Integrated Network Pharmacology and Metabolomics Analysis of the Therapeutic Effects of Zi Dian Fang on Immune Thrombocytopenic Purpura

Current hormone-based treatments for immune thrombocytopenic purpura (ITP) are associated with potentially serious adverse reactions. Zi Dian Fang (ZDF) is a multi-target Traditional Chinese Medicine (TCM) used to treat both the symptoms and root causes of ITP, with fewer side effects than hormone-based treatments. This study analysis of the therapeutic effects of ZDF on ITP from three aspects: platelet proliferation, immunoregulation, and inflammation. After detection of 52 chemical constituents of ZDF by UPLC-Q-TOF/MS, The main targets and pathways affected by ZDF were screened by network pharmacology and verified by Western blot and ELISA. Meanwhile, metabolomics analysis were applied to a mouse model of ITP to identify and screen endogenous terminal metabolites differentially regulated by ZDF. Integrated network pharmacology and metabolomics analysis of the therapeutic effects of ZDF on ITP may be as follows: ZDF counteracts ITP symptoms mainly by inhibiting Ras/MAPKs (Ras/Mitogen-activated protein kinases) pathway, and the expression of upstream protein (Ras) and downstream protein (p-ERK, p-JNK, p-p38) were inhibited, which affects the content of effect index associated with proliferation (Thrombopoietin, TPO; Granulocyte-macrophage colony stimulating factor, GM-CSF), inflammation (Tumor necrosis factor-α, TNF-α; Interleukin-6, IL-6), immune (Interleukin-2, IL-2; Interferon-gamma, IFN-γ; Interleukin-4, IL-4), so that the body’s arginine, Δ12-prostaglandin j2 (Δ12-PGJ2), 9-cis-Retinoic Acid, sphingosine-1-phosphate (S1P), oleic acid amide and other 12 endogenous metabolites significantly changes. Considering the established safety profile, the present study suggests ZDF may be a useful alternative to hormone-based therapies for the treatment of ITP

Physical activity and liver health among urban and rural Chinese adults: results from two independent surveys

Background Increased physical activity has been associated with reduced risks of various physical and mental conditions. However, the association between physical activity and liver health in the Chinese general adult population is not clear. This study investigated whether physical activity, stratified by intensity (i.e. walking (light), moderate-to-vigorous), was associated with alanine aminotransferase (ALT) level in middle-aged and older Chinese adults. Methods Two independent surveys of urban (n = 5,824, males 44%, mean (standard deviation) age 52 (10) years) and rural populations (n = 20,269, males 41%, mean (standard deviation) age 51 (10) years) were undertaken. Physical activity was measured using the International Physical Activity Questionnaire, and in metabolic equivalents of task (MET) × minutes. Elevated serum level of ALT, a clinical surrogate of abnormal liver function, was defined as >40 IU/L (males) and >30 IU/L (females). Multivariable regression models were used. Results Amount of moderate-to-vigorous activity was inversely associated with serum level of ALT (β = −0.147 per 1k MET-minutes, p < 0.001), whereas walking was not associated. People who reached the lower limit of WHO recommendation (≥600 MET-minutes per week) had a reduced odds of ALT elevation, compared to those who did not (adjusted odds ratio: 0.85 95%CI (0.76, 0.95)). Conclusions Meeting the moderate-to-vigorous recommendations for physical activity in adults may be associated with decreased likelihood of abnormal liver function both in Chinese urban and rural populations. Promoting such activities could be a low-cost strategy in maintaining liver health as well as providing many other health-related benefits

Different Growth Responses of an Invasive Weed and a Native Crop to Nitrogen Pulse and Competition.

Resource pulses are a common event in agro-ecosystems. A pot experiment was conducted to assess the effects of nitrogen (N) pulses and competition on the growth of an invasive weed, Amaranthus retroflexus, and a native crop, Glycine max. A. retroflexus and G. max were planted in pure culture with two individuals of one species in each pot and in mixed culture with one A. retroflexus and one G. max individual and subjected to three N pulse treatments. The N treatments included a no-peak treatment (NP) with N applied stably across the growing period, a single-peak treatment (SP) with only one N addition on the planting date, and a double-peak treatment (DP) with two N additions, one on the planting date and the other on the flowering date. N pulse significantly impacted biomass and height of the two species across the whole growing season. However, only the relative growth rate (RGR) of A. retroflexus was significantly affected by N pulse. A. retroflexus had the greatest biomass and height in the SP treatment at the first harvest, and in the DP treatment at the last three harvests. Pure culture G. max produced the greatest biomass in the DP treatment. In mixed culture, G. max produced the greatest biomass in the NP treatment. Biomass production of both species was significantly influenced by species combination, with higher biomass in mixed culture than in pure culture at most growth stages. Relative yield total (RYT) values were all greater than 1.0 at the last three harvests across the three N treatments, suggesting partial resource complementarity occurred when A. retroflexus is grown with G. max. These results indicate that A. retroflexus has a strong adaptive capacity to reduce interspecific competition, likely leading to its invasion of G. max cropland in China

Anti-oxidative-initiated cognitive impairment amelioration in Alzheimer's disease model rats through preventive transcutaneous electrical acupoint stimulation

Background: Alzheimer's disease (AD) is a chronic and irreversible neurodegenerative disease. Oxidative stress emerges at the early AD stage. As a non-invasive therapy with few adverse reactions, transcutaneous electrical acupoint stimulation (TEAS) combines acupuncture points of traditional Chinese medicine (TCM) and electrical stimulation. This study aimed to investigate the amelioration effects of preventive TEAS treatment (P-TEAS) on cognitive impairment and oxidative stress in AD model rats. Methods: The AD model was established via subcutaneous injections of D-galactose (D-gal, 120 mg/kg/d) into the back of neck for 9 weeks in Sprague Dawley (SD) rats to simulate the oxidative stress in the early AD stage. On the first day of the 10th week, Aβ1–42 (1 μg/μl) was injected into the CA1 regions of the bilateral hippocampus. P-TEAS was synchronized from the first day of subcutaneous D-gal injections for 9 weeks. Results: Empirical measurements showed that P-TEAS can improve the spatial memory ability of AD model rats in the Morris water maze. Superoxide dismutase (SOD) was upregulated in the P-TEAS group. Through the detection of the anti-oxidative stress signaling pathway, namely, Kelch-like ECH-associated protein 1 (Keap1)/ NFE2-related factor 2 (Nrf2), it was found that P-TEAS could promote Nrf2 entering into the nucleus and upregulating the production of protective factors heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). It was also found that P-TEAS could downregulate the expressions of BCL2-associated X-protein (Bax), caspase 3, and caspase 9 to inhibit neuronal apoptosis. Conclusions: P-TEAS has similar efficacy to electroacupuncture in preventing AD occurrence and development. P-TEAS is a new non-invasive intervention therapy for the prevention of AD

Numerical Simulation of Bearing Characteristics of Bored Piles in Mudstone Based on Zoning Assignment of Soil around Piles

This study conducts a field indoor simulation test, SEM observation, and penetration test to determine the bearing capacity of the dynamic driving pile in the mudstone foundation. It comprehensively analyzes the variation laws of structure and strength of mudstone around piles after piling. Indeed, the strength of mudstone structure is significantly reduced from outside to inside. Therefore, the numerical simulation of piles in mudstone should consider the actual characteristics of soil damage around piles. The strength of mudstone after pile driving damage is measured, and the scatter diagram depicting the relationship between mudstone strength and pile side distance is produced. Then, the best-fitting curve of the relationship between the strength ratio and the distance ratio of the simulated pile driving test is established by the nonlinear fitting of multiple curves. A numerical simulation method is proposed to consider the damaged area and parameters surrounding the pile. The range of soil damage caused by pile driving in the mudstone foundation is determined to be two times that of the pile diameter. The disturbance area is divided into four parts on average, and the width of each part is 0.5d. The simulation results are compared to the conventional approach of uniform parameter assignment to prove the rationality of the method

Numerical Simulation of Bearing Characteristics of Bored Piles in Mudstone Based on Zoning Assignment of Soil around Piles

This study conducts a field indoor simulation test, SEM observation, and penetration test to determine the bearing capacity of the dynamic driving pile in the mudstone foundation. It comprehensively analyzes the variation laws of structure and strength of mudstone around piles after piling. Indeed, the strength of mudstone structure is significantly reduced from outside to inside. Therefore, the numerical simulation of piles in mudstone should consider the actual characteristics of soil damage around piles. The strength of mudstone after pile driving damage is measured, and the scatter diagram depicting the relationship between mudstone strength and pile side distance is produced. Then, the best-fitting curve of the relationship between the strength ratio and the distance ratio of the simulated pile driving test is established by the nonlinear fitting of multiple curves. A numerical simulation method is proposed to consider the damaged area and parameters surrounding the pile. The range of soil damage caused by pile driving in the mudstone foundation is determined to be two times that of the pile diameter. The disturbance area is divided into four parts on average, and the width of each part is 0.5d. The simulation results are compared to the conventional approach of uniform parameter assignment to prove the rationality of the method

F-values for the effects of nitrogen pulses (N), competition (C), and sampling date (D) on root, shoot, total biomass (Total), height (H), and relative growth rate (RGR) in <i>A</i>. <i>retroflexus</i> and <i>G</i>. <i>max</i> (Three-way RMANOVA).

<p>F-values for the effects of nitrogen pulses (N), competition (C), and sampling date (D) on root, shoot, total biomass (Total), height (H), and relative growth rate (RGR) in <i>A</i>. <i>retroflexus</i> and <i>G</i>. <i>max</i> (Three-way RMANOVA).</p

Changes in height of <i>A</i>. <i>retroflexus</i> (<i>A</i>. <i>r</i>) and <i>G</i>. <i>max</i> (<i>G</i>. <i>m</i>).

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156285#pone.0156285.g001" target="_blank">Fig 1</a> for abbreviations. All values are the average ±S.E.</p

Changes in root, shoot, and total biomass of <i>A</i>. <i>retroflexus</i> (<i>A</i>. <i>r</i>) and <i>G</i>. <i>max</i> (<i>G</i>. <i>m</i>).

<p>Plants were grown in pure culture (pure) or mixed culture (mix) in the three N pulsed treatments (SP, single-peak treatment; DP, double-peak treatment; NP, no-peak treatment). All values are the average ±S.E.</p