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https://www.readbyqxmd.com/read/28723813/effect-of-resistance-training-on-blood-pressure-and-autonomic-responses-in-treated-hypertensives
#1
Gabriela Alves Trevizani, Mariana Balbi Seixas, Paulo Roberto Benchimol-Barbosa, Jeferson Macedo Vianna, Lilian Pinto da Silva, Jurandir Nadal
This study evaluated the effect of resistance training (RT) on heart rate variability (HRV) and on blood pressure (BP) responses to acute and short-term exposure in treated hypertensive subjects. Twenty one men participated in the study, eight hypertensive under drug treatment regimen and achieving adequate blood pressure control prior to inclusion (HT) and thirteen normotensive (NT). The RT protocol consisted of 12 sessions with 8 exercises (leg extension, leg press, leg curl, bench press, seated row, triceps push-down, seated calf flexion and seated arm curl) performed for 2 sets of 15-20 repetitions with 50% of one repetition-maximum (1RM) with 2-minute rest intervals in between sets, 3x/week...
July 17, 2017: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/28723622/dual-targeting-of-mdm2-and-bcl2-as-a-therapeutic-strategy-in-neuroblastoma
#2
Alan Van Goethem, Nurten Yigit, Myrthala Moreno-Smith, Sanjeev A Vasudevan, Eveline Barbieri, Frank Speleman, Jason Shohet, Jo Vandesompele, Tom Van Maerken
Wild-type p53 tumor suppressor activity in neuroblastoma tumors is hampered by increased MDM2 activity, making selective MDM2 antagonists an attractive therapeutic strategy for this childhood malignancy. Since monotherapy in cancer is generally not providing long-lasting clinical responses, we here aimed to identify small molecule drugs that synergize with idasanutlin (RG7388). To this purpose we evaluated 15 targeted drugs in combination with idasanutlin in three p53 wild type neuroblastoma cell lines and identified the BCL2 inhibitor venetoclax (ABT-199) as a promising interaction partner...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723617/small-molecular-floribundiquinone-b-derived-from-medicinal-plants-inhibits-acetylcholinesterase-activity
#3
Bing Niu, Mengying Zhang, Pu Du, Li Jiang, Rui Qin, Qiang Su, Fuxue Chen, Dongshu Du, Yilai Shu, Kuo-Chen Chou
Being a neurodegenerative disorder, Alzheimer's disease (AD) is the one of the most terrible diseases. And acetylcholinesterase (AChE) is considered as an important target for treating AD. Acetylcholinesterase inhibitors (AChEI) are considered to be one of the effective drugs for the treatment of AD. The aim of this study is to find a novel potential AChEI as a drug for the treatment of AD. In this study, instead of using the synthetic compounds, we used those extracted from plants to investigate the interaction between floribundiquinone B (FB) and AChE by means of both the experimental approach such as fluorescence spectra, ultraviolet-visible (UV-vis) absorption spectrometry, circular dichroism (CD) and the theoretical approaches such as molecular docking...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723574/proteomic-analysis-of-the-human-tankyrase-protein-interaction-network-reveals-its-role-in-pexophagy
#4
Xu Li, Han Han, Mao-Tian Zhou, Bing Yang, Albert Paul Ta, Nan Li, Junjie Chen, Wenqi Wang
Tankyrase 1 (TNKS) and tankyrase 2 (TNKS2) belong to the poly(ADP-ribose) polymerase family of proteins, which use nicotinamide adenine dinucleotide to modify substrate proteins with ADP-ribose modifications. Emerging evidence has revealed the pathological relevance of TNKS and TNKS2, and identified these two enzymes as potential drug targets. However, the cellular functions and regulatory mechanisms of TNKS/2 are still largely unknown. Through a proteomic analysis, we defined the protein-protein interaction network for human TNKS/2 and revealed more than 100 high-confidence interacting proteins with numerous biological functions in this network...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28722740/spectroscopic-imaging-studies-of-nanoscale-polarity-and-mass-transport-phenomena-in-self-assembled-organic-nanotubes
#5
Hao Xu, Shinobu Nagasaka, Naohiro Kameta, Mitsutoshi Masuda, Takashi Ito, Daniel A Higgins
Synthetic organic nanotubes self-assembled from bolaamphiphile surfactants are now being explored for use as drug delivery vehicles. In this work, several factors important to their implementation in drug delivery are explored. All experiments are performed with the nanotubes immersed in ethanol. First, Nile Red (NR) and a hydroxylated Nile Red derivative (NR-OH) are loaded into the nanotubes and spectroscopic fluorescence imaging methods are used to determine the apparent dielectric constant of their local environment...
July 19, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28722515/construction-of-a-plga-based-targeted-sirna-delivery-system-for-treatment-of-osteoporosis
#6
Deniz Sezlev Bilecen, Jose Carlos Rodriguez-Cabello, Hasan Uludag, Vasif Hasirci
Osteoporosis is a systemic skeletal disorder which occurs when the bone turnover balance is disrupted. With the identification of the genes involved in the pathogenesis of the disease, studies on development of new osteoporosis treatments has intensified. RNA interference (RNAi) mechanism uses short interfering RNA (siRNA) to knockdown disease related gene expression as a treatment approach. Targeting while protecting siRNA against hydrolysis by nucleases in vivo is, however, challenging. The maintenance of therapeutic plasma level is also hampered by the clearance of siRNA from the body...
July 19, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28722512/in-silico-and-in-vitro-evaluation-of-two-novel-oximes-k378-and-k727-in-comparison-to-k27-and-pralidoxime-against-paraoxon-ethyl-intoxication
#7
Maria Chaudhry, Muhammad Qaiser Fatmi, Kamil Musilek, Alamdar Hussain, Kamil Kuca, Georg Petroianu, Huba Kalasz, Syed Muhammad Nurulain
Organophosphate (OP) poisoning is a major global health issue; while compounds from this group have been used intensively over the last century, an effective antidote is still lacking. Oxime-type AChE reactivators are used to reactivate the OP inhibited AChE. Pralidoxime is the only US Food and Drug Administration, (FDA) approved oxime for therapeutic use but its efficacy has been disappointing. Two novel oximes (K378 and K727) were investigated in silico and in vitro and compared with an experimental oxime (kamiloxime; K-27) and pralidoxime...
July 19, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28722440/life-under-the-microscope-quantifying-live-cell-interactions-to-improve-nanoscale-drug-delivery
#8
Angus P R Johnston
The behavior of cells and how they react to stimuli is critically important for drug development, drug delivery, and understanding the molecular basis of many diseases. However, we still lack a comprehensive understanding of these interactions, particularly in relation to drug delivery from nanoparticles. This Sensors Issues article discusses the importance of quantifying these interactions and highlights some key areas where advances in sensor technology have the potential to transform our understanding of drug delivery and cell biology...
January 27, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722356/hansen-solubility-parameters-for-assay-method-optimization-of-simvastatin-ramipril-atenolol-hydrochlorothiazide-and-aspirin-in-human-plasma-using-liquid-chromatography-with-tandem-mass-spectrometry
#9
Murali Mohan Reddy Devalapalli, Hanumanth Srikanth Cheruvu, Thejaswi Yertha, Vijaya Bhaskar Veeravalli, Sunitha Sampathi, Savithri Shivakumar
A simple, specific, sensitive validated method was developed using liquid chromatography with tandem mass spectrometry with electrospray ionization of human plasma for the simultaneous estimation of drugs (simvastatin, ramipril, atenolol, hydrochlorothiazide and aspirin) of Polycap(TM) capsule used in cardiovascular therapy. The interaction of these actives including internal standards between the stationary and mobile phase were investigated using Hansen solubility parameters. Chromatographic separation was performed on Phenomenex Synergi Polar-RP (30 × 2 mm, 4 μm) column with a gradient mobile phase composition of acetonitrile and 5 mM ammonium formate for positive mode and 0...
July 19, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28722290/development-of-a-cardiovascular-diseases-risk-prediction-model-and-tools-for-chinese-patients-with-type-2-diabetes-mellitus-a-population-based-retrospective-cohort-study
#10
Eric Yuk Fai Wan, Daniel Yee Tak Fong, Colman Siu Cheung Fung, Esther Yee Tak Yu, Weng Yee Chin, Anca Ka Chun Chan, Cindy Lo Kuen Lam
AIMS: Evidence-based cardiovascular diseases(CVD) risk prediction models and tools specific for Chinese patients with type 2 diabetes mellitus(T2DM) are currently unavailable. This study aimed to develop and validate a CVD risk prediction model for Chinese T2DM patients. MATERIALS AND METHODS: A retrospective cohort study was conducted on 137 935 Chinese patients aged 18-79 years with T2DM and without prior history of CVD, who had received public primary care services between 1 January 2010 and 31 December 2010...
July 19, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28722266/second-generation-drug-eluting-stents-versus-bare-metal-stents-for-percutaneous-coronary-intervention-of-the-proximal-left-anterior-descending-artery-an-analysis-of-the-basket-prove-i-and-ii-trials
#11
Fernanda Marinho Mangione, Tor Biering-Sørensen, Kotaro Nochioka, Tannas Jatene, Odilson Marcos Silvestre, Kim Wadt Hansen, Rikke Sørensen, Jan Skov Jensen, Peter Godsk Jorgensen, Raban Jeger, Christoph Kaiser, Matthias Pfisterer, Søren Galatius
OBJECTIVES: To compare mid-term outcomes between patients undergoing proximal left anterior descending artery (LAD) percutaneous coronary intervention (PCI) with second generation drug-eluting stent (DES) or bare-metal stent (BMS). BACKGROUND: PCI with BMS and first-generation DES have shown to be safe options for the treatment of proximal LAD stenosis, however associated with considerable reintervention rates. Overall, second-generation DES has proven to be superior to BMS and first-generation DES, nevertheless, its effect for proximal LAD PCI has not previously been reported...
July 19, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28722255/drug-drug-interactions-between-triazole-antifungal-agents-used-to-treat-invasive-aspergillosis-and-immunosuppressants-metabolized-by-cytochrome-p450-3a4
#12
REVIEW
Andreas H Groll, Robert Townsend, Amit Desai, Nkechi Azie, Mark Jones, Marc Engelhardt, Anne-Hortense Schmitt-Hoffman, Robert J Brüggemann
Patients undergoing treatment with immunosuppressant drugs following solid organ or hematopoietic stem cell transplantation are at particular risk for development of serious infections such as invasive aspergillosis. Four triazole antifungal drugs, voriconazole, posaconazole, itraconazole, and isavuconazole, are approved to treat invasive aspergillosis either as first- or second-line therapy. All of these agents are inhibitors of cytochrome P450 3A4, which plays a key role in metabolizing immunosuppressant drugs such as cyclosporine, tacrolimus, and sirolimus...
July 19, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28722220/developing-new-targeting-strategy-for-androgen-receptor-variants-in-castration-resistant-prostate-cancer
#13
Bin Wang, U-Ging Lo, Kaijie Wu, Payal Kapur, Xiangyang Liu, Jun Huang, Wei Chen, Elizabeth Hernandez, John Santoyo, Shi-Hong Ma, Rey-Chen Pong, Dalin He, Yi-Qiang Cheng, Jer-Tsong Hsieh
The presence of androgen receptor variant 7 (AR-V7) variants becomes a significant hallmark of castration resistant prostate cancer (CRPC) relapsed from hormonal therapy and is associated with poor survival of CRPC patients because of lacking a ligand-binding domain. Currently, it still lacks an effective agent to target AR-V7 or AR-Vs in general. Here, we showed a novel class of agents (thailanstatins, TSTs, spliceostatin A analogs) can significantly suppress the expression of AR-V7 mRNA and protein but in a less extent on the full-length AR expression...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28721542/molecular-characterization-modeling-in-silico-analysis-of-equine-pituitary-gonadotropin-alpha-subunit-and-docking-interaction-studies-with-ganirelix
#14
Anuradha Bhardwaj, Varij Nayan, Parvati Sharma, Sanjay Kumar, Yash Pal, Jitender Singh
Equine pituitary gonadotropins (eLH, eFSH, eCG) are heterodimeric glycoprotein hormones with alpha (α) and beta (β) subunits. It is responsible for maintenance of pregnancy in mares during early gestation and fairly valuable for inducing superovulation in animals other than equines. The alpha subunit is common, while beta subunit is species-specific in all glycoprotein hormones. In the present investigation, molecular cloning and in silico characterization including homology modeling and molecular docking analysis of the equine chorionic gonadotropin (eCG) alpha subunit was carried out for gaining structural and functional insights into the eCG alpha subunit and its possible interaction with ganirelix, a gonadotropin-releasing hormone (GnRH) antagonist...
December 2016: In Silico Pharmacology
https://www.readbyqxmd.com/read/28721072/cxcl12-suppresses-cisplatin-induced-apoptosis-through-activation-of-jak2-stat3-signaling-in-human-non-small-cell-lung-cancer-cells
#15
Meng Wang, Tie Lin, Yicun Wang, Song Gao, Zhaoyang Yang, Xuan Hong, Gongyan Chen
AIMS: Poor efficacy of chemotherapy drugs in non-small-cell lung cancer (NSCLC) is the key reason for the failure of treatment, but the mechanism of this remains largely unknown. Stromal cell-derived factor 1-alpha (SDF-1α/CXCL12) is a small chemotactic cytokine protein that plays an important role in tumor progression. In this study, we investigated the anti-apoptotic mechanism of the CXCL12/CXCR4 axis in response to cisplatin, a commonly used chemotherapeutic drug, in human lung adenocarcinoma A549 cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28721043/preparation-of-exenatide-loaded-linear-poly-ethylene-glycol-brush-poly-l-lysine-block-copolymer-potential-implications-on-diabetic-nephropathy
#16
Fei Tong
The poly(ethylene glycol)-b-brush poly(l-lysine) polymer (PEG-b-(PELG50-g-PLL3)) was synthesized and evaluated as a nanocarrier for prolonging delivery of exenatide through the abdominal subcutaneous injection route. The isoelectric point of exenatide was 4.86, and exenatide could combine with PEG-b-(PELG50-g-PLL3) polymers via electrostatic interactions at pH 7.4. This polymer was a good candidate for achieving prolonged drug delivery for exenatide, considering its high molecular weight. Besides the physicochemical characterization of the polymer, in vitro and in vivo applications were researched as a sustained exenatide delivery system...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28720834/chemical-inhibitors-of-candida-albicans-hyphal-morphogenesis-target-endocytosis
#17
Hagit Bar-Yosef, Nora Vivanco Gonzalez, Shay Ben-Aroya, Stephen J Kron, Daniel Kornitzer
Candida albicans is an opportunistic pathogen, typically found as a benign commensal yeast living on skin and mucosa, but poised to invade injured tissue to cause local infections. In debilitated and immunocompromised individuals, C. albicans may spread to cause life-threatening systemic infections. Upon contact with serum and at body temperature, C. albicans performs a regulated switch to filamentous morphology, characterized by emergence of a germ tube from the yeast cell followed by mold-like growth of branching hyphae...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720769/concentration-dependent-binding-of-small-ligands-to-multiple-saturable-sites-in-membrane-proteins
#18
Letícia Stock, Juliana Hosoume, Werner Treptow
Membrane proteins are primary targets for most therapeutic indications in cancer and neurological diseases, binding over 50% of all known small molecule drugs. Understanding how such ligands impact membrane proteins requires knowledge on the molecular structure of ligand binding, a reasoning that has driven relentless efforts in drug discovery and translational research. Binding of small ligands appears however highly complex involving interaction to multiple transmembrane protein sites featuring single or multiple occupancy states...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720735/a-nonredundant-phosphopantetheinyl-transferase-ppta-is-a-novel-antifungal-target-that-directs-secondary-metabolite-siderophore-and-lysine-biosynthesis-in-aspergillus-fumigatus-and-is-critical-for-pathogenicity
#19
Anna Johns, Daniel H Scharf, Fabio Gsaller, Hella Schmidt, Thorsten Heinekamp, Maria Straßburger, Jason D Oliver, Mike Birch, Nicola Beckmann, Katharine S Dobb, Jane Gilsenan, Bharatkumar Rash, Elaine Bignell, Axel A Brakhage, Michael J Bromley
Secondary metabolites are key mediators of virulence for many pathogens. Aspergillus fumigatus produces a vast array of these bioactive molecules, the biosynthesis of which is catalyzed by nonribosomal peptide synthetases (NRPSs) or polyketide synthases (PKSs). Both NRPSs and PKSs harbor carrier domains that are primed for acceptance of secondary metabolic building blocks by a phosphopantetheinyl transferase (P-pant). The A. fumigatus P-pant PptA has been shown to prime the putative NRPS Pes1 in vitro and has an independent role in lysine biosynthesis; however, its role in global secondary metabolism and its impact on virulence has not been described...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28720707/intrinsically-disordered-chromatin-protein-nupr1-binds-to-the-c-terminal-region-of-polycomb-ring1b
#20
Patricia Santofimia-Castaño, Bruno Rizzuti, Ángel L Pey, Philippe Soubeyran, Miguel Vidal, Raúl Urrutia, Juan L Iovanna, José L Neira
Intrinsically disordered proteins (IDPs) are ubiquitous in eukaryotes, and they are often associated with diseases in humans. The protein NUPR1 is a multifunctional IDP involved in chromatin remodeling and in the development and progression of pancreatic cancer; however, the details of such functions are unknown. Polycomb proteins are involved in specific transcriptional cascades and gene silencing. One of the proteins of the Polycomb complex is the Ring finger protein 1 (RING1). RING1 is related to aggressive tumor features in multiple cancer types...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
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