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https://www.readbyqxmd.com/read/28731826/convergently-evolved-toxic-secondary-metabolites-in-plants-drive-the-parallel-molecular-evolution-of-insect-resistance
#1
Georg Petschenka, Vera Wagschal, Michael von Tschirnhaus, Alexander Donath, Susanne Dobler
Natural selection imposed by natural toxins has led to striking levels of convergent evolution at the molecular level. Cardiac glycosides represent a group of plant toxins that block the Na,K-ATPase, a vital membrane protein in animals. Several herbivorous insects have convergently evolved resistant Na,K-ATPases, and in some species, convergent gene duplications have also arisen, likely to cope with pleiotropic costs of resistance. To understand the genetic basis and predictability of these adaptations, we studied five independent lineages of leaf-mining flies (Diptera: Agromyzidae)...
August 2017: American Naturalist
https://www.readbyqxmd.com/read/28730939/drug-delivery-to-the-brain-how-can-nanoencapsulated-statins-be-used-in-the-clinic
#2
Fabio Sonvico, Francesca Zimetti, Adriana Raffin Pohlmann, Sílvia Stanisçuaski Guterres
Statins are used for the primary and secondary prevention of cardiovascular disease by inhibiting cholesterol synthesis in the liver. Statins have also noncholesterol-related effects, called pleiotropic effects, which arise from statins' anti-inflammatory, immunomodulatory and antioxidant properties. These effects are especially attractive for the treatment of various brain diseases ranging from stroke to neurodegenerative diseases. Still, low brain concentrations after oral drug administration hinder the clinical application of statins in these pathologies...
July 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28730313/derivatization-free-lc-ms-ms-method-for-estrogen-quantification-in-mouse-brain-highlights-a-local-metabolic-regulation-after-oral-versus-subcutaneous-administration
#3
Ecaterina Lozan, Svitlana Shinkaruk, Shaam Alice Al Abed, Valérie Lamothe, Mylène Potier, Aline Marighetto, Jean-Marie Schmitter, Catherine Bennetau-Pelissero, Corinne Buré
17β-Estradiol (17β-E2) is a steroid with pleiotropic actions. In addition to being a sexual hormone, it is also produced in the brain where it modulates the reproductive axis. It has been shown that 17β-E2 also acts on synaptic plasticity and plays a role in neurological pathways and in neurodegenerative diseases. Assaying this steroid in the brain is thus interesting to improve our knowledge of 17β-E2 effects in the brain. However, 17β-E2 concentration in the central nervous system has been reported to be of a few nanograms per gram wet weight (nanomolar range concentration); therefore, its quantification requires both an efficient extraction process and a sensitive detection method...
July 20, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28729344/exogenous-stress-hormones-alter-energetic-and-nutrient-costs-of-development-and-metamorphosis
#4
Lucas J Kirschman, Marshall D McCue, Justin G Boyles, Robin W Warne
Variation in environmental conditions during larval life stages can shape development during critical windows and have lasting effects on the adult organism. Changes in larval developmental rates in response to environmental conditions, for example, can trade-off with growth to determine body size and condition at metamorphosis, which can affect adult survival and fecundity. However, it is unclear how use of energy and nutrients shape trade-offs across life stage transitions because no studies have quantified these costs of larval development and metamorphosis...
July 20, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28728974/activation-of-cryptic-phthoxazolin-a-production-in-streptomyces-avermitilis-by-the-disruption-of-autoregulator-receptor-homologue-avar3
#5
Dian Anggraini Suroto, Shigeru Kitani, Kiyoko T Miyamoto, Yasuko Sakihama, Masayoshi Arai, Haruo Ikeda, Takuya Nihira
The genomes of actinomycetes encode many cryptic novel/useful bioactive compounds, but access to these cryptic secondary metabolites remains limited. Streptomyces avermitilis predominantly produces three polyketide antibiotics (avermectin, filipin, and oligomycin) but has the potential to produce more secondary metabolites based on the number of cryptic biosynthetic gene clusters. Here, we extensively investigated the metabolite profiles of a gene disruptant of AvaR3 (an autoregulator receptor homologue), which is involved in the pleiotropic regulation of antibiotic production and cell morphology...
July 17, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28727746/atorvastatin-reduces-%C3%AE-adrenergic-dysfunction-in-rats-with-diabetic-cardiomyopathy
#6
Aude Carillion, Sarah Feldman, Na Na, Matthieu Biais, Wassila Carpentier, Aurélie Birenbaum, Nicolas Cagnard, Xavier Loyer, Dominique Bonnefont-Rousselot, Stéphane Hatem, Bruno Riou, Julien Amour
BACKGROUND: In the diabetic heart the β-adrenergic response is altered partly by down-regulation of the β1-adrenoceptor, reducing its positive inotropic effect and up-regulation of the β3-adrenoceptor, increasing its negative inotropic effect. Statins have clinical benefits on morbidity and mortality in diabetic patients which are attributed to their "pleiotropic" effects. The objective of our study was to investigate the role of statin treatment on β-adrenergic dysfunction in diabetic rat cardiomyocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28727040/genome-wide-association-studies-and-meta-analysis-reveal-novel-quantitative-trait-loci-and-pleiotropic-loci-for-swine-head-related-traits
#7
H Chen, T Huang, Z Zhang, B Yang, C Jiang, J Wu, Z Zhou, H Zheng, W Xin, M Huang, M Zhang, C Chen, J Ren, H Ai, L Huang
The pig is an important domestic animal that provides a larger amount of meat and serves as a biomedical animal model for human. Head and facial features are closely linked to identity recognition in mammal communication. To uncover the genetic architecture of swine head and facial features, we constructed 5 experimental pig populations and accurately measured 10 traits related to head and facial features, for which genome-wide association studies and meta-analysis were later carried out. As a result, we identified a total of 24 loci harboring 437 SNP on 8 swine chromosomes (SSC) that surpassed suggestively significant levels, of which 17 loci on 6 chromosomes exceeded the 5% genome-wide significance thresholds...
June 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28725914/vascular-complications-in-diabetes-old-messages-new-thoughts
#8
REVIEW
Josephine M Forbes, Amelia K Fotheringham
In parallel with the growing diabetes pandemic, there is an increasing burden of micro- and macrovascular complications, occurring in the majority of patients. The identification of a number of synergistic accelerators of disease, providing therapeutic pathways, has stabilised the incidence of complications in most western nations. However, the primary instigators of diabetic complications and, thus, prevention strategies, remain elusive. This has necessitated a refocus on natural history studies, where tissue and plasma samples are sequentially taken to determine when and how disease initiates...
July 19, 2017: Diabetologia
https://www.readbyqxmd.com/read/28724841/sphingosine-1-phosphate-and-atherosclerosis
#9
Makoto Kurano, Yutaka Yatomi
Sphingosine 1-phosphate (S1P) is a potent lipid mediator that works on five kinds of S1P receptors located on the cell membrane. In the circulation, S1P is distributed to HDL, followed by albumin. Since S1P and HDL share several bioactivities, S1P is believed to be responsible for the pleiotropic effects of HDL. Plasma S1P levels are reportedly lower in subjects with coronary artery disease, suggesting that S1P might be deeply involved in the pathogenesis of atherosclerosis. In basic experiments, however, S1P appears to possess both pro-atherosclerotic and anti-atherosclerotic properties; for example, S1P possesses anti-apoptosis, anti-inflammation, and vaso-relaxation properties and maintains the barrier function of endothelial cells, while S1P also promotes the egress and activation of lymphocytes and exhibits pro-thrombotic properties...
July 20, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28724458/clinical-and-therapeutic-potential-of-protein-kinase-pkr-in-cancer-and-metabolism
#10
M B Garcia-Ortega, G J Lopez, G Jimenez, J A Garcia-Garcia, V Conde, H Boulaiz, E Carrillo, M Perán, J A Marchal, M A Garcia
The protein kinase R (PKR, also called EIF2AK2) is an interferon-inducible double-stranded RNA protein kinase with multiple effects on cells that plays an active part in the cellular response to numerous types of stress. PKR has been extensively studied and documented for its relevance as an antiviral agent and a cell growth regulator. Recently, the role of PKR related to metabolism, inflammatory processes, cancer and neurodegenerative diseases has gained interest. In this review, we summarise and discuss the involvement of PKR in several cancer signalling pathways and the dual role that this kinase plays in cancer disease...
July 20, 2017: Expert Reviews in Molecular Medicine
https://www.readbyqxmd.com/read/28722327/transforming-growth-factor-beta-matrix-metalloproteinases-and-urokinase-type-plasminogen-activator-interaction-in-the-cancer-epithelial-to-mesenchymal-transition
#11
REVIEW
Juan F Santibanez, Hristina Obradović, Tamara Kukolj, Jelena Krstić
Transforming growth factor beta (TGF-β) is a pleiotropic factor that acts as a tumor suppressor in the early stages, while it exerts tumor promoting activities in advanced stages of cancer development. One of the hallmarks of cancer progression is the capacity of cancer cells to migrate and invade surrounding tissues with subsequent metastasis to different organs. Matrix metalloproteinases (MMPs) together with urokinase-type plasminogen activator (uPA) and its receptor (uPAR), whose main original function described is the proteolytic degradation of the extracellular matrix, play key cellular roles in the enhancement of cell malignancy during cancer progression...
July 19, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28721827/melatonin-as-pleiotropic-molecule-with-therapeutic-potential-for-type-2-diabetes-and-cancer
#12
Marzena Wojcik, Michal Krawczyk, Pawel Wojcik, Katarzyna Cypryk, Lucyna Alicja Wozniak
The incidence both of diabetes, particularly type 2 (T2DM), and cancer is increasing worldwide, making these diseases growing global health problem along with increasing healthcare expenditures. The current therapeutic approach for the treatment of these multifactorial diseases is far from satisfactory. Therefore, there is still considerable interest in searching new therapeutic strategies with the use of both natural and synthetic compounds exhibiting higher efficiency and lower toxicity compared to medicines used currently in clinical practice...
July 18, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28721151/moderate-dose-atorvastatin-improves-arterial-endothelial-function-in-patients-with-angina-pectoris-and-normal-coronary-angiogram-a-pilot-study
#13
Amela Kabaklić, Zlatko Fras
INTRODUCTION: Endothelial dysfunction could contribute to the pathophysiology of angina pectoris (AP) in patients with normal coronary angiograms. Besides lipid-lowering effects, statins exert pleiotropic effects including improving endothelial function. MATERIAL AND METHODS: Our double-blind study included 58 patients with AP, noninvasively confirmed myocardial ischemia and a normal coronary angiogram. The effect of once-daily 20 mg atorvastatin (A) was compared with placebo (P) for 6 months...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28718822/a-bacterial-toxin-with-analgesic-properties-hyperpolarization-of-drg-neurons-by-mycolactone
#14
Ok-Ryul Song, Han-Byul Kim, Samuel Jouny, Isabelle Ricard, Alexandre Vandeputte, Nathalie Deboosere, Estelle Marion, Christophe J Queval, Pierre Lesport, Emmanuel Bourinet, Daniel Henrion, Seog Bae Oh, Guillaume Lebon, Guillaume Sandoz, Edouard Yeramian, Laurent Marsollier, Priscille Brodin
Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans, is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT₂ receptors (angiotensin II type 2 receptors; AT₂R), and leading to potassium-dependent hyperpolarization...
July 18, 2017: Toxins
https://www.readbyqxmd.com/read/28718667/hydroxytyrosol-induces-apoptosis-and-cell-cycle-arrest-and-suppresses-multiple-oncogenic-signaling-pathways-in-prostate-cancer-cells
#15
Haseeb Zubair, Arun Bhardwaj, Aamir Ahmad, Sanjeev Kumar Srivastava, Mohammad Aslam Khan, Girijesh Kumar Patel, Seema Singh, Ajay Partap Singh
SCOPE: Hydroxytyrosol (HT), a polyphenol from olives, is a potential anticancer agent. This study was designed to evaluate the anticancer activity of HT against prostate cancer cells, and the mechanism thereof. METHODS AND RESULTS: Treatment of LNCaP and C4-2 prostate cancer cells with HT resulted in a dose-dependent inhibition of proliferation. This was in contrast to HT's ineffectiveness against normal prostate epithelial cells RWPE1 and PWLE2, suggesting cancer-cell-specific effect...
July 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28718426/targeting-tgf-%C3%AE-signaling-in-cancer
#16
REVIEW
Selcuk Colak, Peter Ten Dijke
The transforming growth factor (TGF)-β signaling pathway is deregulated in many diseases, including cancer. In healthy cells and early-stage cancer cells, this pathway has tumor-suppressor functions, including cell-cycle arrest and apoptosis. However, its activation in late-stage cancer can promote tumorigenesis, including metastasis and chemoresistance. The dual function and pleiotropic nature of TGF-β signaling make it a challenging target and imply the need for careful therapeutic dosing of TGF-β drugs and patient selection...
January 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718097/regulatory-genes-and-their-roles-for-improvement-of-antibiotic-biosynthesis-in-streptomyces
#17
REVIEW
Fengjuan Lu, Yanyan Hou, Heming Zhang, Yiwen Chu, Haiyang Xia, Yongqiang Tian
The numerous secondary metabolites in Streptomyces spp. are crucial for various applications. For example, cephamycin C is used as an antibiotic, and avermectin is used as an insecticide. Specifically, antibiotic yield is closely related to many factors, such as the external environment, nutrition (including nitrogen and carbon sources), biosynthetic efficiency and the regulatory mechanisms in producing strains. There are various types of regulatory genes that work in different ways, such as pleiotropic (or global) regulatory genes, cluster-situated regulators, which are also called pathway-specific regulatory genes, and many other regulators...
August 2017: 3 Biotech
https://www.readbyqxmd.com/read/28717990/iron-based-phosphate-binders-a-paradigm-shift-in-the-treatment-of-hyperphosphatemic-anemic-ckd-patients
#18
REVIEW
Francesco Locatelli, Lucia Del Vecchio
The partial correction of anemia and the normalization of phosphate and blood pressure are the mainstay of treatment of patients with chronic kidney disease (CKD). Available anti-hypertensive drugs, erythropoiesis stimulating agents (ESAs) and iron supplements have resolved quite satisfactorily the goal of controlling hypertension and partially correcting anemia. Unfortunately, the treatment of hyperphosphatemia is still far from resolved. Phosphate binders have poor tolerability and/or limited efficacy, leading to the prescription of many tablets that achieve only a mild-to-moderate effect...
July 17, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28716883/role-of-the-%C3%AE-common-%C3%AE-c-family-of-cytokines-in-health-and-disease
#19
Timothy R Hercus, Winnie L T Kan, Sophie E Broughton, Denis Tvorogov, Hayley S Ramshaw, Jarrod J Sandow, Tracy L Nero, Urmi Dhagat, Emma J Thompson, Karen S Cheung Tung Shing, Duncan R McKenzie, Nicholas J Wilson, Catherine M Owczarek, Gino Vairo, Andrew D Nash, Vinay Tergaonkar, Timothy Hughes, Paul G Ekert, Michael S Samuel, Claudine S Bonder, Michele A Grimbaldeston, Michael W Parker, Angel F Lopez
The β common ([βc]/CD131) family of cytokines comprises granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5, all of which use βc as their key signaling receptor subunit. This is a prototypic signaling subunit-sharing cytokine family that has unveiled many biological paradigms and structural principles applicable to the IL-2, IL-4, and IL-6 receptor families, all of which also share one or more signaling subunits. Originally identified for their functions in the hematopoietic system, the βc cytokines are now known to be truly pleiotropic, impacting on multiple cell types, organs, and biological systems, and thereby controlling the balance between health and disease...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28714387/macrophage-migration-inhibitory-factor-a-favorable-marker-in-inflammatory-diseases
#20
Johannes Hertelendy, Georg Reumuth, David Simons, Christian Stoppe, Bong-Sung Kim, Jan-Philipp Stromps, Paul C Fuchs, Jürgen Bernhagen, Norbert Pallua, Gerrit Grieb
Macrophage migration inhibitory factor (MIF) was firstly described in the 1960s as a pleiotropic cytokine affecting a variety of immune cells. Different physiological functions mainly involving inflammatory reactions such as chemokine-like function and regulating systemic stress responses have been reported. In several clinical studies the use of MIF as a biomarker has been investigated promising support for diseases with an inflammatory aspect such as sepsis, systemic infections and autoimmune diseases. This article in detail reviews clinical data and evaluates the function as biomarker focusing on inflammatory and autoimmune diseases...
July 14, 2017: Current Medicinal Chemistry
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