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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.

Comprehensive Summary: A chemical investigation of the deep‐sea‐derived fungus Penicillium allii‐sativi MCCC 3A00580 resulted in the discovery of four new meroterpenoids (1—4) and one related known co‐metabolite (5). These meroterpenoids showcase unique carbon skeletons featuring a common drimane sesquiterpene part with highly diverse polyketide units. Particularly, compound 1 incorporates a salicylic acid moiety while 2 possesses a rare peroxide bridge in the polyketide part. The structures of new compounds were assigned by extensive spectroscopic analysis, quantum calculations, and biogenetic considerations. Notably, 3 significantly blocked the mTOR signaling pathway, resulting in the arrest of cell cycle at G0‐G1 phase and triggering mitochondrial apoptosis in Hela cells. While the previously reported co‐metabolite macrophorin A (MPA) effectively triggered cell death in MDA‐MB‐231 cancer cells by activating apoptosis pathways involving death receptors, mitochondria, mTOR, and TNF. [ABSTRACT FROM AUTHOR]

Paclitaxel (PTX), an antimitotic drug from the taxanes group, prevents the proliferation of breast cancer cells through mitosis arrest and activation by a cascade of signaling pathways that lead to apoptosis. Mitochondria is one of the important signaling routes for inducing apoptosis. For mitochondria targeting, triphenylphosphonium (TPP) with a delocalized charge and hydrophobic nature was utilized as a moiety to facilitate penetration through a phospholipid membrane of mitochondria. PTX-TPP was synthesized via pH-sensitive ester bond between hydroxyl groups of PTX and carboxylic acid of (4-carboxybutyl) TPP. Then PTX-TPP prodrug encapsulated in alginate nanoparticles, which were self-assembled by the ionotropic complexation technique for enhancement of mitochondrial apoptosis in breast cancer cells. The loading of PTX-TPP conjugation in self-assembled alginate nanoparticles was 16.5% and the particle size of nanoparticles was 123 nm with zeta potential around − 25.8 Mv. The in vitro cytotoxicity and IC50 of PTX-TPP nanoparticles in the growth of MCF7 cancer cell increased 6.3-fold higher than free PTX. The early apoptotic cells and the late apoptotic/necrotic cells for PTX-TPP nanoparticles were 11.6 and 3.9-fold higher than free PTX. This study indicated this mitochondrial-targeted self-assembled nanoparticles can inhibit the tumor cell growth of breast cancer. [ABSTRACT FROM AUTHOR]

4',5,7-Trihydroxy-8-methoxyflavone is an anticancer monomer component isolated from the traditional Chinese medicine Sorbaria sorbifolia. 4',5-Dihydroxy-7-piperazinemethoxy-8-methoxy flavonoids (DMF) with good solubility and anti-tumor effects was obtained by chemical modification in the early stage. This study explored the mechanism by which DMF regulates the mitochondrial apoptosis of human hepatoma cells through Bcl-2-associated transcription factor 1 (Bclaf1). DMF inhibited the proliferation of human hepatoma cells in a concentration- and time-dependent manner and induced cell mitochondrial apoptosis. The molecular docking and cell assay results demonstrated that DMF inhibits Bclaf1 expression by binding to its active site. Lentivirus transfection was used to construct cells with stable knockout and overexpression of Bclaf1, and a Hep3B xenograft model was constructed in nude mice. The mechanism by which DMF induced the mitochondrial apoptosis of human hepatoma cells through Bclaf1 was further verified in vitro and in vivo. These findings indicated that DMF induced human hepatoma cell mitochondrial apoptosis through Bclaf1. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive forms of pancreatic cancer with a poor prognosis. YAP1 expression is markedly elevated in PDAC, but how it works is not clear. GL-V9, a derivative of the natural compound wogonin, effectively fights a variety of tumors; however, its effect on PDAC has not yet been studied. Methods: TCGA database analysis, Western blots, immunofluorescence, and real-time PCR were used to evaluate GL-V9's effect on YAP1 expression and mRNA levels. Immunofluorescence was used to examine the co-location of YAP1 with LAMP2 and p62. Co-immunoprecipitation was used to assess the binding of YAP1 to ubiquitin, p62, and TEAD1. A PDAC graft tumor model was used to test GL-V9's pharmacological effects. Western blots and immunohistochemistry were used to measure apoptosis- and autophagy-related protein expression. Results: GL-V9 effectively promoted the degradation of YAP1, reduced YAP1 nuclear localization, and induced mitochondrial apoptosis in PDAC cells. YAP1 overexpression led to the upregulation of Bcl-2 and attenuated the caspase cascade induced by GL-V9. Furthermore, we demonstrated that GL-V9 induced autophagosome–lysosome fusion via the AKT/mTOR/TFEB pathway, leading to mitochondrial apoptosis in PDAC cells. In vivo studies also confirmed that GL-V9 exerts anti-tumor effects by suppressing YAP1 expression, while also activating autophagy and inducing mitochondrial apoptosis in BXPC-3-bearing BALB/c nude mice. Conclusions: Our findings underscore the importance of autophagy-mediated YAP1 degradation in PDAC, providing a novel molecular rationale (GL-V9) as a promising treatment for this disease. [ABSTRACT FROM AUTHOR]

Dysfunction of Schwann cells, including cell apoptosis, autophagy inhibition, dedifferentiation, and pyroptosis, is a pivotal pathogenic factor in induced diabetic peripheral neuropathy (DPN). Histone deacetylases (HDACs) are an important family of proteins that epigenetically regulate gene transcription by affecting chromatin dynamics. Here, we explored the effect of HDAC1 on high glucose-cultured Schwann cells. HDAC1 expression was increased in diabetic mice and high glucose-cultured RSC96 cells, accompanied by cell apoptosis. High glucose also increased the mitochondrial pathway apoptosis-related Bax/Bcl-2 and cleaved caspase-9/caspase-9 ratios and decreased endoplasmic reticulum response-related GRP78, CHOP, and ATF4 expression in RSC96 cells (P < 0.05). Furthermore, overexpression of HDAC1 increased the ratios of Bax/Bcl-2, cleaved caspase-9/caspase-9, and cleaved caspase-3 and reduced the levels of GRP78, CHOP, and ATF4 in RSC96 cells (P < 0.05). In contrast, knockdown of HDAC1 inhibited high glucose-promoted mitochondrial pathway apoptosis and suppressed the endoplasmic reticulum response. Moreover, RNA sequencing revealed that U4 spliceosomal RNA was significantly reduced in HDAC1-overexpressing RSC96 cells. Silencing of U4 spliceosomal RNA led to an increase in Bax/Bcl-2 and cleaved caspase-9 and a decrease in CHOP and ATF4. Conversely, overexpression of U4 spliceosomal RNA blocked HDAC1-promoted mitochondrial pathway apoptosis and inhibited the endoplasmic reticulum response. In addition, alternative splicing analysis of HDAC1-overexpressing RSC96 cells showed that significantly differential intron retention (IR) of Rpl21, Cdc34, and Mtmr11 might be dominant downstream targets that mediate U4 deficiency-induced Schwann cell dysfunction. Taken together, these findings indicate that HDAC1 promotes mitochondrial pathway-mediated apoptosis and inhibits the endoplasmic reticulum stress response in high glucose-cultured Schwann cells by decreasing the U4 spliceosomal RNA/IR of Rpl21, Cdc34, and Mtmr11. [ABSTRACT FROM AUTHOR]

Malignant gliomas are an exceptionally lethal form of cancer with limited treatment options. Dihydroartemisinin (DHA), a sesquiterpene lactone antimalarial compound, has demonstrated therapeutic effects in various solid tumors. In our study, we aimed to investigate the mechanisms underlying the anticancer effects of DHA in gliomas. To explore the therapeutic and molecular mechanisms of DHA, we employed various assays, including cell viability, flow cytometry, mitochondrial membrane potential, glucose uptake and glioma xenograft models. Our data demonstrated that DHA significantly inhibited glioma cell proliferation in both temozolomide-resistant cells and glioma stem-like cells. We found that DHA-induced apoptosis occurred via the mitochondria-mediated pathway by initiating mitochondrial dysfunction before promoting apoptosis. Moreover, we discovered that DHA treatment substantially reduced the expression of the mitochondrial biogenesis-related gene, ERRα, in glioma cells. And the ERRα pathway is a critical target in treating glioma with DHA. Our results also demonstrated that the combination of DHA and temozolomide synergistically inhibited the proliferation of glioma cells. In vivo, DHA treatment remarkably extended survival time in mice bearing orthotopic glioblastoma xenografts. Thus, our findings suggest that DHA has a novel role in modulating cancer cell metabolism and suppressing glioma progression by activating the ERRα-regulated mitochondrial apoptosis pathway. [ABSTRACT FROM AUTHOR]

We investigated the effects of mitochondrial damage via carbon ion irradiation on the proliferation of human non-small cell lung cancer (A549) cells by monitoring mitochondrial morphological changes, mitochondrial membrane potential transformation, release of membrane-associated proteins, and mitophagy. A549 cell proliferation and activity were monitored by CCK-8 and colony formation assays. Changes in mitochondrial morphology and mitochondrial membrane potential were detected by mitochondrial membrane-specific fluorescence staining. Expression of associated proteins was detected by western blot and real-time quantitative PCR. Annexin V-FITC and PI staining were used to detect cell apoptosis. Mitophagy was detected by immunofluorescence co-localization and western blot. The apoptosis rate of mitochondria-lacking A549 cells after carbon ion irradiation was also quantitated. Irradiation with carbon ions at dose of 4 Gy significantly depressed the proliferation capacity of A549 cells, and induced mitochondrial shrinkage and decreased mitochondrial membrane potential. Levels of mitochondrial membrane protein Bax/Bak, and intermembrane proteins Cyto-C and SMAC were elevated, with increased apoptosis and mitophagy. In cells depleted of mitochondria, carbon ion irradiation exerted no significant effect on A549 cell apoptosis. Carbon ion irradiation can inhibit A549 cell proliferation. The half maximal inhibitory exposure dose is 4 Gy. Carbon ions lose their anti-proliferative function in mitochondria-free A549 cells. In summary, carbon ion irradiation can decrease mitochondrial membrane potential and induce the release of pro-apoptotic proteins, thereby inhibiting A549 cell proliferation.

Abstract Long-term exposure to hyperglycemic conditions leads to β-cell dysfunction, particularly mitochondrial dysfunction, and inflammatory and oxidative stress responses, which are considered the primary causes of β-cell death and the hallmarks of diabetes. Plant-active ingredients may play a key role in glycemic control. Epigallocatechin gallate (EGCG) is a characteristic catechin derived from tea that possesses anti-diabetic properties. Nonetheless, its underlying mechanisms remain elusive. Herein, the protective role of EGCG on high glucose (33 mM)-induced pancreatic beta cell dysfunction and its possible molecular mechanisms were investigated. Briefly, MIN6 cells were treated with glucose and EGCG (10 µM, 20 µM, and 40 µM) for 48 h. Our results revealed that EGCG dose-dependently restored mitochondrial membrane potential and concomitantly alleviated cell apoptosis. Mechanistically, the expression level of apoptotic protein BAX and Dynamic related protein 1 (DRP1) was significantly downregulated following EGCG treatment, whereas that of the anti-apoptotic protein BCL-2 was significantly upregulated. Taken together, EGCG alleviated high glucose-induced pancreatic beta cell dysfunction by targeting the DRP1-related mitochondrial apoptosis pathway and thus can serve as a nutritional intervention for the preservation of beta cell dysfunction in patients with type 2 diabetes mellitus.

Background: Leukopenia can be caused by chemotherapy, which suppresses bone marrow function and can impact the effectiveness of cancer treatment. Qijiao Shengbai Capsule (QJSB) is commonly used to treat leukopenia, but the specific bioactive components and mechanisms of action are not well understood. Objectives and results: This study aimed to analyze the active ingredients of QJSB and its potential targets for treating leukopenia using network pharmacology and molecular docking. Through a combination of serum pharmacochemistry, multi-omics, network pharmacology, and validation experiments in a murine leukopenia model, the researchers sought to understand how QJSB improves leukopenia. The study identified 16 key components of QJSB that act in vivo to increase the number of white blood cells in leukopenic mice. Multi-omics analysis and network pharmacology revealed that the PI3K-Akt and MAPK signaling pathways are important in the treatment of leukopenia with QJSB. Five specific targets (JUN, FOS, BCl-2, CASPAS-3) were identified as key targets. Conclusion: Validation experiments confirmed that QJSB regulates genes related to cell growth and inhibits apoptosis, suggesting that apoptosis may play a crucial role in leukopenia development and that QJSB may improve immune function by regulating apoptotic proteins and increasing CD4+ T cell count in leukopenic mice. [ABSTRACT FROM AUTHOR]

Background: It is unknown how cancer cells override apoptosis and maintain progression under nutrition-deprived conditions within the tumor microenvironment. Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting reaction in gluconeogenesis, which is an essential metabolic alteration that is required for the proliferation of cancer cells under glucose-limited conditions. However, if PCK-mediated gluconeogenesis affects apoptotic cell death of non small cell lung cancer (NSCLC) and its potential mechanisms remain unknown. Methods: RNA-seq, Western blot and RT-PCR were performed in A549 cell lines cultured in medium containing low or high concentrations of glucose (1 mM vs. 20 mM) to gain insight into how cancer cells rewire their metabolism under glucose-restriction conditions. Stable isotope tracing metabolomics technology (LC-MS) was employed to allow precise quantification of metabolic fluxes of the TCA cycle regulated by PCK2. Flow Cytometry was used to assess the rates of early and later apoptosis and mitochondrial ROS in NSCLC cells. Transwell assays and luciferase-based in vivo imaging were used to determine the role of PCK2 in migration and invasion of NSCLC cells. Xenotransplants on BALB/c nude mice to evaluate the effects of PCK2 on tumor growth in vivo. Western blot, Immunohistochemistry and TUNEL assays to evaluate the protein levels of mitochondrial apoptosis. Results: This study report that the mitochondrial resident PCK (PCK2) is upregulated in dependent of endoplasmic reticulum stress-induced expression of activating transcription factor 4 (ATF4) upon glucose deprivation in NSCLC cells. Further, the study finds that PCK2-mediated metabolism is required to decrease the burden of the TCA cycles and oxidative phosphorylation as well as the production of mitochondrial reactive oxygen species. These metabolic alterations in turn reduce the activation of Caspase9-Caspase3-PARP signal pathway which drives apoptotic cell death. Importantly, silencing PCK2 increases apoptosis of NSCLC cells under low glucose condition and inhibits tumor growth both in vitro and in vivo. Conclusion: In summary, PCK2-mediated metabolism is an important metabolic adaptation for NSCLC cells to acquire resistance to apoptosis under glucose deprivation. [ABSTRACT FROM AUTHOR]

Laryngeal squamous cell carcinoma is a challenging malignancy with increasing incidence globally, necessitating the exploration of novel therapeutic strategies. Platycodin D, a saponin derived from Platycodon grandiflorum, has shown promise in cancer therapy, exhibiting anticancer effects in various tumor types. However, the specific mechanisms of action of Platycodin D in laryngeal squamous cell carcinoma remain poorly understood. Therefore, our study aimed to investigate the anticancer effects of Platycodin D in laryngeal squamous cell carcinoma. We revealed that Platycodin D effectively inhibited the proliferation of laryngeal squamous cell carcinoma cells and induced mitochondrial apoptosis. Furthermore, we found that Platycodin D downregulated the expression of S-phase kinase-associated protein 2, indicating a novel target for PD's action. Finally, the suppression of S-phase kinase-associated protein 2 by Platycodin D led to cell cycle arrest and enhanced apoptosis in laryngeal squamous cell carcinoma cells. Collectively, these findings underscore the potential of Platycodin D as a novel therapeutic agent for laryngeal squamous cell carcinoma, with implications for targeting mitochondrial apoptosis and S-phase kinase-associated protein 2 in cancer treatment. [ABSTRACT FROM AUTHOR]

Long-term exposure to hyperglycemic conditions leads to β-cell dysfunction, particularly mitochondrial dysfunction, and inflammatory and oxidative stress responses, which are considered the primary causes of β-cell death and the hallmarks of diabetes. Plant-active ingredients may play a key role in glycemic control. Epigallocatechin gallate (EGCG) is a characteristic catechin derived from tea that possesses anti-diabetic properties. Nonetheless, its underlying mechanisms remain elusive. Herein, the protective role of EGCG on high glucose (33 mM)-induced pancreatic beta cell dysfunction and its possible molecular mechanisms were investigated. Briefly, MIN6 cells were treated with glucose and EGCG (10 µM, 20 µM, and 40 µM) for 48 h. Our results revealed that EGCG dose-dependently restored mitochondrial membrane potential and concomitantly alleviated cell apoptosis. Mechanistically, the expression level of apoptotic protein BAX and Dynamic related protein 1 (DRP1) was significantly downregulated following EGCG treatment, whereas that of the anti-apoptotic protein BCL-2 was significantly upregulated. Taken together, EGCG alleviated high glucose-induced pancreatic beta cell dysfunction by targeting the DRP1-related mitochondrial apoptosis pathway and thus can serve as a nutritional intervention for the preservation of beta cell dysfunction in patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

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.

Phellinus igniarius (PI) has various kinds of biological activities, such as antitumour activities, and polysaccharides are one of its main components. In this study, polysaccharides from PI (PIP) were prepared, purified, analysed for their structure and investigated for their antitumour activity and mechanism in vitro. PIP consists of 12138 kDa of carbohydrates containing 90.5 ± 1.6% neutral carbohydrates. PIP consists of glucose, galactose, mannose, xylose, D-fructose, L-guluronic acid, glucosamine hydrochloride, rhamnose, arabinose and D-mannoturonic acid. PIP can significantly inhibit HepG2 cell proliferation, induce cell apoptosis and also inhibited migration and invasion in a concentration-dependent manner. PIP increased reactive oxygen species (ROS), increased the expression of p53, and induced cytochrome c release into the cytoplasm to activate caspase-3. PIP is a promising potential candidate for the therapeutic treatment of hepatic carcinoma via the ROS-mediated mitochondrial apoptosis pathway. [ABSTRACT FROM AUTHOR]

Background: Hexokinase (HK) is the first rate‐limiting enzyme of glycolysis, which can convert glucose to glucose‐6‐phosphate. There are several subtypes of HK, including HK2, which is highly expressed in a variety of different tumors and is closely associated with survival. Methods: Non‐small cell lung cancer (NSCLC) A549 cells with stable overexpression and knockdown of HK2 were obtained by lentivirus transfection. The effects of overexpression and knockdown of HK2 on proliferation, migration, invasion, and glycolytic activity of A549 cells were investigated. The effects on apoptosis were also analyzed using western blot and flow cytometry. In addition, the mitochondria and cytoplasm were separated and the expression of apoptotic proteins was detected by western blot respectively. Results: Upregulation of HK2 could promote glycolysis, cell proliferation, migration, and invasion, which would be inhibited through the knockdown of HK2. HK2 overexpression contributed to cisplatin resistance, whereas HK2 knockdown enhanced cisplatin‐induced apoptosis in A549 cells. Conclusions: Overexpression of HK2 can promote the proliferation, migration, invasion, and drug resistance of A549 cells by enhancing aerobic glycolysis and inhibiting apoptosis. Reducing HK2 expression or inhibiting HK2 activity can inhibit glycolysis and induce apoptosis in A549 cells, which is expected to be a potential treatment method for NSCLC. [ABSTRACT FROM AUTHOR]

Imidacloprid (IMI) is a neonicotinoid insecticide with the highest global market share, and IMI exposure in the environment can negatively affect many nontarget organisms (a general term for organisms affected by drugs other than target organisms). Resveratrol (RSV), a non‐flavonoid polyphenolic organic compound derived from peanuts, grapes, and other plants, has anti‐inflammatory and antioxidant effects. It is currently unclear how RSV protects against cell damage caused by IMI. Therefore, we established an experimental model of chicken lymphocyte lines exposed to 110 μg/mL IMI and/or 0.5 μM RSV for 24 h. According to the experimental results, IMI markedly raised intracellular reactive oxygen species levels and diminished the activity of the cellular antioxidant enzymes (CAT, SOD, and GPx), leading to MDA accumulation and decreased T‐AOC. JNK, ERK, and P38, the essential components of the mitogen‐activated protein kinase (MAPK) signaling pathway, were also expressed more when IMI was present. Additionally, IMI resulted in upregulation of mitochondrial apoptosis (Caspase 3, Caspase 9, Bax, and Cyt‐c) and necroptosis (Caspase 8, RIPK1, RIPK3, and MLKL) related factors expression, downregulation of Bcl‐2 expression, induction of upregulation of cytokine IL‐6 and TNF‐α expression, and downregulation of IFN‐γ expression. The combined treatment of RSV and IMI significantly reduced cellular oxidative stress levels, inhibited the MAPK signaling pathway, and alleviated IMI‐induced mitochondrial apoptosis, necroptosis, and immune dysfunction. To summarize, RSV antagonized IMI‐induced mitochondrial apoptosis, necroptosis, and immune dysfunction in chicken lymphocyte lines by inhibiting the ROS/MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate and discuss the mechanism of fluoride-induced osteoblast apoptosis in TGF-β2 signaling pathway. Materials and Methods: The osteoblasts were divided into 0 (control group), 5.0, 10.0, 20.0, and 40.0 mg/L sodium-fluoride induction groups, and the cells were collected after 24 hr and 48 hr induction (T1 and T2, respectively) to detect the changes in the mitochondrial-apoptosis pathway-related molecules (FoxO1, BAD, BCL-XL, BCL-2, and BAX). At the same time, the apoptosis index of fluoride-exposed osteoblasts was detected by flow cytometry. Results: The expression of TGF-β2 in the osteoblasts decreased with the increase in fluoride dose at T1 and T2. The expression levels of FoxO1 increased significantly at T1 and T2 in each dose group except for the 40 mg/L group (which had decreased expression). The expressions of p-BAD, BCL-XL, BCL-2, BAX, and other molecules increased with the increase in fluoride dose and exposure time. Conclusion: Fluoride can directly activate the TGF-β2 signaling molecules in osteoblasts and affect apoptosis. TGF-β2 plays an anti-apoptosis role in fluoride-exposed osteoblasts through the mitochondrial-apoptosis pathway. [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to investigate the effects of Chinese herbal formula Weichang'an (WCA) on the proliferation and mitochondria-mediated apoptosis of human gastric cancer cells.

Abstract Background Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, with poor outcomes for patients with metastatic disease or chemotherapy resistance. Cirsiliol is a recently found flavonoid with anti-tumor effects in various tumors. However, the effects of cirsiliol in the regulation of aggressive behaviors of OS remain unknown. Methods The effect of cirsiliol on the proliferation of OS cells was detected using a cell counting kit-8 (CCK-8) assay and 5-ethynyl-2′-deoxyuridine (EdU) staining, while cell apoptosis was detected using flow cytometry. Immunofluorescence was applied to visualize the expression level of the mitochondria, lysosomes and microtubule-associated protein light chain 3 (LC3). A computational molecular docking technique was used to predict the interaction between cirsiliol and the AKT protein. The impact of cirsiliol on resistance was investigated by comparing it between a methotrexate (MTX)-sensitive OS cell line, U2OS, and a MTX-resistant OS cell line, U2OS/MTX. Finally, in situ xenogeneic tumor models were used to validate the anti-tumor effect of cirsiliol in OS. Results Cirsiliol inhibited cell proliferation and induced apoptosis in both U2OS and U2OS/MTX300 OS cells. In addition, treatment with cirsiliol resulted in G2 phase arrest in U2OS/MTX300 and U2OS cells. Cell fluorescence probe staining results showed impaired mitochondria and increased autophagy in OS cells after treatment with cirsiliol. Mechanistically, it was found that cirsiliol targeted AKT by reducing the phosphorylation of AKT, which further activated the transcriptional activity of forkhead Box O transcription factor 1 (FOXO1), ultimately affecting the function of OS cells. Moreover, in situ tumorigenesis experiments showed that cirsiliol inhibited the tumorigenesis and progression of OS in vivo. Conclusions Cirsiliol inhibits OS cell growth and induces cell apoptosis by reducing AKT phosphorylation and further promotes FOXO1 expression. These phenomena indicate that cirsiliol is a promising treatment option for OS.

Pollution of aquatic environment by difenoconazole (DFZ) significantly affects survival and safety of freshwater aquaculture. Due to its anti-inflammatory and antioxidant properties, plant-derived quercetin (QUE) is often used as a dietary supplement. The main purpose of this study was to explore the protective effect of QUE on heart damage caused by exposure to pesticide DFZ and the potential mechanisms of these effects. This study found that QUE could effectively reduce the myocardial enzyme spectrum index of carp after exposure to DFZ, increase the levels of total antioxidant capacity (T-AOC), glutathione (GSH), and catalase (CAT), inhibit the content of malondialdehyde (MDA), and increase the transcription levels of superoxide dismutase (sod), glutathione peroxidase (gsh-px), and cat. By reducing the expression of keap1, QUE increased the transcription levels of nrf2 and nqo-1, reduced the production of reactive oxygen species (ROS) in the heart after exposure to DFZ, and restored the redox homeostasis of the heart. QUE upregulated the expression of anti-inflammatory cytokines il-10 and tgf-β1 levels, downregulated the transcription levels of pro-inflammatory factor inos, il-1β, il-6 and tnf-α, and alleviated the in vivo redox imbalance caused by exposure to DFZ, leading to myocardial interstitial inflammatory cell infiltration. The results showed that QUE inhibited the apoptosis after exposure to DFZ by affecting the expression of apoptotic factors in the mitochondrial apoptotic pathway. In summary, QUE can effectively decrease myocardial injury caused by exposure to DFZ in aquatic environment.

Background: Wnt signalling pathway, is mediated by members of T-cell factor (TCF) transcription factors family, is essential for the control of epithelial cell proliferation and death. Glucose transporter-5 (GLUT5), fructose-specific transporter, is also important in allowing transcellular fructose uptake. The goal of this work to determine how the High fructose Corn Syrup (HFCS) affected Wingless-related integration site (Wnt) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling in the 7,12 –dimethylbenzaanthracene (DMBA)-induced hamster buccal pouch carcinogenesis (HBPCs) model. Methods: Four groups of hamsters were created. For 12 weeks, 0.5 % DMBA was applied 3 times/week to the left side buccal pouches of the hamsters in groups (2 & 4). Additionally, the animals in groups (3 & 4) were given through drinking water of HFCS 25 %. The control animals were from group 1. By using western blot analysis, signalling network markers of the GLUT-5, Wnt, TCF-4, GSK-3β and NF-κB as well as mitochondrial apoptotic pathway marker expression B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and cyclooxygenase – 2 (COX-2) was assessed. Results: Drinking water uptake of 25% HFCS encouraged progress of HBP carcinomas by constitutive stimulating of the Wnt pathway via GSK-3β overexpression. HFCS suppressed Wnt signalling which contributed the NF-κB attenuation and changes the signalling markers in apoptotic network. Conclusions: Our hypothesis suggests a mechanically crosstalk between Wnt and NF-κB signalling pathways in HBP carcinomas that is developed by HFCS. HFCS that targets the Wnt pathway and its downstream signalling mediators could be additive reason for cancer development.

Porcine epidemic diarrhea virus (PEDV), a member of the Alpha-coronavirus genus in the Coronaviridae family, induces acute diarrhea, vomiting, and dehydration in neonatal piglets. This study aimed to investigate the genetic dependencies of PEDV and identify potential therapeutic targets by using a single-guide RNA (sgRNA) lentiviral library to screen host factors required for PEDV infection. Protein kinase C θ (PKCθ), a calcium-independent member of the PKC family localized in the cell membrane, was found to be a crucial host factor in PEDV infection. The investigation of PEDV infection was limited in Vero and porcine epithelial cell-jejunum 2 (IPEC-J2) due to defective interferon production in Vero and the poor replication of PEDV in IPEC-J2. Therefore, identifying suitable cells for PEDV investigation is crucial. The findings of this study reveal that human embryonic kidney (HEK) 293T and L929 cells, but not Vero and IPEC-J2 cells, were suitable for investigating PEDV infection. PKCθ played a significant role in endocytosis and the replication of PEDV, and PEDV regulated the expression and phosphorylation of PKCθ. Apoptosis was found to be involved in PEDV replication, as the virus activated the PKCθ-B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) axis in HEK293T and L929 cells to increase viral endocytosis and replication via mitochondrial apoptosis. This study demonstrated the suitability of HEK293T and L929 cells for investigating PEDV infection and identified PKCθ as a host factor essential for PEDV infection. These findings provide valuable insights for the development of strategies and drug targets for PEDV infection. [ABSTRACT FROM AUTHOR]

Remote Ischemic Preconditioning (RIPC) can reduce myocardial ischemia-reperfusion injury, but its mechanism is not clear. In order to explore the mechanism of RIPC in myocardial protection, we collected myocardial specimens during cardiac surgery in children with tetralogy of Fallot for sequencing. Our study found RIPC reduces the expression of the calcium channel subunit cacna2d3, thereby impacting the function of calcium channels. As a result, calcium overload during ischemia-reperfusion is reduced, and the activation of calpain 1 is inhibited. This ultimately leads to a decrease in calpain 1 cleavage of Bax, consequently inhibiting increased mitochondrial permeability-mediated apoptosis. Notably, in both murine and human models of myocardial ischemia-reperfusion injury, RIPC inhibiting the expression of the calcium channel subunit cacna2d3 and the activation of calpain 1, improving cardiac function and histological outcomes. Overall, our findings put forth a proposed mechanism that elucidates how RIPC reduces myocardial ischemia-reperfusion injury, ultimately providing a solid theoretical foundation for the widespread clinic application of RIPC. [Display omitted] • Remote ischemic preconditioning reduces myocardial ischemia-reperfusion injury. • RIPC can reduce calcium overload during myocardial ischemia-reperfusion by decreasing the expression of the calcium channel subunit cacna2d3. • Remote ischemic preconditioning decreased the expression of calpain 1 in myocardial ischemia-reperfusion injury. • Calpain 1 cleavage activates Bax in myocardial ischemia-reperfusion injury, ultimately resulting in mitochondrial damage. [ABSTRACT FROM AUTHOR]

I propose a new strategy to suppress human cancer completely with two entirely new drug compounds exploiting cancer's Warburg effect characterized by a defective mitochondrial aerobic respiration, substituted by cytosolic aerobic fermentation/glycolysis of D-(+)-glucose into L-(+)-lactic acid. The two essentially new drugs, compound 1 [P(op)T(est)162] and compound 3 (PT167), represent new highly symmetric, four-bladed propeller-shaped polyammonium cations. The in vitro antineoplastic highly efficacious drug compound 3 represents a covalent combination of compound 1 and compound 2 (PT166). The intermediate drug compound 2 is an entirely new colchic(in)oid derivative synthesized from colchicine. Compound 2's structure was determined using X-ray crystallography. Compound 1 and compound 3 were active in vitro versus 60 human cancer cell lines of the National Cancer Institute (NCI) Developmental Therapeutics Program (DTP) 60-cancer cell testing. Compound 1 and compound 3 not only stop the growth of cancer cells to ±0% (cancerostatic effect) but completely kill nearly all 60 cancer cells to a level of almost −100% (tumoricidal effect). Compound 1 and compound 3 induce mitochondrial apoptosis (under cytochrome c release) in all cancer cells tested by (re)activating (in most cancers impaired) p53 function, which results in a decrease in cancer's dysregulated cyclin D1 and an induction of the cell cycle-halting cyclin-dependent kinase inhibitor p21Waf1/p21Cip1. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) is a malignant tumor with a high mortality rate. Resistance to chemotherapy remains a major challenge related to cancer treatment, and increasing the sensitivity of cancer cells to therapeutic drugs is a major focus of cancer treatment. Aims: We purposed to explore the role of Metformin in CCA involved in chemotherapeutic sensitivity and Pyruvate kinase M2 (PKM2) through regulating mitochondrial apoptosis in the present study. Methods: CCA cell lines of HCC9810 and RBE were treated with Metformin companied with antagonists or agonists of PKM2, cells sensitivity to Gemcitabine, cell migration and invasion along with apoptosis, which is mediated by JC-1 and LDH were assayed. Results: Our results indicated that Metformin and Gemcitabine exhibit synergistic effect on inhibition of cholangiocarcinoma cell viability, cell migration and invasion as well as promotion apoptosis of cholangiocarcinoma cells. In vivo, Metformin combined with Gemcitabine has cooperation in inhibiting the growth of cholangiocarcinoma cell-derived tumors. Moreover, Metformin and Gemcitabine inhibited expression of PKM2 and PDHB in HCC9810 and RBE. Conclusion: Our study suggested that Metformin may increase the response of cholangiocarcinoma cells to Gemcitabine by suppressing PKM2 to activate mitochondrial apoptosis. [ABSTRACT FROM AUTHOR]

Chronic myelogenous leukemia (CML) that is resistant to tyrosine kinase inhibitors is one of the deadliest hematologic malignancies, and the T315I mutation in the breakpoint cluster region‐Abelson (BCR‐ABL) kinase domain is the most prominent point mutation responsible for imatinib resistance in CML. Glaucocalyxin A (GLA), a natural bioactive product derived from the Rabdosia rubescens plant, has strong anticancer activity. In this study, the effect and molecular mechanism of GLA on imatinib‐sensitive and imatinib‐resistant CML cells harboring T315I mutation via a combined deconvolution strategy of chemoproteomics and label‐free proteomics is investigated. The data demonstrated that GLA restrains proliferation and induces mitochondria‐dependent apoptosis in both imatinib‐sensitive and resistant CML cells. GLA covalently binds to the cysteine residues of mitochondrial voltage‐dependent anion channels (VDACs), resulting in mitochondrial damage and overflow of intracellular apoptotic factors, eventually leading to apoptosis. In addition, the combination of GLA with elastin, a mitochondrial channel VDAC2/3 inhibitor, enhances mitochondria‐dependent apoptosis in imatinib‐sensitive and ‐resistant CML cells, representing a promising therapeutic approach for leukemia treatment. Taken together, the results show that GLA induces mitochondria‐dependent apoptosis via covalently targeting VDACs in CML cells. GLA may thus be a candidate compound for the treatment of leukemia. [ABSTRACT FROM AUTHOR]

In recent years, the application of engineering nanomaterials has significantly contributed to the development of various biomedical fields. Zinc oxide nanomaterials (ZnO NMts) have gained wide popularity due to their biocompatibility, unique physical and chemical properties, stability, and cost‐effectiveness for large‐scale production. They have emerged as potential materials for anticancer applications. This article provides a comprehensive review of the synthesis methods of ZnO NMts and highlights the advantages of combining ZnO NMts with anticancer drugs as a nano platform for cancer treatment. Additionally, the article briefly explains the mechanism of action of ZnO NMts in tumor cells, focusing on the mitochondrial pathways that target cell apoptosis and autophagy. It is observed that these pathways are primarily influenced by reactive oxygen species generated through oxidative stress. The article discusses the promising prospects of ZnO NMts combined with anticancer drugs in the field of cancer medicine and emphasizes the need for further in‐depth research on the mitochondrial apoptosis and mitochondrial autophagy pathways. Significance statement: The application of engineered nanomaterials has helped promote the development of various biomedical fields in recent years. Zinc oxide nanomaterials (ZnO NMts) have been widely used in many biomedical fields and become one of the candidate materials for anticancer applications due to their biocompatibility, unique physicochemical properties, stability, and low‐cost large‐scale production. This article reviews the advantages of ZnO NMts nanoplatform in cancer treatment, abnormal apoptosis—the occurrence of cancer, the development of glioma, the effects of ZnO NMts in vitro and in vitro tumor cell models, as well as the mitochondrial pathway of apoptosis and autophagy. It was found that it was mainly related to reactive oxygen species produced by oxidative stress, and the proapoptotic proteins Bcl‐2‐related X protein (BAX), Bcl‐2 antagonist/killer (BAK) and p53 indirectly or directly led to the increase of mitochondrial membrane permeability and ultimately mitochondrial apoptosis. Hypoxia inducible factor‐1α (HIF‐1α) involved HIF‐1α‐BNIP3‐LC3B pathway mediates the mitophagy pathway. [ABSTRACT FROM AUTHOR]

Ultra‐high dose rate radiotherapy (FLASH‐RT) has emerged as a novel tool for cancer radiotherapy owing to its extremely rapid radiation delivery to target species. Although FLASH‐RT can protect normal tissues and organs, tumor self‐protection mechanisms limit its therapeutic effect, thus necessitating technological improvement. Here, a multipathway ferroptosis‐enhanced radioimmunotherapeutic strategy that combines single‐atom nanozyme (SAzyme)‐based GSH depletion and CO gas therapy is reported. Personalized FLASH radioimmunotherapy is achieved through encapsulation of the carbon monoxide donor (MnCO)‐loaded porous Pd‐C SAzyme (SM) within 4T1 cancer cell membranes (CSM). Camouflaging with the cancer cell membrane enables the navigation of the MnCO‐loaded Pd‐C SAzyme to the tumor region via homologous targeting. There, it releases MnCO, which generates CO from overexpressed H2O2 to induce mitochondrial apoptosis. Furthermore, the generated CO and Pd‐C SAzyme oxidized glutathione and downregulates glutathione peroxidase 4 (GPX4) expression to induce ferroptosis. The palladium in the SAzyme of the CSM further enhances the photoelectric effects of FLASH‐RT. The CSM‐mediated FLASH‐RT also invokes potent antitumor immunity, suppressing distant tumors, and immune memory, inhibiting tumor recurrence. This work presents a unique personalized nanozyme and CO gas synergistic approach wherein FLASH radioimmunotherapy avoids damage of normal tissues while simultaneously inducing ferroptosis for orthotopic tumor treatment. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, with poor outcomes for patients with metastatic disease or chemotherapy resistance. Cirsiliol is a recently found flavonoid with anti-tumor effects in various tumors. However, the effects of cirsiliol in the regulation of aggressive behaviors of OS remain unknown. Methods: The effect of cirsiliol on the proliferation of OS cells was detected using a cell counting kit-8 (CCK-8) assay and 5-ethynyl-2′-deoxyuridine (EdU) staining, while cell apoptosis was detected using flow cytometry. Immunofluorescence was applied to visualize the expression level of the mitochondria, lysosomes and microtubule-associated protein light chain 3 (LC3). A computational molecular docking technique was used to predict the interaction between cirsiliol and the AKT protein. The impact of cirsiliol on resistance was investigated by comparing it between a methotrexate (MTX)-sensitive OS cell line, U2OS, and a MTX-resistant OS cell line, U2OS/MTX. Finally, in situ xenogeneic tumor models were used to validate the anti-tumor effect of cirsiliol in OS. Results: Cirsiliol inhibited cell proliferation and induced apoptosis in both U2OS and U2OS/MTX300 OS cells. In addition, treatment with cirsiliol resulted in G2 phase arrest in U2OS/MTX300 and U2OS cells. Cell fluorescence probe staining results showed impaired mitochondria and increased autophagy in OS cells after treatment with cirsiliol. Mechanistically, it was found that cirsiliol targeted AKT by reducing the phosphorylation of AKT, which further activated the transcriptional activity of forkhead Box O transcription factor 1 (FOXO1), ultimately affecting the function of OS cells. Moreover, in situ tumorigenesis experiments showed that cirsiliol inhibited the tumorigenesis and progression of OS in vivo. Conclusions: Cirsiliol inhibits OS cell growth and induces cell apoptosis by reducing AKT phosphorylation and further promotes FOXO1 expression. These phenomena indicate that cirsiliol is a promising treatment option for OS. [ABSTRACT FROM AUTHOR]

Programmed cell death pathways play an important role in innate immune responses to infection. Activation of intrinsic apoptosis promotes infected cell clearance; however, comparatively little is known about how this mode of cell death is regulated during infections and whether it can induce inflammation. Here, we identify that the pro‐survival BCL‐2 family member, A1, controls activation of the essential intrinsic apoptotic effectors BAX/BAK in macrophages and monocytes following bacterial lipopolysaccharide (LPS) sensing. We show that, due to its tight transcriptional and post‐translational regulation, A1 acts as a molecular rheostat to regulate BAX/BAK‐dependent apoptosis and the subsequent NLRP3 inflammasome‐dependent and inflammasome‐independent maturation of the inflammatory cytokine IL‐1β. Furthermore, induction of A1 expression in inflammatory monocytes limits cell death modalities and IL‐1β activation triggered by Neisseria gonorrhoeae‐derived outer membrane vesicles (NOMVs). Consequently, A1‐deficient mice exhibit heightened IL‐1β production in response to NOMV injection. These findings reveal that bacteria can induce A1 expression to delay myeloid cell death and inflammatory responses, which has implications for the development of host‐directed antimicrobial therapeutics. Synopsis: Cell death and inflammatory signalling crosstalk is critical for innate immune responses to pathogens. This study identifies the BCL‐2 family member A1 as a temporal regulator of these processes in myeloid cells upon bacterial recognition. LPS‐induced A1 expression in macrophages and monocytes delays apoptosis and NLRP3 inflammasome activation.Monocyte survival upon pathogen sensing is regulated by the short‐lived pro‐survival proteins MCL‐1 and A1.A1‐deficient myeloid cells can engage necroptotic signalling when apoptotic caspase activity is compromised.A1‐deficiency enhances IL‐1β responses to Neisseria gonorrhoeae‐derived outer membrane vesicles (NOMVs). [ABSTRACT FROM AUTHOR]