Water extract of Pingchuan formula ameliorated murine asthma through modulating metabolites and gut microbiota.

BACKGROUND: Pingchuan formula is a traditional Chinese herbal prescription for asthma, but its components and underlying mechanisms remain unclear. Here, we evaluated its anti-asthmatic actvity and regulatory effects on the gut microbiota in mice based on the traditional Chinese medicine Zang-Fu theory, which proposed the exterior-interior relationship between the lung and the large intestine. METHODS: Mouse model withovalbumin (OVA)-induced asthma was used to assess the protective effect of the water extract of Pingchuan formula (PC). The chemical compounds of PC and mouse serum metabolites were identified by Ultraperformance liquid chromatography-Q Exactive HF-X spectrometry. Gut microbiota was evaluated by 16 S rRNA gene sequencing. The gut microbiota was depleted with a broad-spectrum antibiotic mixture (Abx) to explore whether it plays a role in the protective effects of PC. RESULTS: PC mainly contains phenols, flavonoids, alkaloids, carboxylic acids, and their derivatives. PC attenuated OVA-induced asthma in mice by alleviating inflammatory infiltration, indicated by decreased levels of IL-18, IL-6, IL-4, and Eotaxin in lung tissues. PC treatment altered the serum metabolites and affected the pyrimidine pathway. In addition, our results showed that acacetin and abscisic acid were the key serum metabolites PC treatment changed the composition of gut microbiota by increasing the relative abundance of Clostridia_UCG_014 and Akkermansia while decreasing Blautia, Barnesiella, and Clostridium_Ⅲ at the genus level. Importantly, the Abx treatment partly abolished the anti-asthmatic effect of PC. CONCLUSION: We demonstrated that PC could alleviate OVA-induced asthma in mice and protect against inflammatory infiltration in lungs via modulating the serum metabolites and gut microbiota, thereby providing a new reference for the therapeutic effect of PC.

Low Weight Polysaccharide of Hericium erinaceus Ameliorates Colitis via Inhibiting the NLRP3 Inflammasome Activation in Association with Gut Microbiota Modulation.

Ulcerative colitis (UC), one of the typical inflammatory bowel diseases caused by dysregulated immunity, still requires novel therapeutic medicine with high efficacy and low toxicity. Hericium erinaceus has been widely used to treat different health problems especially gastrointestinal sickness in China for thousands of years. Here, we isolated, purified, and characterized a novel low weight polysaccharide (HEP10, Mw: 9.9 kDa) from the mycelia of H. erinaceus in submerged culture. We explored the therapeutic effect of HEP10 on UC and explored its underlying mechanisms. On one hand, HEP10 suppressed the production of TNF-α, IL-1ß, IL-6, inducible iNOS, and COX-2 in LPS challenged murine macrophage RAW264.7 cells, as well as in colons from DSS-induced colitis mice. On the other hand, HEP10 treatment markedly suppressed the activation of NLRP3 inflammasome, NF-κB, AKT, and MAPK pathways. Moreover, HEP10 reversed DSS-induced alternation of the gut community composition and structure by significantly increasing Akkermansia muciniphila and also promoting functional shifts in gut microbiota. Structural equation modeling also highlighted that HEP10 can change widely through gut microbiota. In conclusion, HEP10 has a better prebiotic effect than the crude polysaccharides of H. erinaceus, which can be used as a novel dietary supplement and prebiotic to ameliorate colitis.

The Influence of Alcohol Consumption, Depressive Symptoms and Sleep Duration on Cognition: Results from the China Health and Retirement Longitudinal Study.

AIM: Healthy cognition-related factors include alcohol consumption, depressive symptoms, and sleep duration. However, less is known about the role of these factors in the dyad or tripartite relationships. In this study, we examined whether there were potential mediation effects, moderation effects, and interactions between these factors in the longitudinal study. METHODS: Both cross-sectional data analysis and a longitudinal study were performed using baseline and 2018 data from the China Health and Retirement Longitudinal Study (CHARLS) cohort. CHARLS is a nationwide survey program covering 450 villages and 150 counties in 28 provinces that aims to investigate comprehensive demographic information. After selecting participants from the CHARLS cohort, 15,414 were included in the study. Non-drinkers, those who drink more than once a month, and those who drink less than once a month were defined by their alcohol consumption. Depressive symptoms were defined as nondepressed (less than or equal to 12) and depressed (more than 12). Sleep duration was defined as 7-8 h per night, ≤6 h per night, and ≥9 h per night. The total cognitive scores were calculated from memory, orientation, and executive tests. The PROCESS macro in SPSS was used to analyze all mediations and moderating mediations. RESULTS: Alcohol consumption has a positive correlation with cognition. The global cognition z scores of participants with depressive symptoms were significantly lower than those of the control (all p's < 0.001), in different models. The memory score (ß: -0.148; 95% CI: -0.240 to -0.056; p = 0.002), the executive score (ß: -0.082; 95% CI: -0.157 to -0.006; p = 0.033), and the global cognition score (ß: -0.105; 95% CI: -0.187 to -0.023; p = 0.012) of participants defined as ≤6 h per night were, obviously, less than the control (7-8 h per night). An association between depression and alcohol consumption has been found, and the protective effects have been reversed by depression, which caused the cognition decline. Sleep duration was identified as a moderator, influencing the relationship between depressive symptoms and cognitive function. Besides, there was an interaction causing cognition decline among alcohol consumption, depressive symptoms, and sleep duration. Cognitive function showed a marked downward trend with increasing age. CONCLUSIONS: In this model, depression primarily mediates the relationship between alcohol consumption and cognition, and sleep duration changes the mediation effect. Furthermore, there is a significant interaction between alcohol consumption, depressive symptoms, and sleep duration, which are significantly associated with cognitive function.

Spore Powder of Paecilomyces hepiali Shapes Gut Microbiota to Relieve Exercise-Induced Fatigue in Mice.

Paecilomyces hepiali, a fungal strain isolated from natural Ophiocordyceps sinensis, contains similar pharmacologically active components, has been used widely as a substitute of O. sinensis in functional food and medicine. However, the components and anti-fatigue effects of P.hepiali spores and their mechanisms of action are largely unknown. Here, we compared the chemical composition in P.hepiali spore (HPS) and mycelium (HPM) by liquid chromatography with tandem mass spectrometry analysis. We found 85 metabolites with significant differences, and HPS contains more L-Malic acid, Oxalacetic acid, Fructose-1,6-bisphosphate, and L-Arginine than HPM. Then we evaluated their anti-fatigue effects and regulatory effects on the gut microbiota in mice. The forced swimming time (SW) was only significantly increased in HPS groups: the high and low dose of the HPS group was 101% and 72% longer than the control group, respectively. Both HPS and HPM treatment decreased lactic acid, blood urea nitrogen, creatine kinase while increased lactate dehydrogenase (LDH) levels in the blood. Moreover, mice treated with HPS and HPM showed less skeletal muscle fiber spacing and breakage. The relative abundance of Alistips, Eubacterium, Bacterium, Parasutterella, and Olsenella in the gut microbiota of the HPS group was higher than that in the HPM group through 16S rRNA gene sequencing analysis. These changes may be related to the regulation of nucleotide, amino acid, and carbohydrate metabolism. Correlation analysis between the gut microbiota and fatigue-related indicators suggested that Alistips, Clostridium, Akkermansia, Olsenella, and Lactobacillus were positively correlated with the SW and LDH content. Our findings demonstrated that HPS has beneficial anti-fatigue effects by regulating gut microbiota.

Association between serum vitamin D level during pregnancy and recurrent spontaneous abortion: A systematic review and meta-analysis.

PROBLEM: Previous studies had shown that there might be an association between serum vitamin D concentrations and the occurrence of recurrent spontaneous abortion (RSA). However, the conclusions remained controversial. The objective of this study was to systematically review the evidence for an epidemiological association between vitamin D and RSA. METHOD OF STUDY: The literature search was performed in the following databases: PubMed, Web of Science, Embase and Chinese databases. The I2 statistic was used to evaluate heterogeneity. Effect sizes were calculated using fixed or random effects models, including standardized mean difference (SMD), odds ratios (OR) and their 95% confidence intervals (95% CI). Then, we performed subgroup analysis, sensitivity analysis and publication bias analysis. RESULTS: Fourteen studies from five countries were included. Based on the results, patients with RSA had lower vitamin D levels than controls (SMD = -1.48, 95% CI: -2.01, -.94, P < .001), and pregnant women with vitamin D deficiency (VDD) had a higher risk of developing RSA (OR = 4.02, 95% CI: 2.23, 7.25, P < .001). There was remarkable heterogeneity between studies (I2SMD  = 97.3%, P < .001; I2OR  = 82.2%, P < .001). The results of the subgroup analysis suggested that heterogeneity may be caused by the assay method, age and region. Sensitivity analysis showed the analysis results were robust. CONCLUSION: Patients with RSA had lower serum vitamin D levels than normal pregnant women, and pregnant women with VDD might be at higher risk for RSA.

Association of serum bisphenol AF concentration with depressive symptoms in adolescents: A nested case-control study in China.

BACKGROUND: As an important alternative to bisphenol A (BPA), bisphenol AF (BPAF) is widely used and can be detected in multiple human biological samples. However, there are few studies on neurotoxicity of BPAF at present. In particular, no epidemiological studies have investigated BPAF in relation to depressive symptoms in adolescents. Here, our study aimed to evaluate the associations between serum BPAF concentrations and depressive symptoms in adolescents. METHODS: A nested case-control study within an ongoing longitudinal prospective adolescent cohort that was established in Huaibei, China was conducted. A total of 175 participants who had new-onset depressive symptoms (cases) and 175 participants without depressive symptoms (controls) were included. Serum BPAF concentrations was measured using ultra-high-performance liquid chromatography-tandem mass spectrometry. The associations between BPAF exposure and the risk of depressive symptoms in adolescents were assessed using conditional logistic regression. The dose-response relationship between BPAF level and depressive symptoms was estimated using restricted cubic spline analyses. RESULTS: In this study, the detection rate of serum BPAF was 100%, and the median (interquartile range, IQR) serum BPAF concentration was 5.24 (4.41-6.11) pg/mL in the case group and 4.86 (4.02-5.77) pg/mL in the control group (P = 0.009). Serum BPAF exposure was a risk factor for depressive symptoms (odds ratio (OR)= 1.132, 95% confidence interval (CI):1.013-1.264). After adjustment for all for confounders, compared with the low-exposure group, the high-exposure group had a 2.806-fold increased risk of depressive symptoms (OR=2.806, 95% CI: 1.188-6.626). Stratified analysis by sex revealed that males were more vulnerable to BPAF exposure than females. After adjustment for all confounders, compared with the low-exposure group, the relative risk of depressive symptoms in the high-exposure group was 3.858 (95% CI: 1.118-12.535) for males, however, no significant association between BPAF exposure and depressive symptoms was found in females. In addition, there was a marked linear association between BPAF exposure and the risk of depressive symptoms in the total population and in males. CONCLUSIONS: The adolescents in this study were widely exposed to low levels of BPAF. A significant positive association was found between serum BPAF levels and the risk of depressive symptoms. The association was significantly modified by sex, and males were more vulnerable to BPAF exposure than females.

Finite Element Analysis of Crack Propagation in Adhesive Joints with Notched Adherends.

The adherends notching technique has been the subject of a few recent studies and consists of tailoring the geometry of the adjoined layers to mitigate the bondline peak stresses and enhance the joint strength. In the present study, we explored the effect of the adherends notching technique on crack propagation using finite element (FE) simulations based on the cohesive zone model (CZM) of fracture. Double cantilever beam (DCB) adhesive joints subjected to quasistatic loading were considered as a model material system. An array of equally spaced notches was placed on the faying sides of the adherends, oriented perpendicularly to the direction of crack growth. A parametric investigation was carried out to ascertain the role of the notches and the input cohesive properties on various performance metrics, e.g., load-displacement response and dissipated energy. The proposed notching strategy promotes an unstable crack pinning/depinning process, which effectively delays crack growth and increases the effective work of fracture. Additionally, we found that the overall behaviour is tunable by changing geometric (i.e., notch spacing and depth) and bondline material properties.