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https://www.readbyqxmd.com/read/28339489/human-subtilisin-kexin-isozyme-1-ski-1-site-1-protease-s1p-regulates-cytoplasmic-lipid-droplet-abundance-a-potential-target-for-indirect-acting-anti-dengue-virus-agents
#1
Anastasia Hyrina, Fanrui Meng, Steven J McArthur, Sharlene Eivemark, Ivan R Nabi, François Jean
Viral hijacking and manipulation of host-cell biosynthetic pathways by human enveloped viruses are shared molecular events essential for the viral lifecycle. For Flaviviridae members such as hepatitis C virus and dengue virus (DENV), one of the key subsets of cellular pathways that undergo manipulation is the lipid metabolic pathways, underlining the importance of cellular lipids and, in particular, lipid droplets (LDs) in viral infection. Here, we hypothesize that targeting cellular enzymes that act as key regulators of lipid homeostasis and LD formation could represent a powerful approach to developing a novel class of broad-spectrum antivirals against infection associated with all DENV serotypes (1-4) circulating around the world...
2017: PloS One
https://www.readbyqxmd.com/read/28338871/renal-sympathetic-denervation-a-viable-option-for-treating-resistant-hypertension
#2
Markus P Schlaich
Accumulating evidence from mainly uncontrolled clinical studies with various types of ablation catheters have shown that renal denervation (RDN) can be applied safely and is effective in lowering blood pressure (BP) in patients with treatment-resistant hypertension. Sustained BP lowering has been documented up to 3 years. Furthermore, RDN has been associated with regression of target organ damage, such as left ventricular hypertrophy, arterial stiffness, and others. Several studies indicate potential benefit in other common clinical conditions associated with increased sympathetic tone including chronic kidney disease and heart failure...
March 1, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28338617/egfr-family-members-regulation-of-autophagy-is-at-a-crossroads-of-cell-survival-and-death-in-cancer
#3
REVIEW
Elizabeth Henson, Yongqiang Chen, Spencer Gibson
The epidermal growth factor receptor (EGFR) signaling pathways are altered in many cancers contributing to increased cell survival. These alterations are caused mainly through increased expression or mutation of EGFR family members EGFR, ErbB2, ErbB3, and ErbB4. These receptors have been successfully targeted for cancer therapy. Specifically, a monoclonal antibody against ErbB2, trastuzumab, and a tyrosine kinase inhibitor against EGFR, gefitinib, have improved the survival of breast and lung cancer patients...
March 24, 2017: Cancers
https://www.readbyqxmd.com/read/28337940/genome-wide-analysis-of-lps-induced-inflammatory-response-in-the-rat-ventral-hippocampus-modulatory-activity-of-the-antidepressant-agomelatine
#4
Andrea Carlo Rossetti, Maria Serena Paladini, Giorgio Racagni, Marco Andrea Riva, Annamaria Cattaneo, Raffaella Molteni
OBJECTIVES: Several studies reported that antidepressant drugs have immune-regulatory effects by acting on specific inflammatory mediators. However, considering the highly complex nature of the inflammatory response, we have adopted an unbiased genome-wide strategy to investigate the immune-regulatory activity of the antidepressant agomelatine in modulating the response to an acute inflammatory challenge. METHODS: Microarray analysis was used to identify genes modulated in the ventral hippocampus of adult rats chronically treated with agomelatine (40 mg/kg, os) before being challenged with a single injection of lipopolysaccharide (LPS; 250 μg/kg, i...
March 24, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28337325/tetrahydroisoquinoline-7-carboxamide-derivatives-as-new-selective-discoidin-domain-receptor-1-ddr1-inhibitors
#5
Zhen Wang, Yali Zhang, Sergio G Bartual, Jinfeng Luo, Tingting Xu, Wenting Du, Qiuju Xun, Zhengchao Tu, Rolf A Brekken, Xiaomei Ren, Alex N Bullock, Guang Liang, Xiaoyun Lu, Ke Ding
Acute lung injury (ALI) is a deadly symptom for serious lung inflammation. Discoidin Domain Receptor 1 (DDR1) is a new potential target for anti-inflammatory drug discovery. A new selective tetrahydroisoquinoline-7-carboxamide based DDR1 inhibitor 7ae was discovered to tightly bind the DDR1 protein and potently inhibit its kinase function with a Kd value of 2.2 nM and an IC50 value of 6.6 nM, respectively. The compound dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) release in mouse primary peritoneal macrophages (MPMs)...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28337300/mutation-of-mir-21-targets-endogenous-lipoprotein-receptor-related-protein-6-and-nonalcoholic-fatty-liver-disease
#6
Chang-Ping Li, Hong-Jue Li, Jiao Nie, Xia Chen, Xian Zhou
Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Although miR-21 has been implicated in nonalcoholic fatty liver disease, it is unknown whether miR-21 could function as a therapeutic target. Here, we perform transfection analysis of miR-21 mimic or control mimic to evaluate the effects of miR-21 expression levels on human HepG2 nonalcoholic fatty liver cells. We used siRNA techniques to knock down miR-21 in HepG2 and control 293T cell lines, and then monitored lipid production and the expression levels of genes involved in lipid metabolism...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337285/preclinical-and-clinical-evaluation-of-the-liver-tumor-irreversible-electroporation-by-magnetic-resonance-imaging
#7
Matteo Figini, Xifu Wang, Tianchu Lyu, Zhanliang Su, Daniele Procissi, Vahid Yaghmai, Andrew C Larson, Zhuoli Zhang
Irreversible electroporation (IRE) is a relatively new technique for tumor ablation. It has shown promising results in difficult cases where surgery is not recommended and delicate anatomic structures are present near or within the tumor. Currently, liver cancer is one of the most common targets for IRE treatment. Pre-operative and post-operative imaging has a key role in IRE procedures and research studies. Although ultrasound is usually the first choice, especially for intra-operative guidance, magnetic resonance imaging (MRI) plays an important role in the visualization and characterization of tumor before and after IRE in clinical and preclinical studies...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337236/adalimumab-for-endoscopic-and-histopathological-mucosal-healing-in-paediatric-patients-with-moderate-to-severe-crohn-s-disease
#8
Edyta Szymanska, Maciej Dadalski, Wieslawa Grajkowska, Sylwia Szymanska, Maciej Pronicki, Jaroslaw Kierkus
INTRODUCTION: Deep remission, defined as clinical remission with mucosal healing (MH), with anti-tumor necrosis factor (TNF)-α agents is a new target for therapy in Crohn's disease (CD). Provided that the efficacy of infliximab (IFX) for induction of MH in CD has been demonstrated, there are much less data for adalimumab (ADA), and none concerning MH on histopathological examination. AIM: To assess the impact of biological therapy with ADA on both endoscopic and histopathological MH in paediatric patients with CD...
2017: Przegla̜d Gastroenterologiczny
https://www.readbyqxmd.com/read/28337120/antidyskinetic-effects-of-mek-inhibitor-are-associated-with-multiple-neurochemical-alterations-in-the-striatum-of-hemiparkinsonian-rats
#9
Guiqin Chen, Shuke Nie, Chao Han, Kai Ma, Yan Xu, Zhentao Zhang, Stella M Papa, Xuebing Cao
L-DOPA-induced dyskinesia (LID) represents one of the major problems of the long-term therapy of patients with Parkinson's disease (PD). Although, the pathophysiologic mechanisms underlying LID are not completely understood, activation of the extracellular signal regulated kinase (ERK) is recognized to play a key role. ERK is phosphorylated by mitogen-activated protein kinase kinase (MEK), and thus MEK inhibitor can prevent ERK activation. Here the effect of the MEK inhibitor PD98059 on LID and the associated molecular changes were examined...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28337021/different-drugs-for-bad-bugs-antivirulence-strategies-in-the-age-of-antibiotic-resistance
#10
REVIEW
Seth W Dickey, Gordon Y C Cheung, Michael Otto
The rapid evolution and dissemination of antibiotic resistance among bacterial pathogens are outpacing the development of new antibiotics, but antivirulence agents provide an alternative. These agents can circumvent antibiotic resistance by disarming pathogens of virulence factors that facilitate human disease while leaving bacterial growth pathways - the target of traditional antibiotics - intact. Either as stand-alone medications or together with antibiotics, these drugs are intended to treat bacterial infections in a largely pathogen-specific manner...
March 24, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28336474/the-evolution-of-heart-failure-with-reduced-ejection-fraction-pharmacotherapy-what-do-we-have-and-where-are-we-going
#11
REVIEW
Ahmed Selim, Ronald Zolty, Yiannis S Chatzizisis
Cardiovascular diseases represent a leading cause of mortality and increased healthcare expenditure worldwide. Heart failure, which simply describes an inability of the heart to meet the body's needs, is the end point for many other cardiovascular conditions. The last three decades have witnessed significant efforts aiming at the discovery of treatments to improve the survival and quality of life of patients with heart failure; many were successful, while others failed. Given that most of the successes in treating heart failure were achieved in patients with reduced left ventricular ejection fraction (HFrEF), we constructed this review to look at the recent evolution of HFrEF pharmacotherapy...
March 21, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28336473/unravelling-the-complexities-of-vascular-smooth-muscle-ion-channels-fine-tuning-of-activity-by-ancillary-subunits
#12
REVIEW
Thomas A Jepps
Which ion channel is the most important for regulating vascular tone? Which one is responsible for controlling the resting membrane potential or repolarization? Which channels are recruited by different intracellular signalling pathways or change in certain vascular diseases? Many different ion channels have been identified in the vasculature over the years and claimed as future therapeutic targets. Unfortunately, several of these ion channels are not just found in the vasculature, with many of them also found to have prominent functional roles in different organs of the body, which then leads to off-target effects...
March 20, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28335830/international-non-governmental-organizations-provision-of-community-based-tuberculosis-care-for-hard-to-reach-populations-in-myanmar-2013-2014
#13
Kyaw Thu Soe, Saw Saw, Johan van Griensven, Shuisen Zhou, Le Win, Palanivel Chinnakali, Safieh Shah, Myo Myo Mon, Si Thu Aung
BACKGROUND: National tuberculosis (TB) programs increasingly engage with international non-governmental organizations (INGOs), especially to provide TB care in complex settings where community involvement might be required. In Myanmar, however, there is limited data on how such INGO community-based programs are organized and how effective they are. In this study, we describe four INGO strategies for providing community-based TB care to hard-to-reach populations in Myanmar, and assess their contribution to TB case detection...
March 24, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28335408/n-hexane-insoluble-fraction-of-plantago-lanceolata-exerts-anti-inflammatory-activity-in-mice-by-inhibiting-cyclooxygenase-2-and-reducing-chemokines-levels
#14
Nanang Fakhrudin, Eny Dwi Astuti, Rini Sulistyawati, Djoko Santosa, Ratna Susandarini, Arief Nurrochmad, Subagus Wahyuono
Inflammation is involved in the progression of many disorders, such as tumors, arthritis, gastritis, and atherosclerosis. Thus, the development of new agents targeting inflammation is still challenging. Medicinal plants have been used traditionally to treat various diseases including inflammation. A previous study has indicated that dichloromethane extract of P. lanceolata leaves exerts anti-inflammatory activity in an in vitro model. Here, we examined the in vivo anti-inflammatory activities of a n-hexane insoluble fraction of P...
March 13, 2017: Scientia Pharmaceutica
https://www.readbyqxmd.com/read/28334884/improvement-in-the-prognosis-of-ovarian-cancer-in-the-era-before-addition-of-molecular-targeting-therapy
#15
Takako Shimada, Toshiaki Saito, Mototsugu Shimokawa, Kumi Shimamoto, Shuhei Matsushita, Shinichiro Yamaguchi, Kazuya Ariyoshi, Masao Okadome
Objective: The prognosis of ovarian cancer has improved because of platinum- and taxane-containing chemotherapy. We investigated the 5-year disease-specific overall survival and prognostic factors of patients with advanced ovarian cancer to elucidate the change in clinical course of ovarian cancer with the advance of chemotherapy for patients who developed relapse in the era before the addition of molecular targeting therapy. Methods: We reviewed the clinical course of 134 patients with advanced ovarian cancer (FIGO Stage III and IV) treated in the past 11 years (1999-2010)...
February 24, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28334509/disturbed-testicular-expression-of-the-estrogen-metabolizing-enzymes-cyp1a1-and-comt-in-infertile-men-with-primary-spermatogenic-failure-possible-negative-implications-on-sertoli-cells
#16
A Parada-Bustamante, C Molina, C Valencia, M Flórez, M C Lardone, F Argandoña, A Piottante, M Ebensperguer, P A Orihuela, A Castro
Estradiol (E2 ) is normally metabolized to hydroxyestradiols and methoxyestradiols by CYP1A1, CYP1B1 and COMT. However, an altered production of these metabolites by a disturbed expression of these enzymes is associated with reproductive and non-reproductive pathologies. In vitro studies suggest that increased hydroxyestradiols and methoxyestradiols intratesticular generation is related to male infertility, but no studies have explored whether infertile men have a disturbed testicular expression of the enzymes that generate these E2 metabolites...
March 23, 2017: Andrology
https://www.readbyqxmd.com/read/28333714/novel-regulators-of-plasma-lipid-levels
#17
Natalia Loaiza, Federico Oldoni, Jan A Kuivenhoven
PURPOSE OF REVIEW: To highlight very recent studies identifying novel regulatory molecules and mechanisms in plasma lipid metabolism. RECENT FINDINGS: Two novel regulatory mechanisms of LDL receptor (LDLR) intracellular trafficking have been described. The "COMMD/CCDC22/CCDC93" and "Wiskott-Aldrich syndrome protein and SCAR homologue" complexes were found to be involved in LDLR endosomal sorting and recycling, whereas the GRP94 was shown to protect LDLR from early degradation within the hepatocyte secretory pathway...
March 22, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28333443/systematic-investigation-of-ginkgo-biloba-leaves-for-treating-cardio-cerebrovascular-diseases-in-an-animal-model
#18
Yinfeng Yang, Yan Li, Jinghui Wang, Ke Sun, Weiyang Tao, Zhenzhong Wang, Wei Xiao, Yanqiu Pan, Shuwei Zhang, Yonghua Wang
Globally, cardio-cerebrovascular diseases (CCVDs) account for the leading cause of death, and thus the development of novel strategies for preventing and treating such diseases is in urgent need. Traditional Chinese Medicine (TCM), used for thousands of years in Asia and other regions, have been proven effective in certain disorders. As a medicinal herb for a long time in TCM, Ginkgo Biloba Leaves (GBLs), have been widely used to treat various diseases including CCVDs. However, the underlying molecular mechanisms of medicinal herb in treating these diseases are still unclear...
March 23, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28333335/saccharomyces-boulardii-cncm-i-745-restores-intestinal-barrier-integrity-by-regulation-of-e-cadherin-recycling
#19
Chloé Terciolo, Aurélie Dobric, Mehdi Ouaissi, Carole Siret, Gilles Breuzard, Françoise Silvy, Bastien Marchiori, Sébastien Germain, Renaté Bonier, Adel Hama, Roisin Owens, Dominique Lombardo, Véronique Rigot, Frédéric André
Background and Aims: Alteration in intestinal permeability is the main factor underlying the pathogenesis of many diseases affecting the gut, such as inflammatory bowel disease (IBD). Characterization of molecules targeting the restoration of intestinal barrier integrity is therefore vital for the development of alternative therapies. The yeast Saccharomyces boulardii CNCM I-745 (Sb), used to prevent and treat antibiotic-associated infectious and functional diarrhea, may have a beneficial effect in the treatment of IBD...
February 22, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28332316/golph3-induces-epithelial-mesenchymal-transition-via-wnt-%C3%AE-catenin-signaling-pathway-in-epithelial-ovarian-cancer
#20
Jing Sun, Xiaoming Yang, Ru Zhang, Suqing Liu, Xupei Gan, Xiaowei Xi, Zhenbo Zhang, Youji Feng, Yunyan Sun
Golgi phosphoprotein 3 (GOLPH3), a newly recognized oncogene, is associated with tumor growth, metastasis, and poor prognosis in several types of cancer. However, its biological role and underlying mechanism in epithelial ovarian cancer (EOC) remain poorly understood. Here, we found that GOLPH3 was overexpressed in EOC tissues and cell lines. This overexpression promoted the migration and invasion of EOC cells. Moreover, GOLPH3 upregulated the expression of epithelial-mesenchymal transition (EMT) markers, such as N-cadherin and Snail, and the Wnt/β-catenin-related genes cyclin-D1 and c-Myc, which were restored via silencing of GOLPH3 expression...
March 23, 2017: Cancer Medicine
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