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https://www.readbyqxmd.com/read/28630469/c2238-anp-gene-variant-promotes-increased-platelet-aggregation-through-the-activation-of-nox2-and-the-reduction-of-camp
#1
Roberto Carnevale, Pasquale Pignatelli, Giacomo Frati, Cristina Nocella, Rosita Stanzione, Daniele Pastori, Simona Marchitti, Valentina Valenti, Maria Santulli, Emanuele Barbato, Teresa Strisciuglio, Leonardo Schirone, Carmine Vecchione, Francesco Violi, Massimo Volpe, Speranza Rubattu, Sebastiano Sciarretta
Subjects carrying the C2238 variant of the atrial natriuretic peptide (ANP) gene have a higher occurrence of stroke and acute coronary syndrome, suggesting an increased predisposition to acute thrombotic events in these subjects. We evaluated for the first time the direct effects of mutant ANP (C2238/αANP) on platelet activation in vitro and in human subjects. In vitro, platelets were incubated with no peptide, with T2238/αANP (WT) or with C2238/αANP at different concentrations. C2238/αANP (10(-10) M) induced higher collagen-induced platelet aggregation with respect to both control without ANP and T2238/αANP...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28628279/acyclic-nucleoside-phosphonates-containing-9-deazahypoxanthine-and-a-5-membered-heterocycle-as-selective-inhibitors-of-plasmodial-6-oxopurine-phosphoribosyltransferases
#2
Martin Maxmilian Kaiser, Ondřej Baszczyňski, Dana Hocková, Lenka Poštová-Slavětínská, Martin Dračínský, Dianne T Keough, Luke W Guddat, Zlatko Janeba
Acyclic nucleoside phosphonates (ANPs) are an important class of therapeutic drugs that act as antiviral agents by inhibiting viral DNA polymerases and reverse transcriptases. ANPs containing a 6-oxopurine instead of 6-aminopurine or pyrimidine bases are inhibitors of the purine salvage enzyme, hypoxanthine-guanine-[xanthine]-phosphoribosyltransferase (HG[X]PRT). Such compounds, and their prodrugs, are able to arrest the growth of Plasmodium falciparum (Pf) in cell culture. A new series of ANPs has been synthesized and tested as inhibitors of human HGPRT, PfHGXPRT and Plasmodium vivax (Pv) HGPRT...
June 19, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28626572/optical-control-of-a-receptor-linked-guanylyl-cyclase-using-a-photoswitchable-peptidic-hormone
#3
Tom Podewin, Johannes Broichhagen, Christina Frost, Dieter Groneberg, Julia Ast, Helena Meyer-Berg, Nicholas H F Fine, Andreas Friebe, Martin Zacharias, David J Hodson, Dirk Trauner, Anja Hoffmann-Röder
The optical control over biological function with small photoswitchable molecules has gathered significant attention in the last decade. Herein, we describe the design and synthesis of a small library of photoswitchable peptidomimetics based upon human atrial natriuretic peptide (ANP), in which the photochromic amino acid [3-(3-aminomethyl)phenylazo]phenylacetic acid (AMPP) is incorporated into the peptide backbone. The endogeneous hormone ANP signals via the natriuretic peptide receptor A (NPR-A) through raising intracellular cGMP concentrations, and is involved in blood pressure regulation and sodium homeostasis, as well as lipid metabolism and pancreatic function...
June 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28624424/fusaric-acid-fa-protects-heart-failure-induced-by-isoproterenol-isp-in-mice-through-fibrosis-prevention-via-tgf-%C3%AE-1-smads-and-pi3k-akt-signaling-pathways
#4
Xin Li, Zhou-Long Zhang, Hui-Fen Wang
Fusaric acid (FA) is a novel compound derived from a class of nicotinic acid derivatives, exhibiting activity against cancers. However, its role in regulating cardiac injury is limited. Our study was aimed to investigate the role and the underlying molecular mechanism of FA in heart fibrosis and hypertrophy. Isoproterenol (ISP) was used to induce cardiac fibrosis and hypertrophy in vitro and in vivo. FA administration ameliorated hypertrophy by reducing atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β -myosin heavy chain (β-MHC) in vitro and in vivo...
June 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28617435/interaction-between-autophagy-and-senescence-is-required-for-dihydroartemisinin-to-alleviate-liver-fibrosis
#5
Zili Zhang, Zhen Yao, Shifeng Zhao, Jiangjuan Shao, Anping Chen, Feng Zhang, Shizhong Zheng
Autophagy and cellular senescence are stress responses essential for homeostasis. Therefore, they may represent new pharmacologic targets for drug development to treat diseases. In this study, we sought to evaluate the effect of dihydroartemisinin (DHA) on senescence of activated hepatic stellate cells (HSCs), and to further elucidate the underlying mechanisms. We found that DHA treatment induced the accumulation of senescent activated HSCs in rat fibrotic liver, and promoted the expression of senescence markers p53, p16, p21 and Hmga1 in cell model...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28616041/efficacy-of-intraorbital-electroacupuncture-for-diabetic-abducens-nerve-palsy-study-protocol-for-a-prospective-single-center-randomized-controlled-trial
#6
Ling-Yun Zhou, Xue-Mei Li, Tie-Juan Liu, Xiao-Jie Ji, Ming Zhao, Chang Su, Ji-Chao Liu, Jiang-Yun Sun
Abducens nerve palsy (ANP) is commonly seen in patients with diabetes mellitus. The validity of acupuncture as a traditional Chinese medicine method in peripheral nerve repair is well established. However, its efficacy in randomized controlled trials remains unclear. Herein, we designed a protocol for a prospective, single-center, randomized controlled trial to investigate the effect of intraorbital electroacupuncture on diabetic ANP. We plan to recruit 60 patients with diabetic ANP, and randomly divide them into treatment and control groups...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28611684/protective-role-for-lpa3-in-cardiac-hypertrophy-induced-by-myocardial-infarction-but-not-by-isoproterenol
#7
Lin Cai, Guangpu Fan, Fang Wang, Si Liu, Tiewei Li, Xiangfeng Cong, Jerold Chun, Xi Chen
Background: We previously reported that lysophosphatidic acid (LPA) promoted cardiomyocyte hypertrophy in vitro via one of its G protein-coupled receptor subtypes, LPA3. In this study, we examined the role of LPA3 in cardiac hypertrophy induced by isoproterenol (ISO) and myocardial infarction. Methods:In vitro, neonatal rat cardiomyocytes (NRCMs) were subjected to LPA3 knocked-down, or pretreated with a β-adrenergic receptor (β-AR) antagonist (propranolol) before LPA/ISO treatment. Cardiomyocyte size and hypertrophic gene (ANP, BNP) mRNA levels were determined...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28611128/decreased-kcne2-expression-participates-in-the-development-of-cardiac-hypertrophy-by-regulation-of-calcineurin-nfat-nuclear-factor-of-activated-t-cells-and-mitogen-activated-protein-kinase-pathways
#8
Wenjuan Liu, Jianxin Deng, Wenwen Ding, Gang Wang, Yuanyuan Shen, Junmeng Zheng, Xiaoming Zhang, Yizhi Luo, Chifei Lv, Yonghui Wang, Liqing Chen, Dewen Yan, Ryan L Boudreau, Long-Sheng Song, Jie Liu
BACKGROUND: KCNE2 is a promiscuous auxiliary subunit of voltage-gated cation channels. A recent work demonstrated that KCNE2 regulates L-type Ca(2+) channels. Given the important roles of altered Ca(2+) signaling in structural and functional remodeling in diseased hearts, this study investigated whether KCNE2 participates in the development of pathological hypertrophy. METHODS AND RESULTS: We found that cardiac KCNE2 expression was significantly decreased in phenylephrine-induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes and in transverse aortic constriction-induced cardiac hypertrophy in mice, as well as in dilated cardiomyopathy in human...
June 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28609373/multiorgan-failure-predicts-mortality-in-emphysematous-pancreatitis-a-case-report-and-systematic-analysis-of-the-literature
#9
Vadim Bul, Cemal Yazici, Jonas J Staudacher, Barbara Jung, Brian R Boulay
Emphysematous pancreatitis (EP) is a subtype of acute necrotizing pancreatitis (ANP) characterized by the presence of gas in and around the pancreas. Although investigators have studied prognostic factors in ANP, less is known about EP. We aimed to determine predictors of mortality and identify changes in management strategies for EP. A PubMed search was performed to identify EP cases. Data were gathered about patient demographics, clinical findings, laboratory results, radiological studies, procedures, outcomes, and mortality...
July 2017: Pancreas
https://www.readbyqxmd.com/read/28601022/nrf2-induces-lipocyte-phenotype-via-a-socs3-dependent-negative-feedback-loop-on-jak2-stat3-signaling-in-hepatic-stellate-cells
#10
Chunfeng Lu, Wenxuan Xu, Jiangjuan Shao, Feng Zhang, Anping Chen, Shizhong Zheng
Hepatic stellate cells (HSCs) are universally acknowledged to play a core role in the pathogenesis of hepatic fibrosis. HSCs when activated are characterized by dramatic loss of intracellular lipid droplets. Accumulative evidence has suggested that recovery of lipid droplets could suppress HSC activation. However, the underlying molecular mechanisms still remain largely unclear. In this study, we found that the expression and activity of nuclear factor (erythroid-derived 2) - like 2 (Nrf2) were decreased in activated HSCs and negatively correlated with hepatic fibrosis severity in human liver specimens...
June 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28599248/the-multifaceted-role-of-natriuretic-peptides-in-metabolic-syndrome
#11
REVIEW
Prasanna K Santhekadur, Divya P Kumar, Mulugeta Seneshaw, Faridoddin Mirshahi, Arun J Sanyal
Due to globalization and sophisticated western and sedentary lifestyle, metabolic syndrome has emerged as a serious public health challenge. Obesity is significantly increasing worldwide because of increased high calorie food intake and decreased physical activity leading to hypertension, dyslipidemia, atherosclerosis, and insulin resistance. Thus, metabolic syndrome constitutes cardiovascular disease, type 2 diabetes, obesity, and nonalcoholic fatty liver disease (NAFLD) and recently some cancers are also considered to be associated with this syndrome...
June 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28596054/a-potent-and-selective-natriuretic-peptide-receptor-3-blocker-11-mer-peptide-created-by-hybridization-of-musclin-and-atrial-natriuretic-peptide
#12
Naoki Nishizawa, Goshi Nakamura, Yoko Noguchi, Hideyuki Nakagawa, Ayako Shimizu, Masaharu Nakayama, Shiro Takekawa, Taiji Asami
The natriuretic peptide (NP) system is a critical endocrine, autocrine, and paracrine system and has been investigated for potential use against cardiovascular and metabolic diseases. The clearance of NPs is regulated by the proteolysis of neutral endopeptidase (NEP) and by endocytosis via natriuretic peptide receptor-3 (NPR3). A linear NPR3-selective peptide, [Cha(8)]-ANP(7-16)-NH2 (1), showed potent binding affinity for NPR3 but poor predicted chemical stability due to its free thiol group. A 12-mer peptide (9) without a thiol group was designed by the hybridization of two NPR3-binding peptides: a linear ANP fragment peptide analog and musclin, a murine member of the bHLH family of transcription factors, possessed high binding affinity and strict selectivity for NPR3...
May 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28593564/activation-of-adrenergic-receptor-in-h9c2-cardiac-myoblasts-co-stimulates-nox2-and-the-derived-ros-mediate-the-downstream-responses
#13
Nikhat Saleem, Shyamal K Goswami
In recent years, NADPH oxidases (Noxes) have emerged as an important player in cardiovascular pathophysiology. Despite the growing evidences on the role of specific Nox isoforms, mechanisms of their activation, targets of reactive oxygen species (ROS) generated, and their downstream effects are poorly understood as yet. In this study, we treated H9c2 cardiac myoblasts with norepinephrine (NE, 2 µM), inducing ROS generation that was inhibited by Nox2-specific peptide inhibitor gp91ds-tat. Organelle-specific hydrogen peroxide-sensitive probe HyPer showed that the site of ROS generation is primarily in the cytosol, to some extent in the endoplasmic reticulum (ER) but not the mitochondria...
June 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28591668/the-selective-estrogen-receptor-modulators-serms-raloxifene-and-tamoxifen-improve-anp-levels-and-decrease-nuclear-translocation-of-nf-kb-in-estrogen-deficient-rats
#14
Aline Z Lamas, Andrews M Nascimento, Ana Raquel S Medeiros, Izabela F Caliman, Polyana L M Dalpiaz, Luciana B Firmes, Glauciene J Sousa, Phablo Wendell C Oliveira, Tadeu U Andrade, Adelina M Reis, Sônia A Gouvea, Nazaré S Bissoli
BACKGROUND: The selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen are used for the treatment of osteoporosis and cancer, respectively, in women. The impairment of both the Atrial Natriuretic Peptide (ANP) cell signaling system and the translocation of nuclear factor-kappa B (NF-kB) to the cell nucleus are associated with detrimental cardiovascular effects and inflammation. The effects of SERMs on these parameters in the cardiac tissue of estrogen-deficient rats has not been reported...
March 16, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28586010/resveratrol-protects-against-l-arginine-induced-acute-necrotizing-pancreatitis-in-mice-by-enhancing-sirt1-mediated-deacetylation-of-p53-and-heat-shock-factor-1
#15
Nian Wang, Fen Zhang, Liu Yang, Jiang Zou, Hao Wang, Ke Liu, Meidong Liu, Huali Zhang, Xianzhong Xiao, Kangkai Wang
Acute necrotizing pancreatitis (ANP) is a common severe critical illness with a high mortality rate. Resveratrol, a polyphenol compound derived from various plants such as grape skin, peanut, berry and veratrum, exhibits multiple biological activities, especially potent anti‑inflammatory activity, but its effect on ANP has not yet been fully elucidated. The present study aimed to investigate the effects of resveratrol on L-arginine-induced ANP and the possible mechanisms. A mouse model of ANP was established by 2 hourly intraperitoneal injections of 8% L-arginine (4 g/kg)...
June 6, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28577190/17%C3%AE-estradiol-and-or-estrogen-receptor-alpha-blocks-isoproterenol-induced-calcium-accumulation-and-hypertrophy-via-gsk3%C3%AE-pp2a-nfat3-anp-pathway
#16
Peiying Pai, Bharath Kumar Velmurugan, Chia-Hua Kuo, Chung-Yi Yen, Tsung-Jung Ho, Yueh-Min Lin, Yu-Feng Chen, Chao-Hung Lai, Cecilia Hsuan Day, Chih-Yang Huang
The present study was aimed to investigate the protective effects of 17β-estradiol (E2) and estrogen receptor α (ERα) on isoproterenol (ISO)-treated H9c2 cardiomyoblast cells. In the present study, we treated H9c2 cells with ISO, a β-adrenergic receptor agonist, to induce myocardiac hypertrophy. Pre-administration of E2 or ERα (induced by doxycycline) and E2 plus ERα significantly prevented ISO-induced increase of cell size and cytosolic calcium accumulation, accompanied with increased mRNA of atrial natriuretic peptide and brain natriuretic peptide...
June 2, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28569144/the-incidence-risk-factors-and-in-hospital-mortality-of-acute-kidney-injury-in-patients-after-abdominal-aortic-aneurysm-repair-surgery
#17
Ying Tang, Junzhe Chen, Kai Huang, Dan Luo, Peifen Liang, Min Feng, Wenxin Chai, Erik Fung, Hui Yao Lan, Anping Xu
BACKGROUND: Acute kidney injury (AKI) is a severe complication associated with abdominal aortic aneurysm (AAA) repair. In this study, we evaluated the incidence, risk factors and in-hospital mortality of AKI in patients after the AAA repair surgery. METHODS: A total of 314 Chinese AAA patients who underwent endovascular aneurysm repair (EVAR) or open aneurysm repair (OPEN) were enrolled in this study. AKI was diagnosed according to the 2012 KDIGO criteria. Logistic regression modeling was used to explore risk factors of AKI, while risk factors associated with in-hospital mortality in AKI patients were investigated using Cox proportional hazards model and Kaplan-Meier analysis, respectively...
May 31, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28566468/smad7-protects-against-acute-kidney-injury-by-rescuing-tubular-epithelial-cells-from-the-g1-cell-cycle-arrest
#18
Sha Fu, Ying Tang, Xiao Ru Huang, Min Feng, Anping Xu, Hui Y Lan
Smad7 plays a protective role in chronic kidney disease; however, its role in acute kidney injury (AKI) remains unexplored. Here we report that Smad7 protects against AKI by rescuing the G1 cell cycle arrest of tubular epithelial cells (TECs) in ischemia/reperfusion-induced AKI in mice in which Smad7 gene is disrupted or restored locally into the kidney. In Smad7 gene knockout (KO) mice, more severe renal impairment including higher levels of serum creatinine and massive tubular necrosis was developed at 48 h after AKI...
May 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28552863/atrial-natriuretic-peptide%C3%A3-old-but-new-therapeutic-in-cardiovascular-diseases
#19
Tomoko Ichiki, John C Burnett
With the discovery of atrial natriuretic peptide (ANP), the heart as an endocrine organ was established. Basic science revealed that ANP, through the particulate guanylyl cyclase A receptor and cGMP, plays a fundamental role in cardiorenal biology. This work has led to the development of ANP as a therapeutic, especially in heart failure (HF). Human genomics has strengthened our understanding of ANP, revealing specific ANP gene variants that may be associated with biological dysfunction, but also may mediate protective properties, including in metabolic syndrome...
May 27, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28551095/an-in-depth-analysis-identifies-two-new-independent-signals-in-11q23-3-associated-with-vitiligo-in-the-chinese-han-population
#20
Suli Zhao, Fang Fang, Xianfa Tang, Jinfa Dou, Wenjun Wang, Xiaodong Zheng, Liangdan Sun, Anping Zhang
BACKGROUND: Vitiligo is an autoimmune disease, characterized by progressive loss of skin pigmentation, which is caused by the interactions of multiple factors, such as heredity, immunity and environment. Recently, a single nucleotide polymorphism (SNP) rs638893 at 11q23.3 region was identified as a risk factor for vitiligo in genome-wide association studies and multiple SNPs in this region have been associated with other autoimmune diseases. OBJECTIVE: This study aims to identify additional susceptibility variants associated with vitiligo at 11q23...
May 3, 2017: Journal of Dermatological Science
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