International journal of molecular medicine最新文献

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].

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 Fe²⁺ were quantified using commercial reagent kits. Reactive oxygen species (ROS) were assessed through immunofluorescence. Additionally, a tumor xenograft mouse model was employed for in vivo 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, Fe²⁺, 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 in vivo 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.

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 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.

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.

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.

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.

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 in vivo and in vitro 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.

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. Antrodia cinnamomea, 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.

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.