N6-methyladenosine (m6A) Writer WTAP Potentiates Hepatocellular Carcinoma Immune Evasion and Aerobic Glycolysis.

Hepatocellular carcinoma (HCC) is one of most prevalent malignant tumors with poor prognosis and a high mortality rate. Recent research indicates that N6-methyladenosine (m6A) and tumor immunotherapy are important factors in HCC. More research is still needed to fully understand the profound roles that m6A writer Wilms tumor 1-associated protein (WTAP) and CD8+ T cells play in the antitumor immunity that prevents HCC from progressing. According to the findings of our investigation, WTAP was significantly elevated in HCC cells and was associated with a poor prognosis. Functionally, WTAP accelerated HCC immune evasion and aerobic glycolysis while suppressing the tumor-killing ability of CD8+ T cells. On the other hand, WTAP knockdown had the opposite effect. WTAP targets the m6A site on the 3'-UTR of PD-L1 mRNA, which mechanistically increases the stability of PD-L1 mRNA. These results showed that WTAP inhibited CD8+ T cells' antitumor activity, which in turn deteriorated HCC immune evasion and aerobic glycolysis. In conclusion, our research uncovers a novel mechanism for WTAP on the tumor-killing ability of CD8+ T cells, which helps to overcome HCC immune evasion.

Aprepitant Alleviates Poststroke Pneumonia in a Mouse Model of Middle Cerebral Artery Occlusion.

Elevated substance P can be utilized to predict early mortality during the first week of cerebral infarction. Whether aprepitant, a substance P receptor blocker could be utilized to alleviate poststroke pneumonia which is investigated in this study. Intraluminal monofilament model of middle cerebral artery occlusion (MCAO) was constructed in C57BL/6J male mice, and the relative expression of substance P was detected in collected bronchoalveolar lavage fluid (BALF) and lung tissue homogenate at 24 hours, 48 hours, and 72 hours poststroke. On the other hand, different concentrations of aprepitant (0.5, 1, and 2 mg/kg) were atomized and inhaled into MCAO mice. Inflammation cytokines and bacterial load were detected in collected BALF and lung tissue homogenate at 72-hour poststroke, and lung injury was revealed by histological examination. Aprepitant administration decreased total proteins, total cells, neutrophils, and macrophages in BALF. The concentrations of interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, interferon γ, monocyte chemoattractant protein-1, and IL-10 in lung tissue homogenates were also diminished by the administration of aprepitant. In conclusion, aprepitant could attenuate poststroke pneumonia in mice suggesting its potential therapeutic use in the clinic.

Metabolomic biomarkers for hepatocellular carcinoma: A systematic review.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly malignant cancer which lack of effective diagnosis and prognosis biomarkers, therefore surging studies focused on the metabolite candidates for HCC. The current study was designed to systematically review the metabolic studies for HCC, summarize the current available evidence and provide implication for further studies within this area. By systematically screening Pubmed and Embase, and eligibility assessment, we eventually included 55 pieces of studies. After summarized their characteristics, we reviewed them by 3 parts, regarding to the different biofluid they carried out the experiments. By collecting the candidates from all the included studies, we carried out pathway enrichment to see the representative of the reported candidates, as expected the pathway consistent with the current knowledge of HCC. Next, we conduct quality assessment on the included studies. Only 36% of the current evidence grouped as high quality, indicating the quality of metabolic studies needs further improvement.