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https://www.readbyqxmd.com/read/28650422/the-effects-of-valsartan-on-renal-klotho-expression-and-oxidative-stress-in-alleviation-of-cyclosporine-nephrotoxicity
#1
Sina Raeisi, Amir Ghorbanihaghjo, Hassan Argani, Siavoush Dastmalchi, Babollah Ghasemi, Teimour Ghazizadeh, Nadereh Rashtchizadeh, Mahboob Nemati, Mehran Mesgari Abbasi, Nasrin Bargahi, Hossein Samadi Kafil, Amir Mansour Vatankhah
BACKGROUND: Nephrotoxicity side effect of the immunosuppressive drug, cyclosporine A (CsA), can be a major issue in transplantation medicine. Cyclosporine A-induced nephrotoxicity is multifactorial but oxidative stress has a critical role in this process. It has been demonstrated that Valsartan (Val) as an angiotensin receptor blocker has renoprotective effects, but the molecular mechanisms responsible for the renal protection, independent from its blood pressure lowering effect, have not yet been fully understood...
June 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28650175/bioactive-peptide-natural-products-as-lead-structures-for-medicinal-use
#2
Tam Dang, Roderich D Süssmuth
The need for new drugs for the treatment of various diseases is enormous. From the previous century until the present, numerous peptide and peptide-derived natural products have been isolated from bacteria and fungi. Hence, microorganisms play a pivotal role as sources for novel drugs with an emphasis on anti-infective agents. Various disciplines from biology, chemistry, and medicine are involved in early stages of the search for peptide natural products including taxonomy, microbiology, bioanalytics, bioinformatics, and medicinal chemistry...
June 26, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28649643/molecular-stratification-of-early-breast-cancer-identifies-drug-targets-to-drive-stratified-medicine
#3
Jane Bayani, Cindy Q Yao, Mary Anne Quintayo, Fu Yan, Syed Haider, Alister D'Costa, Cassandra L Brookes, Cornelis J H van de Velde, Annette Hasenburg, Dirk G Kieback, Christos Markopoulos, Luc Dirix, Caroline Seynaeve, Daniel Rea, Paul C Boutros, John M S Bartlett
Many women with hormone receptor-positive early breast cancer can be managed effectively with endocrine therapies alone. However, additional systemic chemotherapy treatment is necessary for others. The clinical challenges in managing high-risk women are to identify existing and novel druggable targets, and to identify those who would benefit from these therapies. Therefore, we performed mRNA abundance analysis using the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial pathology cohort to identify a signature of residual risk following endocrine therapy and pathways that are potentially druggable...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28649437/integrating-personalized-gene-expression-profiles-into-predictive-disease-associated-gene-pools
#4
Jörg Menche, Emre Guney, Amitabh Sharma, Patrick J Branigan, Matthew J Loza, Frédéric Baribaud, Radu Dobrin, Albert-László Barabási
Gene expression data are routinely used to identify genes that on average exhibit different expression levels between a case and a control group. Yet, very few of such differentially expressed genes are detectably perturbed in individual patients. Here, we develop a framework to construct personalized perturbation profiles for individual subjects, identifying the set of genes that are significantly perturbed in each individual. This allows us to characterize the heterogeneity of the molecular manifestations of complex diseases by quantifying the expression-level similarities and differences among patients with the same phenotype...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28648701/universal-genomic-testing-the-next-step-in-oncological-decision-making-or-a-dead-end-street
#5
Julian Walter Holch, Klaus Hans Metzeler, Andreas Jung, Kristina Riedmann, Philipp Jakob Jost, Wilko Weichert, Thomas Kirchner, Volker Heinemann, Christoph Benedikt Westphalen
The concept of 'personalised medicine' aims at allocating patients to different treatment options based on individual characteristics to optimise treatment benefit and side effects. In oncology, personalised treatments coupled to biomarkers have led to the approval of targeted agents with high anti-tumour activity. However, these therapies are often limited to narrow, molecularly defined subsets of patients with a specific morphomolecular tumour profile. Recently, it became obvious that the same molecular alteration might drive oncogenesis in many different tumours, and it might be beneficial to target the alteration in a histology informed but entity-overarching way...
June 22, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28648452/advances-in-decoding-axolotl-limb-regeneration
#6
REVIEW
Brian J Haas, Jessica L Whited
Humans and other mammals are limited in their natural abilities to regenerate lost body parts. By contrast, many salamanders are highly regenerative and can spontaneously replace lost limbs even as adults. Because salamander limbs are anatomically similar to human limbs, knowing how they regenerate should provide important clues for regenerative medicine. Although interest in understanding the mechanics of this process has never wavered, until recently researchers have been vexed by seemingly impenetrable logistics of working with these creatures at a molecular level...
June 22, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28647625/thermoresponsive-poly-glycidyl-ether-brushes-on-gold-surface-engineering-parameters-and-their-implication-for-cell-sheet-fabrication
#7
Silke Heinen, José Luis Cuellar-Camacho, Marie Weinhart
Thermoresponsive polymer coatings, optimized for cell adhesion and thermally-triggered cell detachment, allow the fabrication of confluent cell sheets with intact extracellular matrix. However, rational design guidelines for such coatings are rare, since temperature-triggered cell adhesion and detachment from thermoresponsive surfaces are mechanistically not well understood. Herein, we investigated the impact of molecular weight (2, 9, 24 kDa), grafting density (0.04 - 1.4 chains nm(-2)), morphology, and roughness of well-characterized thermoresponsive poly(glycidyl ether) brushes on the cell response at 37 and 20°C...
June 21, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#8
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of SCD1 in regulation of liver T-ICs and sorafenib resistance...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28647135/ultrasound-dependent-cytoplasmic-internalization-of-a-peptide-sonosensitizer-conjugate
#9
Yuki Inaba, Kazunori Watanabe, Mizuki Kitamatsu, Eiji Nakata, Atsushi Harada, Takashi Ohtsuki
A method to induce cytoplasmic peptide delivery, using ultrasound, was demonstrated using a molecular conjugate of a cell-penetrating peptide (CPP), a functional peptide, and a sonosensitizer. As a model of such molecular conjugates, TatBim-RB, consisting of the Tat CPP, the Bim apoptosis inducing peptide, and the sonosensitizer rose bengal was synthesized. CPPs have been widely used for intracellular delivery of various cargos; however, CPP-fused molecules tend to become entrapped in endosomes, as was observed for TatBim-RB molecules applied to cells...
June 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28647085/in-vivo-phenotypic-screening-clinical-proof-of-concept-for-a-drug-repositioning-approach
#10
REVIEW
John R Ciallella, Andrew G Reaume
In vivo phenotypic screening and drug repositioning are strategies developed as alternatives to underperforming hypothesis-driven molecular target based drug discovery efforts. This article reviews examples of drugs identified by phenotypic observations and describes the use of the theraTRACE(®)in vivo screening platform for finding and developing new indications for discontinued clinical compounds. Clinical proof-of-concept for the platform is exemplified by MLR-1023, a repositioned compound that has recently shown significant clinical efficacy in Type 2 diabetes patients...
March 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/28646793/shexiang-baoxin-pills-promotes-angiogenesis-in-myocardial-infarction-rats-via-up-regulation-of-20-hete-mediated-endothelial-progenitor-cells-mobilization
#11
Feifei Huang, Yang Liu, Xia Yang, Di Che, Kaifeng Qiu, Bruce D Hammock, Jingfeng Wang, Mong-Heng Wang, Jie Chen, Hui Huang
BACKGROUND AND AIMS: Therapeutic angiogenesis is a pivotal strategy for ischemic heart disease. The aim of the present study was to determine the effect and molecular mechanism of Shexiang Baoxin pills, a widely-used traditional Chinese medicine for ischemic heart disease, on angiogenesis in a rat model of myocardial infarction (MI). METHODS: We used the occlusion of left anterior descending coronary artery of Sprague-Dawley rats as a model of MI. The MI rats were treated with distilled water, Shexiang Baoxin pills, or Shexiang Baoxin pills + HET0016 (a selective blocker of the biosynthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) at 10 mg/kg/day), respectively...
June 7, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28646744/systematic-biobanking-novel-imaging-techniques-and-advanced-molecular-analysis-for-precise-tumor-diagnosis-and-therapy-the-polish-mobit-project
#12
Jacek Niklinski, Adam Kretowski, Marcin Moniuszko, Joanna Reszec, Anna Michalska-Falkowska, Magdalena Niemira, Michal Ciborowski, Radoslaw Charkiewicz, Dorota Jurgilewicz, Miroslaw Kozlowski, Rodryg Ramlau, Cezary Piwkowski, Miroslaw Kwasniewski, Monika Kaczmarek, Andrzej Ciereszko, Tomasz Wasniewski, Robert Mroz, Wojciech Naumnik, Ewa Sierko, Magdalena Paczkowska, Joanna Kisluk, Anetta Sulewska, Adam Cybulski, Zenon Mariak, Boguslaw Kedra, Jacek Szamatowicz, Paweł Kurzawa, Lukasz Minarowski, Angelika Edyta Charkiewicz, Barbara Mroczko, Jolanta Malyszko, Christian Manegold, Lothar Pilz, Heike Allgayer, Mohammed L Abba, Hartmut Juhl, Frauke Koch
Personalized and precision medicine is gaining recognition due to the limitations by standard diagnosis and treatment; many areas of medicine, from cancer to psychiatry, are moving towards tailored and individualized treatment for patients based on their clinical characteristics and genetic signatures as well as novel imaging techniques. Advances in whole genome sequencing have led to identification of genes involved in a variety of diseases. Moreover, biomarkers indicating severity of disease or susceptibility to treatment are increasingly being characterized...
June 21, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28646406/podocytes-and-the-quest-for-precision-medicines-for-kidney-diseases
#13
REVIEW
Peter Mundel
In this review, I describe a 30-year journey in the quest for precision medicines for patients with kidney diseases. In 1987, when I started my reseach career, most scientists studying glomerular disease biology were focused on mesangial cells. The crucial role of the podocyte in many kidney diseases characterized by proteinuria, including focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, had not yet been recognized. We were not aware of genetic causes or drivers of kidney diseases nor of molecular markers and cell culture systems for mechanistic studies of podocyte biology...
June 23, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28646156/mahanine-exerts-in-vitro-and-in-vivo-antileishmanial-activity-by-modulation-of-redox-homeostasis
#14
Saptarshi Roy, Devawati Dutta, Eswara M Satyavarapu, Pawan K Yadav, Chhabinath Mandal, Susanta Kar, Chitra Mandal
Earlier we have established a carbazole alkaloid (mahanine) isolated from an Indian edible medicinal plant as an anticancer agent with minimal effect on normal cells. Here we report for the first time that mahanine-treated drug resistant and sensitive virulent Leishmania donovani promastigotes underwent apoptosis through phosphatidylserine externalization, DNA fragmentation and cell cycle arrest. An early induction of reactive oxygen species (ROS) suggests that the mahanine-induced apoptosis was mediated by oxidative stress...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645780/salvia-miltiorrhiza-bunge-danshen-extract-attenuates-permanent-cerebral-ischemia-through-inhibiting-platelet-activation-in-rats
#15
Yu-Xiang Fei, Si-Qi Wang, Li-Jian Yang, Yan-Ying Qiu, Yi-Ze Li, Wen-Yuan Liu, Tao Xi, Wei-Rong Fang, Yun-Man Li
ETHNOPHARMACOLOGICAL RELEVANCE: Danshen is a crude herbal drug isolated from dried roots of Salvia miltiorrhiza Bunge. This plant is widely used in oriental medicine for the treatment of cardiovascular and cerebrovascular diseases. The supercritical CO2 extract from Danshen (SCED) (57.85%, 5.67% and 4.55% for tanshinone IIA, tanshinone I and cryptotanshinone respectively) was studied in this article, whose potential molecular mechanism remains unclear, especially in anti-thrombosis. AIM OF THE STUDY: The present study was designed to observe the protective effect of SCED on ischemic stroke in rats and to explore the underlying anti-thrombosis mechanism...
June 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28644958/translating-cancer-epigenomics-into-the-clinic-focus-on-lung-cancer
#16
REVIEW
Josep Mari-Alexandre, Angel Diaz-Lagares, Maria Villalba, Oscar Juan, Ana B Crujeiras, Alfonso Calvo, Juan Sandoval
Epigenetic deregulation is increasingly being recognized as a hallmark of cancer. Recent studies have identified many new epigenetic biomarkers, some of which are being introduced into clinical practice for diagnosis, molecular classification, prognosis or prediction of response to therapies. O-6-methylguanine-DNA methyltransferase gene is the most clinically advanced epigenetic biomarker as it predicts the response to temozolomide and carmustine in gliomas. Therefore, epigenomics may represent a novel and promising tool for precision medicine, and in particular, the detection of epigenomic biomarkers in liquid biopsies will be of great interest for monitoring diseases in patients...
June 2, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28644430/the-clinical-landscape-for-sma-in-a-new-therapeutic-era
#17
REVIEW
K Talbot, E F Tizzano
Despite significant advances in basic research, the treatment of degenerative diseases of the nervous system remains one of the greatest challenges for translational medicine. The childhood onset motor neuron disorder spinal muscular atrophy (SMA) has been viewed as one of the more tractable targets for molecular therapy, due to a detailed understanding of the molecular genetic basis of the disease. In SMA, inactivating mutations in the SMN1 gene can be partially compensated for by limited expression of SMN protein from a variable number of copies of the SMN2 gene, which provides both a molecular explanation for phenotypic severity and a target for therapy...
June 23, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28643945/athens-based-meeting-to-discuss-the-paediatric-virology-crossroad-in-october-2017
#18
Ioannis N Mammas, Demetrios A Spandidos
Viral infections are common diseases and they are well-described in the Ancient Greek Hippocratic Corpus (1), together with a limited spectrum of diagnostic and treatment options. However, over the past two decades, several exciting developments in the fields of clinical virology and molecular medicine have expanded our knowledge on the pathogenesis of viral infections in neonates and children (2,3). Since 2015, the workshop on paediatric virology has tried enthusiastically to explore these advances and to investigate recent challenges in the prevention strategies, molecular diagnostics, multimodality imaging and therapeutics of paediatric viral infections (2-5)...
June 23, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/28643294/-saccharomyces-boulardii-cncm-i-745-influences-the-gut-associated-immune-system
#19
Heike Stier, Stephan C Bischoff
BACKGROUND: The impact of the intestinal microbiome is increasing steadily with regard to the immune function und the defense against pathogens. The medicinal yeast Saccharomyces boulardii CNCM I-745 (S. boulardii) has been used as probiotic for the prevention and treatment of infectious diarrhea since more than 50 years. Meta-analyses confirm the clinical efficacy of S. boulardii to treat diarrhea of various origins in children and adults. METHOD: This review article summarizes experimental studies on molecular and immunological mechanisms which explain the proven clinical efficacy of S...
June 2017: MMW Fortschritte der Medizin
https://www.readbyqxmd.com/read/28643176/a-promising-tool-in-retina-regeneration-current-perspectives-and-challenges-when-using-mesenchymal-progenitor-stem-cells-in-veterinary-and-human-ophthalmological-applications
#20
REVIEW
Anna Cislo-Pakuluk, Krzysztof Marycz
Visual impairment is a common ailment of the current world population, with more exposure to CCD screens and fluorescent lighting, approximately 285 billion people suffer from this deficiency and 13% of those are considered clinically blind. More common causes for visual impairment include age-related macular degeneration (AMD), glaucoma and diabetic retinopathy (Zhu et al. Molecular Medicine Reports, 2015; Kolb et al. 2007; Machalińska et al. Current Eye Research, 34(9),748-760, 2009) among a few. As cases of retinal and optic nerve diseases rise, it is vital to find a treatment, which has led to investigation of the therapeutic potential of various stem cells types (Bull et al...
June 22, 2017: Stem Cell Reviews
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