notable increase in the risk of kidney failure and cardiovascular events. Post‑translational modifications (PTMs) are biochemical modifications that occur on specific residues on proteins, leading to an increase in the diversity of proteins and modulation of protein functions. PTMs encompass numerous processes, including phosphorylation, acetylation, methylation, ubiquitination, small ubiquitin‑like modifier‑ylation, glycosylation, palmitoylation, glutathionylation, S‑nitrosylation, sulfhydration, as well as lactylation and neddylation. PTMs are associated with the occurrence and progression of DKD. The present review aimed to summarize PTMs and their roles in the pathophysiological mechanisms of DKD, including cell death, oxidative stress, mitochondrial dysfunction, inflammation and fibrosis.
Hypothermic machine perfusion protects DCD graft liver from ischemia‑reperfusion injury by enhancing macrophage efferocytosis via KLF2‑NLRP3 signaling.
Deng Q, Liu Z, Ye Q … +8 more , Liu J, Fu Z, Zhang X, Luo J, Lu Z, Yue P, Xiao J, Xiao Q
Int J Mol Med · 2026 Apr · PMID 41645764 · Full text
Donation after circulatory death (DCD) is a key source of liver grafts but it is associated with more severe ischemia‑reperfusion injury (IRI) and poorer transplant outcomes compared with donation after brain death. Hypo...
Donation after circulatory death (DCD) is a key source of liver grafts but it is associated with more severe ischemia‑reperfusion injury (IRI) and poorer transplant outcomes compared with donation after brain death. Hypothermic machine perfusion (HMP) effectively decreases DCD graft injury, but its protective molecular mechanisms remain unclear. Kruppel‑like factor 2 (KLF2) is an endothelial protective transcription factor induced by hemodynamic mechanical stimulation. However, the role of KLF2 in IRI during HMP in DCD livers is unclear. Rat livers undergoing DCD modeling followed by static cold storage (CS) or HMP were used to assess KLF2 expression and macrophage efferocytosis. Injury was assessed by serum alanine transferase/aspartate transferase levels, histology, TUNEL apoptosis assay and immunofluorescence (IF) for in situ efferocytosis. Protein markers were analyzed via western blotting, immunohistochemistry and IF. , HUVECs and macrophages were subjected to simulated CS/reperfusion. Macrophages efferocytosis was quantified using fluorescently labeled apoptotic Jurkat cells. Mechanisms were explored by RNA sequencing and co‑immunoprecipitation. Compared with the CS group, HMP decreased pathological injury, apoptosis and inflammation in DCD liver injury. KLF2 expression was upregulated. However, knockdown of KLF2 abrogated these endothelial protective effects . Furthermore, overexpression of KLF2 enhanced macrophage efferocytosis, whereas suppression of KLF2 impaired this. Moreover, enhanced efferocytosis contributed to inflammation resolution, ultimately improving overall graft injury and decreasing apoptosis. Mechanistically, KLF2 inhibited the NOD‑like receptor protein 3 (NLRP3) inflammasome to suppress pyroptosis, thereby indirectly enhancing efferocytosis. HMP alleviated IRI in DCD liver grafts by upregulating endothelial KLF2, which inhibited NLRP3 inflammasome‑mediated pyroptosis, thereby improving the inflammatory microenvironment and promoting macrophage efferocytosis.
[Corrigendum] Inhibition of acid‑sensing ion channel 1a attenuates acid‑induced activation of autophagy via a calcium signaling pathway in articular chondrocytes.
Gao WF, Xu YY, Ge JF … +1 more , Chen FH
Int J Mol Med · 2026 Apr · PMID 41645760 · Full text
Following the publication of the above article, an interested reader drew to the authors' attention that the control β‑actin western blots shown in Figs. 2C and 5A were strikingly similar, even though the experimental co...
Following the publication of the above article, an interested reader drew to the authors' attention that the control β‑actin western blots shown in Figs. 2C and 5A were strikingly similar, even though the experimental conditions reported in these figures were different. After having re‑examined the original data, the authors have realized that these western blots were inadvertently included in Fig. 2C erroneously. The revised version of Fig. 2, now incorporating the correct data for the β‑actin bands in Fig. 2C, is shown below. The authors confirm that the error associated with this figure did not have a 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 43: 1778‑1788, 2019; DOI: 10.3892/ijmm.2019.4085].
Ebastine targets HER2/HER3 signaling and cancer stem cell traits to overcome trastuzumab resistance in HER2‑positive breast cancer.
Jung E, Kim JY, Ko D … +12 more , Seo J, Lee SY, Lee D, Kim S, Park M, Kim S, Park S, Lee K, Kang YK, Nam KD, Kim YJ, Seo JH
Int J Mol Med · 2026 Apr · PMID 41645758 · Full text
Despite advances in HER2‑targeted therapy for HER2‑positive breast cancer, resistance to trastuzumab and tumor recurrence remain major barriers to durable outcomes. The present study evaluated the therapeutic potential o...
Despite advances in HER2‑targeted therapy for HER2‑positive breast cancer, resistance to trastuzumab and tumor recurrence remain major barriers to durable outcomes. The present study evaluated the therapeutic potential of ebastine, a second‑generation H1‑antihistamine, as a repurposing candidate to overcome trastuzumab resistance by targeting HER2 signaling and cancer stem cell (CSC)‑associated phenotypes in HER2‑positive breast cancer cells. Molecular docking studies revealed that ebastine bound to the ATP‑binding site of the HER2 tyrosine kinase domain, thereby suppressing the phosphorylation of HER2, p95HER2 and HER3, as assessed by immunoblotting. Immunoprecipitation assay further demonstrated that this binding disrupted HER2/HER3 and HER2/EGFR heterodimerization, leading to reduced downstream AKT activation. Ebastine significantly decreased aldehyde dehydrogenase (ALDH)1 activity, decreased the CD44/CD24 CSC‑like population, as assessed by flow cytometry, and inhibited mammosphere formation. In a trastuzumab‑resistant xenograft model, ebastine markedly suppressed tumor growth, decreased the Ki‑67 proliferation index and angiogenesis and induced apoptosis. These effects were accompanied by decreased expression of HER2, HER3, ALDH1, CD44, and vimentin in tumor tissues, as determined by immunohistochemistry. Furthermore, serum biochemical analyses revealed no significant hepatotoxicity or nephrotoxicity, indicating a favorable safety profile. These findings demonstrated that ebastine effectively disrupts key pathways involved in CSC‑like traits and HER2 activity, even under trastuzumab‑resistant conditions. Its multifaceted inhibitory effects support the repositioning of ebastine as a promising therapeutic strategy for treating refractory HER2‑positive breast cancer.
Signalling pathways regulated by FSTL1 in inflammation and potential therapeutic applications (Review).
Ma C, Li J, Jiang W … +6 more , Chen X, Liu J, Tao X, Li W, Deng Z, Zhao Z
Int J Mol Med · 2026 Apr · PMID 41645756 · Full text
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,...
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.
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