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Background: Eukaryotic Initiation Factor 5A1 (EIF5A1) is a translation factor, and its pro-tumorigenic role has been extensively documented across various cancer types. However, its specific function in bladder cancer (BLCA) remains unclear. Methods: We integrated proteomics and transcriptomics data with clinical data from BLCA patients to investigate the correlation between EIF5A1 expression and BLCA, as well as its potential clinical applications. Transcriptomic data were employed to explore the downstream signaling pathways regulated by EIF5A1. Furthermore, ChIP analysis and luciferase reporter assays were conducted to identify the upstream transcription factors regulating EIF5A1. Results: EIF5A1 expression is significantly upregulated in cancer tissues and cells and is strongly associated with poor prognosis. Silencing EIF5A1 in BLCA cells significantly reduced invasiveness, and proliferative capacity. Mechanistic studies identified YAP/TEAD4 as a transcription factor that regulates EIF5A1, influencing mitochondrial-mediated apoptosis by activating the JAK2/STAT3 signaling pathway, thereby promoting BLCA progression. Conclusion: Our research demonstrates that EIF5A1 is upregulated in BLCA and associated with poor prognosis. We identified TEAD4 as a potential transcriptional regulator of EIF5A1 and showed that EIF5A1 expression is associated with changes in JAK2/STAT3 signaling and mitochondrial apoptosis in BLCA. [ABSTRACT FROM AUTHOR]

In patients with acute myocardial infarction (AMI), thrombolytic therapy and revascularization strategies allow complete recanalization of occluded epicardial coronary arteries. However, approximately 35% of patients still experience myocardial ischemia/reperfusion (I/R) injury, which contributing to increased AMI mortality. Therefore, an accurate understanding of myocardial I/R injury is important for preventing and treating AMI. The death of each cell (cardiomyocytes, endothelial cells, vascular smooth muscle cells, cardiac fibroblasts, and mesenchymal stem cells) after myocardial ischemia/reperfusion is associated with apoptosis due to mitochondrial dysfunction. Abnormal opening of the mitochondrial permeability transition pore, aberrant mitochondrial membrane potential, Ca2+ overload, mitochondrial fission, and mitophagy can lead to mitochondrial dysfunction, thereby inducing mitochondrial apoptosis. The manifestation of mitochondrial apoptosis varies according to cell type. Here, we reviewed the characteristics of mitochondrial apoptosis in cardiomyocytes, endothelial cells, vascular smooth muscle cells, cardiac fibroblasts, and mesenchymal stem cells following myocardial ischemia/reperfusion. [ABSTRACT FROM AUTHOR]

Abstract Previous research suggests mitochondrial apoptosis alleviates rheumatoid arthritis (RA), but the role of mitochondrial apoptosis-related genes (MARGs) is unclear. Urgent exploration of RA-related mitochondrial apoptosis biomarkers is needed. Gene Expression Ontology (GEO)-derived RA datasets were used to identify differentially expressed genes (DEGs) compared to normal controls, intersected with MARGs to obtain differentially expressed mitochondrial apoptosis-related genes (DE-MARGs). Three ML algorithms screened diagnostic biomarkers. A nomogram was built and validated by receiver operating characteristic (ROC) analysis. Gene Set Enrichment Analysis (GSEA), regulatory network, and drug prediction explored biomarker mechanisms. Finally, key cells analysis included clustering, type annotation, pseudo-temporal study, and interaction, focusing on validated biomarker expression in those cells. A total of 147 DE-MARGs linked to energy & ROS metabolism were identified. Four validated biomarkers (MRPS10, EEF2, HSPA9, TUFM) formed a new RA diagnostic model. Moreover, GSEA linked them to oxidative phosphorylation. YY1 regulates EEF2, HSPA9, MRPS10; FOXO3 regulates EEF2, TUFM. Drugs like Nonoxynol-9, Nedocromil, Gadobutrol target these biomarkers. In addition, biomarkers are expressed in plasmablasts, with CD74 as a key receptor binding multiple ligands. RA biomarkers (MRPS10, EEF2, HSPA9, TUFM) linked to energy & ROS, progression tied to AMPK/mTOR, CD74-MIF crucial. Study advances RA pathogenesis knowledge, supporting clinical diagnosis.

ObjectiveTo investigate the protective effect of naringin on mitochondrial apoptosis in osteoarthritic (OA) chondrocytes by regulating lncRNA GAS5.MethodsIn vivo experiments, a rat OA model was constructed using the modified Hulth method and treated with naringin at 70 mg/kg by gavage for 8 weeks. Magnetic resonance imaging and ultrasound were used to identify the success of modeling; histopathological changes in rat articular cartilage were assessed using toluidine blue and saffron O staining; changes in the levels of lncRNA GAS5 in rat cartilage tissues after naringin intervention were detected by Real-time PCR; Western blot detected Caspase-3, Bax, MMP-13 and Cyt-C in rat cartilage tissues. In vitro experiments, Lenti-lncRNA GAS5 was used to infect sodium nitroprusside (SNP)-induced chondrocytes, and the expression of lncRNA GAS5 was detected by fluorescence in situ hybridization in rat chondrocytes; after silencing of lncRNA GAS5, the expression level of lncRNA GAS5 in rat chondrocytes was detected by Real-time PCR; Western blot detected the protein levels of Caspase-3, Bax, MMP-13 and Cyt-C.Results① Pathological changes of cartilage tissue: The articular cartilage matrix in naringenin group was relatively complete, the surface was relatively smooth, the structure was clear, the tide line was more complete, the number of chondrocytes was more full, the arrangement was more orderly, the cartilage staining was more uniform, and the structure was significantly restored than that in the model group. ② lncRNA GAS5 expression in cartilage tissue: Compared with model group, lncRNA GAS5 expression in naringin group was decreased (PPPP< 0.01). In addition, silencing lncRNA GAS5 will weaken the therapeutic effect of naringin on OA.ConclusionNaringin inhibits chondrocyte mitochondrial apoptosis and protects degraded cartilage tissues by down-regulating the expression of lncRNA GAS5, which has therapeutic value for OA diseases.

Coccidiosis in chickens is a parasitic disease caused by Eimeria species, resulting in significant economic losses to the poultry industry. Among these species, Eimeria tenella is considered the most virulent pathogen, with its infection strongly associated with the apoptotic response of host cells. Eimeria tenella modulates host cell apoptosis in a stage-specific manner, suppressing apoptosis in the early phase to promote its intracellular development and triggering apoptosis in later stages to facilitate parasite egress and disease progression. This study established an in vitro infection model using 60 fifteen-day-old chick embryo cecal epithelial cells and infecting the cells with Eimeria tenella sporozoites at a 1:1 ratio of host cells to sporozoites. The aim was to examine the relationship between parasitic infection and the apoptotic response of host cells in the chick embryo cecal epithelial cells infected with E. tenella. The roles of the mitochondrial permeability transition pore (MPTP) and cytochrome c in intrinsic apoptosis were examined through the application of cyclosporine A (CsA), N, N, N’, N’-tetramethyl-1,4-phenylenediamine (TMPD), and ascorbate (Asc). TUNEL staining, ELISA, and flow cytometry were performed to evaluate apoptotic rates. CsA, TMPD, and Asc significantly (p < 0.01) decreased cytochrome c release, caspase-9 activation, and apoptotic rates from 24 to 120 h post-E. tenella infection. These findings highlight the significance of cytochrome c-mediated, mitochondria-dependent apoptotic pathways in parasitized chick embryo cecal epithelial cells.

Several alkaloids found in the Zanthoxylum genus have demonstrated significant anticancer activity. However, the antitumor effects of Ethoxychelerythrine (Eth) have not been previously reported. Cell viability, colony formation, apoptosis and cell cycle analysis, intracellular and reactive oxygen species (ROS), mitochondrial membrane potential (MMP) levels of Eth against SW480 cells were evaluated. Subcutaneously transplanted SW480 cells model was used to determine the effect of Eth on tumor growth in vivo. Inflammation levels, angiogenic factors, pathological observations, quantitative reverse-transcription PCR (qRT-PCR), quantitative proteomics, metabolite profiles and western blotting were conducted. It found that Eth significantly inhibited the proliferation of SW480 and HT29 cells in vitro, with stronger inhibitory activity observed against SW480 cells. Therefore, subsequent studies focused on SW480 cells. In vitro, we observed that Eth arrested the cell cycle at the G0/G1 phase, decreased MMP levels, elevated cellular ROS levels, and induced mitochondrial apoptosis. In vitro, Eth significantly inhibited tumor proliferation and metastasis, and regulated the molecule levels of angiogenesis and inflammatory factors in serum, as well as apoptotic protein in tumor tissues. The serum proteomic revealed that the differential proteins were primarily involved in the PI3K/AKT/mTOR pathway, including laminin β1 (Lamb1), and type I collagen (Col1a1). Metabolomics showed that many abnormal levels of metabolites regulated by the PI3K/AKT/mTOR pathway were obviously reversed towards normal levels after Eth intervention. The correlation analysis between the two-omics revealed that different proteins in the PI3K/AKT pathway, particularly lactate dehydrogenase B (LDHB) and glutathione synthetase (GSS), can interact with most of different metabolites. In summary, Eth exerts anti-tumour effects by inhibiting the activation of the PI3K/AKT/mTOR pathway, which in turn activates mitochondrial apoptosis. Eth may be considered in the development of drugs for relieving colon cancer patients in the future., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The animal study protocol was approved by the Animal Ethics Committee of the Henan University of Chinese Medicine (protocol code DWLL202003253)., (© 2025. The Author(s).)

Nanomaterial-based mild photothermal therapy (mPTT, 42-45 °C) with controllable light-triggered thermal diffusion holds potential in reversing immunosuppressive microenvironments and activating antitumor immunity in tumors. However, the limited antitumor efficacy of mPTT alone always requires sophisticated synergistic strategies to promote its overall therapeutic outcome. Herein, we employ an immune-active natural polymer, peach gum polysaccharide (PGP), as the nanocarrier to encapsulate the photothermal reagent of TTQPL to yield PLA-T nanoparticles (NPs). We demonstrate the capability of a PGP-based encapsulation matrix in stimulating the polarization of M0/M2-like macrophages to the pro-inflammatory M1 phenotype. Under NIR light irradiation, PLA-T NPs induce profound apoptosis of CT26 cells by a mitochondrial pathway, which leads to upregulated Bax, downregulated Bcl-2, and released cytochrome C (Cyt C) from the mitochondria to the cytoplasm. Additionally, such a formulation synergistically exploits the intrinsic immunoregulatory function of PGP and NIR light-triggered mPTT, showing superior in vivo antitumor effects by evoking the adaptive immune response with a reversed immunosuppressive tumor microenvironment. In summary, this work highlights the potential of PGP as a natural polymer carrier to deliver therapeutic reagents, offering synergistically enhanced immune activation with superior antitumor performance of phototherapy.

Understanding the interplay between gasotransmitters is essential for unlocking their therapeutic potential. However, achieving spatiotemporally controlled co-delivery to target cells remains a significant challenge. Herein, we propose an innovative strategy for the intracellular co-delivery of carbon monoxide (CO) and nitric oxide (NO) gasotransmitters under clinically relevant wavelengths. This approach rationally couples aerobic photooxidative and anaerobic photocatalytic reactions within a polymeric micelle platform, using palladium(II) tetraphenyltetrabenzoporphyrin (PdTPTBP) as both photosensitizer and photocatalyst. Notably, the photooxidation-mediated release of CO generates a local hypoxic microenvironment, which facilitates the photoredox catalyzed release of NO. This self-adaptive micelle platform enables efficient uptake by tumor cells and intracellular co-delivery of CO and NO under 630 nm light irradiation, demonstrating potent anti-tumor activity in a 4T1 tumor-bearing mouse model via the synergistic induction of mitochondrial apoptosis., (© 2025 Wiley-VCH GmbH.)