Protective effect of wild Corni fructus methanolic extract against acute alcoholic liver injury in mice

Background: In Chinese folk medicine, Corni fructus (C. fructus) has traditionally been used to improve liver function, although the mechanism underlying its activity remains unclear. The aim of the present study was to evaluate the protective effects of wild C. fructus methanolic extract against acute alcoholic liver injury.Methods: Alcohol was administered to mice for three consecutive days, either alone or in combination with C. fructus methanolic extract (50, 100, or 200mg/kg body weight/d). Serum and liver tissue were collected from the animals and subjected to biochemical and histopathological analyses.Results:C. fructus significantly alleviated alcohol-induced liver injury by reducing serum alanine aminotransferase, aspartate aminotransferase, and thiobarbituric acid reactive species, inhibiting hydroxyl radicals (center dot OH), and increasing total superoxide dismutase, glutathione peroxidase, and glutathione in the liver (P<0.05). In addition, the C. fructus treatment inhibited the expression and activity of cytochrome P450 2E1 (P<0.05)Conclusions:C. fructus could be a promising natural substance for ameliorating acute alcohol-induced oxidative stress and hepatic injury.- This work was supported by the Construction Project of Shaanxi Collaborative Innovation Center (2015, Shaanxi Sci-tech University); High-End Foreign Experts Recruitment Program [Grant GDW20146100228]; and Key Construction Program of International Cooperation Base in S&T Shaanxi Province, China [Grant 2015SD0018].info:eu-repo/semantics/publishedVersio

Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

Helicobacter pylori infection and gastroduodenal diseases in Vietnam: a cross-sectional, hospital-based study

<p>Abstract</p> <p>Background</p> <p>The rate of <it>H. pylori </it>infection in Vietnam is reportedly high, but the spectrum of <it>H. pylori</it>-associated gastroduodenal diseases has not been systematically investigated. Moreover, despite the similarities of ethnicity and diet, the age-standardized incidence rate of gastric cancer in the northern city of Hanoi is higher than that in the southern city of Ho Chi Minh, but the reason for this phenomenon is unknown. The virulence of Vietnamese <it>H. pylori </it>has also not been investigated in detail.</p> <p>Methods</p> <p>Individuals undergoing esophagogastroduodenoscopy were randomly recruited. <it>H. pylori </it>infection status was determined based on the combined results of culture, histology, immunohistochemistry, rapid urine test and serum ELISA. Peptic ulcer (PU) and gastroesophageal reflux disease was diagnosed by endoscopy, and chronic gastritis was determined histologically. <it>H. pylori </it>virulence factors were investigated by PCR and sequencing.</p> <p>Results</p> <p>Among the examined patients, 65.6% were infected with <it>H. pylori</it>. The prevalence of infection was significantly higher in those over 40 years of age than in those aged ≤40. Chronic gastritis was present in all <it>H. pylori</it>-infected individuals, 83.1% of whom had active gastritis, and 85.3% and 14.7% had atrophy and intestinal metaplasia, respectively. PU was present in 21% of infected patients, whereas its incidence was very low in non-infected individuals. The prevalence of PU was significantly higher in Hanoi than in Ho Chi Minh. The prevalence of <it>vacA m1</it>, which has been identified as an independent risk factor for PU in Vietnam, was significantly higher among <it>H. pylori </it>isolates from Hanoi than among those from Ho Chi Minh.</p> <p>Conclusions</p> <p><it>H. pylori </it>infection is common in Vietnam and is strongly associated with PU, active gastritis, atrophy and intestinal metaplasia. <it>vacA m1 </it>is associated with an increased risk for PU and might contribute to the difference in the prevalence of PU and gastric cancer between Hanoi and Ho Chi Minh.</p

Numerical analysis of seepage–deformation in unsaturated soils

A coupled elastic–plastic finite element analysis based on simplified consolidation theory for unsaturated soils is used to investigate the coupling processes of water infiltration and deformation. By introducing a reduced suction and an elastic–plastic constitutive equation for the soil skeleton, the simplified consolidation theory for unsaturated soils is incorporated into an in-house finite element code. Using the proposed numerical method, the generation of pore water pressure and development of deformation can be simulated under evaporation or rainfall infiltration conditions. Through a parametric study and comparison with the test results, the proposed method is found to describe well the characteristics during water evaporation/infiltration into unsaturated soils. Finally, an unsaturated soil slope with water infiltration is analyzed in detail to investigate the development of the displacement and generation of pore water pressure

Macro deformation and micro structure of 3D granular assemblies subjected to rotation of principal stress axes

This paper presents a numerical investigation on the behavior of three dimensional granular materials during continuous rotation of principal stress axes using the discrete element method. A dense specimen has been prepared as a representative element using the deposition method and subjected to stress rotation at different deviatoric stress levels. Significant plastic deformation has been observed despite that the principal stresses are kept constant. This contradicts the classical plasticity theory, but is in agreement with previous laboratory observations on sand and glass beads. Typical deformation characteristics, including volume contraction, deformation non-coaxiality, have been successfully reproduced. After a larger number of rotational cycles, the sample approaches the ultimate state with constant void ratio and follows a periodic strain path. The internal structure anisotropy has been quantified in terms of the contact-based fabric tensor. Rotation of principal stress axes densifies the packing, and leads to the increase in coordination numbers. A cyclic rotation in material anisotropy has been observed. The larger the stress ratio, the structure becomes more anisotropic. A larger fabric trajectory suggests more significant structure re-organization when rotating and explains the occurrence of more significant strain rate. The trajectory of the contact-normal based fabric is not centered in the origin, due to the anisotropy in particle orientation generated during sample generation which is persistent throughout the shearing process. The sample sheared at a lower intermediate principal stress ratio (b=0.0) (b=0.0) has been observed to approach a smaller strain trajectory as compared to the case b=0.5 b=0.5 , consistent with a smaller fabric trajectory and less significant structural re-organisation. It also experiences less volume contraction with the out-of plane strain component being dilative

Reproductive performance in sows in relation to Japanese Encephalitis Virus seropositivity in an endemic area

Japanese Encephalitis Virus (JEV) is considered an important reproductive pathogen in pigs. Most studies of the reproductive impact of JEV have been conducted in areas where the disease occurs in seasonal epidemics. In this study, the associations between seropositivity for JEV, measured with an IgG ELISA, and the number of piglets born alive and stillborn were investigated in a tropical area endemic for JEV in Vietnam. Sixty percent of sows from four farms in the Mekong delta of Vietnam were seropositive to JEV and the Odds Ratio for a sow being infected was highest (6.4) in sows above 3.5 years (95% confidence interval 2.2–18.3). There was an association between increasing Optical Density (OD) values from the ELISA and the number of stillborn piglets in sows less than 1.5 years, but no effect of seropositivity could be shown when all sows were studied. OD values had an effect (p = 0.04) on the number of piglets born alive in the statistical analysis only when interacting with the effect of the breeds. An increase in mean OD value of the herd was correlated (p < 0.0001) with an increase in the number of piglets born alive. In this study, there was evidence of a negative association between seropositivity for JEV and the reproductive performance only in sows less than 1.5 years in endemic areas. This could be explained by a year-round infection with the virus, which would lead to immunity in many gilts before their first pregnancy. This, in turn, may imply that JEV infection in pigs is of minor importance for the reproductive performance in endemic areas

Molecular Dynamics Simulation of Phosphorylated KID Post-Translational Modification

BACKGROUND:Kinase-inducible domain (KID) as transcriptional activator can stimulate target gene expression in signal transduction by associating with KID interacting domain (KIX). NMR spectra suggest that apo-KID is an unstructured protein. After post-translational modification by phosphorylation, KID undergoes a transition from disordered to well folded protein upon binding to KIX. However, the mechanism of folding coupled to binding is poorly understood. METHODOLOGY:To get an insight into the mechanism, we have performed ten trajectories of explicit-solvent molecular dynamics (MD) for both bound and apo phosphorylated KID (pKID). Ten MD simulations are sufficient to capture the average properties in the protein folding and unfolding. CONCLUSIONS:Room-temperature MD simulations suggest that pKID becomes more rigid and stable upon the KIX-binding. Kinetic analysis of high-temperature MD simulations shows that bound pKID and apo-pKID unfold via a three-state and a two-state process, respectively. Both kinetics and free energy landscape analyses indicate that bound pKID folds in the order of KIX access, initiation of pKID tertiary folding, folding of helix alpha(B), folding of helix alpha(A), completion of pKID tertiary folding, and finalization of pKID-KIX binding. Our data show that the folding pathways of apo-pKID are different from the bound state: the foldings of helices alpha(A) and alpha(B) are swapped. Here we also show that Asn139, Asp140 and Leu141 with large Phi-values are key residues in the folding of bound pKID. Our results are in good agreement with NMR experimental observations and provide significant insight into the general mechanisms of binding induced protein folding and other conformational adjustment in post-translational modification

Uncoupled Embryonic and Extra-Embryonic Tissues Compromise Blastocyst Development after Somatic Cell Nuclear Transfer

Somatic cell nuclear transfer (SCNT) is the most efficient cell reprogramming technique available, especially when working with bovine species. Although SCNT blastocysts performed equally well or better than controls in the weeks following embryo transfer at Day 7, elongation and gastrulation defects were observed prior to implantation. To understand the developmental implications of embryonic/extra-embryonic interactions, the morphological and molecular features of elongating and gastrulating tissues were analysed. At Day 18, 30 SCNT conceptuses were compared to 20 controls (AI and IVP: 10 conceptuses each); one-half of the SCNT conceptuses appeared normal while the other half showed signs of atypical elongation and gastrulation. SCNT was also associated with a high incidence of discordance in embryonic and extra-embryonic patterns, as evidenced by morphological and molecular “uncoupling”. Elongation appeared to be secondarily affected; only 3 of 30 conceptuses had abnormally elongated shapes and there were very few differences in gene expression when they were compared to the controls. However, some of these differences could be linked to defects in microvilli formation or extracellular matrix composition and could thus impact extra-embryonic functions. In contrast to elongation, gastrulation stages included embryonic defects that likely affected the hypoblast, the epiblast, or the early stages of their differentiation. When taking into account SCNT conceptus somatic origin, i.e. the reprogramming efficiency of each bovine ear fibroblast (Low: 0029, Med: 7711, High: 5538), we found that embryonic abnormalities or severe embryonic/extra-embryonic uncoupling were more tightly correlated to embryo loss at implantation than were elongation defects. Alternatively, extra-embryonic differences between SCNT and control conceptuses at Day 18 were related to molecular plasticity (high efficiency/high plasticity) and subsequent pregnancy loss. Finally, because it alters re-differentiation processes in vivo, SCNT reprogramming highlights temporally and spatially restricted interactions among cells and tissues in a unique way