Combinatorial metabolic engineering provides a new strategy for further improvement of L-tyrosine or other metabolic biosynthesis pathways in S. cerevisiae.
The intestinal flora plays an important role in the development of many human and animal diseases. Microbiome association studies revealed the potential regulatory function of intestinal bacteria in many liver diseases, such as autoimmune hepatitis, viral hepatitis and alcoholic hepatitis. However, the key intestinal bacterial strains that affect pathological liver injury and the underlying functional mechanisms remain unclear. We found that the gut microbiota from gentamycin (Gen)-treated mice significantly alleviated concanavalin A (ConA)-induced liver injury compared to vancomycin (Van)-treated mice by inhibiting CD95 expression on the surface of hepatocytes and reducing CD95/CD95L-mediated hepatocyte apoptosis. Through the combination of microbiota sequencing and correlation analysis, we isolated 5 strains with the highest relative abundance,
Bacteroides acidifaciens
(BA),
Parabacteroides distasonis
(PD),
Bacteroides thetaiotaomicron
(BT),
Bacteroides dorei
(BD) and
Bacteroides uniformis
(BU), from the feces of Gen-treated mice. Only BA played a protective role against ConA-induced liver injury. Further studies demonstrated that BA-reconstituted mice had reduced CD95/CD95L signaling, which was required for the decrease in the L-glutathione/glutathione (GSSG/GSH) ratio observed in the liver. BA-reconstituted mice were also more resistant to alcoholic liver injury. Our work showed that a specific murine intestinal bacterial strain, BA, ameliorated liver injury by reducing hepatocyte apoptosis in a CD95-dependent manner. Determination of the function of BA may provide an opportunity for its future use as a treatment for liver disease.
The
use of particulate adjuvants offers an interesting method for
enhancing and modulating the immune responses elicited by vaccines.
Aluminum salt (Alum) is one of the most important immune adjuvants
approved by the Food and Drug Administration for use in humans because
of its safety and efficacy, but it lacks the capacity to induce strong
cellular and mucosal immune responses. In this study, we designed
an antigen delivery system that combines aluminum salts with β-glucan
particles. The β-glucan-aluminum particles (GP-Al) exhibited
a highly uniform size of 2–4 μm and could highly specifically
target antigen-presenting cells (APCs) and strongly induce dendritic
cell (DC) maturation and cytokine secretion. In vivo studies showed that both WT mice and HBV-Tg mice immunized with
hepatitis B surface antigen (HBsAg)-containing GP-Al displayed high
anti-HBsAg IgG titers in the serum. Furthermore, in contrast to mice
receiving the antigen alone, mice immunized with the particulate adjuvant
exhibited IgG2a antibody titers and higher antigen-specific IFN-γ
levels in splenocytes. In conclusion, we developed GP-Al microspheres
to serve as a hepatitis B vaccine to enhance both humoral and cellular
immune responses, representing a safe and promising system for antigen
delivery.
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