Pathogenesis of NASH and Promising Natural Products.

Nonalcoholic steatohepatitis (NASH) is a common clinical condition that can lead to advanced liver diseases. The mechanism of the diaease progression, which is lacking effective therapy, remains obsure. Therefore, there is a need to understand the pathogenic mechanisms responsible for disease development and progression in order to develop innovative therapies. To accomplish this goal, experimental animal models that recapitulate the human disease are necessary. Currently, an increasing number of studies have focused on natural constituents from medicinal plants which have been emerged as a new hope for NASH. This review summarized the pathogenesis of NASH, animal models commonly used, and the promising targets for therapeutics. We also reviewed the natural constituents as potential NASH therapeutic agents.

Pathogenesis of NASH and Promising Natural Products / 中国天然药物

Nonalcoholic steatohepatitis (NASH) is a common clinical condition that can lead to advanced liver diseases. The mechanism of the diaease progression, which is lacking effective therapy, remains obsure. Therefore, there is a need to understand the pathogenic mechanisms responsible for disease development and progression in order to develop innovative therapies. To accomplish this goal, experimental animal models that recapitulate the human disease are necessary. Currently, an increasing number of studies have focused on natural constituents from medicinal plants which have been emerged as a new hope for NASH. This review summarized the pathogenesis of NASH, animal models commonly used, and the promising targets for therapeutics. We also reviewed the natural constituents as potential NASH therapeutic agents.

Traditional Chinese medicine network pharmacology study on exploring the mechanism of Xuebijing Injection in the treatment of coronavirus disease 2019.

As a representative drug for the treatment of severe community-acquired pneumonia and sepsis, Xuebijing (XBJ) injection is also one of the recommended drugs for the prevention and treatment of coronavirus disease 2019 (COVID-19), but its treatment mechanism for COVID-19 is still unclear. Therefore, this study aims to explore the potential mechanism of XBJ injection in the treatment of COVID-19 employing network pharmacology and molecular docking methods. The corresponding target genes of 45 main active ingredients in XBJ injection and COVID-19 were obtained by using multiple database retrieval and literature mining. 102 overlapping targets of them were screened as the core targets for analysis. Then built the PPI network, TCM-compound-target-disease, and disease-target-pathway networks with the help of Cytoscape 3.6.1 software. After that, utilized DAVID to perform gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to predict the action mechanism of overlapping targets. Finally, by applying molecular docking technology, all compounds were docked with COVID-19 3 CL protease(3CLpro), spike protein (S protein), and angiotensin-converting enzyme II (ACE2). The results indicated that quercetin, luteolin, apigenin and other compounds in XBJ injection could affect TNF, MAPK1, IL6 and other overlapping targets. Meanwhile, anhydrosafflor yellow B (AHSYB), salvianolic acid B (SAB), and rutin could combine with COVID-19 crucial proteins, and then played the role of anti-inflammatory, antiviral and immune response to treat COVID-19. This study revealed the multiple active components, multiple targets, and multiple pathways of XBJ injection in the treatment of COVID-19, which provided a new perspective for the study of the mechanism of traditional Chinese medicine (TCM) in the treatment of COVID-19.

Clinical effect of catgut implantation at acupoints for the treatment of simple obesity: A multicentre randomized controlled trial.

BACKGROUND: Catgut implantation at acupoints (CIA) is a subtype of acupuncture that has been widely used to treat simple obesity, but evidence for its effectiveness remains scarce. The aim of this study is to evaluate the efficacy and safety of treating simple obesity with CIA. OBJECTIVE: This clinical trial aims to evaluate the effectiveness and safety of CIA used for treatment of simple obesity. METHODS: This is a multicentre, randomized, parallel, sham-controlled clinical trial. A total of 216 patients with simple obesity will be recruited. They will be randomly assigned in a 1:1 ratio to either the CIA group or the sham control group. All treatments will be given once every 2 weeks. The primary outcome measure is the rate of waistline reduction. Secondary outcome measures are the rates of reduction of body measurements, including weight, body mass index (BMI), hipline, waist-hip-ratio (WHR) and body fat percentage (BFP), the changes in scores on scales, including the Impact of Weight on Quality of Life Questionnaire (IWQOL-Lite), Short Form 36 (SF-36), the Hospital Anxiety and Depression Scale (HAD) and the Self-Esteem Scale (SES), Outcomes will be evaluated at baseline and at weeks 4, 8, 12, 16, 28, and 40, respectively. All adverse events that occur during this study will be recorded. If any participant withdraws from the trial, an intention-to-treat analysis (ITT) will be performed. CONCLUSION: This is a randomized, sham-controlled trial of CIA treatment for simple obesity. The results of this trial will provide more evidence on whether CIA is efficacious and safe for treating obesity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02936973. Registered on October 18, 2016.

Traditional Chinese medicine network pharmacology study on exploring the mechanism of Xuebijing Injection in the treatment of coronavirus disease 2019 / 中国天然药物

As a representative drug for the treatment of severe community-acquired pneumonia and sepsis, Xuebijing (XBJ) injection is also one of the recommended drugs for the prevention and treatment of coronavirus disease 2019 (COVID-19), but its treatment mechanism for COVID-19 is still unclear. Therefore, this study aims to explore the potential mechanism of XBJ injection in the treatment of COVID-19 employing network pharmacology and molecular docking methods. The corresponding target genes of 45 main active ingredients in XBJ injection and COVID-19 were obtained by using multiple database retrieval and literature mining. 102 overlapping targets of them were screened as the core targets for analysis. Then built the PPI network, TCM-compound-target-disease, and disease-target-pathway networks with the help of Cytoscape 3.6.1 software. After that, utilized DAVID to perform gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to predict the action mechanism of overlapping targets. Finally, by applying molecular docking technology, all compounds were docked with COVID-19 3 CL protease(3CLpro), spike protein (S protein), and angiotensin-converting enzyme II (ACE2). The results indicated that quercetin, luteolin, apigenin and other compounds in XBJ injection could affect TNF, MAPK1, IL6 and other overlapping targets. Meanwhile, anhydrosafflor yellow B (AHSYB), salvianolic acid B (SAB), and rutin could combine with COVID-19 crucial proteins, and then played the role of anti-inflammatory, antiviral and immune response to treat COVID-19. This study revealed the multiple active components, multiple targets, and multiple pathways of XBJ injection in the treatment of COVID-19, which provided a new perspective for the study of the mechanism of traditional Chinese medicine (TCM) in the treatment of COVID-19.

High-dose vitamin C suppresses the invasion and metastasis of breast cancer cells via inhibiting epithelial-mesenchymal transition.

PURPOSE: Vitamin C (VC) is a kind of essential nutrient in the body regarded as a canonical antioxidant during the past hundred years. However, the anti-cancer effect of VC is controversial. Our study is trying to clarify the relationship between VC dosage and breast cancer metastasis. METHODS: Human breast cancer cell lines Bcap37 and MDA-MB-453 were treated with VC at three different concentrations (low-dose, 0.01 mM; medium-dose, 0.1 mM; high-dose, 2 mM). Wound healing assays were conducted for migration assay; transwell tests were performed to detect the ability of cell invasion. The protein levels were evaluated by Western blot analysis or immunohistochemistry. Tumor xenografts in nude mice were built to test the effects of VC on breast cancer cell proliferation and metastasis. RESULTS: 0.01 and 0.1 mM VC promoted cell migration and invasion when compared with the control group, but 2 mM VC significantly suppressed cell migration and invasion of breast cancer cell lines. High-dose VC increased E-cadherin and reduced Vimentin, indicating that high-dose VC suppressed epithelial-mesenchymal transition (EMT) in breast cancer cells. Besides, high-dose VC inhibited cell invasion promoted by TGF-ß1 in breast cancer cells. Meanwhile, high-dose VC reversed the suppression of E-cadherin and enhancement of Vimentin induced by TGF-ß1 in breast cancer cells. Furthermore, high-dose VC significantly inhibited breast cancer metastasis in vivo. CONCLUSION: High-dose VC inhibits cell migration and invasion of breast cancer cell lines through suppressing EMT. Thus, it may be considered as an anticancer drug candidate for breast cancer patients.

Lactobacillus plantarum 299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men With Stable Coronary Artery Disease.

RATIONALE: A strong association has emerged between the gut microbiome and atherosclerotic disease. Our recent data suggest Lactobacillus plantarum 299v (Lp299v) supplementation reduces infarct size in male rats. Limited human data are available on the impact of Lp299v on the vasculature. OBJECTIVE: To determine whether oral Lp299v supplementation improves vascular endothelial function and reduces systemic inflammation in humans with stable coronary artery disease (CAD). METHODS AND RESULTS: Twenty men with stable CAD consumed a drink containing Lp299v (20 billion CFU) once daily for 6 weeks. After a 4-week washout, subjects were given an option of additionally participating in a 10-day study of oral liquid vancomycin (250 mg QID). Vascular endothelial function was measured by brachial artery flow-mediated dilation. Before and after Lp299v, plasma short-chain fatty acids, trimethylamine oxide, and adipokine levels were measured. Additional plasma samples underwent unbiased metabolomic analyses using liquid chromatography/mass spectroscopy. 16S rRNA sequencing was used to determine changes of the stool microbiome. Arterioles from patients with CAD were obtained, and endothelium-dependent vasodilation was measured by video microscopy after intraluminal incubation with plasma from Lp299v study subjects. Lp299v supplementation improved brachial flow-mediated dilation ( P=0.008) without significant changes in plasma cholesterol profiles, fasting glucose, or body mass index. Vancomycin did not impact flow-mediated dilation. Lp299v supplementation decreased circulating levels of IL (interleukin)-8 ( P=0.01), IL-12 ( P=0.02), and leptin ( P=0.0007) but did not significantly change plasma trimethylamine oxide concentrations ( P=0.27). Plasma propionate ( P=0.004) increased, whereas acetate levels decreased ( P=0.03). Post-Lp299v plasma improved endothelium-dependent vasodilation in resistance arteries from patients with CAD ( P=0.02).16S rRNA analysis showed the Lactobacillus genus was enriched in postprobiotic stool samples without other changes. CONCLUSIONS: Lp299v improved vascular endothelial function and decreased systemic inflammation in men with CAD, independent of changes in traditional risk factors and trimethylamine oxide. Circulating gut-derived metabolites likely account for these improvements and merit further study. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01952834.

Traditional Chinese medicine versus western medicine as used in China in the management of rheumatoid arthritis: a randomized, single-blind, 24-week study.

This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM (n = 247), MTX and SSZ (n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5-15 mg weekly. The maintenance dose was 2.5-7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5-1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, (P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, (P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, (P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects.

Interaction of cadmium and zinc on accumulation and sub-cellular distribution in leaves of hyperaccumulator Potentilla griffithii.

Potentilla griffithii Hook is a newly found hyperaccumulator plant capable of high tolerance and accumulation of Zn and Cd. We investigated the interactive effects between Cd and Zn on accumulation and vacuolar sequestration in P. griffithii. Stimulatory effect of growth was noted at 0.2 mM Cd and 1.25 and 2.5 mM Zn tested. Accumulation of Zn and Cd in roots, petioles and leaves were increased significantly with addition of these metals individually. However, the Zn supplement decreased root Cd accumulation but increased the concentration of Cd in petioles and leaves. The results from sub-cellular distribution showed that up to 94% and 70% of the total Zn and Cd in the leaves were present in the protoplasts, and more than 90% Cd and Zn in the protoplasts were localized in the vacuoles. Nearly, 88% and 85% of total Cd and Zn were extracted in the cell sap of the leaves suggesting that most of the Cd and Zn in the leaves were available in soluble form. The present results indicate that Zn supplement significantly enhanced the petiole accumulation of Cd and further vacuolar sequestration plays an important role in tolerance, detoxification and hyperaccumulation of these metals in P. griffithii.

[Thinking about the key points in developing guidelines for Chinese and integrated medical clinical therapy].

The author offered in this paper that in developing the guidelines for Chinese and integrated medical clinical therapy, the specialties of Chinese medicine and clinical needs should be considered, and put stress on the following key points: (1) give priorities to the diseases on which plentiful evidences and practical experiences have been achieved in researches; (2) set up the clinical issues of diseases from an integral view, with Chinese medicine syndromes subordinated to diseases; (3) in making choice of clinical questions, problems that clinicians and researchers concerned should be taken in to consideration; (4) adopt the concepts and methods of complex intervention and reflect prominently the preponderant holistic thinking of Chinese medicine; (5) intensify the cognition-centered basic research of Chinese medicine through combining "disease diagnosis" and "syndrome differentiation" to acquaint the rules of disease/syndrome transformation from the integral dynamic views; (6) use the guidance establishing process of Western medicine as reference to collect, identify, review and classify the evidences from modern literature, while for those from ancient literature, the content analyzing method should be followed; (7) make the contents of design methods perfect and put emphasis on the control and guarantee of quality.