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https://www.readbyqxmd.com/read/29782898/incorporation-of-absorption-and-metabolism-into-liver-toxicity-prediction-for-phytochemicals-a-tiered-in-silico-qsar-approach
#1
Yitong Liu
An increased use of herbal dietary supplements has been associated with adverse liver effects such as elevated serum enzymes and liver failure. The safety assessment for herbal dietary supplements is challenging since they often contain complex mixtures of phytochemicals, most of which have unknown pharmacokinetic and toxicological properties. Rapid tools are needed to evaluate large numbers of phytochemicals for potential liver toxicity. The current study demonstrates a tiered approach combining identification of phytochemicals in liver toxic botanicals, followed by in silico quantitative structure-activity relationship (QSAR) evaluation of these phytochemicals for absorption (e...
May 18, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29782150/-site-and-mutation-specific-predictions-enable-minimal-directed-evolution-libraries
#2
Jeffrey C Moore, Agustina Rodriguez-Granillo, Alejandro Crespo, Sridhar Govindarajan, Mark Welch, Kaori Hiraga, Katrina Lexa, Nicholas Marshall, Matthew David Truppo
Directed evolution experiments designed to improve the activity of a biocatalyst have increased in sophistication from the early days of completely random mutagenesis. Sequence-based and structure-based methods have been developed to identify "hotspot" positions that when randomized provide a higher frequency of beneficial mutations that improve activity. These focused mutagenesis methods reduce library sizes and therefore reduce screening burden, accelerating the rate of finding improved enzymes...
May 21, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29779216/glutamate-metabolism-in-cerebral-mitochondria-after-ischemia-and-post-ischemic-recovery-during-aging-relationships-with-brain-energy-metabolism
#3
Federica Ferrari, Antonella Gorini, Siegfried Hoyer, Roberto Federico Villa
Glutamate is involved in cerebral ischemic injury, but its role has not been completely clarified and studies are required to understand how minimize its detrimental effects, contemporarily boosting the positive ones. In fact, glutamate is not only a neurotransmitter, but primarily a key metabolite for brain bioenergetics. Thus, we investigated the relationships between glutamate and brain energy metabolism in an in vivo model of complete cerebral ischemia of 15 min and during post-ischemic recovery after 1, 24, 48, 72 and 96 hrs in 1 year- adult and 2 year-old aged rats...
May 20, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29775111/tamoxifen-prevents-d-galactosamine-lipopolysaccharide-induced-murine-acute-hepatic-failure-through-inhibition-of-oxidative-stress-and-mmd-2-upregulation
#4
Xiaoxue Gong, Peng Cao, Liping Liu, Yan Lin, Qing Yang, Linyu Zhou, Tianen Wu, Mansheng Luo
Oxidative stress is considered one of the major mechanisms underlying lipopolysaccharide (LPS)-induced acute liver failure (ALF). Tamoxifen has been reported to ameliorate LPS-induced ALF via the induction of monocyte to macrophage differentiation-associated 2 (Mmd-2). Whether antioxidant effects are involved remains unknown. Mice were given tamoxifen (TAM) once a day for 3 days. Twelve hours later, d-galactosamine (GaIN) and LPS were injected intraperitoneally to induce ALF. N-Acetylcysteine (NAC) was administered immediately after ALF induction as a positive control...
May 18, 2018: Immunological Investigations
https://www.readbyqxmd.com/read/29774028/nlrp3-inflammasome-and-caspase-1-11-pathway-orchestrate-different-outcomes-in-the-host-protection-against-trypanosoma-cruzi-acute-infection
#5
Augusto F Paroli, Patricia V Gonzalez, Cintia Díaz-Luján, Luisina I Onofrio, Alfredo Arocena, Roxana C Cano, Eugenio A Carrera-Silva, Susana Gea
Infection with protozoan parasite Trypanosoma cruzi results in activation of nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1β and IL-18. Considering that inflammasome activation and IL-1β induction by macrophages are key players for an appropriate T cell response, we investigated the relevance of NLR pyrin domain-containing 3 (NLRP3) and caspase-1/11 to elucidate their roles in the induction of different T cell phenotypes and the relationship with parasite load and hepatic inflammation during T...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773188/the-toxic-effect-of-gallic-acid-on-biochemical-factors-viability-and-proliferation-of-rat-bone-marrow-mesenchymal-stem-cells-was-compensated-by-boric-acid
#6
Mohammad Hussein Abnosi, Somayeh Yari
OBJECTIVE: Gallic acid (GA) and boron are found in many plants. Our previous studies showed 6 ng/ml boric acid (BA) had positive effect on biochemistry of rat bone marrow mesenchymal stem cells (MSCs) and their osteogenic differentiation. Therefore, we investigate the effect of different doses of GA alone and in the presence of BA on MSCs. MATERIALS AND METHODS: the viability of MSCs was assayed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and trypan blue at 12, 24 and 36 h in presence of different concentration of GA...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29770798/combined-treatment-with-apatinib-and-docetaxel-in-a549-xenograft-mice-and-its-cellular-pharmacokinetic-basis
#7
Si-Qi Feng, Guang-Ji Wang, Jing-Wei Zhang, Yuan Xie, Run-Bin Sun, Fei Fei, Jing-Qiu Huang, Ying Wang, Ji-Ye Aa, Fang Zhou
Apatinib, a small-molecule inhibitor of VEGFR-2, has attracted much attention due to its encouraging anticancer activity in third-line clinical treatment for many malignancies, including non-small cell lung cancer (NSCLC). Its usage in second-line therapy with chemotherapeutic drugs is still under exploration. In this study we investigated the antitumor effect of apatinib combined with docetaxel against NSCLC and its cellular pharmacokinetic basis. A549 xenograft nude mice were treated with apatinib (100 mg/kg every day for 20 days) combined with docetaxel (8 mg/kg, ip, every four days for 5 times)...
May 17, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29769055/one-visceral-artery-may-be-enough-successful-pancreatectomy-in-a-patient-with-total-occlusion-of-the-celiac-and-superior-mesenteric-arteries
#8
Evangelos Tagkalos, Florian Jungmann, Hauke Lang, Stefan Heinrich
BACKGROUND: The anatomic variations of the visceral arteries are not uncommon. The liver arterial blood supply shows 50% variability between humans, with the most common anatomy being one hepatic artery arising from the celiac trunk and one pancreatico-duodenal arcade between the celiac trunk and the superior mesenteric artery. Occlusion of one artery are mostly asymptomatic but may become clinically relevant when surgery of the liver, bile duct or the pancreas is required. If these pathologies are not reversible, an oncologic pancreatic head resection cannot be performed...
May 16, 2018: BMC Surgery
https://www.readbyqxmd.com/read/29767334/are-phloem-derived-amino-acids-the-origin-of-the-elevated-malate-concentration-in-the-xylem-sap-following-mineral-n-starvation-in-soybean
#9
Simone C Vitor, Luciano do Amarante, Ladaslav Sodek
A substantial increase in malate in the xylem sap of soybean subjected to mineral N starvation originates mainly from aspartate, a prominent amino acid of the phloem. A substantial increase in xylem malate was found when non-nodulated soybean plants were transferred to a N-free medium. Nodulated plants growing in the absence of mineral N and, therefore, dependent on symbiotic N2 fixation also contained elevated concentrations of malate in the xylem sap. When either nitrate or ammonium was supplied, malate concentrations in the xylem sap were low, both for nodulated and non-nodulated plants...
May 16, 2018: Planta
https://www.readbyqxmd.com/read/29766812/switching-dipeptidyl-peptidase-4-inhibitors-to-tofogliflozin-a-selective-inhibitor-of-sodium-glucose-cotransporter-2-improves-arterial-stiffness-evaluated-by-cardio-ankle-vascular-index-in-patients-with-type-2-diabetes
#10
Nobuhiro Tahara, Sho-Ichi Yamagish, Munehisa Bekki, Atsuko Tahara, Sachiyo Igata, Akihiro Honda, Yoichi Sugiyama, Tomohisa Nakamura, Jiahui Sun, Yuki Kumashiro, Takanori Matsui, Yoshihiro Fukumoto
BACKGROUND: We have found that anagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4) significantly ameliorates arterial stiffness in type 2 diabetes mellitus (T2DM) patients compared with an equivalent hypoglycemic agent, glimepiride. However, it remains unclear whether and how switching DPP-4 inhibitors to tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2) improves arterial stiffness in T2DM patients. METHODS: Nineteen T2DM patients who had received DPP-4 inhibitors for at least 1 year were enrolled in this study...
May 15, 2018: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29765504/polyphenolic-compounds-antioxidant-and-cardioprotective-effects-of-pomace-extracts-from-feteasc%C3%A4-neagr%C3%A4-cultivar
#11
Ştefania Silvia Balea, Alina Elena Pârvu, Nastasia Pop, Fernando Zamora Marín, Marcel Pârvu
Grape pomace is a potential source of natural antioxidant agents. Phenolic compounds and antioxidant and cardioprotective properties of fresh and fermented pomace extracts obtained from Vitis vinifera L. red variety Fetească neagră grown in Romania in 2015 were investigated. Grape pomace extracts total phenolic index, total tannins, total anthocyanins, proanthocyanidins, flavan-3-ol monomers, stilbenes, and DPPH free radical scavenger were measured. The effect of a seven-day pretreatment with grape pomace extracts on the isoprenaline-induced infarct-like lesion in rats was assessed by ECG monitoring, serum levels of creatine kinase, aspartate transaminase, and alanine transaminase...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29764004/editorial-comment-from-dr-yuasa-to-prognostic-impact-of-the-pretreatment-aspartate-transaminase-alanine-transaminase-ratio-in-patients-treated-with-first-line-systemic-tyrosine-kinase-inhibitor-therapy-for-metastatic-renal-cell-carcinoma
#12
Takeshi Yuasa
No abstract text is available yet for this article.
May 15, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29763372/acetyl-coa-from-inflammation-induced-fatty-acids-oxidation-promotes-hepatic-malate-aspartate-shuttle-activity-and-glycolysis
#13
Tongxin Wang, Weilei Yao, Ji Li, Qiongyu He, Yafei Shao, Feiruo Huang
Hepatic metabolic syndrome is associated with inflammation, as it stimulates the reprogramming of nutrient metabolism and hepatic mitochondria-generated acetyl-CoA. But how acetyl-CoA affects the reprogramming of nutrient metabolism, especially glucose and fatty acids, in the condition of inflammation is still unclear. Here, we used an acute inflammation model in which pigs were injected with lipopolysaccharide (LPS), and found that hepatic glycolysis and fatty acid oxidation are both promoted. Acetyl-proteome profiling of LPS-infected pigs liver showed that inflammatory stress exacerbates the acetylation of mitochondrial proteins...
May 15, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29761171/coding-variants-in-pnpla3-and-tm6sf2-are-risk-factors-for-hepatic-steatosis-and-elevated-serum-alanine-aminotransferases-caused-by-a-glucagon-receptor-antagonist
#14
Cristina B Guzman, Suman Duvvuru, Anthony Akkari, Pallav Bhatnagar, Chakib Battioui, Wendra Foster, Xiaotian Michelle Zhang, Sudha S Shankar, Mark A Deeg, Naga Chalasani, Thomas A Hardy, Christof M Kazda, Sreekumar G Pillai
LY2409021 is a glucagon receptor antagonist that was associated with hepatic steatosis and elevated aminotransferases in phase 2 diabetes studies. We investigated the relationship between selected genetic variants and hepatic steatosis and elevated alanine aminotransferases (ALTs) associated with LY2409021. Patients participated in a 6-week placebo-controlled trial (I1R-MC-GLDI [GLDI], n = 246) and a 52-week placebo- and active comparator-controlled trial (I1R-MC-GLDJ [GLDJ], n = 158). GLDJ had endpoints at 6 months, including measures of hepatic fat fraction (HFF) by magnetic resonance imaging...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29760789/higher-cardiometabolic-risk-in-idiopathic-versus-autoimmune-type-1-diabetes-a-retrospective-analysis
#15
Valentina Guarnotta, Enrica Vigneri, Giuseppe Pillitteri, Alessandro Ciresi, Giuseppe Pizzolanti, Carla Giordano
Background: Idiopathic type 1 diabetes mellitus (IDM) is characterized by an onset with insulinopenia and ketoacidosis with negative β-cell autoimmunity markers and lack of association with HLA. The aim of the study is to compare the clinical and metabolic parameters, the macro and microvascular complications, the adipose tissue dysfunction and the insulin secretion and sensitivity indexes in patients with IDM and autoimmune type 1 diabetes mellitus (ADM) at clinical onset. Methods: Thirty patients with IDM and 30 with ADM, matched for age and gender, were retrospectively analyzed...
2018: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/29760423/simultaneous-amelioratation-of-colitis-and-liver-injury-in-mice-by-bifidobacterium-longum-lc67-and-lactobacillus-plantarum-lc27
#16
Se-Eun Jang, Jin-Ju Jeong, Jeon-Kyung Kim, Myung Joo Han, Dong-Hyun Kim
Disturbances in the gut microbiota composition are associated with chronic inflammatory diseases of the intestine and the liver. In a preliminary study, Lactobacillus plantarum LC27 and Bifidobacterium longum LC67 could inhibit Escherichia coli growth and lipopolysaccharide-induced NF-κB activation linked to gut inflammation. Here, we investigated their effects on 2,4,6-trinitrobenzesulfonic acid (TNBS)-induced colitis and liver damage in mice. First, oral administration of LC27 or LC67 (1 × 109 CFU/mouse) inhibited TNBS-induced colon shortening [F(5,30) = 100...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29760045/gfpt2-expressing-cancer-associated-fibroblasts-mediate-metabolic-reprogramming-in-human-lung-adenocarcinoma
#17
Weiruo Zhang, Gina Bouchard, Alice Yu, Majid Shafiq, Mehran Jamali, Joseph B Shrager, Kelsey Ayers, Shaimaa Bakr, Andrew J Gentles, Maximilian Diehn, Andrew Quon, Robert B West, Viswam Nair, Matt van de Rijn, Sandy Napel, Sylvia K Plevritis
Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer (NSCLC) together with 18FDG-positron emission tomography scans, which provide a clinical measure of glucose uptake. Tumors with higher glucose uptake were functionally enriched for molecular processes associated with invasion in adenocarcinoma (AD) and cell growth in squamous cell carcinoma (SCC)...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29758351/development-of-microreactors-with-surface-immobilized-biocatalysts-for-continuous-transamination
#18
Nataša Miložič, Gorazd Stojkovič, Andreas Vogel, Dominique Bouwes, Polona Žnidaršič-Plazl
The industrial importance of optically pure compounds has thrown a spotlight on ω-transaminases that have shown a high potential for the synthesis of bioactive compounds with a chiral amine moiety. The implementation of biocatalysts in industrial processes relies strongly on fast and cost effective process development, including selection of a biocatalyst form and the strategy for its immobilization. Here, microscale reactors with selected surface-immobilized amine-transaminase (ATA) in various forms are described as platforms for high-throughput process development...
May 11, 2018: New Biotechnology
https://www.readbyqxmd.com/read/29757899/determination-of-minimal-hemoglobin-level-necessary-for-normothermic-porcine-ex-situ-liver-perfusion
#19
Mariusz Bral, Boris Gala-Lopez, Aducio Thiesen, Sanaz Hatami, David L Bigam, Darren M Freed, A M James Shapiro
BACKGROUND: In current studies of ex situ liver perfusion there exists considerable variability in perfusate composition, including the type of oxygen carrier. Herein we aim to clarify the minimal hemoglobin level necessary during normothermic porcine ex situ liver perfusion. METHODS: Livers procured from 35- 45 Kg domestic pigs were connected to our experimental ex situ circuit (n=10). In the treatment group, perfusate was sequentially diluted hourly to predetermined hemoglobin levels...
May 7, 2018: Transplantation
https://www.readbyqxmd.com/read/29756394/prognostic-impact-of-the-pretreatment-aspartate-transaminase-alanine-transaminase-ratio-in-patients-treated-with-first-line-systemic-tyrosine-kinase-inhibitor-therapy-for-metastatic-renal-cell-carcinoma
#20
Minyong Kang, Jiwoong Yu, Hyun Hwan Sung, Hwang Gyun Jeon, Byong Chang Jeong, Se Hoon Park, Seong Soo Jeon, Hyun Moo Lee, Han Yong Choi, Seong Il Seo
OBJECTIVES: To examine the prognostic role of the pretreatment aspartate transaminase/alanine transaminase or De Ritis ratio in patients with metastatic renal cell carcinoma receiving first-line systemic tyrosine kinase inhibitor therapy. METHODS: We retrospectively searched the medical records of 579 patients with metastatic renal cell carcinoma who visited Samsung Medical Center, Seoul, Korea, from January 2001 through August 2016. After excluding 210 patients, we analyzed 360 patients who received first-line tyrosine kinase inhibitor therapy...
May 13, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
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