International Journal Of Molecular Medicine[JOURNAL]
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200 papers
IL‑37/IL‑1R8 blocks keratinocyte acantholysis via suppressing ADAM17/EGFR.
Hu F, Chen W, Wang Q … +4 more , Zhang X, Xiao F, Zhang J, Liang J
Int J Mol Med · 2026 May · PMID 41823548 · Full text
Pemphigus vulgaris (PV) is a life‑threatening autoimmune blistering disease characterized by acantholysis (the loss of cell‑cell adhesion of keratinocytes) and the formation of non‑healing suprabasal intraepidermal blist...
Pemphigus vulgaris (PV) is a life‑threatening autoimmune blistering disease characterized by acantholysis (the loss of cell‑cell adhesion of keratinocytes) and the formation of non‑healing suprabasal intraepidermal blisters. The progression of keratinocyte acantholysis in PV is complex. Interleukin‑37 (IL‑37), which functions through receptor binding, exerts a protective role in PV. However, the specific receptor mediating the effect of IL‑37 in PV and the underlying mechanisms remain unclear. The present study found elevated levels of IL‑37, a natural suppressor of innate inflammatory and immune responses, in patients with PV. IL‑37 treatment directly suppressed both acantholysis and apoptosis in keratinocytes. Mechanistic investigations using co‑immunoprecipitation revealed that IL‑37 binds to interleukin‑1 receptor 8 (IL‑1R8). Knockdown of IL‑1R8 (or IL‑18Rα) abolished the inhibitory effects of IL‑37 on acantholysis and apoptosis. Furthermore, the IL‑37/IL‑1R8 complex suppressed epidermal growth factor receptor (EGFR) signaling, and reduced the expression of TNF‑alpha‑converting enzyme (ADAM17). Activation of EGFR using specific agonists reversed the IL‑37‑mediated reduction in acantholysis and apoptosis in HaCaT cells. In conclusion, IL‑37 treatment markedly attenuated keratinocyte dissociation and apoptosis in PV through the IL‑1R8/ADAM17/EGFR pathway. These findings provide novel mechanistic insights into the immunoregulatory functions of IL‑37.
Mechanotransduction and its impact on regenerative medicine in orthopedic rehabilitation (Review).
Wang B, Zeng X, Liu H … +6 more , Li L, Lei T, Li Y, Fang Q, Cao Y, Dong B
Int J Mol Med · 2026 May · PMID 41823544 · Full text
Mechanotransduction, the process by which cells convert mechanical stimuli into biochemical signals, serves as a fundamental biological mechanism driving tissue adaptation and repair in orthopedic rehabilitation. The pre...
Mechanotransduction, the process by which cells convert mechanical stimuli into biochemical signals, serves as a fundamental biological mechanism driving tissue adaptation and repair in orthopedic rehabilitation. The present review explores how mechanical forces regulate cellular behavior in bone, cartilage, tendon and ligament healing, emphasizing their critical role in optimizing regenerative outcomes. Specialized mechanosensors, including integrins, ion channels and primary cilia, detect physical cues such as compression, tension and shear stress, activating downstream pathways that direct stem cell differentiation, matrix synthesis and tissue remodeling. The extracellular matrix functions not only as a structural scaffold but also as a dynamic mediator of mechanical signaling, influencing cellular responses to therapeutic loading. Clinically, mechanotherapy strategies, including controlled weight‑bearing, eccentric exercises and devices providing dynamic compression, are designed to exploit these principles, promoting anabolic activity while preventing catabolic damage. Advances in biomechanically optimized scaffolds, bioreactor systems and technologies (such as low‑intensity pulsed ultrasound) further demonstrate how targeted mechanical conditioning enhances tissue‑engineered constructs and accelerates functional recovery. However, challenges remain in defining optimal loading parameters across diverse tissues and individual patients. Future directions should prioritize personalized rehabilitation protocols informed by real‑time biomechanical monitoring and genetic profiling, alongside biomaterials that can adapt to in vivo mechanical cues. The integration of mechanobiology with regenerative medicine is paving the way for a new era in orthopedic rehabilitation. This evolution promises more precise, effective and biologically driven interventions that harness the innate mechanoresponsive capacity of the body to restore function.
HELLS inhibits autophagy‑dependent ferroptosis in nasopharyngeal carcinoma by modulating the Nrf2/HO‑1/GPX4 pathway.
Jin C, Li J, Han S … +3 more , Bai C, Yang J, Wang Z
Int J Mol Med · 2026 May · PMID 41823538 · Full text
The present study aimed to elucidate the role of lymphoid‑specific helicase (HELLS) in autophagy‑dependent ferroptosis in nasopharyngeal carcinoma (NPC) cells and associated mechanisms. Bioinformatics analyses were condu...
The present study aimed to elucidate the role of lymphoid‑specific helicase (HELLS) in autophagy‑dependent ferroptosis in nasopharyngeal carcinoma (NPC) cells and associated mechanisms. Bioinformatics analyses were conducted to identify the key gene. Gene knockout was accomplished through short‑hairpin RNA transfection. Reverse transcription‑quantitative polymerase chain reaction was conducted to evaluate mRNA expression, whereas protein expression was assessed through immunohistochemistry and western blotting. Furthermore, cell proliferation, migration, invasion and apoptosis were investigated via the Cell Counting Kit‑8, Transwell and flow cytometry assays. Glutathione (GSH), malondialdehyde (MDA) and Fe were quantified using commercial reagent kits. Reactive oxygen species (ROS) were assessed through immunofluorescence. Additionally, a tumor xenograft mouse model was employed for validation. HELLS, upregulated in human NPC tissue, was selected from 15 candidate genes. HELLS knockout resulted in decreased proliferation, migration and invasion while promoting apoptosis and autophagy in NPC/HK1 cells. Furthermore, the administration of ferroptosis and autophagy agonists increased the levels of MDA, Fe, 4‑hydroxynonenal and ROS, as well as the expression of acyl‑CoA synthetase long‑chain family member 4 and prostaglandin‑endoperoxide synthase 2. Conversely, GSH levels decreased. These observed trends can be reversed by ferroptosis and autophagy inhibitors. HELLS knockout also caused the downregulation of nuclear factor‑erythroid 2‑related factor 2 (Nrf2), heme oxygenase‑1 (HO‑1) and glutathione peroxidase 4 (GPX4), which can be modulated by Nrf2 agonist. In experiments, HELLS expression reduction inhibited tumor growth and the expression of Nrf2, HO‑1 and GPX4 while promoting autophagy. In conclusion, HELLS activates the Nrf2/HO‑1/GPX4 pathway, which inhibits autophagy‑dependent ferroptosis in NPC cells, thereby promoting NPC progression.
Research progress on the molecular mechanisms of tanshinone IIA in the treatment of cardiovascular and cerebrovascular diseases (Review).
Pei W, Lu P, Ding C … +2 more , Li Y, Li Y
Int J Mol Med · 2026 May · PMID 41823534 · Full text
Cardiovascular and cerebrovascular diseases (CCVDs) have become prominent global health threats, presenting substantial challenges due to their intricate pathological mechanisms and diverse clinical manifestations. Tansh...
Cardiovascular and cerebrovascular diseases (CCVDs) have become prominent global health threats, presenting substantial challenges due to their intricate pathological mechanisms and diverse clinical manifestations. Tanshinone IIA (TSA), an active compound derived from the traditional Chinese medicinal herb Salvia miltiorrhiza, exhibits notable therapeutic potential in these diseases due to its multifaceted mechanism of action. TSA protects the cardiovascular and cerebrovascular systems by inhibiting inflammation, reducing oxidative stress, preventing apoptosis and fibrosis, and modulating key signaling pathways, including toll‑like receptor 4/NF‑κB, PI3K/AKT and nuclear factor erythroid 2‑related factor 2/heme oxygenase‑1. Notably, considerable progress has been made in applying TSA to conditions such as atherosclerosis, myocardial infarction, heart failure and hypertension. The present review synthesizes current research on the molecular mechanisms of TSA in treating CCVDs and highlights innovations in nanodelivery systems (for example, rHDL, TPP‑TPGS/LPNs and CBSA‑PEG‑TSA‑NPs) that enhance its therapeutic efficacy by improving solubility, prolonging its half‑life and enhancing targeting capabilities. These advancements not only establish a foundation for the broader clinical application of TSA in CCVDs but also offer valuable insights for the development of new therapeutic agents.
[Expression of Concern] Visfatin/PBEF/Nampt induces EMMPRIN and MMP‑9 production in macrophages via the NAMPT‑MAPK (p38, ERK1/2)‑NF‑κB signaling pathway.
Fan Y, Meng S, Wang Y … +2 more , Cao J, Wang C
Int J Mol Med · 2026 May · PMID 41823533 · Full text
Following the publication of the above paper, a concerned reader has drawn the Editor's attention to the fact that, regarding the western blot data shown in Fig. 4A and E on p. 612, the p‑p38 blots featured in these figu...
Following the publication of the above paper, a concerned reader has drawn the Editor's attention to the fact that, regarding the western blot data shown in Fig. 4A and E on p. 612, the p‑p38 blots featured in these figure parts were strikingly similar, although the blots were rotated through 180° relative to each other. Upon investigating the data in this paper independently in the Editorial Office, it also came to light that β‑actin control blots featured in Fig. 1E, and p‑p38 blots featured in Fig. 5I, subsequently appeared in another paper written by the same research group in an article published in the journal . Finally, control western blots appeared to have been re‑used in Fig. 4A and C, although the experimental conditions reported for the western blots in these figure parts were different. The authors have been contacted by the Editorial Office to offer an explanation for these apparent anomalies in the presentation of the data in this paper, and we are awaiting their response. 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 these potential problems while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 27: 607‑615, 2011; DOI: 10.3892/ijmm.2011.621].
Ferritin in ferroptosis: Implications for neurodegenerative diseases (Review).
Chen W, Tian H, Wei R … +2 more , Chen X, Jia Y
Int J Mol Med · 2026 May · PMID 41823531 · Full text
Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, are characterized by progressive loss of neurons. Although the precise pathogenesis of such diseases is co...
Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, are characterized by progressive loss of neurons. Although the precise pathogenesis of such diseases is complex and multifactorial, several molecular pathways have been implicated, including the aggregation of misfolded proteins, mitochondrial dysfunction, oxidative stress, neuroinflammation and disrupted iron homeostasis. Emerging evidence has underscored the pivotal role of ferroptosis, an iron‑dependent, non‑apoptotic form of cell death, in neurodegenerative disease progression. Ferritin, characterized by a 24‑subunit hollow sphere structure composed of heavy and light chains, plays a key role in the network regulating cerebral iron homeostasis. In response to cellular iron overload, ferritin expression is upregulated to sequester labile iron and mitigate Fenton reaction‑mediated toxicity, thus exerting a cytoprotective function. Paradoxically, ferritin can be degraded via ferritinophagy, a selective autophagic process that releases toxic ferrous iron and directly triggers ferroptosis. This review systematically reviews the role of ferritin within the iron homeostasis network to elucidate the connection between the dysregulation of iron metabolism and the pathological mechanisms of neurodegenerative diseases. The study focused on the potential role of ferritin as a biomarker for early diagnosis, therapeutic strategies targeting ferritin pathways to restore iron homeostasis and the clinical translational value of magnetic resonance imaging‑based non‑invasive quantification of cerebral iron deposition. It is crucial to elucidate the multidimensional roles of ferritin in neurodegeneration to provide a theoretical foundation for precision diagnostic and therapeutic approaches.
[Corrigendum] Ursolic acid protects against cisplatin‑induced ototoxicity by inhibiting oxidative stress and TRPV1‑mediated Ca‑signaling.
Di Y, Xu T, Tian Y … +8 more , Ma T, Qu D, Wang Y, Lin Y, Bao D, Yu L, Liu S, Wang A
Int J Mol Med · 2026 May · PMID 41823526 · Full text
Following the publication of this paper, it was drawn to the Editor's attention by an interested reader that, regarding the immunohistochemical images in Fig. 2A on p 809, the Control/SG and UA/SG data panels contained...
Following the publication of this paper, it was drawn to the Editor's attention by an interested reader that, regarding the immunohistochemical images in Fig. 2A on p 809, the Control/SG and UA/SG data panels contained an overlapping data section, suggesting that these data panels had been derived from the same original source. In addition, concerning the outer hair cell images shown in Fig. 4A on p. 811, the CDDP/TRITC and UA+CDDP/TRITC data panels appeared to be matching, suggesting that this figure had also been assembled incorrectly. Upon contacting the authors about these issues, they realized that Figs. 2 and 4 in this paper had inadvertently been assembled incorrectly. The revised versions of Figs. 2 and 4, now featuring the correct data for the UA/SG panel in Fig. 2A and the CDDP/TRITC data panel in Fig. 4A, are shown on the next page. The authors wish to emphasize that the errors made in assembling the data in these 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 46: 806‑816, 2020; DOI: 10.3892/ijmm.2020.4633].
Reactive oxygen species in fetal growth restriction mechanisms and therapeutic directions (Review).
Cheng D, Yang S, Wang C … +3 more , Fan K, Gao F, Sun Q
Int J Mol Med · 2026 May · PMID 41823521 · Full text
Fetal growth restriction (FGR) is strongly associated with adverse perinatal outcomes, and placental oxidative stress has been identified as a central pathological mechanism. In maternal plasma, cord blood and placental...
Fetal growth restriction (FGR) is strongly associated with adverse perinatal outcomes, and placental oxidative stress has been identified as a central pathological mechanism. In maternal plasma, cord blood and placental tissues from FGR pregnancies, the levels of malondialdehyde, 4‑hydroxynonenal, reactive oxygen metabolites and 8‑hydroxy‑2'‑deoxyguanosine are consistently elevated. In parallel, superoxide dismutase and glutathione peroxidase show compensatory upregulation, while catalase activity declines, reflecting increased oxidative burden coupled with impaired antioxidant defense. Major sources of reactive oxygen species include NADPH oxidase and xanthine oxidase, mitochondrial electron transport and ischemia‑reperfusion events. Mechanistic evidence further indicates that oxidative stress interacts with endoplasmic reticulum stress, metabolic reprogramming and epigenetic alterations, thereby aggravating trophoblast dysfunction and placental vascular injury. Aberrant DNA hypomethylation, histone modifications and dysregulation of noncoding RNAs, such as microRNA (miR)‑199a, miR‑210‑3p and miR‑21, contribute to persistent remodeling of trophoblast behavior and vascular networks. Early clinical studies have suggested that melatonin and pentoxifylline may alleviate placental oxidative injury and improve selected perinatal outcomes, whereas vitamin C and E supplementation shows no clear benefit. Preclinical investigations have highlighted the potential of mitochondria‑targeted and classical antioxidants, including mitoquinone mesylate, N‑acetylcysteine, tempol and resveratrol; however, their efficacy and safety appear to be dependent on gestational timing and dosage. Further well-designed clinical trials are warranted to establish effective antioxidant‑based strategies for FGR.
Research progress in single‑cell omics technologies for kidney disease (Review).
Xu J, Chen Z, Li S … +2 more , Wang X, Chen M
Int J Mol Med · 2026 May · PMID 41789675 · Full text
The kidney is a vital organ for maintaining metabolic balance within the body and facilitating excretion. Its complex tissue structure comprises diverse cell types, including glomerular, tubular, interstitial and immune...
The kidney is a vital organ for maintaining metabolic balance within the body and facilitating excretion. Its complex tissue structure comprises diverse cell types, including glomerular, tubular, interstitial and immune cells. The highly differentiated nature of these cells presents challenges for investigating kidney disease mechanisms. In recent years, the rapid advancement of single‑cell omics technologies has provided novel perspectives for renal research. These techniques have revealed the diversity and heterogeneity of renal cells, enabling precise identification of multiple immune cell types within the kidney. These findings further elucidate the dynamic changes in renal immune cells during disease progression and their interactions with other renal cells, laying a foundation for in‑depth analysis of renal disease pathogenesis. The present review aims to summarize the current applications of single‑cell omics technologies in renal ageing and kidney diseases, providing crucial insights for deciphering disease mechanisms and identifying therapeutic targets.
Treatment of pulmonary fibrosis: From disease mechanisms to future novel therapies (Review).
Lu S, Liu Y, Li X … +1 more , Yao Q
Int J Mol Med · 2026 May · PMID 41789674 · Full text
Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease characterized by irreversible lung scarring and frequently associated with lung cancer. Currently, there remains a lack of effective therapies...
Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease characterized by irreversible lung scarring and frequently associated with lung cancer. Currently, there remains a lack of effective therapies capable of significantly improving long‑term outcomes or reversing the disease course. Although antifibrotic drugs are widely used and have enhanced the mechanistic understanding of PF, their efficacy is limited. This review systematically explores the core pathobiological processes and epigenetic regulatory networks involved in PF pathogenesis. Simultaneously, a critical review of the most promising emerging therapeutic strategies in recent years, including stem cell therapy, novel targeted agents, nucleic acid delivery technologies and epigenetic interventions, is provided. An in‑depth analysis of the transformative role of artificial intelligence (AI) in integrating multi‑omics data, predicting disease trajectories and optimizing personalized treatment plans is also presented. However, significant challenges hinder the clinical translation of these novel approaches. While AI‑based models offer valuable insights, they are constrained by the complex heterogeneity of PF. Epigenetic therapies, despite their promise, face obstacles related to drug development, delivery efficiency and long‑term clinical impact. Moving forward, the fundamental shift from palliative management to a disease‑modifying paradigm for PF will not rely on a single technological breakthrough. Instead, it necessitates deep interdisciplinary integration. This involves the systematic convergence of the potential of regenerative medicine, the precision of gene editing, the molecular intervention of targeted therapy and the dynamic decision‑making capabilities driven by AI. The goal is to construct a next‑generation, individualized treatment framework capable of adapting to disease heterogeneity and evolving with the patient's condition. Despite the considerable challenges, this multimodal integrated strategy is paving a viable new path toward ultimately conquering pulmonary fibrosis.
Propofol upregulates MFG‑E8 in BV2 cells to inhibit pyroptosis mediated by the NF‑κB/NLRP3 pathway, thereby ameliorating ischemic‑reperfusion neuronal injury.
Guo S, Zhen Y, Zhou G … +1 more , Zhao Z
Int J Mol Med · 2026 May · PMID 41789673 · Full text
Abnormal activation and pyroptosis of microglia caused by cerebral ischemia‑reperfusion injury (CIRI) are key mechanisms underlying neuronal damage. The NF‑κB/NLRP3 pathway is a core mediator of microglial pyroptosis and...
Abnormal activation and pyroptosis of microglia caused by cerebral ischemia‑reperfusion injury (CIRI) are key mechanisms underlying neuronal damage. The NF‑κB/NLRP3 pathway is a core mediator of microglial pyroptosis and neuroinflammatory cascades in CIRI. Milk fat globule‑EGF factor 8 (MFG‑E8) is a critical anti‑inflammatory and neuroprotective factor. Propofol (PPF) exhibits antioxidant activity and ameliorates neuronal injury, but its effects on CIRI and underlying mechanisms remain unclear. The present study aimed to investigate whether PPF alleviates neuronal injury by modulating NF‑κB/NLRP3 pathway via regulating MFG‑E8 expression. An oxygen‑glucose deprivation/reoxygenation (OGD/R) model was established using mouse microglial BV‑2 and hippocampal neuronal HT22 cells and cell survival was assessed via Cell Counting Kit‑8 assay. Polarity in BV‑2 cells was evaluated using flow cytometry, while cell death was assessed by Calcein AM/PI and TUNEL staining. A transient middle cerebral artery occlusion (tMCAO) mouse model was established and neurological deficit scores were assessed. The impacts of PPF on cortical damage, neuroinflammation, apoptosis and pyroptosis in tMCAO mice were observed by histopathological staining. Inflammatory factor levels were assessed using ELISA kits. Western blotting was performed to assess MFG‑E8, pyroptosis and NF‑κB/NLRP3 pathway‑related proteins. OGD/R decreased viability, increased apoptosis and pyroptosis rates in BV‑2 and HT22 cells and promoted M1 polarization in BV‑2 cells; PPF treatment reversed these effects. MFG‑E8 was downregulated in OGD/R‑treated BV2 cells, while PPF upregulated MFG‑E8 expression. Additionally, PPF decreased cerebral infarction volume in tMCAO mice, improved neurological deficit score, mitigated pathological brain tissue damage and decreased the number of degenerating neurons. PPF also inhibited pro‑inflammatory microglia activation and decreased pro‑inflammatory factor levels. Mechanistically, PPF suppressed NF‑κB pathway activation and downregulated NLRP3 by upregulating MFG‑E8; silencing MFG‑E8 reduced the protective effects of PPF in tMCAO mice and OGD/R cell models. PPF improved neuronal injury in CIRI by upregulating MFG‑E8 to inhibit pyroptosis induced by the NF‑κB/NLRP3 pathway.
[Expression of Concern] Syringin prevents cardiac hypertrophy induced by pressure overload through the attenuation of autophagy.
Li F, Zhang N, Wu Q … +5 more , Yuan Y, Yang Z, Zhou M, Zhu J, Tang Q
Int J Mol Med · 2026 May · PMID 41789671 · Full text
Following the publication of the above paper, a concerned reader has drawn to the Editor's attention that the data shown for the p-AMPKα blots with the RT-qPCR analysis in Fig. 2B on p. 203 are strikingly similar to the...
Following the publication of the above paper, a concerned reader has drawn to the Editor's attention that the data shown for the p-AMPKα blots with the RT-qPCR analysis in Fig. 2B on p. 203 are strikingly similar to the ATG7 blots shown in Fig. 4A on p. 205. The authors were contacted by the Editorial Office to offer an explanation for this apparent anomaly in the presentation of the data in this paper, although up to this time, no response from the authors 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 39: 199-207, 2017; DOI: 10.3892/ijmm.2016.2824].
CLDN7: Epithelial gatekeeper from physiology to pathology‑roles in cancer and epithelial‑related diseases (Review).
Lai X, Yan Y, Sun L … +2 more , Lei Z, Yang Y
Int J Mol Med · 2026 May · PMID 41789662 · Full text
Claudin‑7 (CLDN7) is a key component of epithelial tight junctions. It plays a vital role in maintaining cell polarity, barrier integrity and paracellular transport. Abnormal CLDN7 expression is closely related to the on...
Claudin‑7 (CLDN7) is a key component of epithelial tight junctions. It plays a vital role in maintaining cell polarity, barrier integrity and paracellular transport. Abnormal CLDN7 expression is closely related to the onset and progression of various diseases. It is especially markedly associated with the growth and metastasis of multiple cancers. Additionally, dysregulated CLDN7 expression contributes to the progression of intestinal, skin and respiratory system diseases. The present review summarized the structure, expression, physiological functions, stability and regulatory mechanisms of CLDN7, emphasizing its role in tumors. The expression patterns, regulatory mechanisms, effect on malignant phenotypes and clinical significance of CLDN7 were also discussed.
Exosomal circ0000549 promotes MNNG‑induced gastric cancer through miR‑15b‑5p/KIF1B.
Liang Z, Gao Z, Zhang Y … +3 more , Song J, Qian H, Xu X
Int J Mol Med · 2026 May · PMID 41789656 · Full text
Accumulating evidence indicates that environmental exposures, particularly to nitrites, play a critical role in the initiation and progression of gastric cancer (GC). During carcinogenesis, exosomes act as key mediators...
Accumulating evidence indicates that environmental exposures, particularly to nitrites, play a critical role in the initiation and progression of gastric cancer (GC). During carcinogenesis, exosomes act as key mediators of intercellular communication. Exosomes derived from N‑methyl-N'‑nitro‑N‑nitrosoguanidine (MNNG)‑induced malignantly transformed GES‑1 cells (TGES‑1), as well as serum exosomes from gastric cancer patients with a history of high nitrite exposure, were found to influence normal cells and promote GC initiation. The present study established a malignant transformation model and applied bioinformatics analyses to screen and validate candidate circRNAs. A series of functional and mechanistic experiments were performed to elucidate the regulatory role of exosomes in GC progression. Circ0000549 was markedly upregulated in MNNG‑exposed GES‑1 cells, their derived exosomes and serum exosomes from patients with GC. Further investigations revealed that circ0000549 overexpression enhanced GES‑1 cell malignant features, while also modulating epithelial‑mesenchymal transition and stemness‑related properties. Nude mouse experiments demonstrated that circ0000549, carried by malignantly transformed exosomes, plays a crucial role in MNNG‑induced gastric carcinogenesis. Mechanistically, miR‑15b‑5p was identified as a potential target of circ0000549. Circ0000549 functioned as a sponge for miR‑15b‑5p, leading to increased KIF1B expression and subsequent activation of the PI3K/AKT signaling pathway. Collectively, these findings reveal that exosomal circ0000549 promotes malignant transformation of GES‑1 cells through the miR‑15b‑5p/KIF1B/PI3K/AKT axis. Exosomal circ0000549 may serve as a promising biomarker for GC diagnosis and prognosis, highlighting its potential as a target for future therapeutic investigation.
Dynamic regulation and targeted intervention of neutrophils in hepatic ischemia‑reperfusion injury (Review).
Lu S, Tong J, Jiang J … +2 more , Zhang Q, Huang Y
Int J Mol Med · 2026 May · PMID 41789651 · Full text
Ischemia‑reperfusion injury (IRI) is a complex pathophysiological process characterized by oxidative stress, inflammatory response and cell death during tissue reperfusion, leading to organ dysfunction. In liver transpla...
Ischemia‑reperfusion injury (IRI) is a complex pathophysiological process characterized by oxidative stress, inflammatory response and cell death during tissue reperfusion, leading to organ dysfunction. In liver transplantation, hepatic ischemia‑reperfusion injury (HIRI) can result in irreversible liver failure and subsequently trigger rejection. Neutrophils, as the first recruited innate immune cells, play a central role in the initiation, progression and resolution stages of HIRI. However, current research predominantly focuses on their pro‑inflammatory and damaging mechanisms, lacking a theoretical framework that systematically integrates their dual functions. Based on a systematic review of key processes involving neutrophils in HIRI, including recruitment, adhesion, migration, neutrophil extracellular trap (NET) formation and phenotypic polarization, the present review proposed the 'injury‑repair balance' theory. It emphasized that neutrophils are dynamically regulated by the hepatic microenvironment and can undergo functional conversion between pro‑inflammatory N1 and anti‑inflammatory/repair N2 phenotypes. Their polarization state is a critical factor determining the progression and recovery of HIRI. The present review further explores multi‑dimensional intervention strategies targeting neutrophils, including inhibiting excessive recruitment and activation, regulating migration to reduce local accumulation, suppressing NET formation and promoting their clearance, as well as combining antioxidant and anti‑inflammatory therapies to reestablish immune homeostasis. Additionally, extracellular vesicles, due to their excellent targeting delivery and immunomodulatory capabilities, have emerged as potential tools for precise regulation of neutrophil function. Notably, current research on neutrophil polarization mechanisms remains incomplete. Future studies should delve into the temporal regulatory mechanisms of polarization and explore the possibility of driving neutrophils toward an N2‑like reparative phenotype through pharmacological or biological interventions. This strategy is expected to shift the treatment paradigm for HIRI from traditional 'cell suppression' to a more precise 'functional reprogramming,' transforming the approach from merely mitigating injury to actively promoting tissue regeneration.
[Corrigendum] Astragaloside IV promotes the proliferation and migration of osteoblast‑like cells through the hedgehog signaling pathway.
Guo LH, Cao Y, Zhuang RT … +2 more , Han Y, Li J
Int J Mol Med · 2026 May · PMID 41789649 · Full text
Following the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 2D on p. 834 showing the results of Transwell cell migration assay experiments for the U‑2OS cell line, th...
Following the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 2D on p. 834 showing the results of Transwell cell migration assay experiments for the U‑2OS cell line, the 'U‑2OS 24 h/Control' and 'U‑2OS 24 h/AST‑IV' data panels contained an overlapping section, such that these data panels were apparently derived from the same original source, where the results of differently performed experiments were intended to have been portrayed. Upon performing an independent analysis of the data in this paper in the Editorial Office, it also came to light that two pairs of data panels comparing Figs. 2C and 4C, and 2D and 4D, also contained overlapping sections. After having consulted their original data, the authors realized that Fig. 2 had inadvertently been assembled incorrectly. The revised version of Fig. 2, now showing the correct data for the 'MG‑64 48 h/AST‑IV', U‑2OS 24 h/AST‑IV' and 'U‑2OS 48 h/AST‑IV' panels in Fig. 2C and D, 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 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: 830‑838, 2019; DOI: 10.3892/ijmm.2018.4013].
Mechanistic insights into inflammatory cytokines in adenomyosis‑induced infertility (Review).
Yang B, Li F, Cao G … +6 more , Nuo M, Shi Y, Wang Z, Jia J, Shi W, Liu Z
Int J Mol Med · 2026 May · PMID 41789648 · Full text
Adenomyosis (AM), an estrogen‑dependent chronic inflammatory disease with a rising incidence, has emerged as a major cause of infertility and reduced clinical pregnancy rates in reproductive‑aged women, severely impairin...
Adenomyosis (AM), an estrogen‑dependent chronic inflammatory disease with a rising incidence, has emerged as a major cause of infertility and reduced clinical pregnancy rates in reproductive‑aged women, severely impairing reproductive health and quality of life. The core pathological mechanisms of AM are closely linked to aberrant local expression of inflammatory cytokines, including interleukin (IL)‑6, C‑X‑C motif chemokine ligand 8 (CXCL8), IL1B, tumor necrosis factor‑α, NF‑κB, cyclooxygenase‑2 and TGF‑β, which disrupt the immune barrier at the endometrial‑myometrial junction. This disruption further breaks the critical balance between proinflammatory and anti‑inflammatory cytokines, ultimately fostering an immune microenvironment hostile to embryo survival. Concurrently, inflammatory cytokine‑activated cellular processes, including proliferation, invasion, tissue injury and repair, epithelial‑mesenchymal transition and fibrosis, further induce pathological neovascularization and impair blood perfusion in the junctional zone. These pathological changes, in turn, compromise endometrial receptivity and inhibit decidualization, ultimately resulting in implantation failure. Based on these mechanisms, key inflammatory cytokines such as IL‑6, CXCL8, IL1B and IL‑10 hold potential as diagnostic biomarkers for AM‑related infertility and provide a theoretical basis for developing fertility‑preserving therapies targeting the inflammatory cascade (such as IL‑6 receptor monoclonal antibodies and TGF‑β inhibitors). These findings offer new approaches to achieve the dual goals of lesion control and fertility preservation in clinical practice.
The dual role of the crosstalk between autophagy and ferroptosis in lung cancer treatment: Advances in mechanisms and therapeutic strategies (Review).
Zhang Y, Shen R
Int J Mol Med · 2026 May · PMID 41789644 · Full text
The interaction between autophagy and ferroptosis has resulted in the identification of novel approaches for the treatment of lung cancer (LC). The two processes are closely interconnected via three core regulatory modes...
The interaction between autophagy and ferroptosis has resulted in the identification of novel approaches for the treatment of lung cancer (LC). The two processes are closely interconnected via three core regulatory modes: Negative regulation, positive regulation and feedback regulation, thereby forming a complex and context‑dependent regulatory network. Within the context of LC progression, the interaction between autophagy and ferroptosis exhibits a dual role. On one hand, it promotes LC development by enabling cancer cell survival in adverse microenvironments, remodeling metabolic pathways and orchestrating the tumor microenvironment to facilitate immune evasion. On the other hand, it can suppress LC by removing damaged cellular components, inducing ferroptosis, and boosting immune surveillance and clearance of cancer cells. Consequently, therapeutic strategies for LC are continuously evolving. In the field of pharmacotherapy, traditional agents such as chloroquine and its derivatives are being repurposed with subtype‑dependent efficacy, and their antitumor activity can be potentiated via nanoparticle delivery systems. When combined with ferroptosis inducers or other drugs, these agents can augment therapeutic efficacy and surmount drug resistance. Current research and development efforts are focused on small‑molecule compounds that target key nodes in autophagy‑ferroptosis crosstalk. Moreover, combination therapy represents a central focus of research. When combined with chemotherapy, radiotherapy, targeted therapy and immunotherapy, this combination approach shows potential for synergistic efficacy. However, current research faces several challenges, including the complexity of regulatory mechanisms and inter‑individual variability. Most therapeutic strategies remain in the preclinical research phase and the synergistic mechanisms of combination therapies are not yet fully elucidated. Comprehensive investigations into the molecular processes, coupled with the application of multi‑omics technologies, are crucial for clarifying the regulatory network. The development of precise biomarkers, along with the integration of artificial intelligence and big data analytics, is essential to accelerate the advancement of novel drugs and therapeutic strategies, with the ultimate goal of improving the prognosis for patients with LC.
[Retracted] A novel role for Livin in the response to ultraviolet B radiation and pterygium development.
Wu SQ, Xu QB, Sheng WY … +2 more , Su LY, Zhu LW
Int J Mol Med · 2026 Apr · PMID 41789636 · Full text
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric data shown in Fig. 6E on p. 1109 were strikingly similar to data that had app...
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric data shown in Fig. 6E on p. 1109 were strikingly similar to data that had appeared previously in a paper in the journal written by different authors at different research institutes. In addition, a subsequent assessment of the data in the Editorial Office revealed that the cleaved caspase‑3 western blot data in Fig. 4A appeared to match with the protein bands featured in a larger gel slice shown to represent the Livin data in Fig. 5A. In view of the fact that the abovementioned data had already apparently been published prior to its submission to , the Editor 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 satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 45: 1103‑1111, 2020; DOI:10.3892/ijmm.2020.4481].
mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review).
Huo R, Yang Y, Wei C … +4 more , Yang Y, Meng D, Lin J, Huang X
Int J Mol Med · 2026 Apr · PMID 41789635 · Full text
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder that can progress from asymptomatic glandular involvement to systemic manifestations affecting multiple organs, thereby imposing a notable economic burden...
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder that can progress from asymptomatic glandular involvement to systemic manifestations affecting multiple organs, thereby imposing a notable economic burden on both patients and society. The pathogenesis of pSS is complex and involves multifactorial interactions between genetic, environmental and immune components. Although pSS is a common rheumatic disease, current therapeutic approaches primarily focus on symptom management and no curative treatment is available. Therefore, it is key to identify novel and effective therapeutic strategies for affected individuals. The mTOR signaling pathway is a key regulatory pathway in numerous types of cell, playing a crucial role in immune regulation, inflammation and autophagy. Activation of this pathway can promote inflammation by inducing immune dysregulation, thereby contributing to the pathogenesis of pSS. Conversely, inhibition of the mTOR signaling pathway mitigates these pathological processes and may help alleviate disease severity. Thus, the mTOR signaling pathway represents a promising therapeutic target for pSS. The present review aimed to elucidate the role and underlying mechanisms of the mTOR signaling pathway in pSS and provide a theoretical foundation for developing targeted therapeutic interventions.
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