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Bi-Yu Yuan, Wei-Zhe Liu, Xiao-Fang Wang, Yu-Zhe Zhang, Dai-Jun Yang, Chang-Lin Wang
For clinical use, it is essential to develop potent endomorphin (EM) analogs with reduced antinociceptive tolerance. In the present study, the antinociceptive activities and tolerance development of four potent EM-1 analogs with C-terminal oligoarginine-conjugation was evaluated and compared in the radiant heat paw withdrawal test. Following intracerebroventricular (i.c.v.) administration, all analogs 1-4 produced potent and prolonged antinociceptive effects. Notably, analogs 2 and 4 with the introduction of D-Ala in position 2 exhibited relatively higher analgesic potencies than those of analogs 1 and 3 with β-Pro substitution, consistent with their μ-opioid binding characteristic...
July 14, 2018: Peptides
Han-Ning Huang, Chieh-Yu Pan, Jyh-Yih Chen
Picornavirus is a highly contagious virus that usually infects cloven hoofed animals and causes foot-and-mouth disease. This disease is a major threat to livestock breeding worldwide and may lead to huge economic losses. Because effective vaccines or antiviral drugs remain unavailable, the search for new agents to combat FMDV infections is ongoing. Antimicrobial peptides are known to possess a broad range of biological activities, including antibacterial, antiviral, antitumor and immunomodulatory effects. In this work, we used a cell culture FMDV replication assay to evaluate several antimicrobial peptides for their ability to act as antiviral agents...
July 13, 2018: Peptides
Junling Liu, Kun Yang, Wenhua Xiao, Yunyi Le, Shan Lang, Jingjing Zhang, Rui Wei, Jin Yang, Tianpei Hong
The level of serum angiopoietin-like protein 8 (ANGPTL8), a novel hepatokine, is associated with obesity and type 2 diabetes mellitus (T2DM). To investigate whether serum ANGPTL8 level in patients with T2DM was affected by treatment with exenatide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, and to determine whether and how GLP-1R agonists regulated ANGPTL8 production in hepatocytes. A multiple-center trial was conducted in China. Among 240 patients with T2DM enrolled in this trial, 195 patients adhered to a 16-week exenatide treatment and follow-up...
July 9, 2018: Peptides
Predrag Jovanovic, Natasa Spasojevic, Nela Puskas, Bojana Stefanovic, Sladjana Dronjak
Social stress produces behavioral alterations, and autonomic and cardiac dysfunction in animals. In addition to the well-known roles of oxytocin on birth and maternal bonding, recent evidence shows that this neuropeptide possesses cardio-protective properties. However less is known about its role in the regulation of the autonomic nervous system. The direct influence of oxytocin on the cardiac catecholamine synthesizing enzyme, transport beta-adrenoceptors and muscarinic receptors in animals exposed to chronic social isolation stress has not yet been studied...
June 30, 2018: Peptides
Shun Onishi, Tatsuru Kaji, Waka Yamada, Kazuhiko Nakame, Seiro Machigashira, Masato Kawano, Keisuke Yano, Toshio Harumatsu, Koji Yamada, Ryuta Masuya, Takafumi Kawano, Motoi Mukai, Taiji Hamada, Masakazu Souda, Takako Yoshioka, Akihide Tanimoto, Satoshi Ieiri
BACKGROUND: Since short bowel syndrome (SBS) patients face life-threatening conditions, the development of therapeutic strategies to induce intestinal adaptation has been investigated. Ghrelin, a ligand of growth hormone (GH) secretagogue-receptor that stimulates the release of GH and insulin like growth factor-1 (IGF-1), has several pleiotropic effects. We investigated whether ghrelin induces intestinal adaptation in parenterally fed rats with SBS. METHODS: Sprague-Dawley rats underwent venous catheterization and were divided into 3 groups: those receiving 90% small bowel resection while leaving the proximal jejunum and distal ileum (90% SBR) with TPN (SBS/TPN group), those receiving 90% SBR with TPN + ghrelin (SBS/TPN/ghrelin group), and those receiving sham operation and fed chow (sham group)...
June 29, 2018: Peptides
Gleuber Henrique Marques-Oliveira, Thaís Marques da Silva, William Gustavo Lima, Helder Magno Silva Valadares, Valéria Ernestânia Chaves
Leptin and its receptor are widely distributed in several tissues, mainly in white adipose tissue. The plasma leptin is highly correlated with body mass index in rodents and humans, being documented that serum leptin levels reduces in the fasting state and increase during refeeding, similarly to insulin release by pancreatic islets. Insulin appears to increase leptin mRNA and protein expression and its release by adipocytes. Some studies have suggested that insulin acts through the activation of the transcription factors: sterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein-α (C/EBP-α) and specificity protein 1 (Sp1)...
June 25, 2018: Peptides
Md Abdullah Al Baki, Jin Kyo Jung, Yonggyun Kim
A disaccharide, trehalose, is a main hemolymph sugar of the legume pod borer, Maruca vitrata larvae, but its titers fluctuated with feeding activity. During diurnal feeding in the photophase, hemolymph trehalose remained at a relatively low level (69 mM) and increased (98 mM) during scotophase. Starvation significantly increased the hemolymph trehalose level, in which the elevation of trehalose titers was dependent on the non-feeding period. The down-regulation of the trehalose level during the active feeding period seemed to result from mediation of the insulin/IGF signal (IIS)...
June 20, 2018: Peptides
Diego A T Pires, Luisa M R Arake, Luciano P Silva, Alejandro Lopez-Castillo, Maura V Prates, Claudia J Nascimento, Carlos Bloch
A previously undescribed six residues long peptide His-Arg-Phe-Leu-Arg-His was identified and purified from the skin secretion of the amphibian Phyllomedusa centralis. A synthetic analogue carboxyamidated HRFLRH-NH2 showed structural changes induced by CO2 and metal ions in aqueous solution when analyzed by NMR. The present work reports NMR structures for the carboxyamidated hexapeptide in the presence CO2 , Zn2+ and Cd2+ , suggesting possible affinity regions on the polypeptide chain for each ligand. The NMR structures were optimized by DFT to identify probable biding sites of these species in the polypeptide structure...
June 19, 2018: Peptides
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
Takayuki Yamagishi, Haruka Endo, Keisuke Fukumura, Shinji Nagata, Tohru Hayakawa, Satomi Adegawa, Mayu Kasubuchi, Ryoichi Sato
Enteroendocrine cells in the insect midgut are thought to secrete peptide hormones in response to the nutritional state. However, the role of dietary compounds in inducing peptide hormone secretion from enteroendocrine cells in insects remains unknown. In the present study, we demonstrated that several dietary compounds from mulberry leaves, including glucose, amino acids, and the secondary metabolite chlorogenic acid, induced significant secretion of tachykinin-related peptides from isolated silkworm midguts at the luminal concentrations measured in fed larvae...
June 19, 2018: Peptides
Jens P Goetze, Jens F Rehfeld
The mammalian heart is by now an established endocrine organ whose myocytes in a regulated manner release atrial and ventricular natriuretic peptides (ANP and BNP). But like other hormone-producing cells in classic endocrine organs, the cardiac myocytes also express genes of additional peptide hormones. One such hormone gene is that of the well-known pleiotropic gut-brain peptide system, cholecystokinin (CCK), which is expressed at mRNA and protein levels in both atrial and ventricular cardiac myocytes. The posttranslational processing of proCCK in the myocytes, however, deviates substantially from that of other CCK-producing cells...
June 11, 2018: Peptides
Yasuaki Nakagawa, Toshio Nishikimi, Koichiro Kuwahara
The natriuretic peptide family consists of three biologically active peptides: atrial natriuretic peptide (ANP), brain (or B-type) natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Among these, ANP and BNP are secreted by the heart and act as cardiac hormones. Both ANP and BNP preferentially bind to natriuretic peptide receptor-A (NPR-A or guanylyl cyslase-A) and exert similar effects through increases in intracellular cyclic guanosine monophosphate (cGMP) within target tissues. Expression and secretion of ANP and BNP are stimulated by various factors and are regulated via multiple signaling pathways...
May 31, 2018: Peptides
Biswajit Mishra, Xiuqing Wang, Tamara Lushnikova, Yingxia Zhang, Radha M Golla, Jayaram Lakshmaiah Narayana, Chunfeng Wang, Timothy R McGuire, Guangshun Wang
Antimicrobial peptides are a special class of natural products with potential applications as novel therapeutics. This study focuses on six temporins (four with no activity data and two as positive controls). Using synthetic peptides, we report antibacterial, antifungal, and anticancer activities of temporins-CPa, CPb, 1Ga, 1Oc, 1Ola, and 1SPa. While temporin-1Ga and temporin-1OLa showed higher antifungal and anticancer activity, most of these peptides were active primarily against Gram-positive bacteria. Temporin-1OLa, with the highest cell selectivity index, could preferentially kill methicillin-resistant Staphylococcus aureus (MRSA), consistent with a reduced hemolysis in the presence of bacteria...
May 26, 2018: Peptides
Ian Warbrick, Simon W Rabkin
Heart failure with preserved ejection fraction (HFpEF) represents an important cardiac condition because of its increasing prevalence, resistance to treatment and high associated morbidity and mortality. Two of the major mechanisms responsible for HFpEF are impaired cardiomyocyte sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA2a), which is responsible for calcium reuptake into the SR, and cardiac fibroblasts/myofibroblasts that produce collagen or myocardial fibrosis. Phospholamban (PLB), in the SR and endoplasmic reticulum, is the primary regulator of SERCA2a in the heart and acts as a reversible inhibitor of SERCA2a...
May 25, 2018: Peptides
Selvinaz Dalaklioglu, Arda Tasatargil, Nilay Kuscu, Soner Celik, Ciler Celik-Ozenci, Sebahat Ozdem, Ayse Barutcigil, Ikbal Kucukcetin
OBJECTIVE: The aim of this study was to investigate the effect of chronic exendin-4 (Ex-4) treatment on corpus cavernosum (CC) dysfunction in methylglyoxal (MGO) administered rats. METHODS: Male rats were divided into four groups as control, MGO (75 mg/kg/day in drinking water for 12 weeks), MGO + low-dose Ex-4 (0.1 μg/kg twice daily subcutaneously for 12 weeks concomitant with MGO), and MGO + high-dose Ex-4 (1 μg/kg twice daily subcutaneously for 12 weeks concomitant with MGO)...
May 21, 2018: Peptides
Takeshi Tokudome, Kentaro Otani, Mikiya Miyazato, Kenji Kangawa
Ghrelin, a growth hormone-releasing peptide that was first discovered in the stomach of rats in 1999, is an endogenous ligand of growth hormone secretagogue receptor. Ghrelin exerts its potent growth hormone-releasing and orexigenic activities by binding to specific receptors in the brain. Subsequent studies showed that ghrelin participates in the regulation of diverse processes, including energy balance, body weight maintenance, and glucose and fat metabolism, and demonstrated that ghrelin is beneficial for treatment of cardiac diseases...
May 20, 2018: Peptides
Larisa Serebryakova, Marina Pal'keeva, Irina Studneva, Alexander Molokoedov, Oksana Veselova, Michael Ovchinnikov, Radik Gataulin, Maria Sidorova, Oleg Pisarenko
Agonists and antagonists for galanin receptor subtypes GalR1-3 can be used as putative therapeutics targets for the treatment of various human diseases. However, effects of galanin and its N-terminal fragments on myocardial ischemia/reperfusion injury remain unclear. This study was designed to assess the ability of the full-length galanin (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2, G1), the natural fragments WTLNSAGYLL-NH2 (G2) and WTLNSAGYLLGPHA (G3), and their modified analogs WTLNAAGYLL (G4) and WTLNSAGYLLGPβAH (G5) to limit acute myocardial infarction in rats in vivo...
May 3, 2018: Peptides
François Marceau, Marie-Thérèse Bawolak, Jean-Philippe Fortin, Guillaume Morissette, Caroline Roy, Hélène Bachelard, Lajos Gera, Xavier Charest-Morin
Kinins are the small and fragile hydrophilic peptides related to bradykinin (BK) and derived from circulating kininogens via the action of kallikreins. Kinins bind to the preformed and widely distributed B2 receptor (B2 R) and to the inducible B1 receptor (B1 R). B2 Rs and B1 Rs are related G protein coupled receptors that possess natural agonist ligands of nanomolar affinity (BK and Lys BK for B2 Rs, Lys-des-Arg9 -BK for B1 R). Decades of structure-activity exploration have resulted in the production of peptide analogs that are antagonists, one of which is clinically used (the B2 R antagonist icatibant), and also non-peptide ligands for both receptor subtypes...
July 2018: Peptides
Ya Wen, Rong Chen, Chunhua Zhu, Huimin Qiao, Ying Liu, Hui Ji, Jiangyong Miao, Linyu Chen, Xiaoxia Liu, Yi Yang
Endothelial progenitor cells (EPCs) are of great importance in the process of endogenous blood vessel repair to maintain endothelial integrity and have been applied in a wide range of models of ischemic diseases. MicroRNAs represent a class of non-protein coding endogenous RNAs with 19-24 nucleotides in length and serve an important role in multiple physiological and pathological processes, including angiogenesis. It has been reported that miR-503 reduces angiogenesis in tumorigenesis. However, to our knowledge, the precise role of miR-503 in the regulation of EPCs remains unclear...
July 2018: Peptides
Ilaria Serra, Mariano Casu, Matteo Ceccarelli, Paula Gameiro, Andrea C Rinaldi, Mariano Andrea Scorciapino
Antimicrobial peptides attracted increasing interest in last decades due to the rising concern of multi-drug resistant pathogens. Dendrimeric peptides are branched molecules with multiple copies of one peptide functional unit bound to the central core. Compared to linear analogues, they usually show improved activity and lower susceptibility to proteases. Knowledge of structure-function relationship is fundamental to tailor their properties. This work is focused on SB056, the smallest example of dendrimeric peptide, whose amino acid sequence is WKKIRVRLSA...
July 2018: Peptides
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