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https://www.readbyqxmd.com/read/28812250/miv-150-and-zinc-acetate-combination-provides-potent-and-broad-activity-against-hiv-1
#1
Olga Mizenina, Mayla Hsu, Ninochka Jean-Pierre, Meropi Aravantinou, Keith Levendosky, Gabriela Paglini, Thomas M Zydowsky, Melissa Robbiani, José A Fernández-Romero
We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG. The MZC gel was shown to be safe in a phase 1 clinical trial. Herein, we used in vitro approaches to study the antiviral properties of ZA and the MIV-150/ZA combination, compared to other NNRTIs...
August 15, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28811495/low-protein-induced-increases-in-fgf21-drive-ucp1-dependent-metabolic-but-not-thermoregulatory-endpoints
#2
Cristal M Hill, Thomas Laeger, Diana C Albarado, David H McDougal, Hans-Rudolf Berthoud, Heike Münzberg, Christopher D Morrison
Dietary protein restriction increases adipose tissue uncoupling protein 1 (UCP1), energy expenditure and food intake, and these effects require the metabolic hormone fibroblast growth factor 21 (FGF21). Here we test whether the induction of energy expenditure during protein restriction requires UCP1, promotes a resistance to cold stress, and is dependent on the concomitant hyperphagia. Wildtype, Ucp1-KO and Fgf21-KO mice were placed on control and low protein (LP) diets to assess changes in energy expenditure, food intake and other metabolic endpoints...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811361/chemoradiotherapy-resistance-in-colorectal-cancer-cells-is-mediated-by-wnt-%C3%AE-catenin-signaling
#3
Georg Emons, Melanie Spitzner, Sebastian Reineke, Janneke Möller, Noam Auslander, Frank Kramer, Yue Hu, Tim Beissbarth, Hendrik A Wolff, Margret Rave-Fränk, Elisabeth Heßmann, Jochen Gaedcke, B Michael Ghadimi, Steven Johnsen, Thomas Ried, Marian Grade
Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer (CRC). The Wnt-transcription factor, TCF7L2, is overexpressed in primary rectal cancers that are resistant to chemoradiotherapy (CRT) and TCF7L2 mediates resistance to CRT. However, it is unclear whether the resistance is mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Here, inhibition of β-catenin by siRNAs or a small molecule inhibitor (XAV-939) resulted in sensitization of CRC cells to CRT...
August 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28811343/comparative-genomics-of-escherichia-coli-isolated-from-skin-and-soft-tissue-and-other-extraintestinal-infections
#4
Amit Ranjan, Sabiha Shaik, Nishant Nandanwar, Arif Hussain, Sumeet K Tiwari, Torsten Semmler, Savita Jadhav, Lothar H Wieler, Munirul Alam, Rita R Colwell, Niyaz Ahmed
Escherichia coli, an intestinal Gram-negative bacterium, has been shown to be associated with a variety of diseases in addition to intestinal infections, such as urinary tract infections (UTIs), meningitis in neonates, septicemia, skin and soft tissue infections (SSTIs), and colisepticemia. Thus, for nonintestinal infections, it is categorized as extraintestinal pathogenic E. coli (ExPEC). It is also an opportunistic pathogen, causing cross infections, notably as an agent of zoonotic diseases. However, comparative genomic data providing functional and genetic coordinates for ExPEC strains associated with these different types of infections have not proven conclusive...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28811168/an-ontogenetic-perspective-on-symphyseal-fusion-occlusion-and-mandibular-loading-in-alpacas-vicugna-pacos
#5
Kristin K Stover, JoAnna Sidote, Susan H Williams
A primary hypothesis for the evolution of mandibular symphyseal fusion in some mammals is that it functions to resist loads incurred during routine mastication. Anecdotal support for this hypothesis is based on the fact that when the symphysis fuses, it typically does so early during postnatal ontogeny prior to or around the time of weaning. However, little is known about the process of fusion, particularly relative to feeding behaviors and the dynamics of mastication, including occlusion and masticatory loading...
June 17, 2017: Zoology: Analysis of Complex Systems, ZACS
https://www.readbyqxmd.com/read/28811163/climate-change-co2-and-defense-the-metabolic-redox-and-signaling-perspectives
#6
REVIEW
Graham Noctor, Amna Mhamdi
Ongoing human-induced changes in the composition of the atmosphere continue to stimulate interest in the effects of high CO2 on plants, but its potential impact on inducible plant defense pathways remains poorly defined. Recently, several studies have reported that growth at elevated CO2 is sufficient to induce defenses such as the salicylic acid pathway, thereby increasing plant resistance to pathogens. These reports contrast with evidence that defense pathways can be promoted by photorespiration, which is inhibited at high CO2...
August 12, 2017: Trends in Plant Science
https://www.readbyqxmd.com/read/28810911/outcomes-from-patients-with-presumed-drug-resistant-tuberculosis-in-five-reference-centers-in-brazil
#7
D M P Ramalho, P F C Miranda, M K Andrade, T Brígido, M P Dalcolmo, E Mesquita, C F Dias, A N Gambirasio, J Ueleres Braga, A Detjen, P P J Phillips, I Langley, P I Fujiwara, S B Squire, M M Oliveira, A L Kritski
BACKGROUND: The implementation of rapid drug susceptibility testing (DST) is a current global priority for TB control. However, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistant tuberculosis (pDR-TB) evaluated under field conditions in high burden countries. METHODS: Observational study of pDR-TB patients referred by primary and secondary health units. TB reference centers addressing DR-TB in five cities in Brazil. Patients age 18 years and older were eligible if pDR-TB, culture positive results for Mycobacterium tuberculosis and, if no prior DST results from another laboratory were used by a physician to start anti-TB treatment...
August 15, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28810535/curcumin-enhances-the-radiosensitivity-of-renal-cancer-cells-by-suppressing-nf-%C3%AE%C2%BAb-signaling-pathway
#8
Gang Li, Ziming Wang, Tie Chong, Jie Yang, Hongliang Li, Haiwen Chen
The radiation resistance of renal cell carcinoma (RCC) remains the primary obstacle to improve patient survival. This study aimed to investigate the effects of curcumin on the radiosensitivity of RCC cells. Human RCC cell (ACHN) was exposed to irradiation (IR) and/or curcumin treatment. Cell viability, DNA repair, cell cycle, and apoptosis, were evaluated by MTT, immunofluoresence staining and flow cytometry. Moreover, ACHN cells were xenografted into nude mice and subjected to IR and/or curcumin treatment...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28810024/effect-of-an-intensive-lifestyle-intervention-on-glycemic-control-in-patients-with-type-2-diabetes-a-randomized-clinical-trial
#9
Mette Yun Johansen, Christopher Scott MacDonald, Katrine Bagge Hansen, Kristian Karstoft, Robin Christensen, Maria Pedersen, Louise Seier Hansen, Morten Zacho, Anne-Sophie Wedell-Neergaard, Signe Tellerup Nielsen, Ulrik Wining Iepsen, Henning Langberg, Allan Arthur Vaag, Bente Klarlund Pedersen, Mathias Ried-Larsen
Importance: It is unclear whether a lifestyle intervention can maintain glycemic control in patients with type 2 diabetes. Objective: To test whether an intensive lifestyle intervention results in equivalent glycemic control compared with standard care and, secondarily, leads to a reduction in glucose-lowering medication in participants with type 2 diabetes. Design, Setting, and Participants: Randomized, assessor-blinded, single-center study within Region Zealand and the Capital Region of Denmark (April 2015-August 2016)...
August 15, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28809765/cyclin-dependent-kinase-5-modulates-the-p2x2a-receptor-channel-gating-through-phosphorylation-of-c-terminal-threonine-372
#10
Claudio Coddou, Rodrigo Sandoval, Patricio Castro, Pablo Lazcano, Maria José Hevia, Milos Rokic, Bradford Hall, Anita Terse, Christian Gonzalez-Billault, Ashok B Kulkarni, Stanko S Stojilkovic, Elias Utreras
The purinergic P2X2 receptor (P2X2R) is an adenosine triphosphate-gated ion channel widely expressed in the nervous system. Here, we identified a putative cyclin-dependent kinase 5 (Cdk5) phosphorylation site in the full-size variant P2X2aR (TPKH), which is absent in the splice variant P2X2bR. We therefore investigated the effects of Cdk5 and its neuronal activator, p35, on P2X2aR function. We found an interaction between P2X2aR and Cdk5/p35 by co-immunofluorescence and co-immunoprecipitation in HEK293 cells...
July 17, 2017: Pain
https://www.readbyqxmd.com/read/28809743/outcomes-for-cirrhotic-patients-with-hepatitis-c-virus-1b-treated-with-asunaprevir-and-daclatasvir-combination
#11
Akihiro Tamori, Hoang Hai, Sawako Uchida-Kobayashi, Masaru Enomoto, Ritsuzo Kozuka, Hiroyuki Motoyama, Etsushi Kawamura, Atsushi Hagihara, Yuga Teranishi, Kanako Yoshida, Hiroyasu Morikawa, Yoshiki Murakami, Norifumi Kawada
BACKGROUND: The efficacy and safety of asunaprevir + daclatasvir combination therapy for treatment of hepatitis C virus (HCV) in compensated cirrhotic patients was not fully evaluated in real-world. Outcomes were assessed in cirrhotic patients with sustained viral response (SVR). MATERIAL AND METHODS: A total of 145 patients without resistance-associated substitutions (RASs) at L31 and Y93 in the nonstructural protein 5A of HCV genotype 1b, consisting of 49 hepatic cirrhotic and 96 non-cirrhotic patients, were enrolled to the therapy...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28808690/the-hemagglutinin-esterase-fusion-glycoprotein-is-a-primary-determinant-of-the-exceptional-thermal-and-acid-stability-of-influenza-d-virus
#12
Jieshi Yu, Busha Hika, Runxia Liu, Zizhang Sheng, Ben M Hause, Feng Li, Dan Wang
Influenza D virus (IDV) is unique among four types of influenza viruses in that it utilizes cattle as a primary reservoir. The thermal and acid stability of IDV were examined and directly compared with those of influenza A virus (IAV), influenza B virus (IBV), and influenza C virus (ICV). The results of our experiments demonstrated that only IDV had a high residual infectivity (~2.5 log units of 50% tissue culture infective dose [TCID50]/ml) after a 60-min exposure to 53°C in solution at a neutral pH, and remarkably, IDV retained this infectivity even after exposure to 53°C for 120 min...
July 2017: MSphere
https://www.readbyqxmd.com/read/28806542/outcome-of-patients-with-lung-adenocarcinoma-with-transformation-to-small-cell-lung-cancer-following-tyrosine-kinase-inhibitors-treatment-a-systematic-review-and-pooled-analysis
#13
REVIEW
Elisa Roca, Cristina Gurizzan, Vito Amoroso, William Vermi, Vittorio Ferrari, Alfredo Berruti
BACKGROUND: Lung adenocarcinoma can transform to small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. This phenomenon has repeatedly been described in several case reports and small patient series. The characteristics and treatment outcomes of this population, however, have not been comprehensively reported. METHODS: We performed a systematic review of the published literature to obtain explorative information on the clinical and pathological features and prognosis of the reported cases...
July 31, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28805822/intrinsic-bet-inhibitor-resistance-in-spop-mutated-prostate-cancer-is-mediated-by-bet-protein-stabilization-and-akt-mtorc1-activation
#14
Pingzhao Zhang, Dejie Wang, Yu Zhao, Shancheng Ren, Kun Gao, Zhenqing Ye, Shangqian Wang, Chun-Wu Pan, Yasheng Zhu, Yuqian Yan, Yinhui Yang, Di Wu, Yundong He, Jun Zhang, Daru Lu, Xiuping Liu, Long Yu, Shimin Zhao, Yao Li, Dong Lin, Yuzhuo Wang, Liguo Wang, Yu Chen, Yinghao Sun, Chenji Wang, Haojie Huang
Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising anticancer therapies. The gene encoding the E3 ubiquitin ligase substrate-binding adaptor speckle-type POZ protein (SPOP) is the most frequently mutated in primary prostate cancer. Here we demonstrate that wild-type SPOP binds to and induces ubiquitination and proteasomal degradation of BET proteins (BRD2, BRD3 and BRD4) by recognizing a degron motif common among them. In contrast, prostate cancer-associated SPOP mutants show impaired binding to BET proteins, resulting in decreased proteasomal degradation and accumulation of these proteins in prostate cancer cell lines and patient specimens and causing resistance to BET inhibitors...
August 14, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28805788/nrf2-keap1-pathway-promotes-cell-proliferation-and-diminishes-ferroptosis
#15
Z Fan, A-K Wirth, D Chen, C J Wruck, M Rauh, M Buchfelder, N Savaskan
Cancer cells are hallmarked by high proliferation and imbalanced redox consumption and signaling. Various oncogenic pathways such as proliferation and evading cell death converge on redox-dependent signaling processes. Nrf2 is a key regulator in these redox-dependent events and operates in cytoprotection, drug metabolism and malignant progression in cancer cells. Here, we show that patients with primary malignant brain tumors (glioblastomas, WHO °IV gliomas, GBM) have a devastating outcome and overall reduced survival when Nrf2 levels are upregulated...
August 14, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28805266/hypothermic-pulsatile-preservation-of-kidneys-from-uncontrolled-deceased-donors-after-cardiac-arrest
#16
Xavier Matillon, Fabrice Danjou, Palmina Petruzzo, Olivier Thaunat, Thomas Rimmele, Claire Delsuc, Alexandre Faure, Maud Rabeyrin, Vannary Meas Yedid, William Hanf, Emmanuel Morelon, Lionel Badet, Ricardo Codas
Kidneys from uncontrolled donors after cardiac arrest (uDCD) suffer from a period of warm ischemia between cardiac arrest and cold flushing. Aim of the study was to evaluate renal outcomes of uDCD kidneys selected on the basis of renal Resistance Index (RI) and its influence on graft function and survival. The study included 44 kidneys procured from 26 uDCD starting 1.1.2006 until 31.12.2013. The donors (Maastricht category II) underwent cardiopulmonary resuscitation by assisted ventilation and chest compression; the organs were preserved with "in situ" cold perfusion or a normothermic regional perfusion...
August 14, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28805230/the-influence-of-topological-phase-transition-on-the-superfluid-density-of-overdoped-copper-oxides
#17
V R Shaginyan, V A Stephanovich, A Z Msezane, G S Japaridze, K G Popov
We show that a quantum phase transition, generating flat bands and altering Fermi surface topology, is a primary reason for the exotic behavior of the overdoped high-temperature superconductors represented by La2-xSrxCuO4, whose superconductivity features differ from what is predicted by the classical Bardeen-Cooper-Schrieffer theory. This observation can open avenues for chemical preparation of high-Tc materials. We demonstrate that (1) at temperature T = 0, the superfluid density ns turns out to be considerably smaller than the total electron density; (2) the critical temperature Tc is controlled by ns rather than by doping, and is a linear function of the ns; (3) at T > Tc the resistivity ρ(T) varies linearly with temperature, ρ(T) ∝ αT, where α diminishes with Tc → 0, whereas in the normal (non superconducting) region induced by overdoping, Tc = 0, and ρ(T) ∝ T(2)...
August 14, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28804449/loss-of-leptin-induced-modulation-of-hippocampal-synaptic-trasmission-and-signal-transduction-in-high-fat-diet-fed-mice
#18
Marco Mainardi, Matteo Spinelli, Federico Scala, Andrea Mattera, Salvatore Fusco, Marcello D'Ascenzo, Claudio Grassi
Hippocampal plasticity is triggered by a variety of stimuli including sensory inputs, neurotrophins and inflammation. Leptin, whose primary function is to regulate food intake and energy expenditure, has been recently shown to affect hippocampal neurogenesis and plasticity. Interestingly, mice fed a high-fat diet (HFD) exhibit impaired hippocampal function, but the underlying mechanisms are poorly understood. To address this issue, we compared leptin responsiveness of hippocampal neurons in control and HFD-fed mice by combining single-cell electrophysiology and biochemical assays...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28803675/the-yale-fitness-intervention-trial-in-female-cancer-survivors-cardiovascular-and-physiological-outcomes
#19
M Tish Knobf, Sangchoon Jeon, Barbara Smith, Lyndsay Harris, Siobhan Thompson, Mitchel R Stacy, Karl Insogna, Albert J Sinusas
BACKGROUND: Induced premature menopause and cardio-toxic therapy increase cardiovascular disease risk in female cancer survivors. OBJECTIVE: To compare the effects of a 12 month aerobic-resistance fitness center intervention to home based physical activity on cardiovascular function and metabolic risk factors. METHODS: Subjects (N = 154) who had completed primary and/or adjuvant chemotherapy (past 3 years) were randomized to a fitness center intervention or a home based group...
August 10, 2017: Heart & Lung: the Journal of Critical Care
https://www.readbyqxmd.com/read/28802832/retroviral-gene-transfer-into-primary-human-nk-cells-activated-by-il-2-and-k562-feeder-cells-expressing-membrane-bound-il-21
#20
Maria A Streltsova, Eugene Barsov, Sofia A Erokhina, Elena I Kovalenko
Natural killer (NK) cells are capable of rapidly recognizing and efficiently killing tumor cells. This makes them a potentially promising agent for cancer immunotherapy. Additional genetic modifications of NK cells may further improve their anti-tumor efficacy. Numerous technical challenges associated with gene delivery into NK cells have significantly tempered this approach. We achieved efficient retroviral vector transduction of primary human NK cells that were stimulated by a combination of IL-2 and engineered K562 cells expressing membrane-bound IL-21...
August 9, 2017: Journal of Immunological Methods
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