PARP-1 inhibitor alleviates liver lipid accumulation of atherosclerosis via modulating bile acid metabolism and gut microbes.

Background: The DNA damage repair enzyme, poly(ADP-ribose) polymerase 1 (PARP1), is crucial for lipid and glucose metabolism. However, no evidence has been presented on the relationship between liver lipid accumulation and the PARP1 inhibitor, 3-aminobenzamide (3-AB), in atherosclerosis. Methods: ApoE-/- mice were used to explore the effect of 3-AB on atherosclerotic liver lipid accumulation, and the experiment of Sprague Dawley (SD) rats was designed to determine if the lowering of liver lipid levels by 3-AB was linked to gut bacteria. The levels of bile acid metabolism-related targets were assessed by ELISA, western blotting, and RT-qPCR. The relative abundances of gut microbes and biomarkers were determined using 16S rRNA sequencing analysis. Bile acid levels in the liver and ileum were examined by ultra-performance liquid chromatography-tandem mass spectrometry. The relationship between gut microbes and bile acids was assessed by Spearman's correlation analysis. Results: 3-AB significantly reduced the formation of aortic plaques in apoE-/- mice, according to gross oil red staining. H & E and Oil Red O staining revealed that 3-AB significantly reduced the hepatic lipid droplet area in ApoE-/- mice and SD rats. Compared with the atherosclerosis (ATH) group, 3-AB dramatically decreased the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) in the serum of SD rats and apoE-/- mice, and the levels of TC, TG, and LDL-C in the serum and liver of apoE-/- mice. Furthermore, in apoE-/- mice and SD rats, 3-AB increased the mRNA and protein levels of farnesoid X receptor (FXR) and bile salt export pump (BSEP) in the liver, while inhibiting the mRNA and protein levels of FXR and fibroblast growth factor 15 (FGF15) in the ileum, respectively. 3-AB clearly inhibited the mRNA and protein levels of PARP1 in the liver and ileum of apoE-/- mice and rats. Following treatment with 3-AB, the levels of conjugated bile acids decreased in the liver of apoE-/- mice and increased in the ileum of SD rats, according to targeted metabolomic analysis. Microbiome sequencing analysis revealed that 3-AB reduced the relative abundance of Lactobacillus, Bifidobacterium, Listeria, Clostridium, Bacillus, and Staphylococcus in the feces of apoE-/- mice, and the relative abundance of Blautia, Clostridium, and Listeria in the feces of SD rats, eventually decreasing the total abundance of 10 bile salt hydrolase-associated gut microbes. According to the correlation analysis, 3-AB regulates bile acid metabolism, which is primarily related to Bifidobacterium. Conclusion: 3-AB alleviated atherosclerosis by modulating the bile acid metabolism and bile salt hydrolase-related gut microbes.

A nano-preparation approach to enable the delivery of daphnoretin to potentiate the therapeutical efficacy in hepatocellular cancer.

Daphnoretin (DAP), isolated from a traditional Chinese medicine Wikstroemia indica (Linn. C. A. Meyer), could induce apoptosis of hepatocellular cancer (HCC) and inhibit tumor growth. However, the application of DAP in cancer therapies was hampered because to its poor solubility. Herein, this study aimed to design an approach of double-targeted nano-preparation to enable the delivery of DAP to potentiate the therapeutical efficacy in liver cancer via glycyrrhetinic acid-polyethylene glycol-block-poly (D,L-lactic acid)/polyethylene glycol-block-poly (D,L-lactic acid)-DAP (GPP/PP-DAP). In particular, the purity of separated DAP was up to 98.12% for preparation research. GPP/PP-DAP was successfully prepared by the thin-film hydration method. Subsequently, the GPP/PP-DAP was optimized by univariate analysis and the response surface methodology, producing a stable and systemically injectable nano-preparation. Impressively, on the one hand, cytotoxicity studies showed that the IC50 of the GPP/PP-DAP was lower than that of free DAP. On the other hand, the GPP/PP-DAP was more likely to be endocytosed by HepG2 cells and targeted to the liver with orthotopic tumors, potentiating the therapeutical efficacy in HCC. Collectively, both in vitro and in vivo results indicated the excellent tumor inhibition and liver targeting of GPP/PP-DAP, suggesting the nano-preparation could serve as a potential drug delivery system for natural ingredients with anti-hepatoma activity to lay the theoretical foundation for clinical application.

Psychometric Properties of the Chinese version of UPPS-P Impulsive Behavior Scale.

OBJECTIVE: The present study aimed to assess the psychometric properties of a Chinese version of the UPPS-P Impulsive Behavior Scale. The associations between the UPPS-P scale and impulsivity choice, gender, smoking, and drinking status were also assessed. METHODS: A total of 127 adults ranging from 21 to 65 years old participated in the study. Participants were administered with the Chinese version of the UPPS-P Impulsive Behavior Scale, Beck Depression Inventory II (BDI-II), and State-Trait Anxiety Inventory (STAI). Impulsivity choice tasks were also tested including the Delay Discounting Task (DDT), Balloon Analogue Risk Task (BART), and Beads Task (Beads). RESULTS: A new version of the UPPS-P Impulsive Behavior Scale was formed that includes 40 items. The scores of the UPPS-P Impulsive Behavior Scale demonstrated adequate internal consistency on five subscales but less sufficient structure validity in the present sample. In addition, positive urgency was negatively related to the Beads task; negative urgency and positive urgency were positively related to the DDT and BART. Moreover, positive and negative urgency were positively correlated with depression; all five subscales were positively correlated with anxiety; sensation seeking was higher in males than females and in alcohol drinkers than non-drinkers; and lack of premeditation and lack of perseverance were higher in nonsmokers than smokers. CONCLUSIONS: The present study supports the reliability but not the structure validity of the UPPS-P Impulsive Behavior Scale. The impulsivity personality trait assessed by the UPPS-P scale was associated with impulsivity choice, depression, anxiety, gender, and drinking and smoking status. Further studies should be conducted to explore the structure of impulsivity in the Chinese population.

Thermodynamics Analysis of Multiple Microelements' Coupling Behavior in High Fatigue Resistance 50CrVA Spring Steel with Nanoparticles.

Solid solution and coupling precipitation behavior of multiple microelements in 50CrVA spring steel under different temperatures were analyzed based on thermodynamics. Quantitative relationships between the multiple microelements' contents and secondary phases, and their effects on fatigue life, were systematically studied in conjunction with the secondary phase microstructure characterization using scanning and transmission electron microscopy, etc. The solid solution contents of different microelements decreased as the temperature decreased, especially N and Ti, but the number of compounds gradually increased when the temperature decreased. Carbonitride constitutional liquation occurred in 50CrVA-S1# spring steel-containing microparticles, and without carbonitrides, constitutional liquation occurred in 50CrVA-S2# spring steel-containing nanoparticles. The experimental results indicate that the fatigue life reduces by about an order of magnitude when the secondary phase size changes from nanometers to microns, and the corresponding relationship among multiple microelements, microstructure of secondary phases, and fatigue life, was established in this spring steel.

Mixed methods to explore factors associated with the decline of patients in the methadone maintenance treatment program in Shanghai, China.

BACKGROUND: This study was to characterize the Methadone Maintenance Treatment (MMT) in Shanghai, China, and to explore factors associated with the decline of patients in MMT during 2005-2016. METHODS: Both qualitative and quantitative methods were used in this study. Based on the data from Shanghai Centers for Disease Control (CDC), we described the changes in the number of patients who received MMT, and new enrollment each year from 2005 to 2016. Focus groups were conducted with 22 patients, and in-depth interviews were conducted with 9 service providers. RESULTS: Quantitative data demonstrate that the number of new enrollment began to decline in 2009, and the number of patients receiving MMT began to decline in 2012. The main reasons for dropout include (1) discontinuing medication due to unknown reasons (25%), (2) criminal activities other than drug-related crimes (20%), (3) relapse to heroin use (16%), and (4) physical disease (10%). Qualitative assessment results indicate that the major reasons for the decline of patients in MMT are as follows: (1) the increase of Amphetamine-type stimulants (ATS) use in recent years, (2) limited knowledge about MMT in both patients and MMT staff, (3) complicated enrollment criteria, and (4) discrimination against drug use. CONCLUSION: Various reasons to explain the decline of patients in MMT in Shanghai, China, were identified. Government agencies, service providers, and other stakeholders need to work together and overcome identified barriers to support MMT programs in China.

[Determination of 7 elements in chemical treatment agent polyaluminium chloride and iron sulfate by inductively coupled plasma mass spectrometry].

OBJECTIVE: To establish a new rapid method for determination of 7elements( arsenic, selenium, mercury, cadmium, chromium, lead and silver) in two kinds of chemical water treatment agents polyaluminium chloride and iron sulfate by inductively coupled plasma mass spectrometry( ICP-MS). METHODS: Pure water was added to two kinds of chemical water treatment agents. Nitric acid was added to the solution, and the solution was incubated by water bath for 1 h. Matrix effects was eliminated by the employment of Sc, Y, In and Bi as internal standards. The concentrations of 7 elements were determined. RESULTS: The linear ranges for 7 elements were between 0 and 50. 0µg/L with a correlation coefficient for each element of higher than 0. 999. The detection limits were between 0. 05 and 0. 96 µg/L, the recoveries were between 90. 1% and106. 4%, the relative standard deviations were between 1. 6% and 5. 7%. The concentration of arsenic, selenium, and lead in certain samples of the 40 samples tested did not meet the health standards. The large majority of the unqualified samples were caused by the concentration of element lead. CONCLUSION: This method is simple, rapid, accurate and sensitive. It is very suitable for the determination of multi-elements inchemical water treatment agents.

Factors associated with one year retention to methadone maintenance treatment program among patients with heroin dependence in China.

OBJECTIVE: The aim of this study was to evaluate the risk factors associated with dropout from Methadone Maintenance Treatment (MMT) clinics within a 1 year follow-up cohort study in China. METHODS: A data analysis is to explore the adherence of MMT during one year from three hundred and twenty patients with heroin dependence at five clinics (3 in Shanghai, 2 in Kunming) in China. All participants were from the part of China-United States cooperation project entitled "Research about improving the compliance and efficacy of methadone maintenance treatment in China". Our data analysis includes the patients' attendance in the 6 months clinical study and the data in another 6 months afterward. The data of patients at baseline were collected with the Addiction Severity Index (ASI) which is a semi-structured questionnaire covering socio-demographic characteristics and drug use history. The one year attendance after recruitment at the clinics and daily dose were abstracted from the MMT clinic register system. The Cox proportional hazards model were used to explore the risk factor of dropout, defined as seven consecutive days without methadone. RESULTS: By the end of 1 year of treatment 86 patients still remained in MMT without dropout (87% in Shanghai and 13% patients in Kunming). Over the entire 1-year period the median days of remaining in the program were 84 days (in Shanghai and Kunming were 317 days and 22 days).The factors associated with retention included age (HR=0.98, 95%C.I.:0.96-0.99, P=0.0062) and ASI alcohol scores (HR=5.72, 95%C.I.:1.49-21.92, P=0.0109) at baseline. CONCLUSION: One year retention of newly recruited patients with heroin dependence was related to age and ASI alcohol scores at baseline. The adherence is poorer for the patients who are young and having more serious alcohol problems.

[Method establishment for the determination of 6 organophosphorus pesticides metabolites in human urine using LC-MS/MS].

OBJECTIVE: To establish a method to determine the presence and concentration of DEP, DMDTP, DEDTP, PNP, CMHC and TCPY organophosphorus pesticides metabolites in human urine by LC-MS/MS. METHOD: 2.0 ml of urine was enzymatically hydrolyzed in water bath 37 degrees C for 4 hours, then the urine samples were solid-phase extracted by Oasis HLB and eluted with methanol, after centrifugation and concentration the urine samples were separated on waters symmetry C18 5 microm (2.1 mm x 150 mm) column with ammonium acetate buffer solution acetonitrile-water as mobile phase to constant gradient elution. Electrospray ionization source (ESI) was applied and operated in positive ion mode, and multiple reaction monitoring (MRM) mode was adopted. RESULTS: Within concentration ranging from 0 - 1000 ng/ml the correlation coefficient for 5 compounds of 6 were greater than 0.990, recoveries were between 79% - 130%, RSD < 8.2%. The RSD of intra-day and inter-day were less than 15% (n = 6). CONCLUSION: The procedure of samples collection is simple. This is a accurate and specific method for testing organophosphorus pesticides metabolites in human urine.

[Method establishment for the determination of 8 organophosphorus pesticides in serum using LC/MS/MS].

OBJECTIVE: To establish the method to determine the presence and concentration of 8 organophosphors pesticides in serum by LC/MS/MS. METHOD: The serum samples were extracted by ethyl acetateether and then separated on C18 5 microm (2.1 mm x 150 mm) column with pH = 3.5 acid-ammonium acetate buffer solution, methanol--water as mobile phase to mixed gradient elution. Electro-spray ionization source (ESI) was applied and operated in positive ion mode, and multiple reaction monitoring(MRM) mode was adopted. RESULT: Within concentration ranging from 0-1000 ng/ml the correlation coefficient for each compound was greater than 0.990, recoveries were between 95%-129%, RSD < 7.9%. The RSD of intra-day and inter-day were less 12% (n = 6). CONCLUSION: The procedure of preparing serum samples is sample and the result of this method is efficient, accurate and specific.

[Determination of 16 kinds of organophosphorus pesticides in serum by using GC/MS/MS].

OBJECTIVE: To establish a method of determining the presence and concentration of 16 kinds of organophosphorus pesticides in serum by GC/MS/MS. METHOD: The parent ions of each pesticide was detected by running GC/MS in a full scan mode, and the peak areas and the ratio of signal to noise of each product ion were compared by setting different CID voltages. The CID voltage for each parent ion was optimized and determined. Serum samples were solid-phase extracted by Oasis HLB and eluted with ethyl ether after being concentrated and made to constant volume with ethyl ether, and then were tested by GC/MS/MS. RESULTS: The correlation coefficient for each compound in the range of 0 - 1000ng/ml was greater than 0. 990. Recoveries of standard addition were 75% - 129% ,RSD < 10%. The intra-day and inter-day RSD was less than 15% (n = 6). The limits of quantification were less than 2ng/ml except for dichlorovos (55ng/ml). CONCLUSION: GC/MS/MS assay is sensitive and accurate for the determination of pesticides in serum.

[Determination of six kinds of estrogens in cosmetics by liquid chromatograph-tandem mass spectrometry].

OBJECTIVE: To develop methods for the determination of six kinds of estrogens in cosmetics by Liquid Chromatograph-Tandem Mass Spectrometry (LC-MS/MS). METHODS: Through choosing and optimizing experimental conditions, Methanol was chosen as the extracted solvent, super sonic extraction, then centrifuging, filtrating, and the filtrate was analysed by LC-MS/MS. RESULTS: Using this method, the LC-MS/MS response to these six estrogens was linear in the range 0-1000 ng/ml. Level limit of detection of six estrogens were 2.4, 0.2, 0.7, 12, 6 and 5 ng/g, respectively, and level limit of quantification of six estrogens were 8, 0.7, 2.4, 40, 20 and 17 ng/g, respectively, the average spiking recovery rate was 85.2%-102.8%, and relative standard deviation (RSD) was within 2.76%-8.69%. 28 cosmetics were sampled and analyzed and no estrogens were measured. CONCLUSIONS: This method possesses fairly high sensitivity and good specificity.

[Determination of volatile organic compounds in drinking water by purge and trap gas chromatography/mass spectrometry].

OBJECTIVE: To establish a method for determination of volatile organic compounds in drinking water by purge and trap GC/MS. METHODS: Volatile organic compounds in water were purged and trapped by Tekmar 3100, then desorbed and analyzed by GC/MS. Selective ion masses were used in quantitative measurement. RESULTS: 60 VOCs were separated and analyzed in 36 min. Within concentration range from 0 microg/L to 12 microg/L, the correlation coefficient for 51 target compounds was greater than 0.995. The method detection Limits were in the range from 0.021 microg/L to 0.70 microg/L. Recoveries were between 90% and 120%. RF RSD was less than 30%. CONCLUSION: Purge and trap gas chromatography/ mass spectrometry is a sensitive and accurate method for determination of volatile organic compounds in drinking water.