No abstract

Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in industrialized societies. The lack of metabolite biomarkers has impeded the clinical diagnosis of atherosclerosis so far. In this study, stable atherosclerosis patients (n=16) and age- and sex-matched non-atherosclerosis healthy subjects (n=28) were recruited from the local community (Harbin, P. R. China). The plasma was collected from each study subject and was subjected to metabolomics analysis by GC/MS. Pattern recognition analyses (principal components analysis, orthogonal partial least-squares discriminate analysis, and hierarchical clustering analysis) commonly demonstrated plasma metabolome, which was significantly different from atherosclerotic and non-atherosclerotic subjects. The development of atherosclerosis-induced metabolic perturbations of fatty acids, such as palmitate, stearate, and 1-monolinoleoylglycerol, was confirmed consistent with previous publication, showing that palmitate significantly contributes to atherosclerosis development via targeting apoptosis and inflammation pathways. Altogether, this study demonstrated that the development of atherosclerosis directly perturbed fatty acid metabolism, especially that of palmitate, which was confirmed as a phenotypic biomarker for clinical diagnosis of atherosclerosis.

Traditional Chinese medicine (TCM) has good clinical application prospects in diabetes treatment. In addition, TCM is less toxic and/or has fewer side effects and provides various therapeutic effects. Berberine (BBR) is isolated as the main component in many TCM kinds (e.g., Rhizoma Coptidis and Berberidis Cortex). Furthermore, BBR can reduce blood sugar and blood fat, alleviate inflammation, and improve the state of patients. Based on the recent study results of BBR in diabetes treatment, the BBR pharmacokinetics and mechanism on diabetes are mainly studied, and the specific molecular mechanism of related experimental BBR is systematically summarized and analyzed. Clinical studies have proved that BBR has a good therapeutic effect on diabetes, suggesting that BBR may be a promising drug candidate for diabetes. More detailed BBR mechanisms and pathways of BBR need to be studied further in depth, which will help understand the BBR pharmacology in diabetes treatment.

Neuroinflammation is considered as one of the crucial pathogenesis in promoting neurodegenerative progress of Alzheimer’s disease (AD). As complementary and alternative therapy, electroacupuncture (EA) stimulation has been widely used in clinical practice for anti-inflammation. However, whether EA promotes the cognitive deficits resulting from neuroinflammation in AD remains unclear. In this study, the presenilin 1 and 2 conditional double knockout (PS cDKO) mice, exhibited a series of AD-like pathology, robust neuroinflammatory responses, and memory deficits, were used to evaluate the potential neuroprotective effect of EA at Baihui (GV 20) and Shenting (GV 24) by behavioral testing, electrophysiology recording, and molecular biology analyzing. First, we observed that EA improved memory deficits and impaired synaptic plasticity. Moreover, EA possesses an ability to suppress the hyperphosphorylated tau and robust elevated NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in PS cDKO mice. Importantly, MCC950, a potent and selective inhibitor of NLPR3 inflammasome, has similar effects on inhibiting the hyperphosphorylated tau and the robust elevated NLRP3 components and neuroinflammatory responses of PS cDKO mice as well as EA treatment. Furthermore, EA treatment is not able to further improve the AD-like phenotypes of PS cDKO mice in combination with the MCC950 administration. Therefore, EA stimulation at GV 20 and GV 24 acupoints may be a potential alternative therapy for deterring cognitive deficits in AD through suppression of NLRP3 inflammasome activation.

No abstract

Background Given the clinical low efficient treatment based on mono-brain-target design in Alzheimer’s disease (AD) and an increasing emphasis on microbiome-gut-brain axis which was considered as a crucial pathway to affect the progress of AD along with metabolic changes, integrative metabolomic signatures and microbiotic community profilings were applied on the early age (2-month) and mature age (6-month) of presenilin1/2 conditional double knockout (PS cDKO) mice which exhibit a series of AD-like phenotypes, comparing with gender and age-matched C57BL/6 wild-type (WT) mice to clarify the relationship between microbiota and metabolomic changes during the disease progression of AD. Materials and methods Urinary and fecal samples from PS cDKO mice and gender-matched C57BL/6 wild-type (WT) mice both at age of 2 and 6 months were collected. Urinary metabolomic signatures were measured by the gas chromatography-time-of-flight mass spectrometer, as well as 16S rRNA sequence analysis was performed to analyse the microbiota composition at both ages. Furthermore, combining microbiotic functional prediction and Spearman’s correlation coefficient analysis to explore the relationship between differential urinary metabolites and gut microbiota. Results In addition to memory impairment, PS cDKO mice displayed metabolic and microbiotic changes at both of early and mature ages. By longitudinal study, xylitol and glycine were reduced at both ages. The disturbed metabolic pathways were involved in glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions, starch and sucrose metabolism, and citrate cycle, which were consistent with functional metabolic pathway predicted by the gut microbiome, including energy metabolism, lipid metabolism, glycan biosynthesis and metabolism. Besides reduced richness and evenness in gut microbiome, PS cDKO mice displayed increases in Lactobacillus, while decreases in norank_f_Muribaculaceae, Lachnospiraceae_NK4A136_group, Mucispirillum, and Odoribacter. Those altered microbiota were exceedingly associated with the levels of differential metabolites. Conclusions The urinary metabolomics of AD may be partially mediated by the gut microbiota. The integrated analysis between gut microbes and host metabolism may provide a reference for the pathogenesis of AD.

Chronic neuroinflammation has been shown to exert adverse influences on the pathology of Alzheimer's disease (AD), associated with the release of abundant proinflammatory mediators by excessively activated microglia, causing synaptic dysfunction, neuronal degeneration, and memory deficits. Thus, the prevention of microglial activation‐associated neuroinflammation is important target for deterring neurodegenerative disorders. Peony seed oil (PSO) is a new food resource, rich in α‐linolenic acid, the precursor of long chain omega‐3 polyunsaturated fatty acids, including docosahexaenoic acid and eicosapentaenoic acid, which exhibit anti‐inflammatory properties by altering cell membrane phospholipid fatty acid compositions, disrupting lipid rafts, and inhibiting the activation of the proinflammatory transcription factor NF‐κB. However, few studies have examined the anti‐neuroinflammatory effects of PSO in AD, and the relevant molecular mechanisms remain unclear. Presenilin1/2 conditional double knockout (PS cDKO) mice display obvious AD‐like phenotypes, such as neuroinflammatory responses, synaptic dysfunction, and cognitive deficits. Here, we assessed the potential neuroprotective effects of PSO against neuroinflammation‐mediated cognitive deficits in PS cDKO using behavioral tests and molecular biologic analyses. Our study demonstrated that PSO suppressed microglial activation and neuroinflammation through the down‐regulation of proinflammatory mediators, such as inducible NOS, COX‐2, IL‐1β, and TNF‐α, in the prefrontal cortex and hippocampus of PS cDKO mice. Further, PSO significantly lessened memory impairment by reversing hyperphosphorylated tau and synaptic proteins deficits in PS cDKO mice. Importantly, PSO's therapeutic effects on cognitive deficits were due to inhibiting neuroinflammatory responses mediated by NF‐κB signaling pathway. Taken together, PSO may represent an effective dietary supplementation to restrain the neurodegenerative processes of AD.

QGYD improves the immune response to pseudomonal infection in rats by stimulating the production of protective antibodies against drug-resistant proteins VIM-1, SPM-1, and TEM-1. In addition, it protects the immune system and maintains immune responsiveness by restoring IL-1β and Th1/Th2 levels.