International Journal Of Molecular Medicine[JOURNAL]
Sun
200 papers
Macrophage SH3 domain‑containing GRB2‑like protein B1 is required for Rab7‑mediated mitophagy in inflammation during sea water drowning acute lung injury.
Ning H, Deng J, Gao Y … +4 more , Zhang W, Chen J, Guo X, Jin F
Int J Mol Med · 2026 May · PMID 41891976 · Full text
Acute lung injury (ALI) accompanied by an inflammatory response is an important complication after drowning. Macrophage activation and polarization are implicated in the inflammatory process of lipopolysaccharide (LPS)‑i...
Acute lung injury (ALI) accompanied by an inflammatory response is an important complication after drowning. Macrophage activation and polarization are implicated in the inflammatory process of lipopolysaccharide (LPS)‑induced ALI (LPS‑ALI), but little is known about drowning‑induced ALI (drowning‑ALI). SH3 domain‑containing GRB2‑like protein B1 (SH3GLB1) is a member of the endophilin family and has been shown to be involved in mitochondrial morphological changes and autophagy. However, its role in ALI remains unclear. Thus, the present study aimed to examine the effects of macrophages in drowning‑ALI and to elucidate the underlying molecular mechanism involved. In the present study, single‑cell RNA‑sequencing indicated that the regulation of macrophages in drowning‑ALI was similar to that in LPS‑ALI by single‑cell profiling of lung immune cells isolated from the lungs. Specifically, SH3GLB1 was highly expressed in macrophages of drowning‑ALI mouse models and was related to inflammation. Furthermore, SH3GLB1 deletion ameliorated LPS‑ALI or drowning‑ALI. By contrast, the restoration of SH3GLB1 expression provoked LPS‑ALI and drowning‑ALI. Mechanistically, SH3GLB1 was shown to interact with Rab7 to contribute to mitophagy, which resulted in mitochondrial dysfunction. Overall, these findings indicated that SH3GLB1 is required for Rab7‑mediated mitophagy in inflammation during ALI and could be a novel target for lung protection.
Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).
Xiao Y, Wang N, Gui D … +1 more , Xu Y
Int J Mol Med · 2026 Jun · PMID 41891971 · Full text
Emerging insights into lactate‑mediated protein lactylation illuminate novel regulatory axes in the pathogenesis of diabetic nephropathy (DN). While histone lactylation has established epigenetic associations with metabo...
Emerging insights into lactate‑mediated protein lactylation illuminate novel regulatory axes in the pathogenesis of diabetic nephropathy (DN). While histone lactylation has established epigenetic associations with metabolic memory, expanding proteomic evidence reveals dynamic lactylation landscapes across extracellular matrix components, inflammatory mediators and redox regulators in renal compartments. The present review systematically catalogues DN‑relevant histones and non‑histone substrates undergoing functional lactylation, while mechanistically dissecting how hyperglycemia‑fueled lactate flux drives DN through lactate‑mediated protein modification landscapes. The present review further delineates the progress of research on the potential regulatory mechanisms involved in DN and delve into the possible functions and related mechanisms. This mechanistic reappraisal establishes lactylation topology mapping as a prerequisite for developing precision modulation approaches in DN management.
circOMA1 delivered by exosomes regulates DRD2‑mediated prolactinoma resistance.
Rao Q, Zhu D, Wang Z … +7 more , Zhang S, Li X, Tagilapalli S, Wang N, Hu W, Chen W, Zhu Y
Int J Mol Med · 2026 Jun · PMID 41891968 · Full text
Among pituitary adenomas, prolactin‑secreting pituitary neuroendocrine tumours (PRL‑PitNETs) are unique in that pharmacotherapy, specifically cabergoline (CAB), can be used as a first‑line treatment, and it is the recomm...
Among pituitary adenomas, prolactin‑secreting pituitary neuroendocrine tumours (PRL‑PitNETs) are unique in that pharmacotherapy, specifically cabergoline (CAB), can be used as a first‑line treatment, and it is the recommended therapeutic option. However, the mechanisms underlying CAB resistance remain incompletely understood. In the present study, gene microarray analysis and clinical tissue specimens were used to identify circular RNAs (circRNAs) associated with CAB resistance. circOMA1 expression was quantified in PRL‑PitNET tissues and patient plasma using reverse transcription‑quantitative PCR, and its diagnostic potential was evaluated in 219 patients with pituitary adenoma. Gain‑ and loss‑of‑function assays, combined with molecular biology techniques, were used to investigate the biological function of circOMA1 and the underlying molecular mechanism. circOMA1 was identified as a critical circular RNA influencing CAB resistance and prognosis in PRL‑PitNET. Mechanistically, circOMA1 acted as a miR‑145‑5p sponge, leading to upregulation of the E3 ubiquitin ligase Kelch‑repeat and BTB domain‑containing protein 7. This promoted ubiquitination of the CAB‑specific, high‑affinity G‑protein‑coupled receptor dopamine D2 receptor. Consequently, downstream autophagy was attenuated, and AKT pathway inhibition was impaired, which underlied the resistance. Furthermore, and studies demonstrated that circOMA1 was transported via exosomes, facilitating the transmission of CAB resistance among PRL‑PitNET cells. Plasma exosomal circOMA1 levels were significantly elevated in PRL‑PitNET patients preoperatively. These findings established circOMA1 as a key mediator of CAB resistance and a potential prognostic indicator in patients with a PRL‑PitNET.
Deferoxamine mitigates neuronal loss following spinal cord injury via ferroptosis inhibition and Nrf2/HO‑1 pathway activation.
Ma Z, Zhang X, Liu T … +7 more , Zhang Y, Li G, Yuan X, Tang B, Zhao H, Liu L, Chen X
Int J Mol Med · 2026 May · PMID 41891961 · Full text
Spinal cord injury (SCI) is a debilitating condition associated with significant morbidity and permanent disability. The neuroprotective potential of deferoxamine (DFO) in SCI by targeting ferroptosis has been highlighte...
Spinal cord injury (SCI) is a debilitating condition associated with significant morbidity and permanent disability. The neuroprotective potential of deferoxamine (DFO) in SCI by targeting ferroptosis has been highlighted; however, the underlying molecular mechanisms remain elusive. The present study aimed to investigate the role of the Nrf2/heme oxygenase‑1 (HO‑1) signaling pathway in mediating the inhibitory effects of DFO on neuronal ferroptosis following SCI. The study commenced with a bioinformatics analysis of the SCI microarray dataset, GSE162610. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated significant activation of ferroptosis following SCI, while Gene Ontology analysis revealed that oxidative stress, inflammatory response and glutathione peroxidase activity were key biological processes associated with ferroptosis post‑SCI. The Nrf2, glutathione peroxidase 4 (GPX4), HO‑1 (encoded by Hmox1) and xCT (encoded by Slc7a11) genes were selected for further investigation. Subsequent experiments employed the Nrf2‑specific inhibitor ML385 to evaluate the regulatory role of the Nrf2/HO‑1 pathway. , an erastin‑induced neuronal ferroptosis model was established using ventral spinal cord 4.1 cells, while in vivo, a spinal cord contusion model was constructed using C57BL/6J mice for behavioral, histopathological and immunological assessments. The results demonstrated that, compared with the SCI group, DFO treatment significantly upregulated the expression of Nrf2, HO‑1, xCT and GPX4 both in vitro and in vivo as well as attenuated neuronal loss and tissue damage and promoted motor functional recovery in mice. Conversely, the administration of ML385 largely reversed these molecular and functional effects of DFO, thereby diminishing its neuroprotective efficacy. These findings indicated that DFO alleviated neuronal ferroptosis and promoted functional recovery after SCI, at least in part, through activation of the Nrf2/HO‑1 signaling pathway and enhancement of the xCT/GPX4 antioxidant system. Therefore, the present study elucidated the involvement of the Nrf2/HO‑1 signaling pathway in mediating the neuroprotective effects of DFO in SCI, highlighting the therapeutic potential of DFO and providing a theoretical foundation for future targeted strategies against ferroptosis in SCI management.
[Expression of Concern] Involvement of Cyr61 in the growth, invasiveness and adhesion of esophageal squamous cell carcinoma cells.
Xie JJ, Xu LY, Xie YM … +4 more , Du ZP, Feng CH, Dong H, Li EM
Int J Mol Med · 2026 Jun · PMID 41891960 · Full text
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the cell migration assay data shown in Fig. 4A on p. 432, the 'EC109' and 'Vector' data panels we...
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the cell migration assay data shown in Fig. 4A on p. 432, the 'EC109' and 'Vector' data panels were found to contain 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. The authors have been contacted by the Editorial Office to offer an explanation for the apparent anomaly in the presentation of the data in their 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 this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 27: 429-434, 2011; DOI: 10.3892/ijmm.2011.603].
USP10 deubiquitinase: Physiological function, diseases and therapeutic target (Review).
Zhang L, Sun H, Wang Z … +3 more , Wang Z, Mu Q, Liu Y
Int J Mol Med · 2026 May · PMID 41891958 · Full text
Ubiquitination is crucial for regulating diverse cellular functions, including protein degradation, cell cycle progression, signal transduction and gene expression. This intricate process is mediated by the ubiquitin pro...
Ubiquitination is crucial for regulating diverse cellular functions, including protein degradation, cell cycle progression, signal transduction and gene expression. This intricate process is mediated by the ubiquitin proteasome system. Within this system, ubiquitin‑specific protease 10 (USP10) is a key member that, through its deubiquitinase activity, orchestrates multiple cellular processes, such as DNA damage repair, immune and inflammatory responses, environmental adaptation and autophagy. The biological activity and protein stability of USP10 are extensively regulated by post‑translational modifications, including PARylation, histone methylation and ubiquitination. Functionally, USP10 has a dual role in tumorigenesis: It can either promote or suppress cancer progression and metastasis by influencing oncogenic signaling pathways. Beyond cancer, USP10 has been implicated in the pathogenesis of cardiovascular and neurodegenerative diseases, as well as organ fibrosis, underscoring its broad physiological relevance. Decades of research have spurred the development of a range of USP10 inhibitors, such as Spautin‑1, P22077, HBX19818, Wu‑5 and D1. The present review provides a comprehensive overview of recent advances in understanding the role of USP10 in maintaining homeostasis and dissects the pathological mechanisms in human diseases. The review further highlights the potential of precise USP10‑targeted interventions as promising therapeutic strategies for disease prevention and treatment.
Novel Hsp90 inhibitor JD‑02 inhibits HSV‑1 infection via the Raf/MEK/ERK signaling pathway.
Zhu Y, Wang X, Lin J … +5 more , Wang X, Zheng K, Ren Z, Xiao J, Wang Y
Int J Mol Med · 2026 Jun · PMID 41891956 · Full text
Herpes simplex virus type 1 (HSV‑1) is a neurotropic pathogen with an extremely high infection rate. The excessive use of acyclovir (ACV) and nucleoside analogs has resulted in the emergence of drug‑resistant HSV‑1 strai...
Herpes simplex virus type 1 (HSV‑1) is a neurotropic pathogen with an extremely high infection rate. The excessive use of acyclovir (ACV) and nucleoside analogs has resulted in the emergence of drug‑resistant HSV‑1 strains, thereby underscoring the need for the development of novel therapeutic agents against HSV‑1. The present study sought to evaluate the efficacy and elucidate the mechanism of action of the novel Hsp90 inhibitor, JD‑02, in the context of HSV‑1 infection, as well as to assess its potential as an anti‑HSV‑1 therapeutic agent. The results of the present study demonstrated that JD‑02 exhibits lower cytotoxicity relative to the conventional Hsp90 inhibitor, AT533, and effectively inhibits infection by both standard and ACV‑resistant HSV‑1 strains . Additionally, JD‑02 markedly suppresses the expression of viral‑associated genes and proteins. The present investigation further revealed that the Raf/MEK/ERK signaling pathway is activated during HSV‑1 infection, and that JD‑02 exerts its antiviral effects through the inhibition of this pathway. Moreover, the in vivo administration of JD‑02 mitigated the symptoms of Herpes simplex encephalitis (HSE), extended the lifespan of mice with HSE, and decreased both the viral gene copy number and the expression of inflammatory factors. In contrast to targeting viral DNA polymerases, Hsp90 inhibitors, which target host proteins, exhibit a significantly lower likelihood of inducing drug resistance. These findings indicate that JD‑02, a novel HSP90 inhibitor, holds promise for development as a therapeutic agent for the treatment of HSV‑1 infection and associated diseases.
Role of itaconate in intestinal disease (Review).
Li X, Liu Q, Li J … +9 more , Zhang L, Yao S, Tang L, Yang B, Wang Y, Wen G, An J, Jin H, Tuo B
Int J Mol Med · 2026 Jun · PMID 41891955 · Full text
Itaconate (ITA) is a metabolite produced by immune cells such as macrophages during inflammation or infection. ITA exhibits potent immunomodulatory functions, antioxidant effects and antibacterial properties. The present...
Itaconate (ITA) is a metabolite produced by immune cells such as macrophages during inflammation or infection. ITA exhibits potent immunomodulatory functions, antioxidant effects and antibacterial properties. The present study aimed to provide a systematic review of the synthesis and metabolic regulatory mechanisms of ITA and its key roles in intestinal diseases. ITA affects inflammatory bowel disease (IBD), colorectal cancer (CRC), intestinal infection and other gut disorders via the regulation of signalling pathways, including the nucleotide‑binding oligomerization domain‑like receptor protein 3 inflammasome, NF‑κB and Nrf2 pathways. ITA also modulates the composition of the gut microbiota and enhances intestinal barrier function. The present study also aimed to summarize the therapeutic potential of ITA derivatives, providing a theoretical basis for the development of novel treatment strategies for intestinal disease.
Siglec‑15 dysregulation and its therapeutic implications in new‑onset type 1 diabetes.
Guo H, Tao Y, Li S … +4 more , Gu Y, Huang Y, Fang C, Hu J
Int J Mol Med · 2026 May · PMID 41891952 · Full text
Type 1 diabetes (T1D) is a T cell‑mediated autoimmune disorder characterized by the destruction of insulin‑producing β‑cells. Sialic acid‑binding Ig‑like lectin 15 (Siglec‑15) could inhibit T‑cell activation and suppress...
Type 1 diabetes (T1D) is a T cell‑mediated autoimmune disorder characterized by the destruction of insulin‑producing β‑cells. Sialic acid‑binding Ig‑like lectin 15 (Siglec‑15) could inhibit T‑cell activation and suppress immune responses. However, the association between Siglec‑15 expression levels and T1D is largely unknown. Serum concentrations of soluble Siglec‑15 were quantified in a cohort comprising 34 individuals newly diagnosed with T1D and 21 healthy control subjects. A murine mesenchymal stem cell (MSC) line, C3H10 T1/2, was genetically engineered to stably express SIGLEC15 through lentiviral transduction. Non‑obese diabetic (NOD) mice were administered treatments with Siglec15‑expressing MSCs, control MSCs, or phosphate‑buffered saline. The present study evaluated diabetes incidence, blood glucose concentrations, the severity of insulitis and the composition of immune cell populations in the pancreatic lymph nodes and spleens. In the present study, measurement of human serum specimens by ELISA revealed a positive association between new‑onset T1D and soluble Siglec‑15 levels. In NOD mice, treatment with Siglec15‑MSCs resulted in a significant reduction in diabetes incidence, preservation of insulin‑positive islets and mitigation of insulitis. Flow cytometric analysis demonstrated an increase in CD4effector memory T cells within the pancreatic‑draining lymph nodes of mice treated with Siglec15‑MSCs, while no significant alterations were observed in splenic T cell populations or the frequencies of regulatory T cells. The findings of this study underscore the potential of Siglec‑15‑overexpressing MSCs as a promising cell‑based therapeutic approach for T1D, primarily through the localized modulation of memory T cells within the pancreatic lymph nodes.
Epigenetic regulation in a high-sugar environment (Review).
Zhou H, Lv X, Liang Y … +2 more , Yu D, Wang W
Int J Mol Med · 2026 May · PMID 41860052 · Full text
The prevalence of diabetes and its complications has become a major global health challenge, with its pathological process closely linked to the phenomenon of 'metabolic memory' induced by persistent hyperglycemia. Epige...
The prevalence of diabetes and its complications has become a major global health challenge, with its pathological process closely linked to the phenomenon of 'metabolic memory' induced by persistent hyperglycemia. Epigenetic regulation is recognized as the core molecular mechanism underpinning this process. The present review systematically elucidated how the hyperglycemic microenvironment profoundly regulates cellular functions and drives the onset and progression of diabetes and its vascular complications by reprogramming three major epigenetic pathways: DNA methylation, histone modifications and non‑coding RNA expression. The present review elaborated in detail how high glucose induces alterations in the DNA methylation status of specific genes (such as PDX1 and CXCR4) within key target cells including pancreatic β‑cells, hepatocytes, muscle cells and adipocytes; how it modulates multiple histone modifications, including emerging histone lactylation (such as H3K18la), thereby directly activating pathogenic gene transcription; and how it disrupts non‑coding) RNA networks (such as long non‑coding RNA MALAT1 and microRNA 21) to mediate inflammation, oxidative stress and fibrosis by interfering with signaling pathways such as PI3K/Akt and TGF‑β. Furthermore, the present review specifically emphasized the cellular and tissue specificity of high‑glucose‑induced epigenetic regulation, thereby elucidating its unique mode of action in specific complications such as diabetic nephropathy and cardiovascular disease. Finally, the present review considered the substantial potential of targeting key epigenetic enzymes (such as DNA methyltransferases, histone deacetylases) or using epigenetic markers as biomarkers and novel therapeutic strategies. This provides a conceptual framework and directions for ultimately 'eradicating' metabolic memory and achieving precise prevention and treatment of diabetes and its complications.
[Expression of Concern] Insulin‑dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation.
Hie M, Iitsuka N, Otsuka T … +1 more , Tsukamoto I
Int J Mol Med · 2026 May · PMID 41860049 · Full text
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the TRAP‑stained images shown in Fig. 1 for the 'Diabetes' and 'IGF‑I' panels contained an overlapping section, s...
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the TRAP‑stained images shown in Fig. 1 for the 'Diabetes' and 'IGF‑I' panels contained an overlapping section, such that data which were intended to have shown the results of differently performed experiments were apparently derived from the same original source. The authors have been contacted by the Editorial Office to offer an explanation for the apparent anomaly in the presentation of the data in their 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 this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 28: 455-462, 2011; DOI: 10.3892/ijmm.2011.697].
Mechanism of action and clinical application of autophagy in multiple sclerosis (Review).
Wang D, Fu Q, Zhao Y … +6 more , Li G, Bai Y, Yang Y, Song H, Wang M, Fan H
Int J Mol Med · 2026 May · PMID 41860040 · Full text
Multiple sclerosis (MS) is a progressive, long‑term disorder affecting the central nervous system. The management and treatment of MS require significant medical resources, placing a heavy burden on both individuals and...
Multiple sclerosis (MS) is a progressive, long‑term disorder affecting the central nervous system. The management and treatment of MS require significant medical resources, placing a heavy burden on both individuals and society. Autophagy is essential for the degradation of dysfunctional or excess cellular components. In the context of MS, autophagy exhibits dual roles, both protective and detrimental. On one hand, it mitigates disease progression by reducing oxidative stress and inflammation. On the other hand, autophagy activates various immune and supportive cells pivotal in MS pathogenesis. This review aims to explore the relationship between autophagy and MS, its impact on disease progression and the current challenges in this field.
The roles and heterogeneity of CD8 T cells in inflammatory bowel disease: A narrative review of insights from single‑cell transcriptomics (Review).
Zhong R, Guo J, Ye W … +7 more , Deng Z, Wu H, Qi Q, Li G, Zhu L, Huang Y, Wu L
Int J Mol Med · 2026 May · PMID 41860039 · Full text
The present review investigates the role and characteristics of CD8 T cells in inflammatory bowel disease (IBD) using single‑cell transcriptomics, revealing their pivotal functions and remarkable heterogeneity. In IBD, C...
The present review investigates the role and characteristics of CD8 T cells in inflammatory bowel disease (IBD) using single‑cell transcriptomics, revealing their pivotal functions and remarkable heterogeneity. In IBD, CD8 T cells exhibit marked phenotypic and functional diversity, with distinct subpopulations exhibiting unique signaling pathway activation profiles that associate with varying clinical outcomes. Furthermore, CD8 T cell subsets in IBD participate in complex crosstalk networks involving immune and non‑immune cells, modulating inflammatory responses and tissue homeostasis. The present review synthesizes the dynamic complexity of CD8 T cell behavior in IBD and identifies promising therapeutic opportunities through targeted modulation of specific T cell subsets and their interactions within the colonic microenvironment.
ZEB1 maintains mitochondrial fission and macrophage efferocytosis by restraining MFN2, thereby limiting inflammation and improving tendon‑bone healing.
Zhao Y, Zhang Y, Lei T … +4 more , Zhang S, Nan K, Zhang X, Fan LH
Int J Mol Med · 2026 May · PMID 41860038 · Full text
Excessive inflammation and scar formation at the tendon‑bone interface (TBI) hinder effective healing. Macrophage efferocytosis is critical for resolving inflammation, yet its regulatory mechanisms in TBI healing remain...
Excessive inflammation and scar formation at the tendon‑bone interface (TBI) hinder effective healing. Macrophage efferocytosis is critical for resolving inflammation, yet its regulatory mechanisms in TBI healing remain unclear. The present study investigated the role of zinc finger E‑box binding homeobox 1 (ZEB1) in macrophage efferocytosis and rotator cuff repair. Zeb1 knockdown in rats was achieved using short hairpin RNA (shRNA). Bone marrow‑derived macrophages co‑cultured with apoptotic Jurkat cells were used to evaluate efferocytosis efficiency. Mechanistically, ZEB1 was demonstrated to function as a critical regulator of mitochondrial dynamics by transcriptionally repressing Mitofusin‑2 (MFN2), thereby maintaining the mitochondrial fission necessary for efficient efferocytosis. ZEB1‑knockdown relieved MFN2 suppression, leading to excessive mitochondrial fusion and a subsequent decrease in apoptotic cell clearance. , ZEB1 deficiency resulted in the accumulation of secondary necrotic cells, aggravated the inflammatory microenvironment (increased M1/decreased M2 polarization), and impaired histological and biomechanical healing of the tendon‑bone interface. These findings indicate a novel ZEB1/MFN2/mitochondrial fission axis that governs macrophage efferocytosis. Targeting this axis to restore the immune microenvironment offers a potential therapeutic strategy for improving tendon‑bone healing.
[Expression of Concern] Fasudil, a Rho‑associated protein kinase inhibitor, attenuates retinal ischemia and reperfusion injury in rats.
Song H, Gao D
Int J Mol Med · 2026 May · PMID 41860032 · Full text
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the photomicrographs shown in Fig. 1 on p. 195, the 'I/R' and 'Control' data panels (for the Day...
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the photomicrographs shown in Fig. 1 on p. 195, the 'I/R' and 'Control' data panels (for the Day 1 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. The authors have been contacted by the Editorial Office to offer an explanation for the apparent anomaly in the presentation of the data in their 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 this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 28: 193‑198, 2011; DOI: 10.3892/ijmm.2011.659].
Targeting pyroptosis in renal fibrosis: From molecular mechanisms to therapeutic horizons (Review).
Tian Y, Mushuo Q, Fan H … +3 more , Su H, Li J, Zhang Q
Int J Mol Med · 2026 May · PMID 41860029 · Full text
Pyroptosis, an inflammatory form of lytic programmed cell death intricately linked to innate immunity, is a pivotal driver of renal fibrosis. Its dysregulated activation initiates a self‑amplifying cycle of chronic infla...
Pyroptosis, an inflammatory form of lytic programmed cell death intricately linked to innate immunity, is a pivotal driver of renal fibrosis. Its dysregulated activation initiates a self‑amplifying cycle of chronic inflammation and extracellular matrix deposition, ultimately leading to renal failure. The present review integrates current knowledge primarily from preclinical and studies with clinical observations to delineate the multifaceted regulatory mechanisms governing renal pyroptosis, with emphasis on molecular triggers and execution pathways. The critical roles of core effectors such as NLRP3 and GSDMD, whose expression levels in patients correlate with fibrosis severity, were highlighted. The article systematically evaluates pharmacological interventions and explores multi‑target synergistic strategies aimed at integrated signaling hubs to circumvent pathway redundancy. Furthermore, advanced therapeutic approaches were discussed, including nanoparticle‑based delivery systems, offering a strategic framework to bridge the gap between bench research and clinical applications in the management of renal fibrosis.
[Expression of Concern] Inhibitory effect of curcumin on angiogenesis in ectopic endometrium of rats with experimental endometriosis.
Zhang Y, Cao H, Hu YY … +2 more , Wang H, Zhang CJ
Int J Mol Med · 2026 May · PMID 41823562 · Full text
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the histopathological images shown in Fig. 3 on p. 90, Fig. 3E and F showed an overlapping sectio...
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the histopathological images shown in Fig. 3 on p. 90, Fig. 3E and F showed an overlapping section, suggesting that these data panels were derived from the same original source where different treatment groups were reported. The authors have been contacted by the Editorial Office to offer an explanation for this apparent anomaly in the presentation of the data in this paper, and we are awaiting their response. Due to the fact that we have 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: 87‑94, 2011; DOI: 10.3892/ijmm.2010.552].
Roles of ubiquitin‑specific peptidase 22 in cellular fate: From embryonic survival to tissue repair, inflammation and metabolism (Review).
Xiang JN, Zhou CY, Zhao YD … +2 more , Xu X, Ling SB
Int J Mol Med · 2026 May · PMID 41823558 · Full text
Ubiquitin‑specific peptidase 22 (USP22), a key member of the deubiquitinase family, serves pivotal roles in tumorigenesis by driving tumor proliferation, metastasis and drug resistance. In addition to its role in oncolog...
Ubiquitin‑specific peptidase 22 (USP22), a key member of the deubiquitinase family, serves pivotal roles in tumorigenesis by driving tumor proliferation, metastasis and drug resistance. In addition to its role in oncology, its versatile functions in diverse physiological and pathological contexts have been revealed. These include ensuring embryonic viability through developmental signaling regulation, promoting tissue repair and contributing to ischemia‑reperfusion injury, inflammatory responses and immune activation via cytokine and immune cell regulation. USP22 is also involved in fibrosis, metabolic homeostasis and tissue remodeling in patients with conditions such as asthma and pneumoconiosis. These multifaceted actions are mediated primarily through the deubiquitination of target proteins such as silent mating‑type information regulation 2 homologue 1 and through epigenetic mechanisms, including histone modification. The present review summarized recent advances in USP22‑mediated cell fate regulation and evaluates its therapeutic potential across diseases, underscoring promising prospects for clinical translation.
mA in adipose tissue inflammation: A novel regulator of obesity and metabolic diseases (Review).
Yang X, Wang X, Tang H … +3 more , Tu S, Yin K, Zhu X
Int J Mol Med · 2026 May · PMID 41823557 · Full text
Adipose tissue hypertrophy, the local infiltration of immune cells, the increased production of proinflammatory cytokines, the whitening of brown adipose tissue, local hypoxia and angiogenesis disorders occur in obese in...
Adipose tissue hypertrophy, the local infiltration of immune cells, the increased production of proinflammatory cytokines, the whitening of brown adipose tissue, local hypoxia and angiogenesis disorders occur in obese individuals, which in turn lead to adipose tissue inflammation and promote the occurrence and development of metabolic diseases such as type 2 diabetes (T2DM), atherosclerosis and metabolic dysfunction‑associated steatotic liver disease (MASLD). In recent years, N6‑methyladenine (mA), the most representative epigenetic modification, has been shown to be significantly altered in individuals with obesity and to participate in the regulation of various metabolic diseases. In the present review, the links between m6A modification and obesity‑related metabolic diseases, such as MASLD and T2DM, from the perspective of adipose tissue inflammation are examined. Additionally, the challenges and prospects associated with targeting m6A in adipose tissue inflammation and metabolic diseases are discussed to provide new ideas for the treatment of these conditions.
4‑Acetylantrocamol LT3 suppresses colorectal cancer growth and metastasis via PI3K/AKT and MAPK pathway modulation.
Lin KT, Hsieh YC, Chang PK … +3 more , Lai CW, Lee SY, Yen IC
Int J Mol Med · 2026 May · PMID 41823551 · Full text
Colorectal cancer (CRC) remains one of the leading causes of cancer‑related mortality worldwide. Despite advances in targeted therapies, drug resistance and limited efficacy in KRAS‑mutant CRC continue to present clinica...
Colorectal cancer (CRC) remains one of the leading causes of cancer‑related mortality worldwide. Despite advances in targeted therapies, drug resistance and limited efficacy in KRAS‑mutant CRC continue to present clinical challenges. , a medicinal fungus, demonstrates antitumor properties; however, the mechanisms of its triterpenoid compound, 4‑acetylantrocamol LT3 (LT4), remain unclear. The present study investigated the effects of LT4 on KRAS‑mutant HCT116 CRC cells using cell viability, colony formation and migration assays. Western blotting was also employed to examine key signaling pathways. Transcriptome profiling via RNA sequencing was followed by Kyoto Encyclopedia of Genes and Genomes/Gene Ontology enrichment and protein‑protein interaction network analyses using STRING, CytoHubba and Molecular Complex Detection (MCODE). Molecular docking with PI3Kγ (PDB: 1E7U) was conducted to evaluate the predicted binding position and docking energy of LT4. The results indicated that LT4 significantly inhibited HCT116 cell proliferation and migration, induced a mesenchymal‑to‑epithelial transition, suppressed PI3K/AKT/mTOR and ERK signaling and activated the GSK3β/FOXO and phosphorylated‑p38/p21 axes. LT4 also reduced the levels of cyclooxygenase‑2 and anti‑apoptotic proteins (Bcl‑2 and Bcl‑XL) and reduced the expression of the mitochondrial respiratory chain protein cytochrome c oxidase subunit IV. Transcriptomic analysis identified the PI3K/AKT pathway as the most significantly enriched signaling cascade. Network topology analyses highlighted solute carrier family 3 member 2, Cyclin D1, phosphoserine aminotransferase 1 and ChaC glutathione‑specific γ‑glutamylcyclotransferase 1 as central nodes, linking the effects of LT4 to nutrient signaling, redox homeostasis and serine metabolism. Molecular docking confirmed that LT4 stably occupied the ATP‑binding pocket of PI3Kγ with a binding energy comparable to wortmannin and a conformation similar to antroquinonol. In conclusion, to the best of our knowledge, the present study is the first to comprehensively demonstrate the multi‑target anti‑CRC effects of LT4, highlighting its potential as a therapeutic agent, especially in KRAS‑mutant CRC.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe