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https://www.readbyqxmd.com/read/28641383/neuroprotection-in-stroke-the-importance-of-collaboration-and-reproducibility
#1
Ain A Neuhaus, Yvonne Couch, Gina Hadley, Alastair M Buchan
Acute ischaemic stroke accounts for 6.5 million deaths per year, and by 2030 will result in the annual loss of over 200 million disability-adjusted life years globally. There have been considerable recent advances in the gold standard of acute ischaemic stroke treatment, some aspects of which-aspirin to prevent recurrence, and treating patients in specialized stroke wards-are widely applicable. Recanalization of the occluded artery through thrombolysis and/or endovascular thrombectomy is restricted to only a small proportion of patients, due to contra-indications and the costs associated with establishing the infrastructure to deliver these treatments...
June 20, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28641051/beneficial-role-of-citrus-fruit-polyphenols-against-hepatic-dysfunctions-a-review
#2
Md Mohabbulla Mohib, Kazi Afnan, Tasfiq Zaman Paran, Salma Khan, Juthika Sarker, Nahid Hasan, Istiaque Hasan, Md Abu Taher Sagor
Alcoholic liver diseases and virus-induced hepatic dysfunctions are prevalent in western countries. Evidence also suggests that hyperglycemia and insulin resistance are key players in the development of hepatic diseases and their complications. Since the comorbid diseases like obesity, diabetes and vascular dysfunctions primarily affect liver, the modern therapies against other hepatic dysfunctions are becoming a major challenge to treat. In addition to these, polypharmacy and adverse drug reactions (ADRs) are further aggravating the phenomenon...
June 22, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28640746/a-chromosome-4-trisomy-contributes-to-increased-fluconazole-resistance-in-a-clinical-isolate-of-candida-albicans
#3
Matthew Z Anderson, Amrita Saha, Abid Haseeb, Richard J Bennett
Candida albicans is an important opportunistic fungal pathogen capable of causing both mucosal and disseminated disease. Infections are often treated with fluconazole, a front-line antifungal drug that targets the biosynthesis of ergosterol, a major component of the fungal cell membrane. Resistance to fluconazole can arise through a variety of mechanisms, including gain-of-function mutations, loss of heterozygosity events and aneuploidy. The clinical isolate P60002 was found to be highly resistant to azole-class drugs, yet lacked mutations or chromosomal rearrangements known to be associated with azole resistance...
June 22, 2017: Microbiology
https://www.readbyqxmd.com/read/28640703/integrating-evidence-based-medicine-for-treatment-of-spinal-metastases-into-a-decision-framework-neurologic-oncologic-mechanicals-stability-and-systemic-disease
#4
Ori Barzilai, Ilya Laufer, Yoshiya Yamada, Daniel S Higginson, Adam M Schmitt, Eric Lis, Mark H Bilsky
Patients with cancer are frequently affected by spinal metastases. Treatment is palliative, with the principle goals of pain relief, preservation of neurologic function, and improvement in quality of life. In the past decade, we have witnessed a dramatic change in the treatment paradigms due to the development of improved surgical strategies and systemic and radiation therapy. The most important change to these paradigms has been the integration of spinal stereotactic radiosurgery (SSRS), allowing delivery of tumoricidal radiation doses with sparing of nearby organs at risk...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640599/a-high-throughput-dna-sequencing-approach-to-determine-sources-of-fecal-bacteria-in-a-lake-superior-estuary
#5
Clairessa M Brown, Christopher Staley, Ping Wang, Brent Dalzell, Chan Lan Chun, Michael J Sadowsky
Current microbial source tracking (MST) methods, employed to determine sources of fecal contamination in waterways, use molecular markers targeting host-associated bacteria in animal or human feces. However, there is a lack of knowledge about fecal microbiome composition in several animals and imperfect marker specificity and sensitivity. To overcome these issues, a community-based MST method has been developed. Here, we describe a study done in the Lake Superior-St. Louis River estuary using SourceTracker, a program that calculates the source contribution to an environment...
June 22, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28637178/the-at04a-vaccine-against-proprotein-convertase-subtilisin-kexin-type-9-reduces-total-cholesterol-vascular-inflammation-and-atherosclerosis-in-apoe-3leiden-cetp-mice
#6
Christine Landlinger, Marianne G Pouwer, Claudia Juno, José W A van der Hoorn, Elsbet J Pieterman, J Wouter Jukema, Guenther Staffler, Hans M G Princen, Gergana Galabova
Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hypercholesterolaemia and atherosclerosis. PCSK9 binds to the low density lipoprotein receptor and enhances its degradation, which leads to the reduced clearance of low density lipoprotein cholesterol (LDLc) and a higher risk of atherosclerosis. In this study, the AT04A anti-PCSK9 vaccine was evaluated for its therapeutic potential in ameliorating or even preventing coronary heart disease in the atherogenic APOE*3Leiden...
June 19, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28637056/-urosepsis-in-children
#7
Josef Oswald
Urinary tract infections (UTI) are the most common infectious diseases in children. Urosepsis in childhood, though rare, is the most complicated possible variant. In newborns and infants, unspecific symptoms are a significant barrier to a fast and reliable diagnosis, which is crucial to successful treatment. In addition to urine and laboratory tests as well as non-invasive examinations (ultrasound), there may be an indication for invasive examinations of the kidneys (DMSA scans) in cases of a severe infection...
June 21, 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28637023/cationic-liquid-crystalline-nanoparticles-for-the-delivery-of-synthetic-rnai-based-therapeutics
#8
Emanuela Gentile, Taro Oba, Jing Lin, Ruping Shao, Feng Meng, Xiaobo Cao, Heather Y Lin, Majidi Mourad, Apar Pataer, Veerabhadran Baladandayuthapani, Dong Cai, Jack A Roth, Lin Ji
RNA interference (RNAi)-based therapeutics have been used to silence the expression of targeted pathological genes. Small interfering RNA (siRNAs) and microRNA (miRNAs) inhibitor have performed this function. However, short half-life, poor cellular uptake, and nonspecific distribution of small RNAs call for the development of novel delivery systems to facilitate the use of RNAi. We developed a novel cationic liquid crystalline nanoparticle (CLCN) to efficiently deliver synthetic siRNAs and miRNAs. CLCNs were prepared by using high-speed homogenization and assembled with synthetic siRNA or miRNA molecules in nuclease-free water to create CLCN/siRNA or miRNA complexes...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637019/clinicopathological-characteristics-of-ros1-and-ret-rearranged-nsclc-in-caucasian-patients-data-from-a-cohort-of-713-non-squamous-nsclc-lacking-kras-egfr-her2-braf-pik3ca-alk-alterations
#9
Frédéric Dugay, Francisco Llamas-Gutierrez, Marjory Gournay, Sarah Medane, François Mazet, Dan Christian Chiforeanu, Emmanuelle Becker, Régine Lamy, Hervé Léna, Nathalie Rioux-Leclercq, Marc-Antoine Belaud-Rotureau, Florian Cabillic
Targeted therapies have substantially changed the management of non-small cell lung cancer (NSCLC) patients with driver oncogenes. Given the high frequency, EGFR and ALK aberrations were the first to be detected and paved the way for tyrosine kinase inhibitor (TKI) treatments. Other kinases such as ROS1 and more recently RET have emerged as promising targets, and ROS1 and RET TKIs are already available for precision medicine.We screened a large cohort of 713 Caucasian non-squamous NSCLC patients lacking EGFR/KRAS/BRAF/HER2/PI3KCA/ALK aberrations for ROS1 and RET rearrangements using fluorescence in situ hybridization to determine the frequency and clinicopathological characteristics of ROS1- and RET-positive patients...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636555/overcoming-resistance-to-targeted-therapy-with-immunotherapy-and-combination-therapy-for-metastatic-melanoma
#10
REVIEW
Hilary R Keller, Xin Zhang, Li Li, Helmut Schaider, James W Wells
Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636542/niaoduqing-granules-relieve-chronic-kidney-disease-symptoms-by-decreasing-renal-fibrosis-and-anemia
#11
Xu Wang, Suyun Yu, Qi Jia, Lichuan Chen, Jinqiu Zhong, Yanhong Pan, Peiliang Shen, Yin Shen, Siliang Wang, Zhonghong Wei, Yuzhu Cao, Yin Lu
NiaoDuQing (NDQ) granules, a traditional Chinese medicine, has been clinically used in China for over fourteen years to treat chronic kidney disease (CKD). To elucidate the mechanisms underlying the therapeutic benefits of NDQ, we designed an approach incorporating chemoinformatics, bioinformatics, network biology methods, and cellular and molecular biology experiments. A total of 182 active compounds were identified in NDQ granules, and 397 putative targets associated with different diseases were derived through ADME modelling and target prediction tools...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636484/bezlotoxumab-anti-toxin-b-monoclonal-antibody-to-prevent-recurrence-of-clostridium-difficile-infection
#12
Javier A Villafuerte Gálvez, Ciarán P Kelly
Clostridium difficile infection (CDI) is the most common nosocomial infection in the U.S. 25% of CDI patients go on to develop recurrent CDI (rCDI) following current standard of care (SOC) therapy, leading to morbidity, mortality and economic loss. The first passive immunotherapy drug targeting C.difficile toxin B (bezlotoxumab) has been approved recently by the FDA and EMA for prevention of rCDI. Areas covered: A body of key studies was selected and reviewed by the authors. The unmet needs in CDI care were ascertained with emphasis in rCDI, including the epidemiology, pathophysiology and current management...
June 21, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#13
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28636309/quantitative-chemical-proteomic-profiling-of-the-in-vivo-targets-of-reactive-drug-metabolites
#14
Landon R Whitby, R Scott Obach, Gabriel M Simon, Matthew M Hayward, Benjamin F Cravatt
Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, we describe a quantitative chemical proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogues of four representative hepatotoxic drugs, we demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28636211/resolution-of-donor-non-alcoholic-fatty-liver-disease-following-liver-transplantation
#15
Andrew D Posner, Samuel T Sultan, Norann A Zaghloul, William S Twaddell, David A Bruno, Steven I Hanish, William R Hutson, Laci Hebert, Rolf N Barth, John C LaMattina
INTRODUCTION: Transplant surgeons conventionally select against livers displaying high degrees (>30%) of macrosteatosis (MaS), out of concern for primary non-function or severe graft dysfunction. As such, there is relatively limited experience with such livers, and the natural history remains incompletely characterized. We present our experience of transplanted livers with high degrees of MaS and microsteatosis (MiS), with a focus on the histopathologic and clinical outcomes. METHODS: 29 cases were identified with liver biopsies available from both the donor and the corresponding liver transplant recipient...
June 21, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28635653/virtual-screening-against-phosphoglycerate-kinase-1-in-quest-of-novel-apoptosis-inhibitors
#16
Jie Xia, Bo Feng, Qianhang Shao, Yuhe Yuan, Xiang Simon Wang, Naihong Chen, Song Wu
Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson's disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28635648/deoxyelephantopin-and-isodeoxyelephantopin-as-potential-anticancer-agents-with-effects-on-multiple-signaling-pathways
#17
REVIEW
Tahir Mehmood, Amara Maryam, Hamed A Ghramh, Muhammad Khan, Tonghui Ma
Cancer is the 2nd leading cause of death worldwide. The development of drugs to target only one specific signaling pathway has limited therapeutic success. Developing chemotherapeutics to target multiple signaling pathways has emerged as a new prototype for cancer treatment. Deoxyelephantopin (DET) and isodeoxyelephantopin (IDET) are sesquiterpene lactone components of "Elephantopus scaber and Elephantopus carolinianus", traditional Chinese medicinal herbs that have long been used as folk medicines to treat liver diseases, diabetes, diuresis, bronchitis, fever, diarrhea, dysentery, cancer, and inflammation...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28635632/glucose-and-lipid-dysmetabolism-in-a-rat-model-of-prediabetes-induced-by-a-high-sucrose-diet
#18
Ana Burgeiro, Manuela G Cerqueira, Bárbara M Varela-Rodríguez, Sara Nunes, Paula Neto, Frederico C Pereira, Flávio Reis, Eugénia Carvalho
Glucotoxicity and lipotoxicity are key features of type 2 diabetes mellitus, but their molecular nature during the early stages of the disease remains to be elucidated. We aimed to characterize glucose and lipid metabolism in insulin-target organs (liver, skeletal muscle, and white adipose tissue) in a rat model treated with a high-sucrose (HSu) diet. Two groups of 16-week-old male Wistar rats underwent a 9-week protocol: HSu diet (n = 10)-received 35% of sucrose in drinking water; Control (n = 12)-received vehicle (water)...
June 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28635628/identification-and-validation-of-reference-genes-for-seashore-paspalum-response-to-abiotic-stresses
#19
Yu Liu, Jun Liu, Lei Xu, Hui Lai, Yu Chen, Zhimin Yang, Bingru Huang
Seashore paspalum (Paspalum vaginatum) is among the most salt- and cadmium-tolerant warm-season perennial grass species widely used as turf or forage. The objective of this study was to select stable reference genes for quantitative real-time polymerase chain reaction (qRT-PCR) analysis of seashore paspalum in response to four abiotic stresses. The stability of 12 potential reference genes was evaluated by four programs (geNorm, NormFinder, BestKeeper, and RefFinder). U2AF combined with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) showed stable expression in Cd-treated leaves and cold-treated roots...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28635319/a-case-of-topical-ruxolitinib-treatment-failure-in-alopecia-areata
#20
Maya Deeb, Renée A Beach
Alopecia areata (AA) is an autoimmune-mediated, nonscarring form of hair loss. Despite its prevalence, current management options are limited, especially when the disease has progressed to alopecia totalis (AT) or alopecia universalis (AU). Recent evidence that janus kinase (JAK) signaling contributes to AA pathogenesis prompted the investigation of JAK inhibitors such as tofacitinib and ruxolitinib as possible oral treatments. However, the potential for significant adverse effects with systemic JAK inhibition makes local administration a more attractive option...
June 1, 2017: Journal of Cutaneous Medicine and Surgery
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