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https://www.readbyqxmd.com/read/29935398/involvement-of-brain-natriuretic-peptide-signaling-pathway-in-the-cardioprotective-action-of-sitagliptin
#1
Samah S Abbas, Hesham M Mahmoud, Mona F Schaalan, Hanan S El-Abhar
BACKGROUND: The current study is focusing on the role of brain natriuretic peptide (BNP), a substrate of dipeptidyl peptidase-4 (DPP-4) enzyme, and its signaling survival pathway in the cardioprotective mechanism of sitagliptin, a DPP-4 inhibitor. METHODS: Male Wistar rats were randomized into 7 groups, sham, I/R, KT-5823 (selective protein kinase (PK) G inhibitor), 5-HD (selective mito-KATP channel blocker), sitagliptin (300 mg/kg, po), sitagliptin + KT-5823, and sitagliptin + 5-HD...
February 7, 2018: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29935364/spartan-promotes-genetic-diversification-of-the-immunoglobulin-variable-gene-locus-in-avian-dt40-cells
#2
Arisa Nakazato, Kinumi Kajita, Masato Ooka, Remi Akagawa, Takuya Abe, Shunichi Takeda, Dana Branzei, Kouji Hirota
Prolonged replication arrest on damaged templates is a cause of fork collapse, potentially resulting in genome instability. Arrested replication is rescued by translesion DNA synthesis (TLS) and homologous recombination (HR)-mediated template switching. SPARTAN, a ubiquitin-PCNA-interacting regulator, regulates TLS via mechanisms incompletely understood. Here we show that SPARTAN promotes diversification of the chicken DT40 immunoglobulin-variable λ gene by facilitating TLS-mediated hypermutation and template switch-mediated gene-conversion, both induced by replication blocks at abasic sites...
June 18, 2018: DNA Repair
https://www.readbyqxmd.com/read/29935285/sptoll1-and-sptoll2-modulate-the-expression-of-antimicrobial-peptides-in-scylla-paramamosain
#3
Yan Chen, Jude Juventus Aweya, Wanwei Sun, Xiaoyuan Wei, Yi Gong, Hongyu Ma, Yueling Zhang, Xiaobo Wen, Shengkang Li
Tolls and Toll-like receptors (TLRs) were the first pattern recognition receptors (PRRs) identified to play key roles in host innate immunity. However, relatively little is known about other types of Toll-like receptors in Scylla paramamosain, although a Toll-like receptor (SpToll1) has recently been cloned. In this study, we cloned and characterized another novel Toll-like receptor 2 (SpToll2) from S. paramamosain. The full-length cDNA of SpToll2 is 3391 bp with a 2646 bp open reading frame (ORF) encoding a putative protein of 881 amino acids, and predicted to contain six extracellular leucine-rich repeat (LRR) domains, a transmembrane domain and an intracellular Toll/IL-1 receptor (TIR) domain...
June 20, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29935171/targeting-formyl-peptide-receptors-to-facilitate-the-resolution-of-inflammation
#4
János G Filep, Meriem Shekeri, Driss El Kebir
The formyl peptide receptors (FPRs) are G protein coupled receptors that recognize a broad range of structurally distinct pathogen and danger-associated molecular patterns and mediate host defense to infection and tissue injury. It became evident that the cellular distribution and biological functions of FPRs extend beyond myeloid cells and governing their activation and trafficking. In recent years, significant progress has been made to position FPRs at check points that control the resolution of inflammation, tissue repair and return to homeostasis...
June 20, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29935151/inhibiting-rhoa-signaling-in-mice-increases-glucose-tolerance-and-numbers-of-enteroendocrine-and-other-secretory-cells-in-the-intestine
#5
Natalia Petersen, Thomas M Frimurer, Marianne Terndrup Pedersen, Kristoffer L Egerod, Nicolai J Wewer Albrechtsen, Jens J Holst, Anne Grapin-Botton, Kim B Jensen, Thue W Schwartz
BACKGROUND & AIMS: The glucagon like peptide 1 (GLP1) is produced by L cells in the intestine, and agonists of the GLP1 receptor are effective in treatment of diabetes. Levels of GLP1 increase with numbers of L cells. Agents that increase numbers of L cell might therefore be developed for treatment of diabetes. Ras homolog family member A (RHOA) signaling via Rho associated coiled-coil containing protein kinases 1 and 2 (ROCK1, ROCK2) controls cell differentiation, but it is not clear if this pathway regulates enteroendocrine differentiation in the intestinal epithelium...
June 20, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29935101/the-analysis-of-myotonia-congenita-mutations-discloses-functional-clusters-of-amino-acids-within-cbs2-domain-and-c-terminal-peptide-of-clc-1-channel
#6
Concetta Altamura, Sabrina Lucchiari, Dalila Sahbani, Gianna Ulzi, Giacomo P Comi, Paola D'Ambrosio, Roberta Petillo, Luisa Politano, Liliana Vercelli, Tiziana Mongini, Maria Teresa Dotti, Rosanna Cardani, Giovanni Meola, Mauro Lo Monaco, Emma Matthews, Michael G Hanna, Maria Rosaria Carratù, Diana Conte, Paola Imbrici, Jean-François Desaphy
Myotonia congenita (MC) is a skeletal muscle hyper-excitability disorder caused by loss-of-function mutations in the ClC-1 chloride channel. Mutations are scattered over the entire sequence of the channel protein, with more than 30 mutations located in the poorly characterized cytosolic C-terminal domain. In this study, we characterized, through patch clamp, seven ClC-1 mutations identified in patients affected by MC of various severity and located in the C-terminal region. The p.Val829Met, p.Thr832Ile, p...
June 23, 2018: Human Mutation
https://www.readbyqxmd.com/read/29935027/chemoselective-tyrosine-bioconjugation-through-sulfate-click-reaction
#7
Eun Joung Choi, Dongwook Jung, Jong-Seo Kim, Yan Lee, Byeong Moon Kim
A novel and selective tyrosine functionalization strategy through SuFEx (sulfur fluoride exchange) chemistry is presented. In this approach, we have discovered that free tyrosine (Tyr) reacts selectively with aryl fluorosulfate in the presence of various nucleophilic amino acid residues in bio-tolerable conditions. Chemoselectivity of this unique SuFEx reaction was confirmed in amino acid, peptide, and protein conjugations. The functions of peptides and proteins were well preserved as demonstrated from the Tyr-specific modification of cell-penetrating peptide and erythropoietin...
June 23, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29934949/the-hypolipidemic-effects-of-peptides-prepared-from-cicer-arietinum-in-ovariectomized-rats-and-hepg2-cells
#8
Wen Shi, Tao Hou, Weiwei Liu, Danjun Guo, Hui He
BACKGROUND: The lack of estrogen in postmenopausal women is a key risk factor of the disorders of lipid metabolism and obesity. Except for estrogen replacement therapy(ERT), Chickpea peptides(ChPs) may be a potential candidate for treating hyperlipidemia. RESULTS: In ovariectomized rats model,ChPs were found to decrease the body weight, adipose tissue size, total cholesterol(TC),total triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), atherogenic index(AI) in serum and liver TC, TG...
June 22, 2018: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/29934546/new-role-of-p2x7-receptor-in-an-alzheimer-s-disease-mouse-model
#9
Elodie Martin, Majid Amar, Carine Dalle, Ihsen Youssef, Céline Boucher, Caroline Le Duigou, Matthias Brückner, Annick Prigent, Véronique Sazdovitch, Annett Halle, Jean M Kanellopoulos, Bertrand Fontaine, Benoît Delatour, Cécile Delarasse
Extracellular aggregates of amyloid β (Aβ) peptides, which are characteristic of Alzheimer's disease (AD), act as an essential trigger for glial cell activation and the release of ATP, leading to the stimulation of purinergic receptors, especially the P2X7 receptor (P2X7R). However, the involvement of P2X7R in the development of AD is still ill-defined regarding the dual properties of this receptor. Particularly, P2X7R activates the NLRP3 inflammasome leading to the release of the pro-inflammatory cytokine, IL-1β; however, P2X7R also induces cleavage of the amyloid precursor protein generating Aβ peptides or the neuroprotective fragment sAPPα...
June 22, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29934490/new-tools-for-evaluating-protein-tyrosine-sulphation-tyrosyl-protein-sulphotransferases-tpsts-are-novel-targets-for-raf-protein-kinase-inhibitors
#10
Dominic P Byrne, Yong Li, Pawin Ngamlert, Krithika Ramakrishnan, Claire E Eyers, Carrow Wells, David H Drewry, William J Zuercher, Neil G Berry, David G Fernig, Patrick A Eyers
Protein tyrosine sulphation is a post-translational modification best known for regulating extracellular protein-protein interactions. Tyrosine sulphation is catalysed by two Golgi-resident enzymes termed Tyrosyl Protein Sulpho Transferases (TPSTs) 1 and 2, which transfer sulphate from the co-factor PAPS (3'-phosphoadenosine 5'-phosphosulphate) to a context-dependent tyrosine in a protein substrate. A lack of quantitative tyrosine sulphation assays has hampered the development of chemical biology approaches for the identification of small molecule inhibitors of tyrosine sulphation...
June 22, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29934401/pip30-fam192a-is-a-novel-regulator-of-the-nuclear-proteasome-activator-pa28%C3%AE
#11
Beata Jonik-Nowak, Thomas Menneteau, Didier Fesquet, Véronique Baldin, Catherine Bonne-Andrea, Francisca Méchali, Bertrand Fabre, Prisca Boisguerin, Sylvain de Rossi, Corinne Henriquet, Martine Pugnière, Manuelle Ducoux-Petit, Odile Burlet-Schiltz, Angus I Lamond, Philippe Fort, Séverine Boulon, Marie-Pierre Bousquet, Olivier Coux
PA28γ is a nuclear activator of the 20S proteasome involved in the regulation of several essential cellular processes, such as cell proliferation, apoptosis, nuclear dynamics, and cellular stress response. Unlike the 19S regulator of the proteasome, which specifically recognizes ubiquitylated proteins, PA28γ promotes the degradation of several substrates by the proteasome in an ATP- and ubiquitin-independent manner. However, its exact mechanisms of action are unclear and likely involve additional partners that remain to be identified...
June 22, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29934183/generation-of-bioactive-peptides-during-food-processing
#12
Fidel Toldrá, Milagro Reig, M-Concepción Aristoy, Leticia Mora
Large amounts of peptides are naturally generated in foods through the proteolysis phenomena taking place during processing. Such proteolysis is carried out either by endogenous enzymes in ripened foods or by the combined action of endogenous and microbial enzymes when fermented. Food proteins can also be isolated and hydrolysed by peptidases to produce hydrolysates. endo-peptidases act first followed by the successive action of exo-peptidases (mainly, tri- and di-peptidylpeptidases, aminopeptidases and carboxypeptidases)...
November 30, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29933716/high-sensitivity-troponin-i-in-persistent-atrial-fibrillation-relation-to-nt-probnp-and-markers-of-inflammation-and-haemostasis
#13
Anja Wiedswang Horjen, Sara Reinvik Ulimoen, Jon Norseth, Jesper Hastrup Svendsen, Pål Smith, Harald Arnesen, Ingebjørg Seljeflot, Arnljot Tveit
PURPOSE: As cardiac troponins emerge as prognostic markers in atrial fibrillation (AF), it is important to identify mechanisms initiating and perpetuating cardiac troponin release, including its relations to other circulating biomarkers, in AF populations. We studied associations between high-sensitivity troponin I (hs-TnI) and markers representing myocardial wall tension, inflammation and haemostasis in persistent AF. METHODS: In a double blind, placebo-controlled study, 171 patients referred for electrical cardioversion for persistent AF were randomised to receive candesartan or placebo for 3-6 weeks before and 6 months after cardioversion...
June 22, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29933540/-in-silico-structural-evaluation-of-short-cationic-antimicrobial-peptides
#14
Ilaria Passarini, Sharon Rossiter, John Malkinson, Mire Zloh
Cationic peptides with antimicrobial properties are ubiquitous in nature and have been studied for many years in an attempt to design novel antibiotics. However, very few molecules are used in the clinic so far, sometimes due to their complexity but, mostly, as a consequence of the unfavorable pharmacokinetic profile associated with peptides. The aim of this work is to investigate cationic peptides in order to identify common structural features which could be useful for the design of small peptides or peptido-mimetics with improved drug-like properties and activity against Gram negative bacteria...
June 21, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29933219/ms-based-quantification-of-rhoa-b-and-rhoc-adp-ribosylation
#15
Anke Schröder, Anastasia Benski, Anne Oltmanns, Ingo Just, Astrid Rohrbeck, Andreas Pich
Mono ADP-ribosylation is a common characteristic of bacterial toxins resulting to aberrant activation or inactivation of target proteins. The C3 exoenzyme of Clostridium botulinum (C3bot) ADP-ribosylates the small GTPases RhoA, RhoB and RhoC, leading to inactivation of these important regulators and impaired down-stream signaling. Quantification of ADP-ribosylation using gel migration assays, antibodies, and radioactivity-based methods are limited. Therefore a novel LC-MS-based method to specifically determine and quantify ADP-ribosylation of Rho GTPases was established...
June 7, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29933102/elimination-of-melanoma-by-sortase-a-generated-tcr-like-antibody-drug-conjugates-tl-adcs-targeting-intracellular-melanoma-antigen-mart-1
#16
Jun Lai, Yun Wang, Shan-Shan Wu, Ding Ding, Ze-Yu Sun, Ying Zhang, Jie Zhou, Zhan Zhou, Ying-Chun Xu, Li-Qiang Pan, Shu-Qing Chen
Most tumor-associated proteins are located inside tumor cells and thus are not accessible to current marketed therapeutic monoclonal antibodies or their cytotoxic conjugates. Human leukocyte antigen (HLA) class I can present peptides derived from intracellular tumor-associated proteins and somatically mutated proteins on the cell's surface, forming an HLA/peptide complex as tumor-specific antigens for T cell receptor (TCR) recognition. Therefore, HLA-mediated presentation of intracellular tumor antigen peptides provides a viable way to distinguish tumor cells from normal cells, which is important for broadening antigen selection, especially for antibody-drug conjugates (ADCs) regarding their highly cytotoxic payload...
June 15, 2018: Biomaterials
https://www.readbyqxmd.com/read/29933059/immunomodulatory-and-enhanced-antitumor-activity-of-a-modified-thymosin-%C3%AE-1-in-melanoma-and-lung-cancer
#17
Fanwen Wang, Bin Li, Pengcheng Fu, Qingqing Li, Heng Zheng, Xingzhen Lao
Tumor-targeted therapy is an attractive strategy for cancer treatment. Peptide hormone thymosin α1 (Tα1) has been used against several diseases, including cancer, but its activity is pleiotropic. Herein, we designed a fusion protein Tα1-iRGD by introducing the tumor homing peptide iRGD to Tα1. Results show that Tα1-iRGD can promote T-cell activation and CD86 expression, thereby exerting better effect and stronger inhibitory against melanoma and lung cancer, respectively, than Tα1 in vivo. These effects are indicated by the reduced densities of tumor vessels and Tα1-iRGD accumulation in tumors...
June 19, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29933026/the-phoenixins-from-discovery-of-the-hormone-to-identification-of-the-receptor-and-potential-physiologic-actions
#18
REVIEW
Lauren M Stein, Christopher J Haddock, Willis K Samson, Grant R Kolar, Gina L C Yosten
Using a series of classical protein purification techniques, coupled with more modern molecular approaches, a family of neuropeptides, the Phoenixins, were identified to be produced in brain and heart, and to bind selectively in pituitary gland, ovary and brain. These same binding sites were revealed, using a novel receptor identification strategy, to express the orphan G protein-coupled receptor, GPR173, the expression of which was required for the actions of phoenixin both in vivo and in vitro. In fact, studies using small interfering RNA molecules to compromise GPR173 expression revealed the physiologic relevance of the initially reported pharmacologic actions of the peptides...
June 19, 2018: Peptides
https://www.readbyqxmd.com/read/29933024/fabrication-of-hybrid-scaffold-based-on-hydroxyapatite-biodegradable-nanofibers-incorporated-with-liposomal-formulation-of-bmp-2-peptide-for-bone-tissue-engineering
#19
Marzieh Mohammadi, Mona Alibolandi, Khalil Abnous, Zahra Salmasi, Mahmoud Reza Jaafari, Mohammad Ramezani
In the present study, we fabricated an efficient, simple biomimetic scaffold to stimulate osteogenic differentiation of mesenchymal stem cells (MSCs). Electrospun poly L-lactic acid nanofibers were employed to mimic the nanofibrillar structure of bone proteins and coated with hydroxyapatite nanoparticles to simulate bone minerals. Thereafter, we regulated the release pattern of BMP-2 peptide through covalent attachment of an optimized liposomal formulation to the scaffold. The fabricated platform provided a sustained release profile of BMP-2 peptide up to 21days while supported cellular attachment and proliferation without cytotoxicity...
June 19, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29933008/novel-therapies-for-combating-chronic-neuropathological-sequelae-of-tbi
#20
REVIEW
Milos D Ikonomovic, Eric E Abrahamson, Shaun W Carlson, Steven H Graham, C Edward Dixon
Traumatic brain injury (TBI) is a risk factor for development of chronic neurodegenerative disorders later in life. This review summarizes the current knowledge and concepts regarding the connection between long-term consequences of TBI and aging-associated neurodegenerative disorders including Alzheimer's disease (AD), chronic traumatic encephalopathy (CTE), and Parkinsonism, with implications for novel therapy targets. Several aggregation-prone proteins such as the amyloid-beta (Aβ) peptides, tau proteins, and α-synuclein protein are involved in secondary pathogenic cascades initiated by a TBI and are also major building blocks of the hallmark pathological lesions in chronic human neurodegenerative diseases with dementia...
June 19, 2018: Neuropharmacology
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