BACKGROUND:Mitochondria are the primary organelles that regulate cellular bioenergetic metabolism and maintain homeostasis, providing essential structural support for optimal cell survival. Nonetheless, advancing age leads to cumulative damage to mitochondrial structure and functional integrity, which is a defining characteristic of biological aging and is closely linked to the emergence and progression of numerous age-related diseases, including neurodegenerative disorders, cardiovascular diseases, and metabolic disorders. SCOPE OF REVIEW:This article offers a thorough summary and review of mitochondrial quality control (MQC), emphasizing numerous critical processes, including mitochondrial biosynthesis, dynamic remodeling (fusion and fission), and mitophagy. We thoroughly elucidate the molecular pathways that regulate MQC and demonstrate how age-related dysregulation precipitates cellular senescence, highlighting the transition from physiological maintenance to pathological malfunction, which ultimately culminates in cellular aging. CONCLUSIONS AND IMPLICATIONS:This study systematically elaborates the pathophysiological mechanisms in the field, comprehensively evaluates the clinical translational potential of targeting the MQC pathway, highlights the key objectives of "restoring mitochondrial plasticity and removing dysfunctional mitochondria", and explores novel intervention strategies. The restoration of normal mitochondrial function in cells throughout aging is a very promising path for precision medicine therapeutics with great translational potential, according to recent state-of-the-art research. The development of novel therapeutic approaches to improve functional healthy mitochondria can effectively delay aging and reduce the rising global burden of age-related diseases.

Dysregulated proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs) represent a key pathophysiological mechanism in osteoporosis. Recent studies have demonstrated a significant association between ferroptosis and the advancement of osteoporosis, suggesting that targeting ferroptosis could offer novel therapeutic approaches for osteoporosis treatment. Curcumin, a natural antioxidant, has shown therapeutic potential in bone-related disorders; however, its precise mechanisms for modulating BMSC function-particularly via ferroptosis-related pathways-remain poorly characterized. This study investigated whether curcumin alleviates iron overload-induced BMSC dysfunction by targeting ferroptosis, specifically elucidating its molecular mechanisms in promoting osteogenic differentiation and mitigating cellular senescence. Iron-overloaded BMSC in vitro models and in vivo murine systems were established to model osteoporosis-related microenvironments. Curcumin was administered to assess its effects on cellular and systemic outcomes, including bone microstructure, mechanical property, differentiation capacity, senescence markers, iron metabolism, and redox homeostasis by using micro-CT, RNA-seq, RT-qPCR, western blot, immunohistochemical, immunofluorescence, and transmission electron microscope (TEM). Furthermore, Nrf2 siRNA and the Nrf2 inhibitor ML385 were utilized to interrogate curcumin's mechanism of action in iron-overloaded BMSCs. In vivo, curcumin treatment significantly attenuated iron overload-induced bone microstructural damage, mechanical property, and elevated Nrf2 and GPX4 expression in BMSCs. In vitro, curcumin mitigated iron overload-induced ferroptosis in BMSCs by upregulating Nrf2 expression, thereby increasing GPX4 levels. This mechanism consequently delayed cellular senescence and promoted osteogenic differentiation. Our findings establish the Nrf2/GPX4 axis as a critical therapeutic target of curcumin for ameliorating iron overload-induced osteoporosis. This mechanistic insight provides a foundation for developing novel therapeutics against age-related and postmenopausal osteoporosis.

OBJECTIVE:To investigate the association and potential mechanisms between H7N9 influenza virus infection or vaccination and immune thrombocytopenia (ITP), providing foundational data for the prevention and treatment of related ITP. METHODS:Using laboratory-prepared anti-H7N9 influenza virus monoclonal antibodies (mAbs) (H7N9-98 and H7N9-120) as research subjects, the interactions between these antibodies and human platelets were analyzed through Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) techniques. RESULTS:The mAb H7N9-98 exhibited specific binding to human platelets, showing positive results in both IHC and IF assays. Western blotting results demonstrated that this antibody could specifically recognize approximately 60 kDa human platelet proteins. The isotype control mAb H7N9-120 did not exhibit the aforementioned binding reactions, with all test results being negative. CONCLUSION:These findings suggest that the specific antibodies induced by the H7N9 virus may mediate platelet damage through cross-reactivity with platelet autoantigens. This mechanism warrants further investigation to provide experimental evidence for the pathogenesis of secondary ITP associated with H7N9 infection.

Cancer continues to be one of the leading causes of death worldwide. Although immunotherapy has transformed oncologic treatment by mobilizing the host immune system, the immunosuppressive tumor immune microenvironment (TIME) still constitutes a major barrier to durable clinical responses. Recent studies indicate that iron-based magnetic nanoparticles (Fe-MNPs) offer capabilities that extend beyond those of conventional drug delivery systems, acting instead as active regulators of the TIME. In this review, we outline current progress in Fe-MNP-mediated cancer immunotherapy and propose a conceptual framework to clarify their immunomodulatory effects. Specifically, Fe-MNPs can generate multiple physicochemical stimuli under magnetic field control, including magnetic hyperthermia, magnetically induced mechanical perturbation, and Fenton reaction-mediated oxidative stress. These upstream events converge to induce immunogenic stress, including ferroptosis-associated injury, which in turn promotes hypoxia alleviation, tumor-associated macrophage (TAM) reprogramming, dendritic cell activation, and enhanced effector T-cell responses. Together, these findings support a framework in which Fe-MNP-mediated immunomodulation is understood as an integrated cascade rather than a collection of isolated effects. However, challenges remain regarding biosafety, long-term iron metabolism, delivery efficiency, and large-scale manufacturing. Overall, this review provides a systematic overview of Fe-MNP-mediated immunomodulation and discusses the translational prospects of these materials as multifunctional platforms for cancer immunotherapy.

The occurrence and progression of autoimmune diseases (AIDs) result from the combined effects of genetic susceptibility, immune response defects, and environmental triggers. Among these, microorganisms, as key environmental factors, have been widely hypothesized to play a role in initiating AIDs, but the exact causal relationship remains to be demonstrated. This review aims to deeply explore the core role of specific microbial infections in triggering AIDs by integrating evidence from three dimensions: epidemiological investigations, clinical studies, and animal model research. We focused on analyzing nine AIDs, including Guillain-Barré syndrome, systemic lupus erythematosus, and rheumatoid arthritis, and confirmed that specific pathogens such as Campylobacter jejuni, Epstein-Barr virus, and Porphyromonas gingivalis can induce corresponding autoimmune pathological damage in susceptible individuals through mechanisms including molecular mimicry and bystander activation. Nevertheless, the field still faces important gaps that caused the chain from mechanism association to clinical application to break.This review integrates existing evidence and demonstrates that microbial infections are one of the important triggers for AIDS. It provides a new theoretical basis and direction for mechanistic research, risk early warning, and targeted intervention of related diseases.

Activation of autoreactive lymphocytes leads to cellular and tissue damage, which results in the development of autoimmune diseases. External environmental changes, such as chronic microbial infections, can alter the immune homeostasis and disrupt the balance of autoreactive T and B cells. In this review, we first summarize immune tolerance mechanisms of T and B cells, and then describe the breakthroughs of immune tolerance in T and B cells, followed by related autoimmune diseases. Furthermore, we explore how microbial infections can induce the production of autoreactive antibodies via carrier effects when the balance of autoreactive T and B cells is disrupted. These kinds of antibodies can lead to autoimmune diseases through molecular mimicry mechanisms. Our perspective provides a theoretical framework and novel insights into the mechanism of autoreactive antibodies in the pathogenesis of autoimmune diseases associated with microbial infections. This analysis may offer novel directions for drug discovery of autoimmune diseases.

Breast cancer is among the most prevalent malignant tumors in women globally, with adriamycin (ADM) demonstrating considerable efficacy as a first-line chemotherapeutic agent. The problem of adriamycin resistance significantly impairs its effectiveness, requiring the clarification of resistance mechanisms and the discovery of novel biomarkers to enhance treatment techniques. This research utilizes a blend of cellular studies and data analysis to examine the influence of DLG5 on the expression of autophagy-related genes in doxorubicin-resistant MCF-7 cell lines. The findings imply that autophagy may confer protection to breast cancer cells, whereas the downregulation of DLG5 correlates with adriamycin resistance, indicating its potential as a novel biomarker for predicting treatment responses. Moreover, DLG5 affects the viability of adriamycin-resistant cells by stimulating the autophagy pathway, highlighting its protective function in resistance. This research elucidates the probable pathways by which DLG5 contributes to chemotherapy resistance in breast cancer and underscores its significance as a therapeutic target. This research elucidates the processes of adriamycin resistance, offering valuable insights for the advancement of future breast cancer treatment techniques.

OBJECTIVE:Immature dendritic cells (imDC) are crucial in facilitating transplant immunological regulation. However, imDC is readily amenable to maturation. Sinomenine (Sin) naringin (Nar) are traditional Chinese medicine with immunoregulation and anti-inflammatory activities. We investigated the effect of Sin and Nar on the generation of immature dendritic cells (imDC) and their ability to prolong the survival of skin allografts in mice. METHODS:Hematopoietic stem cells (HSC) obtained from bone marrow prompted to develop into immature dendritic cells (imDC) through treatment with Sin (Sin-HSC-imDC) or Nar (Nar-HSC-imDC). The cell counting kit-8 (CCK-8) assay was employed to assess the differentiating efficacy of Sin-HSC-imDC and Nar-HSC-imDC. DC surface markers and apoptosis following lipopolysaccharide (LPS) treatment were assessed by flow cytometry, while apoptosis-related genes using qPCR. The impact of Sin-HSC-imDC and Nar-HSC-imDC on the generation of regulatory T cells (Tregs) was evaluated by mixed lymphocyte reactions. Cytokine expression was quantified using enzyme-linked immunoassays (ELISA). The immunomodulatory effects of Sin-HSC-imDC and Nar-HSC-imDC were evaluated by performing skin transplantation experiments in Balb/c mice recipients models. Kaplan-Meier technique was employed for graft survival outcomes. RESULTS:In vitro assays, in comparison to Sin-HSC-imDC, Nar-HSC-imDC had higher CD11c expression and lower CD80 as markers for imDCs (P < 0.05) and promoted the generation of Tregs proliferation (P < 0.05). Interleukin 2 (IL-2) and interferon gamma (IFN-γ) levels diminished in Nar-HSC-imDC groups (P < 0.05), but interleukin 10 (IL-10) and transforming growth factor-beta (TGF-β) levels elevated (P < 0.05). And the apoptosis rate of Nar-HSC-DC increased significantly after LPS treatment (P < 0.05). In vivo assays, when Balb/c mice received Nar-HSC-imDC or Sin-HSC-imDC via the tail vein seven days before skin transplantation, mice from the Nar-HSC-imDC group had increased CD4+CD25+CD127- Tregs proliferation in the spleen (P < 0.05), which prolonged skin graft survival, and that was better than in Sin-HSC-imDC group. CONCLUSION:Nar was exposured more efficient in inducing differentiation of HSC into imDC than Sin. Nar-HSC-imDC had stronger ability in inducing specific immune hypo-responsiveness than Sin-HSC-imDC.

Tourette’s syndrome (TS) is a common neurodevelopmental disorder with tics, emerging in childhood or adolescence and linked to neurotransmitter system abnormalities. Given iron’s key role in neurotransmitter synthesis and transport, a close link between serum iron status and TS is hypothesized. But current studies, partly due to their inherent limitations, offer inconclusive evidence. A Mendelian randomization (MR) analysis was conducted. The analysis utilized summary statistics from two genome-wide association studies (GWAS) for TS (primary study: N = 456,348; and replication study: N = 21,081) and four GWASs related to serum iron status. The inverse variance-weighted MR method was used to evaluate the relationship between serum iron status and risk of TS using both the primary dataset and the replication dataset. Additionally, four other MR methods, which are more robust to pleiotropy and outliers, were used for sensitivity analyses. The analysis revealed no significant association between serum iron status and risk of TS (all Ps > 0.05). Repeated analysis with an independent TS sample yielded consistent results. Conclusion: This MR study failed to uncover substantial evidence supporting a causal relationship between serum iron status in risk of TS due to its weak proxies to reflect brain iron levels. Therefore, additional validation from clinical and experimental investigations is warranted.

Influenza A virus infection can cause acute respiratory distress syndrome (ARDS), and to date, viral pneumonia has been the main cause of ARDS. Bone marrow mesenchymal stem cells have shown promise for treating lung injury caused by avian influenza virus infection. At present, studies of the use of other stem cell types to treat human influenza virus-mediated lung damage are sparse. We assessed the use of umbilical cord mesenchymal stem cells (UC-MSCs) to treat damage from serious H1N1 influenza virus infections in cell and animal-based experiments. Maximum viral titers, inflammatory factor expression levels, differential expression of alveolar cell-related proteins, animal weight and survival rate, lung histopathology, and other indicators were evaluated. Compared with the control group, in cellular experiments, UC-MSCs could effectively inhibit H1N1 influenza viral replication and repair damaged host cells. In animal experiments, UC-MSCs reduced expression of pro-inflammatory cytokines, reduced entry of inflammatory cells into the lungs, alleviated lung inflammation, significantly reduced the extent of lung injury in mice, and improved lung histopathology, improving overall survival. A positive role of umbilical cord-derived mesenchymal stem cells in treating lung injury caused by H1N1 influenza virus infection that is worthy of clinical promotion has been demonstrated.

Pseudomonas aeruginosa is an opportunistic pathogen with high antibiotic resistance, often causing hard-to-treat infections. Its quorum sensing (QS) system regulates virulence and drug resistance. Targeting quorum sensing via QS inhibitors is a promising strategy to combat such infections. In this study, isoliquiritigenin, a natural chalcone compound, could inhibit QS-related gene expression (lasR, lasI, rhlR, rhlI, pqsA, pqsR, lasA, rhlA, phzA1) and reduced virulence factor production of Pseudomonas aeruginosa PAO1, including protease, elastase, pyocyanin, rhamnolipid, biofilm formation and motility at subinhibitory concentrations of 50 and 100 µg/mL. The pathogenicity of PAO1 could be also attenuated by isoliquiritigenin at the tested concentrations evidenced by in vitro and vivo infection analysis via Chinese cabbage, Drosophila melanogaster, and Caenorhabditis elegans modles. Isoliquiritigenin might exhibit QSI property by targeting the las, rhl, and pqs systems based on the molecular docking analysis and the infection analysis in mutants. As a novel QSI, isoliquiritigenin develop less tendency drug resistance to PAO1, at least during the 20 generations tested. Moreover, isoliquiritigenin could increase the sensitivity of P. aeruginosa to aminoglycosides of kanamycin, amikacin or tobramycin, enhancing P. aeruginosa infection treatment. Therefore, isoliquiritigenin could function as a potential QSI against P. aeruginosa infection, either separately or synergistically combined with aminoglycosides antibiotics.

Triple-negative breast cancer (TNBC) is among the most aggressive forms of breast cancer, characterized by a dismal prognosis. In the absence of drug-targetable receptors, chemotherapy remains the sole systemic treatment alternative. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs) that target programmed death 1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4), have provided renewed optimism for the treatment of patients with TNBC. Prior research has indicated that the expression level of the cell polarity protein discs large homolog 5 (DLG5) correlates with the malignant progression and prognosis of breast cancer; nevertheless, its influence on PD-L1 expression and its function in immunotherapy for TNBC require further investigation. The hypoxia cell model was established by simulating the cell hypoxic microenvironment in the human SUM159 and MDA-MB-231 cell lines using cobalt II chloride (CoCl2). A combination of PD-L1 inhibitors and DLG5 RNA interference techniques was used, along with various methods including cell counting kit-8 (CCK-8), colony formation, wound healing, transwell migration, reverse transcription-quantitative real-time PCR (RT-qPCR), immunofluorescence, immunohistochemical staining (IHC), expression analysis from datasets and western blotting. These methods were employed to evaluate changes in cell proliferation, migration, and the expression levels of PD-L1 and DLG5. Additionally, the correlation between the expression of PD-L1 and DLG5 in clinical samples was analyzed. (1) In vitro experiments, a cellular hypoxia model was effectively established utilizing 150 µM CoCl₂. Under these conditions, cell clone formation, invasiveness, and migration rate were all significantly inhibited. (2) The expression levels of DLG5 and PD-L1 were significantly increased in both MDA-MB-231 and SUM159 cells following treatment with 150 µM CoCl₂. (3) Silencing DLG5 resulted in a considerable upregulation of PD-L1 expression in MDA-MB-231 and SUM159 cells under normoxic circumstances, but it was markedly downregulated under hypoxic settings. Inhibition of PD-L1 expression resulted in a considerable increase in DLG5 expression under normoxic conditions, but it decreased under hypoxic conditions. Correlation research demonstrated an inverse association between the expression of DLG5 and PD-L1 in TNBC tissues. This study provides new theoretical evidence and potential therapeutic targets for the immunotherapy strategies of TNBC, holding significant clinical application value.

Introduction: Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. It is highly invasive and aggressive, making it the subtype of breast cancer with the poorest prognosis. Currently, systemic chemotherapy is the primary treatment option, but targeted therapies remain unavailable. Therefore, there is an urgent need to identify novel biomarkers for the early diagnosis and treatment of TNBC. Methods: We conducted an integrated analysis of transcriptome and methylation data to identify methylation-regulated differentially expressed genes (MDEGs). Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network analysis were performed on MDEGs to investigate the impact of hub genes on the diagnosis and prognosis of TNBC. Subsequently, the expression levels and DNA methylation patterns of key genes were validated in the TNBC cell line MDA-MB-231 and the normal breast epithelial cell line MCF-10A using reverse transcription quantitative PCR (RT-qPCR) and quantitative methylation-specific PCR (qMSP). Results: A total of 98 upregulated and 87 downregulated genes were identified through transcriptomic profiling integration analysis. By incorporating methylation data, we further identified 22 genes with high expression of hypomethylation (hypo-MDEGs) and 32 genes with low expression of hypermethylation (hyper-MDEGs). The hypo-MDEGs were primarily involved in nuclear division, organelle fission, spindle formation, chromosome and kinetochore development, and protein binding. KEGG pathway analysis revealed that these genes were enriched in progesterone-mediated oocyte maturation, cell cycle regulation, and oocyte meiosis. Hyper-MDEGs were associated with cell proliferation, hormone response, pain, extracellular matrix composition, and binding to sulfur compounds, heparin, and glycosaminoglycans. PPI network analysis identified seven hub genes-EXO1, KIF11, FOXM1, CENPF, CCNB1, PLK1, and KIF23-which were all significantly overexpressed in TNBC tissues and positively correlated with each other (p < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve (AUC) for all seven genes exceeded 0.9 (p < 0.05), suggesting strong diagnostic potential. Kaplan-Meier survival analysis indicated that KIF11, CCNB1, and PLK1 were associated with a higher hazard ratio (HR > 1, p < 0.05) in TNBC. In vitro validation experiments demonstrated that, compared to MCF-10A cells, MDA-MB-231 cells exhibited higher mRNA expression levels of KIF11, CCNB1, and PLK1, while their DNA methylation levels were lower. Conclusions: This study identified seven hypo-MDEGs, including EXO1, KIF11, FOXM1, CENPF, CCNB1, PLK1, and KIF23, which are involved in the regulation of the cell cycle and mitotic processes and have significant potential as diagnostic biomarkers for TNBC. Notably, elevated expression of KIF11, CCNB1, and PLK1 is associated with poor prognosis in patients with TNBC. These findings contribute to an improved understanding of the epigenetic molecular mechanisms underlying TNBC progression and highlight novel biomarkers that may enhance the accuracy of TNBC diagnosis and provide potential targets for therapeutic intervention.

RNA metabolism is an important post‑transcriptional regulatory mode in organisms, and its process is cooperatively regulated by a variety of RNA‑binding proteins. RNA binding motif protein 8A (RBM8A), a regulator of mRNA stability that is implicated in cancer progression, serves an important role in processes such as RNA splicing, transport, translation and decay. However, to the best of our knowledge, its role in the occurrence and development of gastric cancer (GC), as well as its biological functions and molecular mechanisms remain unclear. In the present study, RBM8A expression was on average 1.4‑fold higher (P<0.05), with a maximum log2 fold change of 1.4 (2.6‑fold increase), in GC tissues compared with adjacent normal tissues, as determined by multiplex immunohistochemical analysis of tissue microarrays. In vitro, transfection of RBM8A small interfering RNAs significantly suppressed the proliferation of AGS and HGC27 cells and enhanced apoptosis. Specifically, annexin V‑positive AGS cells exhibited a 2.9‑fold increase with siRBM8A‑1 transfection and a 1.9‑fold increase with siRBM8A‑2 transfection, while annexin V‑positive HGC27 cells exhibited a 2.3‑fold increase with siRBM8A‑1 transfection and a 1.8‑fold increase with siRBM8A‑2 transfection (P<0.05). Using MKN45 cell lines and subcutaneous xenograft models, the present study revealed that RBM8A knockdown reduced subcutaneous tumor growth in nude mice by 51.5% in terms of volume and 62.4% in terms of weight (P<0.05). In terms of the mechanism, integrated mRNA‑sequencing (seq) and RNA immunoprecipitation (RIP)‑seq identified BCL2 binding component 3 (BBC3), a well‑characterized pro‑apoptotic gene, as a direct target of RBM8A. Further results of RIP‑quantitative PCR, fluorescence in situ hybridization‑immunofluorescence and RNA pulldown indicated the direct interaction between RBM8A and BBC3 mRNA. Actinomycin D assays demonstrated that RBM8A promoted BBC3 mRNA degradation. Subsequently, the co‑immunoprecipitation assay showed that RBM8A interacted with UPF3B to jointly regulate the stability of BBC3 mRNA. In conclusion, RBM8A inhibited apoptosis and promoted GC progression by interacting with UPF3B, leading to degradation of the pro‑apoptotic gene BBC3 mRNA. These findings highlighted that interfering with RBM8A expression, or disrupting the interactions between RBM8A and BBC3 mRNA or between RBM8A and UPF3B could serve as potential therapeutic strategies for GC.

Background:RNA modifications are associated to various human diseases. However, the functions of RNA modification-related genes have yet to be thoroughly investigated in dilated cardiomyopathy (DCM). This study sought to conduct a comprehensive analysis of RNA modification-associated genes for the diagnosis and subtype classification of DCM. Methods:We collected DCM and control sample RNA modification-related genes from Gene Expression Omnibus (GEO) microarray datasets. Differential expression analysis was performed on these using the "Limma" package in R. Univariate logistic regression, and the LASSO algorithm were used to identify optimal genes for diagnostic model establishment. Furthermore, ConsensusClusterPlus was used to identify RNA modification-molecular subtypes. Lastly, the expression of the hub RNA modification-related genes and their connection to DCM were confirmed using the clinical samples and mouse models. Results:Twenty-six RNA modification-related genes were identified as dysregulated in DCM, with strong connections noted among these genes. A diagnostic model based on 13 genes (TRMT61B, MBD2, YTHDC2, NOP2, TRMT10C, WDR4, CPSF2, CSTF3, ZBTB4, UNG, NSUN6, TET1, and DNMT3B) with an AUC of 0.980 predicted DCM well. Infiltrating plasma B cells, eosinophils, CD8 T cells, and regulatory T cells correlated strongly with TRMT61B, MBD2, YTHDC2, and CPSF2. Two RNA modification-molecular subtypes (clusters 1 and 2) were identified. Cluster 1 had greater RNA modification scores, lower immune ratings, and lower HLA-DRB1 and HLA-DPB1 expression than Cluster 2. Cluster 2 engaged metabolism-related pathways, while Cluster 1 activated renin-angiotensin system pathways.We further found a substantial link between lower cardiac function and up-regulation of TET1, DNMT3B, and down-regulation of MBD2, TRMT61B in the 13 hub RNA modification-related genes. Conclusion:In conclusion, our RNA modification-related diagnostic model predicts DCM well. The discovery of two RNA modification-molecular subgroups and four key pivotal genes may assist stratify DCM patients by risk.

BACKGROUND:The medicinal phytochemical oleandrin (Ole) is obtained from the Nerium oleander plant. The exact relationship between Ole-induced apoptosis and autophagy in gastric cancer (GC) is unclear despite the fact that it has outstanding anti-tumor capabilities. This research aimed to demonstrate how autophagy and Ole-induced apoptosis interact in GC. METHODS:The Cell Counting Kit (CCK)-8 assay and colony formation assays were employed to evaluate cell proliferation. Cellular apoptosis was evaluated with Calcein/Propidium Iodide (PI) assays and flow cytometry. Confocal and electron microscopes were employed to examine the morphology of autophagy. Protein concentrations were assessed by western blotting. Luciferase-positive HGC-27 cells were administered subcutaneously to Balb/c nude mice to evaluate Ole's anti-tumor activity. Immunohistochemistry assessed Ki67 expression and H&E staining in tumor tissue. RESULTS:Ole causes GC cells to undergo intracellular apoptosis and autophagy at low nanomolar doses, halting the cell cycle at the G0/G1 phase. Whereas 3-methyladenine (3-MA), the inhibitor of autophagy, counteracts the apoptosis generated by Ole in vitro and in vivo. CONCLUSIONS:Ole may trigger apoptosis through the activation of autophagy in GC. It offers a secure and efficacious candidate drug for the treatment of tumors in the digestive system.

Background:Kawasaki disease is the leading cause of acquired heart disease in children, yet timely diagnosis remains difficult due to overlapping symptoms with other febrile illnesses. Methods:In a retrospective case-control study of 38 children with Kawasaki disease and 44 febrile controls, we measured hematological parameters and C-reactive protein (CRP) using standardized analyzers and profiled seven serum microRNAs by qRT-PCR. Biomarkers showing significant differences were used to build logistic regression models with a 70/30 train-test split, and diagnostic accuracy was assessed by receiver operating characteristic analysis. Functional enrichment of miRNA targets was explored using network analysis. Results:CRP and three microRNAs (miR-223-3p, miR-19a-3p, miR-18a-5p) were significantly elevated in Kawasaki disease. Individually, these markers achieved strong discrimination (AUC: 0.846-0.986), while their combination yielded an AUC of 0.990, sensitivity 1.000, and specificity 0.923. The three microRNAs were positively correlated and enriched for pathways including p53 signaling and cell cycle regulation, with KCNQ1OT1 identified as a shared lncRNA interactor. Conclusion:Integrating CRP with a concise serum miRNA panel demonstrates promising discriminatory potential for Kawasaki disease vs. other febrile illnesses and suggests mechanistic involvement of p53-associated pathways, supporting future validation in larger, independent cohorts.