Ilaprazole-amoxicillin dual therapy at high dose as a first-line treatment for helicobacter pylori infection in Hainan: a single-center, open-label, noninferiority, randomized controlled trial.

OBJECTIVES: This study aimed to evaluate the efficacy, adverse events, patient compliance, and cost of dual therapy with Ilaprazole-amoxicillin (IA) at high dose versus Ilaprazole-amoxicillin-furazolidone-bismuth (IAFB) quadruple therapy for the Helicobacter pylori (H.pylori) infection among Chinese patients. METHODS: 200 patients who had tested positive for H. pylori and undergoing upper gastrointestinal endoscopy after being diagnosed with chronic gastritis participated in this open-label randomized controlled clinical trial. Patients were randomized to Group A and Group B: the 14-day IA dual treatment group (101) and IAFB quadruple treatment group (99). The 13 C urea breath test was conducted to determine whether H. pylori had been eliminated 4-6 weeks after the treatment. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the two treatment groups. RESULTS: Eradication rates in group A were 92.1% and 94.9%, depending on the intention-to-treat (ITT), per-protocol (PP), respectively, which was similar to group B (91.9% and 93.6%). There was no significant difference observed in adverse events between the two groups (P = 0.518). Interestingly, compliance was significantly higher in group A compared to the group B (P = 0.031). In addition, drug costs were significantly lower for group A in comparison to the group B. CONCLUSIONS: IA dual therapy was found to be equally effective, safer and less costly than IAFB quadruple therapy. Therefore, these therapies can be potentially considered as first-line regimens for empirical treatment.

Tongguanteng injection reverses paclitaxel resistance via upregulation of TAB1 expression in ovarian cancer in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongguanteng injection (TGT), the water extract from the stem of the Traditional Chinese hebal medicine of Marsdenia tenacissima (Roxb.) Wight et Arn. has been used as anticancer remedy for decades. TGT was not only used in the treatment of many malignant cancers extensively, but also an adjuvant anticancer drug with chemotherapeutics clinically. AIM OF THE STUDY: To evaluate the effects of TGT on reversing paclitaxel (PTX) resistance and investigate the potential mechanism related to TAB1 in ovarian cancer (OC) in vitro and in vivo. MATERIALS AND METHODS: The synergistic effect and reversal ratio were determined by CCK8 assay and median-effect principle after the combination of TGT and PTX in OC A2780 and its PTX-resistant (A2780/T) cells. The biological functions in cell apoptosis, migration and invasion of A2780/T cells treated by PTX 4 µM with TGT 20, 40, 80 mg⋅mL-1 for 24 h were evaluated by colony formation, flow cytometry, wound healing and transwell assays. Proteomics technique and bioinformatic analysis were used to indentify the change of TAB1 expression in A2780/T cells induced by TGT. The association between TAB1 expression and human OC was analyzed by gene expression databases. In A2780/T cells, western blotting and colony formation assays were used to investigate the relationship between TAB1 expression and PTX resistance after TAB1 overexpression by TAB1 plasmids. The mechanism of TGT and PTX regulating TAB1 and its related proteins were explored by western blotting and flow cytometry assays after TAB1 knock-down using siTAB1. Moreover, TUNEL staining, immunohistochemistry (IHC) and histopathology were used to observe the antitumor effects, TAB1 and p-p38 expression and the tissues impairments in nude mice xenograft model established by A2780/T cells after the co-treatment with TGT and PTX by in vivo. RESULTS: TGT combined with PTX showed the synergistic effect (CI<1), which could reverse the IC50 values of PTX in OC A2780 and A2780/T cells about 23.50 and 6.44 times, respectively. Besides, TGT combined with PTX could significantly inhibit the migration, invasion and promote apoptosis of A2780/T cells. We identified that TGT could induce TAB1 expression in A2780/T cells by proteomics analysis. TAB1 downregulation was significantly associated with tumorigenesis and poor prognosis in OC patients and PTX resistance in A2780/T cells. Furthermore, TGT could activate TAB1/TAK1/p38 MAPK signaling pathway targeting TAB1 and regulate the expression of Bax, Bcl-2 proteins to improve the sensitivity of A2780/T cells to PTX. TGT combined with PTX also showed a greater inhibition in tumor growth than PTX monotherapy in vivo. These promising results show the efficacy of TGT in reversing PTX resistance and provide a potential strategy that targeting TAB1/TAK1/p38 MAPK signaling pathway may improve the chemotherapy sensitivity in OC. CONCLUSIONS: Our results revealed that Tongguanteng injection could reverse paclitaxel resistance and the potential mechanism might be associated with the activation of TAB1/TAK1/p38 MAPK signaling pathway in OC in vitro and in vivo. TAB1 might be a pivotal target for reversing PTX resistance. This study will provide a theoretical basis for the combination of Tongguanteng injection and paclitaxel in clinic.

Joint Effects of Cigarette Smoking and Green Tea Consumption with miR-29b and DNMT3B mRNA Expression in the Development of Lung Cancer.

In tumor development, increased expression of DNA methyltransferase (DNMT) has been observed. In particular, cigarette smoke and tea polyphenols may influence DNMT3B mRNA expression by regulating microRNA (miR)-29b expression. Herein, we designed a case−control study to evaluate the joint effects of smoking and green tea consumption, with miR-29b and DNMT3B mRNA expression, in lung cancer development. A total of 132 lung cancer patients and 132 healthy controls were recruited to measure miR-29b and DNMT3B mRNA expression in whole blood. Results revealed that lung cancer patients had lower miR-29b expression (57.2 vs. 81.6; p = 0.02) and higher DNMT3B mRNA expression (37.2 vs. 25.8; p < 0.001) than healthy controls. Compared to non-smokers with both higher miR-29b and lower DNMT3B mRNA expression, smokers with both low miR-29b and higher DNMT3B mRNA expression had an elevated risk of lung cancer development (OR 5.12, 95% CI 2.64−9.91). Interactions of smoking with miR-29b or DNMT3B mRNA expression in lung cancer were significant. Interaction of green tea consumption with miR-29b expression and DNMT3B mRNA expression in lung cancer was also significant. Our study suggests that smokers and green tea nondrinkers with lower miR-29b expression and higher DNMT3B mRNA expression are more susceptible to lung cancer development.

Identification of Key Drug Targets and Molecular Mechanisms of Curcumae Rhizoma Acting on HBV-Related HCC: Weighted Correlation Network and Network Pharmacological Analyses.

Background: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has poor prognosis and high mortality rate. Curcumae Rhizoma, a classic Chinese medicinal herb, is often used to treat tumors. Methods: Active ingredients of Curcumae Rhizoma were extracted from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database, and potential targets were predicted by the TCMSP database and Swiss Target Prediction database. The key drug targets were filtered by intersecting predicted targets, DEGs, and genes in important modules from WGCNA. Besides, the key drug targets were used to construct a network of "herb-active ingredient-target-disease" interactions and subjected to enrichment analysis and protein-protein interaction (PPI) analysis. The hub targets based on PPI analysis was evaluated by the KMplotter database. Results: Three active ingredients of Curcumae Rhizoma were collected with OB ≥ 30% and DL ≥ 0.18, including hederagenin, wenjine, and bisdemethoxycurcumin. The key drug targets were mainly enriched in cell cycle checkpoint, DNA integrity checkpoint, and peptidyl-serine modification. Besides, Curcumae Rhizoma treatment of HBV-related HCC mainly involved the p53 signaling pathway and arachidonic acid metabolism. Finally, ESR1 and PTGS2 were identified as hub targets from PPI analysis. ESR1 was found to be correlated with survival in liver cancer patients with hepatitis. Conclusion: Based on WGCNA and network pharmacological analysis, our results illustrated that Curcumae Rhizoma might work through regulating multitargets and multipathways in HBV-related HCC.

Efficacy and safety of AnluoHuaxian pills on chronic hepatitis B with normal or minimally elevated alanine transaminase and early liver fibrosis: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). AIM OF THE STUDY: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. RESULTS: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. CONCLUSIONS: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.

The Protective Effects of a Modified Xiaohua Funing Decoction against Acute Liver Failure in Mice Induced by D-Gal and LPS.

OBJECTIVE: The aim of this study was to evaluate the effects of a modified Xiaohua Funing decoction (Xfd) on acute liver failure (ALF) and determine whether the protective mechanisms are related to alterations in the gut microbiota. METHODS: An animal model of ALF was induced by intraperitoneal injection of D-galactosamine (D-Gal, 0.5 g/kg) and lipopolysaccharide (LPS, 100 µg/kg). Male BALB/c mice were randomly divided into the following 4 groups: the control group (saline, Con), model group (D-Gal/LPS, Mod), silymarin pretreatment group (200 mg/kg, Sil), and modified Xfd pretreatment group (650 mg/kg, Xfd). The Sil and Xfd groups received the respective intervention orally for 14 days and 2 h before D-Gal/LPS treatment. The liver injury markers included alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and liver histology. 16S rRNA gene sequencing was performed to assess the effects on the caecum content. RESULTS: D-Gal/LPS treatment caused severe ALF, illustrating that the ALF model was successfully established. The administration of Sil and Xfd greatly reduced the serum ALT and AST levels and improved the pathological signs of liver injury. However, no significant difference was found between the two groups. In contrast to the Mod group, the Sil and Xfd groups showed a shift toward the Con group in terms of the gut microbiota structure. The abundances of Firmicutes and Bacteroidetes and the Bacteroidetes/Firmicutes ratio in the Mod group significantly differed from those in the Con group. The Sil and Xfd groups showed restoration of the disordered microbiota. Significantly increased relative abundances of Lachnospiraceae_NK4A136_group and Candidatus_Saccharimonas and a markedly decreased Muribaculaceae abundance were found in the Sil and Xfd mice compared with those in the Mod mice (P < 0.01, P < 0.05). Interestingly, a negative correlation was observed between the abundances of the gut microbiota constituents, specifically Clostridia_UCG-014, and ALT and AST levels. CONCLUSION: In summary, our results indicate that Xfd may protect the liver and modify the gut microbiota in ALF mice.

High phosphorus fertilization changes the speciation and distribution of manganese in wheat grains grown in a calcareous soil.

The physiological disorders in humans resulting from the excess dietary intake of manganese (Mn) via whole-grain food has attracted considerable attention. However, the speciation and bioavailability of Mn in wheat grains and their response to different phosphorus (P) fertilization rates are still unclear. In the current study, using a long-term field trial with P application rates of 0, 21.8, 43.6, 65.5 and 87.3 kg/ha, we examined changes in the concentration, distribution, and speciation of Mn of wheat grains using synchrotron-based X-ray fluorescence microscopy and X-ray absorption spectroscopy. The total Mn concentration in grains was found to be increased by phosphorus fertilization, especially in embryo in the form of Mn(II), but this phosphorus fertilization also decreased Mn concentrations in the nucellar projection. In this study, the speciation of Mn in different wheat grain tissues was examined, and results indicate that in calcareous soils, high rates of P fertilizers can increase Mn concentrations in wheat grain, including Mn which is likely to be of high bioavailability, and thus may increase the risk for human to expose to high Mn intake via whole-grain food.

Differences in MicroRNA Expression in Chronic Hepatitis B Patients with Early Liver Fibrosis Based on Traditional Chinese Medicine Syndromes.

The aim of this study was to determine if microRNA (miRNA) expression is different among chronic hepatitis B (CHB) patients with early liver fibrosis classified according to traditional Chinese medicine (TCM) syndromes. Eighteen CHB-fibrosis patients and 12 CHB patients without fibrosis were enrolled. The CHB-fibrosis group included 9 patients with the TCM syndrome of Ganyu Pixu Xueyu (GYPXXY), characterized by liver stagnation, spleen deficiency, and blood stasis, and 9 patients with the TCM syndrome of Qixu Xueyu (QXXY), characterized by deficiency of qi, blood, and blood stasis. Agilent miRNA microarray was performed first in liver specimens to determine whether miRNA expression is different in patients with these two TCM syndromes of CHB-fibrosis. Gene Ontology (GO) analysis and KEGG analysis were applied to determine the roles of the differentially expressed miRNAs. QRT-PCR was performed to validate the Agilent miRNA microarray results. Compared with GYPXXY patients, 6 differentially expressed miRNAs were upregulated (miR-144-5p, miR-18a-5p, miR-148b-3p, miR-654-3p, miR-139-3p, and miR-24-1-5p) and 1 was downregulated (miR-6834-3p) in QXXY patients. According to qRT-PCR data, miR-144-5p and miR-654-3p were confirmed as upregulated in CHB-liver fibrosis patients compared to CHB patients without fibrosis, whereas the other 4 miRNAs were not significantly different. More importantly, miR-654-3p was confirmed to be significantly upregulated in QXXY patients compared with values in GYPXXY patients, whereas no significant difference was found in miR-144-5p. Moreover, the pathways of central carbon metabolism in cancer and cell cycle related to miR-654-3p and the target genes of PTEN and ATM were found to be different between QXXY patients and GYPXXY patients. These results indicate that there are different miRNAs, pathways, and target genes between QXXY patients and GYPXXY patients. However, due to the limited sample, whether miR-654-3p and the target genes PTEN and ATM could be molecular markers to differentiate TCM syndromes could not be established.

Xiaoaiping injection enhances paclitaxel efficacy in ovarian cancer via pregnane X receptor and its downstream molecules.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoaiping injection, a traditional Chinese medical injection extracted from root of Marsdenia tenacissima (Roxb.) Moon, has been exclusively used on curing malignant tumor in China and as adjuvant therapeutic agent for chemotherapeutics, including paclitaxel. AIM OF THE STUDY: The goal of this study was to investigate the synergistic inhibitory efficacy of Xiaoaiping injection and paclitaxel on ovarian cancer. The mechanism may be associated with nuclear receptor pregnane X receptor (PXR) regulating its downstream molecules. MATERIALS AND METHODS: In vitro, MTT assay, flow cytometry and Hoechst dyeing were used to evaluate the SK-OV-3 cell proliferation, apoptosis and cell cycle respectively. The mRNA and protein expression of PXR and its downstream CYP450 enzymes, transporters and Bcl-2 families were measured by qRT-PCR and Western blot. Rhodamine 123 efflux experiment was conducted to detect the P-gp efflux ability. PXR plasmid and PXR siRNA were transiently transfected into SK-OV-3 cells respectively to establish PXR-overexpressed or PXR-interfered cells. In vivo, xenograft tumor mice model was established by SK-OV-3 cells to estimate the antitumor effect of Xiaoaiping injection combined with paclitaxel. The expressions of PXR and its downstream molecules in tumor tissues were determined to further clarify the potential mechanism. RESULTS: Xiaoaiping injection significantly enhanced the anti-proliferation, pro-apoptosis effect of paclitaxel on SK-OV-3 cells. The synergetic effect was displayed by Xiaoaiping injection inhibiting paclitaxel-induced PXR and CAR expression, which subsequently inhibited CYP450 enzymes CYP2C8 and CYP3A4, transporter P-gp and anti-apoptotic proteins Bcl-2 and Bcl-xl in SK-OV-3 cells. In PXR-overexpressed cells, Xiaoaiping injection down-regulated the expression of PXR and its downstream molecules. The result of xenograft tumor model showed that Xiaoaiping injection combined with paclitaxel enhanced anti-tumor effect on ovarian cancer in vivo. CONCLUSIONS: Xiaoaiping injection enhances anti-tumor effect of paclitaxel by inhibiting cell proliferation, inducing apoptosis process. The mechanism may be associated with Xiaoaiping injection inhibiting PXR and its downstream metabolic enzymes CYP2C8, CYP3A4, transporter P-gp and anti-apoptosis protein Bcl-2.

Intestinal morphology, immunity and microbiota response to dietary fibers in largemouth bass, Micropterus salmoide.

This study is aimed at identifying the effects of dietary fiber on gut health, as well as the association between that understanding and fiber consumption in fish. A total of 300 juvenile largemouth bass (micropterus salmoides, initial average weight: 15.38 ± 0.16g) were randomly divided into three treatment groups (4 replicates per group). Fish were fed with isoproteic and isolipidic diets containing 0% (low fiber, LF), 4% (moderate fiber, MF) and 8% (high fiber, HF) soybean fiber, respectively. The intestine and intestinal content of test fish per treatment group after 56 days of treatment were sampled. The results showed that the anterior intestinal sections had normal histological architecture, and no considerable damage or inflammation was observed in any histological section from all subjects examined. Curiously, fish fed the MF diet had better histological alterations than the other treatments. Meanwhile, the intestinal antioxidant capacity in the MF group was significantly promoted when compared to the other groups, as well as up-regulated expression of antioxidant-related genes including sod, cat and gpx with increasing dietary fiber concentrations. Importantly, the administrations of MF diet remarkably elevated largemouth bass innate immune parameters include intestinal inducible nitric oxide synthase (iNOS) activity, nitric oxide (NO) and total protein content. Similarly, dietary administrations of fiber down-regulated notablely the expression of pro-inflammatory cytokines including IL-8, IL-1ß and TNFα, whereas up-regulated tolerogenic cytokine IL-10 and TGF-ß1 mRNA levels. In addition, dietary fibers also modulated the community structure of the intestinal microbiota by significantly altering bacterial diversity. Dietary supplemental fibers regulated intestinal microbiota in largemouth bass, characterized by a reduced abundance of Fusobacteria along with increased abundances of Proteobacteria and Firmicutes. Taken together, the present results suggested that moderate fiber supplementation was beneficial to promoting intestinal health status of fish through antioxidant and anti-inflammatory effects, which could be at least partially responsible by the modulation of gut microbial composition.

Effect of enzymatic degraded polysaccharides from Enteromorpha prolifera on the physical and oxidative stability of fish oil-in-water emulsions.

To explore the potential application of enzymatic degraded polysaccharides from Enteromorpha prolifra (EEP) as antioxidant in fish oils, a stable fish oil emulsion system incorporating EEP was established. Effects of emulsifier (Tween 80, gum arabic and lecithin) and EEP concentration on the physical characteristics of fish oil emulsions were investigated. The results indicated that Tween 80 was the best choice, and 1% (w/w) of EEP was the optimum concentration for the preparation of fish oil emulsions. Influence of EEP on the oxidative stability and physical stability of fish oil emulsions was compared with that of antioxidants VE and TBHQ by determining the physical properties, lipid hydroperoxide formation, secondary reaction products formation, pH and long chain polyunsaturated fatty acid content, during storage at 45 °C. The results indicated that the fish oil emulsion system (5% oil, 1% EEP and 1% Tween 80, w/w) possessed good physical and oxidative stabilities.

Lowering effects of fish oil supplementation on proinflammatory markers in hypertension: results from a randomized controlled trial.

Reduced inflammation is one of the potential mechanisms underlying the cardioprotective efficacy of fish oil enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Supplementation with fish oil has favorable effects on cardiometabolic profiles in Inner Mongolia patients with hypertension, but whether the cardiovascular benefits can be ascribed to reduced subclinical inflammation is unclear among this population. Seventy-seven middle-aged/elderly hypertensive volunteers were randomly assigned to receive either fish oil (FO, n = 38, 2 g day-1 EPA + DHA) or control corn oil (CO, n = 39) for 90 days. FA compositions in erythrocytes and C-reactive protein (CRP, mg L-1), interleukin-6 (IL-6, pg mL-1) and tumor necrosis factor-α (TNF-α, pg mL-1) concentrations in the plasma were measured before and after the 90-day supplementation, and the cardiometabolic risk was expressed as continuously distributed z-scores calculated by standardizing and then summing the individual cardiovascular risk factors. Significant reductions in the TNF-α (-1.87 ± 2.71 vs. -0.64 ± 2.62, p = 0.02) and CRP levels (-0.85 ± 2.49 vs. 0.56 ± 2.14, p = 0.01) were found in the FO group compared with the CO group, but not in the IL-6 levels (-0.66 ± 1.05 vs. -0.25 ± 0.94, p = 0.10). The decreases in the changes of TNF-α levels were positively correlated with the reductions in the cardiometabolic risk scores in the subjects supplemented with FO (r = 0.35, p = 0.02), but not in the control subjects supplemented with CO (r = 0.09, p = 0.54). FO supplementation increased the levels of EPA (p = 0.013), DHA (p = 0.040) and total n-3 FA (p = 0.035), and decreased the levels of 20:4n-6 (p = 0.041) and total n-6 FA (p = 0.011) and the ratio of n-6 to n-3 FA (p = 0.001), compared with the changes related to the CO group. The increases in the changes of erythrocyte total n-3 FA levels were inversely correlated with the concentrations of TNF-α (r = -0.34, p = 0.001) and CRP (r = -0.29, p = 0.020). The present findings suggest that fish oil supplementation may attenuate the proinflammatory reactions in hypertension, which might help promote the cardiometabolic benefits in this Inner Mongolia population.

Effects of supplemental dietary bile acids on growth, liver function and immunity of juvenile largemouth bass（Micropterus salmoides）fed high-starch diet.

The present study was conducted to investigate the effects of bile acids (BAs) on the growth, liver function and immunity of the largemouth bass fed high-starch diet. The experiment set three isonitrogenous and isoenergetic semi-purified diets, LS: low-starch diet (5%), HS: high-starch diet (19%) and SB: high-starch diet with BAs (350 mg/kg diet). An 8-week feeding trial was conducted in largemouth bass of initial weight 23.69 ± 0.13 g. The results indicated that the weight gain (WG) and protein efficiency ratio (PER) of fish fed LS and SB were significantly higher than HS treatment. The superoxide dismutase (SOD) and catalase (CAT) activities of SB group were significantly increased, while malondialdehyde (MDA) content significantly reduced in liver compared with HS group. The activities of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and glucose contents in plasma of SB group were significantly lower than HS treatment, whereas the content of triglyceride (TG) and total cholesterol (TC) in plasma were significantly higher than HS treatment. Additionally, the plasma immunoglobulin count, lysozyme activity and the blood leukocyte count (WBC) in SB group were significantly higher than HS group. The results of paraffin section of liver showed the histopathological alterations were significantly reduced in the SB group compared to HS group. All in all, this study revealed that bile acids supplement could significantly improve growth performance, enhance liver function and immune ability, and alleviate stress responses of M. salmoides fed high-starch diet.

High dietary lipid level alters the growth, hepatic metabolism enzyme, and anti-oxidative capacity in juvenile largemouth bass Micropterus salmoides.

The present study was conducted to investigate the effects of high dietary lipid levels on growth, metabolism, antioxidant capacity, and immune responses of largemouth bass. Fish (initial body weight 13.38 ± 0.11 g) were fed three isonitrogenous semi-purified diets containing 5%, 10%, and 20% lipid, respectively. The results indicated that fish fed 10% lipid diet showed significantly better final body weight, specific growth rate (SGR), protein efficiency ratio (PER), and feed conversion ratio (FCR) compared with that fed 5% lipid diet. Meanwhile, fish fed 20% lipid diet had a significantly higher viscera ratio (VR), hepatosomatic index (HSI), intraperitoneal fat ratio (IPF), and liver lipid content than those fed the other diets. Higher alanine aminotransferase (ALT) and aspartate transaminase (AST) activities, total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) contents, and LDL-C/HDL-C value in plasma were recorded in fish fed 20% lipid diet, while higher insulin contents were obtained in fish fed 5% lipid diet. In addition, the highest carnitine palmitoyltransferase I (CPT1), AMP-activated protein kinase (AMPK), fructose-1,6-bisphosphatase (FBPase), and phosphoenolpyruvate carboxykinase (PEPCK) activities in the liver were also observed in fish fed 20% lipid diet. However, fish fed 20% lipid diet had a significantly lower superoxide dismutase (SOD) and catalase (CAT) activities and higher MDA contents in liver than those fed the other diets. The higher nitric oxide (NO) contents and inducible nitric oxide synthase (iNOS) activity in liver were recorded in fish fed 10% lipid diet. Moreover, the alkaline phosphatase (ALP), inducible nitric oxide synthase (iNOS) and lysozyme activities, and nitric oxide (NO) contents in plasma were higher in fish fed the 10% diets than the other groups. In conclusion, high dietary lipid levels could suppress growth performance and liver anti-oxidative capacity, and reduce immune responses of largemouth bass.

Larger regional volume of the thalamus in diarrhea-predominant irritable bowel syndrome: a cross-sectional study.

As a relay center between the cerebral cortex and various subcortical brain areas, the thalamus is repeatedly associated with the dysfunction of brain-gut interaction in patients with irritable bowel syndrome (IBS). However, the regional morphological alterations of the thalamus in IBS are not well defined. We acquired structural magnetic resonance data from 34 patients with IBS and 34 demographically similar healthy subjects. Data processing was performed using FMRIB's Integrated Registration and Segmentation Tool (FIRST). Volumetric analysis and surface-based vertex analysis were both carried out to characterize the morphology of the thalamus and other subcortical structures. Our results suggested that the majority (31 cases) of the patients with IBS had diarrhea-predominant symptoms. Volumetric analysis revealed a larger normalized volume of the right thalamus and left caudate nucleus in patients with IBS than in healthy controls. Surface analysis indicated that the difference arose mainly from the laterodorsal nucleus of the right thalamus, and the body of the left caudate nucleus. In addition, patients with IBS had different hemispheric asymmetries of the thalamus (rightward) and caudate nucleus (leftward) from controls (leftward for the thalamus and rightward for the caudate nucleus). In general, our results indicated that patients with diarrhea-predominant IBS had enlarged thalamus and caudate nucleus volumes, as well as altered hemispheric asymmetries of these two structures, compared with healthy controls. The neuroimaging evidence of these structural alterations helps clarify the underlying pathophysiology of diarrhea-predominant IBS.

Effect of Xiao-Ai-Ping injection on paclitaxel pharmacokinetics in rats by LC-MS/MS method.

Xiao-Ai-Ping injection (XAP) has been shown to be clinically effective in treatment of gastric carcinoma, liver cancer and lung cancer, when it was combined with anticancer drug paclitaxel (PTX). To analyze the effect of XAP on the pharmacokinetics of PTX, a liquid chromatography-tandem mass spectroscopy (LCMS/MS) assay method was developed and validated to quantify PTX simultaneously and its main metabolite 3'-p-hydroxypaclitaxel (C3'-OHP) in rat plasma. PTX and C3'-OHP were quantified using positive MRM mode. The analysis method was validated for specificity, recovery, carry-over, accuracy, precision, sample stability and dilution integrity under various storage conditions. The pharmacokinetic parameters were determined in rats after tail intravenous administration of 6 mg/mL PTX in the absence (control group) or presence of intraperitoneal administration of 10 mL/kg、20 mL/kg XAP (study groups). Compared to control group, the area under the plasma concentration-time curve (AUC) of PTX and C3'-OHP in study groups increased significantly following consecutive administration with XAP for 10 days. In conclusion, pretreatment with XAP enhanced the exposure of PTX and C3'-OHP. There would be herb-drug interaction happening between XAP and PTX in rats.

Linseed oil can decrease liver fat deposition and improve antioxidant ability of juvenile largemouth bass, Micropterus salmoides.

A feeding trial was conducted to evaluate the effect of linseed oil (LO) on growth, plasma biochemistry, hepatic metabolism enzymes, and antioxidant capacity of juvenile largemouth bass, Micropterus salmoides. Four isonitrogenous (crude protein, 45%) and isoenergetic (gross energy, 18 MJ/kg) diets were formulated by replacing 0 (the control), 33.3%, 66.7%, and 100% of fish oil with linseed oil. Each diet was fed to three replicate groups of fish (initial body weight, 22.02 ± 0.61 g) for 8 weeks. The results indicated that fish fed diet with 100% LO substitution level had lower weight gain (WG), specific growth rate (SGR), and protein efficiency ratio (PER) than the other groups (P < 0.05), while feed conversion ratio (FCR) was higher compared to the other groups (P < 0.05). Feed intake (FI) and hepatosomatic index (HSI) of 66.7% LO substitution level were significantly lower than the control groups (P < 0.05). Glycogen, lipid, and non-esterified fatty acid content in the liver decreased significantly with increasing dietary LO levels (P < 0.05). Moreover, the replacement of fish oil (FO) with LO could significantly reduce the content of triglyceride (TG) and total cholesterol (TC) and the activity of alanine amiotransferase (ALT) in plasma of M. salmoides (P < 0.05). There were significant differences in hepatic metabolism enzymes in fish fed diets with different dietary LO levels. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR-α) activities in liver significantly increased with increasing dietary LO level (P < 0.05). In addition, phosphoenolpyruvate carboxykinase (PEPCK) and fructose-1,6-bisphosphatase (FBPase) activities in the liver significantly increased with decreasing dietary LO level (P < 0.05). Both the lowest superoxide dismutase (SOD) and catalase (CAT) activities in the liver were recorded in the control group (P < 0.05). Moreover, nitric oxide content, glutathione peroxidase (GPx), and inducible nitric oxide synthase (iNOS) activities in the liver significantly increased with increasing dietary LO level, while malondialdehyde (MDA) content significantly reduced. These findings demonstrated that LO can improve liver function and antioxidant ability of M. salmoides. In addition, replacing partial FO with LO cannot affect growth performance, but all substitutions inhibit growth performance of M. salmoides.

Effects of n-3 fatty acid supplements on cardiometabolic profiles in hypertensive patients with abdominal obesity in Inner Mongolia: a randomized controlled trial.

Daily supplementation with n-3 fatty acid (FA) has been believed to be an adjunct or alternative to drug treatments to reduce blood pressure (BP) and triglyceride (TG) levels in western patients with high risk of cardiovascular disease. The BP-lowering effect of n-3 FA supplements among Chinese hypertensive patients has been reported in our previous 12-week, double-blind, randomized controlled trial (RCT), but the benefits on cardiometabolic profiles among obese Chinese populations are not well known. We therefore used the data from the previous RCT to investigate the effects of marine- and plant-derived n-3 FA supplements on cardiometabolic profiles in middle-aged and elderly Chinese hypertensive patients with abdominal obesity. In total, 108 eligible volunteers from Inner Mongolia, China were randomly assigned to three treatments for 12 weeks: fish oil (FO, n = 35, 2 g day-1 eicosapentaenoic acid + docosahexaenoic acid), flaxseed oil (FLO, n = 39, 2.5 g day-1 α-linolenic acid), and corn oil served as a control (CO, n = 34). BP, blood lipids, waist circumference (WC) and fasting glucose-insulin were measured at baseline and after 12-week intervention by using standard methods. Clustered cardiometabolic risk was expressed as a continuously distributed z-score calculated by standardizing and then summing WC, insulin, glucose, TG, HDL-cholesterol and BP values. The cardiometabolic risk scores were significantly lower in the FO group than in the CO group after the 12-week intervention (-0.41 ± 0.92 vs. 0.02 ± 0.95, p = 0.016), but not in the FLO group (-0.23 ± 1.02 vs. 0.02 ± 0.95, p = 0.109). For individual risk factors, compared with CO, FO significantly decreased LDL-cholesterol (-0.25 ± 0.78 mmol L-1vs. -0.05 ± 0.65 mmol L-1, p = 0.010), ApoB (-012 ± 0.28 mmol L-1vs. -0.03 ± 0.23 mmol L-1, p = 0.036), and WC (-1.58 ± 3.67 cm vs. -0.52 ± 3.27 cm, p = 0.031), whereas no significant difference was found between FLO and CO groups in LDL-cholesterol (p = 0.081), ApoB (p = 0.102) and WC (p = 0.093). The present findings suggest that marine n-3 FA intervention may improve the cardiometabolic traits in this Chinese hypertensive population comorbid with abdominal obesity.

Effects of Danhong injection, a traditional Chinese medicine, on nine cytochrome P450 isoforms in vitro.

Danhong injection (DHI) is made from Salvia miltiorrhiza Bunge. and Carthamus tinctorius L. extract and is widely used in the clinical treatment of cardiovascular and cerebrovascular diseases. This study aimed to evaluate the effect of DHI on cytochrome P450 (CYP450) enzymes in vitro to predict drug-drug interactions based on CYP450 as combination therapy. To assess the inhibitory effect of DHI on CYP450, we detected the IC50 value of DHI on CYP450 in vitro by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Simultaneously, the induction effect of DHI on CYP450s was also evaluated. The relative induction ratios of DHI on CYP1A2, CYP2B6 and CYP3A4 activity were calculated by LC-MS/MS. The expression level of CYP3A4 mRNA was determined by reverse transcription PCR (RT-PCR). The LC-MS/MS data showed DHI intensively inhibit CYP2A6 activity and the intensity of inhibition was followed by CYP2C8, CYP3A4, CYP2C19, CYP2B6, CYP2D6, CYP1A2, CYP2E1 and CYP2C9 in vitro. The results of RT-PCR showed that there is a certain induction of DHI on CYP3A4 mRNA in human primary hepatocytes in vitro. The study suggested that drug-drug interactions might occur in clinical co-administration of drugs owing to the CYP2A6 inhibition and CYP3A4 induction.

Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Predictor of Sorafenib Benefit in Patients with Hepatocellular Carcinoma.

Sorafenib is the most recommended first-line systemic therapy for advanced hepatocellular carcinoma (HCC). Yet there is no clinically applied biomarker for predicting sorafenib response. We have demonstrated that a vascular pattern, named VETC (Vessels that Encapsulate Tumor Clusters), facilitates the release of whole tumor clusters into the bloodstream; VETC-mediated metastasis relies on vascular pattern, but not on migration and invasion of cancer cells. In this study, we aimed to explore whether vascular pattern could predict sorafenib benefit. Two cohorts of patients were recruited from four academic hospitals. The survival benefit of sorafenib treatment for patients with or without the VETC pattern (VETC+ /VETC- ) was investigated. Kaplan-Meier analyses revealed that sorafenib treatment significantly reduced death risk and prolonged overall survival (OS; in cohort 1/2, P = 0.004/0.005; hazard ratio [HR] = 0.567/0.408) and postrecurrence survival (PRS; in cohort 1/2, P = 0.001/0.002; HR = 0.506/0.384) in VETC+ patients. However, sorafenib therapy was not beneficial for VETC- patients (OS in cohort 1/2, P = 0.204/0.549; HR = 0.761/1.221; PRS in cohort 1/2, P = 0.121/0.644; HR = 0.728/1.161). Univariate and multivariate analyses confirmed that sorafenib treatment significantly improved OS/PRS in VETC+ , but not VETC- , patients. Further mechanistic investigations showed that VETC+ and VETC- HCCs displayed similar levels of light chain 3 (LC3) and phosphorylated extracellular signal-regulated kinase (ERK) in tumor tissues (pERK) or endothelial cells (EC-pERK), and greater sorafenib benefit was consistently observed in VETC+ HCC patients than VETC- irrespective of levels of pERK/EC-pERK/LC3, suggesting that the different sorafenib benefit between VETC+ and VETC- HCCs may not result from activation of Raf/mitogen-activated protein kinase kinase (MEK)/ERK and vascular endothelial growth factor (VEGF)A/VEGF receptor 2 (VEGFR2)/ERK signaling or induction of autophagy. Conclusion: Sorafenib is effective in prolonging the survival of VETC+ , but not VETC- , patients. VETC pattern may act as a predictor of sorafenib benefit for HCC.