International Journal Of Molecular Medicine[JOURNAL]
Sun
200 papers
Sex differences in cardiovascular‑kidney‑metabolic syndrome: From pathogenesis to treatment response (Review).
Fan Y, Hu H, Cheng J
Int J Mol Med · 2026 Jul · PMID 42212379 · Full text
Cardiovascular‑kidney‑metabolic (CKM) syndrome is an emerging clinical construct that emphasizes the intertwined pathophysiology of cardiovascular disease, chronic kidney disease, and metabolic disorders. Accumulating ev...
Cardiovascular‑kidney‑metabolic (CKM) syndrome is an emerging clinical construct that emphasizes the intertwined pathophysiology of cardiovascular disease, chronic kidney disease, and metabolic disorders. Accumulating evidence reveals profound sex‑based differences in the incidence, progression, and outcomes across the spectrum of CKM syndrome. These disparities are rooted in complex interactions between sex hormones and pathophysiological processes such as inflammation, endothelial dysfunction, oxidative stress, and metabolic regulation. Premenopausal women generally exhibit protective cardiovascular and renal profiles due to estrogenic effects, whereas men, influenced by androgens, often experience more severe organ damage and faster disease progression. However, this female advantage is attenuated after menopause, and available clinical data suggest that women may experience poorer outcomes at comparable CKM stages in some cohorts. Furthermore, sex differences extend to clinical manifestations, epidemiologic patterns, and therapeutic responses, influencing the efficacy and tolerance of medications including statins, renin‑angiotensin‑aldosterone system inhibitors, sodium‑glucose cotransporter 2 inhibitors, and insulin. Sex‑related factors, including healthcare access, referral patterns, adherence, and trial representation, may further modify clinical outcomes. The present review synthesizes current knowledge on sex‑specific mechanisms of CKM pathogenesis, clinical trajectories, and pharmacologic responses, and highlights gaps between basic and clinical research. Future directions include designing sex‑stratified clinical trials, developing sex‑sensitive guidelines, and leveraging translational research to inform precision medicine. Addressing sex‑related differences in CKM syndrome represents a crucial step toward equitable and personalized care in cardio‑renal‑metabolic medicine.
Integrative transcriptomic analysis unveils FXR as a key regulator of intestinal stemness and inflammation in ulcerative colitis.
Lin H, Cheng X, Ren Y … +4 more , Zhang Y, Chen W, Lu Q, Tian Y
Int J Mol Med · 2026 Jul · PMID 42212373 · Full text
High‑throughput transcriptomic technologies offer a systems‑level approach to unravel the mechanisms of complex immune disorders. Inflammatory Bowel Disease (IBD), a classic example of such disorders, involves intricate...
High‑throughput transcriptomic technologies offer a systems‑level approach to unravel the mechanisms of complex immune disorders. Inflammatory Bowel Disease (IBD), a classic example of such disorders, involves intricate interactions between genetics, microbiota and immune dysfunction. The nuclear receptor farnesoid X receptor (FXR) is implicated in IBD, but its precise mechanisms remain unclear. To investigate the role of FXR in ulcerative colitis (UC), the present study employed an integrative transcriptomic strategy, combining bulk transcriptomics (GSE75214, GSE13367 and GSE87466) and single‑cell RNA‑sequencing data (GSE116222) of human UC samples obtained from the Gene Expression Omnibus database. Subsequently, these findings were validated in a dextran sulfate sodium‑induced colitis model using FXR global knockout mice. The results revealed that FXR expression is downregulated in UC and co‑localizes with the stem cell marker CD133 in intestinal crypts. FXR deficiency exacerbated dextran sulfate sodium‑induced colitis, impaired the expression of stemness‑associated transcription factors (octamer‑binding transcription factor 3/4, homeobox protein NANOG, transcription factor SOX2 and Sal‑like protein 4), and activated the NF‑κB pathway, leading to increased production of pro‑inflammatory cytokines, specifically TNF‑α and IL‑1β. By integrating bulk and single‑cell transcriptomics with genetic validation, the present study uncovered an FXR‑dependent mechanism linking intestinal stem cell dysfunction to NF‑κB‑driven inflammation in colitis, and established a generalizable multi‑layer transcriptomic dissection strategy for complex inflammatory disorders.
Oxygen‑sensing histone demethylase KDM6A modulates chondrocyte‑to‑osteoblast transdifferentiation by activating the Wnt/β‑catenin pathway.
Rong Y, Yu H, Yin H … +8 more , Li S, Wang J, Shen Z, Ding X, Bu F, Dai T, Wu G, Hua Z
Int J Mol Med · 2026 Aug · PMID 42212366 · Full text
Fracture healing is a complex biological process involving chondrocyte (CH) differentiation and endochondral ossification. A subset of CHs may transdifferentiate into osteoblasts, enhancing bone regeneration. The oxygen‑...
Fracture healing is a complex biological process involving chondrocyte (CH) differentiation and endochondral ossification. A subset of CHs may transdifferentiate into osteoblasts, enhancing bone regeneration. The oxygen‑sensing histone demethylase lysine demethylase 6A (KDM6A) and local oxygen microenvironment are hypothesized to serve pivotal roles in modulating this transition; however, the precise regulatory mechanisms remain unclear. To assess the role of KDM6A, an oxygen‑sensitive histone demethylase, in endochondral ossification, an inducible cartilage‑specific Kdm6a‑knockout mouse model was generated. Single‑cell RNA sequencing (scRNA‑seq) analysis was performed in a mouse tibial fracture model to characterize CH subpopulations and their fate transitions during bone repair. scRNA‑seq identified distinct CH subpopulations, including chondrocyte‑derived osteoprogenitors (CDOPs), which acted as osteoblast precursors during endochondral ossification. Pseudotime trajectory analysis revealed a bifurcated differentiation pathway, with CDOPs exhibiting rapid osteoblast conversion. Functional enrichment analyses implicated the Wnt/β‑catenin pathway in this transition. In vitro, CHs isolated from bone callus of KDM6A‑knockout and control mice were induced to undergo transdifferentiation into osteoblasts under varying oxygen tensions. The expression levels of chondrogenic markers, osteogenic differentiation‑related indicators and canonical Wnt signaling molecules, as well as the levels of histone dimethylation of H3K27 (H3K27me2) and trimethylation of H3K27 (H3K27me3) at their promoter regions, were assessed. In vivo, the molecular and functional consequences of KDM6A deficiency were characterized through histopathological evaluation and bone microarchitecture analysis. , CHs cultured under normoxic conditions exhibited greater osteogenic differentiation than those cultured under hypoxic conditions. Conversely, loss of KDM6A impaired the pro‑osteogenic effect of normoxia on CH‑to‑osteoblast transdifferentiation, indicating the importance of KDM6A in oxygen‑mediated CH‑to‑osteoblast transdifferentiation. Mechanistically, chromatin immunoprecipitation analysis revealed that under normoxic conditions, KDM6A‑knockout CHs exhibited higher levels of the repressive histone marks H3K27me2 and H3K27me3 at the Wnt3a promoter region, as well as increased H3K27me3 levels at the Runt‑related transcription factor 2 (RUNX2) promoter region, compared with control cells. These findings indicated that KDM6A catalyzed the removal of H3K27 methylation at the promoters of Wnt3a and RUNX2, thereby relieving their transcriptional repression. , KDM6A‑knockout mice exhibited osteogenic defects and delayed fracture healing compared with control mice. KDM6A serves as a pivotal oxygen sensor that drives CH‑to‑osteoblast transdifferentiation and enhances fracture healing through Wnt/β‑catenin pathway activation. The KDM6A‑mediated oxygen response mechanism is a potential target for enhancing bone regeneration during fracture repair.
[Retracted] BAMBI inhibits inflammation through the activation of autophagy in experimental spinal cord injury.
Yang Y, Guo C, Liao B … +3 more , Cao J, Liang C, He X
Int J Mol Med · 2026 Jul · PMID 42212359 · Full text
Following the publication of the above article, a concerned reader drew the Editor's attention to the fact that the Nissl staining images shown in Fig. 3C on p. 427 contained a series of internally duplicated groupings/r...
Following the publication of the above article, a concerned reader drew the Editor's attention to the fact that the Nissl staining images shown in Fig. 3C on p. 427 contained a series of internally duplicated groupings/repeated patternings of cells within the various data panels that could not easily be attributed to coincidence. A subsequent investigation of the data in this paper revealed that the Nissl staining images shown in Fig. 2C were similarly affected by the same phenomenon. After having conducted an internal investigation of the data in this paper, the Editor of has decided that this article should be retracted from the publication on the grounds of an overall lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor sincerely apologizes to the readership for any incovenience caused, and we thank the reader for drawing this matter to our attention. [International Journal of Molecular Medicine 39: 423‑429, 2017; DOI: 10.3892/ijmm.2016.2838].
[Corrigendum] Activated Wnt signaling induces myofibroblast differentiation of mesenchymal stem cells, contributing to pulmonary fibrosis.
Sun Z, Wang C, Shi C … +5 more , Sun F, Xu X, Qian W, Nie S, Han X
Int J Mol Med · 2026 Jul · PMID 42169658 · Full text
Following the publication of the above article, a concerned reader drew to the authors' attention that the immunohistochemical data shown for the 'Collagen I/Control' panel in Fig. 5B on p. 1104, and the 'β‑catenin/DKK'...
Following the publication of the above article, a concerned reader drew to the authors' attention that the immunohistochemical data shown for the 'Collagen I/Control' panel in Fig. 5B on p. 1104, and the 'β‑catenin/DKK' panel for the immunofluorescence data shown in Fig. 7B on p. 1106, subsequently appeared in a pair of later publications by the same research group. In addition, in Fig. 5B, the 'Vimentin/ALI' and 'Vimentin/ALI+MSC‑GFP' data panels were found to contain an overlapping section, such that data which were intended to show the results of differently performed experiments had apparently been derived from the same original source. Furthermore, upon performing an independent analysis of the data in this paper in the Editorial Office, it also came to light that the 'α‑SMA/ALI+MSC‑CXCR4' data panel in Fig. 5B had subsequently reappeared in an article by the same research group; the Control panel for the 'MSC (GFP+)' experiment in Fig. 3A on p. 1102 was matching with the Control panel shown in Fig. 6A on p. 1105; certain of the β‑actin and MMP2 protein bands shown for the ALI+MSC‑CXCR4 and ALI+MSC‑GFP experiments in Fig. 7A appeared to be identical in the two sets of western gels; and finally, in Fig. 5A, two sets of data [namely, the data for the IL‑6 and TNF‑α blots for the ALI+MSC‑GFP experiments (central panel of blots), and the pair of Con and 3d 18S blots for the ALI experiments and the 7d and 14d 18S blots for the ALI+MSC‑GFP experiments], bore strikingly resemblances to each other. On re‑examining their original data, the authors realized that they had inadvertently included some of the data incorrectly in Figs. 5, 6 and 7. The revised versions of these three figures, now featuring the correct data for Fig. 5A (the PCR analysis results of TNF‑α and 18S in the ALI+MSC‑GFP group), Fig. 5B (vimentin antibody immunohistochemical staining of the ALI+MSC‑GFP group, α‑SMA antibody immunohistochemical staining of the ALI+MSC‑CXCR4 group, and Collagen Ⅰ antibody immunohistochemical staining of the Control group); Fig. 6A (α‑SMA immunofluorescence staining), Fig. 6C (IgG immunofluorescence staining), Fig. 7A (western blotting results of β‑catenin in the ALI group, MMP2 and β‑actin in the ALI+MSC‑CXCR4 group, and MMP2 and β‑actin in the ALI+MSC‑GFP group) and Fig. 7B (β‑catenin antibody immunofluorescence staining of the DKK1 group), are shown on the subsequent three pages. The image duplications were caused by accidental mix‑up of the files during figure sorting and final manuscript preparation. The authors regret that they did not perform more rigorous cross‑checking of the figures before submission. The corrected figures are consistent with the original experimental data; moreover, there are now no overlaps with any of the group's previously published work, Notably, the overall experimental results and scientific conclusions of the article remain entirely unchanged following the correction of these figures. All the authors agree with the publication of this corrigendum, and they are grateful to the Editor of for granting them the opportunity to publish this; furthermore, they apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 33: 1097‑1109, 2014; DOI: 10.3892/ijmm.2014.1672].
polysaccharides improve liver metabolic disorders by modulating gut microbiota of ovariectomized mice.
Jin X, Liu X, Wang YJ … +2 more , Lei ZL, Yang YH
Int J Mol Med · 2026 Jul · PMID 42169656 · Full text
The morbidity of cardiovascular disease in postmenopausal patients increases due to the lack of estrogen protection. One of the most common conditions is hyperlipidemia characterized by abnormally elevated low‑density li...
The morbidity of cardiovascular disease in postmenopausal patients increases due to the lack of estrogen protection. One of the most common conditions is hyperlipidemia characterized by abnormally elevated low‑density lipoprotein cholesterol (LDL‑C) and total cholesterol (TC). GLP has multiple effects such as lowering lipid levels, reducing inflammation, and regulating gut microbiota, but its effect on regulating metabolism in menopausal patients is not clear. The present study aimed to study the regulatory effect of polysaccharides (GLPs) on cholesterol metabolism in the liver. A bilateral ovariectomy mouse model was generated and GLP was given by gavage. Serum biochemistry, hepatic architecture and histopathology were assessed, expression of genes governing glucose and lipid homeostasis and circadian rhythm in the hepatic tissue was detected and the changes of intestinal microbiota of ovariectomized mice was analyzed by 16S rDNA sequencing. The GLPs directly affected the intestinal flora, upregulated the abundance of probiotics and improved the structure of microbiota and might indirectly affect the liver metabolism through the gut‑liver axis. GLP administration markedly lowered circulating TC and LDL‑C, decreased hepatic steatosis and modulated the expression of genes associated with the circadian clock, lipid synthesis and glucose metabolism in hepatic tissue. Collectively, these data position GLP as a promising therapeutic candidate for correcting postmenopausal dysmetabolism and curbing cardiovascular risk in aging female patients.
CTRP3 alleviates neuropathic pain by improving mitochondrial biogenesis and mitochondrial unfolded protein response via spinal SIRT1 in rats.
Liu T, Zhang L, Mei W
Int J Mol Med · 2026 Jul · PMID 42169654 · Full text
Neuropathic pain arises from an intricate network of interconnected pathophysiological mechanisms, yet the arsenal of effective therapeutic strategies remains frustratingly limited. Accumulating evidence has linked mitoc...
Neuropathic pain arises from an intricate network of interconnected pathophysiological mechanisms, yet the arsenal of effective therapeutic strategies remains frustratingly limited. Accumulating evidence has linked mitochondrial dysfunction to the progression of neuropathic pain. C1q‑tumor necrosis factor‑related protein‑3 (CTRP3), a newly identified adipokine with diverse cytoprotective capacities, has not been previously explored for its role in nociceptive processing. To explore the role of CTRP3 in pain hypersensitivity, pain‑related behavioral assessments were conducted using von Frey filaments and acetone drop method in male rats subjected to spared nerve injury (SNI). To unravel the underlying mechanisms, spinal cord tissues were subjected to western blotting, reverse transcription‑quantitative PCR, immunofluorescence staining, dihydroethidium staining, small interfering RNA (siRNA) technologies and biochemical assays for quantifying oxidative markers. The findings showed that SNI markedly reduced endogenous CTRP3 expression in spinal neurons. Intrathecal administration of recombinant CTRP3 (rCTRP3) alleviated mechanical allodynia and cold hyperalgesia in SNI‑induced rats. Additionally, rCTRP3 treatment enhanced PGC‑1α‑mediated mitochondrial biogenesis, ATF5‑triggered mitochondrial unfolded protein response (UPR), and mitigated spinal oxidative stress. Mechanistically, pharmacological inhibition of SIRT1 with EX‑527, or siRNA‑mediated silencing of PGC‑1α or ATF5, reversed the effects of CTRP3 on pain hypersensitivity, mitochondrial biogenesis, UPR and oxidative stress. The present study demonstrates that CTRP3 mitigates mechanical allodynia and cold hyperalgesia in male SNI rats by activating spinal SIRT1, thereby enhancing PGC‑1α‑mediated mitochondrial biogenesis and ATF5‑induced UPR. CTRP3 may therefore represent a novel therapeutic target for the management of neuropathic pain.
Endothelial NOX4‑driven oxidative stress inhibition reverses HtrA1 deficiency‑induced blood‑brain barrier disruption and cognitive impairment.
Song SN, Wu JY, Song MM … +5 more , Li XF, Wang JM, Jia WH, Li CX, Xu SY
Int J Mol Med · 2026 Jul · PMID 42169653 · Full text
Heterozygous high temperature requirement serine peptidase A1 () mutations are associated with autosomal dominant cerebral small vessel disease (CSVD), but their pathogenic mechanisms remain elusive. In the present study...
Heterozygous high temperature requirement serine peptidase A1 () mutations are associated with autosomal dominant cerebral small vessel disease (CSVD), but their pathogenic mechanisms remain elusive. In the present study, clinical data were collected from two families carrying heterozygous mutations, with pathogenic mutations verified through Sanger sequencing. Between January 2018 and December 2023, four patients with CSVD were recruited from the Department of Neurology, First Hospital of Shanxi Medical University (Taiyuan, China). Whole blood RNA sequencing (RNA‑seq) was performed to identify differentially expressed genes. Lentiviral vectors were constructed for HtrA1 overexpression and knockdown in mouse brain microvascular endothelial bEnd.3 cells to assess cell viability, oxidative stress, tight junction integrity and apoptosis. Adeno‑associated virus (AAV) technology was used to assess how gene interference affects the function of cerebral vascular endothelial cells in mice. Finally, the NOX4 inhibitor GLX351322 was administered to investigate its regulatory effects on cell permeability and apoptosis. Behavioral changes were assessed through open field and novel object recognition test and Morris water maze experiments to evaluate its impact on cognitive behavior in mice. The present study analyzed clinical data from two enrolled families with heterozygous HTRA1 mutations [c.854C>T (p.P285L) and c.905G>A (p.R302Q)] and observed stroke, cognitive decline and gait disturbances. RNA‑seq of patient blood revealed downregulated , occludin‑like protein 1 and claudin 5, alongside upregulated , with apoptotic pathways prominently enriched. HtrA1 overexpression in bEnd.3 cells enhanced viability, decreased oxidative stress and apoptosis and elevated tight junction protein expression, whereas HtrA1 knockdown exacerbated these effects. In mice, AAV‑mediated HtrA1 suppression in cerebrovascular endothelial cells increased NOX4 and caspase3 levels, disrupted blood‑brain barrier (BBB) integrity and induced anxiety‑ and depressive‑like behaviors, measured by the open field test, along with cognitive and memory impairment evaluated using the novel object recognition and Morris water maze tests. The NOX4 inhibitor GLX351322 partially restored endothelial function, mitigated BBB damage and alleviated behavioral impairment. The present findings demonstrated that heterozygous mutations promoted CSVD via NOX4‑mediated oxidative stress, endothelial dysfunction and BBB breakdown. Targeting the HTRA1‑NOX4 interaction using GLX351322 rescued cerebrovascular and cognitive pathology, offering preclinical validation for therapeutic intervention.
[Retracted] Cocktail therapy with a combination of interferon, ribavirin and angiotensin‑II type 1 receptor blocker attenuates murine liver fibrosis development.
Yoshiji H, Noguchi R, Ikenaka Y … +6 more , Kaji K, Aihara Y, Shirai Y, Yoshii J, Yanase K, Fukui H
Int J Mol Med · 2026 Jul · PMID 42169651 · Full text
Following the publication of the above article, a concerned reader drew the Editor's attention to the fact that, regarding the microphotographs shown in Fig. 1, panels B and C, and E, F and G contained overlapping sectio...
Following the publication of the above article, a concerned reader drew the Editor's attention to the fact that, regarding the microphotographs shown in Fig. 1, panels B and C, and E, F and G contained overlapping sections, where different treatment groups for the respective figure parts were reported in the figure legend. In addition, for the immunohistochemical images shown in Fig. 3, panels A‑C also contained overlapping sections; moreover, Fig. 3A, C, F and H contained a series of internally duplicated groupings/repeated patternings of cells within these panels that could not easily be attributed to coincidence. Finally, concerning the tube formation experiments shown in Fig. 7, the 'ARB', 'Rib', 'IFN+Rib' and 'ARB+Rib' panels all apparently contained overlapping sections. After having conducted an internal investigation of the data in this paper, the Editor of has decided that this article should be retracted from the publication on the grounds of an overall lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor sincerely apologizes to the readership for any incovenience caused, and we thank the reader for drawing this matter to our attention. [International Journal of Molecular Medicine 28: 81‑88, 2011; DOI: 10.3892/ijmm.2011.658].
Unraveling the molecular landscape of chronic radiation injury: From oxidative stress signaling to translational modeling (Review).
Xi Z, Li X, Yang C … +17 more , Wang L, Mao J, Liu Q, Liu C, Li Q, Hou Y, Wan J, Yang C, Sun F, Yu C, Wang M, Yuan B, Liu Y, Hu Q, Zhang L, Li X, Li X
Int J Mol Med · 2026 Jul · PMID 42169650 · Full text
The expanding footprint of human radiation exposure, driven by advances in interventional diagnostics, the resurgence of the nuclear industry and the deep‑space exploration, has necessitated a paradigm shift from underst...
The expanding footprint of human radiation exposure, driven by advances in interventional diagnostics, the resurgence of the nuclear industry and the deep‑space exploration, has necessitated a paradigm shift from understanding acute syndromes to the biological effects of chronic, low‑dose‑rate irradiation. Unlike acute injury, chronic radiation injury (CRI) is a distinct biological entity characterized by the progressive accumulation of sublethal damage, niche remodeling and the propagation of the senescence‑associated secretory phenotype, which collectively drive systemic inflammaging. Deciphering these non‑linear dose‑response dynamics requires high‑fidelity animal models that deconstruct mechanisms often obscured by latency in human epidemiological studies. The present review critically synthesizes the methodological evolution of CRI modeling, contrasting continuous external beam paradigms with internal radionuclide contamination systems. The present study aimed to summarize the pathophysiology of multi‑organ exhaustion, specifically detailing the mechanisms of hematopoietic niche senescence, pulmonary fibrosis and stochastic carcinogenesis, and propose a multidimensional validation framework integrating deep phenotyping, digital pathology and circulating biomarkers to establish rigorous construct validity. Finally, the present study aimed to bridge the translational gap by aligning preclinical screening with the Food and Drug Administration Animal Rule‑a regulatory pathway permitting the approval of medical countermeasures based on animal efficacy data when human trials are unethical, advocating a future defined by single‑cell spatial omics and artificial intelligence‑driven precision radioprotection.
Ginsenoside Rg3 potentiates cisplatin antitumor activity while mitigating nephrotoxicity through SIRT1‑mediated suppression of the NLRP3 inflammasome.
Zhai J, Zhang Y, Gong J … +2 more , Fu L, Zhang S
Int J Mol Med · 2026 Jul · PMID 42169649 · Full text
Lung cancer is one of the most common causes of cancer‑related mortality worldwide, with cisplatin (CP) being a key chemotherapeutic agent. However, its use is limited by nephrotoxicity and drug resistance. Ginsenoside R...
Lung cancer is one of the most common causes of cancer‑related mortality worldwide, with cisplatin (CP) being a key chemotherapeutic agent. However, its use is limited by nephrotoxicity and drug resistance. Ginsenoside Rg3 (Rg3) has anticancer properties and potential protective effects on normal tissues. The present study investigated the therapeutic effect of Rg3 and CP in suppressing the proliferation of lung carcinoma cells (LLCs) and inhibiting tumor growth, using both and models. LLC cells were exposed to Rg3 and/or CP and the effects on cell proliferation were measured by MTT assay. Tumor‑bearing mouse models were constructed to evaluate the impact on tumor growth. Modulation of biological pathways was analyzed using flow cytometry, western blotting and immunohistochemistry. Co‑treatment with Rg3 and CP enhanced apoptosis in LLC cells and tumor tissues by upregulating cleaved caspase‑3/9 and phosphorylated (p‑)p53, while suppressing vascular cell adhesion molecule 1, intercellular adhesion molecule 1 (ICAM1), macrophage migration inhibitory factor (MIF) and p‑p65 activation. The downregulation of Organic Cation Transporter 2 (OCT2) and P‑glycoprotein (P‑gp) expression in renal tissues of xenograft mice by Rg3 may explain its dual effects in alleviating CP nephrotoxicity and reversing drug resistance. Mechanistic studies in HK‑2 cells demonstrated that Rg3 (80 g/ml) attenuated CP‑induced NLRP3 inflammasome activation (NLRP3, apoptosis‑associated speck‑like protein with CARD (ASC), caspase‑1) and p‑p65 expression; these effects were reversed by the SIRT1 inhibitor Ex527, implicating SIRT1 pathway dependency. Molecular docking provided a hypothetical model for binding of Rg3 to SIRT1 (‑7.492 kcal/mol) and NLRP3 (‑6.764 kcal/mol), providing a structural basis for the regulatory interactions. Rg3 showed potential as a renal protector, anti‑inflammatory agent and adjunct to CP chemotherapy. The combination offers a promising therapeutic strategy for lung cancer by enhancing efficacy and decreasing nephrotoxicity. Further investigation into mechanisms and long‑term effects is warranted.
Identification of diagnostic markers for diabetic kidney disease by weighted gene co‑expression network analysis and machine learning.
Xu Q, Xu C, Liu Z … +3 more , Lu J, Hu J, Liao L
Int J Mol Med · 2026 Jul · PMID 42169644 · Full text
Diabetic kidney disease (DKD) represents a major complication associated with diabetes mellitus, notably contributing to patient morbidity and mortality. However, early diagnosis of DKD remains challenging due to the lac...
Diabetic kidney disease (DKD) represents a major complication associated with diabetes mellitus, notably contributing to patient morbidity and mortality. However, early diagnosis of DKD remains challenging due to the lack of clear diagnostic biomarkers. Therefore, in the present study, microarray and RNA‑sequencing data from the Gene Expression Omnibus database were systematically analyzed. Using differential expression and weighted gene co‑expression network analysis, 49 genes with marked expression changes in DKD were identified. Subsequent analyses, including functional enrichment, protein‑protein interaction network construction, machine learning techniques and assessment of immune cell infiltration, led to the identification of three hub genes: Spleen‑associated tyrosine kinase, apoptotic peptidase activating factor 1 and ADAM metallopeptidase domain 10, as promising diagnostic markers, which were further evaluated by receiver operating characteristic curve analysis. Expression changes of the identified hub genes were validated in both DKD mouse models and clinical patient samples. Collectively, the present study provided a novel perspective on the molecular basis of DKD, and highlighted novel candidates for potential diagnostic and therapeutic applications.
Bone‑origin repair in diabetic foot ulcers: Mechanisms of callus formation and endocrine effects in healing (Review).
Chen S, Cui X
Int J Mol Med · 2026 Jul · PMID 42169638 · Full text
Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus, affecting ~1/3 of diabetic patients during their lifetime and imposing substantial clinical and economic burdens globally. While conventio...
Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus, affecting ~1/3 of diabetic patients during their lifetime and imposing substantial clinical and economic burdens globally. While conventional understanding attributes DFU pathogenesis primarily to peripheral neuropathy, vascular insufficiency and infection, emerging evidence reveals that bone involvement plays a previously underappreciated but important role in wound chronicity. The present review introduces the concept of 'bone‑origin repair', a therapeutic framework that leverages the skeleton's intrinsic regenerative and endocrine capacity to support soft‑tissue healing in bone‑adjacent DFUs. Diabetes profoundly impairs bone health through cortical thinning, bone marrow stromal cell exhaustion and disrupted callus biology, creating a permissive environment for ulceration and delayed healing. Beyond structural compromise, bone functions as a multifunctional endocrine organ secreting bioactive molecules (osteokines) including osteocalcin (OCN), sclerostin, fibroblast growth factor‑23 and receptor activator of nuclear factor‑κB ligand/osteoprotegerin that regulate systemic metabolism, angiogenesis and immune function. In diabetic patients, dysregulated osteokine secretion, characterized by reduced OCN and elevated sclerostin, establishes a catabolic milieu that impairs wound healing capacity. Controlled bone injury triggers substantial osteokine release, with platelet‑derived growth factor‑BB reaching distant wound sites to accelerate healing through enhanced angiogenesis and re‑epithelialization. This bone‑wound crosstalk operates via a coordinated endocrine loop involving macrophage polarization, type‑H vessel formation and neurovascular coupling. While promising, bone‑origin repair requires careful patient selection, exclusion of active osteomyelitis and integration with standard DFU care. The present review synthesizes current understanding of bone‑DFU pathophysiology, examines the molecular mechanisms underlying the endocrine influence of the bone on wound healing and discusses the translational potential of bone‑targeted strategies as adjunctive therapies in diabetic wound management.
Spatial hepatology: Decoding liver zonation for metabolic and regenerative therapeutics (Review).
Chen G, Jia H, Zhao K … +5 more , Gao C, Liu Y, Zhu H, Yang D, Cai Y
Int J Mol Med · 2026 Jul · PMID 42138208 · Full text
The integration of spatial omics and single‑cell technologies has redefined liver zonation as a dynamic regulator of regeneration, extending beyond its traditional role in metabolic compartmentalization. This progress ha...
The integration of spatial omics and single‑cell technologies has redefined liver zonation as a dynamic regulator of regeneration, extending beyond its traditional role in metabolic compartmentalization. This progress has given rise to the emerging field of 'spatial hepatology', which aims to integrate spatial information with molecular features. Compared with conventional bulk or single‑cell approaches, spatial hepatology incorporates tissue architecture into molecular analyses, thereby revealing region‑specific regulatory mechanisms during liver regeneration and disease progression. From this perspective, the present review proposes the concept of zonation‑guided therapeutic strategies. It systematically summarized recent advances in the molecular mechanisms governing liver zonation, examined the role of zonal disruption in liver disease pathogenesis, clarified the dynamic functions of zonated hepatocytes during regeneration and outlined related targeted therapeutic approaches. The present review aimed to establish a framework that integrates basic research with clinical application, providing a theoretical basis for precision hepatology.
Hepatic p38γ exacerbates acetaminophen‑induced acute liver injury via PI3K/Akt‑dependent mechanisms.
Fang H, Shu M, Wang J … +7 more , Tian H, Zhang J, Hu Y, Li H, Zhou H, Gu K, Ren Z
Int J Mol Med · 2026 Jul · PMID 42138207 · Full text
An acetaminophen (APAP) overdose can result in acute and chronic liver injury. Thus, the discovery of biomarkers for the management of APAP‑induced liver injury is crucial from a therapeutic standpoint. As one of the fou...
An acetaminophen (APAP) overdose can result in acute and chronic liver injury. Thus, the discovery of biomarkers for the management of APAP‑induced liver injury is crucial from a therapeutic standpoint. As one of the four isoforms of p38 mitogen activated protein kinases, p38γ plays a notable role in the inflammatory processes associated with various diseases. However, the underlying molecular mechanisms of p38γ in liver injury are largely unknown. In the present study, it was demonstrated that AML‑12 cells and liver tissues induced with APAP had elevated p38γ expression. DCFH‑DA fluorescent probe and oil red O staining was used to investigate oxidative stress and lipid metabolism in APAP‑induced AML‑12 cells and western blotting was used to assess the expression levels of oxidative stress and lipid metabolism‑related protein inflammatory cytokines. The results showed that p38γ knockdown significantly attenuated the inflammatory response, oxidative stress and lipid accumulation, whereas overexpression of p38γ exhibited the opposite effect. Downstream, p38γ induced the activation of the PI3K/Akt signaling pathway via upregulation of phosphorylated (p‑)PI3K and p‑Akt levels. Additionally, TargetScan analysis and dual luciferase reporter assays showed that microRNA‑125 selectively targeted the 3'‑untranslated region of p38γ, resulting in the repression of APAP‑induced inflammation, lipid accumulation and oxidative stress. Furthermore, adeno‑associated virus 9‑short hairpin RNA p38γ was used via tail vein injection to cause p38γ downregulation . The results showed that knockdown of p38γ significantly reduced the inflammatory response, lipid accumulation and oxidative stress in APAP‑induced liver injury. Together, these findings demonstrated that targeting p38γ could be an effective approach for treating liver injury caused by APAP.
[Corrigendum] Expression of FKBP52 in the ovaries of PCOS rats.
Song S, Tan Y
Int J Mol Med · 2026 Jul · PMID 42138206 · Full text
Following the publication of the above article, an interested reader drew to the authors' attention that, concerning the images showing the green fluorescence of granulosa cells in Fig. 5 on p. 874, the images selected f...
Following the publication of the above article, an interested reader drew to the authors' attention that, concerning the images showing the green fluorescence of granulosa cells in Fig. 5 on p. 874, the images selected for Fig. 5B and C were apparently matching, albeit with different levels of brightness, even though the experimental conditions for these figure parts were reported to be different. Upon investigating this figure, the authors realized that the image correctly shown for Fig. 5C had also inadvertently been included as Fig. 5B. A revised version of Fig. 5, now showing the correct data panel for Fig. 5B, is shown below. The authors confirm that the error made during the assembly of 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 43: 868‑878, 2019; DOI: 10.3892/ijmm.2018.3998].
Rab27: Molecular switch of tumor exosome secretion (Review).
Tang M, Zhu Z, Duan H … +8 more , Tan S, Shen M, Jiang X, Peng Q, Oyang L, Ren Z, Zhou Y, Liao Q
Int J Mol Med · 2026 Jul · PMID 42138205 · Full text
Rab proteins are core regulators of vesicle trafficking during membrane transport. As key members of this family, Rab27 comprises two functionally distinct isoforms, Rab27a and Rab27b, and participates in the regulation...
Rab proteins are core regulators of vesicle trafficking during membrane transport. As key members of this family, Rab27 comprises two functionally distinct isoforms, Rab27a and Rab27b, and participates in the regulation of exosome secretion by mediating the selective anchoring of multivesicular bodies to the plasma membrane. In tumor cells, Rab27 promotes malignant progression by modulating exosome secretion. Aberrantly expressed Rab27 is associated with the prognosis of patients with cancer, suggesting its potential as a prognostic biomarker for various malignant tumors. Furthermore, the development of novel small‑molecule drugs targeting Rab27 is promising because these drugs can exert antitumor effects through interference with the exosome secretory pathway. The present review systematically summarizes the molecular mechanisms underlying the Rab27‑mediated regulation of exosome secretion and its role in tumorigenesis and cancer progression and discusses the application prospects and challenges of Rab27‑targeted antitumor therapeutic strategies, aiming to provide a reference for basic research and clinical translation of Rab27.
Pharmacological activity, molecular mechanisms and therapeutic potential of erianin (Review).
Ming C, Zhu N, Yu Y … +2 more , Zhou H, Hu M
Int J Mol Med · 2026 Jul · PMID 42138202 · Full text
As a natural active ingredient extracted from , erianin shows multi‑target regulatory characteristics. The present review aimed to summarize the physiological effects, molecular mechanisms and therapeutic potential of er...
As a natural active ingredient extracted from , erianin shows multi‑target regulatory characteristics. The present review aimed to summarize the physiological effects, molecular mechanisms and therapeutic potential of erianin. Erianin has application bottlenecks such as poor water solubility and low bioavailability. The druggability of erianin could be effectively improved through structural modification, development of new drug delivery systems and combined drug use strategies. Although the synthesis process of erianin has been optimized for high yield and reproducibility, the toxicity and targeting need to be further optimized. The current review provides novel ideas for the systematic development of natural products, and guidance for promoting the clinical transformation of erianin.
[Corrigendum] Induction of cardiomyocyte‑like cells from hair follicle cells in mice.
Kim YH, Kim BJ, Kim SM … +2 more , Kim SU, Ryu BY
Int J Mol Med · 2026 Jul · PMID 42138200 · Full text
Following the publication of the above article, an interested reader drew to the authors' attention that, concerning the micrographic images shown in Fig. 3B on p. 2234, the 'OP9' and 'MEF' data panels showed an overlapp...
Following the publication of the above article, an interested reader drew to the authors' attention that, concerning the micrographic images shown in Fig. 3B on p. 2234, the 'OP9' and 'MEF' data panels showed an overlapping section, such that data which were intended to show the results from differently performed experiments had apparently been derived from the same original source. Upon investigating this figure, the authors realized that, during the revision process when several figures needed to be replaced with higher‑quality images, an inadvertent error occurred, resulting in the unintentional duplication of the 'MEF' cell image in the 'OP9' data panel. The revised version of Fig. 3, now showing the correct data for the 'OP9' panel, is shown on the next page. The authors confirm that the error made when this figure was reassembled 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: 2230‑2240, 2019; DOI: 10.3892/ijmm.2019.4133].
miR‑223‑3p promotes microglial lactylation and M1 polarization via the FBXW7/Notch1/Hes1/SIRT1 axis.
Wang X, Song L, Wang J … +5 more , Xie Q, Wang Y, Li C, Wang T, Du Y
Int J Mol Med · 2026 Jul · PMID 42138198 · Full text
Neuroinflammation is a hallmark of Alzheimer's disease (AD) and is closely linked to microglial M1 polarization. In the present study, miR‑223‑3p was identified as a critical regulator of microglial metabolic reprogrammi...
Neuroinflammation is a hallmark of Alzheimer's disease (AD) and is closely linked to microglial M1 polarization. In the present study, miR‑223‑3p was identified as a critical regulator of microglial metabolic reprogramming. Analyses of Gene Expression Omnibus and AD Neuroimaging Initiative datasets revealed significant upregulation of miR‑223‑3p in the brain, blood, and cerebrospinal fluid of patients with AD. The overexpression of miR‑223‑3p promoted M1 polarization and increased reactive oxygen species (ROS) levels. Transcriptomic, metabolomic and Seahorse analyses revealed increased glycolysis, lactate production and lactylation, whereas inhibition of lactylation reduced M1 polarization and ROS accumulation. Mechanistically, miR‑223‑3p suppressed SIRT1 expression and directly targeted , leading to activation of the Notch1/Hes1 pathway and further suppression of . In summary, these findings demonstrate that miR‑223‑3p drives microglial lactylation‑mediated M1 polarization through the FBXW7/Notch1/Hes1/SIRT1 signaling axis. The present study provides new insight into the role of lactylation in neuroinflammation and highlights miR‑223‑3p as a potential therapeutic target for AD.
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