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AIMTo investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl4)-induced acute hepatic dysfunction.METHODSA rat model of HE was established with CCl4. Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was examined.RESULTSFMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating pro-inflammatory factors such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment.CONCLUSIONFMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.

To explore the relationship between the extent of central nervous system (CNS) injury and patient outcomes meanwhile research the potential risk factors associated with neurologic sequelae. In this retrospective cohort study, we analyzed data from 117 consecutive patients (86 survivors, 31 nonsurvivors) with exertional heat stroke (EHS) who had been admitted to intensive care unit (ICU) at 48 Chinese hospitals between April 2003 and July 2015. Extent of CNS injury was dichotomized according to Glasgow coma scale (GCS) score (severe 3–8, not severe 9–15). We then assessed differences in hospital mortality based on the extent of CNS injury by comparing 90-day survival time between the patient groups. Exploring the risk factors of neurologic sequelae. The primary outcomewas the 90-day survival ratewhich differed between the 2 groups (P = .023). The incidence of neurologic sequelae was 24.4%. For its risk factors, duration of recurrent hyperthermia (OR = 1.73, 95% CI: 1.20–2.49, P = .003), duration of CNS injury (OR = 1.39, 95% CI: 1.04–1.85, P = .025), and low GCS in the first 24 hours after admission (OR = 2.39, 95% CI: 1.11–5.15, P = .025) were selected by multivariable logistic regression. Cooling effect was eliminated as a factor (OR = 2641.27, 95% CI 0.40–1.73_107, P = .079). Significant differences in 90-day survival ratewere observed based on the extent of CNS injury in patients with EHS, and incidence was 24.4% for neurologic sequelae. Duration of recurrent hyperthermia, duration of CNS injury, and low GCS score in the first 24 hours following admission may be independent risk factors of neurologic sequelae. Cooling effect should be validated in the further studies.

Japanese encephalitis (JE) is prevalent throughout eastern and southern Asia and the Pacific Rim. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. Despite the importance of JE, little is known about its pathogenesis. The role of oxidative stress in the pathogenesis of viral infections has led to increased interest in its role in JEV infections. This review focuses mainly on the role of oxidative stress in the pathogenesis of JEV infection and the antiviral effect of antioxidant agents in inhibiting JEV production. First, this review summarizes the pathogenesis of JE. The pathological changes include neuronal death, astrocyte activation, and microglial proliferation. Second, the relationship between oxidative stress and JEV infection is explored. JEV infection induces the generation of oxidants and exhausts the supply of antioxidants, which activates specific signaling pathways. Finally, the therapeutic efficacy of a variety of antioxidants as antiviral agents, including minocycline, arctigenin, fenofibrate, and curcumin, was studied. In conclusion, antioxidants are likely to be developed into antiviral agents for the treatment of JE.

Burkholderia pseudomallei is a gram-negative, facultative intracellular bacterium, which causes a disease known as melioidosis. Professional phagocytes represent a crucial first line of innate defense against invading pathogens. Uptake of pathogens by these cells involves the formation of a phagosome that matures by fusing with early and late endocytic vesicles, resulting in killing of ingested microbes. Host Rab GTPases are central regulators of vesicular trafficking following pathogen phagocytosis. However, it is unclear how Rab GTPases interact with B . pseudomallei to regulate the transport and maturation of bacterial-containing phagosomes. Here, we showed that the host Rab32 plays an important role in mediating antimicrobial activity by promoting phagosome maturation at an early phase of infection with B . pseudomallei . And we demonstrated that the expression level of Rab32 is increased through the downregulation of the synthesis of miR-30b/30c in B . pseudomallei infected macrophages. Subsequently, we showed that B . pseudomallei resides temporarily in Rab32-positive compartments with late endocytic features. And Rab32 enhances phagosome acidification and promotes the fusion of B . pseudomallei -containing phagosomes with lysosomes to activate cathepsin D, resulting in restricted intracellular growth of B . pseudomallei . Additionally, Rab32 mediates phagosome maturation depending on its guanosine triphosphate/guanosine diphosphate (GTP/GDP) binding state. Finally, we report the previously unrecognized role of miR-30b/30c in regulating B . pseudomallei -containing phagosome maturation by targeting Rab32 in macrophages. Altogether, we provide a novel insight into the host immune-regulated cellular pathway against B . pseudomallei infection is partially dependent on Rab32 trafficking pathway, which regulates phagosome maturation and enhances the killing of this bacterium in macrophages.