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Agonist triggering

Mohamad Elbaz, Dinesh Ahirwar, Zhang Xiaoli, Xinyu Zhou, Maryam Lustberg, Mohd W Nasser, Konstantin Shilo, Ramesh K Ganju
Transient receptor potential vanilloid type-2 (TRPV2) is an ion channel that is triggered by agonists like cannabidiol (CBD). Triple negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Chemotherapy is still the first line for the treatment of TNBC patients; however, TNBC usually gains rapid resistance and unresponsiveness to chemotherapeutic drugs. In this study, we found that TRPV2 protein is highly up-regulated in TNBC tissues compared to normal breast tissues. We also observed that TNBC and estrogen receptor alpha negative (ERβ-) patients with higher TRPV2 expression have significantly higher recurrence free survival compared to patients with lower TRPV2 expression especially those who were treated with chemotherapy...
September 11, 2018: Oncotarget
Miriam Martínez-Navarro, Rafael Maldonado, Josep-E Baños
Injury to peripheral nerves often lead to abnormal pain states (hyperalgesia, allodynia and spontaneous pain), which can remain long after the injury heals. Although opioid agonists remain the gold standard for the treatment of moderate to severe pain, they show reduced efficacy against neuropathic pain. In addition to analgesia, opioid use is also associated to hyperalgesia and analgesia tolerance, whose underlying mechanisms share some commonalities with nerve injury-induced hypersensitivity. Here we reviewed up-to-day research exploring the contribution of mu-opioid receptor (MOR) on the pathophysiology of neuropathic pain and on analgesic opioid actions under these conditions...
October 14, 2018: European Journal of Pain: EJP
Caitlin Dunne, Angel Shan, Gary Nakhuda
OBJECTIVE: To study whether the measurement of LH after GnRH agonist trigger is correlated with the proportion of mature oocytes. METHODS: We performed a retrospective cohort study at a private, university-affiliated fertility centre in Vancouver, BC. Patients who underwent IVF/ICSI cycles and used a GnRH agonist trigger were included. Serum LH levels were measured on the day of trigger and one day later. The main study outcome measure was the proportion of mature oocytes...
October 10, 2018: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
Melissa A Maczis, Michael Maceyka, Michael R Waters, Jason Newton, Manjulata Singh, Madisyn F Rigsby, Tia H Turner, Mohammad A Alzubi, J Chuck Harrell, Sheldon Milstien, Sarah Spiegel
In breast cancer, 17β-estradiol (E2) plays critical roles mainly by binding to its canonical receptor, estrogen receptor (ER) α66, and eliciting genomic effects. E2 also triggers rapid, non-genomic responses. E2 activates sphingosine kinase 1 (SphK1), increasing sphingosine-1-phosphate (S1P) that binds to its receptors leading to important breast cancer signaling. However, the E2 receptor responsible for SphK1 activation has not yet been identified. Here we demonstrate in triple negative breast cancer cells, which lack the canonical ERα66 but express the novel splice variant ERα36, that ERα36 is the receptor responsible for E2-induced activation of SphK1 and formation and secretion of S1P and dihydro-S1P, the ligands for S1PRs...
October 12, 2018: Journal of Lipid Research
Jason M Tarkin, Juan Carlos Kaski
Nicorandil and long-acting nitrates are vasodilatory drugs used commonly in the management of chronic stable angina pectoris. Both nicorandil and long-acting nitrates exert anti-angina properties via activation of nitric oxide (NO) signalling pathways, triggering vascular smooth muscle cell relaxation. Nicorandil has additional actions as an arterial K+ ATP channel agonist, resulting in more "balanced" arterial and venous vasodilatation than nitrates. Ultimately, these drugs prevent angina symptoms through reductions in preload and diastolic wall tension and, to a lesser extent, epicardial coronary artery dilatation and lowering of systemic blood pressure...
August 2018: European Cardiology
Ramin Rokhzan, Chandra C Ghosh, Niccole Schaible, Jacob Notbohm, Haruka Yoshie, Allen J Ehrlicher, Sarah J Higgins, Ruyuan Zhang, Hermann Haller, Corey C Hardin, Sascha David, Samir M Parikh, Ramaswamy Krishnan
Vascular leakage, protein exudation, and edema formation are events commonly triggered by inflammation and facilitated by gaps that form between adjacent endothelial cells (ECs) of the vasculature. In such paracellular gap formation, the role of EC contraction is widely implicated, and even therapeutically targeted. However, related measurement approaches remain slow, tedious, and complex to perform. Here, we have developed a multiplexed, high-throughput screen to simultaneously quantify paracellular gaps, EC contractile forces, and to visualize F-actin stress fibers, and VE-cadherin...
October 11, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Chang Keun Kim, Zak Callaway, Jin Sung Park, Hisashi Nishimori, Tikatoshi Ogino, Mizuho Nagao, Takao Fujisawa
PURPOSE: Several markers for eosinophilic inflammation have been proposed to predict response to asthma treatment. However, definitive criteria for treatment decisions have not yet been established. We investigate a potentially useful relatively non-invasive biomarker, eosinophil-derived neurotoxin (EDN), to predict favorable responses to budesonide or montelukast, common treatment for children with asthma. METHODS: Young children (1 to 6 years old) were enrolled in this randomized, parallel, 2-group, open-label trial...
November 2018: Allergy, Asthma & Immunology Research
Serge Sicouri, Luiz Belardinelli, Charles Antzelevitch
INTRODUCTION: Extrasystoles arising from the muscular sleeves associated with pulmonary veins (PV), superior vena cava (SVC) and coronary sinus (CS) are known to precipitate atrial fibrillation (AF). The late sodium channel current (INa ) inhibitor ranolazine has been reported to exert antiarrhythmic effects in canine PV and SVC sleeves by suppressing late phase 3 early and delayed afterdepolarization (EAD and DAD)-induced triggered activity induced by parasympathetic and/or sympathetic stimulation...
October 9, 2018: Journal of Cardiovascular Electrophysiology
Neal Van Hoeven, Steven Wiley, Emily Gage, Andrew Fiore-Gartland, Brian Granger, Sean Gray, Christopher Fox, David E Clements, D Elliot Parks, Scott Winram, Dan T Stinchcomb, Steven G Reed, Rhea N Coler
Members of the Flaviviridae family are the leading causes of mosquito-borne viral disease worldwide. While dengue virus is the most prevalent, the recent Zika virus outbreak in the Americas triggered a WHO public health emergency, and yellow fever and West Nile viruses (WNV) continue to cause regional epidemics. Given the sporadic nature of flaviviral epidemics both temporally and geographically, there is an urgent need for vaccines that can rapidly provide effective immunity. Protection from flaviviral infection is correlated with antibodies to the viral envelope (E) protein, which encodes receptor binding and fusion functions...
2018: NPJ Vaccines
Jee-Hyeon Kim, Byeol Namgung, Ye Ji Jeon, Wan Seok Song, Jeonghyun Lee, Seung Goo Kang, Sung-Il Yoon
Helicobacter pylori is a flagellated bacterium of the Epsilonproteobacteria class that causes peptic ulcers. Flagellin is a primary structural protein that assembles into the flagellar filament. Flagellins from bacteria that belong to the Gammaproteobacteria and Firmicutes groups are detected by Toll-like receptor 5 (TLR5) in the host, triggering the innate immune response, and thus have been studied for the development of vaccines against diverse infections through fusion with protein antigens. However, H...
October 6, 2018: Biochemical and Biophysical Research Communications
Darlene A Pena, Mariana Lemos Duarte, Dimitrius T Pramio, Lakshmi A Devi, Deborah Schechtman
It is well accepted that treatment of chronic pain with morphine leads to μ opioid receptor (MOR) desensitization and the development of morphine tolerance. MOR activation by the selective peptide agonist, D-Ala2, N-MePhe4, Gly-ol]-enkephalin(DAMGO), leads to robust G protein receptor kinase activation, β-arrestin recruitment, and subsequent receptor endocytosis, which does not occur in an activation by morphine. However, MOR activation by morphine induces receptor desensitization, in a Protein kinase C (PKC) dependent manner...
October 6, 2018: Proteomes
James J McDonald, Donald C McMillan, Barry J Laird
PURPOSE OF REVIEW: Cachexia is defined as ongoing loss of skeletal muscle mass, with or without depletion of adipose tissue and is a common syndrome in cancer patients, affecting 50% of those diagnosed. Cachexia, which cannot be fully reversed and causes significant functional impairment is caused by various mechanisms such as an altered energy balance and disruption of homeostatic control by the central nervous system. This central nervous system deregulation involves hypothalamic pituitary adrenal (HPA) axis stimulation, which can be triggered by IL-1R1 engagement on neuronal processes and endothelium in the microvasculature of the hypothalamus...
October 8, 2018: Current Opinion in Supportive and Palliative Care
Jared S Magee, Luke M Pittman, Leslie A Jette-Kelly
BACKGROUND Asthma is a common disease in the U.S. POPULATION: Initial therapy in the stepwise approach for asthma management is short-acting β₂-agonist (SABA) therapy as needed for symptom control. However, a significant adverse event that can occur with administration is bronchospasm. Here, we report a case of paradoxical bronchospasm with administration of SABAs during multiple pulmonary function tests (PFTs). CASE REPORT A 25-year-old, non-smoking, African American male with a history of moderate asthma and allergic rhinitis treated with fluticasone/salmeterol diskus, albuterol hydrofluoroalkane (HFA) inhaler, and montelukast presented to our clinic complaining of recurrent episodes of acute shortness of breath immediately following each administration of albuterol for 4 weeks...
October 9, 2018: American Journal of Case Reports
Yingyin Yang, Huawei Gu, Qiuli Sun, Jufang Wang
Christensenella minuta (C. minuta) is a gram-negative gastrointestinal bacterium associated with weight loss. However, recent studies have shown that C. minuta might be a potential pathogen and thus limited its application in the control of obesity. Research into the genetic characteristics and pathogenicity of C. minuta remain elusive. As a major virulence factor of gram-negative bacteria, lipopolysaccharide (LPS) can induce various diseases. In this study, we report the complete genome sequence of C. minuta and have also identified some genes related to LPS biosynthesis...
October 2, 2018: Microbial Pathogenesis
Baland Jalal
Sleep paralysis is a state of involuntary immobility occurring at sleep onset or offset, often accompanied by uncanny "ghost-like" hallucinations and extreme fear reactions. I provide here a neuropharmacological account for these hallucinatory experiences by evoking the role of the serotonin 2A receptor (5-HT2A R). Research has shown that 5-HT2A R activation can induce visual hallucinations, "mystical" subjective states, and out-of-body experiences (OBEs), and modulate fear circuits. Hallucinatory experiences triggered by serotonin-serotonergic ("pseudo") hallucinations, induced by hallucinogenic drugs-tend to be "dream-like" with the experiencer having insight ("meta-awareness") that he is hallucinating, unlike dopaminergic ("psychotic" and "life-like") hallucinations where such insight is lost...
October 5, 2018: Psychopharmacology
Maho Shibata, Eisuke Ishizaki, Ting Zhang, Masanori Fukumoto, Alma Barajas-Espinosa, Tong Li, Donald G Puro
P2X7 receptor/channels in the retinal microvasculature not only regulate vasomotor activity, but can also trigger cells in the capillaries to die. While it is known that this purinergic vasotoxicity is dependent on the transmembrane pores that form during P2X7 activation, events linking pore formation with cell death remain uncertain. To better understand this pathophysiological process, we used YO-PRO-1 uptake, dichlorofluorescein fluorescence, perforated-patch recordings, fura-2 imaging and trypan blue dye exclusion to assess the effects of the P2X7 agonist, benzoylbenzoyl-ATP (BzATP), on pore formation, oxidant production, ion channel activation, [Ca2+ ]i and cell viability...
September 2018: Vision
Qiongyuan Hu, Quan Zhou, Jie Wu, Xiuwen Wu, Jianan Ren
Ischemia/reperfusion (I/R) injury is a common occurrence resulting from acute mesenteric ischemia, traumatic or septic shock, burns, and surgical procedures that can lead to multiple organ failure and high mortality in critically ill patients. Mitochondria are often considered as the cellular power factory via their capacity for ATP generation. Recently, mitochondria have been further identified as vital regulators of cell death, inflammation, and oxidative stress, all of which can aggravate I/R injury. Studies have indicated that mitochondrial DNA (mtDNA) damage leads to mitochondrial dysfunction and aggravates I/R injury...
October 3, 2018: Shock
Luke Grundy, Andrea M Harrington, Joel Castro, Sonia Garcia-Caraballo, Annemie Deiteren, Jessica Maddern, Grigori Y Rychkov, Pei Ge, Stefanie Peters, Robert Feil, Paul Miller, Andre Ghetti, Gerhard Hannig, Caroline B Kurtz, Inmaculada Silos-Santiago, Stuart M Brierley
Irritable bowel syndrome (IBS) patients suffer from chronic abdominal pain and extraintestinal comorbidities, including overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC-PBS). Mechanistic understanding of the cause and time course of these comorbid symptoms is lacking, as are clinical treatments. Here, we report that colitis triggers hypersensitivity of colonic afferents, neuroplasticity of spinal cord circuits, and chronic abdominal pain, which persists after inflammation. Subsequently, and in the absence of bladder pathology, colonic hypersensitivity induces persistent hypersensitivity of bladder afferent pathways, resulting in bladder-voiding dysfunction, indicative of OAB/IC-PBS...
October 4, 2018: JCI Insight
Mansoor Ali Syed, Dilip Shah, Pragnya Das, Sture Andersson, Gloria Pryhuber, Vineet Bhandari
Hyperoxia-induced injury to the developing lung, impaired alveolarization and dysregulated vascularization are critical factors in the pathogenesis of bronchopulmonary dysplasia (BPD); however, mechanisms for hyperoxia-induced development of BPD are not fully known. Here we show that the triggering receptor expressed on myeloid cells 1 (TREM-1) is upregulated in hyperoxia-exposed neonatal mice lungs as well as in tracheal aspirates (TA) and lungs of human neonates with respiratory distress syndrome (RDS) and BPD as an adaptive response to survival in hyperoxia...
October 3, 2018: American Journal of Respiratory Cell and Molecular Biology
Hakan Golbasi, Onur Ince, Ceren Golbasi, Mehmet Ozer, Mustafa Demir, Bulent Yilmaz
This study investigates the predictive power of serum progesterone/estradiol (P/E2 ) level for estimating the live birth rate in patients who had a serum progesterone (P) rate ≥ 1.5 ng/mL on the human chorionic gonadotropin (hCG) administration day and who received the gonadotropin-releasing hormone (GnRH) antagonist protocol and intracytoplasmic sperm injection (ICSI). This retrospective cohort study included 176 cycles. The P/E2 ratio was lower in patients with a live birth (0.73 ± 0.54) than those without a live birth (1...
October 3, 2018: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
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