International Journal Of Molecular Medicine[JOURNAL]
Sun
200 papers
IL‑17A γδT cell activation via the HMGB1‑TLR2/4‑NF‑κB signaling pathways in biliary atresia.
Zhang MX, Tang JF, Hong M … +8 more , Yang Y, Zhou Y, Chi SQ, Rong LY, Cao GQ, Zhang X, Zhang JX, Tang ST
Int J Mol Med · 2026 Jul · PMID 42138197 · Full text
IL‑17A γδT cells are involved in biliary atresia (BA) inflammatory injury; however, the mechanism underlying their activation remains unclear. The present study aimed to elucidate the mechanism by which γδT cells are act...
IL‑17A γδT cells are involved in biliary atresia (BA) inflammatory injury; however, the mechanism underlying their activation remains unclear. The present study aimed to elucidate the mechanism by which γδT cells are activated to secrete IL‑17A in BA. Clinical samples from 27 patients with BA and 23 control individuals were collected and analyzed using reverse transcription‑quantitative PCR (RT‑qPCR), western blotting, ELISA, flow cytometry, Opal multiplex immunohistochemistry and immunohistochemistry. In addition, wild‑type (WT) and BA murine models were developed through infection with rhesus rotavirus (RRV) and assessed by RT‑qPCR, western blotting, ELISA, flow cytometry, immunohistochemistry and hematoxylin and eosin staining. The release of high‑mobility group box‑1 (HMGB1) from RRV‑infected biliary epithelial cells (BECs) and macrophages was investigated by ELISA and immunofluorescence confocal microscopy. In addition, co‑culture systems of γδT cells with BECs or macrophages were established. The results revealed that the levels of hepatic IL‑17A were higher in patients with BA, with γδT cells serving an important role in producing IL‑17A. In the BA murine model, the IL‑17A levels increased from day 3 to 14, and IL‑17A γδT cells peaked on day 7. The BA murine model exhibited lower IL‑17A levels, improved liver and bile duct morphology, and lower BA incidence compared with in the WT BA murine model, which was reversed through adoptive transfer of murine IL‑17A γδT cells. HMGB1, and Toll‑like receptor (TLR)2 and 4 were upregulated in liver tissues from both patients with BA and the BA murine model. By contrast, hepatic IL‑17A levels were decreased in the BA murine model treated with the HMGB1 inhibitor. In addition, HMGB1 was released from RRV‑infected BECs or macrophages, and exogenous HMGB1 stimulation enhanced IL‑17A production in γδT cells. The and γδT cell co‑culture system inhibited IL‑17A production and NF‑κB activation, whereas NF‑κB inhibition abolished HMGB1‑induced IL‑17A production in WT γδT cells. In conclusion, HMGB1 released from injured BECs or macrophages may activate IL‑17A γδT cells to mediate BA inflammatory injury via the HMGB1‑TLR2/4‑NF‑κB pathways. The present study was registered with the Chinese Clinical Trial Registry (registration ID: ChiCTR2000039619; registered November 3, 2020).
CircRAD18 promotes glioblastoma proliferation, migration and invasion via the miR‑1231/LUC7L2 axis.
Song L, Xiong P, Jike A … +10 more , Xia X, Mao L, Wang Z, Cheng Y, Wang S, Tan S, Yu D, Li Z, Tang X, Li S
Int J Mol Med · 2026 Jul · PMID 42138196 · Full text
Glioblastoma (GBM) is an exceptionally aggressive and malignant central nervous system tumor with a poor prognosis. Studies suggest that circular RNAs (circRNAs) play a vital role in GBM progression. Exosomes, key mediat...
Glioblastoma (GBM) is an exceptionally aggressive and malignant central nervous system tumor with a poor prognosis. Studies suggest that circular RNAs (circRNAs) play a vital role in GBM progression. Exosomes, key mediators of intercellular communication, carry circRNAs that may regulate this process. The present study aimed to investigate how circRAD18 modulates GBM cell proliferation, migration and invasion through the miR‑1231/LUC7L2 axis and to evaluate the potential of exosomal circRAD18 as a diagnostic biomarker for GBM. Bioinformatics analyses identified differentially expressed circRAD18, miR‑1231 and LUC7L2 in GBM and predicted their interactions. Expression levels were assessed using western blot analysis, immunohistochemistry and reverse transcription‑quantitative polymerase chain reaction. Regulatory mechanisms were examined via dual‑luciferase reporter assays, RNA pull‑down assays, CCK‑8 assays, wound healing assays, Transwell assays, fluorescence hybridization and subcutaneous xenograft tumor models in nude mice. Exosomes were isolated by ultracentrifugation and characterized using transmission electron microscopy and nanoparticle tracking analysis. circRAD18 expression was markedly upregulated in GBM samples and cell lines. Knockdown of circRAD18 markedly inhibited GBM cell proliferation, migration and invasion both and . Suppression of miR‑1231 or overexpression of LUC7L2 enhanced GBM cell proliferation, migration and invasion , but these effects were counteracted by simultaneous circRAD18 knockdown. Additionally, exosomes derived from GBM cells contained high levels of circRAD18. circRAD18 promotes GBM proliferation, migration and invasion by regulating the miR‑1231/LUC7L2 axis. Given its substantial expression in GBM‑derived exosomes, circRAD18 holds promise as both a therapeutic target and a diagnostic biomarker for GBM.
Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review).
Ma X, Zhao Y
Int J Mol Med · 2026 Jul · PMID 42138193 · Full text
The gut‑brain axis (GBA) has emerged as a critical mediator of acute brain dysfunction, particularly postoperative delirium and sepsis‑associated encephalopathy, in surgical and critically ill patients. Anesthesia, surgi...
The gut‑brain axis (GBA) has emerged as a critical mediator of acute brain dysfunction, particularly postoperative delirium and sepsis‑associated encephalopathy, in surgical and critically ill patients. Anesthesia, surgical stress, and critical illness collectively disrupt gut microbiota composition and intestinal barrier integrity, leading to increased systemic translocation of microbial products. This process triggers neuroinflammation and compromises blood‑brain barrier function through defined molecular pathways, including alterations in microbe‑derived short‑chain fatty acids, tryptophan metabolites, and potent neuroimmune signaling via the LPS‑TLR4‑NF‑κB axis. The present review synthesizes current evidence on the molecular crosstalk within the GBA, highlighting how perioperative and intensive care interventions drive dysbiosis and subsequent neurological sequelae. Furthermore, it evaluates promising GBA‑targeted therapeutic strategies, including dietary modulation, biotherapeutics and pharmacological interventions, are evaluated for their potential to mitigate delirium and improve long‑term cognitive outcomes. A deeper understanding of these mechanisms is essential for developing novel preventive and therapeutic approaches in vulnerable patient populations.
Primary cilia dysfunction: A critical driver of metabolic diseases (Review).
Wang X, Jin Y, Xie K … +4 more , Yao P, Song L, Liu H, Tan Y
Int J Mol Med · 2026 Jul · PMID 42138192 · Full text
Cilia dysfunction has been identified as a crucial but frequently overlooked factor in the pathogenesis of metabolic diseases, including obesity and diabetes. This review examines the multifaceted roles of primary cilia...
Cilia dysfunction has been identified as a crucial but frequently overlooked factor in the pathogenesis of metabolic diseases, including obesity and diabetes. This review examines the multifaceted roles of primary cilia in various metabolic tissues, framed by a central bidirectional model. This model posits a self‑reinforcing cycle where disruptions in ciliary function contribute to dysregulated appetite control, impaired insulin secretion and increased fat storage. Conversely, the hallmarks of metabolic disease, including chronic inflammation, lipotoxicity and hyperglycemia, contribute to the impairment of ciliary structure and function, thereby accelerating disease progression. The review underscores this reciprocal causality and proposes that therapeutic strategies targeting ciliary function could break this vicious cycle. Emerging treatments aim to restore ciliary function and thereby mitigate the progression of metabolic diseases. By elucidating the mechanisms of this bidirectional relationship, this review aims to pave the way for innovative strategies that optimize clinical outcomes and improve patient quality of life.
Autophagy and metabolic homeostasis: Exploration in obesity‑related metabolic diseases (Review).
Lu C, Qi X, Tong Y … +4 more , Lu P, Luo D, Guan Q, Yu C
Int J Mol Med · 2026 Jul · PMID 42138190 · Full text
Autophagy is an evolutionarily conserved catabolic process in which excessive nutrients, toxic protein aggregates, damaged organelles, and invading microorganisms in the cytoplasm can be isolated by the double‑membrane s...
Autophagy is an evolutionarily conserved catabolic process in which excessive nutrients, toxic protein aggregates, damaged organelles, and invading microorganisms in the cytoplasm can be isolated by the double‑membrane structure of autophagosomes and delivered to lysosomes for degradation. Over the past two decades, research on autophagy has made significant progress. Autophagy not only plays a crucial role in maintaining intracellular homeostasis but also contributes to the development of various metabolic diseases. Metabolic imbalance of nutrients in obesity‑related metabolic diseases can interfere with the autophagy process through a variety of mechanisms, resulting in further aggravation of the pathological damage of related organs. However, under certain conditions, inhibition of autophagy can have beneficial effects, thereby alleviating some of the harmful consequences of obesity. In this review, we will focus on the latest advances in the study of autophagy in obesity‑related metabolic disorders, including type 2 diabetes, non‑alcoholic fatty liver disease, and atherosclerosis. We will systematically discuss the definition and types of autophagy, the regulation of autophagy by nutrients, the imbalance of autophagy in obesity‑related metabolic diseases and its molecular mechanism, and finally, we will summarize some drugs targeting the autophagy pathway.
Betulinic acid alleviates the inflammatory injury of osteoblasts in osteoporosis by augmenting autophagy via the AMPK-mTOR signaling pathway.
Zhao Y, Qu Z, Liu L … +5 more , Zhang Y, Wang X, Zhang B, Gong Y, Yan L
Int J Mol Med · 2026 Jul · PMID 42138188 · Full text
Osteoporosis (OP) is a systemic disease characterized by a reduction in the number of trabecular bone structures and damage to the bone microstructure. It is commonly found in people who are aging or have estrogen defici...
Osteoporosis (OP) is a systemic disease characterized by a reduction in the number of trabecular bone structures and damage to the bone microstructure. It is commonly found in people who are aging or have estrogen deficiency. Oxidative stress and chronic inflammation caused by pathological factors such as aging and estrogen deficiency are key pathogenic factors. Betulinic acid (BA), a natural pentacyclic triterpenoid compound, exhibits anti‑inflammatory and antioxidant biological effects. However, its role and potential mechanisms in the inflammatory injury of osteoblasts in OP remain unclear. In the present study, in vivo experiments were conducted using an ovariectomized (OVX) rat model of OP, with bone microstructure analyzed by micro‑CT, protein expression detected by immunohistochemistry, and serum inflammatory factors measured by ELISA. BA was revealed to alleviate bone loss in OVX rats and inhibit the expression of NOD‑like receptor pyrin domain‑containing 3 (NLRP3), Asc and caspase‑1 in the femur of OVX rats, as well as suppress the release of inflammatory factors such as interleukin‑1 β, interleukin‑6, and tumor necrosis factor‑αin the serum of rats. The inflammatory injury osteoblast model of BA intervention was also studied with hydrogen peroxide (H2O2) in vitro, with reactive oxygen species (ROS) levels assessed by fluorescence assay, osteogenic differentiation evaluated by ALP staining and alizarin red staining, and autophagy‑related proteins detected by western blotting. BA pretreatment reduced production of ROS, inhibited expression of NLRP3 and downstream pathway activation, improved alkaline phosphatase activity, mineralization ability, and osteogenic differentiation ability of MC3T3‑E1 cells. Administration of BA increased the autophagy of MC3T3‑E1 cells treated with H2O2, which was confirmed by the increased expression levels of LC3b II and Beclin‑1 and the decreased expression levels of P62. In addition, BA could enhance the phosphorylation of AMPK in MC3T3‑E1 cells treated with H2O2 and reduce the phosphorylation of mTOR, but this effect could be rescued by Compound C (an AMPK blocker). BA can protect osteoblasts from inflammatory injury by reducing the production of ROS and inhibiting the activation of NLRP3 through autophagy mediated by the AMPK/mTOR pathway.
[Retracted] Regulation of p38 MAPK phosphorylation inhibits chondrocyte apoptosis in response to heat stress or mechanical stress.
Takebe K, Nishiyama T, Hayashi S … +7 more , Hashimoto S, Fujishiro T, Kanzaki N, Kawakita K, Iwasa K, Kuroda R, Kurosaka M
Int J Mol Med · 2026 Jul · PMID 42099250 · Full text
Following the publication of the above article, a concerned reader drew the Editor's attention to the fact that, regarding the caspase‑9 and cleaved caspase‑9 bands in Fig. 5D on p. 333, the bands shown for the '10% 0h'...
Following the publication of the above article, a concerned reader drew the Editor's attention to the fact that, regarding the caspase‑9 and cleaved caspase‑9 bands in Fig. 5D on p. 333, the bands shown for the '10% 0h' and the '10% 12h' lanes/experiments were strikingly similar, albeit with a small downwards displacement of the cleaved caspase‑9 band in the right‑hand lane of the gel compared with the left‑hand lane. A visual inspection of this figure part also revealed the probable presence of breaks in continuity in the affected gel slices, comparing the left‑ and the right‑hand lanes. Given that this issue has come to light, the Editor of has decided that this article should be retracted from the publication on the grounds of an overall lack of confidence in these 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 inconvenience caused, and we thank the reader for drawing this matter to our attention. [International Journal of Molecular Medicine 27: 329‑335, 2011; DOI: 10.3892/ijmm.2010.588].
Ferroptosis in musculoskeletal disorders: Emerging mechanisms and therapeutic opportunities (Review).
Gu W, Zhang H, Ye L … +4 more , Liu F, Xu T, Yu Y, Wang G
Int J Mol Med · 2026 Jul · PMID 42099247 · Full text
Ferroptosis, an iron‑dependent form of regulated cell death driven by lipid peroxidation, has emerged as a key mechanism underlying tissue degeneration and impaired regeneration in musculoskeletal disorders. Although fer...
Ferroptosis, an iron‑dependent form of regulated cell death driven by lipid peroxidation, has emerged as a key mechanism underlying tissue degeneration and impaired regeneration in musculoskeletal disorders. Although ferroptosis is associated with conditions such as tendinopathy, sarcopenia, osteoarthritis and osteoporosis, systematic synthesis connecting molecular mechanisms with disease‑specific contexts and translational implications remains limited. The present review summarizes the fundamental molecular mechanisms of ferroptosis, including iron metabolism dysregulation, lipid peroxidation processes and antioxidant defense systems centered on GPX4 and glutathione. Subsequently, the involvement of ferroptosis across major musculoskeletal diseases was investigated, highlighting how iron imbalance, oxidative stress and age‑related alterations collectively contribute to tissue dysfunction and degeneration. Particular emphasis is placed on aging‑associated changes in iron homeostasis and antioxidant capacity as potential amplifiers of ferroptotic vulnerability in musculoskeletal tissues. Experimental modeling strategies and pharmacological modulation approaches used to investigate ferroptosis in musculoskeletal research are further discussed and their mechanistic relevance and translational challenges are analyzed. Finally, the present review outlines emerging therapeutic perspectives and future research directions aimed at improving the understanding and potential clinical targeting of ferroptosis in musculoskeletal disorders. By providing a structured and integrative synthesis, the present review clarifies the role of ferroptosis at the intersection of iron dysregulation, redox imbalance and musculoskeletal decline.
Dapagliflozin attenuates ferroptosis in diabetic nephropathy through activation of the Nrf2/HO‑1 signaling pathway.
Liu H, Zhang X, Cui Y … +5 more , Xiong S, Huang L, Li M, Shao C, Hu X
Int J Mol Med · 2026 Jul · PMID 42099241 · Full text
Renal tubular injury has emerged as a critical determinant in the pathogenesis of diabetic nephropathy (DN). Ferroptosis, a recently characterized mode of iron‑dependent regulated cell death, has been implicated in the d...
Renal tubular injury has emerged as a critical determinant in the pathogenesis of diabetic nephropathy (DN). Ferroptosis, a recently characterized mode of iron‑dependent regulated cell death, has been implicated in the development of renal tubular damage. Dapagliflozin (DAPA), a sodium‑glucose cotransporter 2 inhibitor, has demonstrated efficacy in attenuating DN progression and preserving renal function. The present study sought to elucidate the inhibitory mechanisms by which DAPA modulates ferroptosis in DN. To this aim, the expression profiles of key molecular markers within the ferroptosis cascade were systematically evaluated using 6‑week‑old male C57BL/6J mice and high‑glucose‑cultured human renal tubular epithelial cells as experimental models. The findings revealed that DAPA notably ameliorated renal histopathological alterations, upregulated the expression of solute carrier family 7 member 11, glutathione peroxidase 4 and ferritin heavy chain 1, whilst concomitantly downregulating transferrin receptor 1. These effects were mediated through the activation of nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase‑1 (HO‑1) in C57BL/6J mice. Collectively, these data indicate that the reno‑protective effects of DAPA in DN may be attributable to the suppression of ferroptosis via activation of the Nrf2/HO‑1 signaling axis.
Advances in understanding the NLRP3 inflammasome‑mediated mechanisms and therapeutic targets in diabetic nephropathy (Review).
Wang X, Li S, Ge X … +5 more , Xie T, Li S, Yuan R, Li T, Yuan H
Int J Mol Med · 2026 Jul · PMID 42099240 · Full text
Diabetic nephropathy (DN), a severe microvascular complication of diabetes, has exhibited a steadily increasing global incidence and is a major contributor to diabetes‑related morbidity and mortality. DN is characterized...
Diabetic nephropathy (DN), a severe microvascular complication of diabetes, has exhibited a steadily increasing global incidence and is a major contributor to diabetes‑related morbidity and mortality. DN is characterized by glomerular sclerosis, podocyte loss, tubular atrophy and excessive extracellular matrix deposition, among other features. The pathogenesis of DN is complex, involving multiple pathological processes, with the inflammatory cascade recognized as the core driver of its progression. Abnormal activation of the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome, a key component of the innate immune system, can trigger pyroptosis and thereby aggravate renal injury. Whilst current literature primarily describes isolated mechanisms of DN, the present review summarizes the pathogenesis of DN and the NLRP3 inflammasome‑related signaling pathways, proposing a novel three‑tier hierarchical regulatory framework (upstream priming, midstream activation and downstream execution) for the five core NLRP3‑related signaling pathways in DN, and systematically dissects the mitochondrial metabolic‑cGAS‑STING synergistic mechanism that drives NLRP3 activation, thus addressing the research gap in metabolic‑immune crosstalk in DN. Furthermore, potential therapeutic agents targeting the NLRP3 inflammasome are discussed, and targeted therapeutic strategies stratified according to and validation evidence (such as small‑molecule inhibitors, traditional Chinese medicine monomers/compounds and gene therapy) to provide a clear roadmap to clinical translation. Although current research on DN is limited, the findings and analyses assessed in the present review provide valuable insights into its pathogenesis, treatment, prognosis and directions for future experimental studies.
Phosphorylation beyond the plasma membrane: How secretory pathway kinases sculpt the cellular dialogue in cancer (Review).
Geng Z, Guan S, Du S … +5 more , Zhang S, Hao J, Tian S, Zhu C, Du S
Int J Mol Med · 2026 Jul · PMID 42099239 · Full text
Intercellular communication is critical for tissue homeostasis, development and immune responses, with its disruption often implicated in various diseases, particularly cancer. Secretory pathway kinases and kinase‑like p...
Intercellular communication is critical for tissue homeostasis, development and immune responses, with its disruption often implicated in various diseases, particularly cancer. Secretory pathway kinases and kinase‑like proteins (SPKKPs) constitute a distinctive enzyme class operating within the luminal secretory pathway or extracellular space, positioning them as pivotal regulators of cellular communication. This review consolidates current insights into the role of SPKKPs, including the FAM20 family, four‑jointed box kinase 1 (FJX1) and others, in orchestrating intercellular interactions through the phosphorylation of secreted proteins, extracellular matrix components and extracellular vesicle (EV) cargo. The molecular mechanisms by which SPKKPs modulate key oncogenic signaling pathways, such as PI3K/AKT, ERK/MAPK and SMAD family member 2, across diverse cancer types are examined. Additionally, their involvement in EV‑mediated signaling, extracellular matrix remodeling and regulation of fundamental biological processes, including development, tissue homeostasis and immune coordination, is explored. The review further addresses SPKKP dysregulation in a range of pathologies, from nervous system tumors to gastrointestinal and reproductive cancers, and discusses emerging therapeutic strategies. These strategies include specific kinase inhibitors, FJX1‑targeted peptide vaccines and innovative approaches targeting exosomes carrying SPKKPs substrates. Ultimately, this work highlights the essential role of SPKKPs in intercellular communication networks and their promising potential as diagnostic biomarkers and therapeutic targets, particularly in cancer.
[Expression of Concern] ISL1 promotes cancer progression and inhibits cisplatin sensitivity in triple‑negative breast cancer cells.
Zhang Y, Wang L, Gao P … +8 more , Sun Z, Li N, Lu Y, Shen J, Sun J, Yang Y, Dai H, Cai H
Int J Mol Med · 2026 Jul · PMID 42099237 · Full text
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, regarding the cell invasion assay experiments shown in Fig. 3A, B and C on p. 2348, two pairs of data panels wer...
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, regarding the cell invasion assay experiments shown in Fig. 3A, B and C on p. 2348, two pairs of data panels were overlapping, such that data which were intended to show the results from differently performed experiments had apparently been derived from a smaller number of original sources. In addition, an independent investigation of the data in this paper undertaken by the Editorial Office revealed that flow cytometric data in Fig. 4A were shared with a paper that was published in the journal featuring no authors in common (which was received at that journal one month after the submission of the above paper to ), and flow cytometric data in Fig. 5C were shared with a different paper also having no authors in common that was subsequently submitted to the journal . The authors have been contacted by the Editorial Office to offer an explanation for the issues described above, 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 this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 42: 2343‑2352, 2018; DOI: 10.3892/ijmm.2018.3842].
Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).
Zhou S, Jiang Y, Fan J … +3 more , Guo M, Wen Y, Dai C
Int J Mol Med · 2026 Jul · PMID 42099233 · Full text
Radiotherapy (RT) is increasingly recognized as a system‑level immunomodulator capable of reshaping cytokine networks across spatial, temporal and dosimetric dimensions. This review synthesizes existing evidence on RT pa...
Radiotherapy (RT) is increasingly recognized as a system‑level immunomodulator capable of reshaping cytokine networks across spatial, temporal and dosimetric dimensions. This review synthesizes existing evidence on RT parameters, key signaling axes, major effector cells, organ‑specific contexts and clinical translation. It describes how the cyclic GMP‑AMP synthase/stimulator of interferon genes (STING)/IFN‑I, NF‑κB and TGF‑β pathways coordinate immune activation and immune suppression after irradiation. It then summarizes macrophage‑centered regulatory circuits and chemokine axes, including C‑C motif chemokine ligand (CCL)2/CCR2 and CCL22/CCR4 that govern T‑cell trafficking and functional states. A map of organ‑specific cytokine programs that link therapeutic benefit and toxicity in the brain, lung, gastrointestinal tract, oral mucosa and liver is then provided, and actionable targets within inflammasome‑associated pyroptosis and fibrogenic cascades are highlighted. RT technical parameters, including fractionation, treatment volume, stereotactic body RT, Fast Linear Accelerator‑based Scanning Hybrid ultra‑high dose-rate delivery and proton therapy can differentially shape cytokine dynamics and modify the therapeutic window. The DNA damage response network with poly (ADP‑ribose) polymerase (PARP)1 as a central node represents a second hub that interfaces with antigen presentation and IFN signaling, supporting rational combinations with PARP inhibitors and immune checkpoint blockade. Finally, a translational algorithm with three pillars is proposed. The first pillar uses IFN‑related gene signatures and circulating cytokine profiles to stratify tumors by baseline IFN activity. The second pillar aligns RT timing with endogenous STING or IFN pulses and incorporates CCR2, CCR4 or colony stimulating factor 1 receptor blockade to counter myeloid cell‑mediated immunosuppression. The third pillar co‑manages treatment‑related toxicities by targeting the NLR family pyrin domain containing 3/gasdermin D axis or by using fibrosis‑modulating interventions. Furthermore, ongoing clinical trials of cytokine-directed agents combined with RT are summarized. This framework positions cytokines as measurable and modifiable variables for individualizing combined RT and immunotherapy.
Gilteritinib overcomes second‑generation TKIs resistance in ALK‑rearranged non‑small‑cell lung cancer by inhibiting PD‑L1 and CD8 co‑expression.
Guo H, Li Y, Jin C … +4 more , Qi X, Wang J, Li B, Wang C
Int J Mol Med · 2026 Jun · PMID 42059267 · Full text
The present study investigated how gilteritinib overcomes resistance to second‑generation tyrosine kinase inhibitors in anaplastic lymphoma kinase (ALK)‑rearranged non‑small‑cell lung cancer (NSCLC), providing new theore...
The present study investigated how gilteritinib overcomes resistance to second‑generation tyrosine kinase inhibitors in anaplastic lymphoma kinase (ALK)‑rearranged non‑small‑cell lung cancer (NSCLC), providing new theoretical support for NSCLC treatment. The GSE191078 dataset was downloaded from Gene Expression Omnibus database. Cell clustering was performed using the FindClusters function, followed by uniform manifold approximation and projection dimensionality reduction and data filtering. Epithelial and T cells were extracted for single‑cell transcriptome sequencing and pseudotime analysis was conducted using the Monocle 2 algorithm. The inhibitory effects of gilteritinib on H2228/Al cells were evaluated using CCK8 and TUNEL assays. Western blotting, reverse transcription‑quantitative PCR and immunofluorescence were used to examine programmed death‑ligand 1 (PD‑L1) and cluster of differentiation 8 (CD8) expression. A PD‑L1/CD8 co‑culture system was established for rescue experiments and a nude mouse xenograft model was used to assess the anti‑tumor efficacy of gilteritinib. A total of 21,866 cells were obtained and grouped into 12 major cell types. In ALK‑rearranged NSCLC, epithelial cells were associated with regulation of the P53, glycolysis and hypoxia pathways, while pseudotemporal analysis linked T cells to endothelial cell‑related processes and ribosomal functions. , gilteritinib inhibited H2228/Al cell growth, induced apoptosis and reduced ALK protein levels. Co‑culture and rescue experiments suggested the mechanism involved inhibiting PD‑L1 and CD8 co‑expression, corroborated by animal experiments. Gilteritinib can overcome alectinib resistance and inhibit PD‑L1 and CD8 co‑expression in ALK‑rearranged NSCLC, providing a new therapeutic strategy.
[Corrigendum] Differential regulation of the biosynthesis of glucose transporters by the PI3‑K and MAPK pathways of insulin signaling by treatment with novel compounds from .
Lee YK, Kim JE, Nam SH … +7 more , Goo JS, Cho SI, Choi YH, Bae CJ, Woo OM, Cho JS, Hwang DY
Int J Mol Med · 2026 Jul · PMID 42059259 · Full text
Following the publication of the above article, an interested reader drew to the authors' attention that the β‑actin blots featured for the western blots in Figs. 5A and 8A were apparently the same, even though the sampl...
Following the publication of the above article, an interested reader drew to the authors' attention that the β‑actin blots featured for the western blots in Figs. 5A and 8A were apparently the same, even though the samples came from different tissues (liver and brain, respectively). Upon re‑examining their original data, the authors have realized that the control blots were erroneously selected for Fig. 8A; moreover, the same processing error was made with the control blots for Fig. 6A (duplicated from those for Fig. 4A) and Fig. 9A (duplicated from Fig. 7A). The revised versions of Figs. 6, 8 and 9, now showing the correct control western blots in Figs. 6A, 8A and 9A, are shown opposite and on the subsequent page. Note that the errors made in assembling these figures did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and 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 27: 319‑327, 2011; DOI: 10.3892/ijmm.2010.581].
Ligustroflavone protects against acute kidney injury by inhibiting ferroptosis via acting on GSK3β/NRF2 signaling.
Song J, Wang L, Wang Y … +7 more , Meng J, Sheng J, Zhao Y, Xu SY, Lei J, Cai F, Yang Y
Int J Mol Med · 2026 Jul · PMID 42059248 · Full text
Ferroptosis exerts a recognized role in the pathogenesis of acute kidney injury (AKI) and is considered a critical target for improving its prognosis. Emerging evidence indicates that ferroptosis serves a pivotal role in...
Ferroptosis exerts a recognized role in the pathogenesis of acute kidney injury (AKI) and is considered a critical target for improving its prognosis. Emerging evidence indicates that ferroptosis serves a pivotal role in pathogenesis of AKI and targeting ferroptosis provides a promising therapeutic strategy in treatment of AKI. In the present study, ligustroflavone (LIG), which is a flavonoid with oral activity extracted from , was found to inhibit ferroptosis through activation of nuclear factor erythroid 2‑related factor 2 (NRF2) via inhibition of GSK3β and ., cisplatin (CDDP) and ischemia‑reperfusion injury (IRI)‑induced murine models of AKI were constructed to evaluate the possible effects of LIG. , the protective effects of LIG were assessed in cultured mouse renal proximal tubular epithelial cells (TKPTs). Immunostaining, reverse transcription‑quantitative PCR, western blot and lipid peroxidation assays were performed to detect renal tubular injury and ferroptosis. The results of the present study demonstrated that LIG administration significantly ameliorated CDDP or IRI induced renal damage in mice. Additionally, administration of LIG significantly ameliorated lipid peroxide accumulation and inhibited ferroptosis in the kidneys of AKI mice. , LIG treatment markedly ameliorated CDDP‑induced lipid peroxidation and ferroptosis in cultured TKPTs via GSK3β inhibition and NRF2 activation. Furthermore, knockout of GSK3β also protected against CDDP‑induced cell death and LIG exerted no additional protective effects in GSK3β‑knockout TKPTs. Together, the present findings offer a new potential strategy for AKI therapies by targeting ferroptosis.
High‑altitude polycythemia: Unveiling the molecular landscape beyond erythropoietin (Review).
Li H, Zhang H, Zhang H … +3 more , Li Y, He Y, Luan J
Int J Mol Med · 2026 Jun · PMID 42028782 · Full text
High‑altitude polycythemia (HAP) is classically attributed to erythropoietin (EPO)‑driven erythrocytosis, yet epidemiological and mechanistic evidence increasingly challenges this monocular view. Field data have demonstr...
High‑altitude polycythemia (HAP) is classically attributed to erythropoietin (EPO)‑driven erythrocytosis, yet epidemiological and mechanistic evidence increasingly challenges this monocular view. Field data have demonstrated that up to 40% of individuals with a hematocrit level >68% circulate EPO within the sea‑level reference range, whereas multi‑omics studies have revealed sustained HIF activity, mitochondrial oxidative stress, iron dysregulation, gut dysbiosis and epigenetic reprogramming as parallel, EPO‑independent drivers. Hypoxia‑inducible microRNAs, hepcidin suppression, TLR4‑IL‑6 signaling and defective mitophagy converge to lock erythroid precursors into a survival‑plus‑proliferation state even after ambient oxygen levels normalize. The purpose of the present review is to integrate these disparate pathways into a unified molecular framework and to outline a phased, biomarker‑guided therapeutic roadmap for the precise prevention of maladaptive polycythemia at high altitudes.
Mechanistic roles of interleukin‑18 in colonic immunity across infection, inflammatory bowel disease, and colorectal cancer (Review).
Zhang J, Bao L, Li X … +13 more , Li J, Cui J, Qiao L, He X, Zhang M, Lu J, Zhang X, Dong J, Tao G, Bai T, Tian YP, Zhao P, Tuo Y
Int J Mol Med · 2026 Jun · PMID 42028753 · Full text
The colon, functioning as a central organ for digestion, absorption, and immune defense in the human body, depends on intricate interactions among the epithelial barrier, immune cells, and gut microbiota to sustain mucos...
The colon, functioning as a central organ for digestion, absorption, and immune defense in the human body, depends on intricate interactions among the epithelial barrier, immune cells, and gut microbiota to sustain mucosal homeostasis. Dysregulation within cytokine networks constitutes a key pathogenic driver of colonic disorders, including inflammation, infection, and tumorigenesis. Interleukin (IL)‑18, a pivotal cytokine in colonic immune modulation, exhibits dual roles in maintaining homeostasis and mediating pathology: IL‑18 orchestrates immune responses through both inflammasome‑dependent and ‑independent mechanisms, exerting bidirectional influences on colonic pathogen eradication and inflammatory exacerbation. The coordinated actions of IL‑18 and IL‑22, mediated via epithelium‑specific receptor signaling, primarily govern colonic barrier restoration and antimicrobial defense, undergoing functional transitions throughout disease progression. The present review systematically elucidates the molecular characteristics of IL‑18 and its mechanistic functions in colonic pathogen defense and disorders such as inflammatory bowel disease and colorectal cancer, following the logical framework of molecular mechanisms, physiological roles, pathological regulation, and interactive networks. The synergistic and antagonistic interactions among IL‑18 and IL‑22 are analyzed, and their clinical translational potential is explored, providing a theoretical basis for precision intervention in colonic pathologies. Based on clinical and mechanistic studies, this review systematically integrates existing experimental evidence to provide a theoretical framework for understanding the complex roles of IL‑18 in colonic immunity. Although targeted intervention of IL‑18 holds promise in animal models, its clinical translation warrants further validation through human studies, given its context‑dependent functions and potential risks.
[Retracted] Metformin‑induced activation of AMPK inhibits the proliferation and migration of human aortic smooth muscle cells through upregulation of p53 and IFI16.
Hao B, Xiao Y, Song F … +5 more , Long X, Huang J, Tian M, Deng S, Wu Q
Int J Mol Med · 2026 Jun · PMID 42028752 · Full text
Following the publication of the above article, a concerned reader drew the Editor's attention to the fact that the figures presented in this paper appeared to contain the following anomalies: In Fig. 4D, the 'Met 5 mM'...
Following the publication of the above article, a concerned reader drew the Editor's attention to the fact that the figures presented in this paper appeared to contain the following anomalies: In Fig. 4D, the 'Met 5 mM' and 'Met 10 mM' data panels were overlapping; in Fig. 8F, the 'IF116 si' and 'IF116 si + Met' data panels were overlapping; in Fig 5A, the 'Un' and 'Ctr' rows of data were overlapping; and in Fig. 7A, the 'Ctr' and 'IF116 Si' rows of data were overlapping. In addition, after having performed an independent analysis of the data in this paper in the Editorial office, it came to light that the 'Met 0 mM' panel in Fig. 4D contained an overlapping section with the Control panel in Fig. 8F. Given that these issues have come to light, 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 satisfactory 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 41: 1365‑1376, 2018; DOI: 10.3892/ijmm.2017.3346].
[Retracted] Puerarin attenuates glucocorticoid‑induced apoptosis of hFOB1.19 cells through the JNK‑ and Akt‑mediated mitochondrial apoptotic pathways.
Yu D, Mu S, Zhao D … +4 more , Wang G, Chen Z, Ren H, Fu Q
Int J Mol Med · 2026 Jun · PMID 42028748 · Full text
Following the publication of the above paper, a concerned reader has drawn to the Editor's attention that, regarding the TUNEL assay data shown in Fig. 4A on p. 348, the images shown for the 'control' and 'puerarin 0M' e...
Following the publication of the above paper, a concerned reader has drawn to the Editor's attention that, regarding the TUNEL assay data shown in Fig. 4A on p. 348, the images shown for the 'control' and 'puerarin 0M' experiments contained an overlapping section, such that data which were intended to show the results of differently performed experiments were apparently derived from the same original source. In addition, regarding the flow cytometric plots shown in Fig. 10A on p. 351, the 'SP600125+DEX' and 'LY294002+DEX' data panels were also strikingly similar. Upon investigating the data in this paper independently in the Editorial Office, it also came to light that certain of the western blot data in Fig. 8A and C were overlapping with data included in Fig. 9A and C, and moreover, western blot data featured in Fig. 5 subsequently appeared in an article featuring a pair of the same authors in the journal . In view of the large number of apparent errors that were made in assembling various of the data in the figures reported above, and given the re-use of some of the data in a subsequently published paper that featured a pair of the authors on the above paper, 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 for any inconvenience caused. [International Journal of Molecular Medicine 36: 345‑354, 2015; DOI: 10.3892/ijmm.2015.2258].
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe