Tang (2020) Phlorizin ameliorates obesity-associated endotoxemia and insulin resistance in high-fat diet-fed mice by targeting the gut microbiota and intestinal barrier integrity,

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Alzheimer's disease (AD) is a neurodegenerative disease that primarily occurs in elderly individuals with cognitive impairment. Although extracellular β-amyloid (Aβ) accumulation and tau protein hyperphosphorylation are considered to be leading causes of AD, the molecular mechanism of AD remains unknown. Therefore, in this study, we aimed to explore potential biomarkers of AD. Next-generation sequencing (NGS) datasets, GSE173955 and GSE203206, were collected from the Gene Expression Omnibus (GEO) database. Analysis of differentially expressed genes (DEGs), gene ontology (GO) functional enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein networks were performed to identify genes that are potentially associated with AD. Analysis of the DEG based protein-protein interaction (PPI) network using Cytoscape indicated that neuroinflammation and T-cell antigen receptor (TCR)-associated genes (LCK, ZAP70, and CD44) were the top three hub genes. Next, we validated these three hub genes in the AD database and utilized two machine learning models from different AD datasets (GSE15222) to observe their general relationship with AD. Analysis using the random forest classifier indicated that accuracy (78%) observed using the top three genes as inputs differed only slightly from that (84%) observed using all genes as inputs. Furthermore, another data set, GSE97760, which was analyzed using our novel eigenvalue decomposition method, indicated that the top three hub genes may be involved in tauopathies associated with AD, rather than Aβ pathology. In addition, protein-protein docking simulation revealed that the top hub genes could form stable binding sites with acetylcholinesterase (ACHE). This suggests a potential interaction between hub genes and ACHE, which plays an essential role in the development of anti-AD drug design. Overall, the findings of this study, which systematically analyzed several AD datasets, illustrated that LCK, ZAP70, and CD44 may be used as AD biomarkers. We also established a robust prediction model for classifying patients with AD.

“Lianzhifan solution” (LZF) is produced by the natural fermentation of coptis root and gardenia fruit, and it is a classic prescription for external use in anorectal department. During the fermentation process, the structural evolution of microbial communities led to significant changes in the chemical profile. In this study, we first analyzed the dynamic changes of chemical components as well as the composition and succession of microbial community during the whole fermentation process of LZF, and confirmed the changes of characteristics of nine compounds during the whole fermentation process by metabolic profile. Further analysis found that there was no significant change of alkaloids in all stages of fermentation of LZF, but there were significant changes of iridoids in the middle and late stage of fermentation by deglycosylation. Genipin gentiobioside and geniposide were converted to genipin by biotransformation, showing that deglycosylation was the main event occurring in the fermentation. The community composition and abundance of species in 10 and 19days LZF fermentation broth were analyzed with high-throughput sequencing technology, and 16 dominant bacterial genera and 15 dominant fungal genera involved in the fermentation process were identified. Correlation analysis revealed that Penicillium expansum and Aspergillus niger involved in the fermentation were the dominant genera closely related to the dynamic changes of the deglycosylation of the main chemical components, and P. expansum YY-46 and A. niger YY-9 strains were obtained by the further fractionation. Then the monoculture fermentation process was evaluated, whereby we found that the deglycoside conversion rate of iridoid glycosides was greatly improved and the fermentation cycle was shortened by 3–4 times. This finding combined with equivalence evaluation of chemical component and pharmacodynamics to confirm that P. expansum YY-46 and A. niger YY-9 strains were key strains for fermentation concoction. This study established an efficient and practical screening strategy “Microfauna communities-Chemical component-Pharmacodynamic” axis for key strain, to improve the production process and formulating good manufacturing practice (GMP) work, and it is also applicable to the whole fermentation drugs industry.Graphical AbstractThe figure highly summarizes the research content of this study and shows the screening process of key strains in LZF fermentation.

The fungal cell wall is an ideal target for the design of antifungal drugs. In this study we used an analog of cell wall polymer, a highly deacetylated long-chain chitosan oligosaccharide (HCOS), to test its effect against pathogenic Candida strains. Results showed that HCOS was successfully incorporated into the dynamic cell wall organization process and exhibited an apparent antifungal activity against both plankton and mature fungal biofilm, by impairing the cell wall integrity. Unexpectedly, mechanistic studies suggested that HCOS exerts its activity by interfering with family members of PHR β-(1,3)-glucanosyl transferases and affecting the connection and assembly of cell wall polysaccharides. Furthermore, HCOS showed great synergistic activity with different fungicides against Candida cells, especially those in biofilm. These findings indicated HCOS has a great potential as an antifungal drug or drug synergist and proposed a novel antifungal strategy with structure-specific oligosaccharides mimicking cell wall polysaccharide fragments.