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https://www.readbyqxmd.com/read/28107393/t-cell-subset-and-stimulation-strength-dependent-modulation-of-t-cell-activation-by-kv1-3-blockers
#1
Wai-Ping Fung-Leung, Wilson Edwards, Yi Liu, Karen Ngo, Julianty Angsana, Glenda Castro, Nancy Wu, Xuejun Liu, Ronald V Swanson, Alan D Wickenden
Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1...
2017: PloS One
https://www.readbyqxmd.com/read/28106207/natural-sweetener-agave-inhibits-gastric-emptying-in-rats-by-a-cholecystokinin-2-and-glucagon-like-peptide-1-receptor-dependent-mechanism
#2
E Bihter Gürler, Dilek Özbeyli, Hülya Buzcu, Sezin Bayraktar, İrem Carus, Beyza Dağ, Yasemin Geriş, Seda Jeral, Berrak Ç Yeğen
Low-calorie sweeteners are considered to be beneficial in calorie control, but the impact of these sweeteners on gastric emptying is not well described. The purpose of this study was to compare the gastric emptying rate of agave nectar with those of glucose and fructose, and to evaluate the interaction of cholecystokinin (CCK)-1, CCK-2 and glucagon-like peptide-1 (GLP-1) receptors in agave-induced alterations in gastric emptying. Female Sprague-Dawley rats were fitted with gastric cannulas. Following the recovery, the gastric emptying rates of glucose, fructose and agave at 12...
January 20, 2017: Food & Function
https://www.readbyqxmd.com/read/28106152/cancer-immunotherapy-immune-checkpoint-blockade-and-associated-endocrinopathies
#3
REVIEW
David J Byun, Jedd D Wolchok, Lynne M Rosenberg, Monica Girotra
Advances in cancer therapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (IRAEs), which resemble autoimmune disease...
January 20, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28106020/renin-angiotensin-aldosterone-system-blockers-and-cardiovascular-outcomes-a-meta-analysis-of-randomized-clinical-trials
#4
Pınar Kızılırmak, Yağız Üresin, Oktay Özdemir, Burçak Kılıçkıran Avcı, Lale Tokgözoğlu, Zeki Öngen
OBJECTIVE: Hypertension is the most prevalent modifiable risk factor for cardiovascular (CV) and cerebrovascular morbidity and mortality. This study aimed to assess the effects of renin-angiotensin-aldosterone system (RAAS) blockade on CV outcomes. METHODS: This study was designed according to the Preferred Reporting Items for Systemic reviews and Meta-Analyses statement. Databases were searched for articles published as of December 2014. Two sets of studies were selected...
January 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28105751/stim-1-and-orai-1-channel-mediate-angiotensin-ii-induced-expression-of-egr-1-in-vascular-smooth-muscle-cells
#5
Estelle R Simo-Cheyou, Ju Jing Tan, Ryszard Grygorczyk, Ashok K Srivastava
An upregulation of Egr-1 expression has been reported in models of atherosclerosis and intimal hyperplasia and, various vasoactive peptides and growth promoting stimuli have been shown to induce the expression of Egr-1 in vascular smooth muscle cells (VSMC). Angiotensin-II (Ang-II) is a key vasoactive peptide that has been implicated in the pathogenesis of vascular diseases. Ang-II elevates intracellular Ca(2+) through activation of the store-operated calcium entry (SOCE) involving an inositol-3-phosphate receptor (IP3R)-coupled depletion of endoplasmic reticular Ca(2+) and a subsequent activation of the stromal interaction molecule 1 (STIM-1) /Orai-1 complex...
January 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28105664/visceral-and-somatic-pain-modalities-reveal-nav-1-7-independent-visceral-nociceptive-pathways
#6
James R F Hockley, Rafael González-Cano, Sheridan McMurray, Miguel A Tejada-Giraldez, Cian McGuire, Antonio Torres, Anna L Wilbrey, Vincent Cibert-Goton, Francisco R Nieto, Thomas Pitcher, Charles H Knowles, José Manuel Baeyens, John N Wood, Wendy J Winchester, David C Bulmer, Cruz Miguel Cendán, Gordon McMurray
Voltage-gated sodium channel NaV 1.7 is required for acute and inflammatory pain in mice and humans but its significance for visceral pain is unknown. Here we examine the role of NaV 1.7 in visceral pain processing and the development of referred hyperalgesia using a conditional nociceptor-specific NaV 1.7 knockout mouse (NaV 1.7(Nav1.8) ) and selective small-molecule NaV 1.7 antagonist PF-5198007. NaV 1.7(Nav1.8) mice showed normal nociceptive behaviours to intracolonic application of either capsaicin or mustard oil, stimuli known to evoke sustained nociceptor activity and sensitization following tissue damage, respectively...
January 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28105368/clinical-and-immunologic-correlates-of-response-to-pd-1-blockade-in-a-patient-with-metastatic-renal-medullary-carcinoma
#7
Kathryn E Beckermann, Pradeep C Jolly, Ju Y Kim, Jennifer Bordeaux, Igor Puzanov, W Kimryn Rathmell, Douglas B Johnson
BACKGROUND: Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically in association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, and dismal clinical outcomes. Currently available therapies, including cisplatin-based combination chemotherapy, multi-tyrosine kinase, and mTOR inhibitor strategies demonstrate either transient responses or minimal activity. Therefore, further molecular characterization and additional treatment strategies are urgently needed in this aggressive disease...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28104840/tumor-aneuploidy-correlates-with-markers-of-immune-evasion-and-with-reduced-response-to-immunotherapy
#8
Teresa Davoli, Hajime Uno, Eric C Wooten, Stephen J Elledge
Immunotherapies based on immune checkpoint blockade are highly effective in a subset of patients. An ongoing challenge is the identification of biomarkers that predict which patients will benefit from these therapies. Aneuploidy, also known as somatic copy number alterations (SCNAs), is widespread in cancer and is posited to drive tumorigenesis. Analyzing 12 human cancer types, we find that, for most, highly aneuploid tumors show reduced expression of markers of cytotoxic infiltrating immune cells, especially CD8(+) T cells, and increased expression of cell proliferation markers...
January 20, 2017: Science
https://www.readbyqxmd.com/read/28104456/rapid-stimulation-of-sodium-intake-combining-aldosterone-into-the-4-th-ventricle-and-the-blockade-of-the-lateral-parabrachial-nucleus
#9
S Gasparini, M R Melo, G F Leite, P A Nascimento, G M F Andrade-Franzé, J V Menani, E Colombari
Chronic infusion of aldosterone into the 4(th) ventricle (4(th) V) induces robust daily sodium intake, whereas acute injection of aldosterone into the 4(th) V produces no sodium intake. The inhibitory mechanism of the lateral parabrachial nucleus (LPBN) restrains sodium intake induced by different natriorexigenic stimuli and might affect the acute response to aldosterone into the 4(th) V. In the present study, 1.8% NaCl and water intake was tested in rats treated with acute injections of aldosterone into the 4(th) V combined with the blockade of the inhibitory mechanisms with injections of moxonidine (α2 adrenergic/imidazoline agonist) or methysergide (a serotonergic antagonist) into the LPBN...
January 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28104442/prostaglandin-e2-receptor-4-mediates-renal-cell-carcinoma-intravasation-and-metastasis
#10
Yushan Zhang, Hamsa Thayele Purayil, Joseph B Black, Francis Fetto, Lauren D Lynch, Jude N Masannat, Yehia Daaka
Treatment options for metastatic renal cell carcinoma (RCC) are limited. In this study, we investigated impact of prostaglandin E2 (PGE2) receptor 4 (EP4) on RCC metastasis. We found that knockdown of EP4 in two RCC cell lines, ACHN and SN12C, does not affect xenograft tumor take or growth rate in mice, but reduces metastasis by decreasing tumor intravasation. Using chick chorioallantoic membrane (CAM) assay, we confirmed that blockade of EP4 signaling inhibits tumor intravasation. In vitro studies associated EP4 expression and activity with RCC cell transendothelial migration (TEM)...
January 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28104435/inhibition-of-nrf2-enhances-the-anticancer-effect-of-6-o-angeloylenolin-in-lung-adenocarcinoma
#11
Yang Wang, Ru-Yuan Yu, Jing Zhang, Wei-Xia Zhang, Zhi-Hao Huang, Hui-Fang Hu, Yao-Lan Li, Bin Li, Qing-Yu He
6-O-Angeloylenolin (6-OA), a sesquiterpene lactone isolated from Centipeda minima (L.) A. Br. (Compositae), has been used to treat respiratory diseases for centuries. However, whether and how 6-OA exerts anticancer effects against lung cancer remains to be elucidated. In this study, we showed that 6-OA markedly suppressed the cell viability and colony formation of lung cancer cells H1299 and A549, with no significant toxic effect on non-cancer cells HBE. Annexin V/7-AAD assay revealed that 6-OA induced cell apoptosis in dose- and time-dependent manners, which was further confirmed by the increased expression of cleaved caspase-3...
January 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28103888/photoreceptor-protection-via-blockade-of-bet-epigenetic-readers-in-a-murine-model-of-inherited-retinal-degeneration
#12
Lei Zhao, Jun Li, Yingmei Fu, Mengxue Zhang, Bowen Wang, Jonathan Ouellette, Pawan K Shahi, Bikash R Pattnaik, Jyoti J Watters, Wai T Wong, Lian-Wang Guo
BACKGROUND: The bromodomain and extraterminal domain (BET) family proteins (BET2, BET3, and BET4) "read" (bind) histone acetylation marks via two distinct bromodomains (Brom1 and Brom2) facilitating transcriptional activation. These epigenetic "readers" play crucial roles in pathogenic processes such as inflammation. The role of BETs in influencing the degenerative process in the retina is however unknown. METHODS: We employed the rd10 mouse model (Pde6b (rd10) mutation) of retinitis pigmentosa (RP) to examine the involvement of BET proteins in retinal neurodegeneration...
January 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28103733/essential-oil-composition-and-antinociceptive-activity-of-thymus-capitatus
#13
Juan Carlos Ramos Gonçalves, Danilo Andrade de Meneses, Aliny Pereira de Vasconcelos, Celyane Alves Piauilino, Fernanda Regina de Castro Almeida, Edoardo Marco Napoli, Giuseppe Ruberto, Demetrius Antônio Machado de Araújo
CONTEXT: The essential oil (EO) from Thymus capitatus Hoff. et Link. (Lamiaceae) has been traditionally used for its medicinal properties, such as anti-inflammatory, analgesic, antioxidant and antimicrobial properties. OBJECTIVE: Characterize the constituents from T. capitatus EO and further evaluate the antinociceptive activity by in vivo and in vitro procedures. MATERIALS AND METHODS: Gas chromatography-mass spectrometry was used to identify and quantify the constituents of the T...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28103678/an-advance-in-prescription-opioid-vaccines-overdose-mortality-reduction-and-extraordinary-alteration-of-drug-half-life
#14
Atsushi Kimishima, Cody J Wenthur, Bin Zhou, Kim D Janda
Prescription opioids (POs) such as oxycodone and hydrocodone are highly effective medications for pain management, yet they also present a substantial risk for abuse and addiction. The consumption of POs has been escalating worldwide, resulting in tens of thousands of deaths due to overdose each year. Pharmacokinetic strategies based upon vaccination present an attractive avenue to suppress PO abuse. Herein, the preparation of two active PO vaccines is described that were found to elicit high-affinity antiopioid antibodies through a structurally congruent drug-hapten design...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28103447/pharmacotherapy-for-treating-metastatic-clear-cell-renal-cell-carcinoma
#15
Camillo Porta, Silvia Chiellino, Alessandra Ferrari, Sara Mariucci, Wanda Liguigli
Over the past decade metastatic renal cell carcinoma (RCC) treatment landscape has dramatically evolved from the era of cytokines-based immunotherapy (which benefited very few patients, at the expenses of high toxicities) to the present era of targeted agents and novel immunotherapeutics, greatly improving the prognosis of our patients. Areas covered: Here we have reviewed the present status of the medical treatment of metastatic RCC. To do this, we interrogated the Medline database, as well as the proceedings of the main Oncological and Urological conferences for the relevant trials coducted so far...
January 19, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28103315/multiple-acid-sensors-control-helicobacter-pylori-colonization-of-the-stomach
#16
Julie Y Huang, Emily Goers Sweeney, Karen Guillemin, Manuel R Amieva
Helicobacter pylori's ability to respond to environmental cues in the stomach is integral to its survival. By directly visualizing H. pylori swimming behavior when encountering a microscopic gradient consisting of the repellent acid and attractant urea, we found that H. pylori is able to simultaneously detect both signals, and its response depends on the magnitudes of the individual signals. By testing for the bacteria's response to a pure acid gradient, we discovered that the chemoreceptors TlpA and TlpD are each independent acid sensors...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28103263/splenic-cd4-t-cells-in-progressive-visceral-leishmaniasis-show-a-mixed-effector-regulatory-phenotype-and-impair-macrophage-effector-function-through-inhibitory-receptor-expression
#17
Audrie A Medina-Colorado, Elvia Y Osorio, Omar A Saldarriaga, Bruno L Travi, Fanping Kong, Heidi Spratt, Lynn Soong, Peter C Melby
Visceral leishmaniasis (VL), caused by infection with the intracellular protozoan Leishmania donovani, is a chronic progressive disease with a relentlessly increasing parasite burden in the spleen, liver and bone marrow. The disease is characterized by fever, splenomegaly, cachexia, and pancytopenia, and progresses to death if not treated. Control of Leishmania infection is mediated by Th1 (IFNγ-producing) CD4+ T cells, which activate macrophages to produce nitric oxide and kill intracellular parasites. However, despite expansion of CD4+ T cells and increased IFNγ expression in the spleen, humans with active VL do not control the infection...
2017: PloS One
https://www.readbyqxmd.com/read/28102521/clinical-assessment-and-train-of-four-measurements-in-critically-ill-patients-treated-with-recommended-doses-of-cisatracurium-or-atracurium-for-neuromuscular-blockade-a-prospective-descriptive-study
#18
Pierre Bouju, Jean-Marc Tadié, Nicolas Barbarot, Julien Letheulle, Fabrice Uhel, Pierre Fillatre, Guillaume Grillet, Angélique Goepp, Yves Le Tulzo, Arnaud Gacouin
BACKGROUND: Despite few studies, a monitoring of a neuromuscular blockade with a train of four (TOF) is recommended in intensive care unit (ICU). Our objective was to compare the results of ulnar and facial TOF measurements with an overall clinical assessment for neuromuscular blockade in ICU patients treated with recommended doses of atracurium or cisatracurium, including patients with acute respiratory disease syndrome (ARDS). METHODS: We prospectively included in two ICUs 119 patients, 94 with ARDS, who required a neuromuscular blockade for more than 24 h...
December 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/28102321/the-chaperonin-cct-inhibits-assembly-of-%C3%AE-synuclein-amyloid-fibrils-by-a-specific-conformation-dependent-interaction
#19
Begoña Sot, Alejandra Rubio-Muñoz, Ahudrey Leal-Quintero, Javier Martínez-Sabando, Miguel Marcilla, Cintia Roodveldt, José M Valpuesta
The eukaryotic chaperonin CCT (chaperonin containing TCP-1) uses cavities built into its double-ring structure to encapsulate and to assist folding of a large subset of proteins. CCT can inhibit amyloid fibre assembly and toxicity of the polyQ extended mutant of huntingtin, the protein responsible for Huntington's disease. This raises the possibility that CCT modulates other amyloidopathies, a still-unaddressed question. We show here that CCT inhibits amyloid fibre assembly of α-synuclein A53T, one of the mutants responsible for Parkinson's disease...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102051/t-cell-immunoglobulin-mucin-3-blockade-drives-an-antitumor-immune-response-in-head-and-neck-cancer
#20
Jian-Feng Liu, Si-Rui Ma, Liang Mao, Lin-Lin Bu, Guang-Tao Yu, Yi-Cun Li, Cong-Fa Huang, Wei-Wei Deng, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
T-cell immunoglobulin mucin 3 (TIM3) contributes to immune suppression during progression of many cancers, but the precise role of TIM3 in head and neck squamous cell carcinoma (HNSCC) is not clearly understood. In this study, we report that TIM3 expression was significantly up-regulated in patients with HNSCC and associated with lymph node metastasis. Additionally, TIM3 expression was increased in patients with recurrent HNSCC and patients with preradiotherapy or prechemotherapy. We also characterized CD8(+) T cells and CD11b(+) CD33(+) myeloid-derived suppressor cells (MDSCs) in human HNSCC, and found that their expression was positively correlated with TIM3 expression...
December 15, 2016: Molecular Oncology
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