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https://www.readbyqxmd.com/read/28109197/everolimus-is-better-than-rapamycin-in-attenuating-neuroinflammation-in-kainic-acid-induced-seizures
#1
Ming-Tao Yang, Yi-Chin Lin, Whae-Hong Ho, Chao-Lin Liu, Wang-Tso Lee
BACKGROUND: Microglia is responsible for neuroinflammation, which may aggravate brain injury in diseases like epilepsy. Mammalian target of rapamycin (mTOR) kinase is related to microglial activation with subsequent neuroinflammation. In the present study, rapamycin and everolimus, both as mTOR inhibitors, were investigated in models of kainic acid (KA)-induced seizure and lipopolysaccharide (LPS)-induced neuroinflammation. METHODS: In vitro, we treated BV2 cells with KA and LPS...
January 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28109168/integrated-omics-analysis-of-specialized-metabolism-in-medicinal-plants
#2
Amit Rai, Kazuki Saito, Mami Yamazaki
Medicinal plants are the rich source of highly diverse specialized metabolites with important pharmacological properties. Until recently, plant biologists were limited in their approach to explore biosynthetic pathways of these metabolites, mainly due to the scarcity of plant genomics resources. Recent advancements in the high-throughput large-scale analytical methods have enabled plant biologists to discover biosynthetic pathways for important plant-based medicinal metabolites. Reduced cost to generate omics datasets, and the development of computational tools for their analysis and integration have led to the elucidation of biosynthetic pathways of several plant origin bio-active metabolites...
January 21, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28109077/simultaneous-but-not-consecutive-combination-with-folinate-salts-potentiates-5-fluorouracil-antitumor-activity-in-vitro-and-in-vivo
#3
Antonello Di, Paola Orlandi, Teresa Di, Romano Danesi, Guido Bocci
The combination of folinate salts to 5-fluoruracil (5-FU)-based schedules is an established clinical routine in the landscape of the colorectal cancer treatment. The aim of this study was to investigate the pharmacological differences between the sequential administration of folinate salts (1 h before, as in clinical routine) followed by 5-FU and the simultaneous administration of both drugs. Proliferation and apoptotic assays were performed on human colon cancer cells exposed to 5-FU, calcium (CaLV) or disodium (NaLV) levofolinate or their simultaneous and sequential combination for 24 and 72h...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28109049/production-of-the-antibiotic-secondary-metabolite-solanapyrone-a-by-the-fungal-plant-pathogen-ascochyta-rabiei-during-fruiting-body-formation-in-saprobic-growth
#4
Wonyong Kim, Jeong-Jin Park, Frank M Dugan, Tobin L Peever, David R Gang, George Vandemark, Weidong Chen
Fungi are noted producers of a diverse array of secondary metabolites, many of which are of pharmacological importance. However, the biological roles of the vast majority of these molecules during the fungal life cycle in nature remain elusive. Solanapyrones are polyketide-derived secondary metabolites produced by diverse fungal species including the plant pathogen Ascochyta rabiei. This molecule was originally thought to function as a phytotoxin facilitating pathogenesis of A. rabiei. Chemical profiling and gene expression studies showed that solanapyrone A was specifically produced during saprobic, but not parasitic growth of A...
January 21, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28108860/early-cardioversion-in-atrial-fibrillation-earlier-is-better-but-not-always-and-maybe-not-immediately
#5
REVIEW
Paloma G Piña, Alexandru B Chicos
Atrial fibrillation (AF) is the most common cardiac arrhythmia in humans. One of its important features is the tendency to become more persistent over time, even in the absence of underlying progressive heart disease. Conversion and maintenance of sinus rhythm by pharmacological or electrical methods become increasingly difficult the longer the arrhythmia persists. Electrical, mechanical, structural, and autonomic remodeling processes have been implicated in the mechanisms of AF initiation, perpetuation, and progression...
January 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28108836/smad-dependent-signaling-plays-a-detrimental-role-in-a-fly-model-of-smarcb1-deficiency-and-the-biology-of-atypical-teratoid-rhabdoid-tumors
#6
Astrid Jeibmann, Jacqueline Schulz, Kristin Eikmeier, Pascal D Johann, Katharina Thiel, Isabel Tegeder, Oliver Ambrée, Michael C Frühwald, Stefan M Pfister, Marcel Kool, Werner Paulus, Martin Hasselblatt
Atypical teratoid/rhabdoid tumors (ATRT) are highly malignant brain tumors arising in young children. The majority of ATRT is characterized by inactivation of the chromatin remodeling complex member SMARCB1 (INI1/hSNF5). Little is known, however, on downstream pathways involved in the detrimental effects of SMARCB1 deficiency which might also represent targets for treatment. Using Drosophila melanogaster and the Gal4-UAS system, modifier screens were performed in order to identify the role of SMAD dependent signaling in the lethal phenotype associated with knockdown of snr1, the fly homolog of SMARCB1...
January 20, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28108814/the-small-neurotoxin-apamin-blocks-not-only-small-conductance-ca-2-activated-k-channels-sk-type-but-also-the-voltage-dependent-kv1-3-channel
#7
Patrick Voos, Mehtap Yazar, René Lautenschläger, Oliver Rauh, Anna Moroni, Gerhard Thiel
Apamin is frequently used as a specific blocker of small-conductance Ca(2+)-activated (SK type) K(+) channels. Here we show that the small neurotoxin is not as specific as anticipated. It is also a high-affinity inhibitor with an IC50 of 13 nM of the Kv1.3 channel; it blocks the latter with potency similar to the Kv1.3 blocker PAP-1. Since SK type channels and Kv1.3 channels are frequently coexpressed in different tissues such as cells of the immune system, apamin must be used with caution as a pharmacological tool...
January 20, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28108781/potentially-inappropriate-medications-predictor-for-mortality-in-a-cohort-of-community-dwelling-older-adults
#8
Mariana Martins Gonzaga do Nascimento, Juliana Vaz de Melo Mambrini, Maria Fernanda Lima-Costa, Josélia Oliveira Araújo Firmo, Sérgio William Viana Peixoto, Antônio Ignácio de Loyola Filho
PURPOSE: The objective of this study was to investigate whether the potentially inappropriate medication (PIM) use is a predictor for mortality in a community-based population of older adults. METHODS: A cohort study was performed between January 1, 1997, and December 31, 2011, based on data from a representative sample of the population aged 60 years or older living in Bambuí, Brazil. Univariate and multivariate analyses of the association between the variable of interest (use of PIM or pharmacological groups of PIM) and mortality were based on the extended Cox model for proportional hazards...
January 20, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28108775/-injection-therapy-for-cervical-and-lumbar-syndromes
#9
J Grifka, A Benditz, D Boluki
In cervical and lumbar pain syndromes special injections are key for effective pain therapy. Depending on the origin of pain injections are placed at the nerve root or the joints. Thus, the vicious cycle can be stopped. A correct technical procedure is of enormous importance. Because pharmacological effects and special complications are possible, monitoring and precautions are mandatory.
January 20, 2017: Der Orthopäde
https://www.readbyqxmd.com/read/28108747/national-guidelines-for-smoking-cessation-in-primary-care-a-literature-review-and-evidence-analysis
#10
Marjolein Verbiest, Evelyn Brakema, Rianne van der Kleij, Kate Sheals, Georgia Allistone, Siân Williams, Andy McEwen, Niels Chavannes
: National guidelines for smoking cessation in primary care can be effective in improving clinical practice. This study assessed which parties are involved in the development of such guidelines worldwide, which national guidelines address primary care, what recommendations are made for primary care settings, and how these recommendations correlate with each other and with current evidence. We identified national guidelines using an online resource. Only the most recent version of a guideline was included...
December 2017: NPJ Primary Care Respiratory Medicine
https://www.readbyqxmd.com/read/28108508/two-pore-channel-function-is-crucial-for-migration-of-invasive-cancer-cells
#11
Ong Nam Phuong Nguyen, Christian Grimm, Lina S Schneider, Yu-Kai Chao, Carina Atzberger, Karin Bartel, Anna Watermann, Melanie Ulrich, Doris Mayr, Christian Wahl-Schott, Martin Biel, Angelika M Vollmar
Metastatic invasion is the major cause of cancer-related deaths. In this study, we introduce two-pore channels (TPC), a recently described class of NAADP- and PI(3,5)P2-sensitive Ca2+-permeable cation channels in the endolysosomal system of cells, as candidate targets for the treatment of invasive cancers. Inhibition of the channel abrogated migration of metastatic cancer cells in vitro. Silencing or pharmacological inhibition of the two-pore channel TPC2 reduced lung metastasis of mammary mouse cancer cells...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108482/inhibition-of-prolyl-4-hydroxylase-decreases-muscle-fibrosis-following-chronic-rotator-cuff-tear
#12
J P Gumucio, M D Flood, A Bedi, H F Kramer, A J Russell, C L Mendias
OBJECTIVES: Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics...
January 2017: Bone & Joint Research
https://www.readbyqxmd.com/read/28108460/enhancer-remodeling-during-adaptive-bypass-to-mek-inhibition-is-attenuated-by-pharmacological-targeting-of-the-p-tefb-complex
#13
Jon S Zawistowski, Samantha M Bevill, Daniel R Goulet, Timothy J Stuhlmiller, Adriana S Beltran, Jose F Olivares-Quintero, Darshan Singh, Noah Sciaky, Joel S Parker, Naim U Rashid, Xin Chen, James S Duncan, Martin C Whittle, Steven P Angus, Sara Hanna Velarde, Brian T Golitz, Xiaping He, Charlene Santos, David B Darr, Kristalyn Gallagher, Lee M Graves, Charles M Perou, Lisa A Carey, H Shelton Earp, Gary L Johnson
Targeting the dysregulated BRaf-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRaf and MEK, resistance develops often involving non-genomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in triple negative breast cancer (TNBC) patients induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTKs) comparing tumor samples before and after one week of treatment...
January 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28108383/traditional-uses-of-medicinal-plants-reported-by-the-indigenous-communities-and-local-herbal-practitioners-of-bajaur-agency-federally-administrated-tribal-areas-pakistan
#14
Muhammad Abdul Aziz, Amir Hasan Khan, Muhammad Adnan, Izatullah Izatullah
ETHNOPHARMACOLOGICAL RELEVANCE: In the study area, knowledge related to the traditional uses of medicinal plants is totally in the custody of elder community members and local herbalists. The younger generation is unaware of the traditional knowledge, however with only few exceptions. Therefore, this study was planned with objective to document the medicinal importance of plants, conserve this precious indigenous knowledge, and share it among other communities through published literature...
January 17, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28108356/lipid-a-structural-modifications-in-extreme-conditions-and-identification-of-unique-modifying-enzymes-to-define-the-toll-like-receptor-4-structure-activity-relationship
#15
REVIEW
Alison J Scott, Benjamin L Oyler, David R Goodlett, Robert K Ernst
Strategies utilizing Toll-like receptor 4 (TLR4) agonists for treatment of cancer, infectious diseases, and other targets report promising results. Potent TLR4 antagonists are also gaining attention as therapeutic leads. Though some principles for TLR4 modulation by lipid A have been described, a thorough understanding of the structure-activity relationship (SAR) is lacking. Only through a complete definition of lipid A-TLR4 SAR is it possible to predict TLR4 signaling effects of discrete lipid A structures, rendering them more pharmacologically relevant...
January 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28108311/rip1-and-rip3-contribute-to-shikonin-induced-dna-double-strand-breaks-in-glioma-cells-via-increase-of-intracellular-reactive-oxygen-species
#16
Zijian Zhou, Bin Lu, Chen Wang, Zongqi Wang, Tianfei Luo, Meihua Piao, Fankai Meng, Guangfan Chi, Yinan Luo, Pengfei Ge
Shikonin has been reported to induce glioma cell death via necroptosis, a type of programmed necrosis primarily mediated by RIP1 and RIP3. Although RIP1 and RIP3 are found to regulate some features of necrosis such as energy depletion and cellular membrane disruption, it remains unclear whether RIP1 and RIP3 could modulate DNA double strand breaks (DSBs), which is a crucial event leading to chromatinolysis. In this study, we used glioma cell lines and mice model of xenograft glioma to investigate the roles of RIP1 and RIP3 in shikonin-induced DNA DSBs...
January 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28108245/japanese-guidelines-for-childhood-asthma-2017
#17
REVIEW
Hirokazu Arakawa, Yuhei Hamasaki, Yoichi Kohno, Motohiro Ebisawa, Naomi Kondo, Sankei Nishima, Toshiyuki Nishimuta, Akihiro Morikawa
The Japanese Guideline for the Diagnosis and Treatment of Allergic Diseases 2017 (JAGL 2017) includes a minor revision of the Japanese Pediatric Guideline for the Treatment and Management of Asthma 2012 (JPGL 2012) by the Japanese Society of Pediatric Allergy and Clinical Immunology. The section on child asthma in JAGL 2017 provides information on how to diagnose asthma between infancy and adolescence (0-15 years of age). It makes recommendations for best practices in the management of childhood asthma, including management of acute exacerbations and non-pharmacological and pharmacological management...
January 18, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28108196/homovanillic-acid-in-csf-of-mild-stage-parkinson-s-disease-patients-correlates-with-motor-impairment
#18
Alessandro Stefani, Mariangela Pierantozzi, Enrica Olivola, Salvatore Galati, Rocco Cerroni, Vincenza D'Angelo, Atticus H Hainsworth, Valentina Saviozzi, Ernesto Fedele, Claudio Liguori
In Parkinson's disease (PD), several efforts have been spent in order to find biochemical parameters able to identify the progression of the pathological processes at the basis of the disease. It is already known that advanced PD patients manifesting dyskinesia are featured by the high homovanillic acid (HVA)/dopamine (DA) ratio, suggesting the increased turnover of DA in these patients. Less clear is whether similar changes affect mild and moderate stages of the disease (between 1 and 2.5 of Hoehn & Yahr -H&Y- stage)...
January 18, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28108179/symptomatic-treatment-of-cough-among-adult-patients-with-lung-cancer-chest-guidelines-and-expert-panel-report
#19
Alex Molassiotis, Jaclyn A Smith, Peter Mazzone, Fiona Blackhall, Richard S Irwin
BACKGROUND: Cough among patients with lung cancer is a common but often undertreated symptom. We have used a recent Cochrane systematic review, among other sources of evidence, to update the recommendations and suggestions of the CHEST 2006 guideline on this topic. METHODS: The American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework were used. The Expert Cough Panel based their recommendations on data from the Cochrane systematic review on the topic, uncontrolled studies, case studies, and the clinical context...
January 17, 2017: Chest
https://www.readbyqxmd.com/read/28108129/cardiovascular-impact-in-patients-undergoing-maintenance-hemodialysis-clinical-management-considerations
#20
REVIEW
Srisakul Chirakarnjanakorn, Sankar D Navaneethan, Gary S Francis, W H Wilson Tang
Patients undergoing maintenance hemodialysis develop both structural and functional cardiovascular abnormalities. Despite improvement of dialysis technology, cardiovascular mortality of this population remains high. The pathophysiological mechanisms of these changes are complex and not well understood. It has been postulated that several non-traditional, uremic-related risk factors, especially the long-term uremic state, which may affect the cardiovascular system. There are many cardiovascular changes that occur in chronic kidney disease including left ventricular hypertrophy, myocardial fibrosis, microvascular disease, accelerated atherosclerosis and arteriosclerosis...
January 4, 2017: International Journal of Cardiology
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