Trichoderma asperellum as a novel source to prepare chitooligosaccharides by enzymatic hydrolysis and its antimicrobial activity.

Chitooligosaccharides (COS), an important biological functional component, are mainly extracted from marine products, but its raw materials are currently facing challenges such as marine resources pollution and demineralization. This study aimed to explore Trichoderma asperellum as a novel source to prepare COS. The COS were prepared by the enzymatic degradation of chitosan from T. asperellum, and single factor experiment and orthogonal designs were used to optimize the enzymatic conditions for the preparation of COS. The composition of COS was performed by thin-layer chromatography, high-performance liquid chromatography, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The results showed that the degree of deacetylation of T. asperellum chitosan was 87.59%, and its enzymatic hydrolysis yield was 89.37 % under optimized extraction conditions. Moreover, the composition of COS in T. asperellum included chitotriose, chitopentaose, and chitohexaose. Compared with shrimp shells, COS prepared from T. asperellum showed stronger antibacterial properties against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Salmonella bacilli.

Preparation, structural characterization and neuroprotective effects to against H2O2-induced oxidative damage in PC12 cells of polysaccharides from Pleurotus ostreatus.

Pleurotus ostreatus is one of the most common edible and medicinal fungi in life, and its polysaccharide has been a hot research topic in recent years. In this paper, a new intracellular polysaccharide component named P. ostreatus polysaccharide (POP-W) was obtained from the mycelium of P. ostreatus, and its structure was analyzed. The results showed that its molecular weight was Mw = 3.034 × 103 kDa, and it did not contain protein and nucleic acid. POP-W was composed of mannose, glucose, galactose and xylose in a molar ratio of 40.34:47.60:7.97:4.09. The backbone of POP-W was α-D-Glcp(1→,→3,4)-α-D-Glcp(1→, →3,4)-α-D-Manp(1→,→3)-α -D-Galp(1→, →4)-α-D-Glcp(1→, →3)-α-D-Glcp(1→, →2)-ß-D-Manp(1→, →4) -ß-D-Xylp(1 â†’. SEM and TGA analysis showed the structure of POP-W and good thermal stability. In addition, POP-W showed significant antioxidant activity in vitro. More importantly, POP-W protected PC12 cells induced by H2O2 by inhibiting the contents of lactate dehydrogenase (LDH) and malondialdehyde (MDA) and increasing the levels of superoxide dismutase (SOD) and reduced glutathione (GSH). Western blot detection of Caspase-3, BAX, Bcl-2, PI3K/Akt protein expression. The results showed that POP-W inhibited the expression of caspase-3 and BAX, while promoting the expression of Bcl-2. In addition, POP-W can also promote the phosphorylation of Akt. In conclusion, POP-W pretreatment can protect PC12 cells from H2O2-induced oxidative damage through PI3K/Akt signaling pathway and regulation of apoptosis-related pathway proteins. It provided a theoretical basis for the practical application of the polysaccharide of P. ostreatus in production.

Taurine enhances the antitumor efficacy of PD-1 antibody by boosting CD8+ T cell function.

The functional state of CD8+ T cells determines the therapeutic efficacy of PD-1 blockade antibodies in tumors. Amino acids are key nutrients for maintaining T cell antitumor immunity. In this study, we used samples from lung cancer patients treated with PD-1 blockade antibodies to assay the amino acids in their serum by mass spectrometry. We found that lung cancer patients with high serum taurine levels generally responded to PD-1 blockade antibody therapy, in parallel with the secretion of high levels of cytotoxic cytokines (IFN-γ and TNF-α). CD8+ T cells cultured with exogenous taurine exhibited decreased apoptosis, enhanced proliferation, and increased secretion of cytotoxic cytokines. High SLC6A6 expression in CD8+ T cells was positively associated with an effector T cell signature. SLC6A6 knockdown limited the function and proliferation of CD8+ T cells. RNA sequencing revealed that SLC6A6 knockdown altered the calcium signaling pathway, oxidative phosphorylation, and T cell receptor signaling in CD8+ T cells. Furthermore, taurine enhanced T cell proliferation and function in vitro by stimulation of PLCγ1-mediated calcium and MAPK signaling. Taurine plus immune checkpoint blockade antibody significantly attenuated tumor growth and markedly improved the function and proliferation of CD8+ T cells in a mouse tumor model. Thus, our findings indicate that taurine is an important driver for improving CD8+ T cell immune responses and could serve as a potential therapeutic agent for cancer patients.

Rheological properties of polysaccharides from Pholiota nameko with different temperature extraction: Concentration, pH, temperature, and saltion.

Cold and hot water extracted polysaccharides (CW-PNPs and HW-PNPs) were isolated from Pholiota nameko. The rheological properties of PNPs were investigated by steady shear and oscillatory rheological measurements. The PNPs exhibited typical non-Newtonian and shear-thinning behavior, which are affected by PNP concentration, temperature, pH value, salt ion, and concentration. Specifically, the apparent viscosity of the two PNPs solutions at concentration of 1% (w/w) was shown as HW-PNPs > CW-PNPs. The apparent viscosity of PNPs decreases under acidic and alkaline conditions and when the temperature rises; K+ and Na+ cause the apparent viscosity of CW-PNPs to decrease, while Ca2+ and Al3+ are opposite. The addition of four different salt ions all caused the apparent viscosity of the HW-PNPs to decrease. The results of dynamic rheological experiments show that G' and G″ showed slightly frequency dependency with G' exceeding G″ throughout the accessible range of frequency for CW-PNPs and HW-PNPs.

m6A demethylase FTO promotes tumor progression via regulation of lipid metabolism in esophageal cancer.

BACKGROUND: Epitranscriptomics studies have contributed greatly to the development of research on human cancers. In recent years, N6-methyladenosine (m6A), an RNA modification on the N-6 position of adenosine, has been found to play a potential role in epigenetic regulation. Therefore, we aimed to evaluate the regulation of cancer progression properties by m6A. RESULTS: We found that m6A demethylase fat mass and obesity-associated protein (FTO) was highly expressed in esophageal cancer (EC) stem-like cells, and that its level was also substantially increased in EC tissues, which was closely correlated with a poor prognosis in EC patients. FTO knockdown significantly inhibited the proliferation, invasion, stemness, and tumorigenicity of EC cells, whereas FTO overexpression promoted these characteristics. Furthermore, integrated transcriptome and meRIP-seq analyses revealed that HSD17B11 may be a target gene regulated by FTO. Moreover, FTO promoted the formation of lipid droplets in EC cells by enhancing HSD17B11 expression. Furthermore, depleting YTHDF1 increased the protein level of HSD17B11. CONCLUSIONS: These data indicate that FTO may rely on the reading protein YTHDF1 to affect the translation pathway of the HSD17B11 gene to regulate the formation of lipid droplets in EC cells, thereby promoting the development of EC. The understanding of the role of epitranscriptomics in the development of EC will lay a theoretical foundation for seeking new anticancer therapies.

Structural characterization and protective effect on PC12 cells against H2O2-induced oxidative damage of a polysaccharide extracted from mycelia of Lactarius deliciosus Gray.

The crude polysaccharide LDP was extracted from mycelia of Lactarius deliciosus Gray and then purified by DEAE-52 cellulose and Sephadex G-200 to obtain a novel polysaccharide named LDP-CP. LDP-CP was mainly composed of mannose, glucose and galactose with an average molecular weight of 2.33 × 103 kDa. The structure of LDP-CP was determined by FT-IR, methylation and NMR analysis, and the results showed that the sugar linkage units of LDP-CP were composed of (1 â†’ 3)-linked ß-D-Manp, (1 â†’ 2,4)-linked α-D-Manp, (1→)-linked α-D-Manp, (1 â†’ 4)-linked ß-D-Glcp, (1 â†’ 2)-linked ß-D-Manp, (1 â†’ 4,6)-linked α-D-Manp, (1 â†’ 4)-linked α-D-Galp, (1 â†’ 2,3)-linked α-D-Glcp and (1→)-linked α-D-Glcf. The protective effects of LDP and LDP-CP on PC12 cells against H2O2-induced oxidative injury were exhibited by enhancing cell viability and morphological protection. The improvement to the level of LDH, SOD and GSH further indicated that LDP and LDP-CP had ability to alleviate H2O2-induced oxidative damage on PC12 cells. The polysaccharides in Lactarius deliciosus Gray mycelia exhibited the great advantages in the management of oxidative toxicity, which indicated that the polysaccharides can be further developed in application of natural functional food source.

ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a lethal malignancy with metastasis, a major tumor feature that predominantly correlated with progression, but the molecules that mediated tumor metastasis remain elusive. To declare the critical regulatory genes, RNA sequencing data in LUAD patients was acquired from The Cancer Genome Atlas (TCGA) and found that ALDH3A1 was distinctly highly expressed in LUAD patients with metastasis (M1) compared with those without metastasis (M0), linked to the property of cancer stem cell and epithelial-mesenchymal transition (EMT). Besides, high ALDH3A1 expression predicted a poor prognosis. Knockdown of ALDH3A1 showed decreased proliferation, migration, and invasion in A549 cell line. Furthermore, BAG1 was regulated by ALDH3A1 through p53, enhanced cell proliferation, and predicted clinical prognosis. Our findings collectively uncovered a novel mechanism that orchestrates tumor cells' metastasis, and decreasing ALDH3A1 represented a potential therapeutic target for reprogramming metastasis.

Polycyclic aromatic hydrocarbon exposure, miRNA genetic variations, and associated leukocyte mitochondrial DNA copy number: A cross-sectional study in China.

Mitochondria DNA was preferentially attacked by the exogenous carcinogens including polycyclic aromatic hydrocarbons (PAHs) relative to nuclear DNA, and nuclear gene variants may account for variability in the mitochondrial DNA copy number (mtDNAcn). However, it remains unclear whether miRNA genetic variations are associated with mitochondrial DNA damage in the PAH-exposed workers. Therefore, we measured the leukocyte mtDNAcn, urinary 1-hydroxypyrene (1-OHPYR), environmental PAH exposure, and miRNA genetic polymorphisms among 544 coke oven workers and 238 healthy control participants. We found that the mtDNAcn in the exposure group (0.60 ± 0.29) was significantly lower than that in the control group (1.03 ± 0.31) (t = 18.931, P < 0.001). Spearman correlation analysis showed that the peripheral blood leukocyte mtDNAcn had significantly negative correlations with the levels of 1-OHPYR and environmental PAH exposure (P < 0.001). Covariance analysis indicated that miR-210 rs11246190 AA, miR-210 rs7395206 CC, and miR-126 rs2297538 GG probably promoted a decrease in leukocyte mtDNAcn in the exposure or control groups (P < 0.05). In generalized linear model, miR-210 rs11246190 GG was a protective factor of mtDNAcn, and environmental PAH exposure was the risk factor of the mtDNAcn. In conclusion, the decrease of leukocyte mtDNAcn is the result of a combination of environmental and genetic factors.