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https://www.readbyqxmd.com/read/28432956/introduction-of-n-cadherin-binding-motif-to-alginate-hydrogels-for-controlled-stem-cell-differentiation
#1
Jae Won Lee, Hyoseok An, Kuen Yong Lee
Control of stem cell fate and phenotype using biomimetic synthetic extracellular matrices (ECMs) is an important tissue engineering approach. Many studies have focused on improving cell-matrix interactions. However, proper control of cell-cell interactions using synthetic ECMs could be critical for tissue engineering, especially with undifferentiated stem cells. In this study, alginate hydrogels were modified with a peptide derived from the low-density lipoprotein receptor-related protein 5 (LRP5), which is known to bind to N-cadherin, as a cell-cell interaction motif...
April 9, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28432776/exploring-non-obvious-hydrophobic-binding-pockets-on-protein-surfaces-increasing-affinities-in-peptide-protein-interactions
#2
Lars Baltzer, Aleksandra Balliu
A 42-residue polypeptide conjugated to a small organic molecule capable of targeting the phosphorylated side chain of Ser-15 was shown to bind glycogen phosphorylase a (GPa) with a KD of 280 nM. The replacement of hydrophobic amino acids by Ala reduced affinities, whereas the incorporation of L-2-aminooctanoic acid (Aoc) increased affinities. Replacing Nle-5, Ile-9 and Leu-12 by Aoc reduced the KD from 280 nM to 27 nM. Downsizing the 42-mer to an 11-mer gave rise to an order of magnitude lower affinity for GPa but the 11-mer where Nle-5, Ile-9 and Leu-12 were replaced by Aoc showed a KD of 550 nM, comparable to that of the parent 42-mer...
April 22, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28432752/incretin-based-glucose-lowering-medications-and-the-risk-for-acute-pancreatitis-and-or-pancreatic-cancer-risk-reassuring-data-from-cardio-vascular-outcome-trials
#3
Michael A Nauck, Juris J Meier, Wolfgang E Schmidt
Incretin-based medications (glucagon-like peptide-1 [GLP-1] receptor agonists and inhibitors of dipeptidyl peptidase-4 [DPP-4] are glucose-lowering drugs approved and introduced after 2006 (1). Although both classes of drugs appeared to be relatively safe based on results from clinical trials and standard animal toxicology studies, epidemiological data (2, 3) and histological findings (4) in genetically modified rodents exposed to such agents have raised concern that pancreatitis and pancreatic cancer may be long-term risks associated with this therapy...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432748/future-challenges-and-therapeutic-opportunities-in-type-2-diabetes-changing-the-paradigm-of-current-therapy
#4
REVIEW
D R Owens, L Monnier, A H Barnett
Most algorithms for type 2 diabetes mellitus (T2DM) do not recommend treatment escalation until glycated haemoglobin (HbA1c) fails to reach the recommended target of 7% (53 mmol/mol) within approximately 3 months on any treatment regimen ('treat to failure'). Clinical inertia and/or poor adherence to therapy contribute to patients not reaching glycaemic targets when managed according to this paradigm. Clinical inertia exists across the entire spectrum of anti-diabetes therapies, although it is most pronounced when initiating and optimizing insulin therapy...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432691/tenapanor-administration-and-the-activity-of-the-h-coupled-transporter-pept1-in-healthy-volunteers
#5
Susanne Johansson, David P Rosenbaum, Johan Palm, Bergur Stefansson, Mikael Knutsson, Eleanor A Lisbon, Constanze Hilgendorf
AIM: Tenapanor (RDX5791/AZD1722), an inhibitor of gastrointestinal Na(+) /H(+) exchanger NHE3, is being evaluated for the treatment of patients with constipation-predominant irritable bowel syndrome and the treatment of hyperphosphataemia in patients with chronic kidney disease on dialysis. By reducing intestinal H(+) secretion, inhibition of NHE3 by tenapanor could indirectly affect H(+) -coupled transporter activity, leading to drug-drug interactions. We investigated the effect of tenapanor on the activity of the H(+) -coupled peptide transporter PepT1 via assessment of the pharmacokinetics of cefadroxil - a compound transported by PepT1 - in healthy volunteers...
April 22, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28432659/current-role-of-blood-and-urine-biomarkers-in-the-clinical-care-of-adults-with-congenital-heart-disease
#6
REVIEW
Saurabh Rajpal, Laith Alshawabkeh, Alexander R Opotowsky
PURPOSE OF REVIEW: There is an increasing number of adult patients with congenital heart disease (CHD). While several biomarkers have been validated and integrated into general cardiology clinical practice, these tests are often applied to adults with CHD in the absence of disease-specific validation. Although these patients are often grouped into a single population, there is heterogeneous pathophysiology, variable disease chronicity, extensive multisystem involvement, and a low event rate relative to acquired heart disease...
June 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28432619/assessment-of-saxagliptin-efficacy-meta-analysis-of-14-phase-2-and-3-clinical-trials
#7
Mikaela Sjöstrand, Cheryl Wei, William Cook, Kristina Johnsson, Pia S Pollack, Christina Stahre, Boaz Hirshberg
INTRODUCTION: This meta-analysis of data from 14 phase 2 and 3, double-blind, randomized, controlled 12- and 24-week studies (N = 4632) summarizes saxagliptin efficacy in patients with type 2 diabetes (T2D) across treatment regimens. METHODS: Patients received saxagliptin 5 mg/d or control as either monotherapy (n = 1196 vs placebo), add-on therapy (n = 2139 vs placebo and n = 514 vs uptitrated sulfonylurea), or initial combination therapy (n = 619 vs control monotherapy)...
April 21, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28432618/the-identification-of-key-genes-and-pathways-in-hepatocellular-carcinoma-by-bioinformatics-analysis-of-high-throughput-data
#8
Chaoyang Zhang, Li Peng, Yaqin Zhang, Zhaoyang Liu, Wenling Li, Shilian Chen, Guancheng Li
Liver cancer is a serious threat to public health and has fairly complicated pathogenesis. Therefore, the identification of key genes and pathways is of much importance for clarifying molecular mechanism of hepatocellular carcinoma (HCC) initiation and progression. HCC-associated gene expression dataset was downloaded from Gene Expression Omnibus database. Statistical software R was used for significance analysis of differentially expressed genes (DEGs) between liver cancer samples and normal samples. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, based on R software, were applied for the identification of pathways in which DEGs significantly enriched...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28432603/immunoprophylaxis-of-multi-antigen-peptide-map-vaccine-for-human-lymphatic-filariasis
#9
Christiana Immanuel, Aparnaa Ramanathan, Malathi Balasubramaniyan, Vishal Kishor Khatri, Nitin Purushottam Amdare, Donthamsetty Nageswara Rao, Maryada Venkata Rami Reddy, Kaliraj Perumal
Human lymphatic filariasis, the parasitic disease caused by the filarial nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori, is ranked as the second most complex clinical condition leading to permanent and long-term disability. The multiple antigen peptide (MAP) approach is an effective method to chemically synthesize and deliver multiple T and B cell epitopes as the constituents of a single immunogen. Here, we report on the design, chemical synthesis, and immunoprophylaxis of three epitopes that have been identified from promising vaccine candidates reported in our previous studies, constructed as MAP on an inert lysine core for human lymphatic filariasis in Jird model...
April 21, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28432554/epigallocatechin-gallate-protects-beas-2b-cells-from-lipopolysaccharide-induced-apoptosis-through-upregulation-of-gastrin-releasing-peptide
#10
Peethambaran Divya, Bijesh Puthusseri, Denny Joseph Kollareth Manual, Mohammed Azharuddin Savanur
Gastrin-releasing peptide (GRP) plays a major role in the development and maintenance of lung epithelial cells by promoting cell division, whereas its suppression causes growth arrest and apoptosis. The present study shows that human bronchial epithelial BEAS-2B cells challenged with lipopolysaccharide (LPS), an endotoxin from gram-negative bacteria, downregulated GRP expression and induced apoptosis via upregulation of p53 and active caspase-3, signifying the importance of GRP in lung epithelial cell survival...
April 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28432473/vasopressin-and-vasopressin-antagonists-in-heart-failure
#11
Julie K Vishram-Nielsen, Finn Gustafsson
Despite the introduction of multiple new pharmacological agents over the past three decades in the field of heart failure (HF), overall prognosis remains poor. Hyponatremia is prevalent in HF patients and has been suggested as a contributor to poor response to standard therapy. Elevated levels of arginine vasopressin (AVP), a peptide hormone produced in the hypothalamus, play a role in development of hyponatremia, and AVP and its surrogate, copeptin, are related to changes in osmolality, hemodynamics, neuro-hormones as well as in overall outcome in HF patients...
April 22, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28432464/insights-into-autosomal-dominant-polycystic-kidney-disease-by-quantitative-mass-spectrometry-based-proteomics
#12
REVIEW
Britta Diedrich, Jörn Dengjel
Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disorder that is caused by mutations in the genes PKD1 and PKD2 encoding polycystin-1 and polycystin-2, respectively. Polycystin-1 and -2 form a complex, interact with several proteins involved in signal transduction and localize to discrete subcellular positions, most importantly the primary cilium. Whereas the causative mutations leading to ADPKD are known, the underlying deregulated cellular pathways are not well understood. In the current review, we introduce state-of-the-art mass spectrometry (MS)-based proteomic techniques and summarize their use in kidney and ADPKD research...
April 21, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28432358/differential-sensitivity-to-infections-and-antimicrobial-peptide-mediated-immune-response-in-four-silkworm-strains-with-different-geographical-origin
#13
Ottavia Romoli, Alessio Saviane, Andrea Bozzato, Paola D'Antona, Gianluca Tettamanti, Andrea Squartini, Silvia Cappellozza, Federica Sandrelli
The domesticated silkworm Bombyx mori has an innate immune system, whose main effectors are the antimicrobial peptides (AMPs). Silkworm strains are commonly grouped into four geographical types (Japanese, Chinese, European and Tropical) and are generally characterised by a variable susceptibility to infections. To clarify the genetic and molecular mechanisms on which the different responses to infections are based, we exposed one silkworm strain for each geographical area to oral infections with the silkworm pathogens Enterococcus mundtii or Serratia marcescens...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432329/affinity-biosensors-using-recombinant-native-membrane-proteins-displayed-on-exosomes-application-to-botulinum-neurotoxin-b-receptor
#14
Richard Desplantes, Christian Lévêque, Benjamin Muller, Manuela Lotierzo, Géraldine Ferracci, Michel Popoff, Michael Seagar, Robert Mamoun, Oussama El Far
The development of simple molecular assays with membrane protein receptors in a native conformation still represents a challenging task. Exosomes are extracellular vesicles which, due to their stability and small size, are suited for analysis in various assay formats. Here, we describe a novel approach to sort recombinant fully native and functional membrane proteins to exosomes using a targeting peptide. Specific binding of high affinity ligands to the potassium channel Kv1.2, the G-protein coupled receptor CXCR4, and the botulinum neurotoxin type B (BoNT/B) receptor, indicated their correct assembly and outside out orientation in exosomes...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432311/enteric-innervation-combined-with-proteomics-for-the-evaluation-of-the-effects-of-chronic-fluoride-exposure-on-the-duodenum-of-rats
#15
Carina Guimarães de Souza Melo, Juliana Vanessa Colombo Martins Perles, Jacqueline Nelisis Zanoni, Sara Raquel Garcia de Souza, Erika Xavier Santos, Aline de Lima Leite, Alessandro Domingues Heubel, Camila Oliveira E Souza, Juliana Gadelha de Souza, Marília Afonso Rabelo Buzalaf
Ingested fluoride (F) is absorbed mainly in the small intestine, which is controlled by the Enteric Nervous System (ENS). Although important intestinal symptomatology has been described after excessive F exposure, there have been no studies reporting the effects of F on the ENS. In this study, the effects of chronic F exposure were evaluated on the duodenums of rats through proteomic and morphological analyses. Concentrations of 0, 10, or 50 ppm of F were applied to the drinking water for 30 days. Immunofluorescence techniques were performed in the myenteric plexus of the duodenum to detect HuC/D, neuronal nitric oxide (nNOS), vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), and substance P (SP)...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432261/ccm2-and-pak4-act-downstream-of-atrial-natriuretic-peptide-signaling-to-promote-cell-spreading
#16
Koichi Miura, Takashi Nojiri, Yoshiharu Akitake, Koji Ando, Shigetomo Fukuhara, Masahiro Zenitani, Toru Kimura, Jun Hino, Mikiya Miyazato, Hiroshi Hosoda, Kenji Kangawa
Atrial natriuretic peptide (ANP) is a cardiac hormone released by the atrium in response to stretching forces. Via its receptor, guanylyl cyclase-A (GC-A), ANP maintains cardiovascular homeostasis by exerting diuretic, natriuretic, and hypotensive effects mediated in part by endothelial cells. Both in vivo and in vitro , ANP enhances endothelial barrier function by reducing RhoA activity and reorganizing the actin cytoskeleton. We established mouse endothelial cells that stably express GC-A, and used them to analyze the molecular mechanisms responsible for actin reorganization...
April 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28432195/n-terminal-proteomics-assisted-profiling-of-the-unexplored-translation-initiation-landscape-in-arabidopsis-thaliana
#17
Patrick Willems, Elvis Ndah, Veronique Jonckheere, Simon Stael, Adriaan Sticker, Lennart Martens, Frank Van Breusegem, Kris Gevaert, Petra Van Damme
Proteogenomics is an emerging research field yet lacking a uniform method of analysis. Proteogenomic studies in which N-terminal proteomics and ribosome profiling are combined, suggest that a high number of protein start sites are currently missing in genome annotations. We constructed a proteogenomic pipeline specific for the analysis of N-terminal proteomics data, with the aim of discovering novel translational start sites outside annotated protein coding regions. In summary, unidentified MS/MS spectra were matched to a specific N-terminal peptide library encompassing protein N-termini encoded in the Arabidopsis thaliana genome...
April 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28432177/a-peptide-adhesive-molded-by-magnesium-glues-rubisco-s-subunits-together
#18
Rebekka M Wachter
Rubisco enzymes play central roles in carbon fixation, with potential importance in biotechnology, but have eluded a full description of their multistep assembly and function. A new article describes the fascinating discovery that some archaeal Rubiscos contain a built-in assembly domain inserted into an otherwise canonical Rubisco fold, providing a tremendous expansion of our understanding of the diversity of naturally occurring Rubiscos.
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432082/effect-of-oral-contraceptives-and-or-metformin-on-glp-1-secretion-and-reactive-hypoglycemia-in-pcos
#19
Dorte Glintborg, Hanne Mumm, Jens Juul Holst, Marianne Andersen
CONTEXT: Insulin resistance in polycystic ovary syndrome (PCOS) may increase the risk of reactive hypoglycaemia (RH) and decrease glucagon-like peptide-1 (GLP-1) secretion. The possible effects of treatment with oral contraceptives (OCP) and/or metformin on GLP-1 secretion and risk of RH in PCOS is undetermined. SETTING: Outpatient clinic. PATIENTS AND INTERVENTIONS: Randomized, controlled clinical trial. Ninety women with PCOS were randomized to 12 month treatment with OCP (150 mg desogestrel+30 microgram ethinylestradiol), metformin (2 g/day), or metformin +OCP...
April 21, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28432037/investigating-in-vitro-and-in-vivo-%C3%AE-v%C3%AE-6-integrin-receptor-targeting-liposomal-alendronate-for-combinatory-%C3%AE-%C3%AE-t-cell-immunotherapy
#20
Naomi O Hodgins, Wafa' T Al-Jamal, Julie T-W Wang, Rebecca Klippstein, Jane K Sosabowski, John F Marshall, John Maher, Khuloud T Al-Jamal
The αvβ6 integrin receptor has been shown to be overexpressed on many types of cancer cells, resulting in a more pro-invasive and aggressive phenotype, this makes it an attractive target for selective drug delivery. In tumours that over-express the αvβ6 receptor, cellular uptake of liposomes can be enhanced using ligand-targeted liposomes. It has previously been shown in both in vitro and in vivo studies that liposomal alendronate (L-ALD) can sensitise cancer cells to destruction by Vγ9Vδ2 T cells. It is hypothesised that by using the αvβ6-specific peptide A20FMDV2 as a targeting moiety for L-ALD, the therapeutic efficacy of this therapy can be increased in αvβ6 positive tumours...
April 18, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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