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Haristi Gaitantzi, Christoph Meyer, Pia Rakoczy, Maria Thomas, Kristin Wahl, Franziska Wandrer, Heike Bantel, Hamed Alborzinia, Stefan Wölfl, Sabrina Ehnert, Andreas Nüssler, Ina Bergheim, Loredana Ciuclan, Matthias Ebert, Katja Breitkopf-Heinlein, Steven Dooley
Alcohol abuse is a global health problem causing a substantial fraction of chronic liver diseases. Abundant TGF-β-a potent pro-fibrogenic cytokine-leads to disease progression. Our aim was to elucidate the crosstalk of TGF-β and alcohol on hepatocytes. Primary murine hepatocytes were challenged with ethanol and TGF-β and cell fate was determined. Fluidigm RNA analyses revealed transcriptional effects that regulate survival and apoptosis. Mechanistic insights were derived from enzyme/pathway inhibition experiments and modulation of oxidative stress levels...
January 19, 2018: Cell Death & Disease
Samir M Amer, Kamlesh K Bhopale, Ramu D Kakumanu, Vsevolod L Popov, Bill A Rampy, Inas H El-Mehallawi, Magdy M Ashmawy, G A Shakeel Ansari, Bhupendra S Kaphalia
The single most common cause of chronic pancreatitis (CP, a serious inflammatory disease) is chronic alcohol abuse, which impairs hepatic alcohol dehydrogenase (ADH, a major ethanol oxidizing enzyme). Previously, we found ~5 fold greater fatty acid ethyl esters (FAEEs), and injury in the pancreas of hepatic ADH deficient (ADH-) vs. hepatic normal ADH (ADH+) deer mice fed 3.5g% ethanol via liquid diet daily for two months. Therefore, progression of ethanol-induced pancreatic injury was determined in ADH- deer mice fed ethanol for four months to delineate the mechanism and metabolic basis of alcoholic chronic pancreatitis (ACP)...
January 11, 2018: Experimental and Molecular Pathology
Amina Elahi, Abdul Rehman
In the present work, a yeast strain Pichia kudriavzevii was identified on the basis of 18S rDNA, showing maximum growth at 30°C and pH 7.0. Among all the complex polysaccharides used, wheat bran proved to be the best substrate as indicated by the maximum growth of the yeast strain. The yeast isolate was capable of producing xylanase both intra- and extra-cellularly, the dominant form being extracellular. The maximum enzyme activity was determined at pH 5.0 and at 50°C. Na+, Mg2+ and Fe2+ presence caused a substantial increase in enzyme activity while a slight decrease (4...
January 11, 2018: Revista Argentina de Microbiología
Yangbin Shen, Yulu Zhan, Shuping Li, Fandi Ning, Ying Du, Yunjie Huang, Ting He, Xiaochun Zhou
As an excellent hydrogen storage medium, methanol has many advantages, such as high hydrogen content (12.6 wt%), low-cost and availability from biomass or photocatalysis. However, conventional methanol-water reforming usually proceeds at high temperature. In this research, we successfully designed a new effective strategy to generate hydrogen from methanol at near-room temperature. The strategy involves two main procedures, which are CH3OH→HCOOH→H2 and NADH→HCOOH→H2. The first procedure (CH3OH→HCOOH→H2) is performed by alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and the Ir-catalyst...
January 11, 2018: ChemSusChem
Morgan B Vaughn, Jianyu Zhang, Thomas G Spiro, R Brian Dyer, Judith P Klinman
Previous studies of a thermophilic alcohol dehydrogenase (ht-ADH) demonstrated a range of discontinuous transitions at 30 °C that include catalysis, kinetic isotope effects, protein hydrogen-deuterium exchange rates, and intrinsic fluorescence properties. Using the Förster resonance energy transfer response from a Trp-NADH donor-acceptor pair in T-jump studies of ht-ADH, we now report microsecond protein motions that can be directly related to active site chemistry. Two distinctive transients are observed: a slow, kinetic process lacking a temperature break, together with a faster transient that is only detectable above 30 °C...
January 11, 2018: Journal of the American Chemical Society
Filip Boratyński, Agata Janik-Polanowicz, Ewa Szczepańska, Teresa Olejniczak
Lactone 2a of a bicyclo[4.3.0]nonane structure is a good starting material for synthesis of many attractive compounds. Enantiomerically enriched (-)-(3aR,7aS)-lactone 2a is produced by whole cells of bacteria. In order to examine the impact of the absolute configuration on biological activity we evaluated the process affording the opposite isomer. To this purpose Candida pelliculosa ZP22 characterized by high dehydrogenase activity was used. The goal of presented work was to perform bioreactor scale microbial one-pot oxidation of diol with selected yeast strain C...
January 11, 2018: Scientific Reports
Chuqiao Xiao, Feibai Zhou, Mouming Zhao, Guowan Su, Baoguo Sun
In this study, the ameliorative effect of chicken breast muscle hydrolysates (CBMHs) against acute alcohol-induced liver injury was investigated and its probable mechanism was further elucidated. In vitro studies clearly showed that CBMHs are able to activate alcohol metabolic enzymes (i.e. alcohol dehydrogenase, ADH) in an exponential manner. Meanwhile, an in vivo experiment on male NIH mice indicated that the oral administration of CBMHs (150, 300 and 600 mg per kg bw) 30 min prior to acute alcohol ingestion could significantly promote alcohol metabolism as revealed by the reduced duration of the loss of righting reflex (LORR) and the enhanced activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver, the latter accelerating alcohol oxidation and therefore the decreased blood alcohol concentration (BAC) level...
January 8, 2018: Food & Function
Sunil Kumar, Maria C Vogel, Andrew D Hamilton
A library of N-substituted oligopyrrolamides was designed to modulate the aggregation kinetics of islet amyloid polypeptide (IAPP). IAPP is a hormonal peptide, co-secreted with insulin in the pancreatic β-cells. IAPP samples a variety of conformations, starting from a native random coil to membrane-associated α-helical intermediates and eventually terminates in the amyloid plaques rich in β-sheet structures. A growing body of evidence suggests that membrane bound α-helical intermediates are the key cytotoxic species that impair the functionality and viability of β-cells and contribute to the onset of type 2 diabetes mellitus (DM2)...
January 5, 2018: Organic & Biomolecular Chemistry
Mahboobeh Eslami, Navid Nezafat, Sahar Khajeh, Zohreh Mostafavi-Pour, Samaneh Bagheri Novir, Manica Negahdaripour, Younes Ghasemi, Vahid Razban
Due to the considerable role of N-cadherin in cancer metastasis, tumor growth and progression, inhibition of this protein has been highly regarded in recent years. Although ADH-1 has been known as an appropriate inhibitor of N-cadherin in clinical trials, its chemical nature and binding mode with N-cadherin have not been precisely specified yet. Accordingly, in this study quantum mechanics calculations were used to investigate the chemical nature of ADH-1. These calculations clarify the molecular properties of ADH-1 and determine its reactive sites...
January 4, 2018: Journal of Biomolecular Structure & Dynamics
Francesca Scionti, Maria Teresa Di Martino, Simona Sestito, Angela Nicoletti, Francesca Falvo, Katia Roppa, Mariamena Arbitrio, Pietro Hiram Guzzi, Giuseppe Agapito, Antonio Pisani, Eleonora Riccio, Daniela Concolino, Licia Pensabene
Enzyme replacement therapy (ERT) has been widely used for the treatment of Fabry disease, a rare X-linked recessive disorder due to absent or reduced activity of lysosomal enzyme α-galactosidase A. It is still unclear why some patients under ERT show disease progression typically with renal, cardiovascular and cerebrovascular dysfunctions. Here, we investigated the involvement of drug absorption, distribution, metabolism, and excretion gene variants in response variability to ERT, genotyping 37 patients with the Affymetrix Drug Metabolizing Enzyme and Transporters (DMET) Plus microarray...
December 8, 2017: Oncotarget
Puthupparampil V Scaria, Beth Chen, Christopher G Rowe, David S Jones, Emma Barnafo, Elizabeth R Fischer, Charles Anderson, Nicholas J MacDonald, Lynn Lambert, Kelly M Rausch, David L Narum, Patrick E Duffy
Chemical conjugation of polysaccharide to carrier proteins has been a successful strategy to generate potent vaccines against bacterial pathogens. We developed a similar approach for poorly immunogenic malaria protein antigens. Our lead candidates in clinical trials are the malaria transmission blocking vaccine antigens, Pfs25 and Pfs230D1, individually conjugated to the carrier protein Exoprotein A (EPA) through thioether chemistry. These conjugates form nanoparticles that show enhanced immunogenicity compared to unconjugated antigens...
2017: PloS One
Yujia Jiang, Jie Liu, Weiliang Dong, Wenming Zhang, Yan Fang, Jiangfeng Ma, Min Jiang, Fengxue Xin
A novel thermophilic and butanogenic Thermoanaerobacterium thermosaccharolyticum M5 was successfully isolated and characterized, which could produce butanol from hemicellulose via a unique ethanol-butanol (EB) pathway through consolidated bioprocessing (CBP). This represents the first wild-type bacterium which could produce butanol from hemicellulose via CBP under thermophilic conditions. The assembled draft genome of strain M5 is 2.64 Mp, which contains 2638 genes and 2465 protein-coding sequences with 33...
December 26, 2017: Current Microbiology
Christoph L Käsbauer, Indira Priyadarshini Pathuri, Götz Hensel, Jochen Kumlehn, Ralph Hückelhoven, Reinhard K Proels
The plant primary energy metabolism is profoundly reorganized under biotic stress conditions and there is increasing evidence for a role of the fermentative pathway in biotic interactions. Previously we showed via transient gene silencing or overexpression a function of barley alcohol dehydrogenase 1 (HvADH-1) in the interaction of barley with the parasitic fungus Blumeria graminis f.sp. hordei (Bgh). Here we extend our studies on stable transgenic barley events over- or under-expressing HvADH-1 to analyse ADH-1 functions at the level of whole plants...
December 18, 2017: Plant Physiology and Biochemistry: PPB
Nicolas Ramoz, Philip Gorwood
Genetic factors are involved in the predisposition to alcohol dependence with an heritability of about 0.5. Sequencing or analysis of the polymorphisms of genes or the whole human genome allow to identify genetic markers of alcohol dependence. Genes of the brain pathway of motivation and reward, including DRD2 and ANKK1, are associated with alcohol dependence. Genes encoding the gabaergic receptors show variants link to alcohol dependence. Polymorphisms in the genes encoding the enzymes alcohol desydrogenases (ADH) and aldehyde-dehydrogenases (ALDH) are associated to the susceptibility or the protection of alcohol dependence...
December 20, 2017: La Presse Médicale
Zhaoming Guo, Wenqing Li, Yue Yuan, Kun Zheng, Yu Tang, Kun Ma, Changhao Cui, Li Wang, Bing He, Qiang Zhang
How to overcome drug resistance and prevent tumor metastasis is key to the success of malignant tumor therapy. In this paper, ADH-1 peptide-modified liposomes (A-LP) have been successfully constructed for restoring chemosensitivity and suppressing cancer cell migration. With a particle size of about 90 nm, this functionalized nanocarrier was loaded with fluorescent probe or paclitaxel (PTX). Cellular uptake studies showed that A-LP facilitated the delivery of anticancer drug to tumor cells undergoing EMT...
November 2018: Drug Delivery
Qiong-Hui Huang, Lie-Qiang Xu, Yu-Hong Liu, Jia-Zhen Wu, Xue Wu, Xiao-Ping Lai, Yu-Cui Li, Zi-Ren Su, Jian-Nan Chen, You-Liang Xie
Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD) exerted antioxidant and anti-inflammatory effects and attenuated ethanol-induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol-induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in the serum, suppressed the malonaldehyde (MDA) and triglyceride (TG) content and the production of reactive oxygen species (ROS), and enhanced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), andalcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH), paralleled by an improvement of histopathology alterations...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Qionghua Cui, Linna Peng, Lixuan Wei, Jiang Chang, Wenle Tan, Yingying Luo, Xudong Huang, Yanjie Zhao, Jun Li, Jiahui Chu, Mingming Shao, Chao Zhang, Cheng Li, Wen Tan, Dongxin Lin, Chen Wu
Genome-wide association studies (GWAS) have discovered numerous genetic susceptibility loci including a cluster of alcohol dehydrogenase (ADH) gene family for esophageal squamous-cell carcinoma (ESCC). However, the underlying mechanism has not fully been elucidated. In this study, we integrated the GWAS data, gene-drinking interaction, expression quantitative trait locus (eQTL) analysis and biochemical experiments to clarify the specific mechanism of the polymorphisms in ADH loci. By imputation and eQTL analysis, we identified rs1154402C>G in intron 1 of ADH5 substantially associated with the expression levels of ADH1A...
December 14, 2017: Cancer Letters
Saikat Chakraborty, Joy Mitra, Milan Kumar Samanta, Narattam Sikdar, Jagannath Bhattacharyya, Anulina Manna, Subrata Pradhan, Anirban Chakraborty, Bikas Ranjan Pati
Grass pea (Lathyrus sativus L.) is a worldwide popular pulse crop especially for its protein rich seeds with least production cost. However, the use of the crop became controversial due to the presence of non-protein amino acid, β-N-oxalyl-L-α, β-diaminopropionic acid (β-ODAP) in its seed and leaf, which is known as the principle neurotoxin to cause neurolathyrism (a motor neurodegenerative disease of humans and animals) during prolonged consumption as regular diet. Till date, the knowledge on β-ODAP biosynthesis in Lathyrus sp...
December 13, 2017: Gene Expression Patterns: GEP
Yanfei Yu, Yunyun Qian, Dechao Du, Quan Li, Chenyang Xu, Hanze Liu, Mianmian Chen, Huochun Yao, Chengping Lu, Wei Zhang
Streptococcus suis (S. suis) is an emerging zoonotic agent that is responsible for significant economic losses to the porcine industry worldwide. However, most research regarding the pathogenic mechanisms has used in vitro cultures of S. suis, which may not provide an accurate representation of the in vivo biological activities. In this study, 188 differential abundance S. suis proteins were identified in in vivo samples obtained from the blood of the infected pigs. These were compared with in vitro samples by a Tandem Mass Tags (TMT) experiment...
December 13, 2017: Journal of Proteomics
Matthias Wehrmann, Janosch Klebensberger
Due to their ability for direct electron transfer to electrodes, the utilization of rare earth metals as cofactor, and their periplasmic localization, pyrroloquinoline quinone-dependent alcohol dehydrogenases (PQQ-ADHs) represent an interesting class of biocatalysts for various biotechnological applications. For most biocatalysts protein stability is crucial, either to increase the performance of the protein under a given process condition or to maximize robustness of the protein towards mutational manipulations, which are often needed to enhance or introduce a functionality of interest...
December 14, 2017: Microbial Biotechnology
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