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https://www.readbyqxmd.com/read/27923202/structure-based-optimization-of-salt-bridge-network-across-the-complex-interface-of-ptpn4-pdz-domain-with-its-peptide-ligands-in-neuroglioma
#1
Xian Xiao, Qiang-Hua He, Li-Yan Yu, Song-Qing Wang, Yang Li, Hua Yang, Ai-Hua Zhang, Xiao-Hong Ma, Yu-Jie Peng, Bing Chen
The PTP non-receptor type 4 (PTPN4) is an important regulator protein in learning, spatial memory and cerebellar synaptic plasticity; targeting the PDZ domain of PTPN4 has become as attractive therapeutic strategy for human neuroglioma. Here, we systematically examined the complex crystal structures of PTPN4 PDZ domain with its known peptide ligands; a number of charged amino acid residues were identified in these ligands and in the peptide-binding pocket of PDZ domain, which can constitute a complicated salt-bridge network across the complex interface...
November 30, 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/27923041/crystal-structure-of-the-salmonella-typhimurium-effector-gtge
#2
Caishuang Xu, Guennadi Kozlov, Kathy Wong, Kalle Gehring, Miroslaw Cygler
Salmonella Typhimurium GtgE is an effector protein contributing to the virulence of this pathogen. It was shown to possess highly selective proteolytic activity against a subset of Rab proteins that helps in evasion of Salmonella-containing vacuole (SCV) fusion with lysosomes. Cys45, His151 and Asp169 are essential for proteolytic activity. The structure of a C-terminal fragment GtgE(79-214) indicated the presence of a papain-like fold. Here, we present the structure of GtgE(17-214) containing the fully assembled active site...
2016: PloS One
https://www.readbyqxmd.com/read/27922937/repurposing-ospemifene-for-potentiating-an-antigen-specific-immune-response
#3
Chiao-Jung Kao, Gregory T Wurz, Yi-Chen Lin, Daniel P Vang, Brian Phong, Michael W DeGregorio
OBJECTIVE: Ospemifene, an estrogen receptor agonist/antagonist approved for the treatment of dyspareunia and vaginal dryness in postmenopausal women, has potential new indications as an immune modulator. The overall objective of the present series of preclinical studies was to evaluate the immunomodulatory activity of ospemifene in combination with a peptide cancer vaccine. METHODS: Immune regulating effects, mechanism of action and structure activity relationships of ospemifene and related compounds were evaluated by examining expression of T-cell activating cytokines in vitro, and antigen-specific immune response and cytotoxic T-lymphocyte activity in vivo...
December 5, 2016: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/27922889/pump-speed-optimization-in-stable-patients-with-a-left-ventricular-assist-device
#4
Lotte E Couperus, Victoria Delgado, Mand J H Khidir, Marijke P M Vester, Meindert Palmen, Marta Fiocco, Eduard R Holman, Laurens F Tops, Robert J M Klautz, Harriëtte F Verwey, Martin J Schalij, Saskia L M A Beeres
Optimal left ventricular assist device (LVAD) functioning and preservation of right ventricular (RV) function are major survival determinants in destination therapy (DT)-LVAD recipients. Currently, the indication for routine pump speed optimization in stable patients and its effect on RV function at follow-up remain underexplored. Hemodynamically stable patients (N=17, age 61 [interquartile range {IQR} 51-66]years; 13 [77%] male) underwent a routine speed ramp test. Echocardiographic images were obtained at incremental speed settings to determine optimal pump speed...
December 2, 2016: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/27922860/the-impact-of-radiological-response-to-peptide-receptor-radionuclide-therapy-on-overall-survival-in-patients-with-metastatic-midgut-neuroendocrine-tumors
#5
Mehmet Yalchin, Amelia Oliveira, Eleni Theocharidou, Deborah Pencharz, Shaunak Navalkissoor, Ann-Marie Quigley, Martin Walker, Martyn Caplin, Christos Toumpanakis
PURPOSE OF THE REPORT: Peptide receptor radionuclide therapy (PRRT) is an effective treatment for advanced neuroendocrine tumors (NET); however, long-term survival data are scarce. The aim of this study is to determine long-term survival in patients with metastatic midgut NET, according to response to PRRT. PATIENTS AND METHODS: One hundred thirty-three consecutive patients with progressive metastatic midgut NET underwent PRRT. Response at 1 year post PRRT was classified as partial response, stable disease, disease progression, or death...
December 3, 2016: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/27922697/regulation-of-pd-l1-expression-in-a-high-grade-invasive-human-oral-squamous-cell-carcinoma-microenvironment
#6
Mariko Hirai, Hiroko Kitahara, Yutaka Kobayashi, Koroku Kato, George Bou-Gharios, Hiroyuki Nakamura, Shuichi Kawashiri
Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients...
December 2, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27922666/antimicrobial-peptide-ll-37-promotes-yb-1-expression-and-the-viability-migration-and-invasion-of-malignant-melanoma-cells
#7
Jinjing Jia, Yan Zheng, Wei Wang, Yongping Shao, Zhengxiao Li, Qiong Wang, Yuan Wang, Huling Yan
The cathelicidin antimicrobial peptide, LL-37, is a multifunctional peptide with a broad spectrum of antimicrobial activities, such as chemotaxis and neutralizing endotoxins. Previous studies have demonstrated that it LL‑37 serves a functional role in the development of numerous types of cancer including ovarian, breast, prostate and lung cancer. However, its role in the development of malignant melanoma (MM) remains unclear. To determine the role of LL‑37 and the potential interaction with Y-box binding protein 1 (YB‑1) in MM, RNA interference, western blot, reverse transcription-quantitative polymerase chain reaction, MTT and Transwell assays were performed...
December 2, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27922195/the-neuropeptide-cortistatin-attenuates-experimental-autoimmune-myocarditis-via-inhibition-of-cardiomyogenic-t-cell-driven-inflammatory-responses
#8
Virginia Delgado-Maroto, Clara P Falo, Irene Forte-Lago, Norma Adan, Maria Morell, Elena Maganto-Garcia, Gema Robledo, Francisco O'Valle, Andrew H Lichtman, Elena Gonzalez-Rey, Mario Delgado
BACKGROUND AND PURPOSE: Myocarditis is an inflammatory and autoimmune cardiovascular disease that causes dilated myocardiopathy and is responsible of high morbidity and mortality worldwide. Cortistatin is a neuropeptide produced by neurons and cells of immune and vascular systems. Besides its action in locomotor activity and sleep, cortistatin inhibits inflammation in different experimental models of autoimmune diseases. However, its role in inflammatory cardiovascular disorders is unexplored...
December 6, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27922185/relaxin-family-peptides-structure-activity-relationship-studies
#9
REVIEW
Nitin A Patil, K Johan Rosengren, Frances Separovic, John D Wade, Ross A D Bathgate, Mohammed Akhter Hossain
The human relaxin peptide family consists of seven cystine-rich peptides, four of which are known to signal through relaxin family peptide receptors, RXFP1-4. Considering the vital roles these peptides play in physiology and various diseases, they are of considerable importance for drug discovery and development. Detailed structure-activity relationship (SAR) studies towards understanding the role of important residues in each of these peptides have been reported over the years and utilised for design of antagonists and minimised agonist variants...
December 6, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27922063/design-and-mechanistic-insight-into-ultrafast-calcium-indicators-for-monitoring-intracellular-calcium-dynamics
#10
Nordine Helassa, Borbala Podor, Alan Fine, Katalin Török
Calmodulin-based genetically encoded fluorescent calcium indicators (GCaMP-s) are powerful tools of imaging calcium dynamics from cells to freely moving animals. High affinity indicators with slow kinetics however distort the temporal profile of calcium transients. Here we report the development of reduced affinity ultrafast variants of GCaMP6s and GCaMP6f. We hypothesized that GCaMP-s have a common kinetic mechanism with a rate-limiting process in the interaction of the RS20 peptide and calcium-calmodulin...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922054/first-insight-into-the-proteome-landscape-of-the-porcine-short-posterior-ciliary-arteries-key-signalling-pathways-maintaining-physiologic-functions
#11
Caroline Manicam, Natarajan Perumal, Norbert Pfeiffer, Franz H Grus, Adrian Gericke
Short posterior ciliary arteries (sPCA) provide the major blood supply to the optic nerve head. Emerging evidence has linked structural and functional anomalies of sPCA to the pathogenesis of several ocular disorders that cause varying degrees of visual loss, particularly anterior ischaemic optic neuropathy and glaucoma. Although the functional relevance of this vascular bed is well-recognized, the proteome of sPCA remains uncharacterized. Since the porcine ocular system closely resembles that of the human's and is increasingly employed in translational ophthalmic research, this study characterized the proteome of porcine sPCA employing the mass spectrometry-based proteomics strategy...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921402/developing-a-rat-model-of-dilated-cardiomyopathy-with-improved-survival
#12
Li-Juan Shen, Shu Lu, Yong-Hua Zhou, Lan Li, Qing-Min Xing, Yong-Liang Xu
To compare the continuous infusion and intermittent bolus injection administration protocols of doxorubicin (Dox) under the same cumulative dose (12 mg/kg), and establish a rat dilated cardiomyopathy model with improved survival, a total of 150 Sprague-Dawley (SD) rats were divided into three groups: a control group, administered with normal saline; a Dox 1 group, administration twice a week at 1 mg/kg; a Dox 2, administration once a week at 2 mg/kg. Mortality rates in the Dox 1 and Dox 2 groups were 22% and 48%, respectively (P<0...
2016: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/27921358/low-methoxyl-lemon-pectin-attenuates-inflammatory-responses-and-improves-intestinal-barrier-integrity-in-caerulein-induced-experimental-acute-pancreatitis
#13
Yajun Sun, Yue He, Fei Wang, Hao Zhang, Paul de Vos, Jia Sun
SCOPE: Acute pancreatitis (AP) is a common clinical acute abdominal disease. The intestinal injury associated with AP will aggravate the condition retroactively. This study investigates whether the low-methoxyl pectin (LMP) isolated from lemon could attenuate AP and associated intestinal injury. METHODS AND RESULTS: Experimental AP was induced in BALB/c mice by caerulien (CAE) hyperstimulation. Nutritional prophylactic group was pre-fed with 5% LMP supplemented forage three days before AP induction...
December 6, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27921334/synacton-and-individual-activity-of-synthetic-and-natural-corticotropins
#14
T V Vyunova, L A Andreeva, K V Shevchenko, N F Myasoedov
Short endogenous peptides represent one of the most important constituents of the mammalian body's general regulatory system. Some synthesized analogs and modified natural peptides (eg, corticotropins) also show high biological activity. Nevertheless, the mechanism of action of regulatory peptides remains unclear. To explain the effects of peptides of intermolecular processes, the hypothesis that a synactonal mechanism underlies the action of regulatory peptides, exemplified by the heptapeptide Semax, has been proposed...
December 6, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27921323/the-application-of-strand-invasion-phenomenon-directed-by-peptide-nucleic-acid-pna-and-single-stranded-dna-binding-protein-ssb-for-the-recognition-of-specific-sequences-of-human-endogenous-retroviral-herv-w-family
#15
Grzegorz Machnik, Łukasz Bułdak, Jarosław Ruczyński, Tomasz Gąsior, Małgorzata Huzarska, Dariusz Belowski, Magdalena Alenowicz, Piotr Mucha, Piotr Rekowski, Bogusław Okopień
The HERV-W family of human endogenous retroviruses represents a group of numerous sequences that show close similarity in genetic composition. It has been documented that some members of HERV-W-derived expression products are supposed to play significant role in humans' pathology, such as multiple sclerosis or schizophrenia. Other members of the family are necessary to orchestrate physiological processes (eg, ERVWE1 coding syncytin-1 that is engaged in syncytiotrophoblast formation). Therefore, an assay that would allow the recognition of particular form of HERV-W members is highly desirable...
December 6, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27921280/ph-responsive-triblock-copolymeric-micelles-decorated-with-a-cell-penetrating-peptide-provide-efficient-doxorubicin-delivery
#16
Khen Eng Ng, Mohd Cairul Iqbal Mohd Amin, Haliza Katas, Muhammad Wahab Amjad, Adeel Masood Butt, Prashant Kesharwani, Arun K Iyer
This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly-L-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10(-7) M) and encapsulated doxorubicin in the core region, with a 34.2% (w/w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7...
December 2016: Nanoscale Research Letters
https://www.readbyqxmd.com/read/27921229/an-extracellular-proteasome-releases-endostatin-from-human-collagen-xviii
#17
Maria L V Reiss-Pistilli, Detlef Schuppan, Madalena M S Barroso, Iranaia Assunção-Miranda, Shirley Farias, Letícia Lery, Michael Bauer, Luiz Juliano, Maria A Juliano, Tatiana Coelho-Sampaio
Endostatin is a potent anti-angiogenic and anti-tumor protein capable of regressing tumors without inducing acquired resistance. Since it is a fragment of the parental molecule, collagen XVIII, its endogenous production depends on the activity of a specific proteolytic enzyme. While such an enzyme has been described in mice, a human counterpart has not been identified so far. Here, we searched for this enzyme by using a fluorescence resonance energy transfer peptide containing the cleavage site of human collagen XVIII...
December 5, 2016: Angiogenesis
https://www.readbyqxmd.com/read/27921176/two-feet-on-the-membrane-uptake-of-clostridial-neurotoxins
#18
Andreas Rummel
The extraordinary potency of botulinum neurotoxins (BoNT) and tetanus neurotoxin (TeNT) is mediated by their high neurospecificity, targeting peripheral cholinergic motoneurons leading to flaccid and spastic paralysis, respectively, and successive respiratory failure. Complex polysialo gangliosides accumulate BoNT and TeNT on the plasma membrane. The ganglioside binding in BoNT/A, B, E, F, G, and TeNT occurs via a conserved ganglioside-binding pocket within the most carboxyl-terminal 25 kDa domain HCC, whereas BoNT/C, DC, and D display here two different ganglioside binding sites...
December 1, 2016: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/27921110/multifunctional-pei-entrapped-gold-nanoparticles-enable-efficient-delivery-of-therapeutic-sirna-into-glioblastoma-cells
#19
Lingdan Kong, Jieru Qiu, Wenjie Sun, Jia Yang, Mingwu Shen, Lu Wang, Xiangyang Shi
RNA interference (RNAi) has been considered as a promising strategy for effective treatment of cancer. However, the easy degradation of small interfering RNA (siRNA) limits its extensive applications in gene therapy. For safe and effective delivery of siRNA, a novel vector system possessing excellent biocompatibility, highly efficient transfection efficiency and specific targeting properties has to be considered. In this study, we report the use of polyethyleneimine (PEI)-entrapped gold nanoparticles (Au PENPs) modified with an arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide via a poly(ethylene glycol) (PEG) spacer as a vector for Bcl-2 (B-cell lymphoma-2) siRNA delivery to glioblastoma cells...
December 6, 2016: Biomaterials Science
https://www.readbyqxmd.com/read/27921108/a-novel-antioxidant-peptide-derived-from-wheat-germ-prevents-high-glucose-induced-oxidative-stress-in-vascular-smooth-muscle-cells-in-vitro
#20
Siyuan Chen, Dingbo Lin, Yulong Gao, Xiaozhou Cao, Xinchun Shen
The ingestion of whole wheat products is responsible for the prevention of a number of chronic diseases. The aim of this study is to characterize the molecular properties of a novel wheat germ-derived antioxidant peptide (AOP) in protection against high glucose-induced oxidative stress in vascular smooth muscle cells (VSMCs). AOP (amino acid sequence AREGETVVPG) was isolated from wheat germ albumin using dual-enzymatic hydrolysis/separation, followed by MS/MS. The in vitro IC50 value for Fe(2+) chelation was 0...
December 6, 2016: Food & Function
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