Andrographolide ameliorates sepsis-induced acute lung injury by promoting autophagy in alveolar macrophages via the RAGE/PI3K/AKT/mTOR pathway.

Autophagy in alveolar macrophages (AMs) is an important mechanism for maintaining immune homeostasis and normal lung tissue function, and insufficient autophagy in AMs may mediate the development of sepsis-induced acute lung injury (SALI). Insufficient autophagy in AMs and the activation of the NLRP3 inflammasome were observed in a mouse model with SALI induced by cecal ligation and puncture (CLP), resulting in the release of a substantial quantity of proinflammatory factors and the formation of SALI. However, after andrographolide (AG) intervention, autophagy in AMs was significantly promoted, the activation of the NLRP3 inflammasome was inhibited, the release of proinflammatory factors and pyroptosis were suppressed, and SALI was then ameliorated. In the MH-S cell model stimulated with LPS, insufficient autophagy was discovered to promote the overactivation of the NLRP3 inflammasome. AG was found to significantly promote autophagy, inhibit the activation of the NLRP3 inflammasome, and attenuate the release of proinflammatory factors. The primary mechanism of AG promoting autophagy was to inhibit the activation of the PI3K/AKT/mTOR pathway by binding RAGE to the membrane. In addition, it inhibited the activation of the NLRP3 inflammasome to ameliorate SALI. Our findings suggest that AG promotes autophagy in AMs through the RAGE/PI3K/AKT/mTOR pathway to inhibit the activation of the NLRP3 inflammasome, remodel the functional homeostasis of AMs in SALI, and exert anti-inflammatory and lung-protective effects. It has also been the first to suggest that RAGE is likely a direct target through which AG regulates autophagy, providing theoretical support for a novel therapeutic strategy in sepsis.

[Knockdown of lncRNA CACNA1C-AS2 promotes epithelial-mesenchymal transition and enhances the proliferation, invasion and migration of human esophageal cancer cells].

Objective To investigate the effect of calcium voltage gated channel subunit α 1C antisense RNA2 (CACNA1C-AS2) on malignant biological characteristics of esophageal cancer cells by regulating epithelial mesenchymal transition (EMT). Methods CACNA1C-AS2 expression levels in paracancerous tissues and esophageal cancer tissues were analyzed by TCGA database. Real-time quantitative PCR was used to detect the expression of CACNA1C-AS2 mRNA in esophageal cancer cells. Following the knockdown and high expression of CACNA1C-AS2 in esophageal cancer cells, the viability of the cells was tested by MTT assay and cell colony formation assay. TranswellTM chamber method was used to measure the invasion and longitudinal migration of the cells. The horizontal migration ability of the cells was evaluated by wound healing test. The apoptosis rates of cells were detected by flow cytometry. Western blot analysis was used to detect the expressions of N-cadherin, vimentin and slug. Results CACNA1C-AS2 expression levels were low in esophageal cancer tissues and cell lines. After knocking down the expression of CACNA1C-AS2 in EC-9706 cells and Eca-109 cells, the ability of invasion and migration and viability of esophageal cancer cells were significantly enhanced, and the apoptosis rates were decreased, while the expressions of N-cadherin, vimentin and slug were up-regulated. However, the results are opposite via the over-expression of CACNA1C-AS2. Conclusion CACNA1C-AS2 enhances the proliferation, invasion and migration of esophageal cancer cells by promoting EMT.

Proteomic investigation of resistance to chemotherapy drugs in osteosarcoma.

BACKGROUND: Osteosarcoma, which is also termed osteogenic sarcoma or osteoma sarcomatosum, is the most common form of bone cancer. Typical osteosarcoma can occur at any age, including in infants, children, and the elderly, but more than half of cases occur in individuals who are 10-20 years old. OBJECTIVE: Here, the objective was to search for protein markers to indicate resistance to cisplatin in osteosarcoma and provide a theoretical basis for the early and accurate use of cisplatin to treat osteosarcoma. METHODS: Thirty patients with osteosarcoma were selected for the study. Experimental studies on the chemosensitivity of osteosarcoma using an in vitro kit method were performed, and cisplatin-resistant and cisplatin-sensitive osteosarcoma tissues were obtained. A representative sample was chosen to analyze and identify differentially expressed proteins in cisplatin-resistant tissues. RESULTS: The osteosarcoma-sensitive tissue was analyzed using 2-D electrophoresis and time-of-flight mass spectrometry. Differently expressed proteins were analyzed by western blotting to identify markers. Cisplatin-resistant and cisplatin-sensitive osteosarcoma tissues were obtained. Five significantly differentially expressed proteins were identified, including ALDOA and PGK1. CONCLUSIONS: The results indicate that ALDOA and PGK1 might be appropriate markers that can be used when treating osteosarcoma with cisplatin.