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https://www.readbyqxmd.com/read/29457878/genetic-determinants-of-heart-failure-facts-and-numbers
#1
EDITORIAL
Frauke S Czepluch, Bernd Wollnik, Gerd Hasenfuß
The relevance of gene mutations leading to heart diseases and hence heart failure has become evident. The risk for and the course of heart failure depends on genomic variants and mutations underlying the so-called genetic predisposition. Genetic contribution to heart failure is highly heterogenous and complex. For any patient with a likely inherited heart failure syndrome, genetic counselling is recommended and important. In the last few years, novel sequencing technologies (named next-generation sequencing - NGS) have dramatically improved the availability of molecular testing, the efficiency of genetic analyses, and moreover reduced the cost for genetic testing...
February 19, 2018: ESC Heart Failure
https://www.readbyqxmd.com/read/29454747/plasminogen-activator-inhibitor-1-reduces-tpa-dependent-fibrinolysis-and-intrahepatic-hemorrhage-in-experimental-acetaminophen-overdose
#2
Asmita Pant, Anna K Kopeć, Kevin S Baker, Holly Cline-Fedewa, Daniel A Lawrence, James P Luyendyk
Acetaminophen (APAP)-induced liver injury in mice is associated with activation of the coagulation cascade and deposition of fibrin in liver. Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of tissue-type plasminogen activator (tPA) and plays a critical role in fibrinolysis. PAI-1 expression is increased in both experimental APAP-induced liver injury and patients with acute liver failure. Prior studies have shown that PAI-1 prevents intrahepatic hemorrhage and mortality after APAP challenge, but the downstream mechanisms are not clear...
February 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29452395/mini-extracorporeal-circulation-technology-conventional-bypass-and-prime-displacement-in-isolated-coronary-and-aortic-valve-surgery-a-propensity-matched-in-hospital-and-survival-analysis
#3
Priyadharshanan Ariyaratnam, Lindsay A Mclean, Alexander Cale, Mubarak A Chaudhry, Ajith Vijayan, Neil Richards, Martin A Jarvis, Yama Haqzad, Dumbor Ngaage, Michael E Cowen, Mahmoud Loubani
OBJECTIVES: Conventional cardiopulmonary bypass is the most commonly used means of artificial circulation in cardiac surgery. However, it suffers from the effects of haemodilution and activation of inflammatory/coagulation cascades. Prime displacement (PD) can offset haemodilution and Mini-Extracorporeal Technology (MIECT) can offset both. So far, no study has compared all of these modalities together; hence, we compared the outcomes of these 3 modalities at our institution. METHODS: This was a retrospective analysis of our cardiac surgical database...
February 14, 2018: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/29447430/aucubin-protects-against-pressure-overload-induced-cardiac-remodelling-via-%C3%AE-3-ar-nnos-cascades
#4
Qing-Qing Wu, Yang- Xiao, Ming-Xia Duan, Yuan Yuan, Xiao-Han Jiang, Zheng Yang, Hai-Han Liao, Wei Deng, Qi-Zhu Tang
BACKGROUND AND PURPOSE: Aucubin, the predominant component of Eucommia ulmoides Oliv., plays an indispensable role in regulating oxidative stress. Considering that oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of aucubin on cardiac remodelling and heart failure. EXPERIMENTAL APPROACH: In the first set of experiments, H9c2 cardiomyocytes and neonatal rat cardiomyocytes pre-treated with aucubin (1, 3 10, 25, 50 μM) were challenged with phenylephrine...
February 15, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29443814/danger-signals-in-the-icu
#5
Edward J Schenck, Kevin C Ma, Santosh B Murthy, Augustine M K Choi
OBJECTIVES: Sterile and infectious critical illnesses often result in vasoplegic shock and a robust systemic inflammatory response that are similar in presentation. The innate immune system is at the center of the response to both infectious and traumatic insults. Damage-associated molecular patterns are small molecules that are released from stressed or dying cells. Damage-associated molecular patterns activate pattern recognition receptors and coordinate the leading edge of the innate immune response...
February 13, 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29442469/brain-death-associated-pathological-events-and-therapeutic-options
#6
REVIEW
Paweł Chudoba, Wojciech Krajewski, Joanna Wojciechowska, Dorota Kamińska
BACKGROUND: At present, organ transplantation is the most efficient treatment of end-stage failure of various organs, including the heart, lungs, pancreas, intestines, kidney, and liver. Despite the efforts to use organs from living donors or from donors after circulatory death, most of the organs are recovered from brain dead (BD) donors. METHODS: The Medline and Web of Science databases were searched without time limit on November 2015 using the terms "brain dead donor" and "deceased donor" in conjunction with "transplantation", "graft", "organ", "hemodynamic", "hormonal", or "management"...
December 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29438426/optimization-of-robustness-of-interdependent-network-controllability-by-redundant-design
#7
Zenghu Zhang, Yongfeng Yin, Xin Zhang, Lijun Liu
Controllability of complex networks has been a hot topic in recent years. Real networks regarded as interdependent networks are always coupled together by multiple networks. The cascading process of interdependent networks including interdependent failure and overload failure will destroy the robustness of controllability for the whole network. Therefore, the optimization of the robustness of interdependent network controllability is of great importance in the research area of complex networks. In this paper, based on the model of interdependent networks constructed first, we determine the cascading process under different proportions of node attacks...
2018: PloS One
https://www.readbyqxmd.com/read/29421549/unique-electrophysiological-and-impedance-signatures-between-encapsulation-types-an-analysis-of-biological-utah-array-failure-and-benefit-of-a-biomimetic-coating-in-a-rat-model
#8
Patrick A Cody, James R Eles, Carl F Lagenaur, Takashi D Y Kozai, X Tracy Cui
Intracortical microelectrode arrays, especially the Utah array, remain the most common choice for obtaining high dimensional recordings of spiking neural activity for brain computer interface and basic neuroscience research. Despite the widespread use and established design, mechanical, material and biological challenges persist that contribute to a steady decline in recording performance (as evidenced by both diminished signal amplitude and recorded cell population over time) or outright array failure. Device implantation injury causes acute cell death and activation of inflammatory microglia and astrocytes that leads to a chronic neurodegeneration and inflammatory glial aggregation around the electrode shanks and often times fibrous tissue growth above the pia along the bed of the array within the meninges...
January 31, 2018: Biomaterials
https://www.readbyqxmd.com/read/29417313/sweetening-inhaled-antibiotic-treatment-for-eradication-of-chronic-respiratory-biofilm-infection
#9
Ching-Yee Loo, Wing-Hin Lee, Gianluca Lauretani, Santo Scalia, David Cipolla, Daniela Traini, Paul Young, Hui Xin Ong
PURPOSE: The failure of chronic therapy with antibiotics to clear persistent respiratory infection is the key morbidity and mortality factor for patients with chronic lung diseases, primarily due to the presence of biofilm in the lungs. It is hypothesised that carbon sources, such as mannitol, could stimulate the metabolic activity of persister cells within biofilms and restore their susceptibility to antibiotics. The aims of the current study are to: (1) establish a representative in vitro model of Pseudomonas aeruginosa biofilm lung infection, and (2) investigate the effects of nebulised mannitol on antibiotic efficacy, focusing on ciprofloxacin, in the eradication of biofilm...
February 7, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29410429/transcriptome-of-porcine-pbmcs-over-two-generations-reveals-key-genes-and-pathways-associated-with-variable-antibody-responses-post-prrsv-vaccination
#10
Ting Yang, Fengxia Zhang, Liwei Zhai, Weiyong He, Zhen Tan, Yangyang Sun, Yuan Wang, Lei Liu, Chao Ning, Weiliang Zhou, Hong Ao, Chuduan Wang, Ying Yu
Porcine reproductive and respiratory syndrome virus (PRRSV) is a virus susceptible to antibody dependent enhancement, causing reproductive failures in sows and preweaning mortality of piglets. Modified-live virus (MLV) vaccines are used to control PRRS in swine herds. However, immunized sows and piglets often generate variable antibody levels. This study aimed to detect significant genes and pathways involved in antibody responsiveness of pregnant sows and their offspring post-PRRSV vaccination. RNA sequencing was conducted on peripheral blood-mononuclear cells (PBMCs), which were isolated from pregnant sows and their piglets with high (HA), median (MA), and low (LA) PRRS antibody levels following vaccination...
February 6, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29408195/hydrogen-sulfide-regulates-cardiac-mitochondrial-biogenesis-via-the-activation-of-ampk
#11
Yuuki Shimizu, Rohini Polavarapu, Kattri-Liis Eskla, Chad K Nicholson, Christopher A Koczor, Rui Wang, William Lewis, Sruti Shiva, David J Lefer, John W Calvert
BACKGROUND: Hydrogen sulfide (H2S) is an important regulator of mitochondrial bioenergetics, but its role in regulating mitochondrial biogenesis is not well understood. Using both genetic and pharmacological approaches, we sought to determine if H2S levels directly influenced cardiac mitochondrial content. RESULTS: Mice deficient in the H2S-producing enzyme, cystathionine γ-lyase (CSE KO) displayed diminished cardiac mitochondrial content when compared to wild-type hearts...
January 29, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29398292/nephrogenic-acute-respiratory-distress-syndrome-a-narrative-review-on%C3%A2-pathophysiology-and-treatment
#12
REVIEW
Maryam Malek, Jalal Hassanshahi, Reza Fartootzadeh, Fatemeh Azizi, Somayeh Shahidani
The kidneys have a close functional relationship with other organs especially the lungs. This connection makes the kidney and the lungs as the most organs involved in the multi-organ failure syndrome. The combination of acute lung injury (ALI) and renal failure results a great clinical significance of 80% mortality rate. Acute kidney injury (AKI) leads to an increase in circulating cytokines, chemokines, activated innate immune cells and diffuse of these agents to other organs such as the lungs. These factors initiate pathological cascade that ultimately leads to ALI and acute respiratory distress syndrome (ARDS)...
November 24, 2017: Chinese Journal of Traumatology, Zhonghua Chuang Shang za Zhi
https://www.readbyqxmd.com/read/29394499/anti-inflammatory-therapies-in-myocardial-infarction-failures-hopes-and-challenges
#13
REVIEW
Shuaibo Huang, Nikolaos G Frangogiannis
In the infarcted heart, damage-associated molecular patterns released by necrotic cells trigger both myocardial and systemic inflammatory responses. Induction of chemokines and cytokines and upregulation of endothelial adhesion molecules mediate leukocyte recruitment in the infarcted myocardium. Inflammatory cells clear the infarct from dead cells and matrix debris and activate reparative myofibroblasts and vascular cells, but may also contribute to adverse fibrotic remodeling of viable segments, accentuate cardiomyocyte apoptosis and exert arrhythmogenic actions...
February 2, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29394497/the-current-state-of-gpcr-based-drug-discovery-to-treat-metabolic-disease
#14
REVIEW
Kyle W Sloop, Paul J Emmerson, Michael A Statnick, Francis S Willard
One approach of modern drug discovery is to identify agents that enhance or diminish signal transduction cascades in various cell types and tissues by modulating the activity of G-protein coupled receptors (GPCRs). This strategy has resulted in the development of new medicines to treat many conditions, including cardiovascular disease, psychiatric disorders, HIV/AIDS, certain forms of cancer, and type 2 diabetes mellitus (T2DM). These successes justify further pursuit of GPCRs as disease targets and provide key learning that should help guide identifying future therapeutic agents...
February 2, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29391411/the-weak-interdependence-of-infrastructure-systems-produces-mixed-percolation-transitions-in-multilayer-networks
#15
Run-Ran Liu, Daniel A Eisenberg, Thomas P Seager, Ying-Cheng Lai
Previous studies of multilayer network robustness model cascading failures via a node-to-node percolation process that assumes "strong" interdependence across layers-once a node in any layer fails, its neighbors in other layers fail immediately and completely with all links removed. This assumption is not true of real interdependent infrastructures that have emergency procedures to buffer against cascades. In this work, we consider a node-to-link failure propagation mechanism and establish "weak" interdependence across layers via a tolerance parameter α which quantifies the likelihood that a node survives when one of its interdependent neighbors fails...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29391166/a-speculative-outlook-on-embryonic-aneuploidy-can-molecular-pathways-be-involved
#16
REVIEW
Olga Tšuiko, Tatjana Jatsenko, Lalit Kumar Parameswaran Grace, Ants Kurg, Joris Robert Vermeesch, Fredrik Lanner, Signe Altmäe, Andres Salumets
The journey of embryonic development starts at oocyte fertilization, which triggers a complex cascade of events and cellular pathways that guide early embryogenesis. Recent technological advances have greatly expanded our knowledge of cleavage-stage embryo development, which is characterized by an increased rate of whole-chromosome losses and gains, mixoploidy, and atypical cleavage morphokinetics. Embryonic aneuploidy significantly contributes to implantation failure, spontaneous miscarriage, stillbirth or congenital birth defects in both natural and assisted human reproduction...
January 31, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29386434/-from-a-ph-d-thesis-understanding-the-past-predicting-the-future
#17
Kenichi Watanabe
 Posey et al. have reported multiple molecular diagnoses in 4.5% of cases (101/2076) in which whole-exome sequencing was informative. Distinct disease phenotypes affect different organ systems, whereas overlapping disease phenotypes are more likely to be caused by two genes encoding proteins that interact within the same pathway. My research projects at the Niigata University of Pharmacy have investigated underlying mechanisms involved in human disease, including fatty acid metabolism, diabetic cardiomyopathy, atopic dermatitis, colitis, hepatitis, etc...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29384847/identification-of-key-candidate-genes-and-pathways-in-hepatitis-b-virus-associated-acute-liver-failure-by-bioinformatical-analysis
#18
Huapeng Lin, Qian Zhang, Xiaocheng Li, Yushen Wu, Ye Liu, Yingchun Hu
Hepatitis B virus-associated acute liver failure (HBV-ALF) is a rare but life-threatening syndrome that carried a high morbidity and mortality. Our study aimed to explore the possible molecular mechanisms of HBV-ALF by means of bioinformatics analysis. In this study, genes expression microarray datasets of HBV-ALF from Gene Expression Omnibus were collected, and then we identified differentially expressed genes (DEGs) by the limma package in R. After functional enrichment analysis, we constructed the protein-protein interaction (PPI) network by the Search Tool for the Retrieval of Interacting Genes online database and weighted genes coexpression network by the WGCNA package in R...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29382104/action-of-phytochemicals-on-insulin-signaling-pathways-accelerating-glucose-transporter-glut4-protein-translocation
#19
REVIEW
Abu Sadat Md Sayem, Aditya Arya, Hamed Karimian, Narendiran Krishnasamy, Ameya Ashok Hasamnis, Chowdhury Faiz Hossain
Diabetes is associated with obesity, generally accompanied by a chronic state of oxidative stress and redox imbalances which are implicated in the progression of micro- and macro-complications like heart disease, stroke, dementia, cancer, kidney failure and blindness. All these complications rise primarily due to consistent high blood glucose levels. Insulin and glucagon help to maintain the homeostasis of glucose and lipids through signaling cascades. Pancreatic hormones stimulate translocation of the glucose transporter isoform 4 (GLUT4) from an intracellular location to the cell surface and facilitate the rapid insulin-dependent storage of glucose in muscle and fat cells...
January 28, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29359469/p-and-e-selectin-receptor-antagonism-prevents-human-leukocyte-adhesion-to-activated-porcine-endothelial-monolayers-and-attenuates-porcine-endothelial-damage
#20
Christopher T Laird, Wessam Hassanein, Natalie A O'Neill, Beth M French, Xiangfei Cheng, William E Fogler, John L Magnani, Dawn Parsell, Arielle Cimeno, Carol J Phelps, David Ayares, Lars Burdorf, Agnes M Azimzadeh, Richard N Pierson
BACKGROUND: Alongside the need to develop more effective and less toxic immunosuppression, the shortage of human organs available for organ transplantation is one of the major hurdles facing the field. Research into xenotransplantation, as an alternative source of organs, has unveiled formidable challenges. Porcine lungs perfused with human blood rapidly sequester the majority of circulating neutrophils and platelets, which leads to inflammation and organ failure within hours, and is not significantly attenuated by genetic modifications to the pig targeted to diminish antibody binding and complement and coagulation cascade activation...
January 23, 2018: Xenotransplantation
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