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Arteriosclerosis (AS) is a chronic inflammatory disease and Buyang Huanwu decoction (BHD) has been identified as an anti-atherosclerosis effect, and the study is aimed to investigate the underlying mechanism. The E4 allele of Apolipoprotein E (ApoE) is associated with both metabolic dysfunction and an enhanced pro-inflammatory response, ApoE-knockout (ApoE-/-) mice were fed with a high-fat diet to establish an arteriosclerosis model and treated with BHD or atorvastatin (as a positive control). The atherosclerotic plaque in each mouse was evaluated using Oil red O Staining. Elisa kits were used to evaluate blood lipid, interleukin-6 (IL-6), IL-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), IL-4, IL-10, and tumor growth factor beta (TGF-β) contents, while Western blot was applicated to measure inducible nitric oxide synthase (iNOS), arginase I (Arg-1) expression. Meanwhile, pyruvate kinase M2 (PKM2), hypoxia-inducible factor-1 alpha (HIF-1α) and its target genes glucose transporter type 1 (GLUT1), lactate dehydrogenase A (LDHA), and 3-phosphoinositide-dependent kinase 1 (PDK1), as well as IL-6, IL-1β, TNF-α, IL-4, IL-10, and TGF-β were evaluated by the quantitative reverse transcription-polymerase chain reaction. BHD treatment significantly reduced body weight and arteriosclerosis plaque area and blood lipid levels including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Meanwhile, BHD demonstrated a significant suppression of M1 polarization, by decreased secretion of iNOS and pro-inflammatory factors (IL-6, IL-1β, and TNF-α) in ApoE-/- mice. The present study also revealed that BHD promotes the activation of M2 polarization, characterized by the expression of Arg-1 and anti-inflammatory factors (IL-4 and IL-10). In addition, PKM2/HIF-1α signaling was improved by M1/M2 macrophages polarization induced by BHD. The downstream target genes (GLUT1, LDHA, and PDK1) expression was significantly increased in high fat feeding ApoE-/- mice, and those of which were recused by BHD and Atorvastatin. These results suggested that M1/M2 macrophages polarization produce the inflammatory response against AS progress after BHD exposure.

The incidence of Parkinson's disease (PD) rises rapidly with the increase of age. With the advent of global aging, the number of patients with PD is rising along with the elderly population, especially in China. Previously, we found that Yishen chuchan decoction (YCD), prescribed based on clinical experience, has the potential of alleviating symptoms, delaying the progression, and controlling the development of PD. Nonetheless, the underlying mechanistic role is yet to be explored. Aim: This research examined the possible therapeutic effects of YCD in alleviating PD via a systematic approach with network pharmacology and experimental validation, aiming at providing a new understanding of traditional Chinese medicine management regarding PD. Methods: The chemical structure and properties of YCD were adopted from Traditional Chinese Medicine System Pharmacology Database (TCMSP), SwissADME, PubChem, and PubMed. The potential targets for YCD and PD were identified using Swiss Target Prediction, GeneCard, PubChem, and UniProt. The herbal-component-target network was created via the Cytoscape software. Moreover, by using the STRING database, the protein-protein interaction (PPI) network was screened. Gene function GO and KEGG pathway enrichment analyses were performed via the Metascape database. YCD-medicated Rat Serum from Sprague-Dawley (SD) Rats was prepared, and SH-SY5Y cells were preconditioned with rotenone to develop the PD model. To examine the impact of YCD on these cells and explore the mechanistic role of the p38 mitogen-activated protein kinase (MAPK) pathway, the cells were pretreated with either serum or a p38 MAPK pathway inhibitor. This study employed the Cell Counting Kit (CCK)-8 assay and Hoechst 33,342 staining to evaluate the viability and morphological changes induced by the YCD-medicated rat serum on rotenone-treated SH-SY5Y cells. Apoptosis was assessed by Flow cytometry. Immunofluorescence staining assessed the microtubule-associated protein 2 (MAP2) level. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentrations of inflammatory mediators interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Also, reactive oxygen species (ROS) and superoxide dismutase (SOD) levels were determined. Western Blotting measured the expression of total and phospho-p38 MAPK (p-p38). Results: This study identified 65 active components in YCD, which were found to target 801 specific genes. By screening, 63 potential core targets were identified from a pool of 172 overlapping targets between PD and YCD. These targets were examined by GO and KEGG analyses revealing their substantial correlation to MAPK, PI3K-Akt signaling pathways, positively controlling protein phosphorylation, and pathways of neurodegenerative diseases. SH-SY5Y cells were treated with 2 μM rotenone for 48 h, which reduced cell viability to 50 %, and reduced MAP2 expression, increased the rate of apoptosis, oxidative stress, inflammation, and p-p38 expressions. YCD-medicated rat serum significantly improved the viability, reduced the apoptosis rate, and increased the MAP2 expression. YCD-medicated serum increased SOD, reduced ROS and suppressed IL-6, IL-1β and TNF-α levels, thus inhibiting oxidative stress and inflammation in rotenone-treated SH-SY5Y cells. Moreover, YCD-medicated serum substantially lowered the p-p38 expression induced by rotenone. SB203580, a specific inhibitor of p38 MAPK, could also inhibit the p-p38 expression, apoptosis, and restore morphological damage of cells, also improve inflammation and oxidative stress. Conclusion: YCD enhanced cell viability and reduced apoptosis rate, inflammation, and oxidative stress in vitro. These beneficial effects could potentially involve the suppression of p38 pathway and suppressed the phosphorylation of p38 MAPK.

AbstractContext Previously, we found Alisma orientalis beverage (AOB), a classic traditional Chinese medicine (TCM) formulation, had the potential effect of treating atherosclerosis (AS). The underlying mechanism was still unclear.Objective As an extention of our previous work, to investigate the underlying mechanism of action of AOB in the treatment for AS.Materials and methods Network pharmacology was conducted using SwissTargetPrediction, GeneCards, DrugBank, Metascape, etc., to construct component-target-pathway networks. In vivo, AS models were induced by a high-fat diet (HFD) for 8 consecutive weeks in APOE−/− mice. After the administration of AOB (3.8 g/kg, i.g.) for 8 weeks, we assessed the aortic plaque, four indicators of blood lipids, and expression of the PI3K/AKT/SREBP-1 pathway in liver.Results Network pharmacology showed that PI3K/AKT/SREBP-1 played a role in AOB’s treatment for AS (PI3K: degree = 18; AKT: degree = 17). Moreover, we found that the arterial plaque area and four indicators of blood lipids were all significantly reversed by AOB treatment in APOE−/− mice fed with HFD (plaque area reduced by about 37.75%). In addition, phosphorylated expression of PI3K/AKT and expression of SREBP-1 were obviously increased in APOE−/− mice fed with HFD, which were all improved by AOB (PI3K: 51.6%; AKT: 23.6%; SREBP-1: 40.0%).Conclusions AOB had therapeutic effects for AS by improving blood lipids and inhibition of the PI3K/AKT/SERBP-1 pathway in the liver. This study provides new ideas for the treatment of AS, as well as new evidence for the clinical application of AOB.

Background: Recent studies suggest that gut microbiota was associated with the bidirectional gut-brain axis which could modulate neuropsychological functions of the central nervous system. Gut microbiota could produce gamma aminobutyric acid (GABA) that could modulate the gut–brain axis response. Jianpi Jieyu (JPJY) decoction, a traditional Chinese formula, is mainly composed of Astragalus membranaxeus and Radix Pseudostellariae. Although the JPJY decoction has been used to treat the depression in China, the potential action of its antidepressant has not been well understood. Thus this study was aim to investigate the role of JPJY improve gut microbiota homeostasis in the chronic stress induced depressive mice.Methods: The antidepressant effect of JPJY on chronic unpredictable mild stress (CUMS) mice was evaluated by using sucrose preference test, tail suspension test and forced swim test. Fatigue-like behaviors were evaluated using degree of redness, grip strength test, and exhaustive swimming test. The new object recognition test was used to evaluate cognition performance. Fecal samples were collected and taxonomical analysis of intestinal microbial distribution was conducted with 16S rDNA. Serum level of GABA was measured using high performance liquid chromatography (HPLC). The expression of GluR1 and p-Tau protein in the hippocampus was determined using Western blotting.Results: The dose of 9.2 g/kg JPJY produced antidepressant-like effects. JPJY and its major components also modulated gut microbiota diversity in the CUMS mice. Serum level of GABA and the expressions of hippocampal GluR1 and p-Tau were reversed after the administration of JPJY in CUMS mice.Conclusion: JPJY regulates gut microbiota to produce antidepressant-like effect and improve cognition deficit in depressive mice while its molecular mechanism possibly be enhanced NR1 and Tau expression in hippocampus and increased GABA in serum.

BackgroundAlisma orientalis beverage (AOB) is a Chinese traditional medicine formulated with a diversity of medicinal plants and used for treating metabolic syndrome and atherosclerosis (AS) since time ago. Given the current limited biological research on AOB, the mechanism by which AOB treats AS is unknown. This study investigats the role of AOB-induced gut microbiota regulation in the expansion of AS.MethodsWe established an AS model in male apolipoprotein E-deficient (ApoE−/−) mice that are fed with a high-fat diet (HFD), treated with numerous interventions, and evaluated the inflammatory cytokines and serum biochemical indices. The root of the aorta was stained with oil red O, and the proportion of the lesion area was quantified. Trimethylamine N-oxide (TMAO) and trimethylamine (TMA) levels in serum were evaluated through liquid chromatography with mass spectrometry. Flavin−containing monooxygenase 3 (FMO3) liver protein expression was assessed by Western blotting. 16S rDNA sequencing technique was adopted to establish the changes in the microbiota structure.ResultsAfter 8 weeks of HFD feeding, an inflammatory cytokine, and AS development expression were significantly decreased in mice treated with AOB; the same parameters in the mice treated with the antibiotics cocktail did not change. In the gut microbiota study, mice treated with AOB had a markedly different gut microbiota than the HFD-fed mice. Additionally, AOB also decreased serum TMAO and hepatic FMO3 expression.ConclusionThe antiatherosclerotic effects of AOB were found associated with changes in the content of gut microbiota and a reduction in TMAO, a gut microbiota metabolite, suggesting that AOB has potential therapeutic value in the treatment of AS.

The numerical calculation for nuclear reactor coupled system is the fusion, integration and upgrade of the existing numerical technologies in various related fields. Generally, the whole nuclear power plant has several different coupling mechanisms inherently, such as the multiphysics coupling, multiscale coupling and multisystem coupling, which is an ultralargescale strong nonlinear coupling system. Moreover, each coupling mechanism has its own mathematic features. The combination of different coupling mechanisms is such complicated, which is still an open issue for nuclear engineering community. Simultaneous solution methods, such as Jacobianfree Newton Krylov (JFNK) method and NewtonKrylov (NK) method, are a promising choice for effectively solving such complex nonlinear largescale system. In the first part of this work, the recent progress of numerical calculation for nuclear coupling system worldwide is reviewed, especially, several existing coupling methods are summarized and compared. In the second part, it focuses on the development of simultaneous solution methods as well as the coupling platform for high temperature gas-cooled reactor (HTR) full coupled system by Institute of Nuclear and New Energy Technology (INET), Tsinghua University. Due to the multiphysics, multiscale, multicomponent, multicircuit and multimodule coupling features in HTR, the key technologies, such as the JFNK method with nonlinearelimination, scaling factor and steam generator model, were presented and discussed. In detail, the JFNK method with nonlinearelimination was firstly proposed to deal with the multiscale temperature coupling between the global pebblebed and the local fuel sphere. The scaling factor technology was used to transform the illposed Jacobian matrix into the wellposed one in the multiphysical coupling issue. For the steam generator model, the dynamical residual method is conducted for the twophase flow in the second circuit to avoid the multisolution issue when the phase generation or the phase disappearance occurs. Moreover, a unified framework was proposed to tackle the multi-level coupling structure in HTR system, after several attempts were made. In this framework, the whole coupling system is gradually decomposed into systemlevel issue, componentlevel issue and physical fieldlevel issue, and solved as a whole system by the simultaneous solution method. However, to completely solve the whole HTR nuclear power plant system, there are still many works to do, such as the fundamental algorithm research, program framework development and engineering applications.