mTOR signaling promotes rapid m6A mRNA methylation to regulate NK-cell activation and effector functions.

Natural killer (NK) cells can be rapidly activated in response to cytokines during host defense against malignant cells or viral infection. However, it remains unclear what mechanisms precisely and rapidly regulate the expression of the numerous genes involved in activating NK cells. In this study, we discovered that NK-cell N6-methyladenosine (m6A) methylation levels were rapidly upregulated upon short-term NK-cell activation and were repressed in the tumor microenvironment. Deficiency of methyltransferase-like 3 (METTL3) or METTL14 moderately influenced NK-cell homeostasis, while double knockout of METTL3/14 significantly impacted NK-cell homeostasis, maturation, and antitumor immunity. This suggests a cooperative role of METTL3 and METTL14 in regulating NK-cell development and effector functions. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq), we demonstrated that genes involved in NK-cell effector functions, such as Prf1 and Gzmb, were directly modified by m6A methylation. Furthermore, inhibiting mTOR complex 1 (mTORC1) activation prevented m6A methylation levels from increasing when NK cells were activated, and this could be restored by S-adenosylmethionine (SAM) supplementation. Collectively, we have unraveled crucial roles for rapid m6A mRNA methylation downstream of the mTORC1-SAM signal axis in regulating NK-cell activation and effector functions.

Antioxidant and hepatoprotective activities of modified polysaccharides from Coprinus comatus in mice with alcohol-induced liver injury.

A modified polysaccharide named MPCC from Coprinus comatus (MPCC) was obtained by the snailase hydrolysis. And the hepatoprotective effects on alcohol-induced liver injury and preliminary structure features were investigated. For in vivo hepatoprotective abilities, MPCC significantly attenuated the hepatic and serum lipid levels, obviously enhanced antioxidant enzyme activities, markedly improved alcohol metabolism system and inflammatory response, and mitigated alcohol-induced liver injury histopathologically, providing references for the exploitation of MPCC as functional foods or natural drugs against the alcohol-induced liver injury. Additionally, MPCC containing fucose (Fuc), ribose (Rib), arabinose (Ara), xylose (Xyl), mannose (Man), galactose (Gal) and glucose (Glu) with the a α- and ß-configuration in a percentage composition of 0.91%, 0.71%, 0.45%, 1.60%, 2.04%, 4.41% and 89.88% via gas chromatography (GC), Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) analysis.

The characteristic, antioxidative and multiple organ protective of acidic-extractable mycelium polysaccharides by Pleurotus eryngii var. tuoliensis on high-fat emulsion induced-hypertriglyceridemic mice.

The antioxidant and multiple organ protection effects of acid- extracted mycelia polysaccharides (Ac-MPS) from Pleurotus eryngii var. tuoliensis on HFE-induced hypertriglyceridemic mice were investigated. The results showed that Ac-MPS have potential ability to relieve the hypertriglyceridemia and preventing oxidative stress by decreasing levels of TG, TC LDL-C, elevating contents of HDL-C in serum, increasing the activities of SOD, GSH-Px, CAT and T-AOC, and the down regulating MDA and LPO contents in liver, heart, kidney and spleen. And the histopathological observations also displayed that Ac-MPS could alleviate organ damage. Moreover, the GC, HPGPC, FT-IR and AFM analyses revealed the Ac-MPS possessed the typical polysaccharides structure with the molecular weights (Mw) of 2.712 × 105 Da. These conclusions indicated that the Ac-MPS had the potential to develop new drugs for hypertriglyceridemia-induced multiple organ failure.

Antioxidant and Hypoglycemic Effects of Acidic-Extractable Polysaccharides from Cordyceps militaris on Type 2 Diabetes Mice.

The present work was performed to evaluate the effect of acidic-extractable polysaccharides (AE-PS) from fruit bodies of Cordyceps militaris on type 2 diabetes mellitus (T2DM) and its structural characteristics. The T2DM mice induced by high-fat diet (HFD) and streptozotocin (STZ) were administered with 100 and 400 mg/kg AE-PS for 4 weeks. Our work proved that AE-PS decreased the levels of serum lipid, lipid peroxidation, and blood glucose; improved glucose and insulin resistance; enhanced antioxidant enzyme activities; and attenuated the injuries of the liver, kidney, and pancreas in T2DM mice. These results might offer references for the exploitation of AE-PS as functional foods or natural drug source for preventing and treating HFD- and STZ-induced T2DM. Moreover, gas chromatography (GC) results revealed that AE-PS was heterogeneous and composed of fucose, ribose, arabinose, xylose, mannose, galactose, and glucose with mass percentages of 1.23%, 0.57%, 0.29%, 2.12%, 2.73%, 4.66%, and 88.4%, respectively. Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) analysis indicated that AE-PS was a pyran-type polysaccharide with α- and ß-configurations.