Endophytic fungus Biscogniauxia petrensis produces antibacterial substances.

Widespread drug resistance and limited antibiotics challenge the treatment of pathogenic bacteria, which leads to a focus on searching for new antimicrobial lead compounds. We found the endophytic fungus Biscogniauxia petrensis MFLUCC14-0151 from the medicinal plant Dendrobium harveyanum had antibacterial activity for the first time. This work aimed to reveal the capacity of Biscogniauxia petrensis MFLUCC14-0151 against foodborne pathogenic bacteria and identify its bioactive substances. Bioassay-guided isolation led to the discovery of six infrequent active monomers, including (10R)-Xylariterpenoid B (1), Xylariterpenoid C (2), Tricycloalternarene 1b (3), Tricycloalternarene 3b (4), Funicin (5) and Vinetorin (6) from MFLUCC14-0151 for the first time. The results of antibacterial tests showed that (10R)-Xylariterpenoid B and Xylariterpenoid C exhibited inhibitory activities against Streptococcus agalactiae with MIC values ranging from 99.21 to 100.00 µM, and against Streptococcus aureus with MIC values ranging from 49.60 to 50.00 µM. Tricycloalternarene 1b and Tricycloalternarene 3b showed inhibitory effects on Streptococcus agalactiae with MIC values ranging from 36.13 to 75.76 µM. Unexpectedly, Funicin and Vinetorin exhibited remarkable antagonistic activities against Streptococcus agalactiae with MIC values of 10.35 and 10.21 µM, respectively, and against Streptococcus aureus with MIC values of 5.17 and 20.42 µM, respectively. In conclusion, we suggest that the isolated compounds Funicin and Vinetorin may be promising lead compounds for natural antibacterial agents.

Creatine uptake regulates CD8 T cell antitumor immunity.

T cells demand massive energy to combat cancer; however, the metabolic regulators controlling antitumor T cell immunity have just begun to be unveiled. When studying nutrient usage of tumor-infiltrating immune cells in mice, we detected a sharp increase of the expression of a CrT (Slc6a8) gene, which encodes a surface transporter controlling the uptake of creatine into a cell. Using CrT knockout mice, we showed that creatine uptake deficiency severely impaired antitumor T cell immunity. Supplementing creatine to WT mice significantly suppressed tumor growth in multiple mouse tumor models, and the combination of creatine supplementation with a PD-1/PD-L1 blockade treatment showed synergistic tumor suppression efficacy. We further demonstrated that creatine acts as a "molecular battery" conserving bioenergy to power T cell activities. Therefore, our results have identified creatine as an important metabolic regulator controlling antitumor T cell immunity, underscoring the potential of creatine supplementation to improve T cell-based cancer immunotherapies.

[Protective effect of shenqi fuzheng injection on cerebral ischemia/reperfusion injured aged rats].

OBJECTIVE: To study the protective effects of Shenqi Fuzheng Injection (SFI) on cerebral ischemia/reperfusion injured aged rats. METHODS: Aged SD male rats, weighing 200-300 g, were randomly divided into 4 groups: the model group, the sham-operative group, the nimodipine positive control group (abbreviated as nimodipine group) and the SFI group. Focal cerebral ischemia/reperfusion injured rat model was established by modified Longa method. SFI was administered by intravenous dripping 1 week before ischemia. Nervous function disorder, brain infarction area, serum lactate dehydrogenase (LDH) and creatine kinase (CK) levels, brain contents of Ca2+ , water, MDA and SOD levels were observed 3 hrs after ischemia and 3 hrs after reperfusion. RESULTS: perimental results showed that SFI could obviously improve the deficit of nerve function, decrease water content of brain, reduce the infarction area of brain, and inhibit Ca2 + aggregation. LDH and CK levels in serum and MDA in brain were obviously lower than those in the model group and SOD activity in cerebral tissue was obviously higher than that in the model group. CONCLUSION: SFI had protective effect on cerebral ischemia/reperfusion injured aged rats, whose mechanism might be related to the inhibition of lipid peroxidation and Ca2+ aggregation.