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https://www.readbyqxmd.com/read/27923594/synthesis-of-the-cyp24a1-major-metabolite-of-2%C3%AE-2-tetrazol-2-yl-ethyl-1%C3%AE-25-dihydroxyvitamin-d3
#1
REVIEW
Masashi Takano, Kaori Yasuda, Eri Tohyama, Erika Higuchi, Toshiyuki Sakaki, Atsushi Kittaka
Previously, we found that 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D3 (AH-1) showed higher osteocalcin promoter transactivation activity in human osteosarcoma (HOS) cells and a greater therapeutic effect on ovariectomized (OVX) rats for enhancing bone mineral density than those of 1α,25(OH)2D3 without hypercalcemic side effects in vivo. Although CYP24A1 catalyzes multi-step oxidations toward the CD-ring side chain of the active vitamin D3 [1α,25(OH)2D3], the CYP24A1-dependent metabolism of AH-1 tended to stop at the first step hydroxylation at the C24-position of AH-1...
December 3, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27923450/strategies-to-use-micrornas-as-therapeutic-targets
#2
REVIEW
Jan Krützfeldt
MicroRNAs (miRNAs) provide a unique mechanism of gene regulation and play a key role in different pathologies ranging from metabolic diseases to cancer. miRNAs can impact biological function as either suppressors of gene expression when their expression levels are enhanced in a disease state or they can cause upregulation of gene expression when their expression levels are reduced. Therefore both gain- and loss-of- function strategies are needed to fully exploit their therapeutic potential. miRNA research first focused on inhibition of single miRNAs using oligonucleotide inhibitors...
October 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/27923373/microbial-production-of-next-generation-stevia-sweeteners
#3
Kim Olsson, Simon Carlsen, Angelika Semmler, Ernesto Simón, Michael Dalgaard Mikkelsen, Birger Lindberg Møller
BACKGROUND: The glucosyltransferase UGT76G1 from Stevia rebaudiana is a chameleon enzyme in the targeted biosynthesis of the next-generation premium stevia sweeteners, rebaudioside D (Reb D) and rebaudioside M (Reb M). These steviol glucosides carry five and six glucose units, respectively, and have low sweetness thresholds, high maximum sweet intensities and exhibit a greatly reduced lingering bitter taste compared to stevioside and rebaudioside A, the most abundant steviol glucosides in the leaves of Stevia rebaudiana...
December 7, 2016: Microbial Cell Factories
https://www.readbyqxmd.com/read/27921195/new-developments-in-the-pharmacodynamics-and-pharmacokinetics-of-combination-of-chinese-medicine-and-western-medicine
#4
REVIEW
Di Liu, Xiao-Chun Liang
It is very common to use Chinese medicine (CM) combined with Western medicine (WM) in clinical practice. The appropriate combination of CM with WM can reduce toxicity and enhance effects in order to make the best use of advantages and bypass the disadvantages. However, an inappropriate combination can not only affect the curative effect but even cause death. Therefore, strengthening the complementary advantages of the CM and WM to improve the therapeutic efficacy and reduce side effects has become an important research topic of clinical medicine and pharmacy...
December 5, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27919945/the-leloir-pathway-of-galactose-metabolism-a-novel-therapeutic-target-for-hepatocellular-carcinoma
#5
Manshu Tang, Enoabasi Etokidem, Kent Lai
Hepatocellular carcinoma (HCC) is one of the most lethal types of cancer worldwide, with poor prognosis and limited treatments. In order to identify novel therapeutic targets that will lead to development of effective therapies with manageable side effects, we tested the hypothesis that knocking-down galactokinase (GALK1) or galactose-1 phosphate uridylyltransferase (GALT) gene expression would control the growth of cultured hepatoma cells. Our results showed small interfering RNA (siRNA) against GALK1 or GALT inhibited the growth of HepG2 cells in culture...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27916644/targeted-mitochondrial-uncoupling-beyond-ucp1-the-fine-line-between-death-and-metabolic-health
#6
REVIEW
Mario Ost, Susanne Keipert, Susanne Klaus
In the early 1930s, the chemical uncoupling agent 2,4-dinitrophenol (DNP) was promoted for the very first time as a powerful and effective weight loss pill but quickly withdrawn from the market due to its lack of tissue-selectivity with resulting dangerous side effects, including hyperthermia and death. Today, novel mitochondria- or tissue-targeted chemical uncouplers with higher safety and therapeutic values are under investigation in order to tackle obesity, diabetes and fatty liver disease. Moreover, in the past 20 years, transgenic mouse models were generated to understand the molecular and metabolic consequences of targeted uncoupling, expressing functional uncoupling protein 1 (UCP1) ectopically in white adipose tissue or skeletal muscle...
December 1, 2016: Biochimie
https://www.readbyqxmd.com/read/27916640/ppar-agonists-could-tissue-targeting-pave-the-way
#7
Anne Bugge, Dorte Holst
Over the last couple of decades, the PPAR family of transcription factors has received much attention from the pharmaceutical industry due to their profound ability to improve glucose and lipid metabolism upon agonist activation. However, more recently the interest in these nuclear receptors has faded because several clinical trials have shown that it is difficult to develop a ligand that significantly ameliorates glucose and lipid metabolism disorders without concomitantly inducing unacceptable side-effects...
December 1, 2016: Biochimie
https://www.readbyqxmd.com/read/27915186/role-of-the-purinergic-signaling-in-epilepsy
#8
REVIEW
Marek Cieślak, Andrzej Wojtczak, Michał Komoszyński
Adenine nucleotides and adenosine are signaling molecules that activate purinergic receptors P1 and P2. Activation of A1 adenosine receptors has an anticonvulsant action, whereas activation of A2A receptors might initiate seizures. Therefore, a significant limitation to the use of A1 receptor agonists as drugs in the CNS might be their peripheral side effects. The anti-epileptic activity of adenosine is related to its increased concentration outside the cell. This increase might result from the inhibition of the equilibrative nucleoside transporters (ENTs)...
September 22, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27915048/protective-effects-of-green-tea-and-its-main-constituents-against-natural-and-chemical-toxins-a-comprehensive-review
#9
REVIEW
Maryam Rameshrad, Bibi Marjan Razavi, Hossein Hosseinzadeh
Toxins are natural or chemical poisonous substances with severe side effects on health. Humans are generally exposed by widespread toxic contaminations via air, soil, water, food, fruits and vegetables. Determining a critical antidote agent with extensive effects on different toxins is an ultimate goal for all toxicologists. Traditional medicine is currently perceived as a safe and natural approach against toxins. In this regard, we focused on the protective effects of green tea (Camellia sinensis) and its main components such as catechin, epicatechin, epicatechin gallate, gallocatechin, epigallocatechin and epigallocatechin gallate as a principal source of antioxidants against both natural and chemical toxins...
November 30, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27914698/under-prescription-of-statins-in-patients-with-non-alcoholic-fatty-liver-disease
#10
M Del Ben, F Baratta, L Polimeni, D Pastori, L Loffredo, M Averna, F Violi, F Angelico
BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with high cardiovascular risk. Management of dyslipidaemia plays a pivotal role in the prevention of CV events and statins have proved to be safe in these patients. However, in everyday clinical practice statin prescription is sometimes limited because of the concern of physicians about side-effects. The aim of the study was to investigate if the presence of NAFLD affects the prescription of lipid-lowering treatment in a large series of patients with cardio-metabolic disorders...
September 28, 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27912137/a-novel-continuous-two-phase-partitioning-bioreactor-operated-with-polymeric-tubing-performance-validation-for-enhanced-biological-removal-of-toxic-substrates
#11
M Concetta Tomei, Domenica Mosca Angelucci, Andrew J Daugulis
A continuous two-phase partitioning bioreactor (C-TPPB), operated with coiled tubing made of the DuPont polymer Hytrel 8206, was tested for the bioremediation of 4-chlorophenol, as a model toxic compound. The tubing was immersed in the aqueous phase, with the contaminated water flowing tube-side, and an adapted microbial culture suspended in the bioreactor itself, with the metabolic demand of the cells creating a concentration gradient to cause the substrate to diffuse into the bioreactor for biodegradation...
November 29, 2016: Journal of Environmental Management
https://www.readbyqxmd.com/read/27906007/what-happens-to-cardiovascular-system-behind-the-undetectable-level-of-hiv-viremia
#12
REVIEW
Gabriella d'Ettorre, Giancarlo Ceccarelli, Paolo Pavone, Pietro Vittozzi, Gabriella De Girolamo, Ivan Schietroma, Sara Serafino, Noemi Giustini, Vincenzo Vullo
Despite the combined antiretroviral therapy has improved the length and quality of life of HIV infected patients, the survival of these patients is always decreased compared with the general population. This is the consequence of non-infectious illnesses including cardio vascular diseases. In fact large studies have indicated an increased risk of coronary atherosclerotic disease, myocardial infarction even in HIV patients on cART. In HIV infected patients several factors may contribute to the pathogenesis of cardiovascular problems: life-style, metabolic parameters, genetic predisposition, viral factors, immune activation, chronic inflammation and side effects of antiretroviral therapy...
April 27, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27904608/arnebia-euchroma-ointment-can-reduce-abdominal-fat-thickness-and-abdominal-circumference-of-overweight-women-a-randomized-controlled-study
#13
Mansour Siavash, Mohsen Naseri, Mojgan Rahimi
BACKGROUND: Obesity is a worldwide health problem which is associated with a lot of complications. One of these comorbidities is the metabolic syndrome that is in correlation with abdominal fat thickness and waist circumference. Various methods were used to reduce abdominal fat thickness such as liposuction. A noninvasive method is the topical agent. In this study, we investigated the effectiveness of Arnebia euchroma (AE) ointment on the abdominal fat thickness. MATERIALS AND METHODS: This study was a double-blind clinical trial which was done at the endocrinology clinic in Khorshid Hospital, Isfahan, Iran, in 2014...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27902848/topiramate-in-migraine-prevention-a-2016-perspective
#14
Stephen D Silberstein
BACKGROUND: In evidence-based guidelines published in 2000, topiramate was a third-tier migraine preventive with no scientific evidence of efficacy; recommendation for its use reflected consensus opinion and clinical experience. Its neurostabilizing activity, coupled with its favorable weight profile, made topiramate an attractive alternative to other migraine preventives that caused weight gain. When guidelines for migraine prevention in episodic migraine were published in 2012, topiramate was included as a first-line option based on double-blind, randomized controlled trials involving nearly 3000 patients...
November 30, 2016: Headache
https://www.readbyqxmd.com/read/27901061/inter-individual-variability-and-modeling-of-electrical-activity-a-possible-new-approach-to-explore-cardiac-safety
#15
Jean-Yves Le Guennec, Jérôme Thireau, Aude Ouillé, Julien Roussel, Jérôme Roy, Serge Richard, Sylvain Richard, Eric Martel, Pascal Champéroux
Safety pharmacology aims to predict rare side effects of new drugs. We explored whether rare pro-arrhythmic effects could be linked to the variability of the effects of these drugs on ion currents and whether taking into consideration this variability in computational models could help to better detect and predict cardiac side effects. For this purpose, we evaluated how intra- and inter-individual variability influences the effect of hERG inhibition on both the action potential duration and the occurrence of arrhythmias...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900284/effect-of-pantethine-on-ovarian-tumor-progression-and-choline-metabolism
#16
Marie-France Penet, Balaji Krishnamachary, Flonne Wildes, Yelena Mironchik, Delia Mezzanzanica, Franca Podo, Max de Reggi, Bouchra Gharib, Zaver M Bhujwalla
Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here, we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27899308/insight-gained-from-genome-wide-interaction-and-enrichment-analysis-on-weight-gain-during-citalopram-treatment
#17
Henrik Thyge Corfitsen, Antonio Drago
Weight gain is a possible side effect of the pharmacological antidepressant treatments. Defining antidepressant prescriptions based on personal genetic makeups would decrease the risk of weight gain and increase the quality of the current antidepressant pharmacological treatments. 643 depressed, citalopram treated individuals with available clinical and genome-wide genetic information were investigated to identify the molecular pathways associated with weight gain. 111 individuals experienced weight gain during citalopram treatment...
November 27, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27898586/an-update-on-sodium-glucose-co-transporter-2-inhibitors-for-the-treatment-of-diabetes-mellitus
#18
Daniel S Hsia, Owen Grove, William T Cefalu
PURPOSE OF REVIEW: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are the newest class of oral antihyperglycemic agents that have been approved for the treatment of diabetes mellitus. Over the past year, there have been significant developments in both the safety and efficacy of this class of medications that are presented in this review. RECENT FINDINGS: Apart from data on the glucose-lowering effect of SGLT2 inhibitors, other metabolic benefits have been demonstrated for this class of medications...
November 24, 2016: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/27898069/clozapine-modifies-the-differentiation-program-of-human-adipocytes-inducing-browning
#19
E Kristóf, Q-M Doan-Xuan, A K Sárvári, Á Klusóczki, P Fischer-Posovszky, M Wabitsch, Z Bacso, P Bai, Z Balajthy, L Fésüs
Administration of second-generation antipsychotic drugs (SGAs) often leads to weight gain and consequent cardio-metabolic side effects. We observed that clozapine but not six other antipsychotic drugs reprogrammed the gene expression pattern of differentiating human adipocytes ex vivo, leading to an elevated expression of the browning marker gene UCP1, more and smaller lipid droplets and more mitochondrial DNA than in the untreated white adipocytes. Laser scanning cytometry showed that up to 40% of the differentiating single primary and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes had the characteristic morphological features of browning cells...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27897267/increasing-bmi-is-associated-with-reduced-expression-of-p-glycoprotein-abcb1-gene-in-the-human-brain-with-a-stronger-association-in-african-americans-than-caucasians
#20
J Vendelbo, R H Olesen, J K Lauridsen, J Rungby, J E Kleinman, T M Hyde, A Larsen
The efflux pump, p-glycoprotein, controls bioavailability and excretion of pharmaceutical compounds. In the blood-brain barrier, p-glycoprotein regulates the delivery of pharmaceutical substances to the brain, influencing efficacy and side effects for some drugs notably antipsychotics. Common side effects to antipsychotics include obesity and metabolic disease. Polymorphisms in the ABCB1 gene coding for p-glycoprotein are associated with more severe side effects to neuro-pharmaceuticals as well as weight gain, indicating a potential link between p-glycoprotein function and metabolic regulation...
November 29, 2016: Pharmacogenomics Journal
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