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https://www.readbyqxmd.com/read/28547865/re-imagining-alzheimer-s-disease-the-diminishing-importance-of-amyloid-and-a-glimpse-of-what-lies-ahead
#1
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 etiology 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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-tradeoff-biorelevant-dissolution-and-the-unstirred-water-layer
#8
Noa Fine-Shamir, Avital Beig, Moran Zur, David Lindley, Jon 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 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28501115/postconditioning-attenuates-coronary-perivascular%C3%A2-and-interstitial-fibrosis-through-modulating-angiotensin-ii-receptors-and-angiotensin-converting-enzyme-2-after-myocardial-infarction
#9
Zhang-Feng Wang, Ning-Ping Wang, Suzanna Harmouche, Tiji Philip, Xue-Fen Pang, Feng Bai, Zhi-Qing Zhao
BACKGROUND: Postconditioning (Postcon) is known to reduce infarct size. This study tested the hypothesis that Postcon attenuates the perivascular and interstitial fibrosis after myocardial infarction through modulating angiotensin II-activated fibrotic cascade. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to 45-min coronary occlusion followed by 1 and 6 wk of reperfusion. Postcon was applied at the onset of reperfusion with four cycles of 10/10-s reperfusion-ischemia at the onset of reperfusion...
May 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28497371/sestrin-2-attenuates-neonatal-rat-cardiomyocyte-hypertrophy-induced-by-phenylephrine-via-inhibiting-erk1-2
#10
Bin Dong, Ruicong Xue, Yu Sun, Yugang Dong, Chen Liu
Cardiac hypertrophy is an adaptive response triggered by many physiological and pathological conditions and will lead to heart failure eventually. Sestrin 2, which is a stress-responsive protein, was reported to protect heart from ischemia reperfusion injury. However, the role of Sestrin 2 in cardiac hypertrophy remains unknown. In our present study, we aimed to explore the effects of Sestrin 2 on cardiomyocyte hypertrophy. We found that knockdown of Sestrin 2 protein aggravated cardiomyocyte hypertrophy induced by phenylephrine (PE), featured by increased hypertrophic marker ANP and cell surface area...
May 11, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28494828/treatment-of-persistent-pulmonary-hypertension-of-the-newborn-use-of-pulmonary-vasodilators-in-term-neonates
#11
Caitlyn Luecke, Christopher McPherson
Persistent pulmonary hypertension of the newborn (PPHN) represents a challenging condition associated with significant morbidity. A successful transition from intrauterine to extrauterine life is contingent on adequate pulmonary vasodilation. Several pathophysiologies contribute to the failure of this cascade and may result in life-threatening hypoxia and acidosis in the newborn. Management includes optimal respiratory support, adequate sedation and analgesia, and support of vascular tone and cardiac function...
May 1, 2017: Neonatal Network: NN
https://www.readbyqxmd.com/read/28479018/levosimendan-mitigates-coagulopathy-and-organ-dysfunction-in-rats-with-endotoxemia
#12
Hsieh-Chou Huang, Hsin-Jung Tsai, Chao-Chun Wang, Cheng-Ming Tsao, Shuk-Man Ka, Wen-Jinn Liaw, Chin-Chen Wu
BACKGROUND: In patients with severe sepsis, pro-inflammatory cytokines and subsequent activation of tissue factors trigger a cascade of events that lead to coagulation dysfunction and multiple organ failure. It has been shown that levosimendan has protective effects against tissue injury caused by endotoxin. The purpose of this study was to evaluate the effects of levosimendan on consumptive coagulopathy and organ dysfunction in an endotoxemic animal model induced by lipopolysaccharide (LPS)...
May 3, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28476660/%C3%AE-adrenergic-induced-sr-ca-2-leak-is-mediated-by-an-epac-nos-pathway
#13
Laëtitia Pereira, Dan J Bare, Samuel Galice, Thomas R Shannon, Donald M Bers
Cardiac β-adrenergic receptors (β-AR) and Ca(2+)-Calmodulin dependent protein kinase (CaMKII) regulate both physiological and pathophysiological Ca(2+) signaling. Elevated diastolic Ca(2+) leak from the sarcoplasmic reticulum (SR) contributes to contractile dysfunction in heart failure and to arrhythmogenesis. β-AR activation is known to increase SR Ca(2+) leak via CaMKII-dependent phosphorylation of the ryanodine receptor. Two independent and reportedly parallel pathways have been implicated in this β-AR-CaMKII cascade, one involving exchange protein directly activated by cAMP (Epac2) and another involving nitric oxide synthase 1 (NOS1)...
May 2, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28467389/on-the-many-actions-of-ouabain-pro-cystogenic-effects-in-autosomal-dominant-polycystic-kidney-disease
#14
REVIEW
Jessica Venugopal, Gustavo Blanco
Ouabain and other cardenolides are steroidal compounds originally discovered in plants. Cardenolides were first used as poisons, but after finding their beneficial cardiotonic effects, they were rapidly included in the medical pharmacopeia. The use of cardenolides to treat congestive heart failure remained empirical for centuries and only relatively recently, their mechanisms of action became better understood. A breakthrough came with the discovery that ouabain and other cardenolides exist as endogenous compounds that circulate in the bloodstream of mammals...
May 3, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28462460/combined-administration-of-ascs-and-bmp-12-promotes-an-m2-macrophage-phenotype-and-enhances-tendon-healing
#15
Richard H Gelberman, Stephen W Linderman, Rohith Jayaram, Anna D Dikina, Shelly Sakiyama-Elbert, Eben Alsberg, Stavros Thomopoulos, Hua Shen
BACKGROUND: Outcomes after intrasynovial tendon repair are highly variable. An intense inflammatory cascade followed by a delayed healing response can cause adhesion formation and repair-site failure that severely impair the function of repaired digits. No effective remedies exist to fully address these issues. Cell- and growth factor-based therapies have been shown to modulate inflammation and improve cell proliferation and matrix synthesis and therefore are promising treatment approaches for intrasynovial tendon repair...
May 1, 2017: Clinical Orthopaedics and related Research
https://www.readbyqxmd.com/read/28448952/sepsis-and-septic-shock-pathogenesis-and-treatment-perspectives
#16
REVIEW
Hayk Minasyan
The majority of bacteremias do not develop to sepsis: bacteria are cleared from the bloodstream. Oxygen released from erythrocytes and humoral immunity kill bacteria in the bloodstream. Sepsis develops if bacteria are resistant to oxidation and proliferate in erythrocytes. Bacteria provoke oxygen release from erythrocytes to arterial blood. Abundant release of oxygen to the plasma triggers a cascade of events that cause: 1. oxygen delivery failure to cells; 2. oxidation of plasma components that impairs humoral regulation and inactivates immune complexes; 3...
April 18, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28435089/cobalt-chloride-induces-rhoa-rock-activation-and-remodeling-effect-in-h9c2-cardiomyoblasts-involvement-of-pi3k-akt-and-mapk-pathways
#17
Cheng-I Cheng, Yueh-Hong Lee, Po-Han Chen, Yu-Chun Lin, Ming-Huei Chou, Ying-Hsien Kao
Chronic heart failure is a serious complication of myocardial infarction, one of the major causes of death worldwide that often leads to adverse cardiac hypertrophy and poor prognosis. Hypoxia-induced cardiac tissue remodeling is considered an important underlying etiology. This study aimed to delineate the signaling profiles of RhoA/ROCK, PI3K/Akt, and MAPK and their involvement in regulation of remodeling events in cultured H9c2 cardiomyoblast cells. In addition to its growth-suppressive effect, the hypoxia-mimetic chemical, cobalt chloride (CoCl2) significantly induced RhoA kinase activation as revealed by increased MBS phosphorylation and ROCK1/2 expression in H9c2 cells...
April 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28427561/molecular-targets-of-ascochlorin-and-its-derivatives-for-cancer-therapy
#18
Jason Chua Min-Wen, Benjamin Chua Yan-Jiang, Srishti Mishra, Xiaoyun Dai, Junji Magae, Ng Shyh-Chang, Alan Prem Kumar, Gautam Sethi
Cancer is an extremely complex disease comprising of a multitude of characteristic hallmarks that continue to evolve with time. At the genomic level, random mutations leading to deregulation of diverse oncogenic signal transduction cascades and polymorphisms coupled with environmental as well as life style-related factors are major causative agent contributing to chemoresistance and the failure of conventional therapies as well as molecular targeted agents. Hence, there is an urgent need to identify novel alternative therapies based on alternative medicines to combat this dreaded disease...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28422386/corticosteroid-might-reduce-serum-levels-of-pro-inflammatory-cytokines-in-fulminant-hepatitis-a-case-series
#19
Keiichi Fujiwara, Seiji Hida, Shin Yasui, Osamu Yokosuka, Shigeto Oda
AIM: There are no beneficial therapies except for emergency liver transplantation for acute liver failure (ALF). However, in Japan, which has a serious problem in the shortage of donor livers, therapies other than transplantation must be further investigated for patients with ALF. Pro-inflammatory cytokines promoting tissue destruction are predominant at an early phase of ALF. Corticosteroid (CS) influences monocyte/macrophage differentiation, by suppressing pro-inflammatory genes, indicating CS treatment might be beneficial during the early phase of ALF...
April 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28413044/expression-profiling-feline-peripheral-blood-monocytes-identifies-a-transcriptional-signature-associated-with-type-two-diabetes-mellitus
#20
Caroline A O'Leary, Mamdouh Sedhom, Mia Reeve-Johnson, John Mallyon, Katharine M Irvine
Diabetes mellitus is a common disease of cats and is similar to type 2 diabetes (T2D) in humans, especially with respect to the role of obesity-induced insulin resistance, glucose toxicity, decreased number of pancreatic β-cells and pancreatic amyloid deposition. Cats have thus been proposed as a valuable translational model of T2D. In humans, inflammation associated with adipose tissue is believed to be central to T2D development, and peripheral blood monocytes (PBM) are important in the inflammatory cascade which leads to insulin resistance and β-cell failure...
April 2017: Veterinary Immunology and Immunopathology
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