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https://www.readbyqxmd.com/read/28644624/extensive-assessment-of-various-computational-methods-for-aspartate-s-pka-shift
#1
Zhaoxi Sun, Xiaohui Wang, Jianing Song
A series of computational methods for pKa shift prediction are extensively tested on a set of benchmark protein systems, aiming at identifying pitfalls and evaluating their performance on high variants. Including 19 ASP residues in 10 protein systems, the benchmark set consists of both residues with highly shifted pKa values as well as those varying little from the reference value, with an experimental RMS free energy differences of 2.49 kcal/mol with respect to blocked amino acid, namely the RMS pKa shift being 1...
June 23, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28644367/oral-cholic-acid-is-efficacious-and-well-tolerated-in-patients-with-bile-acid-synthesis-and-zellweger-spectrum-disorders
#2
James E Heubi, Kevin E Bove, Kenneth D R Setchell
BACKGROUND/AIMS: Patients with bile acid synthesis disorders (BASD) due to single enzyme defects (SED) or Zellweger spectrum disorders (ZSD) accumulate hepatotoxic atypical bile acids resulting in potentially fatal progressive liver disease. We evaluated the efficacy and safety of oral cholic acid in patients with BASD. METHODS: In this phase 3, open-label, single-arm, nonrandomized, noncomparative study conducted over 18 years, patients were administered cholic acid orally 10 to 15 mg/kg/day...
June 21, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28644077/leiomyosarcoma-of-the-wing-in-a-vieilott-s-fireback-pheasant-lophura-rufa
#3
Martín A Zordan, Michael M Garner, Rebecca Smedley, Dana Neelis, Carlos R Sánchez
A 15-year-old, female Vieilott's fireback pheasant (Lophura rufa) presented with a 2-day history of a drooping right wing. Examination revealed severe soft tissue swelling in the area extending from the right shoulder to the humeral-radio-ulnar joint with associated bruising and feather loss. Results of a complete blood cell count revealed marked heterophilia and lymphocytosis, and results of serum biochemical analysis showed severe increases in creatine kinase and aspartate aminotransferase activities, hypoproteinemia, and hypoalbuminemia...
June 2017: Journal of Avian Medicine and Surgery
https://www.readbyqxmd.com/read/28643418/protein-engineering-of-recombinant-human-bone-morphogenetic-protein-2-with-higher-interaction-with-ca-phosphate-based-scaffold-usedfor-osteogenesis
#4
Mohammad Bayat, Sahar Shojaei, Naghmeh Bahrami, Abdol Reza Mohamadnia, Pegah Shojaei, Naeim Bahrami
The aim of the present studywas to assess the recombinant bonemorphogenetic protein 2 (RHBMP-2)with higher substantively and solubility for use in calcium phosphate scaffolds for better release in differentiation of mesenchymal stem cells to osteoblast cells. By using bioinformatics tools,2 mutations (p. L10D and p. S12E) werechosen and applied in BMP2 CDS sequenceto increase interaction with calcium derived composite. The new recombinant mutated sequence (BMP2(mut) ) was synthesized and then subcloned to expression vector pBV220...
June 23, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28642576/upregulation-of-mir-223-in-the-rat-liver-inhibits-proliferation-of-hepatocytes-under-simulated-microgravity
#5
Yongjie Chen, Ji Xu, Chao Yang, Hongyu Zhang, Feng Wu, Jian Chen, Kai Li, Hailong Wang, Yu Li, Yinghui Li, Zhongquan Dai
Long-term spaceflight affects numerous organ systems in the body, including metabolic dysfunction. Recently, ample evidence has demonstrated that the liver is a vulnerable organ during spaceflight. However, the changes in hepatocyte proliferation and cell cycle control under microgravity remain largely unexplored. In the present study, we first confirmed that the serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, biochemical markers of liver function, were altered in rats under tail suspension (TS) conditions to simulate microgravity, as shown in previous reports...
June 23, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28642445/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#6
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28642370/in-vitro-cytochrome-p450-46a1-cyp46a1-activation-by-neuroactive-compounds
#7
Natalia Mast, Kyle W Anderson, Kevin M Johnson, Thanh T N Phan, F Peter Guengerich, Irina A Pikuleva
Cytochrome P450 46A1 (CYP46A1, cholesterol 24-hydroxylase) is the enzyme responsible for the majority of cholesterol elimination from the brain. Previously, we found that the anti-HIV drug efavirenz (EFV) can pharmacologically activate CYP46A1 in mice. Herein, we investigated whether CYP46A1 could also be activated by endogenous compounds, including major neurotransmitters. In vitro experiments with purified recombinant CYP46A1 indicated that CYP46A1 is activated by L-glutamate (L-Glu), L-aspartate, γ-aminobutyric acid, and acetylcholine, with L-Glu eliciting the highest increase (3-fold) in CYP46A1-mediated cholesterol 24-hydroxylation...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28642137/overexpression-cdc42-attenuates-isoflurane-induced-neurotoxicity-in-developmental-brain-of-rats
#8
Xi Fang, Shiyong Li, Qiang Han, Yilin Zhao, Jie Gao, Jing Yan, Ailin Luo
Nowadays many children receive operations with general anesthesia. Isoflurane is a commonly-used general anesthetic. Numbers of studies demonstrated that isoflurane induced neurotoxicity and neurobehavioral deficiency in young rats, however, the underlying mechanism remained unknown. Cell division cycle 42 (cdc42) played an important role in regulating synaptic vesicle trafficking and actin dynamics in neuron, which closely linked to synaptic plasticity and dendritic spine formation. Meanwhile, cdc42 also involved in many neurodegenerative diseases...
June 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28641570/1h-post-load-blood-glucose-in-the-identification-of-proatherogenic-cardiometabolic-profile-in-obesity
#9
Djordje S Popovic, Dragana Tomic-Naglic, Milena Mitrovic, Zeljko Zivanovic, Bojan Vukovic, Edita Stokic
BACKGROUND AND AIM: Current data show that 1h oral glucose tolerance test (OGTT) blood glucose (1h-BG) might identify persons at increased risk of developing type 2 diabetes and cardiovascular diseases more precisely than fasting blood glucose (FBG) and 2h OGTT blood glucose (2h-BG). The aim of study was to determine whether is justified to use 1h-BG, instead of traditional blood glucose measurements, in cardiometabolic profiling of obese individuals. METHOD: Cross-sectional study enrolled 60 obese individuals without previous history of diabetes and other cardiometabolic disorders...
June 13, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28641512/molecular-docking-and-molecular-dynamics-simulation-based-approach-to-explore-the-dual-inhibitor-against-hiv-1-reverse-transcriptase-and-integrase
#10
Subhash Chander, Rajan Kumar Pandey, Ashok Penta, Bhanwar Singh Choudhary, Manish Sharma, Ruchi Malik, Vijay Kumar Prajapati, Sankaranarayanan Murugesan
HIV integrase (IN) and reverse transcriptase (RT) are key enzymes for the replication of HIV-1. DNA polymerase and ribonuclease H (RNase H) are the two catalytic domains of HIV-1 RT which are validated as drug targets because of their essence for replication. IN and RNase H domain of RT share the striking structural similarity; it contains conserved DDE triad (two aspartates and one glutamate) and a pair of divalent Mg2+/Mn2+ ions at their catalytic core domain. Therefore, the search of compounds with dual inhibition of IN and RNase H can be the viable and more efficacious approach for the drug development against both wild and drug resistance strains of HIV...
June 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28640288/prognostic-factors-for-transplant-free-survival-and-validation-of-prognostic-models-in-chinese-patients-with-primary-biliary-cholangitis-receiving-ursodeoxycholic-acid
#11
Ka-Shing Cheung, Wai-Kay Seto, James Fung, Ching-Lung Lai, Man-Fung Yuen
OBJECTIVES: We aimed to validate the prognostic models for primary biliary cholangitis (PBC) in Chinese patients receiving ursodeoxycholic acid (UCDA), and to compare their performances in predicting the long-term survival. METHODS: Chinese patients with PBC from a tertiary center were identified via electronic search of hospital medical registry. Risk factors associated with adverse events (liver transplantation or death from liver-related causes including hepatocellular carcinoma (HCC) and liver decompensation) were determined...
June 22, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28640248/voluntary-distance-running-prevents-tnf-mediated-liver-injury-in-mice-through-alterations-of-the-intrahepatic-immune-milieu
#12
Yvonne Huber, Nadine Gehrke, Jana Biedenbach, Susanne Helmig, Perikles Simon, Beate K Straub, Ina Bergheim, Tobias Huber, Detlef Schuppan, Peter R Galle, Marcus A Wörns, Marcus Schuchmann, Jörn M Schattenberg
Physical activity confers a broad spectrum of health benefits. Beyond the obvious role in metabolically driven diseases, the role of physical activity in acute liver injury is poorly explored. To study the role of physical activity in acute liver injury, a novel model of voluntary distance running in mice was developed and mice were subjected to acute liver injury induced by N-galactosamine (GalN) and lipopolysaccharide (LPS). Analyses included histological stains, immunoblotting, qRT-PCR and FACS analysis...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28640108/correlation-of-hla-dp-dq-polymorphisms-with-transplant-etiologies-and-prognosis-in-liver-transplant-recipients
#13
Yi Li, Qian Huang, Jiang-Tao Tang, Tian-Tian Wei, Lin Yan, Zhi-Qiang Yang, Yang-Juan Bai, Lan-Lan Wang, Yun-Ying Shi
Previous study has identified that the genetic variants in the human leukocyte antigen (HLA)-DP/DQ region were strongly associated with hepatitis B virus (HBV) infection. But their roles in liver function recovery after hepatic transplantation were still obscure. This study aimed to investigate whether HLA-DP/DQ polymorphisms were associated with post-transplant etiologies and prognosis in Chinese liver transplant recipients.A total of 144 liver transplant recipients were enrolled, which were divided into 2 groups according to the transplant etiology: HBV-related disease and non-HBV-related disease...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28639200/treatment-of-liver-cancer-by-c-ebpa-sarna
#14
Xiaoyang Zhao, Jon Voutila, Stephanos Ghobrial, Nagy A Habib, Vikash Reebye
The prognosis for hepatocellular carcinoma (HCC) remains poor and has not improved in over two decades. Most patients with advanced HCC who are not eligible for surgery have limited treatment options due to poor liver function or large, unresectable tumors. Although sorafenib is the standard-of-care treatment for these patients, only a small number respond. For the remaining, the outlook remains bleak. A better approach to target "undruggable" molecular pathways that reverse HCC is therefore urgently needed...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28638943/elevated-serum-heat-shock-protein-70-and-liver-stiffness-reflect-hepatic-dysfunction-and-severity-in-postoperative-biliary-atresia
#15
Sittisak Honsawek, Wanvisa Udomsinprasert, Napaphat Jirathanathornnukul, Voranush Chongsrisawat, Yong Poovorawan
BACKGROUND: Biliary atresia (BA) is a severe chronic liver disease characterized by progressive obstructive cholangiopathy of biliary tract. Heat shock protein 70 (HSP70) is involved in protecting cells against a wide variety of stress and plays a protective role in tissue damage. The purpose of this study was to investigate serum HSP70 and liver stiffness in BA and determine the association of serum HSP70, liver stiffness, and outcome parameters in post-Kasai BA patients. METHODS: One hundred post-Kasai BA patients and 40 controls were enrolled...
June 21, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28638920/-a-study-on-toxic-effects-of-sodium-salicylate-on-rat-cochlear-spiral-ganglion-neurons-dopamine-receptors-mediate-expressions-of-nmda-and-gabaa-receptors
#16
Ting-Jia Wei, Hui-Ying Chen, Xi Huang, Jing-Jin Weng, Jiang-Yuan Qin, Ji-Ping Su
The aim of the present study was to observe whether dopamine receptor (DR) was involved in the effects of sodium salicylate (SS) on the expressions of N-methyl-D-aspartic acid (NMDA) and γ-aminobutyric acid (GABA) receptors in rat cochlear spiral ganglion neurons (SGNs). Forty-eight hours after primary culture of rat SGNs, immunofluorescence technique was applied to detect expressions of DR1 and DR2, the two subtypes of dopamine receptors. Western blot was performed to assess NMDA receptor NR1 subunit and GABAA receptor subunit α2 (GABRα2) protein expressions in the SGNs after the treatments of SS alone or in combination with DR antagonists...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28638880/efficiency-of-borage-seeds-oil-against-gamma-irradiation-induced-hepatotoxicity-in-male-rats-possible-antioxidant-activity
#17
Hala A H Khattab, Inas Z A Abdallah, Fatimah M Yousef, Etimad A Huwait
BACKGROUND: Borage (Borago officinal L.) is an annual herbaceous plant of great interest because its oil contains a high percentage of γ-linolenic acid (GLA). The present work was carried out to detect fatty acids composition of the oil extracted from borage seeds (BO) and its potential effectiveness against γ-irradiation- induced hepatotoxicity in male rats. MATERIALS AND METHODS: GC-MS analysis of fatty acids methyl esters of BO was performed to identify fatty acids composition...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28638434/an-evaluation-of-the-protective-role-of-vitamin-c-in-reactive-oxygen-species-induced-hepatotoxicity-due-to-hexavalent-chromium-in-vitro-and-in-vivo
#18
Xiali Zhong, Ming Zeng, Huanfeng Bian, Caigao Zhong, Fang Xiao
BACKGROUD: Drinking water contamination with hexavalent chromium [Cr (VI)] has become one of the most serious public health problems, thus the investigation of Cr (VI)-induced hepatotoxicity has attracted much attention in recent years. METHODS: In the present study, by determining the indices of hepatotoxicity induced by Cr (VI), the source of accumulated reactive oxygen species (ROS), and the protective effect of the antioxidant Vitamin C (Vit C), we explored the mechanisms involved in Cr (VI)-induced hepatotoxicity in vitro and in vivo...
2017: Journal of Occupational Medicine and Toxicology
https://www.readbyqxmd.com/read/28638431/erzhi-pill%C3%A2-repairs-experimental-liver-injury-via-tsc-mtor-signaling-pathway-inhibiting-excessive-apoptosis
#19
Bu-Gao Zhou, Hai-Mei Zhao, Xiu-Yun Lu, Xin Wang, Yong Zou, Rong Xu, Hai-Yang Yue, Yi Liu, Zheng-Yun Zuo, Duan-Yong Liu
The present study aimed to investigate the mechanism of hepatoprotective effect of Erzhi Pill (EZP) on the liver injury via observing TSC/mTOR signaling pathway activation. The experimental liver injury was induced by 2-acetylaminofluorene (2-AAF) treatment combined with partial hepatectomy (PH). EZP treated 2-AAF/PH-induced liver injury by the therapeutic and prophylactic administration. After the administration of EZP, the activities of aspartic transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AKP), and gamma-glutamyl transpeptidase (γ-GT) were decreased, followed by the decreased levels of hepatocyte apoptosis and caspase-3 expression...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28638351/transcranial-direct-current-stimulation-considerations-for-research-in-adolescent-depression
#20
REVIEW
Jonathan C Lee, Charles P Lewis, Zafiris J Daskalakis, Paul E Croarkin
Adolescent depression is a prevalent disorder with substantial morbidity and mortality. Current treatment interventions do not target relevant pathophysiology and are frequently ineffective, thereby leading to a substantial burden for individuals, families, and society. During adolescence, the prefrontal cortex undergoes extensive structural and functional changes. Recent work suggests that frontolimbic development in depressed adolescents is delayed or aberrant. The judicious application of non-invasive brain stimulation techniques to the prefrontal cortex may present a promising opportunity for durable interventions in adolescent depression...
2017: Frontiers in Psychiatry
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