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Cascading failure

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https://www.readbyqxmd.com/read/29682085/prostaglandin-e-2-produced-by-alginate-encapsulated-mesenchymal-stromal-cells-modulates-the-astrocyte-inflammatory-response
#1
Elizabeth C Stucky, Joshua Erndt-Marino, Rene S Schloss, Martin L Yarmush, David I Shreiber
Astroglia are well known for their role in propagating secondary injury following brain trauma. Modulation of this injury cascade, including inflammation, is essential to repair and recovery. Mesenchymal stromal cells (MSCs) have been demonstrated as trophic mediators in several models of secondary CNS injury, however, there has been varied success with the use of direct implantation due to a failure to persist at the injury site. To achieve sustained therapeutic benefit, we have encapsulated MSCs in alginate microspheres and evaluated the ability of these encapsulated MSCs to attenuate neuro-inflammation...
June 2017: Nano LIFE
https://www.readbyqxmd.com/read/29673908/mechanism-underlying-the-contractile-activity-of-utp-in-the-mammalian-heart
#2
Ulrich Gergs, Daniel Rothkirch, Britt Hofmann, Hendrik Treede, Bernard Robaye, Andreas Simm, Christa E Müller, Joachim Neumann
We previously reported that uridine 5'-triphosphate (UTP), a pyrimidine nucleoside triphosphate produced a concentration- and time-dependent increase in the contraction force in isolated right atrial preparations from patients undergoing cardiac bypass surgery due to angina pectoris. The stimulation of the force of contraction was sustained rather than transient. In the present study, we tried to elucidate the underlying receptor and signal transduction for this effect of UTP. Therefore, we measured the effect of UTP on force of contraction, phosphorylation of p38 and ERK1/2, in human atrial preparations, atrial preparations from genetically modified mice, cardiomyocytes from adult mice and cardiomyocytes from neonatal rats...
April 16, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29670664/novel-model-for-cascading-failure-based-on-degree-strength-and-its-application-in-directed-gene-logic-networks
#3
Yulin Zhang, Maoxian Zhao, Jionglong Su, Xiao Lu, Kebo Lv
A novel model for cascading failures in a directed logic network based on the degree strength at a node was proposed. The definitions of in-degree and out-degree strength of a node were initially reconsidered, and the load at a nonisolated node was proposed as the ratio of in-degree strength to out-degree strength of the node. The cascading failure model based on degree strength was applied to the logic network for three types of cancer including adenocarcinoma of lung, prostate cancer, and colon cancer based on their gene expression profiles...
2018: Computational and Mathematical Methods in Medicine
https://www.readbyqxmd.com/read/29664034/incidence-prognosis-of-acute-kidney-injury-in-individuals-of-snakebite-in-a-tertiary-care-hospital-in-india
#4
Ramulu Pulimaddi, Amruth Rao Parveda, Balkishan Brahmanpally, Paul Marx Kalakanda, K Ramakrishna, Venkata Ramana Devi Chinnapaka
Background & objectives: The snakebites are considered to be an occupational hazard in agriculture workers and the snake handlers, resulting in a considerable morbidity, mortality and economical implications. This study was conducted to determine the incidence, clinical presentation, renal injury and clinical outcome in snakebite victims who developed acute kidney injury (AKI). Methods: This hospital-based prospective, observational study was done on 100 cases who were admitted for the management of snakebite and found to develop AKI in a tertiary care hospital at Hyderabad, India...
December 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/29660212/aiming-for-elimination-outcomes-of-a-consultation-pathway-supporting-regional-general-practitioners-to-prescribe-direct-acting-antiviral-therapy-for-hepatitis-c
#5
A J Wade, A McCormack, C Roder, K McDonald, M Davies, N Scott, M Wardrop, E Athan, M E Hellard
To increase access to treatment, the Australian government enabled general practitioners (GPs) to prescribe direct-acting antivirals (DAA) to treat hepatitis C virus (HCV) - in consultation with a specialist if inexperienced in HCV management. This study describes the establishment and outcomes of a remote consultation pathway supporting GPs to treat HCV. Key stakeholders from primary and tertiary healthcare services in the Barwon South Western region developed and implemented an HCV remote consultation pathway...
April 16, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29650801/the-role-of-jak2-inhibitors-in-mpn-seven-years-after-approval
#6
Francesco Passamonti, Margherita Maffioli
Myeloproliferative neoplasms (MPNs) include essential thrombocythemia, polycythemia vera (PV) and primary myelofibrosis (PMF). Phenotype-driver mutations of JAK2, CALR and MPL genes are present in MPNs and can be variably combined with additional mutations. Driver mutations entail a constitutive activation of the JAK2/STAT pathway, the key signaling cascade in MPNs. Among JAK2 inhibitors (JAKis), ruxolitinib (RUX) has been approved for the treatment of intermediate and high risk myelofibrosis (MF) and of PV inadequately controlled by or intolerant of hydroxyurea...
April 12, 2018: Blood
https://www.readbyqxmd.com/read/29625388/crocin-reverses-unilateral-renal-ischemia-reperfusion-injury-induced-augmentation-of-oxidative-stress-and-toll-like-receptor-4-activity
#7
Hadeer O Abou-Hany, Hoda Atef, Eman Said, Hassan A Elkashef, Hatem A Salem
Renal Ischemia (RI) usually develops as a secondary manifestation of hypertension, various cardiovascular disorders and renal transplantation. It exerts hypoxic oxidative stress to kidneys, together with stimulation of several immune-mediated inflammatory cascades. Such events eventually damage renal tubules and glomeruli, driving acute kidney injury (AKI) and ultimately, renal failure. Crocin; the main bioactive constituent of Crocus sativus extract has been reported to demonstrate numerous pharmacological merits...
March 27, 2018: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29623038/recent-advances-decoding-alzheimer-s-disease-with-stem-cells
#8
REVIEW
Yi Fang, Ting Gao, Baorong Zhang, Jiali Pu
Alzheimer's disease (AD) is an irreversible neurodegenerative disorder that destroys cognitive functions. Recently, a number of high-profile clinical trials based on the amyloid cascade hypothesis have encountered disappointing results. The failure of these trials indicates the necessity for novel therapeutic strategies and disease models. In this review, we will describe how recent advances in stem cell technology have shed light on a novel treatment strategy and revolutionized the mechanistic investigation of AD pathogenesis...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29618707/donor-polymorphisms-in-genes-related-to-b-cell-biology-associated-with-antibody-mediated-rejection-after-heart-transplantation
#9
Grecia M Marrón-Liñares, Lucía Núñez, María G Crespo-Leiro, Eloy Álvarez-López, Eduardo Barge-Caballero, Gonzalo Barge-Caballero, David Couto-Mallón, Concepción Pradas-Irun, Javier Muñiz, Carmela Tan, E Rene Rodríguez, José Manuel Vázquez-Rodríguez, Manuel Hermida-Prieto
BACKGROUND: Heart transplantation (HT) is a well-established lifesaving treatment for endstage cardiac failure. Antibody-mediated rejection (AMR) represents one of the main problems after HT because of its diagnostic complexity and the poor evidence for supporting treatments. Complement cascade and B-cells play a key role in AMR and contribute to graft damage. This study explored the importance of variants in genes related to complement pathway and B-cell biology in HT and AMR in donors and in donor-recipient pairs...
April 3, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/29616025/differences-between-pediatric-and-adult-t-cell-responses-to-in-vitro-staphylococcal-enterotoxin-b-stimulation
#10
Mark E Rudolph, Monica A McArthur, Robin S Barnes, Laurence S Magder, Wilbur H Chen, Marcelo B Sztein
Toxic shock syndrome (TSS) is capable of inducing life-threatening fever, rash, and systemic organ failure, though the specific mechanisms behind these symptoms remain poorly understood. Staphylococcal enterotoxin B (SEB) and other superantigens have shown to be important factors in TSS, capable of promoting cross-linking between T cell receptors and major histocompatibility complexes which results in overwhelming T cell activation, proliferation, and cytokine production. The resulting proinflammatory cytokine cascade, often referred to as the "cytokine storm," seems to be critical to the development of disease...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29608550/amitriptyline-treatment-mitigates-sepsis-induced-tumor-necrosis-factor-expression-and-coagulopathy
#11
Brent T Xia, Nadine Beckmann, Leah K Winer, Young Kim, Holly S Goetzman, Rosalie E Veile, Erich Gulbins, Michael D Goodman, Vanessa Nomellini, Charles C Caldwell
During sepsis, the early innate response and inflammatory cytokine cascade are associated with activation of the coagulation cascade. Acute hypercoagulability can contribute to lethal sequela of vascular thrombosis, tissue ischemia, and organ failure. We investigated if amitriptyline (AMIT), an antidepressant drug with a number of anti-inflammatory effects, could ameliorate sepsis in a murine model of sepsis - cecal ligation and puncture (CLP). We hypothesized that AMIT treatment would reduce inflammation and mitigate sepsis-induced coagulopathy...
March 30, 2018: Shock
https://www.readbyqxmd.com/read/29604206/from-molecules-to-patients-exploring-the-therapeutic-role-of-soluble-guanylate-cyclase-stimulators
#12
Peter Sandner
Nitric Oxide (NO) signaling represents one of the major regulatory pathways for cardiovascular function. After the discovery of NO, awarded with the Nobel Prize in 1998, this signaling cascade was stepwise clarified. We now have a good understanding of NO production and NO downstream targets such as the soluble guanylyl cyclases (sGCs) which catalyze cGMP production. Based on the important role of NO-signaling in the cardiovascular system, intense research and development efforts are currently ongoing to fully exploit the therapeutic potential of cGMP increase...
March 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29593014/ryanodine-receptor-calcium-leak-in-circulating-b-lymphocytes-as-a-biomarker-in-heart-failure
#13
Alexander Kushnir, Gaetano Santulli, Steven R Reiken, Ellie Coromilas, Sarah J Godfrey, Danielle L Brunjes, Paolo C Colombo, Melana Yuzefpolskaya, Seth I Sokol, Richard N Kitsis, Andrew R Marks
Background -Advances in congestive heart failure (CHF) management depend on biomarkers for monitoring disease progression and therapeutic response. During systole, intracellular Ca2+ is released from the sarcoplasmic reticulum (SR) into the cytoplasm through type 2 ryanodine receptor/Ca2+ release channels (RyR2). In CHF, chronically elevated circulating catecholamine levels cause pathologic remodeling of RyR2 resulting in diastolic SR Ca2+ leak, and decreased myocardial contractility. Similarly, skeletal muscle contraction requires SR Ca2+ release through type-1 ryanodine receptors (RyR1), and chronically elevated catecholamine levels in CHF cause RyR1 mediated SR Ca2+ leak, contributing to myopathy and weakness...
March 28, 2018: Circulation
https://www.readbyqxmd.com/read/29587004/developing-a-phosphospecific-ihc-assay-as-a-predictive-biomarker-for-topoisomerase-i-inhibitors
#14
Koji Ando, Yara Hamade Tohme, Adithi Srinivasiah, Julian Taylor-Parker, Yevgeniya Harrington, Ankur K Shah, Eiji Oki, Mohan Brahmandam, Ajit K Bharti
Phosphorylation is the most extensively studied posttranslational modification of proteins. There are approximately 500 kinases known in the human genome. The kinase-activated pathways regulate almost every aspect of cell function and a deregulated kinase cascade leads to impaired cellular function. Impaired regulation of several kinase cascades, including the epidermal growth factor receptor (EGFR) pathway, leading to tumor pathogenesis, is well documented. Thus, a phosphospecific test with prognostic or predictive value was expected in oncology...
March 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29582498/requirement-of-leptinotarsa-decemlineata-gene-within-the-74ef-puff-for-larval-pupal-metamorphosis-and-appendage-growth
#15
Q-Y Xu, Q-W Meng, P Deng, K-Y Fu, W-C Guo, G-Q Li
Two Drosophila melanogaster E-twenty-six domain transcription factor isoforms (E74A and E74B) act differentially at the start of the 20-hydroxyecdysone (20E) signalling cascade to regulate larval-pupal metamorphosis. In the present paper, we identified the two isoforms (LdE74A and LdE74B) in Leptinotarsa decemlineata. During the larval development stage, the mRNA transcript levels of the two LdE74 isoforms were correlated with circulating 20E titres. In vitro midgut culture and in vivo dietary supplementation with 20E revealed that the presence of 20E induced expression peaks of both LdE74A and LdE74B, with similar patterns observed for the two isoforms...
March 26, 2018: Insect Molecular Biology
https://www.readbyqxmd.com/read/29570632/micro-economics-of-apoptosis-in-cancer-ncrnas-modulation-of-bcl-2-family-members
#16
REVIEW
Lidia Villanova, Silvia Careccia, Ruggero De Maria, Micol E Fiori
In the last few years, non-coding RNAs (ncRNAs) have been a hot topic in cancer research. Many ncRNAs were found to regulate the apoptotic process and to play a role in tumor cell resistance to treatment. The apoptotic program is on the frontline as self-defense from cancer onset, and evasion of apoptosis has been classified as one of the hallmarks of cancer responsible for therapy failure. The B-cell lymphoma 2 (BCL-2) family members are key players in the regulation of apoptosis and mediate the activation of the mitochondrial death machinery in response to radiation, chemotherapeutic agents and many targeted therapeutics...
March 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29569259/varicocele-is-the-root-cause-of-bph-destruction-of-the-valves-in-the-spermatic-veins-produces-elevated-pressure-which-diverts-undiluted-testosterone-directly-from-the-testes-to-the-prostate
#17
M Goren, Y Gat
In varicocele, there is venous flow of free testosterone (FT) directly from the testes into the prostate. Intraprostatic FT accelerates prostate cell production and prolongs cell lifespan, leading to the development of BPH. We show that in a large group of patients presenting with BPH, bilateral varicocele is found in all patients. A total of 901 patients being treated for BPH were evaluated for varicocele. Three diagnostic methods were used as follows: physical examination, colour flow Doppler ultrasound and contact liquid crystal thermography...
March 22, 2018: Andrologia
https://www.readbyqxmd.com/read/29566413/rivaroxaban-a-new-treatment-paradigm-in-the-setting-of-vascular-protection
#18
Rupert Bauersachs, Faiez Zannad
The pathophysiology of atherosclerosis involves a diseased endothelium, lipid accumulation and low-grade inflammation. In later stages of coronary artery disease (CAD) and peripheral arterial disease (PAD), plaque rupture may induce atherothrombosis caused by fibrin formation and platelet activation, leading to vessel occlusion with subsequent organ damage such as myocardial infarction, stroke or limb ischaemia. Because of the high disease burden associated with CAD and PAD, there is a need for continuous vascular protection beyond currently available treatments including antiplatelet agents...
March 22, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29562523/multifactorial-hypothesis-and-multi-targets-for-alzheimer-s-disease
#19
Cheng-Xin Gong, Fei Liu, Khalid Iqbal
The amyloid cascade hypothesis has been dominating drug discovery for Alzheimer's disease (AD) for the last two decades. The failure of the development of effective drugs for slowing down or reversing the progression of AD warrants the AD field to consider out-of-the-box thinking and therapeutic approaches. We propose the multifactorial hypothesis of AD, emphasizing that AD is caused by multiple etiological factors, which may result in common brain pathology and functional consequences through several separate but integrated molecular pathways...
March 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29562513/brain-aging-and-late-onset-alzheimer-s-disease-a-matter-of-increased-amyloid-or-reduced-energy
#20
Patrizia Mecocci, Marta Baroni, Umberto Senin, Virginia Boccardi
Alzheimer's disease (AD) represents the most common form of dementia in old age subjects, and despite decades of studies, the underlying etiopathogenetic mechanisms remain unsolved. The definition of AD has changed over the past years, offering an ever more detailed definition of pre-morbid and pre-clinical status, but without a similar strong emphasis on the role of aging as the main risk factor. In fact, while early-onset AD is a clear consequence of gene mutations, late-onset AD is more likely due to a gradual accumulation of age-related damages...
March 16, 2018: Journal of Alzheimer's Disease: JAD
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