The anti-obesity effects of a water-soluble glucan from Grifola frondosa via the modulation of chronic inflammation

Polysaccharides from Grifola frondosa (G. frondosa) have anti-obesity and anti-inflammatory activities. In this study, the major type, molecular weight, homogeneity and structure of a polysaccharide purified from G. frondosa (denoted GFPA) were determined. In high-fat diet (HFD)-treated mice, 8 weeks of GFPA administration efficiently decreased body weight and blood glucose concentration and counteracted hyperlipidemia. GFPA efficiently decreased adipocyte size and ameliorated inflammatory infiltration in the three types of white adipose tissue and alleviated steatosis, fat accumulation and inflammatory infiltration in the livers of HFD-fed mice. GFPA also decreased the concentrations of aspartate aminotransferase, alanine aminotransferase and pro-inflammatory factors in the sera and livers of HFD-treated mice. Furthermore, GFPA was found to regulate lipid metabolism via the inhibition of ceramide levels in HFD-treated mice. GFPA exhibited strong anti-obesity effects via the modulation of chronic inflammation through Toll-like receptor 4/nuclear factor kappa-B signaling, which supports the use of GFPA for the treatment of obesity

Moving beyond size and phosphatidylserine exposure: evidence for a diversity of apoptotic cell-derived extracellular vesicles in vitro

Apoptosis is a form of programmed cell death that occurs throughout life as part of normal development as well as pathologic processes including chronic inflammation and infection. Although the death of a cell is often considered as the only biological outcome of a cell committed to apoptosis, it is becoming increasingly clear that the dying cell can actively communicate with other cells via soluble factors as well as membrane-bound extracellular vesicles (EVs) to regulate processes including cell clearance, immunity and tissue repair. Compared to EVs generated from viable cells such as exosomes and microvesicles, apoptotic cell-derived EVs (ApoEVs) are less well defined and the basic criteria for ApoEV characterization have not been established in the field. In this study, we will examine the current understanding of ApoEVs, in particular, the ApoEV subtype called apoptotic bodies (ApoBDs). We described that a subset of ApoBDs can be larger than 5 μm and smaller than 1 μm based on flow cytometry and live time-lapse microscopy analysis, respectively. We also described that a subset of ApoBDs can expose a relatively low level of phosphatidylserine on its surface based on annexin A5 staining. Furthermore, we characterized the presence of caspase-cleaved proteins (in particular plasma membrane-associated or cytoplasmic proteins) in samples enriched in ApoBDs. Lastly, using a combination of biochemical-, live imaging- and flow cytometry-based approaches, we characterized the progressive lysis of ApoBDs. Taken together, these results extended our understanding of ApoBDs

Oral administration of bovine milk-derived extracellular vesicles induces senescence in the primary tumor but accelerates cancer metastasis

The concept that extracellular vesicles (EVs) from the diet can be absorbed by the intestinal tract of the consuming organism, be bioavailable in various organs, and in-turn exert phenotypic changes is highly debatable. Here, we isolate EVs from both raw and commercial bovine milk and characterize them by electron microscopy, nanoparticle tracking analysis, western blotting, quantitative proteomics and small RNA sequencing analysis. Orally administered bovine milk-derived EVs survive the harsh degrading conditions of the gut, in mice, and is subsequently detected in multiple organs. Milk-derived EVs orally administered to mice implanted with colorectal and breast cancer cells reduce the primary tumor burden. Intriguingly, despite the reduction in primary tumor growth, milk-derived EVs accelerate metastasis in breast and pancreatic cancer mouse models. Proteomic and biochemical analysis reveal the induction of senescence and epithelial-to-mesenchymal transition in cancer cells upon treatment with milk-derived EVs. Timing of EV administration is critical as oral administration after resection of the primary tumor reverses the pro-metastatic effects of milk-derived EVs in breast cancer models. Taken together, our study provides context-based and opposing roles of milk-derived EVs as metastasis inducers and suppressors

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

<i>Pleurotus abieticola</i> Polysaccharide Alleviates Hyperlipidemia Symptoms via Inhibition of Nuclear Factor-κB/Signal Transducer and Activator of Transcription 3-Mediated Inflammatory Responses

Hyperlipidemia (HLP) is a metabolic syndrome induced by obesity, which has been widely recognized as a significant threat to human health. Pleurotus abieticola, an edible lignin-degrading fungus, remains relatively understudied in terms of its bioactivity and medicinal properties. In this study, the lipid-lowering effect of Pleurotus abieticola polysaccharide (PAPS1) was systematically explored in high-fat diet (HFD)-induced HLP mice. The findings demonstrated that the administration of PAPS1 significantly inhibited bodyweight gain, ameliorated blood glucose and lipid levels, reduced fat accumulation, and mitigated hepatic injury in HLP mice. In addition, PAPS1 demonstrated the capability to increase the levels of three distinct fecal metabolites while simultaneously reducing the levels of eight other fecal metabolites in HLP mice. According to biological detection, PAPS1 reduced the hepatic level of reactive oxygen species (ROS) and pro-inflammatory factors, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, -6, -17A, -22, and -23, and increased the expression of anti-inflammatory factor IL-10. Combined with proteomics, Western blot and immunohistochemistry analysis showed that PAPS1 exerted suppressive effects on inflammation and oxidative damage by inhibiting the nuclear factor-κB (NF-κB)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in HLP mice. These findings offer evidence supporting the effectiveness of PAPS1 as a therapeutic agent in reducing lipid levels through its targeting of chronic inflammation

Studies on the Anti-Gouty Arthritis and Anti-hyperuricemia Properties of Astilbin in Animal Models

The purpose of this study was to investigate potential anti-gouty effect of astilbin (AS) and its possible mechanisms. In mice with hyperuricemia induced by potassium oxonate (OXO) and yeast extract powder (YEP), AS and febuxostat (FB) reduced the serum uric acid (UA) and xanthine oxidase (XO). Moreover, AS and FB reduced the levels of reactive oxygen species and increased the content of superoxide dismutase (SOD), glutathione peroxidase and catalase present in the serum. In acute gouty arthritis rats induced by intraarticular monosodium urate crystal injection, AS and Colchicine (COL) alleviated the ankle joints swelling, and reduced the inflammatory cell infiltration. AS also reduced the levels of interleukin 1β, interleukin 6, tumor necrosis factor alpha and monocyte chemoattractant protein 1 in liver. The present study first confirmed the anti-gouty effect of AS in mice with hyperuricemia and rats with acute gouty arthritis, which provides the experimental evidence for further evaluation of AS as a candidate for gout treatment

Intestinal Microbiota and Metabolomics Reveal the Role of <i>Auricularia delicate</i> in Regulating Colitis-Associated Colorectal Cancer

Background: The edible fungus Auricularia delicate (ADe) is commonly employed in traditional medicine for intestinal disorders; however, its inhibitory effect on colitis-associated colorectal cancer (CAC) and the underlying mechanisms remain unexplored. (2) Methods: The inhibitory effect of ADe on CAC was investigated using a mouse model induced by azoxymethane/dextran sulfate sodium. Results: ADe effectively suppressed the growth and number of intestinal tumors in mice. Intestinal microbiota analyses revealed that ADe treatment increased Akkermansia and Parabacteroides while it decreased Clostridium, Turicibacter, Oscillospira, and Desulfovibrio. ADe regulated the levels of 2′-deoxyridine, creatinine, 1-palmitoyl lysophosphatidylcholine, and choline in serum. Furthermore, the levels of these metabolites were associated with the abundance of Oscillospira and Paraacteroides. ADe up-regulated the free fatty acid receptor 2 and β-Arrestin 2, inhibited the nuclear factor kappa B (NF-κB) pathway, and significantly attenuated the levels of inflammatory cytokines, thereby mitigating the inflammatory in CAC mice. Conclusions: The protective effect of ADe in CAC mice is associated with the regulation of intestinal microbiota, which leads to the inhibition of NF-kB pathway and regulation of inflammation