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https://www.readbyqxmd.com/read/28628948/platelet-hyperaggregability-is-associated-with-decreased-adamts13-activity-and-enhanced-endotoxemia-in-patients-with-acute-cholangitis
#1
Hiroaki Takaya, Hideto Kawaratani, Takuya Kubo, Kenichiro Seki, Yasuhiko Sawada, Kosuke Kaji, Yasushi Okura, Kosuke Takeda, Mitsuteru Kitade, Kei Moriya, Tadashi Namisaki, Akira Mitoro, Masanori Matsumoto, Hiroshi Fukui, Hitoshi Yoshiji
AIM: Insufficient ADAMTS13 activity (ADAMTS13:AC) leads to increased levels of unusually large von Willebrand factor (VWF) multimers and causes microcirculatory disturbance and multiple organ failure (MOF). Endotoxin (Et) triggers the activation of coagulation and cytokine cascades, leading to MOF in severe inflammatory response syndrome (SIRS). Here, we investigated the potential role of endotoxemia-related ADAMTS13 in acute cholangitis. METHODS: Twenty-four patients with acute cholangitis, including 7 with severe acute cholangitis, were recruited in this study...
June 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28626800/dna-damage-induced-nuclear-factor-kappa-b-activation-and-its-roles-in-cancer-progression
#2
Wei Wang, Arul M Mani, Zhao-Hui Wu
DNA damage is a vital challenge to cell homeostasis. Cellular responses to DNA damage (DDR) play essential roles in maintaining genomic stability and survival, whose failure could lead to detrimental consequences such as cancer development and aging. Nuclear factor-kappa B (NF-κB) is a family of transcription factors that plays critical roles in cellular stress response. Along with p53, NF-κB modulates transactivation of a large number of genes which participate in various cellular processes involved in DDR...
2017: Journal of Cancer Metastasis and Treatment
https://www.readbyqxmd.com/read/28612487/anagen-effluvium-in-association-with-extracorporeal-membrane-oxygenation
#3
Lisa Cotter, Kyle Cheng, Anna Yasmine Kirkorian
Anagen effluvium (AE) is a type of alopecia with hair loss during the growth phase of a hair follicle and is most often associated with cytotoxic chemotherapy. This report describes a case of AE in a critically ill 2-year-old boy who developed cardiorespiratory failure requiring extracorporeal membranous oxygenation. We postulate that the combination of hypotension and hypoxia with subsequent reperfusion triggered an apoptotic cascade in the hair matrix, resulting in AE.
June 13, 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/28604492/a-microstructural-investigation-of-disc-disruption-induced-by-low-frequency-cyclic-loading
#4
Meredith L Schollum, Kelly R Wade, Peter A Robertson, Ashvin Thambyah, Neil D Broom
STUDY DESIGN: Microstructural investigation of low frequency cyclic loading and flexing of the lumbar disc. OBJECTIVE: To explore micro-level structural damage in motion segments subjected to low frequency repetitive loading and flexing at sub-acute loads. SUMMARY OF BACKGROUND DATA: Cumulative exposure to mechanical load has been implicated in low back pain and injury. The mechanical pathways by which cyclic loading physically affects spine tissues remain unclear, in part due to the absence of high quality microstructural evidence...
June 9, 2017: Spine
https://www.readbyqxmd.com/read/28602971/new-developments-in-hepatorenal-syndrome
#5
Ayse L Mindikoglu, Stephen C Pappas
Hepatorenal Syndrome (HRS) continues to be one of the major complications of decompensated cirrhosis leading to death in the absence of liver transplantation. Challenges in precisely evaluating renal function in the patient with cirrhosis remain due to the limitations of serum creatinine (Cr) alone in estimating glomerular filtration rate (GFR); current GFR estimating models appear to underestimate renal function. Newer models incorporating renal biomarkers, such as the Cr-Cystatin C GFR Equation for Cirrhosis appear to more accurately estimate true GFR...
June 7, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28598381/renin-inhibition-with-aliskiren-a-decade-of-clinical-experience
#6
REVIEW
Nikolaos-Dimitrios Pantzaris, Evangelos Karanikolas, Konstantinos Tsiotsios, Dimitrios Velissaris
The renin-angiotensin-aldosterone system (RAAS) plays a key role in the pathophysiology of arterial hypertension as well as in more complex mechanisms of cardiovascular and renal diseases. RAAS-blocking agents like angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, have long been key components in the treatment of essential hypertension, heart failure, diabetic nephropathy, and chronic kidney disease, showing benefits well beyond blood pressure reduction. Renin blockade as the first step of the RAAS cascade finally became possible in 2007 with the approval of aliskiren, the first orally active direct renin inhibitor available for clinical use and the newest antihypertensive agent on the market...
June 9, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28586203/why-is-research-on-amyloid-%C3%AE-failing-to-give-new-drugs-for-alzheimer-s-disease
#7
Andrew J Doig, Maria P Del Castillo-Frias, Olivia Berthoumieu, Bogdan Tarus, Jessica Nasica-Labouze, Fabio Sterpone, Phuong H Nguyen, Nigel M Hooper, Peter Faller, Philippe Derreumaux
The two hallmarks of Alzheimer's disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1-40 and Aβ1-42. Targeting the production, aggregation, and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting Aβ have failed. From a review of the recent literature and our own experience based on in vitro, in silico, and in vivo studies, we present some reasons to explain this repetitive failure...
June 6, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28581498/dystrophin-glycoprotein-complex-sequesters-yap-to-inhibit-cardiomyocyte-proliferation
#8
Yuka Morikawa, Todd Heallen, John Leach, Yang Xiao, James F Martin
The regenerative capacity of the adult mammalian heart is limited because of the reduced ability of cardiomyocytes (CMs) to progress through mitosis(1). The regenerative capacity of endogenous CMs exists at birth but is lost postnatally, with subsequent organ growth occurring through CM hypertrophy(2,3). The Hippo pathway, a conserved kinase cascade, inhibits CM proliferation in the developing heart to control heart size and in the adult heart to prevent regeneration(4,5). The dystrophin glycoprotein complex (DGC), a multicomponent transmembrane complex linking the actin cytoskeleton to extracellular matrix, is essential for CM homeostasis...
June 5, 2017: Nature
https://www.readbyqxmd.com/read/28578275/mitochondria-meditated-pathways-of-organ-failure-upon-inflammation
#9
REVIEW
Andrey V Kozlov, Jack R Lancaster, Andras T Meszaros, Adelheid Weidinger
Liver failure induced by systemic inflammatory response (SIRS) is often associated with mitochondrial dysfunction but the mechanism linking SIRS and mitochondria-mediated liver failure is still a matter of discussion. Current hypotheses suggest that causative events could be a drop in ATP synthesis, opening of mitochondrial permeability transition pore, specific changes in mitochondrial morphology, impaired Ca(2+) uptake, generation of mitochondrial reactive oxygen species (mtROS), turnover of mitochondria and imbalance in electron supply to the respiratory chain...
May 25, 2017: Redox Biology
https://www.readbyqxmd.com/read/28575052/myogenic-differentiation-of-vcp-disease-induced-pluripotent-stem-cells-a-novel-platform-for-drug-discovery
#10
Katrina J Llewellyn, Angèle Nalbandian, Lan N Weiss, Isabela Chang, Howard Yu, Bibo Khatib, Baichang Tan, Vanessa Scarfone, Virginia E Kimonis
Valosin Containing Protein (VCP) disease is an autosomal dominant multisystem proteinopathy caused by mutations in the VCP gene, and is primarily associated with progressive muscle weakness, including atrophy of the pelvic and shoulder girdle muscles. Currently, no treatments are available and cardiac and respiratory failures can lead to mortality at an early age. VCP is an AAA ATPase multifunction complex protein and mutations in the VCP gene resulting in disrupted autophagic clearance. Due to the rarity of the disease, the myopathic nature of the disorder, ethical and practical considerations, VCP disease muscle biopsies are difficult to obtain...
2017: PloS One
https://www.readbyqxmd.com/read/28569671/degradable-magnesium-implant-associated-infections-by-bacterial-biofilms-induce-robust-localized-and-systemic-inflammatory-reactions-in-a-mouse-model
#11
Muhammad Imran Rahim, Anshu Babbar, Stefan Lienenklaus, Marina Pils, Manfred Rohde
Biomaterial-associated Pseudomonas aeruginosa biofilm infections constitute cascade of host immune reactions ultimately leading towards implant failure. Due to lack of relevant in vivo biofilm models, majority of the studies report host immune responses against free living or planktonic bacteria while bacteria in clinical situations live more frequently as biofilm communities than as single cells. Present study investigated host immune responses against biomaterial-associated P. aeruginosa biofilms in a clinically relevant mouse model...
June 1, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28566502/inhibition-of-hdac-enhances-stat-acetylation-blocks-nf-%C3%AE-b-and-suppresses-the-renal-inflammation-and-fibrosis-in-npr1-haplotype-male-mice
#12
Prerna Kumar, Venkateswara R Gogulamudi, Ramu Peryasamy, Giri Raghavaraju, Umadevi Subramania, Kailash N Pandey
Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) plays a critical role in the regulation of blood pressure and fluid volume homeostasis. Mice lacking functional Npr1 (coding for GC-A/NPRA) exhibit hypertension and congestive heart failure. However, the underlying mechanisms remain largely less clear. The objective of the present study was to determine the physiological efficacy and impact of all-trans retinoic acid (ATRA) and sodium butyrate (NaBu) in ameliorating the renal fibrosis, inflammation, and hypertension in Npr1 gene-disrupted haplotype (1-copy; +/-) mice (50% expression levels of NPRA)...
May 31, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28547865/re-imagining-alzheimer-s-disease-the-diminishing-importance-of-amyloid-and-a-glimpse-of-what-lies-ahead
#13
REVIEW
Kai-Hei Tse, Karl Herrup
Many have criticized the amyloid cascade hypothesis of Alzheimer's disease for its inconsistencies and failures to either accurately predict disease symptoms or guide the development of productive therapies. In addition to criticisms, however, we believe that the field would benefit from having alternative narratives and disease models that can either replace or function alongside of an amyloid-centric view of Alzheimer's. This review is an attempt to meet that need. We offer three experimentally verified amyloid-independent mechanisms, each of which plausibly contributes substantially to the aetiology of Alzheimer's disease: loss of DNA integrity, faulty cell cycle regulation, regression of myelination...
May 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28540669/tropical-enteropathies
#14
REVIEW
John Louis-Auguste, Paul Kelly
PURPOSE OF REVIEW: The term 'tropical enteropathy' originated in observations in the 1960s that small intestinal morphology and function differed in the tropics from the norms found in temperate climates. It was subsequently shown that this enteropathy is more closely related to environmental conditions than latitude, and it was re-labelled 'environmental enteropathy'. It is now recognised that environmental enteropathy (also now called environmental enteric dysfunction) has implications for the health and linear growth of children in low- and middle-income countries, and it may underlie poor responses to oral vaccination in these countries...
July 2017: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/28539707/effector-and-regulatory-t-cell-trafficking-in-corneal-allograft-rejection
#15
REVIEW
Afsaneh Amouzegar, Sunil K Chauhan
Corneal transplantation is among the most prevalent and successful forms of solid tissue transplantation in humans. Failure of corneal allograft is mainly due to immune-mediated destruction of the graft, a complex and highly coordinated process that involves elaborate interactions between cells of innate and adaptive immunity. The migration of immune cells to regional lymphoid tissues and to the site of graft plays a central role in the immunopathogenesis of graft rejection. Intricate interactions between adhesion molecules and their counter receptors on immune cells in conjunction with tissue-specific chemokines guide the trafficking of these cells to the draining lymph nodes and ultimately to the site of graft...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28536642/itraq-based-proteomics-of-chronic-renal-failure-rats-after-fushengong-decoction-treatment-reveals-haptoglobin-and-alpha-1-antitrypsin-as-potential-biomarkers
#16
Yu Yang, Junmeng Wei, Xuekuan Huang, Mingjun Wu, Zhenbing Lv, Pan Tong, Rui Chang
Background. Chronic renal failure (CRF) has become a global health problem and bears a huge economic burden. FuShengong Decoction (FSGD) as traditional Chinese medicine has multiple pharmacological effects. Objectives. To understand the underlying molecular mechanism and signaling pathway involved in the FSGD treatment of CRF and screen differentially expressed proteins in rats with CRF treated with FSGD. Methods. Thirty-three male Sprague-Dawley rats were randomly divided into control group, CRF group, and FSGD group...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28527861/cellular-computational-generalized-neuron-network-for-frequency-situational-intelligence-in-a-multi-machine-power-system
#17
Yawei Wei, Ganesh Kumar Venayagamoorthy
To prevent large interconnected power system from a cascading failure, brownout or even blackout, grid operators require access to faster than real-time information to make appropriate just-in-time control decisions. However, the communication and computational system limitations of currently used supervisory control and data acquisition (SCADA) system can only deliver delayed information. However, the deployment of synchrophasor measurement devices makes it possible to capture and visualize, in near-real-time, grid operational data with extra granularity...
April 4, 2017: Neural Networks: the Official Journal of the International Neural Network Society
https://www.readbyqxmd.com/read/28523980/diverse-endometrial-mrna-signatures-during-the-window-of-implantation-in-patients-with-repeated-implantation-failure
#18
Cheng Shi, Hong Jing Han, Li Juan Fan, Jing Guan, Xing Bang Zheng, Xi Chen, Rong Liang, Xiao Wei Zhang, Kun Kun Sun, Qing Hua Cui, Huan Shen
High endometrial receptivity in the window of implantation (WOI) is essential for successful implantation. However, a diagnostic tool with high specificity for impaired endometrial receptivity remains to be developed. We collected endometrium specimens during the WOI from patients with RIF and women who conceived after one IVF/ICSI attempt. We conducted mRNA microarray on the samples followed by relevant comparative and functional analysis. Microarray analysis revealed 357 dysregulated mRNAs between the two groups...
May 19, 2017: Human Fertility: Journal of the British Fertility Society
https://www.readbyqxmd.com/read/28522681/endothelial-nox1-oxidase-assembly-in-human-pulmonary-arterial-hypertension-driver-of-gremlin1-mediated-proliferation
#19
Imad Al Ghouleh, Sanghamitra Sahoo, Daniel N Meijles, Jefferson H Amaral, Daniel S de Jesus, John Sembrat, Mauricio Rojas, Dmitry A Goncharov, Elena A Goncharova, Patrick J Pagano
Background: Pulmonary arterial hypertension (PAH) is a rapidly degenerating and devastating disease of increased pulmonary vessel resistance leading to right heart failure. Palliative modalities remain limited despite recent endeavors to investigate the mechanisms underlying increased pulmonary vascular resistance, i.e. aberrant vascular remodeling and occlusion. However, little is known of the molecular mechanisms responsible for endothelial proliferation, a root cause of PAH-associated vascular remodeling...
May 18, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28505451/toward-successful-cyclodextrin-based-solubility-enabling-formulations-for-oral-delivery-of-lipophilic-drugs-solubility-permeability-trade-off-biorelevant-dissolution-and-the-unstirred-water-layer
#20
Noa Fine-Shamir, Avital Beig, Moran Zur, David Lindley, Jonathan M Miller, Arik Dahan
The purpose of this work was to investigate key factors dictating the success/failure of cyclodextrin-based solubility-enabling formulations for oral delivery of low-solubility drugs. We have studied the solubility, the permeability, and the solubility-permeability interplay, of the highly lipophilic drug danazol, formulated with different levels (8.5, 10, 20, and 30%) of the commonly used hydroxypropyl-β-cyclodextrin (HPβCD), accounting for the biorelevant solubilization of the drug along the gastrointestinal tract (GIT), the unstirred water layer (UWL) adjacent to the GI membrane, and the overall absorption...
May 24, 2017: Molecular Pharmaceutics
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