Multi-omics analysis and the remedial effects of Swertiamarin on hepatic injuries caused by CCl4.

Hepatic diseases pose a significant threat to community health, impacting the quality of life and longevity of millions worldwide. Despite revolutionary advancements in treatment, liver diseases remain a pressing issue, necessitating the development of more effective therapeutic approaches. Here, we conducted a comprehensive multi-omics analysis to investigate the underlying mechanism of Swertiamarin in alleviating hepatic injuries induced by CCl4 in mice. We divided 100 Kunming mice into five groups: RC (control), RM (CCl4), RD (15 mg/Kg Swertiamarin), RZ (30 mg/Kg Swertiamarin), and RG (60 mg/Kg Swertiamarin). Animals in groups RD, RZ, and RG received daily Swertiamarin via gavage, while those in groups RM, RD, RZ, and RG were treated with CCl4 solution intraperitoneally every four days, nine times in total. Our findings revealed that mice in the RM group exhibited slightly lower average weights compared to other groups, along with significantly higher liver weight (p<0.0001) and liver index (p<0.0001). Pathological analysis indicated liver damage characterized by cell degeneration, inflammatory cell infiltration, and hepatic fibrosis in the CCl4-induced group. In contrast, Swertiamarin supplementation mitigated these effects, reducing denatured cells, inflammatory cells, and collagenous fibers in the liver. Serum analysis showed elevated levels of TNF-α (p<0.001), IL-6 (p<0.05), ALT (p<0.001), AST (p<0.0001), MDA (p<0.001), and Hyp (p<0.001) in CCl4-induced animals, along with lower levels of T-AOC (p<0.001), GSH-px (p<0.0001), SOD (p<0.001), and CAT (p<0.01). Microbiome analysis revealed significant differences among groups, with pathogenic taxa such as Arthrinium and Aureobasidium, and probiotic Saccharomyces showing notable variations. Metabolomics analysis identified numerous differentially abundant metabolites, with Swertiamarin-treated animals exhibiting distinct profiles. Our findings highlight the potential of Swertiamarin ameliorating CCl4-induced liver toxicity through modulation of antioxidant capacity, inflammatory response, gut microbiota, and metabolites. These insights may inform the development of novel therapies for liver injury.

Docosahexaenoic acid (DHA) promotes recovery from postoperative ileus and the repair of the injured intestinal barrier through mast cell-nerve crosstalk.

The objective of this study was to investigate the neuroimmune mechanisms implicated in the enhancement of gastrointestinal function through the administration of oral DHA. Mast cell-deficient mice (KitW-sh) and C57BL/6 mice were used to establish postoperative ileus (POI) models. To further validate our findings, we conducted noncontact coculture experiments involving dorsal root ganglion (DRG) cells, bone marrow-derived mast cells (BMMCs) and T84 cells. Furthermore, the results obtained from investigations conducted on animals and cells were subsequently validated through clinical trials. The administration of oral DHA had ameliorative effects on intestinal barrier injury and postoperative ileus. In a mechanistic manner, the anti-inflammatory effect of DHA was achieved through the activation of transient receptor potential ankyrin 1 (TRPA1) on DRG cells, resulting in the stabilization of mast cells and increasing interleukin 10 (IL-10) secretion in mast cells. Furthermore, the activation of the pro-repair WNT1-inducible signaling protein 1 (WISP-1) signaling pathways by mast cell-derived IL-10 resulted in an enhancement of the intestinal barrier integrity. The current study demonstrated that the neuroimmune interaction between mast cells and nerves played a crucial role in the process of oral DHA improving the intestinal barrier integrity of POI, which further triggered the activation of CREB/WISP-1 signaling in intestinal mucosal cells.

Three-Dimensional Reconstruction and Deformation Identification of Slope Models Based on Structured Light Method.

In this study, we propose a meticulous method for the three-dimensional modeling of slope models using structured light, a swift and cost-effective technique. Our approach aims to enhance the understanding of slope behavior during landslides by capturing and analyzing surface deformations. The methodology involves the initial capture of images at various stages of landslides, followed by the application of the structured light method for precise three-dimensional reconstructions at each stage. The system's low-cost nature and operational convenience make it accessible for widespread use. Subsequently, a comparative analysis is conducted to identify regions susceptible to severe landslide disasters, providing valuable insights for risk assessment. Our findings underscore the efficacy of this system in facilitating a qualitative analysis of landslide-prone areas, offering a swift and cost-efficient solution for the three-dimensional reconstruction of slope models.

Physicochemical properties of esterified/crosslinked quinoa starches and their influence on bread quality.

BACKGROUND: Starch is the main component of quinoa seeds. However, quinoa starch has poor solubility in cold water and poor mechanical resistance and is easily aged, which limit its application. Therefore, modification of its structure to improve its functional properties is necessary. RESULTS: This research used acetic anhydride and sodium trimetaphosphate to modify the structure of starch molecules and investigated their influence on bread quality. The results showed that both esterification and crosslinking prevented the aggregation behavior of starch molecules. Moreover, they both decreased the gelatinization enthalpy change and relative crystallinity of the starch. Compared with native starch, modification significantly decreased the gelatinization temperature from 57.01 to 52.01 °C and the esterified starch exhibited the lowest enthalpy change with a 44.2% decrease. Modified starch increased the specific volume and decreased the hardness and chewiness of bread. Modification did not influence the moisture content in bread but impacted the water retention capacity, depending on the degree of modification. Low and medium degrees of modification improved the water retention capacity during storage. By contrast, a high degree of modification (10 g kg-1 crosslinking agent) decreased the water retention capacity. The dually modified quinoa starch (esterified and crosslinked) showed no influence on the textural properties of bread. CONCLUSION: This study demonstrated that both esterification and crosslinking significantly improved the functional properties of quinoa starch. Crosslinked or esterified quinoa starches have the potential to improve the textural properties of bakery products. © 2024 Society of Chemical Industry.

The effect of Abrus cantoniensis Hance on liver damage in mice.

The liver is a well-known organ contributing to digestion, hemostasis and detoxification, while liver injury is a world-widely distributed health problem with limited treatment choices. We detected the protective effect of Abrus cantoniensis Hance (ACH) on Carbon tetrachloride-induced (CCl4) liver injury in mice. Fifty ICR (Institute of Cancer Research) animals were grouped into five groups of control (a), CCl4 (d), ACH (25 mg/kg) treated group (c), ACH (50 mg/kg) treated group (b), and ACH (100 mg/kg) treated group (e). Mice in groups d, c, b, and e were given CCl4 every four days, and treated animals received daily ACH supplementation. The results showed that the daily body weights in CCl4-induced animals were slightly lower; however, the weight of ACH-treated mice increased, particularly in the higher dose group. Treatment with CCl4 led to increased liver weight and liver indices in mice, whereas supplementation with ACH reduced both liver weights and liver indices in animals. Histo-pathological analysis indicated that CCl4 led to inflammatory cell infiltration and hepatocellular degeneration, with collagenous fibers proliferation in ICR animals. In contrast, supplementation with ACH prominently decreased inflammatory cells and degeneration of hepatocytes and inhibited collagen fiber hyperplasia. Furthermore, the levels or concentrations of AST (p < 0.0001), ALT (p < 0.0001), MDA (p < 0.0001), IL-1ß (p < 0.01), TNF-α (p < 0.01) and IL-6 (p < 0.01) were significantly higher in CCl4 induced ICR animals in group d. However, mice treated with ACH showed lower levels or concentrations of those indices in dose dependent manner. The levels of GSH-px (p < 0.0001), CAT (p < 0.0001) and SOD (p < 0.0001) were significantly reduced in CCl4 group; however, all these three enzymes exhibited significant (p < 0.05) increase in animals supplemented with ACH in dose dependent manner. The microbiome sequencing generated 1,168,327 filtered reads in the mice samples. A notable difference was observed in the composition of 6 phyla and 37 genera among the five ICR animal groups. Supplementation with ACH increased the abundance of beneficial genera of Coprococcus, Blautia and Clostridium, while concurrently decreased the presence of pathogenic genera of Mycoplasma and Helicobacter. In conclusion, we revealed that Abrus cantoniensis Hance has the potential to relieve liver damage induced by CCl4, through the reduction of inflammation, enhancement of antioxidant capacity, and regulation of intestinal microbiota.

Effect of Eucommia ulmoides Leaf Extract on Growth Performance, Carcass Traits, Parameters of Oxidative Stress, and Lipid Metabolism in Broiler Chickens.

Eucommia ulmoides bark has been traditionally used as a Chinese medicine to attenuate stress, but the leaf, which is rich in polyphenols and polysaccharides, has been rarely used. This study aimed to investigate the effect of Eucommia ulmoides leaf extracts (EULEs) on oxidative stress and meat quality of broilers. A total of 252 broilers were randomly divided into 3 treatments and fed with a control basal diet (CON), or a diet containing 250 mg/kg or 1,000 mg/kg of EULE for 51 days. Results showed that dietary supplementation of 250 mg/kg EULE increased significantly the average daily gain of broilers in the early stage (1-21 days), while 250 mg/kg or 1,000 mg/kg of EULE decreased the feed conversion ratio in the whole period (P < 0.05). Supplementation of 250 mg/kg EULE reduced the level of MDA in the liver (P < 0.05), while 1,000 mg/kg EULE decreased the serum level of MDA (P < 0.05), and the HDL level in serum was increased by 250 mg/kg or 1,000 mg/kg EULE (P < 0.05). Additionally, 250 mg/kg EULE decreased abdominal fat ratio and serum triglyceride (TC) level in broilers, while 250 or 1,000 mg/kg of EULE reduced drip loss in breast muscle (P < 0.05), and 1,000 mg/kg EULE reduced the cooking loss in thigh muscle (P < 0.05). In conclusion, dietary supplementation of 250 mg/kg of EULE could attenuate oxidative stress and improve the growth performance and meat quality in broilers.

Anti-Tumor and Anti-Metastasis Effects of Berbamine-Loaded Lipid Nanoparticles on Pancreatic Cancer.

OBJECTIVE: The aim of the study was to investigate the therapeutic potential of Berbamine-loaded lipid nanoparticles (BBM-NPs) in pancreatic cancer. METHODS: Dopamine polymerization-polylactide-TPGS nanoparticles were synthesized to prepare BBM-NPs, and the change in particle size of BBM-NPs was measured. Cell Counting Kit-8 (CCK8) assay, plate cloning experiment, and apoptosis analysis were performed to evaluate the cytotoxicity of BBM-NPs against the pancreatic cancer cells (PANC-1 and AsPC-1). Migration and invasion abilities of the tumor cells were determined by Transwell and wound healing assays. The intracellular level of ROS and expression of tumor progression-related proteins were measured using ROS-kit and western blot assay. Besides, an in vivo study was performed in the Balb/c nude mice to analyze the function of BBM-NPs in tumor growth. RESULTS: The in vitro studies showed that BBM-NPs with stable particle size and sustained drug release effectively inhibited the viability, proliferation, migration, and invasion of pancreatic cancer cells, while promoting cell apoptosis. Moreover, the in vivo experiments revealed that compared to Free BBM, BBM-NPs exhibited a stronger inhibitory effect on the growth of xenograft tumors derived from PANC-1 cells in mice. In addition, increased expressions of ROS, Bax, Cleaved Caspase-3, and γ-H2AX, as well as decreased expressions of MMP2, MMP9 and Bcl-2 were identified in both Free BBM and BBM-NPs groups, while BBM-NPs exhibited a stronger effect on protein expression than Free BBM. CONCLUSION: In summary, BBM-loaded lipid nanoparticles enhanced the therapeutic effects of BBM on pancreatic cancer, providing a promising strategy for targeted cancer therapy.

Local application of triamcinolone acetonide-conjugated chitosan membrane to prevent benign biliary stricture.

Benign biliary stricture (BBS) is the proliferation of fibrous tissue of the biliary tract caused by the biliary operation, bile duct stones, cholangitis, trauma, and other etiologies due to scar contracture. Recent therapeutic strategies to suppress stenosis are insufficient. Here, we developed a sustained-release membrane (SM) of triamcinolone acetonide (TA) with N-succinyl hydroxypropyl chitosan (TASM) for inhibiting fibroblast proliferation in vitro and bile duct hyperplasia in the rabbit model for benign biliary stricture formation. The TASM were successfully placed in 45 of 50 rabbits. Evaluation of subcutaneous stimulation and acute liver injury confirms the safety of TASM in vivo. Compared to the control group, the TASM can significantly inhibit the proliferation of scar muscle fibroblasts in vitro. ELISA and immunofluorescence showed TASM could increase bFGF level and inhibit expression of TGFß1 and αSMA. Cholangiographic and histologic examinations demonstrated significantly decreased tissue hyperplasia in the TASM groups compared with the model group. The immunohistochemical staining showed that TASM could reduce the level of cytokine-induced scars and inhibit the proliferation of myofibroblasts. Taken together, the chitosan membrane chemically conjugated with TA can effectively inhibit the benign biliary stricture. Further clinical usage of this membrane may effectively reduce the occurrence of benign biliary stricture.

Dietary Beta-Hydroxy-Beta-Methyl Butyrate Supplementation Inhibits Hepatic Fat Deposition via Regulating Gut Microbiota in Broiler Chickens.

The present study is aimed to explore the effects of different dietary beta-hydroxy-beta-methyl butyrate (HMB) levels (0, 0.05%, 0.10%, or 0.15%) on liver lipid metabolism on Wenshi broiler chickens. Results showed that HMB reduced the liver weight as well as liver concentrations of triacylglycerol (TG) and total cholesterol (TC) (quadratically, p < 0.05), and the lowest values were observed in the 0.10% HMB group. Meanwhile, HMB supplementation significantly altered the expression levels of key genes related to lipid metabolism in the liver of broiler chickens (p < 0.05). Furthermore, 16S rRNA gene sequencing revealed that HMB supplementation could greatly change the richness, diversity, and composition of the broiler gut microbiota, and the Bacteroidetes relative abundance at the phylum level and the Alistipes relative abundance at the genus level were affected (p < 0.05). Correlation analysis further suggested a strong association between Bacteroidetes relative abundance and lipid metabolism-related parameters (p < 0.05). Together, these data suggest that 0.10% HMB supplementation could inhibit hepatic fat deposition via regulating gut microbiota in broilers.

Dietary ferulic acid and vanillic acid on inflammation, gut barrier function and growth performance in lipopolysaccharide-challenged piglets.

Ferulic acid (FA) and vanillic acid (VA) are considered as major phenolic metabolites of cyanidin 3-glucoside, a polyphenol that widely exists in plants that possess a protective effect against oxidative stress and inflammation in our previous study. This study aimed to investigate the effect of FA and VA on inflammation, gut barrier function, and growth performance in a weaned piglet model challenged with lipopolysaccharide (LPS). Thirty-six piglets (PIC 337 × C48, 28 d of age) were randomly allocated into 3 treatments with 6 replicate pens (2 piglets per pen). They were fed with a basal diet or a diet containing 4,000 mg/kg of FA or VA. Dietary supplementation of VA significantly increased average daily gain (ADG) (P < 0.05). Both FA and VA decreased serum levels of thiobarbituric acid reactive substances (TBARS), interlukin (IL)-1ß, IL-2, IL-6, and tumor necrosis factor (TNF)-α (P < 0.05), and enhanced the expression of tight junction protein oclaudin (P < 0.05). Analysis of gut microbiota indicated that both FA and VA increased the Firmicutes/Bacteroidetes ratio alongside reducing the relative abundance of the Prevotellaceae family including Prevotella 9 and Prevotella 2 genera, but enriched the Lachoiraceaea family including the Lachnospiraceae FCS020 group (P < 0.05). Moreover, VA reduced the relative abundance of Prevotella 7 and Prevotella 1 but enriched Lachnospira, Eubacterium eligens group, and Eubacterium xylanophilum group (P < 0.05), while FA showed a limited effect on these genera. The results demonstrated that both VA and FA could alleviate inflammation and oxidative stress, but only VA has a significant positive effect on the growth performance of LPS-challenged piglets potentially through modulating gut microbiota.

Semi-Reliability Probability Damage Assessment of GFRP Bars Embedded in Steam-Curing Concrete Beams Based on the Multiple Factors Related Moisture Absorption Model.

GFRP bars will be damaged due to a series of irreversible hygroscopic chemical reactions under humid and hot curing environmental conditions. The multiple factors related to the moisture absorption model were established through the moisture absorption test of GFRP bars embedded in steam-curing concrete, which considered different curing temperatures, different thicknesses of the protective layer, and different diameters of GFRP bars. Semi-reliability probability damage assessment of GFRP bars embedded in steam-curing concrete was described by introducing the reliability and stochastic theory. Subsequently, the tensile test of GFRP bars was carried out to verify the feasibility of the damage assessment. The results showed that the moisture absorption curves of GFRP bars were basically in line with Fick's law. In addition, the influences of the curing temperature, the thickness of the protective layer, and the diameter on moisture absorption performance were presented. The semi-reliability probability damage assessment model of GFRP bars embedded in steam-curing concrete beams adequately considered the multiple factors related to moisture absorption and the uncertainty and randomness of the influencing factors during the process of moisture absorption.

Dietary Beta-Hydroxy-Beta-Methyl Butyrate Supplementation Affects Growth, Carcass Characteristics, Meat Quality, and Serum Metabolomics Profile in Broiler Chickens.

This study aimed to explore the effects of beta-hydroxy-beta-methyl butyrate (HMB) on serum metabolic profiles and meat quality of muscles in Wenshi broiler chickens. Birds were fed a basal diet with an additional 0, 0.05, 0.10, or 0.15% HMB, respectively. Results showed that dietary HMB quadratically increased the average daily gain (P = 0.058) and decreased feed:gain (P < 0.05) mainly in the starter phase. At 51 days of age, birds receiving 0.10% HMB diet exhibited less abdominal fat and more breast yield than the control (P < 0.05). Moreover, dietary HMB quadratically decreased the L∗ value and drip loss in selected muscles (P < 0.05) and increased the a∗ value in breast muscle (P < 0.05). Serum metabolome profiling showed that the most differentially abundant metabolites are lipids and lipid-like molecules, including phosphatidylcholines. It was concluded that HMB improved growth performance and meat quality of muscle in broilers.

Flavonoids from Mulberry Leaves Alleviate Lipid Dysmetabolism in High Fat Diet-Fed Mice: Involvement of Gut Microbiota.

Here, we investigated the roles and mechanisms of flavonoids from mulberry leaves (FML) on lipid metabolism in high fat diet (HFD)-fed mice. ICR mice were fed either a control diet (Con) or HFD with or without FML (240 mg/kg/day) by oral gavage for six weeks. FML administration improved lipid accumulation, alleviated liver steatosis and the whitening of brown adipose tissue, and improved gut microbiota composition in HFD-fed mice. Microbiota transplantation from FML-treated mice alleviated HFD-induced lipid metabolic disorders. Moreover, FML administration restored the production of acetic acid in HFD-fed mice. Correlation analysis identified a significant correlation between the relative abundances of Bacteroidetes and the production of acetic acid, and between the production of acetic acid and the weight of selected adipose tissues. Overall, our results demonstrated that in HFD-fed mice, the lipid metabolism improvement induced by FML administration might be mediated by gut microbiota, especially Bacteroidetes-triggered acetic acid production.

Numerical study of air pollution over a typical basin topography: Source appointment of fine particulate matter during one severe haze in the megacity Xi'an.

Many cities are located in lands with typical basin topographies, which are not conducive to the spread of air pollutants. In the winter of 2016/2017, a severe haze happened in Xi'an, the main city in the Guanzhong Basin in central China. When the peak daily concentration of fine particulate matter (PM2.5) reaches 499 µg/m3, the source of the atmospheric pollution needs to be found urgently in order to take countermeasures. The comprehensive air quality model with extensions, coupled with the tracer tagging particulate source apportionment technology (PSAT) module, and an improved emission inventory, higher grid resolution, and bigger inner domain area, have been applied to quantify the contributions of local and regional emissions to the PM2.5 pollutions. The model performed well in time period considered in this study. The correlation of the simulated daily PM2.5 concentration data reaches 0.82, and the fraction of predictions within a factor of two of observations approaches 84%. With the PSAT module, the PM2.5 contributions from local and regional sources to the urban centre and rural areas during the severe winter haze event are analysed in detail. The PM2.5 concentrations in the urban centre in Xi'an is mainly originating from local emissions (60%), and Xianyang City is the largest contributor among the surrounding source regions (11.6%), while the transportation sector outside the Shaanxi Province (5.1%) also contributes significantly. Comparatively, the rural areas have lower local contributions and higher transport contributions. In particular, in the northern rural area Yanliang, the contribution from surrounding source regions approaches 82%. The results of this study suggest that to improve the air quality in a typical basin city, a regional-scale coordinated emissions control should be used, focusing on the emissions from both local and surrounding areas.

d- and l-Aspartate regulates growth performance, inflammation and intestinal microbial community in young pigs.

d-aspartate (d-Asp), an endogenous amino acid, occurs widely in animals and humans with d-enantiomers and plays an important role in the endocrine and nervous systems. However, very few studies are available on growth performance, microbial community, and the intestinal immune and inflammatory status in response to d- and l-aspartate (l-Asp). Thus, in this study, we mainly investigated the effects of dietary 1% d- and l-Asp on growth performance, inflammation, and microbial community in young pigs. Twenty-eight young pigs were randomly divided into four groups (n = 7): a control group, in which piglets were fed a basal diet, and other three groups, in which piglets received 1% d-Asp, 1% l-Asp, and 1% dl-aspartate (dl-Asp) for 35 days. The results showed that dietary 1% d-Asp significantly inhibited average daily feed intake and average daily weight gain. Gut microbes were tested and the results showed that l-Asp enhanced bacterial diversity (Shannon and Simpson). At the phylum level, l-Asp enhanced intestinal Actinobacteria and Bacteroidetes abundance but decreased Firmicutes abundance. In contrast, dl-Asp decreased intestinal Actinobacteria and Bacteroidetes abundance and increased Firmicutes abundance. At the genus level, d-Asp enhanced Clostridium sensu stricto 1 and Intestinibacter abundance. Metagenomic predictions by PICRUSt suggested that the altered microbiota were mainly involved in membrane transport, carbohydrate metabolism, amino acid metabolism, replication and repair, translation, and nucleotide metabolism. In addition, dl-Asp markedly increased the activities of serum alanine aminotransferase, aspartate transaminase and alkaline phosphatase. Also, dietary d- and dl-Asp down-regulated TLR 4, NOD1, and MyD88 in the jejunum to mediate the inflammatory response. Collectively, these results indicated that dietary d-Asp and l-Asp affect the growth performance and inflammation in piglets, which might be associated with gut microbiota.

Intestinal microbiota mediates Enterotoxigenic Escherichia coli-induced diarrhea in piglets.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in humans, cows, and pigs. The gut microbiota underlies pathology of several infectious diseases yet the role of the gut microbiota in the pathogenesis of ETEC-induced diarrhea is unknown. RESULTS: By using an ETEC induced diarrheal model in piglet, we profiled the jejunal and fecal microbiota using metagenomics and 16S rRNA sequencing. A jejunal microbiota transplantation experiment was conducted to determine the role of the gut microbiota in ETEC-induced diarrhea. ETEC-induced diarrhea influenced the structure and function of gut microbiota. Diarrheal piglets had lower Bacteroidetes: Firmicutes ratio and microbiota diversity in the jejunum and feces, and lower percentage of Prevotella in the feces, but higher Lactococcus in the jejunum and higher Escherichia-Shigella in the feces. The transplantation of the jejunal microbiota from diarrheal piglets to uninfected piglets leaded to diarrhea after transplantation. Microbiota transplantation experiments also supported the notion that dysbiosis of gut microbiota is involved in the immune responses in ETEC-induced diarrhea. CONCLUSION: We conclude that ETEC infection influences the gut microbiota and the dysbiosis of gut microbiota after ETEC infection mediates the immune responses in ETEC infection.

Jejunal Metabolic Responses to Escherichia coli Infection in Piglets.

This study aimed to investigate the jejunal metabolic variations in enterotoxigenic Escherichia coli (ETEC)-infected piglets. Piglets were infected with 1 × 1010 CFUs (colony-forming units) of ETEC W25K and assigned into diarrheal, recovered, control, and resistant groups. Jejunal samples were harvested at day 6 and metabolic profiles were analyzed via gas chromatography coupled to time-of-flight mass spectrometry (GC/TOFMS). The results showed that 33 metabolites in the jejunum were identified in ETEC-induced diarrhea, including amino acids, fatty acids, sugars, and organic acids. Compared with the control, resistant, and recovered piglets, diarrheal piglets showed higher concentrations of 4-aminobutyric acid (GABA) and glycine in the jejunum. Compared with the control and resistant piglets, six metabolites were markedly decreased in diarrheal piglets, including ornithine, asparagine, glutamine, citric acid, citrulline, and lysine. Collectively, this study provides insights into jejunal metabolic response to ETEC infection and ETEC induced diarrhea in piglets.

Enterotoxigenic Escherichia coli infection promotes apoptosis in piglets.

Enterotoxigenic Escherichia coli (ETEC), as a universal pathogen, often causes diarrhea in animals and humans. However, whether ETEC infection induces apoptosis in host remains controversial. Herein, we use ETEC-infected piglet to investigate apoptosis in the jejunum. Apoptosis and the activation of capase-3 are observed in piglet jejunum after ETEC infection. Additionally, ETEC infection induces the activation of caspase-8 pathway, but inhibits the activation of caspase-9 pathway in piglet jejunum. These findings demonstrate that ETEC infection may inhibit the intrinsic pathway and activate the extrinsic pathway of apoptosis in piglets.

Resveratrol prevents AngII-induced hypertension via AMPK activation and RhoA/ROCK suppression in mice.

The purpose of this study was to determine the effects of resveratrol (RSV) and the molecular mechanisms by which it regulates vascular smooth muscle contraction and blood pressure in mice. In cultured human vascular smooth muscle cells (VSMCs), we found that the activation of AMP-activated protein kinase (AMPK) by RSV inhibited angiotensin II (AngII)-induced phosphorylation of myosin phosphatase-targeting subunit 1 (MYPT1) and myosin light chain (MLC). Inversely, AMPK inhibition with RNA interference and compound C, an AMPK inhibitor, abolished the inhibitory effect of RSV on AngII-induced MYPT1 and MLC phosphorylation. Thiazovivin, a Rho-associated kinase (ROCK) inhibitor, reversed AngII-induced MYPT1 and MLC phosphorylation, suggesting that ROCK functions as an upstream kinase for MYPT1/MLC. RSV reversed AngII-induced Ras homolog gene family member A (RhoA) and ROCK activity, whereas AMPK inhibition via pharmacological or genetic means abolished this effect. In addition, gene silencing of p190-guanosine triphosphatase-activating protein blocked the effects of RSV-induced AMPK activation on MLC, MYPT1 and RhoA in VSMCs. Ex vivo analyses demonstrated that AngII-induced aorta contractions were dramatically inhibited by RSV, and this effect was abolished by AMPK inhibition. Finally, daily chronic administration of RSVl alleviated hypertension in the experimental model of AngII-induced hypertensive mice, and these effects were accompanied by the activation of AMPK, significantly decreased RhoA activity and phosphorylation levels of MYPT1 and MLC in AngII-treated murine aortic VSMCs. More importantly, administration of compound C significantly abolished the effects of RSV. In conclusion, AMPK suppression of the p190-GAP-dependent RhoA/ROCK/MYPT1/MLC pathway contributes to the hypotensive effect of RSV in AngII-treated mice.

[Measurement of tacrolimus in blood with the method of high performance liquid chromatography-mass spectrometry].

OBJECTIVE: To develop a simple, precise, and specific method for measurement of tacrolimus in whole blood. METHODS: Tacrolimus was extracted from the blood samples of 40 patients treated with tacrolimus by liquid-liquid extraction. Then high performance liquid chromatography-mass spectrometry (HPLC/MS) was used, with ascomycin as internal marker, to isolate the tacrolimus and measure the concentration thereof. The standard curve was drawn. The linearity of quantitative measurement was determined. Detection limits test, CV test, and recovery test were performed. ELISA was used simultaneously. The results of these 2 methods were compared. RESULTS: A good standard curve was drawn based on the results of HPLC/MS assay (y = 0.2464x + 0.0082, R2 = 0.9996). The detected data were highly related to the detected concentrations. The linearity range was 0.100 - 40.000 ng/ml (y = 1.0294x-0.035, R2 = 0.9998). The detection limit of the assay was 0.100 ng/ml. The CV values by this assay were basically < 5%. The recovery rate ranged 95.67% - 98.30% for tacrolimus over the range 0.300 - 16.016 ng/ml. There was a linear correlation (y = 1.0172x + 0.3742, R2 = 0.9630) between the assay results by HPLC/MS to ELISA in blood. The measurement value of ELISA was (19 +/- 9), significantly higher than that of HPLC/MS (18 +/- 9, P < 0.01). CONCLUSION: This newly developed method of HPLC/MS is simple, precise, and specific and with lower cost, it can be used in the clinical practice and experimental study on tacrolimus.