Effect and mechanism of reactive oxygen species-mediated NOD-like receptor family pyrin domain-containing 3 inflammasome activation in hepatic alveolar echinococcosis.

BACKGROUND: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a significant component of the innate immune system that plays a vital role in the development of various parasitic diseases. However, its role in hepatic alveolar echinococcosis (HAE) remains unclear. AIM: To investigate the NLRP3 inflammasome and its mechanism of activation in HAE. METHODS: We assessed the expression of NLRP3, caspase-1, interleukin (IL)-1ß, and IL-18 in the marginal zone and corresponding normal liver of 60 patients with HAE. A rat model of HAE was employed to investigate the role of the NLRP3 inflammasome in the marginal zone of HAE. Transwell experiments were conducted to investigate the effect of Echinococcus multilocularis (E. multilocularis) in stimulating Kupffer cells and hepatocytes. Furthermore, immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay were used to evaluate NLRP3, caspase-1, IL-1ß, and IL-18 expression; flow cytometry was used to detect apoptosis and reactive oxygen species (ROS). RESULTS: NLRP3 inflammasome activation was significantly associated with ROS. Inhibition of ROS production decreased NLRP3-caspase-1-IL-1ß pathway activation and mitigated hepatocyte damage and inflammation. CONCLUSION: E. multilocularis induces hepatocyte damage and inflammation by activating the ROS-mediated NLRP3-caspase-1-IL-1ß pathway in Kupffer cells, indicating that ROS may serve as a potential target for the treatment of HAE.

The effects of hypoxia on mitochondrial function and metabolism in gastric cancer cells.

BACKGROUND: A number of studies have found that metabolic disorders are the characteristic manifestations of tumor cells. However, the effects of hypoxic environment on mitochondrial function and glucose metabolism of tumor cells were still unclear. The study wanted to explore the regulatory mechanism of hypoxic environment on mitochondrial function and metabolism in gastric cancer cells. METHODS: The animal model of gastric cancer and MKN45 were treated in a hypoxic environment. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were analyzed by flow cytometry, qPCR was used to detect the expression levels of glycose metabolism key enzymes, damage repair genes and mitochondrial DNA (mtDNA) copy numbers in gastric cancer. RESULTS: Compared with 2,000 m normal gastric cancer tissue, the decreased of mitochondrial membrane potential and the production of ROS reduced, the expressions of glucose metabolism genes [the M1 isoform of Hexokinase (HK1), pyruvate kinase (PKM), Succinate dehydrogenase (SDHA), Glucose-6-phosphate dehydrogenase (G6PD)], homologous recombination repair gene (RAD51) and repair DNA double-stranded broken gene (ASTCT2) increased, and aerobic respiration reduced in gastric cancer cells. In the hypoxic environment, the decreased of mitochondrial membrane potential reduced, the production of ROS and mtDNA copies increased, HK1 expression increased, the expressions of SDHA, G6PD, RAD51 and ASCT-2 decreased, and the aerobic respiration decreased. CONCLUSIONS: Hypoxia plays an important role in maintaining mitochondrial functions in gastric cancer cells by promoting glycolysis and inhibiting mitochondrial aerobic respiration capacity.