International Journal Of Molecular Medicine[JOURNAL]
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200 papers
Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review).
Li W, Wang WH, Song Y … +6 more , Li XJ, Li Y, Wang X, Tian TT, Huang X, Zhao L
Int J Mol Med · 2026 Apr · PMID 41645754 · Full text
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 cleara...
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.
Lipid droplets beyond storage: Cellular metabolic modulator in the diabetic heart (Review).
Liang Y, Fan X, Geng X … +10 more , Jia Y, Shang W, Sun X, Ge J, Ye G, Zhu B, Zhang Z, Kang Y, Shan X, Zhang J
Int J Mol Med · 2026 Apr · PMID 41645744 · Full text
Diabetic cardiomyopathy (DCM) is a significant complication in patients with diabetes, but its pathogenesis is not fully understood. In recent years, dynamic regulation of lipid droplets (LDs) balance has gradually becom...
Diabetic cardiomyopathy (DCM) is a significant complication in patients with diabetes, but its pathogenesis is not fully understood. In recent years, dynamic regulation of lipid droplets (LDs) balance has gradually become a new therapeutic direction with great potential. LDs regulate lipid storage, energy supply and interconnected drivers; for instance, oxidative damage, inflammation, autophagy, ferroptosis, affect the function and cellular homeostasis of cardiomyocytes, macrophages and fibroblasts, and thus participate in DCM. The present review discusses the multiple functions of LDs in regulating DCM by affecting cell homeostasis and summarizes the research progress of therapies targeting LDs and related metabolic pathways, which may inform novel strategies for preventing and treating DCM.
Role of vascular smooth muscle cell pathobiology in sepsis‑induced vasoplegia (Review).
Ruan H, Shen XY, Liu SY … +1 more , Li SS
Int J Mol Med · 2026 Apr · PMID 41645740 · Full text
Sepsis‑induced vasoplegia, a life‑threatening complication of sepsis, has become a focal point of research endeavors aimed at determining its complex mechanisms. However, existing investigations predominantly focus on th...
Sepsis‑induced vasoplegia, a life‑threatening complication of sepsis, has become a focal point of research endeavors aimed at determining its complex mechanisms. However, existing investigations predominantly focus on the role of endothelial cells (ECs) in sepsis, inadvertently dismissing the pivotal contribution of vascular smooth muscle cells (VSMCs). The present review highlights the frequently underappreciated role of VSMCs in sepsis‑induced vasodilation, and provides a comprehensive and systematic elucidation of the associated pathophysiological mechanisms. The current review examines the structural characteristics, localization, phenotypic transitions and heterogeneity of VSMCs, emphasizing their critical role in maintaining vascular homeostasis and regulating blood pressure. Subsequently, the review delves into the multifaceted effects of sepsis on VSMCs. Direct injury to VSMCs in sepsis occurs through pathogens. Additionally, the sepsis‑associated cytokine storm can activate key signaling pathways, such as the NF‑κB and p38 MAPK pathways, leading to a phenotypic shift in VSMCs from a contractile state to a synthetic state, thus enhancing their proliferative and migratory abilities. Concurrently, sepsis disrupts the intricate interaction between ECs and VSMCs, and interferes with calcium homeostasis, ultimately resulting in reduced vascular reactivity and abnormal vascular remodeling. Together, these mechanisms contribute to sepsis‑related vascular dysfunction and multiorgan failure. The in‑depth analysis of these processes in the present review offers novel insights into the pathological mechanisms of sepsis‑induced vasoplegia. The current study also provides a theoretical foundation for the development of clinical intervention strategies targeting VSMCs, with the potential to advance sepsis treatment strategies.
IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review).
Zhu H, Wang H, Li X … +6 more , Zhang W, Wang Y, Tan Q, Ying D, Shi Z, Song J
Int J Mol Med · 2026 Apr · PMID 41645737 · Full text
Metabolic reprogramming is a hallmark feature of malignant tumors. These metabolic pathways are regulated in a cell‑autonomous manner by oncogenic signaling and transcriptional networks, and tracking their metabolic repr...
Metabolic reprogramming is a hallmark feature of malignant tumors. These metabolic pathways are regulated in a cell‑autonomous manner by oncogenic signaling and transcriptional networks, and tracking their metabolic reprogramming is frequently used in the diagnosis, detection and treatment of cancer. There are currently promising therapeutic prospects for a variety of types targeting fixed core metabolic pathways in tumor metabolic reprogramming. Among these, inosine monophosphate (IMP) is an essential intermediate in purine nucleotide synthesis that demonstrates significant target potential. Nevertheless, further research is needed to elucidate the regulatory networks that control IMP metabolism in tumor cells. This review combines the latest insights into IMP metabolism into an interesting conceptual framework. This includes the supply of IMP precursor substrates (reprogramming of glucose metabolism, serine/one‑carbon metabolism, glutamine and mitochondrial metabolism), the dynamic regulation of important enzymes [phosphoribosyl pyrophosphate synthetase, phosphoribosyl pyrophosphate amidotransferase, IMP dehydrogenase (IMPDH)], purinosomes and signaling pathways (RAS‑ERK, PI3K/AKT‑mTORC1 and Hippo‑YAP) that ultimately regulate IMP synthesis in tumor cells. Additionally, it focused on downstream associations between IMPDH and the immune microenvironment, offering a fresh perspective for current research on tumor therapy targeting IMP metabolism.
[Corrigendum] p57‑mediated inhibition of human trophoblast apoptosis and promotion of invasion .
He GQ, Liu GY, Xu WM … +3 more , Liao HJ, Liu XH, He GL
Int J Mol Med · 2026 Apr · PMID 41645734 · Full text
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 (th...
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 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].
Immunological mechanisms and novel therapeutic strategies for sepsis‑associated acute kidney injury (Review).
Xu L, Jiang W, Song L … +3 more , Wang J, Yu J, Zheng R
Int J Mol Med · 2026 Apr · PMID 41645733 · Full text
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. T...
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.
[Retracted] miR‑124‑3p inhibits the viability and motility of glioblastoma multiforme by targeting RhoG.
Cai S, Shi CJ, Lu JX … +3 more , Wang YP, Yuan T, Wang XP
Int J Mol Med · 2026 Mar · PMID 41614420 · Full text
Following the publication of this paper, a concerned reader drew to the Editor's attention that, according to a study published by Kristin Entrop and colleagues in the journal in 2024, an unspecific anti‑Bax antibody (s...
Following the publication of this paper, a concerned reader drew to the Editor's attention that, according to a study published by Kristin Entrop and colleagues in the journal in 2024, an unspecific anti‑Bax antibody (sc‑7480) had been used in the above study, which was shown to bind to an unrelated protein at the correct molecular weight (20‑25 kDa). Furthermore, it also came to light that, for the cell migration and invasion assay data shown in Fig. 8B on p. 10, at least four pairs of data panels were shown to feature overlapping sections, such that data which were intended to show the results of differently performed experiments had apparently been derived from a smaller number of original sources. After having performed an independent review of the data in the Editorial Office, the Editor of has decided that this paper should be retracted from the Journal on account of a 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 apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 47: 69, 2021; DOI: 10.3892/ijmm.2021.4902].
MicroRNA‑microbiome cross‑kingdom networks drive inflammatory bowel disease through dynamic regulatory ecosystems (Review).
Liang L, Liu X, Li B … +7 more , Lei H, Tang Z, Mai S, Yang C, Zhou Y, Zhang S, Liu L
Int J Mol Med · 2026 Mar · PMID 41614418 · Full text
Inflammatory bowel disease (IBD) pathogenesis reflects complex interactions between host immunity and gut microbiome dynamics, with microRNAs (miRNAs) functioning as key mediators of cross‑kingdom communication. Host‑der...
Inflammatory bowel disease (IBD) pathogenesis reflects complex interactions between host immunity and gut microbiome dynamics, with microRNAs (miRNAs) functioning as key mediators of cross‑kingdom communication. Host‑derived miRNAs modulate bacterial gene expression and reshape microbial communities, while gut microbiota influences host miRNA expression through microbial metabolites and multiple immune signaling. In IBD, dysregulated miRNAs disrupt immune homeostasis by affecting inflammatory responses, lymphocyte differentiation and epithelial barrier integrity. Yet many miRNAs exhibit context‑dependent dual functions, complicating therapeutic targeting. Despite their biomarker potential for distinguishing IBD subtypes and tracking disease activity, clinical validation faces substantial obstacles including methodological inconsistencies, patient heterogeneity and temporal expression variability. Single-target miRNA therapeutics have yielded modest clinical outcomes, exposing the resilience of regulatory networks and compensatory mechanisms that limit intervention efficacy. The bidirectional architecture of miRNA‑microbiome communication argues against reductionist approaches. Effective IBD management requires integrated strategies that address multiple regulatory nodes rather than isolated pathways. Advancing this field demands deeper investigation of temporal dynamics, spatial organization and network‑level interactions. Such understanding will inform precision medicine strategies that restore regulatory equilibrium without compromising the adaptive capacity of host‑microbiome systems. Progress depends on recognizing the integrated nature of these regulatory networks rather than treating components in isolation.
Mechanistic insights into pancreatic cancer progression from circadian rhythm disruption and gut microbiota dysbiosis (Review).
Liu Y, Li Y, Ma H … +2 more , Deng S, Cheng C
Int J Mol Med · 2026 Mar · PMID 41614406 · Full text
Pancreatic cancer has nearly doubled in incidence over the past two decades, becoming one of the deadliest types of malignancy in humans, with poor prognosis. With advances in modern medicine, the 5‑year survival rate fo...
Pancreatic cancer has nearly doubled in incidence over the past two decades, becoming one of the deadliest types of malignancy in humans, with poor prognosis. With advances in modern medicine, the 5‑year survival rate for pancreatic cancer has increased from <5% in 1990 to ~10% in 2021. Most patients are diagnosed at an advanced stage, and ~20% of patients diagnosed at an early stage are eligible for surgical resection, with a 5‑year survival rate after surgery of up to 25%. With the aging population, the incidence of pancreatic cancer is expected to continue rising. The gut microbiota, a crucial ecosystem, comprises >1x10 microorganisms that influence the development of pancreatic cancer through immune modulation and metabolites. Circadian rhythms, as a conserved molecular feedback loop, regulate cell metabolism and immune function, and their dysregulation is associated with metabolic disorders and tumor progression. Circadian rhythm disruption not only affects the gut microbiota and its metabolites but also accelerates pancreatic cancer progression through mechanisms such as promoting inflammation, immune suppression and drug resistance. The present review summarizes the impact of circadian rhythm dysregulation on the gut microbiota and its metabolites, specific microbiota associated with pancreatic cancer and their mechanisms in tumor progression and aims to deepen the understanding of the role of gut microbiota in pancreatic cancer treatment, providing a theoretical basis for future therapeutic strategies.
[Corrigendum] Role of Smad3 signaling in the epithelial‑mesenchymal transition of the lens epithelium following injury.
Meng F, Li J, Yang X … +2 more , Yuan X, Tang X
Int J Mol Med · 2026 Apr · PMID 41614402 · Full text
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...
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 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].
Spatial metabolomics: A new tool for unravelling the metabolic disorders and heterogeneity in diabetic kidney disease (Review).
Li H, Li Y, Zhang B … +6 more , Cheng W, Ma G, Rong J, Duan S, Feng D, Zhao T
Int J Mol Med · 2026 Apr · PMID 41614393 · Full text
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 visua...
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 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.
Ginkgolide C alleviates atherosclerosis via activating Nrf2 to inhibit ROS‑dependent NLRP3 inflammasome activation.
Zhang R
Int J Mol Med · 2026 Mar · PMID 41614391 · Full text
Atherosclerosis (AS), a chronic vascular pathology characterized by endothelial dysfunction, arises from the interplay of lipid dysregulation, oxidative stress, and inflammatory activation. Reactive oxygen species (ROS)...
Atherosclerosis (AS), a chronic vascular pathology characterized by endothelial dysfunction, arises from the interplay of lipid dysregulation, oxidative stress, and inflammatory activation. Reactive oxygen species (ROS) overproduction triggers Nod‑like receptor protein 3 (NLRP3) inflammasome signaling, exacerbating inflammatory cascades that drive plaque progression. The nuclear factor erythroid 2‑related factor 2 (Nrf2)‑mediated antioxidant pathway serves as a critical counterbalance to ROS/NLRP3 axis dysregulation, positioning pharmacological Nrf2 activation as a promising therapeutic strategy. The present study investigated the anti‑atherosclerotic potential of ginkgolide C (GC), a terpene lactone from Ginkgo biloba with established anti‑inflammatory and anti‑ischemia/reperfusion injury properties, through coordinated modulation of redox‑inflammatory pathways. Complementary (high‑fat diet/vitamin D3‑treated ApoE-/- mice) and (oxidized‑low density lipoprotein‑stimulated aortic endothelial cells) models were established. Comprehensive analyses included histopathological characterization, lipid profiling, ultrastructural examination, redox‑inflammatory biomarker quantification, and molecular pathway validation. GC significantly attenuated hyperlipidemia and plaque progression while preserving vascular ultrastructure. Mechanistically, GC enhanced endothelial survival through dual pathway modulation: i) Nrf2 nuclear translocation upregulated antioxidant enzymes [heme oxygenase‑1/NAD(P)H quinone oxidoreductase 1/glutamate‑cysteine ligase modifier subunit], restoring redox homeostasis; ii) NLRP3 inflammasome inhibition via Caspase‑1 suppression mitigated inflammatory cytokine release. The present study demonstrated GC's dual‑target therapeutic efficacy against AS through Nrf2‑mediated oxidative stress resolution and NLRP3 inflammasome inactivation, offering new insights into phytochemical‑based cardiovascular interventions.
Mangiferin in human disease: Multifaceted mechanisms and applications (Review).
Dai Y, Huang Q, Tan M … +5 more , Wang Z, Jiang C, Liu Z, Zhang S, Song S
Int J Mol Med · 2026 Mar · PMID 41574708 · Full text
Mangiferin (MGF) is a natural C‑glucosyl xanthone with multitarget activity relevant to metabolic, inflammatory and cancer diseases. Notably, MGF modulates AMP‑activated protein kinase, NF‑κB, PI3K/AKT and MAPK signaling...
Mangiferin (MGF) is a natural C‑glucosyl xanthone with multitarget activity relevant to metabolic, inflammatory and cancer diseases. Notably, MGF modulates AMP‑activated protein kinase, NF‑κB, PI3K/AKT and MAPK signaling; through these pathways, it affects glucose and lipid metabolism, oxidative stress, apoptosis and inflammatory responses. In metabolic disorders, MGF has been shown to improve insulin sensitivity, support mitochondrial function and reduce diabetic complications. In cancer models, MGF suppresses proliferation, invasion and angiogenesis, and can influence antitumor immunity in the tumor microenvironment. Anti‑inflammatory actions include decreased cytokine release and regulation of the NLR family pyrin domain‑containing 3 inflammasome. Notably, clinical translation remains limited due to its low aqueous solubility, poor oral bioavailability and rapid metabolism. However, benefits of nanocarrier delivery, structural optimization and combination therapy have been reported, which may improve exposure and efficacy in experimental systems. Furthermore, safety signals in animals are favorable at relevant doses, but clinical evidence remains limited. In conclusion, the present review summarizes the pharmacodynamics and mechanisms of MGF across major disease settings and identifies key gaps for translation. Priorities include standardized clinical trials, optimization of delivery strategies, and rigorous assessment of long‑term safety and efficacy.
Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review).
Li Y, Gong Y, Zhao J … +1 more , Ran R
Int J Mol Med · 2026 Mar · PMID 41574706 · Full text
B‑lymphocytes (B‑cells) develop from hematopoietic stem cells in the bone marrow or fetal liver and differentiate into antibody‑secreting cells and memory B‑cells upon encountering antigens in peripheral lymphoid organs....
B‑lymphocytes (B‑cells) develop from hematopoietic stem cells in the bone marrow or fetal liver and differentiate into antibody‑secreting cells and memory B‑cells upon encountering antigens in peripheral lymphoid organs. Throughout this process, the expression of lineage‑associated genes is upregulated, whereas that of lineage‑inappropriate genes is repressed, thereby directing commitment to a specific B‑cell fate. Epigenetic regulatory mechanisms, including DNA methylation, post‑translational histone modifications and non‑coding RNAs, regulate gene transcription and play crucial roles in B‑cell development and differentiation. The dysregulation of these epigenetic processes may contribute to the pathogenesis of autoimmune diseases and B‑cell malignancies. Recent advances in high‑throughput techniques, including single‑cell RNA sequencing, chromatin immunoprecipitation‑sequencing and whole‑genome bisulfite sequencing, have significantly enhanced the understanding of epigenetic dysregulation in these disorders. The present review summarizes recent advances in the understanding of dysregulated epigenetic mechanisms underlying B‑cell‑mediated autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren's syndrome, multiple sclerosis and type 1 diabetes mellitus) and lymphomas (such as diffuse large B‑cell lymphoma, follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma and marginal zone lymphoma), and highlights emerging diagnostic biomarkers and therapeutic strategies.
[Expression of Concern] Long non‑coding RNA SNHG20 promotes bladder cancer via activating the Wnt/β‑catenin signalling pathway.
Zhao Q, Gao S, Du Q … +1 more , Liu Y
Int J Mol Med · 2026 Mar · PMID 41574705 · Full text
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the control GAPDH western blots featured in Fig. 5A and B on p. 2845 were apparently the same (even though it is...
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the control GAPDH western blots featured in Fig. 5A and B on p. 2845 were apparently the same (even though it is possible that the experiments portrayed in these figure parts were performed under the same experimental conditions). The authors have been contacted by the Editorial Office to offer an explanation for the matter described above, although up to this time no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 42: 2839‑2848, 2018; DOI: 10.3892/ijmm.2018.3819].
Natural compound 5,7,8‑trimethoxyflavone mitigates radiation‑induced lung injury by suppressing EMT and PI3K/Akt pathway.
Gong CC, Li HK, Mi YZ … +9 more , Chen JY, Fang ZY, Fu SL, Quan L, Lin B, Lang JY, Chen Q, Xu K, Chen MH
Int J Mol Med · 2026 Mar · PMID 41574704 · Full text
Radiation‑induced lung injury (RILI) remains a dose‑limiting and life‑threatening complication of thoracic radiotherapy. The present study aimed to evaluate the therapeutic efficacy and mechanism of the naturally extract...
Radiation‑induced lung injury (RILI) remains a dose‑limiting and life‑threatening complication of thoracic radiotherapy. The present study aimed to evaluate the therapeutic efficacy and mechanism of the naturally extracted flavonoid, 5,7,8‑trimethoxyflavone (HY‑N7656), in inhibiting RILI. Lung injury in mice was evaluated using micro‑computed tomography, histopathological analysis, enzyme‑linked immunosorbent assay and western blotting. Network pharmacology was conducted to predict the potential therapeutic targets and signaling pathways of HY‑N7656 in RILI. Cell Counting Kit‑8, wound healing, immunofluorescence, reverse transcription‑quantitative (RT‑q) PCR and protein expression analyses were carried out using TGF‑β‑stimulated A549 cells to evaluate epithelial‑mesenchymal transition (EMT) and signaling activity. Results of the present study revealed that HY‑N7656 markedly alleviated pulmonary inflammation and fibrosis in irradiated mice, leading to a reduction in α‑smooth muscle actin expression. In addition, EMT was effectively reversed following treatment with HY‑N7656 in A549 alveolar epithelial cells treated with TGF‑β, accompanied by restoration of E‑cadherin expression and downregulation of mesenchymal markers, such as N‑cadherin and vimentin. Network pharmacology analysis and molecular docking validation identified the PI3K/Akt pathway as a central target, which was subsequently confirmed via western blot analysis. Moreover, results of the present study demonstrated that HY‑N7656 inhibited radiation‑induced activation of PI3K and Akt. To the best of the authors' knowledge, the present study was the first to demonstrate that HY‑N7656 modulates the PI3K/Akt signaling pathway to suppress the progression of EMT in RILI, establishing HY‑N7656 as a multi‑target inhibitor of RILI. These findings present a potential strategy to enhance the safety of radiotherapy, warranting further preclinical and clinical evaluation.
[Retracted] DDAH2 alleviates myocardial fibrosis in diabetic cardiomyopathy through activation of the DDAH/ADMA/NOS/NO pathway in rats.
Zhu ZD, Ye JM, Fu XM … +11 more , Wang XC, Ye JY, Wu XR, Hua P, Liao YQ, Xuan W, Duan JL, Li WY, Fu H, Xia ZH, Zhang X
Int J Mol Med · 2026 Mar · PMID 41574703 · Full text
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that a pair of the data panels shown for the Masson staining experiments in Fig. 3A were overlapping, such that data w...
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that a pair of the data panels shown for the Masson staining experiments in Fig. 3A were overlapping, such that data which were intended to show the results from differently performed experiments had apparently been derived from the same original source. Upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that a pair of the panels in Fig. 4A also contained overlapping sections of data, and moreover, the data in Fig. 3A were strikingly similar to data which had appeared in a number of other articles that were written by different authors at different research institutes, several of which have been retracted, including one that had been published prior to the reciept of the above paper to. Owing to the fact that the contentious data in the above article were found to be strikingly similar to data that had already been published elsewhere, the Editor of has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 43: 49‑760, 2019; DOI: 10.3892/ijmm.2018.4034].
‑folate axis as a modulator of the epigenetic landscape in autoimmune diseases (Review).
Navarro-Rodríguez PM, Bajeca-Serrano RF, Turrubiates-Hernández FJ … +5 more , Ceja-Gálvez HR, Hernández-Bello J, Hernández-Ramírez CO, Ramírez-de Los Santos S, Muñoz-Valle JF
Int J Mol Med · 2026 Mar · PMID 41574701 · Full text
The one‑carbon metabolism pathway, regulated by the methylenetetrahydrofolate reductase (MTHFR) enzyme, represents a key nexus where genetic predisposition and nutrient status converge to shape the epigenetic landscape o...
The one‑carbon metabolism pathway, regulated by the methylenetetrahydrofolate reductase (MTHFR) enzyme, represents a key nexus where genetic predisposition and nutrient status converge to shape the epigenetic landscape of autoimmune diseases. The objective of the present review is to synthesize evidence of how the ‑folate axis drives epigenomic patterns in these conditions. One of the main diseases involved is rheumatoid arthritis, where drug‑naïve patients show T‑cell and synovial hypomethylation with cytokine‑driven DNMT suppression, a process aggravated by reduced folate availability and polymorphisms that constrain S‑adenosylmethionine supply. Similarly, in systemic lupus erythematosus, CD4 T cells exhibit global hypomethylation with an interferon‑skewed signature (such as ), associated with impaired activity and a folate‑dependent SAM:SAH imbalance that further diminishes DNMT function. Finally, in celiac disease, intestinal differential methylation, including LINE‑1 hypomethylation, is observed, driven by gluten‑induced villous atrophy and folate malabsorption. Overall, impaired one‑carbon metabolism and ‑dependent methylation capacity may be key determinants of epigenomic dysfunction underlying autoimmune disease and its clinical severity.17.
Deciphering the CAF‑LCN2 axis: Key to overcoming anti‑PD‑L1 immunotherapy resistance in lung cancer.
Xiao D, Yang J, Zhou J … +2 more , Hu Z, Zhang T
Int J Mol Med · 2026 Mar · PMID 41574700 · Full text
Lung cancer is a highly aggressive malignancy associated with a high global mortality rate. Immunotherapy, particularly anti‑programmed cell death protein 1 (PD‑1) therapy, has offered new hope for patients; however, the...
Lung cancer is a highly aggressive malignancy associated with a high global mortality rate. Immunotherapy, particularly anti‑programmed cell death protein 1 (PD‑1) therapy, has offered new hope for patients; however, therapeutic resistance remains a major obstacle to clinical success. In the present study, single‑cell RNA sequencing was utilized to investigate the molecular characteristics of lung cancer and to elucidate the mechanisms underlying resistance to anti‑PD‑1 immunotherapy. Cancer‑associated fibroblasts (CAFs) were identified as key contributors to immune resistance. Functional assays, including CCK‑8, EdU, TUNEL and Transwell experiments, demonstrated that CAFs regulated the expression of lipocalin 2 (LCN2) in lung cancer cells, and elevated LCN2 levels were found to promote resistance to immunotherapy, as well as to enhance cellular proliferation and invasion. The effects of LCN2 on tumor growth, invasion, immune infiltration and ferroptosis were further validated by molecular and histological analyses. The results showed that silencing LCN2 induced ferroptosis in lung cancer cells, resulting in increased sensitivity to anti‑PD‑1 therapy, suppressed tumor growth and reduced invasiveness. These findings highlight the critical role of the CAF‑LCN2 axis in mediating resistance to anti‑PD‑1 immunotherapy and suggest that targeting this pathway may represent a promising strategy to enhance treatment efficacy in lung cancer.
Research progress on the effects of macrophage‑derived exosomes on muscle factors IGF‑1 and FGF‑2 mediating musculoskeletal crosstalk molecular signaling pathway on bone metabolism (Review).
Cui RM, Zheng M, Hong JB … +6 more , Wang ZX, Cun YF, Gao SJ, Zhu YL, Yang ZB, Liu MW
Int J Mol Med · 2026 Mar · PMID 41574692 · Full text
Musculoskeletal crosstalk is essential for maintaining the balance of bone metabolism, with macrophage‑derived exosomes emerging as key regulators of this process. Exosomes, small extracellular vesicles secreted by cells...
Musculoskeletal crosstalk is essential for maintaining the balance of bone metabolism, with macrophage‑derived exosomes emerging as key regulators of this process. Exosomes, small extracellular vesicles secreted by cells, carry a variety of bioactive molecules; proteins, lipids, mRNAs and miRNAs and facilitate intercellular communication by transferring these cargos to recipient cells. Specifically, macrophage‑derived exosomes mediate muscle‑bone interactions by transferring key regulators such as insulin‑like growth factor‑1 (IGF‑1) and fibroblast growth factor‑2 (FGF‑2), thereby playing a pivotal role in bone metabolic homeostasis. Macrophages are classified into pro‑inflammatory M1 and anti‑inflammatory M2 phenotypes, each performing distinct functions in immune responses. Exosomes from M1 macrophages typically carry pro‑inflammatory factors that can activate osteoclastic bone resorption, disrupting bone metabolism in pathological conditions. By contrast, exosomes from M2 macrophages often contain anti‑inflammatory factors that promote tissue repair and bone formation. In the context of bone metabolism, exosomes from M1 and M2 macrophages modulate muscle‑bone signaling by delivering regulators that influence the expression of IGF‑1 and FGF‑2, affecting osteoblast proliferation, differentiation, and mineralization. M1 macrophage‑derived exosomes activate signaling pathways such as NF‑κB and MAPK through the transfer of pro‑inflammatory cargo, thereby enhancing bone resorption. By contrast, exosomes from M2 macrophages can suppress pro‑inflammatory signaling while activating pathways like TGF‑β and PI3K/Akt, promoting bone synthesis and repair. As critical myokines, IGF‑1 and FGF‑2 not only support muscle growth, repair, and maintenance but also directly influence bone remodeling through musculoskeletal crosstalk.
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