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关键词： cytokeratin‐   18   M30   M65   therapy  

摘要： Incomplete histological remission of autoimmune hepatitis (AIH) is associated with a reduced long-term survival and an increased relapse rate even during biochemical remission (BR). The aim of this international multicentre study was to explore the diagnostic fidelity of cytokeratin-18 cell death markers to noninvasively detect incomplete histological remission. Thereby, cytokeratin-18 cell death marker M65 but not ALT and immunoglobulins was significantly higher in patients with incomplete histological remission (mHAI >= 4) compared to those with mHAI <= 3. M65 levels > 305 U/L, identified in the training cohort, facilitated the noninvasive detection of incomplete histological remission with a sensitivity of 75% and negative predictive value of 86% in the validation cohort. While BR with M65 < 305 U/L suggested complete histological remission (86%), BR with M65 > 305 U/L reduced the rate of histological remission to 60%. In conclusion, M65 may help to better select patients for or to reduce surveillance liver biopsies in the future.

关键词： amino acid   blood   metabolism indicators   poultry  

摘要： We postulated that the use of optimal levels and proportions of Lys, Arg and Met in compound feed allows for optimal exploitation of the growth potential of contemporary slaughter turkey hybrids and reduces metabolic disorders. The aim of the study was to determine the effect of different proportions of Lys, Arg and Met in diets whose Lys content is in accordance with NRC recommendations, that is a low level, on selected parameters of protein, lipid and carbohydrate metabolism and on hormone secretion in turkeys. The lowest Arg content (90% Lys) in the diet resulted in an increase in plasma total cholesterol levels in the turkeys as compared to higher Arg content (100% or 110% of Lys), (2.50 vs. 2.09 vs. 1.83). Plasma HDL and creatinine concentration increased in turkeys fed diets with higher Arg content (100% and 110% Lys) compared to turkeys receiving the diet with the lowest Arg content (90% Lys). Compared to turkeys receiving the lowest and intermediate Arg content (90% and 100% Lys), the diet with the highest content of this AA (110% Lys) resulted in an increase in the plasma T4 level (71.21 vs. 86.60 vs. 128.2). The varied Arg and Met levels relative to Lys did not affect the secretion of neurotransmitters or hormones regulating glucose metabolism. At low levels of Met in the diet, an decrease in Arg relative to Lys from 100% to 90% caused a growth depression of turkeys (10.68 vs. 10.21 kg), which was not noted in the case of the higher Met content. When using the Lys level recommended by NRC in the turkey diet, the optimal Arg level is 100% and Met is 45% compared to Lys.

关键词： Chlorpyrifos-ethyl   Detoxifying enzyme   Antioxidant enzyme   Bioremediation   G. pulex  

摘要： This study reveals out detoxifying and antioxidant enzyme response of Gammarus pulexexposed/polluted to chlorpyrifos-ethyl insecticide before and after biodegradation/bioremediation byMethylobacterium radiotoleransandMicrobacterium arthrosphaerae. Cytochrome P450 1A1, glutathione S-transferase, catalase, and superoxide dismutase activities inG. pulexexposed to chlorpyrifos-ethyl before and after bioremediation/biodegradation by these two bacteria during 24 and 96 h tested by using commercial ELISA kits. The activity of catalase enzyme was decreased depending on chlorpyrifos-ethyl before and after bioremediation/biodegradation the enzyme activity was increased repeatedly. Superoxide dismutase activity level increased after chlorpyrifos-ethyl exposure in 96 h (p> 0.05). Following bioremediation, superoxide dismutase enzyme activity decreased again during 24 h (p> 0.05) and increased during 96 h (p< 0.05). Statistical differences were not found in cytochrome P450 1A1 enzyme activity before and after the process (p> 0.05). No significant differences were determined during the activity of glutathione S-transferase in 24 h (p> 0.05). The activities of glutathione S-transferase were increased after exposure of chlorpyrifos-ethyl during 96 h. After bioremediation;the activity of glutathione S-transferase increased even more (p< 0.05). The results determined that activities ofG. pulexat superoxide dismutase, catalase, and glutathione S-transferase are common biomarkers for revealing out the efficiency of bioremediation of chlorpyrifos-ethyl with these two types of soil bacteria.

关键词： Selenium nanoparticles   kappa-carrageenan   Surfaces charge   Liver   Toxic damage   Malondialdehyde   Alanine aminotransferase   Aspartate aminotransferase  

摘要： The ever-increasing application of selenium nanoparticles in medicine generates a need for thorough assessment of their effects on the living organism to prevent undesirable and dangerous toxic processes. The biological action of selenium nanoparticles strongly depends on the administrated dose. This stimulates in-depth study of possible mechanisms of their toxic effect, especially when they are applied in high doses. In this work, we have studied the effect of a high dose of selenium nanoparticles on rats and found that it is different in a healthy organism and in the case of modeled liver toxic damage. It has been revealed that the administration of a high dose of selenium nanoparticles to rats with toxic liver damage decreases the concentration of lipid peroxidation products in the blood and normalizes the level of liver enzymes at a time of the damage of the urinary system. At the same time, in a healthy organism, excess of selenium nanoparticles augments concentrations of urea, aspartate aminotransferase and malondialdehyde probably due to the fact that excess selenium nanoparticles induces the lipid peroxidation and damage the urinary system. However, the experiments show that, no mortality is observed among the animals treated with selenium in a dose of 6 times higher than the normal one. The use of sulfated polysaccharide kappa-carrageenan as a stabilizer of nanoparticles generates a densely negative charge (zeta-potential -29 mV) on the nanoparticles surface. Probably, the high biocompatibility of nanoparticles is explained by the prolongation of their interaction with cells due to involvement of opsonization stage of negatively charged surface of nanoparticles into their metabolism.

关键词： biochemical response to ursodeoxycholic acid   histological progression   primary biliary cholangitis  

摘要： Primary biliary cholangitis (PBC) is currently diagnosed at an early stage;therefore, the number of patients with PBC without symptoms at the time of diagnosis is increasing. However, up to 30% of patients with PBC exhibit the suboptimal response to ursodeoxycholic acid (UDCA) and are at high risk of end-stage liver disease. Obeticholic acid is an approved second-line therapy for patients with PBC that are refractory to UDCA. Novel surrogate endpoints are required to identify individuals eligible for second-line therapies. An inadequate biochemical response to UDCA is a useful predictor of poor outcomes in patients with PBC. In addition to UDCA effects on biochemical parameters, histological outcomes could be considered as candidate surrogate endpoints. Alterations in liver histology are used as surrogate endpoints in clinical studies. However, current staging systems are insufficient to determine PBC disease severity and progression because of the pathological heterogeneity of the disease. Histological features at baseline and biochemical response to UDCA treatment can affect the disease course of PBC. Therefore, novel surrogate endpoints must be represented by parameters characterized by histological outcomes and treatment responses in PBC. In this review, we discuss the existing histological parameters and newly created factors to identify patients with PBC who are at a high risk of developing end-stage liver disease and, consequently, the potential need for additional treatments.

关键词： beta-carotene   Phycocyanin   Spirulina platensis   Immune-oxidative stress biomarkers   Genes expression   Fish  

摘要： The current trial investigated the roles of beta-carotene and phycocyanin extracted from Spirulina platensis on growth, serum biochemical, digestive enzymes, antioxidant defense, immune responses, and immune gene expression in Nile tilapia (Oreochromis niloticus). Fish (1.52 +/- 0.10 g) were randomly stocked to three treatments with three replicates (12 fish per replicate) in nine aquaria (60 L glass aquarium for each), and reared for 70-days. Three tested diets were formulated to be isonitrogenous and isolipidic, and were offered for experimental fish until ad-libitum three times daily at 09:00 a.m., 11.00 a.m. and 3:00 p.m. The first diet (control) was without supplementation. About 50 mg beta-carotene and 50 mg phycocyanin kg(-1) were supplemented to the other experimental diets, respectively. Results indicated that feed intake was not (P 0.05) differ among experimental diets. Compared to control diet wight gain and specific growth rate were significantly (P < 0.05) in fish fed diet containing beta-carotene, while, the highest weight gain and the best FCR were detected in phycocyanin diet. Survival fish among treatments was significantly (P < 0.05) differ and the highest survival rate was showed in fish fed diet supplemented with phycocyanin. Either 8-carotene or phycocyanin significantly (P < 0.05) improved the intestinal digestive enzymes compared with control diet, where the highest values of chymotrypsin, trypsin, lipase and amylase were noticed in fish fed phycocyanin. Diets supplemented with beta-carotene and phycocyanin significantly (P < 0.05) improved hematology parameters contents compared with to the control diet, and the best contents were detected in fish fed diet supplemented with phycocyanin. The highest significant (P < 0.05) phagocytic, lysozyme, immunoglobulin M (IgM), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and total antioxidant capacity (T-AOC) activities were recorded in diet supplemented with phycocyanin. The trans

关键词： Immune response   Cytokines   Hematology   Mulberry   Hydrophila spp   MAL   Nile tilapia   Morus alba  

摘要： The present work was designed to assess the potential hemato-biochemical protective action, immunemodulatory and antioxidant conclusions of varied concentration of white mulberry Morus alba leaves (MAL) extract supplementation on Nile tilapia (Oreochromis .niloticus). A total two hundred and forty of O. niloticus were haphazardly sorted into four groups. The control (CT) group was fed on basal diet. A group MAL(1), MAL(3) and MAL(5) was fed on 1, 3 and 5 g/kg MAL respectively for thirty days. On day thirty one, half of replicates in each group were challenged by 0.5 ml x 10(8) Aeromonas hydrophila where, the residual replicates were kept without challenge. A. hydrophila challenged tilapias revealed anemia that alleviated by supplementation with 5 g/kg MAL also, recovers the shift of leucogram prompted by the challenge. Elevation of alkaline phosphatase, aminotransferases, lactate dehydrogenase and malondialdehyde (ALP, ALT, AST, LDH and MDA) in CT, MAL(1) and MAL(3) in the challenged replicates respectively where within normal at MAL(5). Supplementation with MAL(5) showed more potent antioxidant and immune reaction than MAL(1) and MAL(3). There were a rapid increase of immunoglobulin M, lysozymes, nitric oxide, catalase and superoxide dismutase and their allied genes expression (IgM, CAT and SOD) in MAL groups with contrast in CT challenged groups. Where in challenged groups, there was suppression in genes expression of interleukins (8 and 1 beta) and interferon gamma (IL8. IL-1 beta and INF gamma). Tilapias challenged by A. hydrophila unveiled plentiful surge in the percentage of mortality in CT challenged fish (80%), followed by the groups supplemented with MAL(1) and MAL(3) were (73.33%) where MAL(5) was 20%. The mortalities have been halted from the 6th, 13th, 14th and 15th days in, MAL(5), MAL(3), MAL(1), and CT correspondingly. These previous results could be fulfilled that using of MAL 5 g/kg protect tilapias from hemato-biochemical alterations and enhance it

关键词： Trichoderma harzianum   Chimeric chit42   Defense-related gene   Real-time PCR   Rhizoctonia solani   Volatile compounds  

摘要： Trichoderma species as biocontrol agents protect plants against several pathogens via multiple mechanisms. This study was aimed to evaluate the in vitro biocontrol activities and, as well as in vivo induction of systemic resistance of Phaseolus vulgaris L. by two Trichoderma harzianum transformants overexpressing a chimeric chitinase42 with chitin binding domain (T13 and T15) and wild-type (Tw) strain with and without Rhizoctonia solani. In order to achieve this goal, T. harzianum strains were compared in vitro for their potential to antagonize activity against R. solani. Also, the expression of biocontrol-associated genes (chit42 and qid74) and the volatile compounds (VOCs) profile with biocontrol activity was analyzed from T. harzianum strains. The real-time PCR was used to measure the expression of defense-related genes involved in systemic acquired resistance (SAR) and induced systemic resistance (ISR) pathways. The results showed that recombinant strains T15 (92%) and T13 (85%) had the higher inhibitory effects against R. solani compared to the Tw strain. Also, gene expression analysis of T. harzianum revealed the up-regulation of biocontrol-associated genes in recombinant strains. Analysis of VOCs from three T. harzianum strains identified a total of twenty-two compounds, including five that were produced by all of them .VOCs analysis of recombinant strains revealed the production of compounds, like caryophyllene oxide, 2-methyl-1-butanol, alpha-farnesene, and beta-bisabolene. These compounds had been reported to induce plant defensive reactions against stress. Inoculation of plants with T13 and specially T15 strains, restricted the R. solani growth. Treatment of bean plants with recombinant strains led to increase in protection mechanisms including enhanced defense enzymes activity and higher expression of defense-related genes, as compared with Tw. The ability of recombinant strains to have better colonization within the soil and the root surface, describes

关键词： mononuclear Fe(II) α-ketoglutarate dependent dioxygenase   structure function   crystallography   stoichiometry   molecular dynamics   enzyme mechanism  

摘要： The isonitrile moiety is found in marine sponges and some microbes, where it plays a role in processes such as virulence and metal acquisition. Until recently only one route was known for isonitrile biosynthesis, a condensation reaction that brings together a nitrogen atom of L-Trp/L-Tyr with a carbon atom from ribulose-5-phosphate. With the discovery of ScoE, a mononuclear Fe(II) alpha-ketoglutarate-dependent dioxygenase from Streptomyces coeruleorubidus, a second route was identified. ScoE forms isonitrile from a glycine adduct, with both the nitrogen and carbon atoms coming from the same glycyl moiety. This reaction is part of the nonribosomal biosynthetic pathway of isonitrile lipopeptides. Here, we present structural, biochemical, and computational investigations of the mechanism of isonitrile formation by ScoE, an unprecedented reaction in the mononuclear Fe(II) alpha-ketoglutarate-dependent dioxygenase superfamily. The stoichiometry of this enzymatic reaction is measured, and multiple high-resolution (1.45-1.96 angstrom resolution) crystal structures of Fe(II)-bound ScoE are presented, providing insight into the binding of substrate, (R)-3-((carboxylmethyl)amino)butanoic acid (CABA), cosubstrate alpha-ketoglutarate, and an Fe(IV)=O mimic oxovanadium. Comparison to a previously published crystal structure of ScoE suggests that ScoE has an "inducible" alpha-ketoglutarate binding site, in which two residues arginine-157 and histidine-299 move by approximately 10 angstrom from the surface of the protein into the active site to create a transient alpha-ketoglutarate binding pocket. Together, data from structural analyses, site-directed mutagenesis, and computation provide insight into the mode of alpha-ketoglutarate binding, the mechanism of isonitrile formation, and how the structure of ScoE has been adapted to perform this unusual chemical reaction.