Hypoglycemic Effect of Nobiletin via Gut Microbiota-Metabolism Axis on Hyperglycemic Mice.

SCOPE: Prediabetes and diabetes are major public health problems worldwide without specific cure currently. Gut microbes have been recognized as one of the vital therapeutic targets for diabetes. The exploration that nobiletin (NOB) whether affects gut microbes provides a scientific basis for its application. METHODS AND RESULTS: A hyperglycemia animal model is established using high-fat-fed ApoE-/- mice. After 24 weeks of NOB intervention, the level of fasting blood glucose (FBG), glucose tolerance, insulin resistance, and glycosylated serum protein (GSP) are measured. Pancreas integrity is observed by hematoxylin-eosin (HE) staining and transmission electron microscopy. 16s RNA sequencing and untargeted metabolomics are to determine the changes of intestinal microbial composition and metabolic pathways. The levels of FBG and GSP in hyperglycemic mice are effectively reduced. The secretory function of pancreas is improved. Meanwhile, NOB treatment restored the gut microbial composition and affected metabolic function. Furthermore, NOB treatment regulates the metabolic disorder mainly through lipid metabolism, amino acid metabolism, and Secondary bile acid metabolism, etc. In addition, it is possibly existed mutual promotion between microbe and metabolites. CONCLUSION: NOB probably plays a vital role in the hypoglycemic effect and pancreatic islets protection by improving microbiota composition and gut metabolism.

The biological regulatory activities of Flammulina velutipes polysaccharide in mice intestinal microbiota, immune repertoire and heart transcriptome.

The effects of a novel Flammulina velutipes polysaccharide (FVP) on intestinal microbiota, immune repertoire and heart transcriptome were investigated in this study. The results showed that FVP treatment could effectively regulate the abundance of colonic microbiota. And FVP exhibited obvious immunoregulatory effect by influencing V gene and J gene fragments usage on TCRα chain. The usage frequency of TRBV1, TRBJ1-6 and TRBJ1-5 were significantly altered, and 41 V-J pairs were identified with obvious difference after FVP treatment. Furthermore, the mRNA of mice heart was analyzed by transcriptome assay. Total 525 genes and 1587 mRNA were significantly changed after FVP treatment. KEGG annotation indicated that the up-regulated mRNA was enriched in 17 pathways including adherens junction, mTOR signaling pathway, insulin signaling pathway, mitophagy, tight junction, PPAR signaling pathway and TNF signaling pathway, etc. Meanwhile, the down-regulated mRNA was gathered in AMPK signaling pathway, metabolism of xenobiotics by cytochrome P450, apelin signaling pathway, PPAR signaling pathway, PI3K-Akt signaling pathway, insulin signaling pathway, cardiac muscle contraction, adrenergic signaling in cardiomyocytes, Fc gamma R-mediated phagocytosis, etc. The great potential exhibited by FVP could make it an ideal candidate as complementary medicine or functional food for promotion of health.

Flammulina velutipes polysaccharide improves C57BL/6 mice gut health through regulation of intestine microbial metabolic activity.

Flammulina velutipes polysaccharides (FVP) can improve gut health through gut microbiota and metabolism regulation. In this study, the 28-days fed experiment was used to investigate gut microbime and metabolic profiling induced by FVP. After treatment, intestinal tissue section showed the higher villus height and villus height/crypt depth (V/C) value in FVP-treated group. The 16 s rRNA gene sequencing revealed microbiota composition alteration caused by FVP, as the Firmicutes phylum increased while Bacteroidetes phylum slightly decreased. The metabolic profiling was detected by LC/MS and results showed 56 and 99 compounds were dramatically changed after FVP treatment in positive and negative ion mode, respectively. Annotation in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways displayed the adjustment of energy metabolism, amino acid metabolism, nucleotide metabolism and other related basic pathways after FVP treatment. Our study suggested that FVP can be developed as a dietary supplement for intestine health promotion.

Multifunctional Biodegradable Prussian Blue Analogue for Synergetic Photothermal/Photodynamic/Chemodynamic Therapy and Intrinsic Tumor Metastasis Inhibition.

To date, various Prussian blue analogues (PBAs) have been prepared for biomedical applications due to their unique structural advantages. However, the safety and effectiveness of tumor treatment still need further exploration. This contribution reports a facile synthesis of PBA with superior tumor synergetic therapeutic effects and a detailed mechanistic evaluation of their intrinsic tumor metastasis inhibition activity. The as-synthesized PBA has a uniform cube structure with a diameter of approximately 220 nm and shows high near-infrared light (NIR) photoreactivity, photothermal conversion efficiency (41.44%), and photodynamic effect. Additionally, PBA could lead to a chemodynamic effect, which is caused by the Fenton reaction and ferroptosis. The combined therapy strategy of PBA exhibits notable tumor ablation properties due to photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) effects without obvious toxicity in vivo. The PBA has also shown potential as a contrast agent for magnetic resonance imaging (MRI) and photoacoustic (PA) imaging. More importantly, careful investigations reveal that PBA displays excellent biodegradation and anti-metastasis properties. Further exploration of the PBA implies that its underlying mechanism of intrinsic tumor metastasis inhibition activity can be attributed to the modulation of epithelial-mesenchymal transition (EMT) expression. The considerable potential exhibited by the as-synthesized PBA makes it an ideal candidate as a synergetic therapeutic agent for tumor treatment.

Exploring the Preventive Effect and Mechanism of Senile Sarcopenia Based on "Gut-Muscle Axis".

Age-related sarcopenia probably leads to chronic systemic inflammation and plays a vital role in the development of the complications of the disease. Gut microbiota, an environmental factor, is the medium of nutritional support to muscle cells, having significant impact on sarcopenia. Consequently, a significant amount of studies explored and showed the presence of gut microbiome-muscle axis (gut-muscle axis for short), which was possibly considered as the disease interventional target of age-related sarcopenia. However, a variety of nutrients probably affect the changes of the gut-muscle axis so as to affect the healthy balance of skeletal muscle. Therefore, it is necessary to study the mechanism of intestinal-muscle axis, and nutrients play a role in the treatment of senile sarcopenia through this mechanism. This review summarizes the available literature on mechanisms and specific pathways of gut-muscle axis and discusses the potential role and therapeutic feasibility of gut microbiota in age-related sarcopenia to understand the development of age-related sarcopenia and figure out the novel perspective of the potential therapeutic interventional targets.

Injectable Hydrogel-Based Nanocomposites for Cardiovascular Diseases.

Cardiovascular diseases (CVDs), including a series of pathological disorders, severely affect millions of people all over the world. To address this issue, several potential therapies have been developed for treating CVDs, including injectable hydrogels as a minimally invasive method. However, the utilization of injectable hydrogel is a bit restricted recently owing to some limitations, such as transporting the therapeutic agent more accurately to the target site and prolonging their retention locally. This review focuses on the advances in injectable hydrogels for CVD, detailing the types of injectable hydrogels (natural or synthetic), especially that complexed with stem cells, cytokines, nano-chemical particles, exosomes, genetic material including DNA or RNA, etc. Moreover, we summarized the mainly prominent mechanism, based on which injectable hydrogel present excellent treating effect of cardiovascular repair. All in all, it is hopefully that injectable hydrogel-based nanocomposites would be a potential candidate through cardiac repair in CVDs treatment.