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https://www.readbyqxmd.com/read/28440659/alleviation-of-multiple-asthmatic-pathologic-features-with-orally-available-and-subtype-selective-gabaa-receptor-modulators
#1
Gloria S Forkuo, Amanda N Nieman, Nina Y Yuan, Revathi Kodali, Olivia B Yu, Nicolas M Zahn, Rajwana Jahan, Guanguan Li, Michael Rajesh Stephen, Margaret L Guthrie, Michael M Poe, Benjamin D Hartzler, Ted William Harris, Gene T Yocum, Charles W Emala, Douglas A Steeber, Douglas C Stafford, James M Cook, Leggy A Arnold
We describe pharmacokinetic and pharmacodynamic properties of two novel oral drug candidates for asthma. Phenolic α4β3γ2 GABAAR selective compound 1 and acidic α5β3γ2 selective GABAAR positive allosteric modulator compound 2 relaxed airway smooth muscle ex vivo and attenuated airway hyperresponsiveness (AHR) in a murine model of asthma. Importantly, compound 2 relaxed acetylcholine contracted human tracheal airway smooth muscle strips. Oral treatment of compound 1 and 2 decreased eosinophils in bronchoalveolar lavage fluid in ovalbumin sensitized and challenged mice, thus exhibiting anti-inflammatory properties...
April 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28435998/a-6-year-old-boy-with-wilson-disease-a-diagnostic-dilemma
#2
Ramaswamy Ganesh, N Suresh, T Vasanthi, Malathi Sathiyasekaran, R Thulasiraman
A 6-year-old boy presented with 2 months history of progressive abdominal distension and jaundice. He was deeply icteric with ascites, hepatosplenomegaly, hyperbilirubinemia, raised transaminases, and coagulopathy. Viral markers and slit lamp examination for Kayser-Fleischer ring were negative. Serum ceruloplasmin and 24-h urinary copper post-D-pencillamine challenge were normal. Anti-smooth muscle antibody was positive 1:20, and liver biopsy showed micronodular cirrhosis with abundant Mallory hyaline and stainable copper deposits...
April 24, 2017: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
https://www.readbyqxmd.com/read/28434118/hyperoside-inhibits-the-effects-induced-by-oxidized-low-density-lipoprotein-in-vascular-smooth-muscle-cells-via-oxldl-lox-1-erk-pathway
#3
Zhengyu Zhang, Dongdong Zhang, Baoling Du, Zhiqiang Chen
Hyperoside is a major active constituent in many medicinal plants traditionally used in Chinese medicines for their anti-inflammatory, antioxidative, and vascular protective effects. Recent studies have focused on the protective effects of hyperoside on hyperlipidemia. However, the molecular mechanisms underlying these effects are unknown. In this study, vascular smooth muscle cells (VSMCs) were treated in vitro with oxidized low-density lipoprotein (oxLDL) in the presence or absence of hyperoside. Western blotting, quantitative PCR, and tetrazolium assay were used to detect lectin-like oxLDL receptor-1 (LOX-1) expression and extracellular signal-regulated kinases (ERK) activation, and to determine VSMCs viability...
April 22, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28434000/apolipoprotein-a1-inhibits-the-tgf-%C3%AE-1-induced-endothelial-to-mesenchymal-transition-of-human-coronary-artery-endothelial-cells
#4
Juling Feng, Jingjing Zhang, Ampadu O Jackson, Xiao Zhu, Hainan Chen, Wen Chen, Qingjun Gui, Kai Yin
OBJECTIVE: Transforming growth factor β1 (TGF-β1) is the major cytokine for stimulating endothelial cells (ECs) to transdifferentiate to mesenchymal cells (MCs) in the process known as endothelial-to-mesenchymal transition (EndMT). Recently, TGF-β1-induced EndMT has been implicated in the pathogenesis of atherosclerosis (AS). It has been identified that apolipoprotein A1 (ApoA-I) obstructs TGF-β1-induced endothelial dysfunction, providing a protective effect for ECs and also anti-AS activity...
April 22, 2017: Cardiology
https://www.readbyqxmd.com/read/28433555/systemic-application-of-sirolimus-prevents-neointima-formation-not-via-a-direct-anti-proliferative-effect-but-via-its-anti-inflammatory-properties
#5
Jan-Marcus Daniel, Jochen Dutzmann, Hannes Brunsch, Johann Bauersachs, Rüdiger Braun-Dullaeus, Daniel G Sedding
BACKGROUND: Systemic treatment with sirolimus, as used for immunosuppression in transplant patients, results in markedly low rates of in-stent restenosis. Since the underlying mechanisms remain obscure, we aimed to determine the molecular and cellular effects of systemic sirolimus treatment on vascular remodeling processes. METHODS AND RESULTS: Systemic sirolimus treatment significantly reduced smooth muscle cell (SMC) proliferation 14days after wire-induced injury and neointima formation 28days after injury in C57BL/6 mice, while simultaneously impairing re-endothelialization...
March 14, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28433552/roscovitine-attenuates-intimal-hyperplasia-via-inhibiting-nf-%C3%AE%C2%BAb-and-stat3-activation-induced-by-tnf-%C3%AE-in-vascular-smooth-muscle-cells
#6
Ming He, Chao Wang, Jia-Huan Sun, Yu Liu, Hong Wang, Jing-Shan Zhao, Yun-Feng Li, Hong Chang, Jian-Ming Hou, Jun-Na Song, Ai-Ying Li, En-Sheng Ji
Roscovitine is a selective CDK inhibitor originally designed as anti-cancer agent, which has also been shown to inhibit proliferation in vascular smooth muscle cells (VSMCs). However, its effect on vascular remodeling and its mechanism of action remain unknown. In our study, we created a new intimal hyperplasia model in male Sprague-Dawley rats by trypsin digestion method, which cause to vascular injury as well as the model of rat carotid balloon angioplasty. Roscovitine administration led to a significant reduction in neointimal formation and VSMCs proliferation after injury in rats...
April 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28429889/omentin-treatment-of-epicardial-fat-improves-its-anti-inflammatory-activity-and-paracrine-benefit-on-smooth-muscle-cells
#7
Ángel Fernández-Trasancos, Rosa María Agra, Jose María García-Acuña, Ángel Luis Fernández, José Ramón González-Juanatey, Sonia Eiras
OBJECTIVE: Epicardial adipose tissue (EAT) in coronary artery disease is insulin resistant and has a proinflammatory profile. This study examined the regulation of EAT by exogenous omentin and its consequence on vascular cells. METHODS: Stromal vascular cells (SC) of EAT and subcutaneous adipose tissue (SAT) from patients who underwent heart surgery were cultured and exposed to adipogenic factors with or without omentin. Proinflammatory cytokine regulation by omentin was analyzed in SC and mature adipocytes...
April 21, 2017: Obesity
https://www.readbyqxmd.com/read/28428179/adamts13-controls-vascular-remodeling-by-modifying-vwf-reactivity-during-stroke-recovery
#8
Haochen Xu, Yongliang Cao, Xing Yang, Ping Cai, Lijing Kang, Ximin Zhu, Haiyu Luo, Lu Lu, Lixiang Wei, Xiaofei Bai, Yuanbo Zhu, Bing-Qiao Zhao, Wenying Fan
Angiogenic response is essential for ischemic brain repair. However, the mechanisms leading to postischemic neovascularization have not been established, and no therapies have been identified. The VWF-cleaving protease ADAMTS13 is required for endothelial tube formation in vitro However, there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited significantly reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) breakdown and extravascular deposits of serum proteins in the peri-infarct cortex at 14 days after stroke...
April 20, 2017: Blood
https://www.readbyqxmd.com/read/28428070/no-production-and-potassium-channels-activation-induced-by-crotalus-durissus-cascavella-underlie-mesenteric-artery-relaxation
#9
S S Santos, R L C Jesus, L O Simões, W P Vasconcelos, I A Medeiros, R C Veras, L L Casais-E-Silva, D F Silva
Animal toxins are natural resources for pharmacological studies. The venom of Crotalus durissus cascavella (C.d. cascavella) may be a source in the bio-prospecting of new anti-hypertensive agents. The aim of this study was to investigate vascular effects of the venom of C.d. cascavella in normotensive rats. Studies were performed using isolated mesenteric artery segments and aortic endothelial cells. The cumulative administration of the venom of C.d. cascavella (0.001-30 μg/mL) on phenylephrine (Phe; 10 μM) pre-contracted rings induced a concentration-dependent vasorelaxation in the presence of vascular endothelium (Emax = 47...
April 18, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28425867/chemokines-and-relevant-micrornas-in-the-atherogenic-process
#10
Dimitry A Chistiakov, Alexander N Orekhov, Yuri V Bobryshev
Chemokines play a significant role in initial and advanced steps of atherogenesis. In early steps, chemokines control the adhesion of leukocytes to endothelial cells (ECs) followed by transmigration of monocytes and their deposition in the intima where they differentiate to proinflammatory macrophages. Except proinflammatory activity, chemokines are responsible for homeostasis and homing of progenitor cells. Recently, microRNAs (miRs) were found to control expression and activity of chemokines in ECs, vascular smooth muscle cells (VSMCs), and macrophages at different steps of atherogenesis...
April 19, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28421197/ginsenoside-rg1-ameliorates-cigarette-smoke-induced-airway-fibrosis-by-suppressing-the-tgf-%C3%AE-1-smad-pathway-in-vivo-and-in-vitro
#11
Sibin Guan, Qian Liu, Fengfeng Han, Wen Gu, Lin Song, Yue Zhang, Xuejun Guo, Weiguo Xu
Small airway fibrosis is a key pathological process accompanying chronic obstructive pulmonary disease (COPD) and includes fibroblast/myofibroblast transdifferentiation and excessive extracellular matrix deposition. Ginsenoside Rg1, one of the main active ingredients of Panax ginseng, has been shown to exert an antifibrotic effect in many tissues. However, little is known about the underlying mechanism and whether ginsenoside Rg1 can exert an effect on small airway fibrosis. We investigated the anti-small airway fibrosis effects of ginsenoside Rg1 in human embryonic lung fibroblasts and in COPD rats...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28419207/ckii-sirt1-sm22%C3%AE-loop-evokes-a-self-limited-inflammatory-response-in-vascular-smooth-muscle-cells
#12
Ya-Nan Shu, Li-Hua Dong, Han Li, Qian-Qian Pei, Sui-Bing Miao, Fan Zhang, Dan-Dan Zhang, Rong Chen, Ya-Juan Yin, Yan-Ling Lin, Zhen-Ying Xue, Pin Lv, Xiao-Li Xie, Li-Li Zhao, Xi Nie, Peng Chen, Mei Han
Aims: Sirtuin 1 (SIRT1) inhibits nuclear factor kappa B (NF-κB) activity in response to the inflammatory cytokine tumour necrosis factor alpha (TNF-α). Smooth muscle (SM) 22α is a phosphorylation-regulated suppressor of IKK-IκBα-NF-κB signalling cascades in vascular smooth muscle cells (VSMCs). Sm22α knockout results in increased expression of pro-inflammatory genes in the aortas which are controlled by NF-κB. This study aimed to investigate the relationship between SM22α and SIRT1 in the control of vascular inflammation...
April 16, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28417056/therapeutic-effect-of-prostaglandin-e1-in-monocrotaline-induced-pulmonary-arterial-hypertension-rats
#13
Jae Chul Lee
Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in pulmonary arterial pressure and excessive thickening and remodeling of distal small pulmonary arteries. During disease progression, PAH include increase in mean pulmonary arterial pressure, right ventricular (RV) enlargement, increased pulmonary vascular resistance, and smooth muscle hypertrophy in pulmonary arterioles. Several anti-PAH therapies targeting various pathways involved in PAH progression have been approved by the Food and Drug Adminstration...
March 2017: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/28416441/glechoma-hederacea-extracts-attenuate-cholestatic-liver-injury-in-a-bile-duct-ligated-rat-model
#14
Ya-Yu Wang, Shih-Yi Lin, Wen-Ying Chen, Su-Lan Liao, Chih-Cheng Wu, Pin-Ho Pan, Su-Tze Chou, Chun-Jung Chen
ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, Glechoma hederacea is frequently prescribed to patients with cholelithiasis, dropsy, abscess, diabetes, inflammation, and jaundice. Polyphenolic compounds are main bioactive components of Glechoma hederacea. AIM OF THE STUDY: This study was aimed to investigate the hepatoprotective potential of hot water extract of Glechoma hederacea against cholestatic liver injury in rats. MATERIALS AND METHODS: Cholestatic liver injury was produced by ligating common bile ducts in Sprague-Dawley rats...
April 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28414142/doxofylline-does-not-increase-formoterol-induced-camp-nor-mkp-1-expression-in-asm-cells-resulting-in-lack-of-anti-inflammatory-effect
#15
Brijeshkumar S Patel, Michael J Kugel, Gina Baehring, Alaina J Ammit
The xanthine doxofylline has been examined in clinical trials and shown to have efficacy and greater tolerability than theophylline in asthma and chronic obstructive pulmonary disease. The 'novofylline' doxofylline has demonstrated bronchodilatory and anti-inflammatory actions in in vivo and ex vivo experimental models of respiratory disease. However, there are limited studies in vitro. We address this herein and examine whether doxofylline has anti-inflammatory impact on primary cultures of airway smooth muscle (ASM) cells...
April 13, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28412911/pharmacological-therapy-of-abdominal-aortic-aneurysm-an-update
#16
Yi-Dong Wang, Zhen-Jie Liu, Jun Ren, Mei-Xiang Xiang
Abdominal aortic aneurysm (AAA), a progressive segmental abdominal aortic dilation, is associated with high mortality. AAA is characterized by inflammation, smooth muscle cell (SMC) depletion and extracellular matrix (ECM) degradation. Surgical intervention and endovascular therapy are recommended to prevent rupture of large AAAs. Unfortunately, there is no reliable pharmacological agent available to limit AAA expansion. In the past decades, extensive investigations and a body of ongoing clinical trials aimed at defining potent treatments to inhibit and even regress AAA growth...
April 13, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28409388/diethylcarbamazine-attenuates-the-expression-of-pro-fibrogenic-markers-and-hepatic-stellate-cells-activation-in-carbon-tetrachloride-induced-liver-fibrosis
#17
Maria Eduarda Rocha de França, Sura Wanessa Santos Rocha, Wilma Helena Oliveira, Laise Aline Santos, Anne Gabrielle Vasconcelos de Oliveira, Karla Patrícia Sousa Barbosa, Ana Karolina Santana Nunes, Gabriel Barros Rodrigues, Deniele Bezerra Lós, Christina Alves Peixoto
BACKGROUND AND AIM: While diethylcarbamazine citrate (DEC) displays important anti-inflammatory effects in experimental models of liver injury, the mechanisms of its action remain poorly understood. The aim of the present study was to investigate the fibrolytic potential of DEC. METHODS: Mice receive two injections of carbon tetrachloride (CCl4) per week for 8 weeks. DEC 50 mg/kg body weight was administered through drinking water during the last 12 days of liver injury...
April 13, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28408888/prevention-of-bleomycin-induced-pulmonary-inflammation-and-fibrosis-in-mice-by-paeonol
#18
Meng-Han Liu, An-Hsuan Lin, Hsin-Kuo Ko, Diahn-Warng Perng, Tzong-Shyuan Lee, Yu Ru Kou
Pulmonary fibrosis is a severe and progressive disease that is characterized by an abnormal deposition of extracellular matrix, such as collagens. The pathogenesis of this disease may be initiated by oxidative damage of lung epithelial cells by fibrogenic stimuli, leading to lung inflammation, which in turn promotes various lung fibrotic responses. The profibrogenic effect of transforming growth factor-β1 (TGF-β1) on lung fibroblasts is crucial for the pathogenesis of this disease. Paeonol, the main phenolic compound present in the Chinese herb Paeonia suffruticosa, has antioxidant and anti-inflammatory properties...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28405195/corrigendum-agonistic-anti-pdgf-receptor-autoantibodies-from-patients-with-systemic-sclerosis-impact-human-pulmonary-artery-smooth-muscle-cells-function-in-vitro
#19
Silvia Svegliati, Donatella Amico, Tatiana Spadoni, Colomba Fischetti, Doreen Finke, Gianluca Moroncini, Chiara Paolini, Cecilia Tonnini, Antonella Grieco, Marina Rovinelli, Ada Funaro, Armando Gabrielli
[This corrects the article on p. 75 in vol. 8, PMID: 28228756.].
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28397820/bitter-taste-receptor-agonists-mitigate-features-of-allergic-asthma-in-mice
#20
Pawan Sharma, Roslyn Yi, Ajay P Nayak, Nadan Wang, Francesca Tang, Morgan J Knight, Shi Pan, Brian Oliver, Deepak A Deshpande
Asthma is characterized by airway inflammation, mucus secretion, remodeling and hyperresponsiveness (AHR). Recent research has established the bronchodilatory effect of bitter taste receptor (TAS2R) agonists in various models. Comprehensive pre-clinical studies aimed at establishing effectiveness of TAS2R agonists in disease models are lacking. Here we aimed to determine the effect of TAS2R agonists on features of asthma. Further, we elucidated a mechanism by which TAS2R agonists mitigate features of asthma...
April 11, 2017: Scientific Reports
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