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https://www.readbyqxmd.com/read/29454075/the-g-protein-coupled-p2y-6-receptor-promotes-colorectal-cancer-tumorigenesis-by-inhibiting-apoptosis
#1
Morgane Placet, Guillaume Arguin, Caroline M Molle, Jean-Philippe Babeu, Christine Jones, Julie C Carrier, Bernand Robaye, Sameh Geha, Francois Boudreau, Fernand-Pierre Gendron
Colorectal tumors are immersed in an array of tumor-promoting factors including extracellular nucleotides such as uridine 5'‑diphosphate (UDP). UDP is the endogenous agonist of the G protein-coupled P2Y 6 receptor (P2Y 6 R), which may contribute to the formation of a tumor-promoting microenvironment by coordinating resistance to apoptosis. Colorectal cancer (CRC) was chemically induced in P2ry6 knockout (P2ry6 -/- ) mice using azoxymethane and dextran sulfate sodium challenges. Mice were euthanatized and their tumor load determined...
February 14, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29454023/interaction-between-hypothermia-and-delayed-mesenchymal-stem-cell-therapy-in-neonatal-hypoxic-ischemic-brain-injury
#2
Josephine Herz, Christian Köster, Barbara S Reinboth, Mark Dzietko, Wiebke Hansen, Hemmen Sabir, Cindy van Velthoven, Ivo Bendix, Ursula Felderhoff-Müser
Acute hypothermia treatment (HT) is the only clinically established intervention following neonatal hypoxic-ischemic brain injury. However, almost half of all cooled infants still die or suffer from long-lasting neurological impairments. Regenerative therapies, such as mesenchymal stem cells (MSC) appear promising as adjuvant therapy. In the present study, we hypothesized that HT combined with delayed MSC therapy results in augmented protection, improving long-term neurological outcome. Postnatal day 9 (P9) C57BL/6 mice were exposed to hypoxia-ischemia followed by 4 hours HT...
February 14, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29454009/24-vs-72-hours-of-hypothermia-for-pediatric-cardiac-arrest-a-pilot-randomized-controlled-trial
#3
Ericka L Fink, Robert S B Clark, Rachel P Berger, Anthony Fabio, Derek C Angus, R Scott Watson, John J Gianakas, Ashok Panigrahy, Clifton W Callaway, Michael J Bell, Patrick M Kochaneka
AIM: Children surviving cardiac arrest (CA) lack proven neuroprotective therapies. The role of biomarkers in assessing response to interventions is unknown. We hypothesized that 72 versus 24 h of hypothermia (HT) would produce more favorable biomarker profiles after pediatric CA. METHODS: This single center pilot randomized trial tested HT (33 ± 1 °C) for 24 vs. 72 h in 34 children with CA. Children comatose after return of circulation aged 1 week to 17 years and treated with HT by their physician were eligible...
February 14, 2018: Resuscitation
https://www.readbyqxmd.com/read/29453947/evaluation-of-the-effects-of-rp5063-a-novel-multimodal-serotonin-receptor-modulator-as-single-agent-therapy-and-co-administrated-with-sildenafil-bosentan-and-treprostinil-in-a-monocrotaline-induced-pulmonary-arterial-hypertension-rat-model
#4
Laxminarayan Bhat, Jon Hawkinson, Marc Cantillon, Dasharatha G Reddy, Seema R Bhat, Charles-E Laurent, Annie Bouchard, Marzena Biernat, Dany Salvail
Pulmonary arterial hypertension (PAH), a condition that is defined by pulmonary vasculature constriction and remodeling, involves dysfunctional signaling of the serotonin (5-HT) receptors, 5-HT 2/2B/7 . In a rat model of monocrotaline (MCT)-induced PAH, the effectiveness of RP5063 (RP), a dopamine and 5-HT receptor modulator, was evaluated as monotherapy and as an adjunct to standard PAH treatments. After a single 60mg/kg dose of MCT, rats received vehicle (MCT+Veh; gavage twice-daily [b.i.d.]), RP (10mg/kg; gavage b...
February 14, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29453931/comparison-of-return-to-pre-injury-sport-after-10-mm-size-bone-patellar-tendon-bone-bptb-versus-8-mm-hamstring-anterior-cruciate-ligament-reconstruction-a-retrospective-study-with-a-two-year-follow-up
#5
Rimtautas Gudas, Rokas Jurkonis, Alfredas Smailys
BACKGROUND The aim of this study was to evaluate the reconstruction of a torn anterior cruciate ligament (ACL) with 10 mm diameter BPTB (bone-patellar tendon-bone) autograft versus 8 mm HT (hamstring tendon) autografts, to compare the ability to restore pre-injury sports activities and reduce revision risk after these procedures. MATERIAL AND METHODS A prospective clinical review was performed to compare results of patients who underwent primary anatomical ACLR with 10 mm BPTB autografts with patients who underwent 8 mm diameter HT autografts, between January 2011 and January 2014...
February 17, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29453444/positive-regulation-of-raphe-serotonin-neurons-by-serotonin-2b-receptors
#6
Arnauld Belmer, Emily Quentin, Silvina L Diaz, Bruno P Guiard, Sebastian P Fernandez, Stéphane Doly, Sophie M Banas, Pothitos M Pitychoutis, Imane Moutkine, Aude Muzerelle, Anna Tchenio, Anne Roumier, Manuel Mameli, Luc Maroteaux
Serotonin is a neurotransmitter involved in many psychiatric diseases. In humans, a lack of 5-HT 2B receptors is associated with serotonin-dependent phenotypes, including impulsivity and suicidality. A lack of 5-HT 2B receptors in mice eliminates the effects of molecules that directly target serotonergic neurons including amphetamine derivative serotonin releasers, and selective serotonin reuptake inhibitor antidepressants. In this work, we tested the hypothesis that 5-HT 2B receptors directly and positively regulate raphe serotonin neuron activity...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29453120/mycobiota-and-co-occurrence-of-mycotoxins-in-south-african-maize-based-opaque-beer
#7
Ifeoluwa Adekoya, Adewale Obadina, Cynthia Chilaka Adaku, Marthe De Boevre, Sheila Okoth, Sarah De Saeger, Patrick Njobeh
Beer, a beverage consumed throughout the world, is mainly derived from cereals. In this study, fungal and mycotoxin contamination, as well as the physicochemical properties of maize-based opaque beer (umqombothi) obtained from the Gauteng province of South Africa, was investigated. The mean water activity, pH and total titratable acidity of the analysed beer samples were 0.91, 3.76 and 1.20% lactic acid, respectively. The investigation revealed Aspergillus, Penicillium, Phoma and Saccharomyces as the predominant fungal genera with a mean fungal load of 3...
February 9, 2018: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/29452684/evaluation-of-the-safety-tolerability-and-efficacy-of-pimavanserin-versus-placebo-in-patients-with-alzheimer-s-disease-psychosis-a-phase-2-randomised-placebo-controlled-double-blind-study
#8
Clive Ballard, Carol Banister, Zunera Khan, Jeffrey Cummings, George Demos, Bruce Coate, James M Youakim, Randall Owen, Srdjan Stankovic
BACKGROUND: Pimavanserin is a selective 5-HT 2A receptor inverse agonist and antagonist approved in the USA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. No safe or effective pharmacological treatment is approved for psychosis in patients with Alzheimer's disease. Therefore, we aimed to evaluate the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer's disease psychosis. METHODS: We did a phase 2, randomised, double-blind, placebo-controlled, single-centre (with multiple affiliated nursing home sites across the UK) study...
March 2018: Lancet Neurology
https://www.readbyqxmd.com/read/29452127/serotonergic-psychedelics-and-personality-a-systematic-review-of-contemporary-research
#9
REVIEW
José Carlos Bouso, Rafael G Dos Santos, Miguel Ángel Alcázar-Córcoles, Jaime E C Hallak
Serotonergic psychedelics act as agonists at cortical 5-HT 2A receptors and seem to induce personality changes. We conducted a systematic review of studies assessing the effects of these drugs on personality. Papers published from 1985 to 2016 were included from PubMed, LILACS, and SciELO databases. Three hundred and sixty-nine studies were identified, and 18 were included. Specific personality traits, such as Absorption and Self-Transcendence, seem to influence the effects of psychedelics, and psychedelic drug users and nonusers appear to differ in some personality traits...
February 13, 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29451889/effects-of-patterned-peripheral-nerve-stimulation-on-soleus-spinal-motor-neuron-excitability
#10
Samuel Jimenez, Laura Mordillo-Mateos, Michele Dileone, Michela Campolo, Carmen Carrasco-Lopez, Fabricia Moitinho-Ferreira, Tomas Gallego-Izquierdo, Hartwig R Siebner, Josep Valls-Solé, Juan Aguilar, Antonio Oliviero
Spinal plasticity is thought to contribute to sensorimotor recovery of limb function in several neurological disorders and can be experimentally induced in animals and humans using different stimulation protocols. In healthy individuals, electrical continuous Theta Burst Stimulation (TBS) of the median nerve has been shown to change spinal motoneuron excitability in the cervical spinal cord as indexed by a change in mean H-reflex amplitude in the flexor carpi radialis muscle. It is unknown whether continuous TBS of a peripheral nerve can also shift motoneuron excitability in the lower limb...
2018: PloS One
https://www.readbyqxmd.com/read/29451783/sufex-click-chemistry-enabled-late-stage-drug-functionalization
#11
Zilei Liu, Jie Li, Suhua Li, Gencheng Li, K Barry Sharpless, Peng Wu
Sulfur(VI) Fluoride Exchange (SuFEx) is a new family of click chemistry transformations which relies on readily available materials to produce compounds bearing the S VI -F motif. The potential of SuFEx in drug discovery has just started to be explored. We report the first method of SuFEx chemistry for the conversion of phenolic compounds to their respective arylfluorosulfate derivatives in situ in 96-well plates. This method is compatible with automated synthesis and screening to quickly assess the biological activities of the in situ generated, crude products...
February 16, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29451703/mechanisms-of-imidazoline-i-2-receptor-agonist-induced-antinociception-in-rats-involvement-of-monoaminergic-neurotransmission
#12
Justin N Siemian, Kaixuan Wang, Yanan Zhang, Jun-Xu Li
BACKGROUND AND PURPOSE: Although studies have established the antinociceptive efficacies of imidazoline I 2 receptor (I 2 R) agonists, its exact post-receptor mechanism remains unknown. This study tested the hypothesis that monoaminergic transmission is critical for I 2 R agonist-induced antinociception. EXPERIMENTAL APPROACH: The von Frey filament test was used to examine the antinociceptive effects of the I 2 R agonists 2-BFI and CR4056 on chronic constriction injury (CCI)-induced neuropathic pain or complete Freund's adjuvant (CFA)-induced inflammatory pain in rats...
February 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29451407/advancements-in-drug-development-for-diarrhea-predominant-irritable-bowel-syndrome
#13
Giovanni Dothel, Maria Raffaell Barbaro, Emanuel Raschi, Giovanni Barbara, Fabrizio De Ponti
Introduction Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common disorder characterized by a complex pathophysiology hampering optimal targeted drug development. Recent advances in our understanding of key underlying mechanisms prompted novel therapeutics including novel pharmacological approaches. Areas covered This review summarizes the latest advancements in the pipeline of IBS-D drugs focusing on new pharmacological targets, efficacy and safety of medicinal products considering the recent harmonization of regulatory requirements by the FDA and the EMA...
February 16, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29451227/statural-growth-and-prevalence-of-endocrinopathies-in-relation-to-liver-iron-content-lic-in-adult-patients-with-beta-thalassemia-major-btm-and-sickle-cell-disease-scd
#14
Mohamed A Yassin, Ashraf T Soliman, Vincenzo De Sanctis, Mohammad Aj Abdula, Lubna M Riaz, Firdous F Ghori, Anil Yousaf, Abdulqadir J Nashwan, Sandara Abusamaan, Abbas Moustafa, Samah Kohla, Dina S Soliman
Despite regular blood transfusion and iron chelation therapy, growth impairment and pubertal delay are commonly seen in children and adolescents with transfusion-dependent Beta thalassaemia major (BTM) and sickle cell disease (SCD). We evaluated growth parameters and endocrine disorders in relation to the liver iron concentration (LIC) assessed by the Ferriscan® method in a cohort of adults with SCD (n =40) and BTM (n = 52) receiving blood transfusions and iron chelation therapy since early childhood. Before transfusion, hemoglobin concentration had not been less than 9 g/dl in the past 12 years; subcutaneous daily desferrioxamine was administered for all of them since early childhood (2- 5 years of age)...
February 16, 2018: Acta Bio-medica: Atenei Parmensis
https://www.readbyqxmd.com/read/29451226/final-adult-height-and-endocrine-complications-in-young-adults-with-%C3%AE-thalassemia-major-tm-who-received-oral-iron-chelation-oic-in-comparison-with-those-who-did-not-use-oic
#15
Ashraf T Soliman, Mohamed A Yassin, Vincenzo De Sanctis
BACKGROUND: Relatively little is known about endocrine function, bone mineral health, and growth during oral iron chelation therapy in β-thalassemia major patients (TM) on treatment with deferasirox. AIMS OF THE STUDY: To study the frequency of endocrine complications, IGF-1 levels and final adult standing height (FA-Ht) in patients with BTM in two groups of adult patients. PATIENTS AND METHODS: The first group (Group A; 15 patients, 6 females and 9 males) received oral iron chelation therapy (OIC) with deferasirox for 6 years before puberty; the second group (Group B;40 patients) attained the FA-Ht before the use of OIC (iron chelation therapy with deferoxamine (DFO) given subcutaneously, since the age of 2 years)...
February 16, 2018: Acta Bio-medica: Atenei Parmensis
https://www.readbyqxmd.com/read/29451186/-lactobacillus-acidophilus-and-bifidobacterium-longum-supernatants-upregulate-the-serotonin-transporter-expression-in-intestinal-epithelial-cells
#16
Ya-Nan Cao, Li-Juan Feng, Bang-Mao Wang, Kui Jiang, Shu Li, Xin Xu, Wei-Qiang Wang, Jing-Wen Zhao, Yu-Ming Wang
Background/Aims: Probiotics play a role in relieving irritable bowel syndrome (IBS); however, the underlying mechanism is yet unclear. The aim of the study was to investigate the effects of the supernatants of Lactobacillus acidophilus and Bifidobacterium longum on the expression of serotonin transporter (SERT) messenger ribonucleic acid (mRNA) and protein. Materials and Methods: HT-29 and Caco-2 cells were treated with different concentrations of L. acidophilus and B...
January 2018: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/29450258/the-cannabinoids-%C3%AE-8-thc-cbd-and-hu-308-act-via-distinct-receptors-to-reduce-corneal-pain-and-inflammation
#17
Dinesh Thapa, Elizabeth A Cairns, Anna-Maria Szczesniak, James T Toguri, Meggie D Caldwell, Melanie E M Kelly
Background and Purpose: Corneal injury can result in dysfunction of corneal nociceptive signaling and corneal sensitization. Activation of the endocannabinoid system has been reported to be analgesic and anti-inflammatory. The purpose of this research was to investigate the antinociceptive and anti-inflammatory effects of cannabinoids with reported actions at cannabinoid 1 (CB 1 R) and cannabinoid 2 (CB 2 R) receptors and/or noncannabinoid receptors in an experimental model of corneal hyperalgesia. Methods: Corneal hyperalgesia (increased pain response) was generated using chemical cauterization of the corneal epithelium in wild-type (WT) and CB 2 R knockout (CB 2 R -/- ) mice...
2018: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29449787/cumulative-receiver-operating-characteristics-for-analyzing-interaction-between-tissue-visfatin-and-clinicopathologic-factors-in-breast-cancer-progression
#18
Sin-Hua Moi, Yi-Chen Lee, Li-Yeh Chuang, Shyng-Shiou F Yuan, Fu Ou-Yang, Ming-Feng Hou, Cheng-Hong Yang, Hsueh-Wei Chang
Background: Visfatin has been reported to be associated with breast cancer progression, but the interaction between the visfatin and clinicopathologic factors in breast cancer progression status requires further investigation. To address this problem, it is better to simultaneously consider multiple factors in sensitivity and specificity assays. Methods: In this study, a dataset for 105 breast cancer patients (84 disease-free and 21 progressing) were chosen. Individual and cumulative receiver operating characteristics (ROC) were used to analyze the impact of each factor along with interaction effects...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29448140/synthesis-and-structure-activity-relationships-of-asymmetric-dimeric-%C3%AE-carboline-derivatives-as-potential-antitumor-agents
#19
Liang Guo, Wei Chen, Rihui Cao, Wenxi Fan, Qin Ma, Jie Zhang, Bin Dai
A series of newly asymmetric dimeric β-carbolines with a spacer of 4-6 methylene units between the indole nitrogen and the harmine oxygen were synthesized. Structures of all the novel synthesized compounds were confirmed by their spectral and analytical studies. All of the synthesized compounds were screened for their in vitro cytotoxic activity against nine cancer cell lines. The results revealed that compounds 7c, 7o and 7s exhibited the highest cytotoxic activities with IC 50 values of less than 20 μM against the tumor cell lines tested...
February 7, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29447434/alterations-in-melatonin-and-serotonin-signalling-in-the-colonic-mucosa-of-mice-with-dextran-sodium-sulfate-induced-colitis
#20
Sarah J MacEachern, Catherine M Keenan, Evangelia Papakonstantinou, Keith A Sharkey, Bhavik Anil Patel
BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is characterized by pain, bleeding, cramping and altered gastrointestinal (GI) function. Changes in mucosal serotonin (5-HT) signalling occur in animal models of colitis and in humans suffering from IBD. Melatonin is co-released with 5-HT from the mucosa and has a wide variety of actions in the GI tract. Here we examined how melatonin signalling is affected by colitis and determined how this relates to 5-HT signalling. EXPERIMENTAL APPROACH: Using electroanalytical approaches, we investigated how 5-HT release, reuptake and availability as well as melatonin availability are altered in dextran sodium sulfate (DSS)-induced colitis in mice...
February 15, 2018: British Journal of Pharmacology
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