ABSTRACT
The Lachnospiraceae family holds promise as a source of next-generation probiotics, yet a comprehensive delineation of its diversity is lacking, hampering the identification of suitable strains for future applications. To address this knowledge gap, we conducted an in-depth genomic and functional analysis of 1868 high-quality genomes, combining data from public databases with our new isolates. This data set represented 387 colonization-selective species-level clusters, of which eight genera represented multilineage clusters. Pan-genome analysis, single-nucleotide polymorphism (SNP) identification, and probiotic functional predictions revealed that species taxonomy, habitats, and geography together shape the functional diversity of Lachnospiraceae. Moreover, analyses of associations with atherosclerotic cardiovascular disease (ACVD) and inflammatory bowel disease (IBD) indicated that several strains of potentially novel Lachnospiraceae species possess the capacity to reduce the abundance of opportunistic pathogens, thereby imparting potential health benefits. Our findings shed light on the untapped potential of novel species enabling knowledge-based selection of strains for the development of next-generation probiotics holding promise for improving human health and disease management.
ABSTRACT
The senescence of mesenchymal stem cells (MSCs) impairs their regenerative capacity to maintain tissue homeostasis. Numerous studies are focusing on the interventions and mechanisms to attenuate the senescence of MSCs. C-phycocyanin (C-PC) is reported to have multiple functions such as antitumor, antioxidation, anti-inflammation and anti-aging roles, but there is little research about the effects of C-PC on the senescence of MSCs. Here we investigated the roles and mechanism of C-PC on MSCs senescence. In vitro results showed that C-PC could reduce senescence, enhance proliferation, promote the adipogenic and osteogenic differentiation in senescent MSCs induced by oxidative stress. In vivo D-Galactose (D-Gal) induced rats aging models showed C-PC also increased the viability and differentiation of intrinsic senescent bone marrow derived MSCs (BMSCs). Furthermore, C-PC also decreased the levels of oxidative stress markers ROS or MDA, elevated the SOD activity, and increased the anti-inflammatory factors. Proteomic chip analysis showed that C-PC interacted with ZDHHC5, and their interaction was verified by pull down assay. Overexpression of ZDHHC5 aggravated the senescence of MSCs and greatly lessened the beneficial effects of C-PC on senescence. In addition, we found ZDHHC5 regulated autophagy by altering LC3, Beclin1 and PI3K/AKT/mTOR pathway. In summary, our data indicated that C-PC ameliorates the senescence of MSCs through zinc finger Asp-His-His-Cys (DHHC) domain-containing protein 5 (ZDHHC5) mediated autophagy via PI3K/AKT/mTOR pathway. The present study uncovered the key role of autophagy in MSCs senescence and PI3K/AKT/mTOR pathway may be a potential target for anti-senescence studies of MSCs.
ABSTRACT
In recent years, with the development of nanomaterials, the research of drug delivery systems has become a new field of cancer therapy. Compared with conventional antitumor drugs, drug delivery systems such as drug nanoparticles (NPs) are expected to have more advantages in antineoplastic effects, including easy preparation, high efficiency, low toxicity, especially active tumor-targeting ability. Drug delivery systems are usually composed of delivery carriers, antitumor drugs, and even target molecules. At present, there are few comprehensive reports on a summary of drug delivery systems applied for tumor therapy. This review introduces the preparation, characteristics, and applications of several common delivery carriers and expounds the antitumor mechanism of different antitumor drugs in delivery carriers in detail which provides a more theoretical basis for clinical application of personalized cancer nanomedicine in the future.
