240-week entecavir maleate treatment in Chinese chronic hepatitis B predominantly genotype B or C.

This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A) or 0.5 mg/day ETV maleate (group B), then, all patients received treatment with 0.5 mg/day ETV maleate from week 49 onwards. Patients were regularly followed up. Serum hepatitis B virus (HBV) markers were detected. Adverse events (AE) were recorded. The primary endpoint was the decline in HBV DNA in each group at the end of treatment. Secondary endpoints included the rate of HBV DNA below the lower limit of detection (LLOD) (20 I U/ml) at the end of treatment, the rate of hepatitis B e antigen (HBeAg) loss, the rate of HBeAg seroconversion and serum alanine aminotransferase (ALT) normalization. One hundred and thirty-seven (71 in group A) patients with HBeAg-positive CHB and 46 (21 in group A) patients with HBeAg-negative CHB completed the 240-week treatment and follow-up. Baseline characteristics were well balanced between the two groups. For the HBeAg-positive CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.67 log10 IU/ml vs. B: by 6.74 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA (<20 IU/ml) at Week 240 were similar between groups (A:91.55% vs. B:87.88%; p > .05). Both groups achieved similar HBeAg seroconversion rates at week 240 (A:26.98% vs. B:20.97%; p > .05). Both groups achieved similar normalization of ALT (A:87.32% vs. B:83.61%; p > .05) at Week 240 (p > .05). For the HBeAg-negative CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.05 log10 IU/ml vs. B: by 6.10 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA at Week 240 were similar between groups (A:100% vs. B:100%). Both groups achieved similar normalization rates (A:90.91% vs. B: 95.45%; p > .05) of ALT at Week 240 (p > .05). In conclusion, long-term ETV maleate treatment was safe and efficient in Chinese CHB predominantly of genotype B or C.

Bioactivity-Guided Screening of Antimicrobial Secondary Metabolites from Antarctic Cultivable Fungus Acrostalagmus luteoalbus CH-6 Combined with Molecular Networking.

With the increasingly serious antimicrobial resistance, discovering novel antibiotics has grown impendency. The Antarctic abundant microbial resources, especially fungi, can produce unique bioactive compounds for adapting to the hostile environment. In this study, three Antarctic fungi, Chrysosporium sp. HSXSD-11-1, Cladosporium sp. HSXSD-12 and Acrostalagmus luteoalbus CH-6, were found to have the potential to produce antimicrobial compounds. Furthermore, the crude extracts of CH-6 displayed the strongest antimicrobial activities with 72.3-84.8% growth inhibition against C. albicans and Aeromonas salmonicida. The secondary metabolites of CH-6 were researched by bioactivity tracking combined with molecular networking and led to the isolation of two new α-pyrones, acrostalapyrones A (1) and B (2), along with one known analog (3), and three known indole diketopiperazines (4-6). The absolute configurations of 1 and 2 were identified through modified Mosher's method. Compounds 4 and 6 showed strong antimicrobial activities. Remarkably, the antibacterial activity of 6 against A. salmonicida displayed two times higher than that of the positive drug Ciprofloxacin. This is the first report to discover α-pyrones from the genus Acrostalagmus, and the significant antimicrobial activities of 4 and 6 against C. albicans and A. salmonicida. This study further demonstrates the great potential of Antarctic fungi in the development of new compounds and antibiotics.

Sarsasapogenin improves adipose tissue inflammation and ameliorates insulin resistance in high-fat diet-fed C57BL/6J mice.

Insulin resistance is a major cause of type 2 diabetes and metabolic syndrome. Macrophage infiltration into obese adipose tissue promotes inflammatory responses that contribute to the pathogenesis of insulin resistance. Suppression of adipose tissue inflammatory responses is postulated to increase insulin sensitivity in obese patients and animals. Sarsasapogenin (ZGY) is one of the metabolites of timosaponin AIII in the gut, which has been shown to exert anti-inflammatory action. In this study, we investigated the effects of ZGY treatment on obesity-induced insulin resistance in mice. We showed that pretreatment with ZGY (80 mg·kg-1·d-1, ig, for 18 days) significantly inhibited acute adipose tissue inflammatory responses in LPS-treated mice. In high-fat diet (HFD)-fed obese mice, oral administration of ZGY (80 mg·kg-1·d-1, for 6 weeks) ameliorated insulin resistance and alleviated inflammation in adipose tissues by reducing the infiltration of macrophages. Furthermore, we demonstrated that ZGY not only directly inhibited inflammatory responses in macrophages and adipocytes, but also interrupts the crosstalk between macrophages and adipocytes in vitro, improving adipocyte insulin resistance. The insulin-sensitizing and anti-inflammatory effects of ZGY may result from inactivation of the IKK /NF-κB and JNK inflammatory signaling pathways in adipocytes. Collectively, our findings suggest that ZGY ameliorates insulin resistance and alleviates the adipose inflammatory state in HFD mice, suggesting that ZGY may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.

AMPK activator C24 inhibits hepatic lipogenesis and ameliorates dyslipidemia in HFHC diet-induced animal models.

Dyslipidemia is a chronic metabolic disease characterized by elevated levels of lipids in plasma. Recently, various studies demonstrate that the increased activity of adenosine 5'-monophosphate-activated protein kinase (AMPK) causes health benefits in energy regulation. Thus, great efforts have been made to develop AMPK activators as a metabolic syndrome treatment. In the present study, we investigated the effects of the AMPK activator C24 on dyslipidemia and the potential mechanisms. We showed that C24 (5-40 µM) dose-dependently increased the phosphorylation of AMPKα and acetyl-CoA carboxylase (ACC), and inhibited lipogenesis in HepG2 cells. Using compound C, an AMPK inhibitor, or hepatocytes isolated from liver tissue-specific AMPK knockout AMPKα1α2fl/fl;Alb-cre mice (AMPK LKO), we demonstrated that the lipogenesis inhibition of C24 was dependent on hepatic AMPK activation. In rabbits with high-fat and high-cholesterol diet-induced dyslipidemia, administration of C24 (20, 40, and 60 mg · kg-1· d-1, ig, for 4 weeks) dose-dependently decreased the content of TG, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in plasma and played a role in protecting against hepatic dysfunction by decreasing lipid accumulation. A lipid-lowering effect was also observed in high-fat and high-cholesterol diet-fed hamsters. In conclusion, our results demonstrate that the small molecular AMPK activator C24 alleviates hyperlipidemia and represents a promising compound for the development of a lipid-lowering drug.

New Polyketides from the Antarctic Fungus Pseudogymnoascus sp. HSX2#-11.

The species Pseudogymnoascus is known as a psychrophilic pathogenic fungus with a ubiquitous distribution in Antarctica. Meanwhile, the study of its secondary metabolites is infrequent. Systematic research of the metabolites of the fungus Pseudogymnoascus sp. HSX2#-11, guided by the method of molecular networking, led to the isolation of one novel polyketide, pseudophenone A (1), along with six known analogs (2-7). The structure of the new compound was elucidated by extensive spectroscopic investigation and single-crystal X-ray diffraction. Pseudophenone A (1) is a dimer of diphenyl ketone and diphenyl ether, and there is only one analog of 1 to the best of our knowledge. Compounds 1 and 2 exhibited antibacterial activities against a panel of strains. This is the first time to use molecular networking to study the metabolic profiles of Antarctica fungi.

Nitrogenous Compounds from the Antarctic Fungus Pseudogymnoascus sp. HSX2#-11.

The species Pseudogymnoascus is known as a psychrophilic pathogenic fungus which is ubiquitously distributed in Antarctica. While the studies of its secondary metabolites are infrequent. Systematic research of the metabolites of the Antarctic fungus Pseudogymnoascus sp. HSX2#-11 led to the isolation of one new pyridine derivative, 4-(2-methoxycarbonyl-ethyl)-pyridine-2-carboxylic acid methyl ester (1), together with one pyrimidine, thymine (2), and eight diketopiperazines, cyclo-(dehydroAla-l-Val) (3), cyclo-(dehydroAla-l-Ile) (4), cyclo-(dehydroAla-l-Leu) (5), cyclo-(dehydroAla-l-Phe) (6), cyclo-(l-Val-l-Phe) (7), cyclo-(l-Leu-l-Phe) (8), cyclo-(l-Trp-l-Ile) (9) and cyclo-(l-Trp-l-Phe) (10). The structures of these compounds were established by extensive spectroscopic investigation, as well as by detailed comparison with literature data. This is the first report to discover pyridine, pyrimidine and diketopiperazines from the genus of Pseudogymnoascus.

Using 2003-2014 U.S. NHANES data to determine the associations between per- and polyfluoroalkyl substances and cholesterol: Trend and implications.

Exposure to per- and polyfluoroalkyl substances (PFASs) is a major concern due to their widespread occurrence and adverse health outcomes. The possible binding of PFASs to peroxisome proliferator-activated receptors (PPARs) and nuclear receptors raises concerns that PFASs may impact cholesterol levels in human. In this study, the U.S. National Health and Nutrition Examination Survey (NHANES) data were employed to address the temporal trend for PFAS concentrations in biomonitoring and associations between cholesterol levels and PFAS exposure. Compared to the PFAS levels in 2003-2004, the median perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) levels in human serum in 2013-2014 decreased from 3.7 to 1.8 ng/mL, 19.2-4.7 ng/mL, 1.7 ng/mL to 1.3 ng/mL and 0.8 ng/mL to 0.6 ng/mL, respectively. Also, an estimate of 1.5 ±â€¯0.7 mg/dL (95% confidence interval: 0.2 - 2.8) and 0.4 ±â€¯0.2 mg/dL (95% confidence interval: 0.1 - 0.6) total cholesterol increases for unit PFOA and PFOS increase (ng/mL), respectively. By using hybrid approach, RfDs were estimated to be 2.0 ng PFOS/kg per day and 0.8 ng PFOA/kg per day. However, it should be cautious when using proposed RfDs based on data obtained from cross-sectional datasets, especially evidence based on data originating from experimental or animal studies is still controversial.

[Expression and clinical significance of runt-related transcription factor 3 in children with bronchiolitis].

OBJECTIVE: To study the mRNA level of runt-related transcription factor 3 (RUNX3) in children with bronchiolitis and its clinical significance in bronchiolitis. METHODS: A total of 54 young children with bronchiolitis were enrolled as the bronchiolitis group, among whom 28 with atopic constitution were enrolled in the atopic bronchiolitis group and 26 with non-atopic constitution were enrolled in the non-atopic bronchiolitis group. A total of 48 healthy young children were enrolled as the healthy control group, among whom 24 with atopic constitution were enrolled in the atopic healthy control group and 24 with non-atopic constitution were enrolled in the non-atopic healthy control group. Quantitative real-time PCR was used to measure the mRNA level of RUNX3 in peripheral blood mononuclear cells. ELISA was used to measure the serum levels of interleukin-4 (IL-4) and interferon gamma (IFN-γ). RESULTS: The bronchiolitis group had a significantly lower mRNA level of RUNX3 than the healthy control group, and the atopic bronchiolitis group had a significantly lower mRNA level of RUNX3 than the non-atopic bronchiolitis, atopic healthy control, and non-atopic healthy control groups (P<0.05). The bronchiolitis group had a significantly higher serum level of IL-4 than the healthy control group, and the atopic bronchiolitis group had a significantly higher serum level of IL-4 than the non-atopic healthy control group (P<0.05). The bronchiolitis group had a significantly lower serum level of IFN-γ than the healthy control group, and the atopic bronchiolitis group had a significantly lower serum level of IFN-γ than the non-atopic bronchiolitis, atopic healthy control, and non-atopic healthy control groups (P<0.05). The correlation analysis showed that the mRNA level of RUNX3 was negatively correlated with the serum level of IL-4 and was positively correlated with the serum level of IFN-γ (P<0.05). CONCLUSIONS: Measurement of RUNX3 gene expression in peripheral blood mononuclear cells has a certain value in identifying children with atopic constitution at high risk of asthma among children with bronchiolitis.

Structural Elucidation and Bioinspired Total Syntheses of Ascorbylated Diterpenoid Hongkonoids A-D.

Hongkonoids A-D (1-4), the first example of ascorbylated terpenoids featuring a unique 5,5,5-fused tricyclic spiroketal butyrolactone moiety and diterpenoid-derived long chain, were isolated from Dysoxylum hongkongense. Their structures were unambiguously assigned by a combination of spectroscopic data, chemical degradation, X-ray crystallography, CD analysis, and total synthesis. The total syntheses of compounds 1-4 were effectively accomplished by a convergent strategy with the longest linear sequences of 12-14 steps and overall yields of 5.4-9.6%. Notably, we exploited a bioinspired one-pot method to construct the key intermediate 14 from an easily made compound 12 by involving the cascade reactions of an elaborate Claisen rearrangement, deprotections, and a 5-exo-trig cyclization. The desired major epimer 14a was then transformed to the main building block 21. Assembly of 21 and the long chain vinyl iodide 7 was made by an NHK coupling reaction to furnish the framework of 1-4. Some of the hongkonoids and/or synthetic analogs showed significant to moderate inhibitory activities against NF-κB, 11ß-HSD1, and sterol synthesis. The most active NF-κB inhibitor 34 exhibited distinct inhibition on the LPS-induced inflammatory responses in RAW 246.7 and primary BMDM cells.

Novel substituted pyrazolone derivatives as AMP-activated protein kinase activators to inhibit lipid synthesis and reduce lipid accumulation in ob/ob mice.

Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome characterized by hepatic steatosis. NAFLD is closely linked to obesity, insulin resistance and dyslipidemia. AMP-activated protein kinase (AMPK) functions as an energy sensor and plays a central role in regulating lipid metabolism. In this study, we identified a series of novel pyrazolone AMPK activators using a homogeneous time-resolved fluorescence assay (HTRF) based on the AMPKα2ß1γ1 complex. Compound 29 (C29) is a candidate compound that directly activated the kinase domain of AMPK with an EC50 value of 2.1-0.2 µmol/L and acted as a non-selective activator of AMPK complexes. Treatment of HepG2 cells with C29 (20, 40 µmol/L) dose-dependently inhibited triglyceride accumulation. Chronic administration of C29 (10, 30 mg/kg every day, po, for 5 weeks) significantly improved lipid metabolism in both the liver and the plasma of ob/ob mice. These results demonstrate that the AMPK activators could be part of a novel treatment approach for NAFLD and associated metabolic disorders.

MicroRNA21 promotes interstitial fibrosis via targeting DDAH1: a potential role in renal fibrosis.

Scarring of the kidney directly promotes loss of kidney function. A thorough understanding of renal fibrosis at the molecular level is urgently needed. One prominent microRNA, miR-21, was previously reported to be up-regulated in renal fibrosis, but its mechanism is unclear. In the present study, an unbiased search for downstream messenger RNA targets of miR-21 using the HK-2 human tubular epithelial cell line was performed. Effects of the target gene in renal fibrosis and underlying mechanism were explored. Results show that forced expression of miR-21 significantly increased cell apoptosis, interstitial deposition, and decreased E-cadherin level of the HK-2 cells. Conversely, inhibition of miR-21 promoted the opposite effects. We identified that miR-21 directly interacted with the 3'-untranslated region of the suppressor of dimethylarginine dimethylaminohydrolase 1 (DDAH1) by dual-luciferase assay. Moreover, pcDNA3.1-DDAH1 pretreatment could effectively reduce α-SMA, collagen I, fibronectin expression, and promoted E-cadherin expression, as well as inhibiting HK-2 cell apoptosis, while all those effects can be attenuated by pretreatment with the Wnt/ß-catenin signaling activator Licl. Taken together, our results suggest that miR-21 may regulate renal fibrosis by the Wnt pathway via directly targeting DDAH1. Therefore, this study may provide novel strategies for the development of renal fibrosis therapy.

A rapidly new-typed detection of norovirus based on F0F1-ATPase molecular motor biosensor.

In order to adapt port rapid detection of food borne norovirus, presently we developed a new typed detection method based on F0F1-ATPase molecular motor biosensor. A specific probe was encompassed the conservative region of norovirus and F0F1-ATPase within chromatophore was constructed as a molecular motor biosensor through the "ε-subunit antibody-streptomycin-biotin-probe" system. Norovirus was captured based on probe-RNA specific binding. Our results demonstrated that the Limit of Quantification (LOQ) is 0.005 ng/mL for NV RNA and also demonstrated that this method possesses specificity and none cross-reaction for food borne virus. What's more, the experiment used this method could be accomplished in 1 h. We detected 10 samples by using this method and the results were consistent with RT-PCR results. Overall, based on F0F1-ATPase molecular motors biosensor system we firstly established a new typed detection method for norovirus detection and demonstrated that this method is sensitive and specific and can be used in the rapid detection for food borne virus.

Methanol Conversion into Dimethyl Ether on the Anatase TiO2(001) Surface.

Exploring reactions of methanol on TiO2 surfaces is of great importance in both C1 chemistry and photocatalysis. Reported herein is a combined experimental and theoretical calculation study of methanol adsorption and reaction on a mineral anatase TiO2(001)-(1×4) surface. The methanol-to-dimethyl ether (DME) reaction was unambiguously identified to occur by the dehydration coupling of methoxy species at the fourfold-coordinated Ti(4+) sites (Ti(4c)), and for the first time confirms the predicted higher reactivity of this facet compared to other reported TiO2 facets. Surface chemistry of methanol on the anatase TiO2(001)-(1×4) surface is seldom affected by co-chemisorbed water. These results not only greatly deepen the fundamental understanding of elementary surface reactions of methanol on TiO2 surfaces but also show that TiO2 with a high density of Ti(4c) sites is a potentially active and selective catalyst for the important methanol-to-DME reaction.

MicroRNA-34a Suppresses Autophagy in Tubular Epithelial Cells in Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is traditionally described as a condition leading to rapid damage to kidney function, eventually becoming a significant healthcare concern with a high mortality rate. Autophagy deficiency in the tubular epithelial cells is the main cause of AKI; however, the underlying molecular mechanism remains to be defined. MicroRNAs (miRNAs) are related to autophagy in many diseases. This study was aimed at investigating the relationship between miRNA expression and autophagic activity in the pathogenesis of AKI. METHODS: A mouse model of AKI was produced by ischemia reperfusion (I/R). The expressions of microRNA-34a (miR-34a) and the autophagy-related protein LC3 II/I and p62 were determined in renal tissues and the tubular epithelial cells (RTECs). Moreover, the autophagic activity was investigated after miR-34a overexpression and inhibition. Additionally, the effect of miR-34a on its target gene in regulating autophagic activity in RTECs was also investigated. RESULTS: I/R suppressed the autophagic activity and increased the expression of miR-34a in renal tissues. The in vitro data showed that the upregulation of miR-34a suppressed, whereas the inhibition of miR-34a promoted, autophagy in RTECs. Moreover, miR-34a could directly bind to Atg4B 3'-untranslated region. In addition, the knockdown of Atg4B expression inhibited the autophagic activity in RTECs. CONCLUSION: This study indicated that miR-34a might regulate the autophagic activity and can cause injury in I/R RTECs via targeting Atg4B.

Evaluation of sample preparation and chromatographic separation for the parallel determination of taurine and edaravone in rat tissues using HILIC-MS/MS.

The quantitative analysis of taurine and edaravone in biological sample is critical in pharmaceutical studies. Although each of them can be individually analyzed by different approaches, concurrent quantification is still a highly challenging task with respect to their great polarity variation and the complex composition of tissue sample. In the present study, to simultaneously determine taurine and edaravone in rat tissue, the sample preparation and chromatographic separation conditions were evaluated and discussed in detail. As for the sample preparation, four kinds of solvent and the volume ratio of the optimal solvent to biological sample were both tested and evaluated based on the chromatographic profile, extraction recovery, and matrix effect (ME). The chromatographic separation was performed in a reverse phase (RP) and two hydrophilic interaction liquid chromatography (HILIC) modes, and the corresponding separation efficiencies were assessed using chromatographic parameters like half-width (W 1/2 ), tailing factor (f t), theoretical plates number (N), and ME. Furthermore, adopted composition of two mobile phase systems and the concentrations of the additives in the optimum buffer system were also investigated on an Atlantis HILIC silica column according to the resultant chromatographic profiles and peak areas of the analytes. The optimal results were obtained when the biological samples were deproteined by 4-fold volume of methanol/acetonitrile (1:3, v/v) and separated on a HILIC column with a gradient elution of acetonitrile/water containing 0.2 % formic acid and 10 mM ammonium formate. The proposed approach was validated and successfully applied to the parallel determination of the tissue distribution of edaravone and taurine in rat tissues.

NO adsorption and diffusion on hydroxylated rutile TiO2(110).

We report a computational study of NO adsorption and diffusion on the hydroxylated rutile TiO2(110) surface performed with density functional theory (DFT) calculations corrected by on-site Coulomb corrections and long-range dispersion interactions. NO prefers to adsorb with its N-end down at surface Ti5c sites. The excess electron that is located at a subsurface site for the hydroxylated surface localizes in the 2π* orbital of the adsorbed NO. A novel 'roll-over' diffusion scheme is proposed that involves three neighboring Ti5c atoms and one surface hydroxyl, with an O-end down NO at the middle Ti5c as the intermediate state. During the migration, NO can also form bridging species between two Ti5c atoms. The calculated scanning tunneling microscopy (STM) features with the "bright-dark-bright" configuration corresponding to diffusing NO at different positions are consistent with the experimental STM results.

Study on the interaction of plasma protein binding rate between edaravone and taurine in human plasma based on HPLC analysis coupled with ultrafiltration technique.

In this work, two high-performance liquid chromatography (HPLC) assays were developed and validated for the independent determination of edaravone and taurine using 3-methyl-1-p-tolyl-5-pyrazolone and L-glutamine as internal standards. In in vitro experiments, human plasma was separately spiked with a mixture of edaravone and taurine, edaravone or taurine alone. Plasma was precipitated with acetonitrile containing 0.1% formic acid. Ultrafiltration was employed to obtain the unbound ingredients of the two drugs. The factors that might influence the ultrafiltration effiency were elaborately optimized. Plasma supernatant and ultrafiltrate containing taurine were derivated with o-phthalaldehyde and ethanethiol in the presence of 40 mmol/L sodium borate buffer (pH 10.2) at room temperature within 1 min. Chromatographic separations were achieved on an InertSustain C18 column (250 × 4.6 mm, 5 µm). Isocratic 50 mmol/L ammonium acetate-acetonitrile and gradient 50 mmol/L sodium acetate (pH 5.3)-methanol were respectively selected as the mobile phase for the determination of edaravone and taurine. All of the validation data including linearity, extraction recovery, precision, accuracy and stability conformed to the requirements. Results showed that there were no significant alterations in the plasma protein binding rate of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible.

Target cell extraction coupled with LC-MS/MS analysis for screening potential bioactive components in Ginkgo biloba extract with preventive effect against diabetic nephropathy.

A rapid and useful approach for screening potential bioactive components in Ginkgo biloba extract (GBE) with preventive effect against diabetic nephropathy (DN) was developed using mesangial cells extraction coupled with high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Mesangial cells were first divided into two groups according to their treatments with high glucose or high glucose plus GBE. After incubation for 4, 8, 12, 16, 24 and 48 h, the cells were harvested and extracted with 40% acetic acid in water before LC-MS/MS analysis. Then, 19 compounds and five metabolites were found to selectively combine with mesangial cells. Notably, compounds including quercetin and rutin were identified or tentatively characterized according to the results of retention time and MS spectra, which is highly consistent with our previous reports that quercetin and rutin are potent protective agents against glomerulosclerosis in DN. Therefore, all these results indicate that target cell extraction coupled with LC-MS/MS analysis can be successfully applied for predicting the bioactive components in GBE with preventive effect against DN.

Efficacy and safety of esomeprazole with flupentixol/melitracen in treating gastroesophageal reflux disease patients with emotional disorders.

BACKGROUND AND AIM: This study was designed to demonstrate the safety and efficacy of esomeprazole combined with flupentixol/melitracen for the treatment of gastroesophageal reflux disease (GERD) patients with emotional disorders. METHODS Two hundred eighty-nine GERD patients with emotional disorders were divided randomly into two groups: group 1 received esomeprazole only (monotherapy) and group 2 received esomeprazole and flupentixol/melitracen (combination therapy). The patients' GERD questionnaire (GerdQ) and hospital anxiety and depression (HAD) scores were obtained before and after treatment. Changes in the scores, rates of symptom remission, and adverse effects were compared between the two groups. RESULTS: After 2 weeks of treatment, the average decrease in GerdQ score in the combination group (4.04 ± 2.34) was significantly greater than that in the monotherapy group (3.34 ± 2.74; P < 0.05). Significant differences between the two groups were also found for changes in HAD anxiety scores (5.45 ± 2.41 vs 3.34 ± 2.43, P < 0.05), depression scores (5.47 ± 2.47 vs 3.00 ± 3.28, P < 0.05), and anxiety-depression scores (5.20 ± 2.71 vs 3.60 ± 2.56, P < 0.05). The remission of symptoms (eructation, abdominal pain, anorexia, and other accompanying symptoms) in the combination group was significantly better than that in the monotherapy group, and no significant difference in the incidence of adverse events was observed between the two groups. CONCLUSIONS: The combination therapy has better efficacy than the monotherapy in improving the symptoms of gastroesophageal reflux in patients with emotional disorders. In addition, this combination treatment is safe, with a low incidence of adverse events.

Moxibustion preconditioning reduces inflammatory response in rats with cerebral ischemia-reperfusion injury by regulating PI3K / AKT / mTOR signaling pathway. / 艾灸预处理通过调控PI3K/AKT/mTORä¿¡å·é€šè·¯å‡è½»è„‘ç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ ç‚Žæ€§ååº”.

OBJECTIVES: To observe the effect of moxibustion preconditioning on inflammatory response in rats with cerebral ischemia reperfusion injury (CIRI), so as to explore its mechanisms underlying improving CIRI. METHODS: Seventy-five male SD rats were randomly divided into sham operation, model, moxibustion preconditioning 3 days (Moxi 1), moxibustion preconditioning 5 days (Moxi 2) and moxibustion preconditioning 7 days (Moxi 3) groups, with 15 rats in each group. Moxibustion was applied at "Baihui"(GV20), "Dazhui"(GV14) and "Zusanli"(ST36) for 20 min once a day, totally for 3, 5 or 7 days. Thirty minutes after the last moxibustion treatment, the CIRI model was established by occlusion of the middle cerebral artery. The neurological deficit score was assessed by using Longa's method. The infarct size of the brain assessed after staining with 2% triphenyltetrazolium chloride (TTC). The morphological changes of cortical neurons were observed by HE staining. The contents of inflammatory factors interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), S-100ß protein (S-100ß) and neuron-specific enolase (NSE) were detected by ELISA. The expression of phosphatidylinositol-3-kinase (PI3K), p-PI3K, protein kinase B (AKT) and mammalian target of rapamycin (mTOR) proteins in the ischemic cortex tissues were detected by immunohistochemistry and Western blot. RESULTS: Compared with the sham operation group, the neurological function score and the percentage of cerebral ischemic volume were increased (P<0.01). The contents of serum IL-1ß, TNF-α, S-100ß and NSE were significantly increased (P<0.01), while the protein expressions of PI3K, p-PI3K, AKT and mTOR in the cerebral cortex were significantly decreased (P<0.01) in the model group. Compared with the model group, the neurological function score and the percentage of cerebral ischemic volume were significantly decreased (P<0.01). The contents of serum IL-1ß, TNF-α, S-100ß and NSE were significantly decreased (P<0.01), and the expressions of PI3K, p-PI3K, AKT and mTOR proteins in the cerebral cortex were significantly increased (P<0.01) in three moxibustion groups. Compared with the Moxi 1 and Moxi 2 groups, the above indicators were significantly improved in rats of the Moxi 3 group (P<0.01, P<0.05). CONCLUSIONS: Moxibustion preconditioning can significantly improve the neurological function of rats after ischemia-reperfusion, inhibit serum inflammatory factors IL-1 ß and TNF-α, inhibit brain tissue injury markers S-100ß and NSE, which may be related to the activation of PI3K/AKT/mTOR signaling pathway. The protective effect of moxibustion preconditioning for 7 days on CIRI was better than that of 5 days and 3 days.