Extracellular polysaccharides from Sporidiobolus pararoseus alleviates rheumatoid through ameliorating gut barrier function and gut microbiota.

Rheumatoid arthritis (RA) is becoming a prevalent autoimmune disease affecting people worldwide, necessitating the exploration of novel therapeutic approaches due to the associated adverse effects of conventional therapeutic drugs. Sporidiobolus pararoseus polysaccharide (SPP) has been shown to exhibit significant immune stimulation and antioxidant activities. In this study, we constructed a mouse model of type II collagen-induced arthritis (CIA) to investigate the effects and potential mechanisms of SPP intervention on RA. Results showed that SPP intervention alleviated the degree of ankle swelling, joint histopathologic changes, joint pathological score and the expression of serum-associated inflammatory mediators (such as IL-1ß and IL-6). 16S rRNA sequencing results indicated that SPP intervention significantly remodeled the intestinal microbiota composition. In particular, SPP intervention significantly increased the relative abundance of beneficial bacteria (Parabacteroides, Bacteroides and Rikenellaceae_RC9_gut_group) with the potential to degrade fungal polysaccharides or produce short-chain fatty acids (SCFAs). The production of SCFAs (especially acetic acid, propionic acid and butyric acid) indeed increased significantly. These SCFAs played an important role in maintaining intestinal barrier function and regulating immune homeostasis, which helped reduce inflammatory responses and alleviate the symptoms of RA.

Chlorogenic acid improves the cognitive deficits of sleep-deprived mice via regulation of immunity function and intestinal flora.

BACKGROUND: Sleep deprivation (SD) has become a global health concern with serious consequences containing memory deficits and gastrointestinal dysfunctions. The gut-brain axis serves as a crucial link between the brain and gut, and the utilization of chlorogenic acid (CGA) presents a compelling strategy for mitigating or potentially resolving various neuroinflammation-associated disorders. However, it is still unknown how CGA may interact with the gut, microbiota and the brain during SD. PURPOSE: This study aims to explore the therapeutic effect and underlying mechanism of microbiota-gut-brain axis by which CGA prevents SD-induced cognitive deficits. STUDY DESIGN AND METHODS: CGA (30, 60 mg/kg.bw.) was gavaged to C57BL/6 mice, and then they were submitted to 48-h SD. The cognitive and spatial learning abilities were investigated through behavioral tests. Furthermore, we explored the action mechanism of this compound with haematological analysis, histopathological examination, Western blot, ELISA and 16S rRNA gene pyrosequencing from colonic contents. RESULTS: The cognitive deficits induced by SD were significantly relieved by administration of CGA in a dose-dependent manner. The hematoxylin and eosin staining of hippocampus and colon tissues indicated that pretreatment of CGA not only protected brain tissue from SD, but also maintained intestinal integrity. In the hippocampus, the increased pro-inflammatory neurometabolites were significantly prevented by CGA, and an immune profile capable of hippocampal-dependent spatial memory was improved via Nrf2/PPAR signaling pathways. The observed immunomodulatory effect was concomitant with augmentation of the intestinal barrier, as evidenced by the heightened expressions of tight junction proteins. 16S rRNA analysis of colonic contents revealed that levels of Clostridia_UCG-014 and lipopolysaccharide were significantly inhibited, and those of Lactobacillus and intestinal tight junction proteins were upregulated in the CGA group. Pathways of ko05322 (immune disease) and ko04610 (immune system) were significantly regulated by CGA. Based on PICRUSt2 algorithm, CGA probably influenced gut microbial functions via several metabolism pathways, such as arginine biosynthesis, pyrimidine metabolism and purine metabolism. CONCLUSION: The present study first proved the efficacy and mechanism of CGA in alleviating SD-induced cognitive impairment and neuroinflammation via creating a systemic protection, a bidirectional communication system connecting the gut with the brain. The intestinal barrier improvement and the reshaped "SD microbiota" profiles restored immunity functions, which were probably the main contributors to Nrf2/PPAR activation and the neuroprotective effect of CGA. Overall, this work provided novel insights of CGA, which might guide the more reasonable clinical use of CGA in the pathogenesis of sleep-related disorders.

Immunosenescence and macrophages: From basics to therapeutics.

Ageing decreases the function of the immune system and increases susceptibility to some chronic, infectious, and autoimmune diseases. Senescence cells, which produce senescence-associated secretory phenotypes (SASPs), can activate the innate and adaptive immune responses. Macrophages are among the most abundant innate immune cell types in senescent microenvironments. Senescence-associated macrophages, recruited by SASPs, play a vital role in establishing the essential microenvironments for maintaining tissue homeostasis. However, it's important to note that these senescence-associated macrophages can also influence senescent processes, either by enhancing or impeding the functions of tissue-resident senescent cells. In this discussion, we describe the potential targets of immunosenescence and shed light on the probable mechanisms by which macrophages influence cellular senescence. Furthermore, we analyze their dual function in both clearing senescent cells and modulating age-related diseases. This multifaceted influence operates through processes including heightened inflammation, phagocytosis, efferocytosis, and autophagy. Given the potential off-target effects and immune evasion mechanisms associated with traditional anti-ageing strategies (senolytics and senomorphics), 'resetting' immune system tolerance or targeting senescence-related macrophage functions (i.e., phagocytotic capacity and immunosurveillance) will inform treatment of age-related diseases. Therefore, we review recent advances in the use of macrophage therapeutics to treat ageing and age-associated disorders, and outline the key gaps in this field.

Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study.

Hyperlipidemia is a common metabolic disorder, which can lead to obesity, hypertension, diabetes, atherosclerosis and other diseases. Studies have shown that polysaccharides absorbed by the intestinal tract can regulate blood lipids and facilitate the growth of intestinal flora. This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. This study provides a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia.

Reshaped Gut Microbial Composition and Functions Associated with the Antifatigue Effect of Salidroside in Exercise Mice.

SCOPE: Salidroside (SA) is an active compound derived from Rhodiola rosea and is widely used in healthcare foods. However, the underlying mechanism and its specific role in regulating the gut microbial community during exercise (Ex) remains unknown. METHODS AND RESULTS: Mice are subjected to a weight-loaded swimming test (WST) Ex to determine how gut microbiota affects the antifatigue activity of SA. The SA-treated group mice (100 mg kg-1 .bw.) display a significant increase in swimming time compared to the control group (26.2 versus 10.5 min, p < 0.01), as well as an increase in respiratory enzymatic activities after swimming. The respiratory enzymatic activities are significantly higher in the SA-treated group than in the RS (regular rest) group after swimming. The bacteria profiles in the Ex + SA group change significantly with higher species diversity and abundance. Receiver operating characteristic (ROC) curves of Alistipes, Rikenellaceae, Parabacteroides, Candidatus Arthromitus, and Lactobacillus indicate a high diagnostic utility to distinguish SA treatment. Microbial function analysis shows that SA may improve Ex-induced fatigue by modulating energy metabolism-related processes. CONCLUSIONS: SA demonstrates antifatigue effects on various levels of regulating energy metabolism and microbial composition, providing insights into the underlying mechanisms of SA as a natural prebiotic.

Mechanistic toxicity assessment of differently sized and charged polystyrene nanoparticles based on human placental cells.

Nanoplastics, as emerging contaminants, may be degraded from microplastics and released into aquatic systems globally, which pose threats to human health via ingestion with food or water. Although plastic fragments have been isolated from placental tissues in pregnant women, little is known about the direct toxicity of nanoplastics on human placental cells that plays a critical role in maintaining healthy growth of fetus. This study explored the mechanistic toxicity of polystyrene nanoplastics (PS-NPs) with different sizes (25, 50, 100 and 500 nm) and surface charges (-NH2, -COOH and unlabeled) on human placental cells. Results showed that PS-NPs had size- and surface charge-specific toxicity pattern. The smaller the PS-NP size was, the greater the toxicity induced on human placental cells. In terms of surface charges, NH2-labeled PS-NPs caused greater effects on cytotoxicity, inhibition of protein kinase A (PKA) activity, oxidative stress, and cell cycle arrest compared to COOH-labeled and unmodified PS-NPs. PS-NPs also induced size- and surface charge-dependent expression profiles of genes involved in various and interrelated toxicity pathways. In particular, PS-NPs increased intracellular reactive oxygen species in human placental cells, which can induce DNA damage and lead to cell cycle arrest in G1or G2 phase, inflammation and apoptosis. Our findings provide empirical evidences that the negative effects of nanoplastics on human placental cells, and highlight the necessity to conduct risk assessment of nanoplastics on female reproduction and fetal development.

Mechanistic toxicity assessment of fine particulate matter emitted from fuel combustion via pathway-based approaches in human cells.

Fuel exhaust particulate matter (FEPM) is an important source of air pollution worldwide. However, the comparative and mechanistic toxicity of FEPMs emitted from combustion of different fuels is still not fully understood. This study employed pathway-based approaches via human cells to evaluate mechanistic toxicity of FEPMs. The results showed that FEPMs caused concentration-dependent (0.1-200 µg/mL) cytotoxicity and oxidative stress. FEPMs at low concentration (10 µg/mL) induced cell cycle arrest in S and G2 phases, while high level of FEPMs (200 µg/mL) caused cell cycle arrest in G1 phase. Different FEPMs induced distinct expression profiles of toxicity-related genes, illustrating different toxic mechanisms. Furthermore, FEPMs inhibited the phosphorylation of protein kinase A (PKA), which related with reproductive toxicity. Spearman rank correlations among the chemicals carried by FEPMs and the toxic effects revealed that PAHs and metals promoted cell cycle arrest in the G1 phase and suppressed PKA activity. Furthermore, PAHs (Nap and Acy) and metals (Al and Pb) in FEPMs were highly and positively correlated with the expression of genes involved in apoptosis, ER stress, metal stress and inflammation. Our findings offered more mechanistic information of FEPMs at the level of subcellular toxicity and help to better understand their potential health effects.