Resatorvid protects against hypoxic-ischemic brain damage in neonatal rats

Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.

Short‑chain fatty acids(SCFAs)as potential resuscitation factors that promote the isolation and culture of uncultured bacteria in marine sediments

Many marine bacteria are difcult to culture because they are dormant,rare or found in low-abundances.Enrichment culturing has been widely tested as an important strategy to isolate rare or dormant microbes.However,many more mechanisms remain uncertain.Here,based on 16S rRNA gene high-throughput sequencing and metabolomics technology,it was found that the short-chain fatty acids(SCFAs)in metabolites were signifcantly correlated with uncultured bacterial groups during enrichment cultures.A pure culture analysis showed that the addition of SCFAs to media also resulted in high efciency for the isolation of uncultured strains from marine sediments.As a result,238 strains belonging to 10 phyla,26 families and 82 species were successfully isolated.Some uncultured rare taxa within Chlorobi and Kiritimatiellaeota were successfully cultured.Amongst the newly isolated uncultured microbes,most genomes,e.g.bacteria,possess SCFA oxidative degradation genes,and these features might aid these microbes in better adapting to the culture media.A further resuscitation analysis of a viable but non-culturable(VBNC)Marinilabiliales strain verifed that the addition of SCFAs could break the dormancy of Marinilabiliales in 5 days,and the growth curve test showed that the SCFAs could shorten the lag phase and increase the growth rate.Overall,this study provides new insights into SCFAs,which were frst studied as resuscitation factors in uncultured marine bacteria.Thus,this study can help improve the utilisation and excavation of marine microbial resources,especially for the most-wanted or key players.