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https://www.readbyqxmd.com/read/28214509/haplodeficiency-of-activin-receptor-like-kinase-4-alleviates-myocardial-infarction-induced-cardiac-fibrosis-and-preserves-cardiac-function
#1
Yi-He Chen, Qian Wang, Chang-Yi Li, Jian-Wen Hou, Xiao-Meng Chen, Qing Zhou, Jie Chen, Yue-Peng Wang, Yi-Gang Li
Cardiac fibrosis (CF), a repairing process following myocardial infarction (MI), is characterized by abnormal proliferation of cardiac fibroblasts and excessive deposition of extracellular matrix (ECM) resulting in inevitable resultant heart failure. TGF-β (transforming growth factor-β)/ALK5 (Activin receptor-like kinase 5)/Smad2/3/4 pathways have been reported to be involved in the process. Recent studies have implicated both activin and its specific downstream component ALK4 in stimulating fibrosis in non-cardiac organs...
February 15, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28207932/detecting-signals-of-chronic-shedding-to-explain-pathogen-persistence-leptospira-interrogans-in-california-sea-lions
#2
M G Buhnerkempe, K C Prager, C C Strelioff, D J Greig, J L Laake, S R Melin, R L DeLong, F M D Gulland, J O Lloyd-Smith
Identifying mechanisms driving pathogen persistence is a vital component of wildlife disease ecology and control. Asymptomatic, chronically infected individuals are an oft-cited potential reservoir of infection but demonstrations of the importance of chronic shedding to pathogen persistence at the population level remain scarce. Studying chronic shedding using commonly collected disease data is hampered by numerous challenges, including short-term surveillance that focuses on single epidemics and acutely ill individuals, the subtle dynamical influence of chronic shedding relative to more obvious epidemic drivers, and poor ability to differentiate between the effects of population prevalence of chronic shedding versus intensity and duration of chronic shedding in individuals...
February 16, 2017: Journal of Animal Ecology
https://www.readbyqxmd.com/read/28197914/sumoylation-in-development-and-differentiation
#3
Adeline F Deyrieux, Van G Wilson
Tissue morphogenesis is a fascinating aspect of both developmental biology and regeneration of certain adult organs, and timely control of cellular differentiation is a key to these processes. During development, events interrupting cellular differentiation and leading to organ failure are embryonic lethal; likewise, perturbation of differentiation in regenerating tissues leads to dysfunction and disease. At the molecular level, cellular differentiation is orchestrated by a well-coordinated cascade of transcription factors (TFs) and chromatin remodeling complexes that drive gene expression...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28186802/vulnerability-and-cosusceptibility-determine-the-size-of-network-cascades
#4
Yang Yang, Takashi Nishikawa, Adilson E Motter
In a network, a local disturbance can propagate and eventually cause a substantial part of the system to fail in cascade events that are easy to conceptualize but extraordinarily difficult to predict. Here, we develop a statistical framework that can predict cascade size distributions by incorporating two ingredients only: the vulnerability of individual components and the cosusceptibility of groups of components (i.e., their tendency to fail together). Using cascades in power grids as a representative example, we show that correlations between component failures define structured and often surprisingly large groups of cosusceptible components...
January 27, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28134712/diagnosis-and-monitoring-of-hiv-programmes-to-support-treatment-initiation-and-follow-up-and-improve-programme-quality
#5
Willem Daniel Francois Venter, Nathan Ford, Marco Vitoria, Wendy Stevens
PURPOSE OF REVIEW: The HIV 'cascade of care' breaks down at several points, with delayed HIV diagnosis, late treatment initiation, or interruption, leading to new morbidity and mortality and loss of prevention effects. New approaches are needed at each step. RECENT FINDINGS: HIV testing is still not reaching certain communities, resulting in late presentation. Creative ways to reach these communities is being explored, including with self-testing. HIV misdiagnosis is increasingly recognized as undermining testing programmes, highlighting the need for better quality control...
March 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28117074/light-chain-cardiac-amyloidosis
#6
REVIEW
Anit K Mankad, Isata Sesay, Keyur B Shah
Cardiac amyloidosis is an underrecognized condition, in which delays to diagnosis have great implications on management options, prognosis, and morbidity. Once cardiac tissue is infiltrated by amyloid fibrils, there is a cascade of pathologic changes that can display an array of clinical manifestations, from impaired relaxation of the ventricular myocardium to severe restrictive disease or even progressive systolic heart failure. Management is guided not only by recognizing the subtype of amyloidosis (primary, hereditary, and wild-type transthyretin amyloidosis), but also the clinical stage of the disease...
November 17, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28093977/the-amyloid-cascade-hypothesis-in-alzheimer-s-disease-it-s-time-to-change-our-mind
#7
Roberta Ricciarelli, Ernesto Fedele
Since its discovery in 1984, the beta amyloid peptide has treaded the boards of neurosciences as the star molecule in Alzheimer's disease pathogenesis. In the last decade, however, this vision has been challenged by evidence-based medicine showing the almost complete failure of clinical trials that experimented anti-amyloid therapies with great hopes. Moreover, data have accumulated which clearly indicates that this small peptide plays a key role in the physiological processes of memory formation. In the present review, we will discuss the different aspects of the amyloid cascade hypothesis, highlighting its pros and cons, and we will analyse the results of the therapeutic approaches attempted to date that should change the direction of Alzheimer's disease research in the future...
January 16, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28065846/the-association-of-heart-failure-related-micrornas-with-neurohormonal-signaling
#8
Yei-Tsung Chen, Juan Wang, Kai Sing Tong, Lee Lee Wong, Oi Wah Liew, Arthur Mark Richards
Heart failure (HF) is a widely prevalent syndrome imposing a significant burden of morbidity and mortality world-wide. Differential circulating microRNA profiles observed in HF cohorts suggest the diagnostic utility of microRNAs as biomarkers. Given their function in fine tuning gene expression, alternations in microRNA landscape could reflecting the underlying mechanisms of disease and present potential therapeutic targets. Using multiple computational target predicting algorithms together with the luciferase-based reporting platform, the interactions between HF-related microRNAs and the 3' untranslated regions (3'UTRs) of neurohormone associated genes were examined and compared...
January 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28060824/chronological-profiling-of-plasma-native-peptides-after-hepatectomy-in-pigs-toward-the-discovery-of-human-biomarkers-for-liver-regeneration
#9
Kohta Iguchi, Etsuro Hatano, Takashi Nirasawa, Noriyuki Iwasaki, Motohiko Sato, Gen Yamamoto, Kenya Yamanaka, Tatsuya Okamoto, Yosuke Kasai, Naohiko Nakamura, Hiroaki Fuji, Tomohito Sakai, Nobuto Kakuda, Satoru Seo, Kojiro Taura, Kei Tashiro, Shinji Uemoto, Masaya Ikegawa
Liver regeneration after partial hepatectomy (PHx) is a time-dependent process, which is tightly regulated by multiple signaling cascades. Failure of this complex process leads to posthepatectomy liver failure (PHLF), which is associated with a high rate of mortality. Thus, it is extremely important to establish a useful biomarker of liver regeneration to help prevent PHLF. Here, we hypothesized that alterations in the plasma peptide profile may predict liver regeneration following PHx and hence we set up a diagnostic platform for monitoring posthepatectomy outcome...
2017: PloS One
https://www.readbyqxmd.com/read/28052027/estrogen-receptor-%C3%AE-ligation-inhibits-hodgkin-lymphoma-growth-by-inducing-autophagy
#10
Marina Pierdominici, Angela Maselli, Silvia L Locatelli, Laura Ciarlo, Giuseppa Careddu, Mario Patrizio, Barbara Ascione, Antonella Tinari, Carmelo Carlo-Stella, Walter Malorni, Paola Matarrese, Elena Ortona
Although Hodgkin lymphoma (HL) is curable with current therapy, at least 20% of patients relapse or fail to make complete remission. In addition, patients who achieve long-term disease-free survival frequently undergo infertility, secondary malignancies, and cardiac failure, which are related to chemotherapeutic agents and radiation therapies. Hence, new therapeutic strategies able to counteract the HL disease in this important patient population are still a matter of study. Estrogens, in particular 17β-estradiol (E2), have been suggested to play a role in lymphoma cell homeostasis by estrogen receptors (ER) β activation...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28039575/the-high-cost-of-stroke-and-stroke-cytoprotection-research
#11
Paul A Lapchak, John H Zhang
Acute ischemic stroke is inadequately treated in the USA and worldwide due to a lengthy history of neuroprotective drug failures in clinical trials. The majority of victims must endure life-long disabilities that not only affect their livelihood, but also have an enormous societal economic impact. The rapid development of a neuroprotective or cytoprotective compound would allow future stroke victims to receive a treatment to reduce disabilities and further promote recovery of function. This opinion article reviews in detail the enormous costs associated with developing a small molecule to treat stroke, as well as providing a timely overview of the cell-death time-course and relationship to the ischemic cascade...
December 30, 2016: Translational Stroke Research
https://www.readbyqxmd.com/read/28035951/a-systematic-review-of-the-role-of-dysfunctional-wound-healing-in-the-pathogenesis-and-treatment-of-idiopathic-pulmonary-fibrosis
#12
REVIEW
Alan Betensley, Rabab Sharif, Dimitrios Karamichos
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disorder showcasing an interaction between genetic predisposition and environmental risks. This usually involves the coaction of a mixture of cell types associated with abnormal wound healing, leading to structural distortion and loss of gas exchange function. IPF bears fatal prognosis due to respiratory failure, revealing a median survival of approximately 2 to 3 years. This review showcases the ongoing progress in understanding the complex pathophysiology of IPF and it highlights the latest potential clinical treatments...
December 26, 2016: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28024102/elevated-ischaemia-associated-lysyl-oxidase-activity-in-delayed-graft-failure-6-12%C3%A2-months-after-renal-transplantation
#13
Zhi Chen, Yiyang Li, Hongmei Xu, Fuzhe Ma, Jia Li, Lei Zhao, Ying Xu
What is the central question of this study? What potential biochemical changes are associated with renal parenchyma 6-12 months after renal transplantation and delayed graft failure? What is the main finding and its importance? Tissue fibrosis, mediated by tissue ischaemia-induced induction of hypoxia-inducible factor-1α and fibronectin and consequent activation of lysyl oxidase, is a major underlying pathophysiological mechanism that contributes to delayed graft failure several months after renal transplantation...
February 1, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28019006/glucose-and-intermediary-metabolism-and-astrocyte-neuron-interactions-following-neonatal-hypoxia-ischemia-in-rat
#14
Eva Brekke, Hester Rijkje Berger, Marius Widerøe, Ursula Sonnewald, Tora Sund Morken
Neonatal hypoxia-ischemia (HI) and the delayed injury cascade that follows involve excitotoxicity, oxidative stress and mitochondrial failure. The susceptibility to excitotoxicity of the neonatal brain may be related to the capacity of astrocytes for glutamate uptake. Furthermore, the neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance for limiting this kind of injury. Also, in the neonatal brain, neurons depend upon de novo synthesis of neurotransmitters via pyruvate carboxylase in astrocytes to increase neurotransmitter pools during normal brain development...
December 26, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/28012459/down-regulated-long-non-coding-rna-atb-in-preeclampsia-and-its-effect-on-suppressing-migration-proliferation-and-tube-formation-of-trophoblast-cells
#15
Xijing Liu, Hongqin Chen, Weiqi Kong, Yanping Zhang, Liyuan Cao, Linbo Gao, Rong Zhou
Preeclampsia is a pregnancy-specific syndrome and is one of the main causes of maternal, fetal, and neonatal morbidity and mortality. Inadequate trophoblast invasion and failure of uterine spiral artery remodeling exert a major role in the development of preeclampsia, especially the early-onset one. LncRNA-ATB is verified to be aberrantly expressed in many cancers and promote the invasion-metastasis and proliferation cascades. But little is known of lncRNA-ATB's role in preeclampsia. The aim of current study is to identify the changes of lncRNA-ATB in preeclampsia and its effects on trophoblast...
January 2017: Placenta
https://www.readbyqxmd.com/read/28007541/calcineurin-signaling-in-the-heart-the-importance-of-time-and-place
#16
Valentina Parra, Beverly A Rothermel
The calcium-activated protein phosphatase, calcineurin, lies at the intersection of protein phosphorylation and calcium signaling cascades, where it provides an essential nodal point for coordination between these two fundamental modes of intracellular communication. In excitatory cells, such as neurons and cardiomyocytes, that experience rapid and frequent changes in cytoplasmic calcium, calcineurin protein levels are exceptionally high, suggesting that these cells require high levels of calcineurin activity...
December 20, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28001381/treatment-of-sepsis-pathogenesis-with-high-mobility-group-box-protein-1-regulating-anti-inflammatory-agents
#17
Wansang Cho, Ja Young Koo, Yeonju Park, Keunhee Oh, Sanghee Lee, Jin-Sook Song, Myung Ae Bae, Donghyun Lim, Dong-Sup Lee, Seung Bum Park
Sepsis is one of the major causes of death worldwide when associated with multiple organ failure. However, there is a critical lack of adequate sepsis therapies because of its diverse patterns of pathogenesis. The pro-inflammatory cytokine cascade mediates sepsis pathogenesis, and high mobility group box proteins (HMGBs) play an important role as late-stage cytokines. We previously reported the small-molecule modulator, inflachromene (1d), which inhibits the release of HMGBs and, thereby, reduces the production of pro-inflammatory cytokines...
December 21, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27979966/insulin-like-growth-factor-1-receptor-signaling-is-required-for-optimal-atr-chk1-kinase-signaling-in-ultraviolet-b-uvb-irradiated-human-keratinocytes
#18
Michael G Kemp, Dan F Spandau, Richard Simman, Jeffrey B Travers
UVB wavelengths of light induce the formation of photoproducts in DNA that are potentially mutagenic if not properly removed by the nucleotide excision repair machinery. As an additional mechanism to minimize the risk of mutagenesis, UVB-irradiated cells also activate a checkpoint signaling cascade mediated by the ATM and Rad3-related (ATR) and checkpoint kinase 1 (CHK1) kinases to transiently suppress DNA synthesis and cell cycle progression. Given that keratinocytes in geriatric skin display reduced activation of the insulin-like growth factor 1 receptor (IGF-1R) and alterations in DNA repair rate, apoptosis, and senescence following UVB exposure, here we used cultured human keratinocytes in vitro and skin explants ex vivo to examine how IGF-1R activation status affects ATR-CHK1 kinase signaling and the inhibition of DNA replication following UVB irradiation...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27967181/interdependent-lattice-networks-in-high-dimensions
#19
Steven Lowinger, Gabriel A Cwilich, Sergey V Buldyrev
We study the mutual percolation of two interdependent lattice networks ranging from two to seven dimensions, denoted as D. We impose that the length (measured as chemical distance) of interdependency links connecting nodes in the two lattices be less than or equal to a certain value, r. For each value of D and r, we find the mutual percolation threshold, p_{c}[D,r], below which the system completely collapses through a cascade of failures following an initial destruction of a fraction (1-p) of the nodes in one of the lattices...
November 2016: Physical Review. E
https://www.readbyqxmd.com/read/27941592/pathological-role-and-diagnostic-value-of-endogenous-host-defense-peptides-in-adult-and-neonatal-sepsis-a-systematic-review
#20
Jeffery Ho, Lin Zhang, Xiaodong Liu, Sunny H Wong, Maggie H T Wang, Benson W M Lau, Shirley P C Ngai, Hung Chan, Gordon Choi, Czarina C H Leung, Wai T Wong, Sharon Tsang, Tony Gin, Jun Yu, Matthew T V Chan, William K K Wu
BACKGROUND: Sepsis is a systemic host response to an infection leading to organ failure. This is associated with dynamic expression of endogenous host defense peptides. Dysregulation of these peptides is associated with septic morbidity and mortality. METHODS: We performed a systematic search of articles indexed in Pubmed, ISI Web of Knowledge, EmBase and Scopus database from inception to October 2016. Both preclinical and clinical studies investigating the role of host defense peptides in pathogenesis and as biomarkers for sepsis were included...
December 9, 2016: Shock
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