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https://www.readbyqxmd.com/read/28548956/dalbinol-a-rotenoid-from-amorpha-fruticosa-l-exerts-anti-proliferative-activity-by-facilitating-%C3%AE-catenin-degradation-in-hepatocellular-carcinoma-cells
#1
Xiaohui Zhu, Xin Wu, Jing Cheng, Hongbo Liao, Xiaoqing Di, Lili Li, Rong Li, Yanfang Zhou, Xiangning Zhang
Hepatocellular carcinoma (HCC) is a highly malignant tumor, and the main cause of treatment failure is malignant proliferation. Aberrations in Wnt/β-catenin signaling are associated with HCC development. Despite the improvements in overall survival made over the past decade from the advent of molecularly targeted therapies, these treatments do not have efficacy in all patients with different pathogeneses. Therefore, there is a demand for novel chemotherapeutic agents for HCC. To this end, we built a natural compound library and screened out a rotenoid named dalbinol from the seeds of Amorpha fruticosa L...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548676/the-diagnosis-and-management-of-chronic-migraine-in-primary-care
#2
Werner J Becker
BACKGROUND: Chronic migraine is common, affecting approximately 1% of the general population, and causes significant disability. OBJECTIVE: To summarize optimal involvement of primary care physicians in chronic migraine care, and to provide algorithms to assist them in the diagnosis and management of patients with chronic migraine. METHODS: An analysis of diagnostic and treatment needs in chronic migraine, based on a synthesis of the medical literature and clinical experience...
May 26, 2017: Headache
https://www.readbyqxmd.com/read/28548571/correlation-of-cdc42-activity-with-cell-proliferation-and-palmitate-mediated-cell-death-in-human-umbilical-cord-wharton-s-jelly-derived-mesenchymal-stromal-cells
#3
Jun Lu, Qinghua Wang, Lianghu Huang, Huiyue Dong, Lingjing Lin, Jianming Tan
RHO GTPases regulate cell migration, cell-cycle progression, and cell survival in response to extracellular stimuli. However, the regulatory effects of RHO GTPases in mesenchymal stromal cells (MSCs) are unclear. Herein, we show that CDC42 acts as an essential factor in regulating cell proliferation and also takes part in lipotoxic effects of palmitate in human umbilical cord Wharton's jelly derived MSCs (hWJ-MSCs). Cultured human bone marrow (hBM-MSCs), adipose tissue (hAD-MSCs), and umbilical cord Wharton's jelly (hWJ-MSCs) derived cells had varying pro-inflammatory cytokine secretion levels and cell death rates when treated by palmitate...
May 26, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28548286/obesity-gets-on-your-renal-nerves
#4
EDITORIAL
Boye L Jensen
In the present issue of Acta Physiologica(1) , Khan et al. in their article "Improvement in baroreflex control of renal sympathetic nerve activity in obese Sprague-Dawley rats following immunosuppression" confirm that obesity-related hypertension involves resetting of the arterial baroreceptor to a state of less sensitivity and relate this mechanistically to inflammation-induced altered renal afferent nerve activity (1) . Pharmocological treatment with the calcineurin phosphatase inhibitor-type immunosuppressant tacrolimus attenuated inflammation, reversed, paradoxically, the hypertension and restored baroreceptor sensitivity similar to the effect of renal denervation...
May 26, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28548282/estimating-the-effect-of-immortal-time-bias-in-urologic-research-a-case-example-of-testosterone-replacement-therapy
#5
Christopher J D Wallis, Refik Saskin, Steven A Narod, Calvin Law, Girish S Kulkarni, Arun Seth, Robert K Nam
OBJECTIVE: To quantify the effect of immortal-time bias in an observational study examining the effect of cumulative testosterone exposure on mortality. SUBJECTS AND METHODS: We used a population-based matched cohort study of men aged 66 and older newly treated with testosterone replacement therapy and matched-controls from 2007-2012 in Ontario, Canada to quantify the effects of immortal-time bias. We used generalized estimating equations to determine the association between cumulative testosterone replacement therapy exposure and mortality...
May 26, 2017: BJU International
https://www.readbyqxmd.com/read/28548231/combination-therapy-with-telmisartan-and-parecoxib-induces-regression-of-endometriotic-lesions
#6
Anca Nenicu, Yuan Gu, Christina Körbel, Michael D Menger, Matthias W Laschke
BACKGROUND AND PURPOSE: Telmisartan suppresses the development of endometriotic lesions. However, the drug also up-regulates the expression of cyclooxygenase (COX)-2, which has been suggested to promote the progression of endometriosis. Accordingly, we herein analysed whether a combination therapy with telmisartan and a COX-2 inhibitor may be more effective in the treatment of endometriotic lesions than application of telmisartan alone. EXPERIMENTAL APPROACH: Endometriotic lesions were induced in the peritoneal cavity of C57BL/6 mice, which were daily treated with an intraperitoneal (i...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28548225/single-and-combined-effects-of-delta-9-tetrahydrocannabinol-and-cannabidiol-in-a-mouse-model-of-chemotherapy-induced-neuropathic-pain
#7
Kirsten M King, Alyssa M Myers, Ariele J Soroka-Monzo, Ronald F Tuma, Ronald J Tallarida, Ellen A Walker, Sara Jane Ward
BACKGROUND AND PURPOSE: It has been suggested that the non-psychoactive phytocannabinoid cannabidiol (CBD) can impact the pharmacological effects of delta-9-tetrahydrocannabinol (THC). We tested the hypothesis that CBD and THC would significantly mitigate mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain, and that CBD+THC combinations would produce synergistic effects. We also tested the hypothesis that CBD would attenuate oxaliplatin- and vincristine- induced mechanical sensitivity...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28547794/antidepressant-like-effects-of-tetrahydroxystilbene-glucoside-in-mice-involvement-of-bdnf-signaling-cascade-in-the-hippocampus
#8
Hao Wang, Ying Zhao, Ying-Jie Wang, Lu Song, Jin-Liang Wang, Chao Huang, Wei Zhang, Bo Jiang
BACKGROUND AND AIMS: Current antidepressants in clinic need weeks of administration and always have significant limitations. Tetrahydroxystilbene glucoside (TSG) is one of the major bioactive ingredients of Polygonum multiflorum with neuroprotective effects. This study aimed to evaluate the antidepressant effects of TSG in mice. METHODS: The antidepressant-like effects of TSG in mice were examined in the forced swim test (FST), tail suspension test (TST), and chronic social defeat stress (CSDS) model of depression...
May 25, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28547771/translation-of-wnt-developmental-programs-into-stem-cell-replacement-strategies-for-the-treatment-of-parkinson-s-disease
#9
REVIEW
Enrique M Toledo, Daniel Gyllborg, Ernest Arenas
Wnt signalling is a highly conserved pathway across species that is critical for normal development and is deregulated in multiple diseases including cancer and neurodegeneration. Wnt signalling is critically required for midbrain dopaminergic (mDA) neuron development and maintenance. Understanding the molecular processes controlled by Wnt signalling may thus hold the key to understand the physiopathology and to develop novel therapies aimed at preventing the loss of mDA neurons in Parkinson's disease (PD)...
May 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28547702/emerging-treatments-in-eating-disorders
#10
REVIEW
Michael Lutter
Eating disorders (EDs), including anorexia nervosa, bulimia nervosa, and binge-eating disorder, constitute a class of common and deadly psychiatric disorders. While numerous studies in humans highlight the important role of neurobiological alterations in the development of ED-related behaviors, the precise neural substrate that mediates this risk is unknown. Historically, pharmacological interventions have played a limited role in the treatment of eating disorders, typically providing symptomatic relief of comorbid psychiatric issues, like depression and anxiety, in support of the standard nutritional and psychological treatments...
May 25, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28547295/high-loading-dose-of-microencapsulated-gliclazide-formulation-exerted-a-hypoglycaemic-effect-on-type-1-diabetic-rats-and-incorporation-of-a-primary-deconjugated-bile-acid-diminished-the-hypoglycaemic-antidiabetic-effect
#11
Svetlana Golocorbin-Kon, Jelena Calasan, Boris Milijasevic, Sasa Vukmirovic, Mladena Lalic-Popovic, Momir Mikov, Hani Al-Salami
BACKGROUND AND OBJECTIVE: Gliclazide is a drug commonly used in type 2 diabetes mellitus. Recently, gliclazide has shown desirable pharmacological effects such as immunoregulatory and anti-clotting effects, which suggests potential applications in type 1 diabetes mellitus (T1DM). Gliclazide has variable absorption after oral administration, and thus using targeted-delivery techniques, such as microencapsulation, may optimise gliclazide absorption and potential applications in T1DM. Bile acids such as cholic acid have shown microcapsule-stabilising and controlled-release effects, and thus their incorporation into gliclazide microcapsules may further optimise gliclazide release, absorption and antidiabetic effects...
May 25, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28546779/emerging-treatment-options-for-the-management-of-hodgkin-s-lymphoma-clinical-utility-of-nivolumab
#12
REVIEW
David A Bond, Lapo Alinari
Classical Hodgkin's lymphoma (cHL) is a B-cell malignancy comprised of pathologic Reed Sternberg cells with a surrounding immune-tolerant inflammatory milieu. RS cells evade immune recognition in part through programmed death ligand 1 (PD-L1) overexpression, which is genetically programmed through copy number alterations, polysomy, and amplification of the 9p24.1 locus encoding PD-L1. By engaging with PD-1+ T-cells, PD-L1 delivers a potent immune suppressive signal promoting immunologic escape of the tumor cell...
2017: Journal of Blood Medicine
https://www.readbyqxmd.com/read/28546766/abcb1-genetic-variants-in-leukemias-current-insights-into-treatment-outcomes
#13
REVIEW
Ravindran Ankathil
Despite improvements in treatment of different types of leukemia, not all patients respond optimally for a particular treatment. Some treatments will work better for some, while being harmful or ineffective for others. This is due to genetic variation in the form of single-nucleotide polymorphisms (SNPs) that affect gene expression or function and cause inherited interindividual differences in the metabolism and disposition of drugs. Drug transporters are one of the determinants governing the pharmacokinetic profile of chemotherapeutic drugs...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28546566/a-diastereoselective-synthesis-of-cebranopadol-a-novel-analgesic-showing-nop-mu-mixed-agonism
#14
Anna Fantinati, Sara Bianco, Remo Guerrini, Severo Salvadori, Salvatore Pacifico, Maria Camilla Cerlesi, Girolamo Calo, Claudio Trapella
A diastereoselective synthesis of the title compound as a single E diastereomer has been efficiently accomplished by assembling the featured pyrano-indole scaffold of the spiro[cyclohexane-dihydropyrano[3,4-b]-indole]-amine framework through an oxa-Pictet-Spengler reaction, promoted by a cheap and green Zeolite catalyst. Basic pharmacological experiments demonstrate that Cebranopadol acts as a mixed nociception/orphanin FQ (NOP) and mu (MOP) opioid receptor agonist useful for treatment of chronic pain.
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28546450/fatty-acid-binding-protein-4-ap2-dependent-blt1r-expression-and-signaling
#15
Ann V Hertzel, Hongliang Xu, Michael Downey, Nicholas Kvalheim, David A Bernlohr
Previous studies have shown that reduced levels of the adipocyte fatty acid binding protein 4, FABP4 (AFABP/aP2), result in metabolic improvement including potentiated insulin sensitivity and attenuated atherosclerosis. Mechanistically, pharmacologic or genetic inhibition of FABP4 in macrophages upregulates UCP2, attenuates ROS production, polarizes cells towards the anti-inflammatory M2 state and reduces leukotriene secretion. At the protein level, FABP4 stabilizes LTA4 towards chemical hydrolysis thereby potentiating inflammatory LTC4 synthesis...
May 25, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28546431/disruption-of-mitochondrial-electron-transport-chain-function-potentiates-the-pro-apoptotic-effects-of-mapk-inhibition
#16
Andrew P Trotta, Jesse D Gelles, Madhavika N Serasinghe, Patrick Loi, Jack L Arbiser, Jerry E Chipuk
The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma, arising from the Val600Glu mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAFV600E), oncogenic signaling enhances glucose-dependent metabolism, while reducing mitochondrial ATP production. Likewise, when BRAFV600E is pharmacologically inhibited by targeted therapies (e.g. PLX-4032/Vemurafenib), glucose metabolism is reduced and cells increase mitochondrial ATP production to sustain survival...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28546378/pediatric-lung-transplantation
#17
Stuart C Sweet
Pediatric lung transplant is a viable option for treatment of end-stage lung disease in children, with > 100 pediatric lung transplants reported to the Registry of the International Society of Heart and Lung Transplantation each year. Long-term success is limited by availability of donor organs, debilitation as a result of chronic disease, impaired mucus clearance resulting from both surgical and pharmacologic interventions, increased risk for infection resulting from immunosuppression, and most importantly late complications, such as chronic lung allograft dysfunction...
June 2017: Respiratory Care
https://www.readbyqxmd.com/read/28546081/targeting-nuclear-receptors-for-the-treatment-of-fatty-liver-disease
#18
REVIEW
Naoki Tanaka, Toshifumi Aoyama, Shioko Kimura, Frank J Gonzalez
Ligand-activated nuclear receptors, including peroxisome proliferator-activated receptor alpha (PPARα), pregnane X receptor, and constitutive androstane receptor, were first identified as key regulators of the responses against chemical toxicants. However, numerous studies using mouse disease models and human samples have revealed critical roles for these receptors and others, such as PPARβ/δ, PPARγ, farn esoid X receptor (FXR), and liver X receptor (LXR), in maintaining nutrient/energy homeostasis in part through modulation of the gut-liver-adipose axis...
May 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28545666/mahuannin-b-an-adenylate-cyclase-inhibitor-attenuates-hyperhidrosis-via-suppressing-%C3%AE-2-adrenoceptor-camp-signaling-pathway
#19
Zengyong Wang, Yu Cui, Guoyu Ding, Mengge Zhou, Xiaoyao Ma, Yuanyuan Hou, Min Jiang, Dailin Liu, Gang Bai
BACKGROUND: Based on the traditional application of traditional Chinese Medicines (TCMs), Ephedra Herba (EH) is used to cure cold fever by inducing sweating, whereas Ephedra Radix (ER) is used to treat hyperhidrosis. Although they come from the same plant, Ephedra sinica Stapf, but have play opposing roles in clinical applications. EH is known to contain ephedrine alkaloids, which is the driver of the physiological changes in sweating, heart rate and blood pressure. However, the active pharmacological ingredients (APIs) of ER and the mechanisms by which it restricts sweating remain unknown...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28545157/the-aminoestrogen-prolame-increases-recognition-memory-and-hippocampal-neuronal-spine-density-in-aged-mice
#20
Alfonso Diaz, Samuel Treviño, Rubén Vázquez-Roque, Berenice Venegas, Blanca Espinosa, Gonzalo Flores, Juan Manuel Fernández-G, Luis F Montaño, Jorge Guevara
The aging brain shows biochemical and morphological changes in the dendrites of pyramidal neurons from the limbic system associated with memory loss. Prolame (N-(3-hydroxy-1,3,5 (10) -estratrien-17β-yl) -3-hydroxypropylamine) is a non-feminizing aminoestrogen with antithrombotic activity that prevents neuronal deterioration, oxidative stress and neuroinflammation. Our aim was to evaluate the effect of prolame on motor and cognitive processes, as well as its influence on the dendritic morphology of neurons at the CA1, CA3 and granule cells of the dentate gyrus (DG) regions of hippocampus (HP), and medium spiny neurons of the nucleus accumbens (NAcc) of aged mice...
May 25, 2017: Synapse
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