Oral fecal transplantation enriches Lachnospiraceae and butyrate to mitigate acute liver injury

Summary: While fecal microbiota transplantation (FMT) shows promise in treating human diseases, oral capsule FMT is more accepted and accessible to patients. However, microbe selection in the upper gastrointestinal tract (UGIT) through oral administration remains unclear. Here, we demonstrate that short-term oral fecal gavage (OFG) alleviates acetaminophen-induced acute liver injury (AILI) in mice, regardless of the divergent effects of commensal gut microbes. Pasteurized fecal gavage yields similar therapeutic effects. OFG enriches gut Lachnospiraceae and butyrate compared to donor feces. Butyrate mitigates AILI-induced ferroptosis via AMPK-ULK1-p62 signaling to simultaneously induce mitophagy and Nrf2 antioxidant responses. Combined N-acetylcysteine and butyrate administration significantly improves AILI mouse survival rates. These observations indicate the significance of the UGIT in modulating the implanted fecal microbes through oral administration and its potential biological and clinical impacts. Our findings also highlight a possible strategy for applying microbial metabolites to treat acute liver injury

Hsp72 up-regulates Epstein-Barr virus EBNALP coactivation with EBNA2

The Epstein-Barr virus (EBV) transcriptional coactivator EBNALP specifically associates and colocalizes with Hsp72 in lymphoblastoid cell lines. We now find that overexpression of Hsp72 more than doubled EBNALP coactivation with EBNA2 of a transfected EBV LMP1 promoter in B lymphoblasts, did not affect EBNA2 or EBNALP protein levels, and strongly up-regulated EBNA2 and EBNALP coactivation of LMP1 protein expression from the endogenous EBV genome in latency I infected Akata cells. The Hsp72 ATP, protein binding, and the C-terminal regulatory domains were required for full activity. An EBNALP deletion mutant, EBNALPd45, which does not associate with Hsp72, coactivated with EBNA2, but was not affected by Hsp72 overexpression, despite Hsp72 up-regulation of wild-type EBNALP coactivation with EBNA2 at all levels of EBNALP expression, indicating the importance of Hsp72 association with EBNALP for Hsp72 up-regulation of coactivation. Of importance, a 90% RNAi knockdown of Hsp72 reduced EBNALP coactivation with EBNA2 of transfected EBV LMP1 and Cp promoters by approximately 50%. Overexpression of the Hsp72 C-terminal interacting and regulatory protein, CHIP, strongly down-regulated EBNALP coactivation, independently of CHIP ubiquitin ligase activity. CHIP effects were Hsp72 dependent, indicating a background downmodulating role for CHIP in Hsp72 augmentation of EBNA2 and EBNALP coactivation. Based on these and other cited data, we favor a model in which Hsp72 chaperones EBNALP shuttling of repressors from EBNA2-enhanced promoters

Kreislaufstillstand unter besonderen Umständen: Elektrolytstörungen, Vergiftungen, Ertrinken, Unter-kühlung, Hitzekrankheit, Asthma, Anaphylaxie, Herzchirurgie, Trauma, Schwangerschaft, Stromunfall

Soar J, Perkins GD, Abbas G, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 8. Cardiac arrest in special circumstances: Electrolyte abnormalities, poisoning, drowning, accidental hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution. Resuscitation. 2010;81(10):1400-1433