Our study provides evidence indicating that overexpressedmiR-300 enhances autophagy by targeting NAMPT through activation of the AMPK/mTOR signaling pathway in septic mouse models, indicating it may serve as a potential therapeutic target for sepsis.
Background/Aims: Long non-coding RNAs (lncRNAs) play vital roles in carcinogenesis as oncogenes or tumor suppressor genes. This study explored the biological function of lncRNA gastric adenocarcinoma predictive long intergenic non-coding RNA (GAPLINC) in human non-small cell lung cancer (NSCLC). Methods: GAPLINC expression in NSCLC specimens and cell lines was detected by qRT-PCR and Western blot. The effect of GAPLINC on cell proliferation was investigated using CCK8-assay, colony formation assay, and xenograft model. The effects of GAPLINC on apoptosis and cell cycle were determined using flow cytometry. The mechanism of GAPLINC involved in NSCLC was explored using Western blot, luciferase reporter assay, and RNA fluorescence in situ hybridization. Results: We found that GAPLINC expression was up-regulated in NSCLC tissues and cell lines. Overexpression of GAPLINC was associated with poor prognosis in patients with NSCLC. Silencing of GAPLINC significantly inhibited cell proliferation, promoted apoptosis, and induced cell cycle arrest in the G0/G1 phase. Results from xenograft transplantation showed that GAPLINC silencing inhibited the tumor growth in vivo. Interestingly, GAPLINC silencing decreased the expression of eukaryotic elongation factor-2 kinase (eEF2K) protein both in vivo and in vitro. Bioinformatic analysis and luciferase reporter confirmed that miR-661 targeted GAPLINC and eEF2K 3’-UTR and was negatively correlated with the expression of GAPLINC and eEF2K. Conclusion: Our findings indicate that GAPLINC promotes NSCLC tumorigenesis by regulating miR-661/eEF2K cascade and provide new insights for the pathogenesis underlying NSCLC and potential targets for therapeutic strategy.
Sepsis is a syndrome of life-threatening multiorgan dysfunction caused by host response dysregulation to infection. Ulinastatin (UTI), a serine protease inhibitor, possesses anti-inflammatory properties and has been suggested to modulate lipopolysaccharide-induced sepsis. However, little is known about the mechanism underlying its effects on sepsis. In the current study, we investigated the protective effect of UTI on liver injury in a cecal ligation and puncture (CLP)-induced sepsis of C57BL/6 mouse model and explored the possible mechanisms. Mice underwent CLP as sepsis models and were randomized into five groups including the sham group, UTI group, CLP group, UTI-L group, and UTI-H group. UTI was intraperitoneally administered at doses of UTI 1500 U/100 g (UTI-L group) or 3000 U/100 g (UTI-H group), before CLP. The mice were killed, and immunohistochemical changes, cytokine levels, and antioxidant enzyme activities were detected. Our results showed that UTI ameliorated CLP-mediated increases in serum aspartate aminotransferase and alanine aminotransferase activities, histological activity index, degenerative region ratio, and infiltrated inflammatory cell numbers. Moreover, UTI also decreased nitrotyrosine and 4-hydroxynonenal, activated caspase-3, and activated poly (ADP-ribose) polymerase (PARP) levels and inhibited the mitogen-activated protein kinase pathway activation in liver tissues. Our results indicated that UTI could inhibit CLP-induced liver injury by suppressing inflammation and oxidation. Our results indicated that UTI may serve as a potential therapeutic agent for sepsis.
The results of this study indicate that blockade of CXCR1/2 may represent a promising therapeutic strategy for the treatment of sepsis-associated ALI through regulation of neuropeptides and necroptosis.
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