Effects of Tylophora yunnanensis Schltr on regulating the gut microbiota and its metabolites in non-alcoholic steatohepatitis rats by inhibiting the activation of NOD-like receptor protein 3.

ETHNOPHARMACOLOGICAL RELEVANCE: Tylophora yunnanensis Schltr (TYS) is widely distributed in Yunnan, Guizhou, and other places in China. It is commonly used by folks to treat hepatitis and other liver-related diseases; however, its mechanism of action is still unclear. AIM OF THE STUDY: This study aimed to determine the effects of TYS on regulating gut microbiota and its metabolites in non-alcoholic steatohepatitis (NASH) rats by inhibiting the activation of NOD-like receptor protein3 (NLRP3). MATERIAL AND METHODS: An HFD-induced rat model was established to investigate if the intragastric administration of TYS could mediate gut microbiota and their metabolites to ultimately improve the symptoms of NASH. The improving effects of TYS on NASH rats were assessed by measuring their body weight, lipid levels, histopathology, and inflammatory factor levels in the rat models. The regulatory effects of TYS on NLRP3 in the NASH rats were analyzed using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), which determined the levels of NLRP3-related factors. The changes in the composition of the gut microbiota of NASH rats were analyzed using 16S rRNA gene sequencing technology. Meanwhile, the Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for the non-targeted analysis of metabolites in the cecum contents. RESULTS: The results showed that TYS could improve NASH by decreasing the body weight and levels of lipid, AST, ALT, LPS, FFA, VLDL, IL-1ß, IL-6, TNF-α, TGF-ß, NLRP3, ASC, and Caspase-1 in the NASH rats. The analysis of gut microbiota showed that TYS could improve the diversity and abundance of gut microbiota and alter their composition by decreasing the Firmicutes/Bacteroidetes (F/B) ratio and relative abundances of Lachnospiraceae, Christensenellaceae, Blautia, etc. while increasing those of Muribaculaceae, Rumiaococcus, Ruminococcaceae, etc. The analysis of metabolites in the cecum contents suggested that the arachidonic acid metabolism, bile secretion, serotonergic synapse, Fc epsilon RI signaling pathway, etc. were regulated by TYS. The metabolites enriched in these pathways mainly included chenodeoxycholic acid, prostaglandin D2, TXB2, 9-OxoODE, and 13(S)-HOTrE. CONCLUSIONS: These findings suggested that TYS could alleviate the NASH symptoms by decreasing the body weight, regulating the lipid levels, reducing the inflammatory response, and inhibiting the expression levels of NLRP3, ASC, and Caspase-1 in the NASH rats. The changes in the composition of gut microbiota and their metabolic disorder were closely related to the activation of NLRP3. TYS could significantly inhibit the activation of NLRP3 and regulate the composition of gut microbiota and the disorder of metabolites during NASH modeling.

[Application of Reyanning Mixture in evaluating combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome].

In the previous research, our laboratory established a mouse model combining disease with syndrome of human coronavi-rus pneumonia with pestilence attacking the lung syndrome, based on the national traditional Chinese medicine clinical classification of Novel Coronavirus Infected Pneumonia Diagnosis and Treatment Plan. In this study, a mouse model combining disease with syndrome of human coronavirus pneumonia with pestilence attacking the lung syndrome was used to evaluate the effectiveness of Reyanning Mixture to provide animal experimental support for clinical application. Mice were divided into normal group, 229 E infection group, cold-dampness group, cold-dampness+229 E infection group(the model group), Reyanning high and low dose groups. The cold-dampness group, cold-dampness+229 E infection group, two Reyanning groups were given cold and damp stimulation for 7 days. On the 5 th day, the 229 E infection group, cold-dampness+229 E infection group, and two Reyanning groups were infected with HCoV-229 E virus. Reyanning was administered for 3 days, starting from the day of infection. Blood was collected on the 4 th day and the lung tissue was dissected to calculate the lung index and inhibition rate; flow cytometry was used to detect the percentage of T and B lymphocytes in peripheral blood; RT-PCR was used to detect the nucleic acid virus load in lung tissue; ELISA was used to detect motilin and gastrin in serum, and inflammatory factors TNF-α, IFN-γ, IL-6, IL-10 in lung tissue proteins. Reyanning Mixture could reduce the lung index(P<0.01) of coronavirus pneumonia mice with pestilence attacking the lung; it could significantly increase the percentage of CD8~+ T lymphocytes and CD4~+ T lymphocytes in peripheral blood of model mice(P<0.05, P<0.01). The low dose of Reyanning could effectively increase the percentage of total B lymphocytes(P<0.05), reduce virus load in lung tissue of model mice(P<0.01), reduce the levels of TNF-α, IFN-γ, IL-6, IL-10 in the lung tissue of model mice(P<0.01), reduce the content of motilin in the serum of model mice(P<0.01). Reyanning Mixture convey a better effect in treating coronavirus pneumonia mice with pestilence attacking the lung. It manifested obvious effects in improving lung lesions, enhancing the gastrointestinal function of mice, improving the autoimmune function of mice, and reducing the expression of inflammatory factors in vivo, which could provide evidences for clinical research.

Sequential vertical flow trickling filter and horizontal flow multi-soil-layering reactor for treatment of decentralized domestic wastewater with sodium dodecyl benzene sulfonate.

Sequential vertical flow trickling filter and horizontal flow multi-soil-layering bioreactor were investigated for the treatment of decentralized domestic wastewater at various concentrations of sodium dodecyl benzene sulfonate (SDBS). Results have shown that the removal rate of COD could reach 92.1% at initial COD concentration of 960 mg/L (800 mg/L was provided by SDBS). NH4+-N concentration could be reduced from 52.4 to 9.71 mg/L without aeration. Besides, a quadratic function model was fit to describe the relationship between the relative activity of amylase and the protein content in extracellular polymer substance. SDBS could inhibit the transport and metabolisms of amino acids, lipids and carbohydrates in biofilms. The analysis of three-dimensional fluorescence diagram indicated that the peak in excitation/emission wavelengths = 310-340/370-430 nm was the characteristic peaks of some active substances such as some enzymes in EPS. Only Microbacterium could totally offset the toxicity of SDBS degradation products.

Enhanced activation of peroxymonosulfte by LaFeO3 perovskite supported on Al2O3 for degradation of organic pollutants.

In this study, the effect of various supports on activation of peroxymonosulfate and consequent degradation of Acid Orange 7 (AO7) in aqueous solutions was examined at the presence of LaFeO3 perovskite as catalyst. Results showed that the AO7 degradation efficiency by LaFeO3 supported on different supports was in an order of LaFeO3/Al2O3 (86.2%) > LaFeO3 (70.8%) > LaFeO3/CeO2 (59.0%) > LaFeO3/SiO2 (52.3%) > LaFeO3/TiO2 (32.2%). Moreover, the pseudo first-order rate constant for AO7 degradation by LaFeO3/Al2O3 was 3.2 times than that by LaFeO3. The enhancement was attributed to its large surface area, abundant chemisorbed surface-active oxygen, redox property and faster electron transfer. AO7 degradation and the leaching of iron ions decreased with the increase of pH. Data of electron spin resonance spectroscopy and quenching experiments revealed that sulfate and hydroxyl radicals were generated on LaFeO3/Al2O3 surface, while sulfate radicals were identified to be the main reactive species responsible for AO7 degradation. Mechanisms for peroxymonosulfate activation were consequently proposed. Furthermore, LaFeO3/Al2O3 catalyst exhibited a superior stability after five cycles. This work provides a new approach for design of iron-based perovskite catalysts with high and stable catalytic activity for removal of organic pollutants from aqueous solutions.

[Preliminary study on antibacterial activity of artemisinin and its derivatives].

In this study,in order to detect the antimicrobial activity of artemisinin and its derivatives artesunate and dihydroartemisinin,two methods including broth dilution and plate punching method were used to detect the antibacterial activity against gram-negative bacteria(Escherichia coli)and gram-positive bacteria(Staphylococcus aureus)of artemisinin,dihydroartemisinin and artesunate at various concentrations within 5 mmol·L~(-1)and at four time points(8,16,24,32 h).Two antibacterial positive drugs,streptomycin against E.coli and penicillin against S.aureus,were used as positive controls.Plate punching method showed that,unlike the results of 5 mmol·L~(-1)dihydroartemisinin or artesunate,no inhibition zone was detected at the same concentration of artemisinin after 24 h-treatment against E.coli.Broth dilution method showed that,the antibacterial activity of dihydroartemisinin against E.coli.was stronger than those of both artesunate and artemisinin;IC_(50)at24 h-treatment was 155.9µmol·L~(-1)for dihydroartemisinin,370.0µmol·L~(-1)for artesunate and none for artemisinin.Interestingly,dihydroartemisinin and artesunate showed the strongest antibacterial activity between 16-24 h,while artemisinin showed relatively stronger antibacterial activity between 8-16 h.Dihydroartermisinin showed no antibacterial activity against S.aureus.Above all,the antibacterial activity of artemisinins against E.coli is dihydroartemisinin>artesunate>artemisinin.Artemisinin and its derivatives have showed different antibacterial kinetics,and no antibacterial activity against S.aureus.has been detected with dihydroartemisinin.

Network pharmacology and RNA sequencing studies on triterpenoid saponins from Bupleurum chinense for the treatment of breast cancer.

Breast cancer remains the most commonly diagnosed malignancy among women, which is frequently associated with adverse side-effects and high metastasis. Bupleurum chinense DC. has been empirically and extensively used as the core prescription for more than half of Chinese formulations for the adjuvant therapy of breast cancer, and its biological activity against breast cancer has been proven by both in vitro and in vivo experiments. Saikosaponin compounds are the characteristic constituent of B. chinense, which exhibit significant cytotoxicity toward several cancer cells. However, the specific mechanisms of these compounds in the treatment of breast cancer have not been comprehensively understood. Therefore, we aimed to determine more potentially therapeutic targets and investigate the biological mechanisms of B. chinense. In the present study, we adopted network pharmacology and bioinformatics analysis to facilitate this requirement. Consequently, the network analysis revealed that saikosaponin-f (39), saikosaponin-d (14), saikosaponin-c (26), saikosaponin-h (54), saikosaponin-g (41), 3'',6''-O-diacetylsaikosaponin-d (20), 11α-methoxy-saikosaponin-f (40), and 6''-O-acetylsaikosaponin-b1 (48) might play important roles in the treatment of breast cancer. In addition, the apoptosis regulator Bcl-2 (BCL-2), C-X-C chemokine receptor type 4 (CXCR4), probable ATP-dependent RNA helicase DDX5 (DDX5), protein kinase C alpha (PRKCA), and proto-oncogene tyrosine-protein kinase Src (SRC) were the potential therapeutic targets that exhibited intense interactions. Mechanistically, a gene enrichment analysis revealed that the action of B. chinense against breast cancer was achieved by the regulation of several biological signaling pathways, such as pathways in cancer, PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, microRNAs in cancer, etc. More importantly, we verified that the predictions involving saikosaponin-d by the cytotoxicity assay, apoptosis analysis, and RNA sequencing methods were partly consistent with those obtained from the network pharmacology prediction.

Undescribed C-geranylflavonoids isolated from the fruit peel of Paulownia catalpifolia T. Gong ex D.Y. Hong with their protection on human umbilical vein endothelial cells injury induced by hydrogen peroxide.

Six undescribed C-geranylated flavonoids, including five C-geranylflavanones named as paucatalinones F - J, one C-geranylflavonol named as paucatalinone K, along with seven known geranylated flavanones, were isolated from the fruit peel of Paulownia catalpifolia T. Gong ex D.Y. Hong. Their structures were elucidated distinctly according to their UV, IR, MS, NMR, and CD data. Among them, two compounds were substituted with unusual modified geranyl groups, namely paucatalinone F with an oxygenated cyclogeranyl substituent and paucatalinone H with a terminal pyranoid geranyl substituent. Furthermore, the protective effects on human umbilical vein endothelial cells (HUVECs) injury induced by H2O2 were evaluated, and paucatalinone F showed the most potential activity. The bioactive results suggested that the geranyl substituent may be an important factor for restraining oxidative HUVECs damage and Paulownia C-geranylated flavonoids might have the potential for preventing cardiovascular complications.

[Inversion Model and Daily Variation of Total Phosphorus Concentrations in Taihu Lake Based on GOCI Data].

The TP concentration is an important index of water quality and an important influencing factor of eutrophication and algae blooms. Remote sensing technology has advantages of wide scope and high time limited efficacy. Monitoring the concentration of TP by satellite remote sensing is important for the study of water quality and eutrophication. In situ datasets collected during the three times of experiments in Taihu Lake between 2013 and 2014 were used to develop the TP inversion model based on GOCI data. The GOCI data in spring, summer, autumn and winter in 2014 were selected to analyze the time and space changes of TP concentration in Taihu Lake. The results showed that the TP algorithm was built up based on the variables, which was to use the eight band combination of GOCI data as variable, and build model using Multi factor linear regression method. The algorithm achieved more accurate TP estimation with R² = 0.898, MAPE = 14.296%, RMSE = 0.026 mg · L⁻¹. Meantime, a analysis on the precision of the model by using the measured sample points and the synchronous satellite images with MAPE = 33.642%, 22.551%, RMSE = 0.076 mg · L⁻¹, 0.028 mg · L⁻¹ on August 5, 2014 and October 24, 2014. Through the analysis of the 30 images on the four days of the four seasons, it showed that the absolute concentration of total phosphorus was different in different seasons. But temporal and spatial distribution of total phosphorus concentration was similar in the morning and afternoon. In spatial distribution, the TP concentration in Meiliang Bay, Zhushan Bay, Gonghu Bay, Xiaomei Port and Changdou Port in the southwest coast was at a continuously high position. The TP concentration change in different regions was influenced by wind direction, wind speed and other factors. The TP concentration highest in the morning, and then gradually decreased, this phenomenon reflected that the TP concentration was affected by temperature and light.

Concurrent chemoradiotherapy was associated with a higher severe late toxicity rate in nasopharyngeal carcinoma patients compared with radiotherapy alone: a meta-analysis based on randomized controlled trials.

BACKGROUND: To investigate the incidence and risk of severe late toxicity with concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma patients. METHODS: Eligible studies included prospective randomized controlled trials (RCTs) evaluating CCRT versus radiotherapy alone in patients with nasopharyngeal carcinoma and in which data on severe late toxicities were available. Random effects or fixed effect models were applied to obtain the summary incidence, relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Five RCTs with 1102 patients with NPC were included in this analysis. The summary incidence of overall severe late toxicities in patients receiving CCRT was 30.7% (95% CI, 18-47.2%) and the incidence of radiotherapy alone group was 21.7% (95% CI, 13.3-33.4%). The use of concurrent chemotherapy was associated with an increased risk of severe late toxicities, with a RR of 1.349 (95% CI, 1.108-1.643; P = 0.005). As for specific late toxicity, CCRT significantly increased the risk of ear deafness/otitis (RR = 1.567; 95% CI, 1.192-2.052), but other late toxicities were not significantly different. Patients receiving concurrent chemotherapy regimens with 3-week high-dose cisplatin (HC) have a higher risk of ear deafness/otitis (RR = 1.672; 95% CI, 1.174-2.382; P = 0.026). However, there was no significant increase in the RR of severe ear complication with the addition of non-3-week high-dose cisplatin (nonHC) regimens (RR = 1.433; 95% CI, 0.946-2.171; P = 0.095). CONCLUSION: With the present evidence, the addition of concurrent chemotherapy seems to increase the risk of severe late toxicities in patients with NPC, especially when using HC regimen for the occurrence of severe ototoxicity.

Potential prevention and treatment of maifanite for Alzheimer's disease based on behavior test, oxidative stress assay, and trace element analysis in hippocampus of Aß(25₋35)-induced AD rats.

This study aimed to assess whether maifanite can improve the learning and memory, and antioxidant abilities of Alzheimer's disease (AD) rats. The 70 rats were divided into seven groups: [A] normal control group, [B] AD model group, [C] sham group, [D] positive control group (donepezil), [E] low-dose maifanite group, [F] middle-dose maifanite group, [G] high-dose maifanite group. For [B], [D], [E], [F], and [G] groups, Aß(25-35) ventricle injection was carried out, then respective medicine were administered once a day for 60 consecutive days. The step-down and step-through test were used to measure learning and memory ability. The hippocampus levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were assayed. The hippocampus contents of Al, Fe, Cu, Zn, Se, and Mn were analyzed by inductively coupled plasma-atomic emission spectrometer. Maifanite decreased the acquisition errors and the retention errors while prolonging the step-down latency, and decreased the number of electric shocks while prolonging the first latency of AD rats. Aß(25-35) ventricle injection initiated the decrease of SOD and GSH-Px activities and the increase of MDA content, and triggered the rise of Al, Fe, and Cu levels and the decline of Mn, Zn, and Se levels. The SOD and GSH-Px activities were enhanced followed by reduced MDA level, and the levels of Mn, Zn, and Se increased accompanied by Al, Fe, and Cu decreased in the maifanite treat groups. Maifanite could improve the learning and memory, and the antioxidant abilities of AD rats. Maifanite had the potential prevention and treatment for AD.

Biological actions of green tea catechins on cardiac troponin C.

BACKGROUND AND PURPOSE: Catechins, biologically active polyphenols in green tea, are known to have a protective effect against cardiovascular diseases. In this study, we investigated direct actions of green tea catechins on cardiac muscle function to explore their uses as potential drugs for cardiac muscle disease. EXPERIMENTAL APPROACH: The effects of catechins were systematically investigated on the force-pCa relationship in skinned cardiac muscle fibres to determine their direct effects on cardiac myofilament contractility. The mechanisms of action of effective catechins were investigated using troponin exchange techniques, quartz crystal microbalance, nuclear magnetic resonance and a transgenic mouse model. KEY RESULTS: (-)-Epicatechin-3-gallate (ECg) and (-)-epigallocatechin-3-gallate (EGCg), but not their stereoismers (-)-catechin-3-gallate and (-)-gallocatechin-3-gallate, decreased cardiac myofilament Ca(2+) sensitivity probably through its interaction with cardiac troponin C. EGCg restored cardiac output in isolated working hearts by improving diastolic dysfunction caused by increased myofilament Ca(2+) sensitivity in a mouse model of hypertrophic cardiomyopathy. CONCLUSIONS AND IMPLICATIONS: The green tea catechins, ECg and EGCg, are Ca(2+) desensitizers acting through binding to cardiac troponin C. These compounds might be useful compounds for the development of therapeutic agents to treat the hypertrophic cardiomyopathy caused by increased Ca(2+) sensitivity of cardiac myofilaments.

[Studies on chemical constituents in bark of dictamnus dasycarpus].

OBJECTIVE: To study the chemical constituents in bark of Dictamnus dasycarpus. METHOD: Isolation and purification were carried out on silica gel column chromatography, prepared thin layer chromatography and sephadex LH - 20, et al. The structures were identified by spectral analysis. RESULT: Twelve compounds were obtained from bark of D. dasycarpus and the structures were determined as dictamnine (I), fraxinellone (II), skimmianine (III), gamma-fagarine (IV ), beta-sitosterol (V), obacunone (VI), limonin disophenol (VII), fraxinellonone (VIII), wogonin (IX), rutevin (X), kihadinin B (XI), dasycarine (XII). CONCLUSION: Compounds IX and XI were isolated from genus Dictamnus for the first time, and compound VIII was isolated from the species for the first time.

[Determination of lignan glycosides in Gaultheria leucocarpa var. yunnanensis by RP-HPLC].

OBJECTIVE: To control the quality of Gaultheria leucocarpa var. yunnanensis the contents of lignans in these plants from different provinces were detected. METHOD: HPLC was adopted using Hypersil-18 column (0.4 cm x 25 cm), methanol: acetonitrile: water (30:5:65) as mobile phase. RESULT: The calibration curves of D1(gaultherinA), D2[(-)-5'-methoxyisolariciresinol-2 alpha-O-beta-D-xylopyranoside)], D4[(+)-lyoniresinol-2 alpha-O-beta-D-glucopyranoside)] were linear in the range of 0.10-0.40 microgram, 0.03-0.13 microgram, 0.02-0.09 microgram, respectively. The average recovery of D1 was 98.9% and RSD was 2.6%. CONCLUSION: Comparing the samples from Jinxiou(158.2 mg.100 g)-1 and Kumming(154.8 mg.100 g)-1, that of Guiyang showed the highest content of LD(208.8 mg.100 g)-1. The content of LD in the tender above-ground part was 1.3 times higher than that in the wilt.