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Objective To explore the mechanism of notoginsenoside Rg1 in preventing and treating Alzheimer′s disease (AD). Methods Rat model of AD was established by injecting amyloid beta peptide 1-42(Aβ1-42) into the lateral ventricle of SD rats. Then the animals were randomly divided into three groups: sham-operated group, model group and Rg1 treatment group. The treatment group was treated with Rg1 gavage and the sham-operated group was treated with saline gavage. Learning and memory capacity of rats were examined by Morris water maze experiment (MWM). Moreover, the contents of MDA and SOD in cerebral cortex were detected by chemical colorimetry; immuno-histochemistry was used to detect caspase-3 protein in the cerebral cortex and Western blot was employed to detect the expression of p38 and p-p38 proteins. Results Compared with the sham-operated group, the model group had a prolonged escape latency, reduced stay time in the target quadrant and reduced frequency of leaping over platform; increased MDA and decreased SOD in cerebral cortex; increased caspase-3 protein-positive neurons. The difference of p38 expression was not statistically significant and the phosphorylation of p38 was upregulated(P＜0.05). The rats in Rg1 treatment group had a shorter escape latency, increased stay time in quadrant Ⅲ, increased frequency of leaping over platform, decreased caspase-3 positive neurons and the phosphorylation level of p38,decreased MDA and increased SOD compared with the model group(P＜0.05). Conclusions Rg1 significantly improves learning and memory capacities, increases antioxidant capacity and plays neuro-protective effect in AD rat model by inhibition of p38 activation.

AbstractBackgroundMethodsResultsConclusionsThe association of cardiovascular health (CVH) with asthma risk in U.S. adults remains unclear. This study aimed to explore the association of Life’s Essential 8 (LE8), a measurement of CVH, with asthma and investigate the potential mediating effect of inflammation and oxidative stress.The data was obtained from the National Health and Nutrition Examination Survey (NHANES) in 2005–2018. LE8 score (range 0 ∼ 100) was measured and categorized as low (<50), moderate (50 ∼ <80), and high (≥80) CVH. Survey-weighted logistic regression and restricted cubic spline model were employed to explore the association between LE8 score and asthma. Mediation analyses were conducted to identify the mediating effects of inflammation and oxidative stress biomarkers.This study included 10,932 participants aged ≥ 20 years, among whom 890 (8.14%) reported prevalent asthma. After adjusting for all covariates, the odd ratios (OR) for asthma were 0.67 (95% confidence interval (CI): 0.48, 0.94) in the moderate CVH group and 0.52 (95% CI: 0.34, 0.79) in the high CVH group compared with the low CVH group, respectively. The OR for asthma was 0.85 (95% CI: 0.78, 0.93) for every 10 score increase in LE8 score, and linear dose-response relationship was observed (p = 0.0642). Mediation analyses showed that inflammation and oxidative stress mediated 15.97% and 11.50% of the association between LE8 score and asthma, respectively (all p < 0.05).LE8 score was negatively associated with asthma, and inflammation and oxidative stress partially mediated this association. It is recommended that maintaining optimal CVH may prevent asthma. [ABSTRACT FROM AUTHOR]

Background: Protein-based pneumococcal vaccines (PBPVs) may offer expanded protection against Streptococcus pneumoniae and tackle the antimicrobial resistance crisis in pneumococcal infections. This study examined the safety and immunogenicity in healthy adults vaccinated with three doses of a protein-based pneumococcal vaccine containing pneumococcal surface protein A (PspA) (PRX1, P3296 and P5668) and in combination with a recombinant detoxified pneumolysin protein (PlyLD). Methods: This phase Ia randomized, double blind, placebo-controlled clinical study enrolled healthy adults aged 18–49 years. The participants were randomized into experimental (low-dose, medium-dose, high-dose) and placebo groups in a ratio of 3:1. Three doses of investigational vaccine were given to the participants with an interval of two months. Safety endpoints included the occurrence of total adverse reactions, solicited local and systemic adverse reactions, unsolicited adverse reactions, serious adverse events (SAEs), and several laboratory parameters. Immunogenicity endpoints included geometric mean titers (GMT) of anti-PspA (PRX1, P3296 and P5668) and anti-PlyLD antibodies level as determined by ELISA, seropositivity rates of PspA and PlyLD antibodies (>4-fold increase) and neutralization activity of anti-Ply antibody in serum. Results: A total of 118 participants completed the study of three doses. The candidate PBPV was safe and well-tolerated in all experimental groups. No vaccine-related SAEs were observed in this study. Most solicited adverse reactions were mild and transient. The most frequently reported solicited adverse reactions in the medium- and high-dose groups was pain at the injection site, while in the low-dose group it was elevated blood pressure. The immunogenicity data showed a sharp increase in the GMT level of anti-PspA-RX1, anti-PspA-3296, anti-PspA-5668, and anti-PlyLD antibodies in serum. The results also showed that the elicited antibodies were dosage-dependent. The high-dose group showed a higher immune response against PspA-RX1, PspA-3296, PspA-5668, and PlyLD antigens. However, repeat vaccination did not increase the level of anti-PspA antibodies but the level of anti-PlyLD antibody. High seropositivity rates were also observed for anti-PspA-RX1, anti-PspA-3296, anti-PspA-5668, and anti-PlyLD antibodies. In addition, a significant difference in the GMT levels of anti-Ply antibody between the high-, medium-, and low-dose groups post each vaccination were indicated by neutralization activity tests. Conclusions: The PBPV showed a safe and immunogenic profile in this clinical trial. Taking into consideration both safety and immunogenicity data, we propose a single dose of 50 µg (medium dose) of PBPV as the optimum approach in providing expanded protection against Streptococcus pneumoniae. [ABSTRACT FROM AUTHOR]