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Jaweed Haqparwar, Antonio Pepe, Klaus Fassbender, Ulrich Dillmann, Samer Ezziddin, Andrea Schaefer, Daniela Leppert, Jörg Spiegel
INTRODUCTION: Alpha-synuclein pathology (ASP) is a characteristic histopathological finding in idiopathic Parkinson's disease (PD). The ASP involves not only the brain but also extracranial structures. In the present study we utilized MIBG scintigraphy to measure the sympathetic innervation of the major salivary glands. We were interested in whether MIBG uptake in the major salivary glands represents a potential biomarker for ASP in PD. METHODS: We investigated 77 PD patients (age 61 ± 10 years, mean ± SD), while 15 non-PD patients (age 58 ± 15 years) with arterial hypertension, who underwent MIBG scintigraphy to exclude pheochromocytoma, served as age-matched controls...
October 15, 2016: Parkinsonism & related Disorders
Wouter van Ballegooijen, Jeroen Ruwaard, Eirini Karyotaki, David D Ebert, Johannes H Smit, Heleen Riper
BACKGROUND: Ecological momentary assessment (EMA) of mental health symptoms may influence the symptoms that it measures, i.e. assessment reactivity. In the field of depression, EMA reactivity has received little attention. We aim to investigate whether EMA of depressive symptoms induces assessment reactivity. Reactivity will be operationalised as an effect of EMA on depressive symptoms measured by a retrospective questionnaire, and, secondly, as a change in response rate and variance of the EMA ratings...
October 21, 2016: BMC Psychiatry
Qian Lu, Jihong Wang, Junshu Jiang, Shengnan Wang, Qilan Jia, Yue Wang, Weiping Li, Qin Zhou, Li Lv, Qingwei Li
BACKGROUND: The RGD-toxin protein Lj-RGD3 is a naturally occurring 118 amino acid peptide that can be obtained from the salivary gland of the Lampetra japonica fish. This unique peptide contains 3 RGD (Arg-Gly-Asp) motifs in its primary structure. Lj-RGD3 is available in recombinant form (rLj-RGD3) and can be produced in large quantities using DNA recombination techniques. The pharmacology of the three RGD motif-containing peptides has not been studied. This study investigated the protective effects of rLj-RGD3, a novel polypeptide, against ischemia/reperfusion-induced damage to the brain caused by middle cerebral artery occlusion (MCAO) in a rat stroke model...
2016: PloS One
Durga Mahor, Anu Priyanka, Gandham S Prasad, Krishan Gopal Thakur
Consumption of foods and beverages with high purine content increases the risk of hyperuricemia, which causes gout and can lead to cardiovascular, renal, and other metabolic disorders. As patients often find dietary restrictions challenging, enzymatically lowering purine content in popular foods and beverages offers a safe and attractive strategy to control hyperuricemia. Here, we report structurally and functionally characterized purine nucleoside phosphorylase (PNP) from Kluyveromyces lactis (KlacPNP), a key enzyme involved in the purine degradation pathway...
2016: PloS One
Xiao-Bin Fang, Ying-Qi Xu, Hon-Fai Chan, Chun-Ming Wang, Qing Zheng, Fei Xiao, Mei-Wan Chen
Hepatocellular carcinoma (HCC) is an aggressive malignancy and the second leading cause of cancer death worldwide. Most current therapeutic agents lack the tumor-targeting efficiency and result in a nonselective biodistribution in the body. In our previous study, we identified a peptide Ala-Pro-Asp-Thr-Lys-Thr-Gln (APDTKTQ) that can selectively bind to the receptor of advanced glycation end-products (RAGE), an immunoglobulin superfamily cell surface molecule overexpressed during HCC malignant progression. Here, we report the design of a mixed micelles system modified with this peptide to target HCC cells...
October 21, 2016: Molecular Pharmaceutics
Tur-Fu Huang, Chun-Chieh Hsu, Yu-Ju Kuo
Snake venoms affect blood coagulation and platelet function in a complex manner. However, two classes of venom proteins, snaclecs and disintegrins have been shown to specifically target receptors including GPIb, α2β1, GPVI, CLEC-2 and integrins αIIbβ3, αvβ3, α5β1 expressed on platelets, endothelial cells, phagocytes, tumor cells, thus affecting cell-matrices and cell-cell interactions. Here, we focus on disintegrins, a class of low molecular mass Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing, cysteine-rich polypeptide derived from various viper snake venoms...
2016: Thrombosis Journal
Beate Schwer, Fahad Khalid, Stewart Shuman
Saccharomyces cerevisiae Dbr1 is a manganese-dependent RNA debranching enzyme that cleaves the 2'-5' phosphodiester bond of the lariat introns formed during pre-mRNA splicing. Dbr1 is a member of the binuclear metallophosphoesterase enzyme superfamily. We showed previously via alanine scanning that RNA debranching in vivo and in vitro depends on conserved active site residues His13, Asp40, Asn85, His86, His179, His231, and His233. Here, by extending the alanine scan, we added Cys11 to the ensemble of essential active site components...
October 7, 2016: RNA
N C N Perera, G I Godahewa, Jehee Lee
Mitogen-activated protein kinase (MAPK) is involved in the regulation of cellular events by mediating signal transduction pathways. MAPK1 is a member of the extracellular-signal regulated kinases (ERKs), playing roles in cell proliferation, differentiation, and development. This is mainly in response to growth factors, mitogens, and many environmental stresses. In the current study, we have characterized the structural features of a homolog of MAPK1 from disk abalone (AbMAPK1). Further, we have unraveled its expressional kinetics against different experimental pathogenic infections or related chemical stimulants...
October 17, 2016: Fish & Shellfish Immunology
C L Barron, Jessica L Moore, Grayson Baird, Amy P Goldberg
BACKGROUND: Domestic minor sex trafficking (DMST) victims have unique medical and mental health needs and present frequently for medical attention. Little is known about the reported training, screening, comfort and knowledge of DMST among pediatricians in Rhode Island who likely encounter these patient victims without knowing. METHODS: An anonymous electronic survey sent to Rhode Island Hospital staff physicians from November 2014 through January 2015. RESULTS: Of the 109 participants, the majority reported no training, screened no patients for DMST in the past year, did not know any resources available and had limited knowledge and comfort with this pediatric patient population...
October 4, 2016: Rhode Island Medical Journal
Pelin Erkoc, Ahmet Cingöz, Tugba Bagci Onder, Seda Kizilel
Overcoming drug resistance is a major challenge for cancer therapy. Tumor necrosis factor α-related apoptosis-inducing ligand (TRAIL) is a potent therapeutic as an activator of apoptosis, particularly in tumor but not in healthy cells. However, its efficacy is limited by the resistance of tumor cell populations to the therapeutic substance. Here, we have addressed this limitation through the development of a controlled release system, matrix-metalloproteinase (MMP)-sensitive and arg-gly-asp-ser (RGDS) peptide functionalized poly (ethylene-glycol) (PEG) particles which are synthesized via visible-light-induced water-in-water emulsion polymerization...
October 20, 2016: Macromolecular Bioscience
Francesca Bianchini, Silvia Peppicelli, Pierangelo Fabbrizzi, Alessio Biagioni, Benedetta Mazzanti, Gloria Menchi, Lido Calorini, Alberto Pupi, Andrea Trabocchi
Fibrosis is the dramatic consequence of a dysregulated reparative process in which activated fibroblasts (myofibroblasts) and Transforming Growth Factor β1 (TGFβ1) play a central role. When exposed to TGFβ1, fibroblast and epithelial cells differentiate in myofibroblasts; in addition, endothelial cells may undergo endothelial-to-mesenchymal transition (EndoMT) and actively participate to the progression of fibrosis. Recently, the role of αv integrins, which recognize the Arg-Gly-Asp (RGD) tripeptide, in the release and signal transduction activation of TGFβ1 became evident...
October 19, 2016: Molecular and Cellular Biochemistry
Živa Cotič, Rebecca Rees, Petra A Wark, Josip Car
BACKGROUND: In 2013, there was a shortage of approximately 7.2 million health workers worldwide, which is larger among family physicians than among specialists. eLearning could provide a potential solution to some of these global workforce challenges. However, there is little evidence on factors facilitating or hindering implementation, adoption, use, scalability and sustainability of eLearning. This review aims to synthesise results from qualitative and mixed methods studies to provide insight on factors influencing implementation of eLearning for family medicine specialty education and training...
October 19, 2016: Systematic Reviews
Outi Heikkilä, Pirjo Merilahti, Marika Hakanen, Eveliina Karelehto, Jonna Alanko, Maria Sukki, Saija Kiljunen, Petri Susi
BACKGROUND: Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the capsid protein VP1 detected in all studied clinical isolates. However, genetically-modified CV-A9 that lacks the RGD motif (CV-A9-RGDdel) has been shown to be infectious in some cell lines but not in A549, suggesting that RGD-mediated integrin binding is not always essential for efficient entry of CV-A9...
October 18, 2016: Virology Journal
Saleh A Mohamed, Mohamed F Elshal, Taha A Kumosani, Alia M Aldahlawi, Tasneem A Basbrain, Fauziah A Alshehri, Hani Choudhry
Escherichia coli-derived L-asparaginases have been used in the treatment of acute lymphoblastic leukemia (ALL), however, clinical hypersensitivity reactions and silent inactivation due to antibodies against E. coli-asparaginase, lead to inactivation of these preparations in most cases.Therefore, this study was aimed to investigate the cytotoxicity and antitumor effects ofa novel L-asparaginaseenzyme, isolated from Phaseolus vulgaris seeds (P-Asp) on the ALL cell line (Jurkat). The immunogenicity of the enzyme was also evaluated in-vivo and results were compared to commercially available enzymes of microbial sources...
October 14, 2016: International Journal of Environmental Research and Public Health
Karan Kapoor, Michael R Duff, Amit Upadhyay, Joel C Bucci, Arnold M Saxton, Robert J Hinde, Elizabeth E Howell, Jerome Yves Baudry
The dynamics of anion-quadrupole (or anion-) interactions formed between negatively charged (Asp/Glu) and aromatic (Phe) side chains are for the first time computationally characterized in RmlC (PDB: 1EP0), a homodimeric epimerase. Empirical force field-based molecular dynamics simulations predict anion-quadrupole pairs and triplets (anion-anion-anion--) are formed by the protein during the simulated trajectory which suggests that the anion-quadrupole interactions may provide a significant contribution to the overall stability of the protein, with an average of -1...
October 18, 2016: Biochemistry
W L Wan, J Wang, M X Zhu, W Zhang, X Y Ke
OBJECTIVE: To investigate prognostic factors of the T-cell non-Hodgkin's lymphoma (T-NHL), and to study the clinical efficacy of CHOPE plus L-asparaginase(L-ASP) regimen for T-NHL. METHODS: Retrospective analyses were made of 61 T-NHL patients who were treated from July 2007 to August 2013. Randomly divided into two groups CHOPE and CHOPE+L group(Based on CHOPE, added with L-ASP on the 1st, 3rd, 5th, 7th, 9th and 11th day). RESULTS: Of the 61 patients evaluatd with the median survival was 22 (3-65) months,the complete remission rate was 52...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Qing Zhang, Qing Zhang, Yanxing Guan, Shaozheng Liu, Qingjie Chen, Xiangmin Li
BACKGROUND This study was specifically designed to develop a new 99mTc compound with 3-amino-4-[2-(2-methyl-5-nitro-1H-imidazol)-ethylamino]-4-oxo-butyrate (5-ntm-asp) and to verify whether this compound is feasible to be a radiopharmaceutical for hypoxic tumors. MATERIAL AND METHODS Metronidazole derivative 5-ntm-asp was synthesized and then radio-labeled by Na [99mTcO4], forming 99mTc-5-ntm-asp. Another two complexes of 99mTc-2- and 99mTc-5-nitroimidazole-iminodiacetic acid (99mTc-2-ntm-IDA and 99mTc-5-ntm-IDA) were also synthesized based on previous studies...
October 18, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Dae-Weung Kim, Myoung Hyoun Kim, Chang Guhn Kim
In a ProteoChip‑based screening system and subsequent studies, serine‑aspartic acid‑valine (SDV) was demonstrated to specifically bind to integrin αvβ3. An SDV‑containing peptide could target the tumor vessel and it may be an effective replacement for molecular imaging of the tumor. In the present study, a hexapeptide, SDV‑glutamic acid‑cysteine‑glycine (ECG), was developed and evaluated its diagnostic performance as a tumor imaging agent in tumor‑bearing mice. The hexapeptide SDV‑ECG was synthesized using Fmoc solid‑phase peptide synthesis...
October 6, 2016: Molecular Medicine Reports
Yao Lu, Honit Piplani, Stacy L McAllister, Carl M Hurt, Eric R Gross
BACKGROUND: Recent evidence suggests that cross talk exists between cellular pathways important for pain signaling and ischemia-reperfusion injury. Here, the authors address whether the transient receptor potential ankyrin 1 (TRPA1) channel, important in pain signaling, is present in cardiac myocytes and regulates cardiac ischemia-reperfusion injury. METHODS: For biochemical analysis of TRPA1, techniques including quantitative polymerase chain reaction, Western blot, and immunofluorescence were used...
September 30, 2016: Anesthesiology
Kunal Zaveri, Kiranmayi Patnala
BACKGROUND: The prevalence of multi-drug resistance S. aureus is one most challenging task for treatment of nosocomial infections. Proteins and enzymes of peptidoglycan biosynthesis pathway are one among the well-studied targets, but many of the enzymes are unexplored as targets. MurE is one such enzyme featured to be a promising target. As MurE plays an important role in ligating the L-lys to stem peptide at third position that is crucial for peptidoglycan synthesis. OBJECTIVE: To screen the potential MurE inhibitor...
October 10, 2016: Current Computer-aided Drug Design
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