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https://www.readbyqxmd.com/read/28087278/prolyl-trna-synthetase-inhibition-promotes-cell-death-in-sk-mel-2%C3%A2-cells-through-gcn2-atf4-pathway-activation
#1
Takeo Arita, Megumi Morimoto, Yukiko Yamamoto, Hitoshi Miyashita, Satoshi Kitazawa, Takaharu Hirayama, Sou Sakamoto, Kazumasa Miyamoto, Ryutaro Adachi, Misa Iwatani, Takahito Hara
Protein translation is highly activated in cancer tissues through oncogenic mutations and amplifications, and this can support survival and aberrant proliferation. Therefore, blocking translation could be a promising way to block cancer progression. The process of charging a cognate amino acid to tRNA, a crucial step in protein synthesis, is mediated by tRNA synthetases such as prolyl tRNA synthetase (PRS). Interestingly, unlike pan-translation inhibitors, we demonstrated that a novel small molecule PRS inhibitor (T-3861174) induced cell death in several tumor cell lines including SK-MEL-2 without complete suppression of translation...
January 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28069654/reduced-chance-of-hearing-loss-associated-with-therapeutic-drug-monitoring-of-aminoglycosides-in-the-treatment-of-multidrug-resistant-tuberculosis
#2
R van Altena, J A Dijkstra, M E van der Meer, J F Borjas Howard, J G W Kosterink, D van Soolingen, T S van der Werf, J W C Alffenaar
Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our Tuberculosis Center, we have employed therapeutic drug monitoring (TDM) targeting pre-set pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto-)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of TB patients treated with amikacin or kanamycin in the period 2000 - 2012.Patients with culture-confirmed multi- or extensively drug resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study...
January 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28063226/enhancing-physical-activity-and-reducing-obesity-through-smartcare-and-financial-incentives-a-pilot-randomized-trial
#3
Dong Wook Shin, Jae Moon Yun, Jung-Hyun Shin, Hyuktae Kwon, Hye Yeon Min, Hee-Kyung Joh, Won Joo Chung, Jin Ho Park, Kee-Taig Jung, BeLong Cho
OBJECTIVE: A pilot randomized trial assessed the feasibility and effectiveness of an intervention combining Smartcare (activity tracker with a smartphone application) and financial incentives. METHODS: A three-arm, open-label randomized controlled trial design involving traditional education, Smartcare, and Smartcare with financial incentives was involved in this study. The latter group received financial incentives depending on the achievement of daily physical activity goals (process incentive) and weight loss targets (outcome incentive)...
January 7, 2017: Obesity
https://www.readbyqxmd.com/read/28061687/new-targets-for-drug-treatment-of-obesity
#4
Georgios Valsamakis, Panagiota Konstantakou, George Mastorakos
Antiobesity medical management has shown unsatisfactory results to date in terms of efficacy, safety, and long-term maintenance of weight loss. This poor performance could be attributed to the complexity of appetite regulation mechanisms; the serious drug side effects; and, crucially, the lack of profile-matching treatment strategies and individualized, multidisciplinary follow-up. Nevertheless, antiobesity pharmacotherapy remains a challenging, exciting field of intensive scientific interest. According to the latest studies, the future of bariatric medicine lies in developing drugs acting at multiple levels of the brain-gut axis...
January 6, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28053881/effect-of-novel-dietary-supplement-on-metabolism-in%C3%A2-vitro-and-in%C3%A2-vivo
#5
Roger A Vaughan, Ailish C White, Jason R Beam, Nicholas P Gannon, Randi Garcia-Smith, Roy M Salgado, Marco Bisoffi, Kristina A Trujillo, Carole A Conn, Christine M Mermier
Obesity is an increasingly prevalent and preventable morbidity with multiple behavioral, surgical and pharmacological interventions currently available. Commercial dietary supplements are often advertised to stimulate metabolism and cause rapid weight and/or fat loss, although few well-controlled studies have demonstrated such effects. We describe a commercially available dietary supplement (purportedly containing caffeine, catechins, and other metabolic stimulators) on resting metabolic rate in humans, and on metabolism, mitochondrial content, and related gene expression in vitro...
January 2017: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/28053040/disruption-of-glucagon-like-peptide-1-signaling-in-sim1-neurons-reduces-physiological-and-behavioral-reactivity-to-acute-and-chronic-stress
#6
Sriparna Ghosal, Amy E B Packard, Parinaz Mahbod, Jessica M McKlveen, Randy J Seeley, Brent Myers, Yvonne Ulrich-Lai, Eric P Smith, David A D'Alessio, James P Herman
: Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1)-mediated paraventricular hypothalamic circuit coordinating the global stress response. The GLP-1 receptor (Glp1r) in mice was knocked down in neurons expressing single-minded 1, a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with single-minded 1-mediated Glp1r knockdown had reduced hypothalamic-pituitary-adrenal axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28049662/gut-permeability-is-related-to-body-weight-fatty-liver-disease-and-insulin-resistance-in-obese-individuals-undergoing-weight-reduction
#7
Antje Damms-Machado, Sandrine Louis, Anna Schnitzer, Valentina Volynets, Andreas Rings, Maryam Basrai, Stephan C Bischoff
BACKGROUND: Obesity and associated metabolic disorders are related to impairments of the intestinal barrier. OBJECTIVE: We examined lactulose:mannitol (Lac:Man) permeability in obese individuals with and without liver steatosis undergoing a weight-reduction program to test whether an effective weight-loss program improves gut barrier function and whether obese patients with or without liver steatosis differ in this function. DESIGN: Twenty-seven adult, nondiabetic individuals [mean ± SD body mass index (BMI; in kg/m(2)): 43...
January 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28048529/tu-h-campus-tep2-02-flash-irradiation-improves-the-therapeutic-index-following-gi-tract-irradiation
#8
E Schueler, S Trovati, G King, F Lartey, M Rafat, B Loo, P Maxim
PURPOSE: To investigate and characterize the radiobiological effectiveness of very high dose rate radiotherapy (FLASH) compared to conventional irradiation in an in vivo model. METHODS: The gastrointestinal (GI) tract of C57BL/6 mice were irradiated with doses ranging between 10 and 18 Gy using a custom stereotactic jig. A Varian Clinac 21EX was modified to allow dose rates ranging from 0.05 to 240 Gy/s at the position of the mirror. With the gantry at 180 degrees, the jig holding the individual animals was placed above the mirror to take advantage of the reduced source to target distance...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28048032/su-f-j-63-abdominal-diameter-changes-in-children-during-volumetric-modulated-arc-therapy-vmat-is-re-planning-needed
#9
F Guerreiro, G Janssens, E Seravalli, B Raaymakers
PURPOSE: To investigate the dosimetric impact of daily changes in patient's diameter, due to weight gain/loss and air in the bowel, based on CBCT information during radiotherapy treatment of pediatric abdominal tumors. METHODS: 10 pediatric patients with neuroblastoma (n=6) and Wilms' (n=4) tumors were included. Available CBCTs were affinely registered to the planning CT for daily set-up variations corrections. A density override approach assigning air-density to the random air pockets and water-density to the remaining anatomy was used to determine the CBCT and CT dose...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28045548/vitamin-d-reduces-colitis-and-inflammation-associated-colorectal-cancer-in-mice-independent-of-nod2
#10
Ihsan Elimrani, Jamie Koenekoop, Serge Dionne, Valerie Marcil, Edgar Delvin, Emile Levy, Ernest G Seidman
Inflammatory bowel disease (IBD) patients are at increased risk of developing colorectal cancer (CRC). Vitamin D (vD) induces NOD2 gene expression, enhancing immunity, while deficiency impairs intestinal epithelial integrity, increasing inflammation. This study investigated the effect of vD on CRC in colitis, and if preventive benefits are mediated via NOD2. Inflammation-associated CRC was induced by treating C57BL/6J and Nod2(-/-) mice with azoxymethane (AOM) and dextran sodium sulfate (DSS) cycles (×3). vD-deficient mice displayed more severe colitis compared to vD-supplemented mice, with greater weight loss, higher colitis activity index, increased colonic weight/length ratios, and lower survival rates...
January 3, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28042320/heparin-improves-bmsc-cell-therapy-anticoagulant-treatment-by-heparin-improves-the-safety-and-therapeutic-effect-of-bone-marrow-derived-mesenchymal-stem-cell-cytotherapy
#11
Li Liao, Bingzheng Shi, Heran Chang, Xiaoxia Su, Lichao Zhang, Chunsheng Bi, Yi Shuai, Xiaoyan Du, Zhihong Deng, Yan Jin
Systemic infusion of bone marrow-derived mesenchymal stem cells (BMSCs) has become a promising strategy for disease treatment and tissue regeneration. Strategies to enhance the efficiency of BMSC cell therapy are crucial to promote its clinical application. Here, we aimed to improve BMSC cell therapy by inhibiting the BMSC-induced coagulation reaction. Intravenous injection of gradient BMSCs into mice showed that BMSCs were not fully compatible with blood. Large doses of BMSCs induced a series of symptoms of respiratory failure and heart failure...
2017: Theranostics
https://www.readbyqxmd.com/read/28039715/identification-of-differential-pathways-in-papillary-thyroid-carcinoma-utilizing-pathway-co-expression-analysis
#12
Wei-Hai Qiu, Gui-Yan Chen, Lu Cui, Ting-Ming Zhang, Feng Wei, Yong Yang
PURPOSE: To identify differential pathways between papillary thyroid carcinoma (PTC) patients and normal controls utilizing a novel method which combined pathway with co-expression network. METHODS: The proposed method included three steps. In the first step, we conducted pretreatments for background pathways and gained representative pathways in PTC. Subsequently, a co-expression network for representative pathways was constructed using empirical Bayes (EB) approach to assign a weight value for each pathway...
November 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28039475/gpr120-a-potential-therapeutic-target-for-experimental-colitis-in-il-10-deficient-mice
#13
Jie Zhao, Honggang Wang, Peiliang Shi, Wenbo Wang, Ye Sun
It has been proved that interleukin-10-knockout (IL-10 KO) mice display the most similar characteristics to that of human Crohn's disease (CD). Docosahexaenoic acid (DHA) has well established beneficial effects on human and animal models health with potent anti-inflammatory effects with poorly understood mechanisms. This study was aimed at figuring out whether DHA could ameliorate the Crohn's colitis by activating GPR120 and whether GPR120 could be a potential therapeutic target for CD.16 week-old mice included in our present study were divided into three groups, WT group, IL-10 KO group and DHA group(IL-10 KO mice with DHA treatment, i...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035202/nonalcoholic-steatohepatitis-and-endpoints-in-clinical-trials
#14
William N Hannah, Dawn M Torres, Stephen A Harrison
Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in developed countries, and the rates of NAFLD continue to rise in conjunction with the obesity pandemic. While the majority of patients with isolated steatosis generally have a benign course, a diagnosis of nonalcoholic steatohepatitis (NASH) carries a significantly higher risk for progression of disease, cirrhosis, and death. Pharmacologic therapeutic interventions in NASH have largely proven to be ineffective or unappealing due to long-term side-effect profiles, and the majority of patients cannot achieve or sustain targeted weight loss goals, necessitating an urgent need for therapeutic trials and drug development...
December 2016: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28031776/glucagon-like-peptide-1-in-the-pathophysiology-and-pharmacotherapy-of-clinical-obesity
#15
REVIEW
Ananthi Anandhakrishnan, Márta Korbonits
Though the pathophysiology of clinical obesity is undoubtedly multifaceted, several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1 (GLP-1) signalling. Clinical studies assessing GLP-1 responses in normal weight and obese subjects suggest that weight gain may induce functional deficits in GLP-1 signalling that facilitates maintenance of the obesity phenotype. In addition, genetic studies implicate a possible role for altered GLP-1 signalling as a risk factor towards the development of obesity...
December 15, 2016: World Journal of Diabetes
https://www.readbyqxmd.com/read/28028356/sirtuins-and-nonalcoholic-fatty-liver-disease
#16
REVIEW
Fatiha Nassir, Jamal A Ibdah
Mammalian sirtuins are seven members belonging to the silent information regulator 2 family, a group of Class III histone/protein deacetylases. Sirtuins (SIRT 1-7) have different subcellular localization and function and they regulate cellular protein function through various posttranslational modifications. SIRT1 and 3, the most studied sirtuins, use the product of cellular metabolism nicotinamide adenine dinucleotide as a cofactor to post-translationally deacetylate cellular proteins and consequently link the metabolic status of the cell to protein function...
December 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28027950/dietfits-study-diet-intervention-examining-the-factors-interacting-with-treatment-success-study-design-and-methods
#17
Michael Stanton, Jennifer Robinson, Susan Kirkpatrick, Sarah Farzinkhou, Erin Avery, Joseph Rigdon, Lisa Offringa, John Trepanowski, Michelle Hauser, Jennifer Hartle, Rise Cherin, Abby C King, John P A Ioannidis, Manisha Desai, Christopher D Gardner
Numerous studies have attempted to identify successful dietary strategies for weight loss, and many have focused on Low-Fat vs. Low-Carbohydrate comparisons. Despite relatively small between-group differences in weight loss found in most previous studies, researchers have consistently observed relatively large between-subject differences in weight loss within any given diet group (e.g., ~25kg weight loss to ~5kg weight gain). The primary objective of this study was to identify predisposing individual factors at baseline that help explain differential weight loss achieved by individuals assigned to the same diet, particularly a pre-determined multi-locus genotype pattern and insulin resistance status...
December 24, 2016: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28025954/anti-inflammatory-effects-of-an-oxylipin-containing-lyophilised-biomass-from-a-microalga-in-a-murine-recurrent-colitis-model
#18
Javier Ávila-Román, Elena Talero, Azahara Rodríguez-Luna, Sofía García-Mauriño, Virginia Motilva
Diet and nutritional factors have emerged as possible interventions for inflammatory bowel diseases (IBD), which are characterised by chronic uncontrolled inflammation of the intestinal mucosa. Microalgal species are a promising source of n-3 PUFA and derived oxylipins, which are lipid mediators with a key role in the resolution of inflammation. The aim of the present study was to investigate the effects of an oxylipin-containing lyophilised biomass from Chlamydomonas debaryana on a recurrent 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis mice model...
December 27, 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/28011621/a-novel-mouse-model-to-study-image-guided-radiation-induced-intestinal-injury-and-preclinical-screening-of-radioprotectors
#19
Ioannis I Verginadis, Rahul Kanade, Brett Bell, Sravya Koduri, Edgar Ben-Josef, Constantinos Koumenis
Radiation is an important treatment modality for gastrointestinal tumors but intestinal injury is a common side effect. Here we describe a physiologically relevant model for studying the molecular determinants of radiation-induced intestinal damage and testing novel radioprotectors. The model employs a radiopaque marker implanted into the surface of the mouse jejunum, serving as a fiducial marker for precise radiation targeting. Mice were imaged with Cone-Beam CT (CBCT) and irradiated to the marked area using the Small Animal Radiation Research Platform (SARRP)...
December 23, 2016: Cancer Research
https://www.readbyqxmd.com/read/28009788/effect-of-load-carriage-on-upper-limb-performance
#20
Amir Hadid, Inbar Katz, Tal Haker, Gabi Zeilig, Ruth Defrin, Yoram Epstein, Amit Gefen
: Carrying heavy backpacks are often associated with shoulder discomfort or pain, loss of sensorimotor functions, and brachial plexus injuries that might hamper performance. Based on previous research, the cause of these symptoms could be tissue deformations of the brachial plexus and the subclavian artery caused by the shoulder straps. PURPOSE: To evaluate the changes in the upper extremity hemodynamic and neural function, and to assess how they are associated with brachial plexus tissue deformation during heavy load carriage...
December 22, 2016: Medicine and Science in Sports and Exercise
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