“…In our pervious study, we have demonstrated Rabeprazole suppressed HK2 expression, leading to inhibit glycolysis [ 11 ]. Interestingly, glycolysis has been reported to promote cell pyroptosis by activating the NLRP3 inflammasome [ 27 , 33 , 34 ]. The inflammasome NLRP3 is a molecular pathway activated by a wide range of cellular insults to elicit innate immune defenses through the activation of caspase-1 and the maturation of proinflammatory cytokines, such as IL-1βand IL-18 [ 35 ].…”
Background
Helicobacter pylori (H. pylori) is a common pathogen in development of peptic ulcers with pyroptosis. Rabeprazole, a critical component of standard triple therapy, has been widely used as the first-line regimen for H. pylori infectious treatment. The aim of this study to explore the function of Rabeprazole on cell pyroptosis in vitro.
Methods
The clinical sample from patients diagnosed with or without H. pylori-infection were collected to analyze by Immunohistochemistry (IHC). Real-time quantitative PCR (qPCR), western blot (WB) and enzyme linked immunosorbent assay (Elisa) were performed to analyze the effect of Rabeprazole on cell pyroptosis, including LDH, IL-1β and IL-18.
Results
In this study, we showed that Rabeprazole regulated a phenomenon of cell pyroptosis as confirmed by lactate dehydrogenase (LDH) assay. Further results showed that Rabeprazole inhibited cell pyroptosis in gastric epithelial cells by alleviating GSDMD-executed pyroptosis, leading to decrease IL-1β and IL-18 mature and secretion, which is attributed to NLRP3 inflammasome activation inhibition. Further analysis showed that ASC, NLRP3 and Caspase-1, was significantly repressed in response to Rabeprazole stimulation, resulting in decreasing cleaved-caspase-1 expression. Most important, NLRP3 and GSDMD is significantly increased in gastric tissue of patients with H. pylori infection.
Conclusion
These findings revealed a critical role of Rabeprazole in cell pyroptosis in patients with H. pylori infection, suggesting that targeting cell pyroptosis is an alternative strategy in improving H. pylori treatment.
“…In our pervious study, we have demonstrated Rabeprazole suppressed HK2 expression, leading to inhibit glycolysis [ 11 ]. Interestingly, glycolysis has been reported to promote cell pyroptosis by activating the NLRP3 inflammasome [ 27 , 33 , 34 ]. The inflammasome NLRP3 is a molecular pathway activated by a wide range of cellular insults to elicit innate immune defenses through the activation of caspase-1 and the maturation of proinflammatory cytokines, such as IL-1βand IL-18 [ 35 ].…”
Background
Helicobacter pylori (H. pylori) is a common pathogen in development of peptic ulcers with pyroptosis. Rabeprazole, a critical component of standard triple therapy, has been widely used as the first-line regimen for H. pylori infectious treatment. The aim of this study to explore the function of Rabeprazole on cell pyroptosis in vitro.
Methods
The clinical sample from patients diagnosed with or without H. pylori-infection were collected to analyze by Immunohistochemistry (IHC). Real-time quantitative PCR (qPCR), western blot (WB) and enzyme linked immunosorbent assay (Elisa) were performed to analyze the effect of Rabeprazole on cell pyroptosis, including LDH, IL-1β and IL-18.
Results
In this study, we showed that Rabeprazole regulated a phenomenon of cell pyroptosis as confirmed by lactate dehydrogenase (LDH) assay. Further results showed that Rabeprazole inhibited cell pyroptosis in gastric epithelial cells by alleviating GSDMD-executed pyroptosis, leading to decrease IL-1β and IL-18 mature and secretion, which is attributed to NLRP3 inflammasome activation inhibition. Further analysis showed that ASC, NLRP3 and Caspase-1, was significantly repressed in response to Rabeprazole stimulation, resulting in decreasing cleaved-caspase-1 expression. Most important, NLRP3 and GSDMD is significantly increased in gastric tissue of patients with H. pylori infection.
Conclusion
These findings revealed a critical role of Rabeprazole in cell pyroptosis in patients with H. pylori infection, suggesting that targeting cell pyroptosis is an alternative strategy in improving H. pylori treatment.
“…Because ROS elimination prevents neuronal cell apoptosis [125] and boosts survival rate in neural transplantation surgery [128], augmenting BDNF production may represent a compelling method to alleviate the pathological outcomes caused by excessive oxidative stress in the CNS. Recently, BDNF was also found effective in suppressing the oxidized low-density lipoprotein (oxLDL)-induced ROS surge in human umbilical vein endothelial cells (HUVECs) [129]. Hence, it would be tempting to postulate that this function might also be conserved in non-CNS tissues, such as skeletal muscle.…”
Mitochondria are the cellular powerhouses that generate adenosine triphosphate (ATP) to substantiate various biochemical activities. Instead of being a static intracellular structure, they are dynamic organelles that perform constant structural and functional remodeling in response to different metabolic stresses. In situations that require a high ATP supply, new mitochondria are assembled (mitochondrial biogenesis) or formed by fusing the existing mitochondria (mitochondrial fusion) to maximize the oxidative capacity. On the other hand, nutrient overload may produce detrimental metabolites such as reactive oxidative species (ROS) that wreck the organelle, leading to the split of damaged mitochondria (mitofission) for clearance (mitophagy). These vital processes are tightly regulated by a sophisticated quality control system involving energy sensing, intracellular membrane interaction, autophagy, and proteasomal degradation to optimize the number of healthy mitochondria. The effective mitochondrial surveillance is particularly important to skeletal muscle fitness because of its large tissue mass as well as its high metabolic activities for supporting the intensive myofiber contractility. Indeed, the failure of the mitochondrial quality control system in skeletal muscle is associated with diseases such as insulin resistance, aging, and muscle wasting. While the mitochondrial dynamics in cells are believed to be intrinsically controlled by the energy content and nutrient availability, other upstream regulators such as hormonal signals from distal organs or factors generated by the muscle itself may also play a critical role. It is now clear that skeletal muscle actively participates in systemic energy homeostasis via producing hundreds of myokines. Acting either as autocrine/paracrine or circulating hormones to crosstalk with other organs, these secretory myokines regulate a large number of physiological activities including insulin sensitivity, fuel utilization, cell differentiation, and appetite behavior. In this article, we will review the mechanism of myokines in mitochondrial quality control and ROS balance, and discuss their translational potential.
“…Of note, the glucose metabolic and leucine metabolic pathways have been reported to be closely linked to pyroptosis. 20 , 21 Figure 8 The result of gene set enrichment analysis. ( A ) GSEA showed that tumor-associated pathways were significantly enriched in the high-risk CRC patient group.…”
Section: Resultsmentioning
confidence: 99%
“…Of note, the glucose metabolic and leucine metabolic pathways have been reported to be closely linked to pyroptosis. 20,21…”
Purpose
Pyroptosis plays an important role in tumor progression. However, there is no pyroptosis-associated long noncoding RNA (lncRNA) signature to predict the prognosis of patients with colorectal cancer (CRC).
Materials and Methods
The RNA sequencing data (RNA-seq) and corresponding clinical information relating to CRC patients were obtained from the Cancer Genome Atlas (TCGA) database and the GSE39582 dataset. Univariate Cox regression analysis was used to identify pyroptosis-associated lncRNAs linked to CRC prognosis. Subsequently, multivariate Cox regression analysis was performed to construct a pyroptosis-associated lncRNAs signature within the TCGA cohort, which was then validated using the GSE39582 dataset. We used Kaplan–Meier (K-M) analysis, principal component analysis (PCA), and receiver operating characteristic curve (ROC) analysis to evaluate our novel lncRNA signature. Finally, gene set enrichment analysis (GSEA) was performed to explore the potential function of the lncRNA signature.
Results
We constructed a pyroptosis-associated lncRNA signature comprising four lncRNAs (ELFN1-AS1, PCAT6, TNRC6C-AS1, and ZEB1-AS1). CRC patients were subdivided into high- and low-risk groups based on median risk scores. The results of the K-M, PCA, and ROC analyses showed that this signature could accurately predict the prognosis of CRC patients. Univariate and multivariate Cox regression analyses showed that the pyroptosis-associated signature was an independent prognostic factor. Functional analysis suggested that tumor-associated pathways were enriched for in the high-risk CRC patient group.
Conclusion
Our study established an effective prognostic signature for CRC patients that may represent a potential therapeutic target.
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