One-step synthesis of garlic peel derived biochar by concentrated sulfuric acid: Enhanced adsorption capacities for Enrofloxacin and interfacial interaction mechanisms.

This study put forward a one-step carbonization method by concentrated sulfuric acid to prepare garlic peel derived biochar, and the synthetic conditions were optimized by L16(45) orthogonal experiments. Notably, in order to study the differences between the proposed synthetic method and the conventional pyrolysis method, the concentrated sulfuric acid carbonized garlic peels biochar (CSGPB) was compared with pyrolysis derived garlic peel biochar (HTGPB) in characterization and adsorption capacities for Enrofloxacin (ENR). Results showed that CSGPB exhibited more graphite-like structures with more active functional groups on the surface, and the equilibrium adsorption capacity of CSGPB (142.3 mg g-1) was 13.7 times of HTGPB (10.4 mg g-1) under identical conditions. Moreover, the adsorption behaviors including adsorption kinetics, isotherms and thermodynamics of CSGPB for ENR were fully investigated and discussed. Based on the above experiments, density functional theory (DFT) simulations were performed to reveal the interfacial interaction and adsorption mechanism. Results showed π-π interaction between quinolone moieties of ENR and graphite-like structures in CSGPB might be the dominant mechanism. As for the functional groups, the adsorption energies were -40.46, -15.21 and -5.96 kJ mol-1 for -SO3H, -OH and -COOH, respectively, which indicated -SO3H was the most active functional groups on the surface of CSGPB. This study provided a new sustainable perspective for the design of efficient biochars, and explored the interfacial interaction mechanism of antibiotics removal on biochars.

Magnesium lithospermate B improves pulmonary artery banding induced right ventricular dysfunction by alleviating inflammation via p38MAPK pathway.

BACKGROUD: Magnesium lithospermate B (MLB) is a major bioactive component of Slavia miltiorrhiza, which has been widely used in heart diseases on account of its anti-inflammatory, anti-oxidative, anti-proliferative and anti-fibrotic properties. Substance P(SP) is a small molecule neuropeptide, which was secreted much more during heart failure, and has an obvious function of immune enhancement and inflammation induction. This study aimed to investigate the protective effects of MLB on pulmonary artery banding (PAB) induced right ventricular (RV) dysfunction. METHODS: The mouse model of PAB was established. The mice were intraperitoneal (IP) injection treated with MLB (10 mg kg-1·d-1) for 4 weeks and p38 mitogen-activated protein kinase (MAPK) activator was given at the same time. Echocardiography were performed on day 28. Then the hearts were harvested, and substance P (SP), inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and cardiac fibrosis were detected. The macrophages and fibroblasts were stimulated by SP separately, and then treated with MLB as well as p38MAPK activator. The inflammatory cytokines from macrophage, the proliferation and fibrosis of cardiac fibroblasts were measured. The expression of p38MAPK proteins were confirmed by immunoblotting. FINDINGS: MLB preserved RV ejection fraction (EF), FS, RV/(LV + septum), HW/BW index and blunted RV inflammation as well as fibrosis. Phosphorylated-p38 (p-p38) MAPK was up-regulated, which was partially reversed by MLB treatment. However, p38MAPK activator abolished the effects of MLB on RV dysfunction, suggesting a key role of p38MPAK pathway in the effects of MLB reversing RV dysfunction. In external experiment, MLB reversed the increase of inflammatory cytokines from macrophage, the proliferation and fibrosis of cardiac fibroblasts which was simulated by SP. In accordance with in vivo study, p38MAPK activator abolished the effects of MLB on macrophage as well as fibroblasts. INTERPRETATION: MLB improves PAB induced right ventricular remodeling by alleviating inflammation via p38MAPK pathway. Thus, MLB may offer the therapeutic potential for the patients of RV dysfunction.

Tanreqing Injection () for Patients with Influenza: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To systematically evaluate the efficacy and safety of Tanreqing Injection (, TRQI) combined with conventional treatment on clinical outcomes in the treatment of patients with influenza. METHODS: The electronic databases searched were Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (PubMed), EMbase (OvidSP), Chinese Bio-medical Literature and Retrieval System (Sinomed), China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP) and WanFang Data Knowledge Service Platform, and we checked the reference sections of the retrieved articles as well. The search was performed in October 2018, and we used the randomized controlled trials (RCTs) that corresponded to the new diagnostic criteria for influenza. Two review authors independently screened the internalized articles in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) statement checklist. We evaluated the quality of the articles and extracted the data from the studies using the Revmen5.3 software. RESULTS: We included 12 RCTs of over 882 cases in this meta-analysis. Compared to conventional treatment, TRQI combined with conventional treatment could increase the total effective rate [9 RCTs, n=648, odds ratio (OR): 4.92, 95% confidence interval (CI): 2.94, 8.24, P<0.0001, random effects model], decrease the average time for fever clearance [7 RCTs, n=564, mean difference (MD): -1.08, 95% CI: -1.68, -0.48, P=0.0004, random effects model] and decrease the time for resolution of cough (5 RCTs, n=362, MD: -1.76, 95% CI: -2.63, -0.90, P<0.0001, random effects model). CONCLUSION: Based on this meta-analysis of RCTs, TRQI combined with conventional treatment had a statistically significant benefit in increasing the total effective treatment rate and reducing the time for fever clearance as well as time for resolution of cough.

Inhibition of JAK2/STAT3/SOCS3 signaling attenuates atherosclerosis in rabbit.

BACKGROUND: Previous studies have indicated that the JAK/STAT signaling pathway is involved in modulating arterial adventitia inflammation response. In this study, we designed experiments to further investigate the effect of JAK2/STAT3/SOCS3 signaling in rabbit atherosclerosis process. METHODS: Atherosclerosis was induced in the abdominal arteries of rabbits by balloon injury of the aorta supplemented by the atherogenic diet. Simultaneously, in the process of atherosclerosis, animals underwent either ruxolitinib treatment or not for 12 weeks. At the end of the experimental period, all rabbits were sacrificed. The plaque areas in abdominal artery, the lipid burden of plaque and the calcium burden of plaque were detected by H&E staining, Oil Red O staining and Alizarin Red staining, respectively. In addition, rabbit plasma lipids and inflammatory cytokines were measured by biochemical test kits or ELISA kits. Finally, the expression and phosphorylation levels of JAK2/STAT3/SOCS3 pathway-related proteins were detected by RT-qPCR, western blot and immunohistochemistry assays. RESULTS: H&E staining and CT scan analysis showed that rabbit atherosclerosis model was constructed successfully. Ruxolitinib, an inhibitor of the Janus kinase 2 (JAK2), substantially reduced the area of atherosclerotic plaques in rabbits treated with high fat diet and balloon injury of the aorta. Moreover, ruxolitinib significantly decreased IL-6, IL-1ß, IFN-γ and TNF-α, but increased IL-10 and IL-17 levels in plasma of atherosclerotic rabbits. Additionally, ruxolitinib reduced plasma TC, TG and LDL-C contents and AIP value, while enhanced HDL-C level in atherosclerotic rabbits. Furthermore, we found that JAK2 and STAT3 phosphorylation were up-regulated in rabbits with atherosclerosis when compared with those of the control group, followed by the expression of SOCS3 was also increased due to the activation of JAK2 and STAT3. Interestingly, ruxolitinib could inactivate JAK2 and STAT3 pathway and decrease SOCS3 expression. CONCLUSION: Taken together, the inhibition of JAK2/STAT3/SOCS3 signaling pathway may be a novel method for the clinical treatment of artery atherosclerosis.

Tyrosine kinase SYK is a potential therapeutic target for liver fibrosis.

Spleen tyrosine kinase (SYK) plays a critical role in immune cell signaling pathways and has been reported as a biomarker for human hepatocellular carcinoma (HCC). We sought to investigate the mechanism by which SYK promotes liver fibrosis and to evaluate SYK as a therapeutic target for liver fibrosis. We evaluated the cellular localization of SYK and the association between SYK expression and liver fibrogenesis in normal, hepatitis B virus (HBV)-infected, hepatitis C virus (HCV)-infected and non-alcoholic steatohepatitis (NASH) liver tissue (n=36, 127, 22 and 30, respectively). A polymerase chain reaction (PCR) array was used to detect the changes in transcription factor (TF) expression in hepatic stellate cells (HSCs) with SYK knockdown. The effects of SYK antagonism on liver fibrogenesis were studied in LX-2 cells, TWNT-4 cells, primary human HSCs, and three progressive fibrosis/cirrhosis animal models, including a CCL4 mouse model, and diethylnitrosamine (DEN) and bile duct ligation (BDL) rat models. We found that SYK protein in HSCs and hepatocytes correlated positively with liver fibrosis stage in human liver tissue. HBV or HCV infection significantly increased SYK and cytokine expression in hepatocytes. Increasing cytokine production further induced SYK expression and fibrosis-related gene transcription in HSCs. Up-regulated SYK in HSCs promoted HSC activation by increasing the expression of specific TFs related to activation of HSCs. SYK antagonism effectively suppressed liver fibrosis via inhibition of HSC activation, and decreased obstructive jaundice and reduced HCC development in animal models. Conclusion: SYK promotes liver fibrosis via activation of HSCs and is an attractive potential therapeutic target for liver fibrosis and prevention of HCC development. (Hepatology 2018).

PPARγ Alleviates Right Ventricular Failure Secondary to Pulmonary Arterial Hypertension in Rats.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling leading to right ventricular hypertrophy (RVH) and failure. Peroxisome proliferator-activated receptor γ (PPARγ), a member of nuclear receptors, has been proved to ameliorate PAH. However, its effect on PAH-induced right ventricular failure (RVF) remains unknown. Therefore, we investigated the therapeutic potential of PPARγ in preventing monocrotaline (MCT)-induced RV dysfunction. The PAH model was induced by MCT administration. Male rats were administered with MCT to develop PAH and RVF formed by approximately day 30. Significant increase in RV area, RVAW resulted in an ascending RV index. However, the LV function including EF, FS, and LVID did not change significantly. PPARγ agonist prevented PAH-induced RVF by preserving RV index and preventing RVH. PPARγ's beneficial effects seem to result from various factors, including anti-apoptosis, preservation RV index, reversal of inflammation, improvement of glucolipid metabolism, reduction of ROS. In a word, PPARγ agonist prevents the development of RVF.

Identifying panaxynol, a natural activator of nuclear factor erythroid-2 related factor 2 (Nrf2) from American ginseng as a suppressor of inflamed macrophage-induced cardiomyocyte hypertrophy.

ETHNOPHARMACOLOGICAL RELEVANCE: American ginseng is capable of ameliorating cardiac dysfunction and activating Nrf2, a master regulator of antioxidant defense, in the heart. This study was designed to isolate compounds from American ginseng and to determine those responsible for the Nrf2-mediated resolution of inflamed macrophage-induced cardiomyocyte hypertrophy. MATERIALS AND METHODS: A standardized crude extract of American ginseng was supplied by the National Research Council of Canada, Institute for National Measurement Standards. A bioassay-based fractionization of American ginseng was performed to identify the putative substances which could activate Nrf2-mediated suppression of pro-inflammatory cytokine expression in macrophages and macrophage-mediated pro-hypertrophic growth in cardiomyocytes. RESULTS: A hexane fraction of an anti-inflammatory crude extract of American ginseng was found to be most effective in suppressing the inflammatory responses in macrophages. Preparative, reverse-phase HPLC and a comparative analysis by analytical scale LC-UV/MS revealed the hexane fraction contains predominantly C17 polyacetylenes and linolenic acid. Panaxynol, one of the major polyacetylenes, was found to be a potent Nrf2 activator. Panaxynol posttranscriptionally activated Nrf2 by inhibiting Kelch-like ECH-associated protein (Keap) 1-mediated degradation without affecting the binding of Keap1 and Nrf2. Moreover, panaxynol suppressed a selected set of cytokine expression via the activation of Nrf2 while minimally regulating nuclear factor-kappa B (NF-κB)-mediated cytokine expression in macrophages. It also dramatically inhibited the inflamed macrophage-mediated cardiomyocyte death and hypertrophy by activating Nrf2 in macrophages. CONCLUSIONS: These results demonstrate that American ginseng-derived panaxynol is a specific Nrf2 activator and panaxynol-activated Nrf2 signaling is at least partly responsible for American ginseng-induced health benefit in the heart.

Ginsenoside Rg1 of Panax ginseng stimulates the proliferation, odontogenic/osteogenic differentiation and gene expression profiles of human dental pulp stem cells.

Ginsenoside Rg1 is one of the major active components of Panax ginseng C. A. Mey. Human dental pulp stem cells (hDPSCs) play an important role in the dentin formation, reparation and tooth tissue engineering. This study investigated the effects of ginsenoside Rg1 on the proliferation, odontogenic differentiation of hDPSCs and revealed the underlying molecular mechanisms. [³H]-thymidine incorporation assay and cell cycle analysis were applied to investigate the proliferation of hDPSCs after the treatment of ginsenoside Rg1. Immunocytochemistry analysis and fluorescent quantitative reverse transcriptase-polymerase chain reaction (FQ-PCR) were performed to evaluate the odontogenic differentiation of hDPSCs. Gene and protein expressions of bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor 2 (FGF2) were detected by FQ-PCR and enzyme-linked immunosorbent assay. The Roche Nimblegen Whole Human Genome Expression profile microarray was used to detected representative gene expression profiles of hDPSCs by ginsenoside Rg1. The results indicated that ginsenoside Rg1 significantly increased hDPSCs proliferation (p<0.05). Gene expressions of DSPP, ALP, OCN, BMP-2, FGF2 and protein expressions of BMP-2 and FGF2 were increased compared with the untreated group (p<0.05). Gene expression profile analysis revealed that 2059 differentially expressed genes were detected by ginsenoside Rg1. Ginsenoside Rg1 promoted the proliferation and differentiation of hDPSCs through alteration of gene expression profiles.

Chemoprevention of primary liver cancer: a randomized, double-blind trial in Linxian, China.

BACKGROUND: Primary liver cancer is a common malignancy with a dismal prognosis. New primary prevention strategies are needed to reduce mortality from this disease. We examined the effects of supplementation with four different combinations of vitamins and minerals on primary liver cancer mortality among 29450 initially healthy adults from Linxian, China. METHODS: Participants were randomly assigned to take either a vitamin-mineral combination ("factor") or a placebo daily for 5.25 years (March 1986-May 1991). Four factors (at doses one to two times the US Recommended Daily Allowance)-retinol and zinc (factor A); riboflavin and niacin (factor B); ascorbic acid and molybdenum (factor C); and beta-carotene, alpha-tocopherol, and selenium (factor D)-were tested in a partial factorial design. The study outcome was primary liver cancer death occurring from 1986 through 2001. Adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of liver cancer death with and without each factor. All P values are two-sided. RESULTS: A total of 151 liver cancer deaths occurred during the analysis period. No statistically significant differences in liver cancer mortality were found comparing the presence and absence of any of the four intervention factors. However, both factor A and factor B reduced liver cancer mortality in individuals younger than 55 years at randomization (HR = 0.59, 95% CI = 0.34 to 1.00, and HR = 0.54, 95% CI = 0.31 to 0.93, respectively) but not in older individuals (HR = 1.06, 95% CI = 0.71 to 1.59, and HR = 1.12, 95% CI = 0.75 to 1.68, respectively). Factor C reduced liver cancer death, albeit with only borderline statistical significance in males (HR = 0.70, 95% CI = 0.47 to 1.02) but not in females (HR = 1.30, 95% CI = 0.72 to 2.37). Cumulative risks of liver cancer death were 6.0 per 1000 in the placebo arm, 5.4 per 1000 in the arms with two factors, and 2.4 per 1000 in the arm with all four factors. CONCLUSION: None of the factors tested reduced overall liver cancer mortality. However, three factors reduced liver cancer mortality in certain subgroups.