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https://www.readbyqxmd.com/read/28428362/hepatic-lipid-accumulation-cause-and-consequence-of-dysregulated-glucoregulatory-hormones
#1
Caroline E Geisler, Benjamin Jennings Renquist
Fatty liver can be diet, endocrine, genetic, viral, or drug induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic, and ketogenic genes, promoting hyperglycemia, hyperlipidemia, and ketosis. The typical hormonal environment in fatty liver disease consists of hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency, and elevated sympathetic tone...
April 20, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28428276/micellar-delivery-of-mir-34a-modulator-rubone-and-paclitaxel-in-resistant-prostate-cancer
#2
Di Wen, Yang Peng, Feng Lin, Rakesh K Singh, Ram I Mahato
Treatment of prostate cancer with paclitaxel (PTX) often fails due to development of chemoresistance caused by downregulation of the tumor suppressor gene miR-34a. In this study, we demonstrate that co-delivery of PTX and 2'-hydroxy-2,4,4',5,6'-pentamethoxychalcone (termed rubone) drives upregulation of miR-34a and chemosensitizes PTX-resistant prostate cancer cells, killing both cancer stem-like cells (CSCs) and bulk tumor cells. Rubone upregulated miR-34a and reversed its downstream target genes in DU145-TXR and PC3-TXR cells...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427560/stress-adaptive-response-in-ovarian-cancer-drug-resistance-role-of-trap1-in-oxidative-metabolism-driven-inflammation
#3
Maria Rosaria Amoroso, Danilo Swann Matassa, Ilenia Agliarulo, Rosario Avolio, Francesca Maddalena, Valentina Condelli, Matteo Landriscina, Franca Esposito
Metabolic reprogramming is one of the most frequent stress-adaptive response of cancer cells to survive environmental changes and meet increasing nutrient requirements during their growth. These modifications involve cellular bioenergetics and cross talk with surrounding microenvironment, in a dynamic network that connect different molecular processes, such as energy production, inflammatory response, and drug resistance. Even though the Warburg effect has long been considered the main metabolic feature of cancer cells, recent reports identify mitochondrial oxidative metabolism as a driving force for tumor growth in an increasing number of cellular contexts...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28427151/fine-tuning-of-vitamin-d-receptor-vdr-activity-by-post-transcriptional-and-post-translational-modifications
#4
REVIEW
Ondrej Zenata, Radim Vrzal
Vitamin D receptor (VDR) is a member of the nuclear receptor (NR) superfamily of ligand-activated transcription factors. Activated VDR is responsible for maintaining calcium and phosphate homeostasis, and is required for proper cellular growth, cell differentiation and apoptosis. The expression of both phases I and II drug-metabolizing enzymes is also regulated by VDR, therefore it is clinically important.Post-translational modifications of NRs have been known as an important mechanism modulating the activity of NRs and their ability to drive the expression of target genes...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426364/patterns-of-mood-and-personality-factors-and-associations-with-sti-hiv-related-drug-and-sex-risk-among-african-american-male-inmates
#5
Joy D Scheidell, Carl W Lejuez, Carol E Golin, Adaora A Adimora, David A Wohl, Larry D Keen, Michael Hammond, Selena Judon-Monk, Maria R Khan
BACKGROUND: Research on the association between antisocial personality disorder (ASPD) with comorbid mental disorders and sexually transmitted infection (STI)/HIV risk among inmates is scant despite the high prevalence of psychopathology and of STI/HIV in this population. METHODS: We used baseline data from Project DISRUPT, a cohort study conducted among incarcerated African American men (n = 207), to measure associations between ASPD and STI/HIV risk. We also conducted latent class analyses (LCAs) to identify subgroups defined by ASPD with comorbid stress, depression, and borderline personality disorder symptoms and measured associations between latent class membership and STI/HIV risk...
June 7, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28423577/the-cyclin-like-protein-spy1-regulates-the-er%C3%AE-and-erk1-2-pathways-promoting-tamoxifen-resistance
#6
Rosa-Maria Ferraiuolo, Janice Tubman, Indrajit Sinha, Caroline Hamm, Lisa Ann Porter
The Ras/Raf/MEK/ERK pathway conveys growth factor and mitogen signalling to control the phosphorylation of a plethora of substrates regulating proliferation, survival, and migration. The Ras signalling pathway is frequently associated with poor prognosis and drug resistance in various cancers including those of the blood, breast and prostate. Activation of the downstream effector ERK does not always occur via a linear cascade of events; complicating the targeting of this pathway therapeutically. This work describes a novel positive feedback loop where the cell cycle regulatory factor Spy1 (RINGO; gene SPDYA) activates ERK1/2 in a MEK-independent fashion...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421257/histone-deacetylase-inhibitors-reverse-age-related-increases-in-side-effects-of-haloperidol-in-mice
#7
Janitza L Montalvo-Ortiz, Daniel W Fisher, Guadalupe Rodríguez, Deyu Fang, John G Csernansky, Hongxin Dong
BACKGROUND: Older patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility. METHODS: In this study, we treated young (2-3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects...
April 18, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28419659/making-visible-the-politics-and-ethics-of-alcohol-policy-research
#8
David Moore
Although research on alcohol policy has produced a huge international literature, alcohol research and policy itself-its cultural assumptions, methods, politics and ethics-has rarely been subject to critical analysis. In this article, I provide an appreciative review of an exception to this trend: Joseph Gusfield's 1981 classic, The Culture of Public Problems: Drinking-Driving and the Symbolic Order. I first outline Gusfield's argument that the 'problem of drinking-driving' is constructed as a 'drama of individualism' centring on the 'killer drunk'...
April 16, 2017: Addiction
https://www.readbyqxmd.com/read/28417960/normally-lethal-amino-acid-substitutions-suppress-an-ultramutator-dna-polymerase-%C3%AE-variant
#9
Daniel G Dennis, Jill McKay-Fleisch, Kaila Eitzen, Ian Dowsett, Scott R Kennedy, Alan J Herr
In yeast, the pol3-01,L612M double mutant allele, which causes defects in DNA polymerase delta (Pol δ) proofreading (pol3-01) and nucleotide selectivity (pol3-L612M), confers an "ultramutator" phenotype that rapidly drives extinction of haploid and diploid MMR-proficient cells. Here, we investigate antimutator mutations that encode amino acid substitutions in Pol δ that suppress this lethal phenotype. We find that most of the antimutator mutations individually suppress the pol3-01 and pol3-L612M mutator phenotypes...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28416508/hus-and-atypical-hus
#10
T Sakari Jokiranta
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by intravascular hemolysis, thrombocytopenia, and acute kidney failure. HUS is usually categorized as typical, caused by shiga-toxin producing E. coli (STEC) infection, atypical HUS (aHUS), usually caused by uncontrolled complement activation, or secondary HUS with a coexisting disease. In recent years, a general understanding of the pathogenetic mechanisms driving HUS has increased. Typical (i.e. STEC-HUS) follows a gastrointestinal infection with STEC, while aHUS is associated primarily with mutations or autoantibodies leading to dysregulated complement activation...
April 17, 2017: Blood
https://www.readbyqxmd.com/read/28415628/gut-microbiota-drives-the-attenuation-of-dextran-sulphate-sodium-induced-colitis-by-huangqin-decoction
#11
Yang Yang, Gang Chen, Qian Yang, Juan Ye, Xueting Cai, Pamo Tsering, Xiaolan Cheng, Chunping Hu, Shuangquan Zhang, Peng Cao
The gut microbiota, including probiotics and pathogenic microorganisms, is involved in ulcerative colitis (UC) by regulating pathogenic microorganisms and the production of intestinal mucosal antibodies. Huangqin decoction (HQD), a traditional Chinese formula chronicled in the Shanghan lun, has been recognized as an effective drug for UC, owing to its anti-inflammatory and anti-oxidative properties. In the present study, we investigated whether HQD ameliorates dextran sulphate sodium (DSS)-induced colitis through alteration of the gut microbiota...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414173/affinity-interactions-drive-post-implantation-drug-filling-even-in-the-presence-of-bacterial-biofilm
#12
Erika L Cyphert, Sean T Zuckerman, Horst A von Recum, Julius N Korley
Current post-operative standard of care for surgical procedures, including device implantations, dictates prophylactic antimicrobial therapy, but a percentage of patients still develop infections. Systemic antimicrobial therapy needed to treat such infections can lead to downstream tissue toxicities and generate drug-resistant bacteria. To overcome issues associated with systemic drug administration, a polymer incorporating specific drug affinity has been developed with the potential to be filled or refilled with antimicrobials, post-implantation, even in the presence of bacterial biofilm...
April 13, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28413720/direct-imaging-of-app-proteolysis-in-living-cells
#13
Niccoló Parenti, Ambra Del Grosso, Claudia Antoni, Marco Cecchini, Renato Corradetti, Francesco S Pavone, Martino Calamai
Alzheimer's disease is a multifactorial disorder caused by the interaction of genetic, epigenetic and environmental factors. The formation of cytotoxic oligomers consisting of Aβ peptide is widely accepted as being one of the main key events triggering the development of Alzheimer's disease. Aβ peptide production results from the specific proteolytic processing of the amyloid precursor protein (APP). Deciphering the factors governing the activity of the secretases responsible for the cleavage of APP is still a critical issue...
2017: PeerJ
https://www.readbyqxmd.com/read/28413099/second-line-biologic-therapy-optimization-in-rheumatoid-arthritis-psoriatic-arthritis-and-ankylosing-spondylitis
#14
REVIEW
Fabrizio Cantini, Laura Niccoli, Carlotta Nannini, Emanuele Cassarà, Olga Kaloudi, Ennio Giulio Favalli, Andrea Becciolini, Maurizio Benucci, Francesca Li Gobbi, Serena Guiducci, Rosario Foti, Marta Mosca, Delia Goletti
OBJECTIVE: The Italian board for the TAilored BIOlogic therapy (ITABIO) reviewed the most consistent literature to indicate the best strategy for the second-line biologic choice in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). METHODS: Systematic review of the literature to identify English-language articles on efficacy of second-line biologic choice in RA, PsA, and ankylosing spondylitis (AS). Data were extracted from available randomized, controlled trials, national biologic registries, national healthcare databases, post-marketing surveys, and open-label observational studies...
March 22, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28412576/the-occurrence-of-alcohol-drugs-by-toxicological-examination-of-selected-drivers-in-hong-kong
#15
Wing-Chi Cheng, Kwok-Leung Dao
The study is to investigate the extent of alcohol/drug(s) use among selected drivers, i.e. fatally injured drivers from traffic accidents (2006-2015), drink driving (2006-2015) and drug driving (2010-2015) cases, in Hong Kong. Between 2006 and 2015, specimens from a total of 223 fatally injured drivers were received for toxicological examination. Except for one driver, all other drivers with positive findings were male. Alcohol and/or drugs were detected in 60 (27%) cases where alcohol alone was detected in 40 cases (18%) while drugs with/without alcohol were detected in 20 cases (9%)...
April 2, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28412575/the-role-of-illicit-licit-and-designer-drugs-in-the-traffic-in-hungary
#16
László Institóris, Előd Hidvégi, Adrienn Dobos, Éva Sija, Éva M Kereszty, László Balázs Tajti, Gábor Pál Somogyi, Tibor Varga
The aim of this study was to investigate the prevalence and pattern of psychoactive substances among suspected DUID (Driving Under the Influence of Drugs) drivers in Hungary in 2014 and 2015. Blood and/or urine samples of 1252 suspected drivers (600 in 2014 and 652 in 2015) were analyzed for classical illicit and licit drugs, stimulant designer drugs (SDDs), and for synthetic cannabinoids, with 78.3% and 79.6% positive cases for at least one substance in 2014, and 2015, respectively. Impairment was proven in 39...
April 3, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28412251/c-myc-antagonises-the-transcriptional-activity-of-the-androgen-receptor-in-prostate-cancer-affecting-key-gene-networks
#17
Stefan J Barfeld, Alfonso Urbanucci, Harri M Itkonen, Ladan Fazli, Jessica L Hicks, Bernd Thiede, Paul S Rennie, Srinivasan Yegnasubramanian, Angelo M DeMarzo, Ian G Mills
Prostate cancer (PCa) is the most common non-cutaneous cancer in men. The androgen receptor (AR), a ligand-activated transcription factor, constitutes the main drug target for advanced cases of the disease. However, a variety of other transcription factors and signaling networks have been shown to be altered in patients and to influence AR activity. Amongst these, the oncogenic transcription factor c-Myc has been studied extensively in multiple malignancies and elevated protein levels of c-Myc are commonly observed in PCa...
April 5, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28411561/selective-attention-moderates-the-relationship-between-attentional-capture-by-signals-of-nondrug-reward-and-illicit-drug-use
#18
Lucy Albertella, Jan Copeland, Daniel Pearson, Poppy Watson, Reinout W Wiers, Mike E Le Pelley
BACKGROUND: The current study examined whether cognitive control moderates the association between (non-drug) reward-modulated attentional capture and use of alcohol and other drugs (AOD). METHODS: Participants were 66 university students who completed an assessment including questions about AOD use, a visual search task to measure value-modulated attentional capture, and a goal-directed selective attention task as a measure of cognitive control. RESULTS: The association between the effect of value-modulated attentional capture and illicit drug use was moderated by level of cognitive control...
March 30, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28410614/factors-associated-with-high-utilization-in-a-safety-net-setting
#19
Julia Bell, Sara Turbow, Maura George, Mohammed K Ali
BACKGROUND: Patients with frequent hospital readmissions, or high-utilizer patients (HUPs), are a major driver of rising healthcare costs in the United States. This group has a significant burden of medical illness, but less is known about whether or how social determinants of health may drive their increased healthcare use and poor health outcomes. Our study aimed to define the population of HUPs at a large, safety-net hospital system, to understand how these patients differ from patients who are not HUPs, and to analyze how their demographic, medical, and social factors contribute to their healthcare use and mortality rates...
April 14, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28409675/the-relation-between-driving-violations-and-health-promotion-behaviors-among-undergraduate-students-self-report-of-road-behavior
#20
Liat Korn, Yossi Weiss, Tova Rosenbloom
Introduction The purposes of this study are to characterize the Israeli undergraduate students' driving violations in the terms of Problem Behavior Theory and to identify if there is any relationship between driving violations and health risk behaviors, daring behaviors, excitement-seeking, and health promotion behaviors. Methods This study is based on a structured self-reported anonymous questionnaire distributed to undergraduate students in an academic institution. The sample included 533 undergraduate students (374 females and 159 males)...
April 14, 2017: Traffic Injury Prevention
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