Microbial-Derived γ-Aminobutyric Acid: Synthesis, Purification, Physiological Function, and Applications.

γ-Aminobutyric acid (GABA) is an important nonprotein amino acid that extensively exists in nature. At present, GABA is mainly obtained through chemical synthesis, plant enrichment, and microbial production, among which microbial production has received widespread attention due to its safety and environmental benefits. After using microbial fermentation to obtain GABA, it is necessary to be isolated and purified to ensure its quality and suitability for various industries such as food, agriculture, livestock, pharmaceutics, and others. This article provides a comprehensive review of the different sources of GABA, including its presence in nature and the synthesis methods. The factors affecting the production of microbial-derived GABA and its isolation and purification methods are further elucidated. Moreover, the main physiological functions of GABA and its application in different fields are also reviewed. By advancing our understanding of GABA, we can unlock its full potential and further utilize it in various fields to improve human health and well-being.

Insight into the structure, biosynthesis, isolation method and biological function of teichoic acid in different gram-positive microorganisms: A review.

Teichoic acid (TA) is a weakly anionic polymer present in the cell walls of Gram-positive bacteria. It can be classified into wall teichoic acid (WTA) and lipoteichoic acid (LTA) based on its localization in the cell wall. The structure and biosynthetic pathway of TAs are strain-specific and have a significant role in maintaining cell wall stability. TAs have various beneficial functions, such as immunomodulatory, anticancer and antioxidant activities. However, the purity and yield of TAs are generally not high, and different isolation methods may even affect their structural integrity, which limits the research progress on the probiotic functions of TA. This paper reviews an overview of the structure and biosynthetic pathway of TAs in different strains, as well as the research progress of the isolation and purification methods of TAs. Furthermore, this review also highlights the current research status on the biological functions of TAs. Through a comprehensive understanding of this review, it is expected to pave the way for advancements in isolating and purifying high-quality TAs and, in turn, lay a foundation for contributing to the development of targeted probiotic therapies.

Characteristic flavor metabolic network of fish sauce microbiota with different fermentation processes based on metagenomics.

This article purposed to discuss the connection between microbiota and characteristic flavor of different fish sauces (Natural fermentation (WQ), koji outdoor fermentation (YQ), heat preservation with enzyme (BWE), and heat preservation with koji (BWQ)) at the early (3 months) and late stage (7 months). A total of 117 flavor compounds were determined according to SPME-GC-MS analysis. O2PLS-DA and VIP values were used to reveal 15 and 28 flavor markers of different fish sauces at 3 and 7 M of fermentation. Further, the possible flavor formation pathways were analyzed using metagenomic sequencing, and the key microbes associated with flavor formation were identified at the genetic level. The top 10 genera related to flavor generation, such as Lactobacillus, Staphylococcus, Enterobacter, etc., appeared to play a prominent part in the flavor formation of fish sauce. The difference was that only BWQ and BWE groups could produce ethyl-alcohol through amino acid metabolism, while YQ, BWE and BWQ groups could generate phenylacetaldehyde through the transformation of Phe by α-ketoacid decarboxylase and aromatic amino acid transferase. Our research contributes to clarifying the various metabolic roles of microorganisms in the flavor generation of fish sauce.

Eliminating senescent chondrogenic progenitor cells enhances chondrogenesis under intermittent hydrostatic pressure for the treatment of OA.

BACKGROUND: Osteoarthritis (OA) is a major cause of limb dysfunction, and distraction arthroplasty which generates intermittent hydrostatic pressure (IHP) is an effective approach for OA treatment. However, the result was not always satisfactory and the reasons remained unresolved. Because aging is recognized as an important risk factor for OA and chondrogenic progenitor cells (CPCs) could acquire senescent phenotype, we made a hypothesis that CPCs senescence could have harmful effect on chondrogenesis and the outcome of distraction arthroplasty could be improved by eliminating senescent CPCs pharmacologically. METHODS: The role of senescent CPCs on distraction arthroplasty was first determined by comparing the cartilage samples from the failure and non-failure patients. Next, the biological behaviors of senescent CPCs were observed in the in vitro cell culture and IHP model. Finally, the beneficial effect of senescent CPCs clearance by senolytic dasatinib and quercetin (DQ) on cartilage regeneration was observed in the in vitro and in vivo IHP model. RESULTS: Larger quantities of senescent CPCs along with increased IL-1 ß secretion were demonstrated in the failure patients of distraction arthroplasty. Senescent CPCs revealed impaired proliferation and chondrogenic capability and also had increased IL-1 ß synthesis, typical of senescence-associated secretory phenotype (SASP). CPCs senescence and SASP formation were mutually dependent in vitro. Greater amounts of senescent CPCs were negatively correlated with IHP-induced chondrogenesis. In contrast, chondrogenesis could be significantly improved by DQ pretreatment which selectively induced senescent CPCs into apoptosis in the in vitro and in vivo IHP model. Mechanistically, senescent CPCs elimination could decrease SASP formation and therefore promote the proliferation and chondrogenic regeneration capacity of the surrounding survived CPCs under IHP stimulation. CONCLUSIONS: Eliminating senescent CPCs by senolytics could decrease SASP formation and improve the result of joint distraction arthroplasty effectively. Our study provided a novel CPCs senescence-based therapeutic target for improving the outcome of OA treatment.

AKT3 deficiency in M2 macrophages impairs cutaneous wound healing by disrupting tissue remodeling.

AKT signaling and M2 macrophage-guided tissue repair are key factors in cutaneous wound healing. A delay in this process threatens human health worldwide. However, the role of AKT3 in delayed cutaneous wound healing is largely unknown. In this study, histological staining and transcriptomics demonstrated that prolonged tissue remodeling delayed wound healing. This delay was accompanied by defects in AKT3, collagen alpha-1(I) chain (COL1A1), and collagen alpha-1(XI) chain (COL11A1) expression and AKT signaling. The defect in AKT3 expression was M2 macrophage-specific, and decreased AKT3 protein levels were observed in CD68/CD206-positive macrophages from delayed wound tissue. Downregulation of AKT3 in M2 macrophages did not influence cell polarization but impaired collagen organization by inhibiting COL1A1 and COL11A1 expression in human skin fibroblasts (HSFs). Moreover, a co-culture model revealed that the downregulation of AKT3 in the human monocytic cell line (THP-1)-derived M2 macrophages impaired HSF proliferation and migration. Finally, cutaneous wound healing in AKT3-/- mice was much slower than that of AKT3+/+ mice, and F4/80 macrophages from the AKT3-/- mice had an impaired ability to promote wound healing. Thus, the downregulation of AKT3 in M2 macrophages prolonged tissue remodeling and delayed cutaneous wound healing.