Mitigating Downstream Effects of Dams

2012 ◽  
pp. 182-189 ◽  
Author(s):  
David Gaeuman
Keyword(s):  
Downstream Effects

Молекулярная биология менингиом головного мозга

2017 ◽  
pp. 82-91
Author(s):  
В.А. Бывальцев ◽  
И.А. Степанов ◽  
Е.Г. Белых ◽  
А.И. Яруллина
Keyword(s):  
Gene Therapy ◽  
Proton Therapy ◽  
Genetic Factors ◽  
Intracranial Tumor ◽  
Molecular Profile ◽  
Genetic Changes ◽  
Treatment Techniques ◽  
Downstream Effects ◽  
Si Rna ◽  
The Relationship

Цель обзора - анализ современных данных литературы о нарушении внутриклеточных сигнальных путей, играющих ведущую роль в развитии менингиом, генетических и молекулярных профилях данной группы опухолей. К настоящему времени изучено множество аберрантных сигнальных внутриклеточных путей, которые играют важнейшую роль в развитии менингиом головного мозга. Четкое понимание поврежденных внутриклеточных каскадов поможет изучить влияние генетических мутаций и их эффектов на менингиомогенез. Подробное исследование генетического и молекулярного профиля менингиом позволит сделать первый уверенный шаг в разработке более эффективных методов лечения данной группы интракраниальных опухолей. Хромосомы 1, 10, 14, 22 и связанные с ними генные мутации ответственны за рост и прогрессию менингиом. Предполагается, что только через понимание данных генетических повреждений будут реализованы новейшие эффективные методы лечения. Будущая терапия будет включать в себя комбинации таргетных молекулярных агентов, в том числе генную терапию, малые интерферирующие РНК, протонную терапию и другие методы воздействия, как результат дальнейшего изучения генетических и биологических изменений, характерных для менингеальных опухолей. Meningiomas are by far the most common tumors arising from the meninges. A myriad of aberrant signaling pathways involved with meningioma tumorigenesis, have been discovered. Understanding these disrupted pathways will aid in deciphering the relationship between various genetic changes and their downstream effects on meningioma pathogenesis. An understanding of the genetic and molecular profile of meningioma would provide a valuable first step towards developing more effective treatments for this intracranial tumor. Chromosomes 1, 10, 14, 22, their associated genes, have been linked to meningioma proliferation and progression. It is presumed that through an understanding of these genetic factors, more educated meningioma treatment techniques can be implemented. Future therapies will include combinations of targeted molecular agents including gene therapy, si-RNA mediation, proton therapy, and other approaches as a result of continued progress in the understanding of genetic and biological changes associated with meningiomas.

Virome and Inflammasomes, a Finely Tuned Balance with Important Consequences for the Host Health

2019 ◽  
Vol 26 (6) ◽  
pp. 1027-1044 ◽  
Author(s):  
Giulia Freer ◽  
Fabrizio Maggi ◽  
Mauro Pistello
Keyword(s):  
Immune System ◽  
Human Beings ◽  
Review Of The Literature ◽  
Adaptive Immune ◽  
Downstream Effects ◽  
Host Health ◽  
Inflammatory Processes ◽  
Human Immune ◽  
Immune Defences

Background:The virome is a network of viruses normally inhabiting humans. It forms a conspicuous portion of the so-called microbiome, once generically referred to as resident flora. Indeed, viruses infecting humans without leading to clinical disease are increasingly recognized as part of the microbiome and have an impact on the development of our immune system. In addition, they activate inflammasomes, multiprotein complexes that assemble in cells and that are responsible for the downstream effects of sensing pathogens.Objective:This review aims at summarizing the evidence on the role of the virome in modulating inflammation and emphasizes evidence for Anelloviruses as useful molecular markers to monitor inflammatory processes and immune system competence.Method:We carried out a review of the literature published in the last 5 years and summarized older literature to take into account ground-breaking discoveries concerning inflammasome assembly and virome.Results:A massive amount of data recently emerging demonstrate that the microbiome closely reflects what we eat, and many other unexpected variables. Composition, location, and amount of the microbiome have an impact on innate and adaptive immune defences. Viruses making up the virome contribute to shaping the immune system. Anelloviruses, the best known of such viruses, are present in most human beings, persistently without causing apparent disease. Depending on their interplay with such viruses, inflammasomes instruct host defences to tolerate or forfeit a specific microorganism.Conclusion:The virome plays an important role in shaping human immune defences and contributes to inflammatory processes by quenching or increasing them.

scholarly journals Multi-omic regulatory networks capture downstream effects of kinase inhibition in Mycobacterium tuberculosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Albert T. Young ◽  
Xavier Carette ◽  
Michaela Helmel ◽  
Hanno Steen ◽  
Robert N. Husson ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mycobacterium Tuberculosis ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Protein Interaction Data ◽  
Kinase Inhibition ◽  
Protein Protein Interaction ◽  
Downstream Effects ◽  
Regulate Cell Growth ◽  
Regulatory Effects

AbstractThe ability of Mycobacterium tuberculosis (Mtb) to adapt to diverse stresses in its host environment is crucial for pathogenesis. Two essential Mtb serine/threonine protein kinases, PknA and PknB, regulate cell growth in response to environmental stimuli, but little is known about their downstream effects. By combining RNA-Seq data, following treatment with either an inhibitor of both PknA and PknB or an inactive control, with publicly available ChIP-Seq and protein–protein interaction data for transcription factors, we show that the Mtb transcription factor (TF) regulatory network propagates the effects of kinase inhibition and leads to widespread changes in regulatory programs involved in cell wall integrity, stress response, and energy production, among others. We also observe that changes in TF regulatory activity correlate with kinase-specific phosphorylation of those TFs. In addition to characterizing the downstream regulatory effects of PknA/PknB inhibition, this demonstrates the need for regulatory network approaches that can incorporate signal-driven transcription factor modifications.

Acute Strokelike Presentation and Long-term Evolution of Diffusion Restriction Pattern in Ethylmalonic Encephalopathy

2021 ◽  
pp. 088307382110065
Author(s):  
Jaehyung Lim ◽  
Brian J. Shayota ◽  
Erica Lay ◽  
Sarah H. Elsea ◽  
Mir Reza Bekheirnia ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Mitochondrial Disorder ◽  
Brain Magnetic Resonance Imaging ◽  
Restriction Pattern ◽  
Spastic Diplegia ◽  
Ethylmalonic Encephalopathy ◽  
Developmental Regression ◽  
Downstream Effects ◽  
Cystic Changes

Ethylmalonic encephalopathy is a rare autosomal recessive mitochondrial disorder caused by pathogenic biallelic variants in the ETHE1 gene. The phenotype of this disease has been attributed to deficiency in the mitochondrial sulfur dioxygenase leading to many downstream effects. Ethylmalonic encephalopathy classically presents with developmental regression, petechiae, acrocyanosis, and chronic diarrhea. The neurologic phenotype includes hypotonia, spastic diplegia, ataxia, and developmental delay. As more patients with this condition are described, the neurologic phenotype continues to expand. Although strokelike episodes or metabolic strokes have been studied in other mitochondrial disorders, they have not been thoroughly reported in this disorder. Herein, we describe 3 patients with ethylmalonic encephalopathy who presented clinically with strokelike episodes and strokelike abnormalities on brain magnetic resonance imaging in the setting of acute illness, and the long-term sequelae with evolution into cystic changes in one of these subjects.

scholarly journals Ketamine’s effect on inflammation and kynurenine pathway in depression: A systematic review

2021 ◽  
pp. 026988112110264
Author(s):  
Emma Kopra ◽  
Valeria Mondelli ◽  
Carmine Pariante ◽  
Naghmeh Nikkheslat
Keyword(s):  
Systematic Review ◽  
Animal Studies ◽  
Bipolar Depression ◽  
Strong Support ◽  
Kynurenine Pathway ◽  
Future Research ◽  
Downstream Effects ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Anti Inflammatory

Background: Ketamine is a novel rapid-acting antidepressant with high efficacy in treatment-resistant patients. Its exact therapeutic mechanisms of action are unclear; however, in recent years its anti-inflammatory properties and subsequent downstream effects on tryptophan (TRP) metabolism have sparked research interest. Aim: This systematic review examined the effect of ketamine on inflammatory markers and TRP–kynurenine (KYN) pathway metabolites in patients with unipolar and bipolar depression and in animal models of depression. Methods: MEDLINE, Embase, and PsycINFO databases were searched on October 2020 (1806 to 2020). Results: Out of 807 initial results, nine human studies and 22 animal studies on rodents met the inclusion criteria. Rodent studies provided strong support for ketamine-induced decreases in pro-inflammatory cytokines, namely in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α and indicated anti-inflammatory effects on TRP metabolism, including decreases in the enzyme indoleamine 2,3-dioxygenase (IDO). Clinical evidence was less robust with high heterogeneity between sample characteristics, but most experiments demonstrated decreases in peripheral inflammation including in IL-1β, IL-6, and TNF-α. Preliminary support was also found for reduced activation of the neurotoxic arm of the KYN pathway. Conclusion: Ketamine appears to induce anti-inflammatory effects in at least a proportion of depressed patients. Suggestions for future research include investigation of markers in the central nervous system and examination of clinical relevance of inflammatory changes.

scholarly journals Cytokines as Biomarkers and Their Respective Clinical Cutoff Levels

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Rebecca N. Monastero ◽  
Srinivas Pentyala
Keyword(s):  
Tumor Necrosis ◽  
Inflammatory Diseases ◽  
Low Cost ◽  
The Body ◽  
Tumor Necrosis Factors ◽  
Biochemical Pathways ◽  
Downstream Effects ◽  
Future Work ◽  
Receiver Operator Characteristics ◽  
Cutoff Levels

Cytokines, including interleukins, interferons, tumor necrosis factors, and chemokines, have a variety of pro- and anti-inflammatory effects in the body through a number of biochemical pathways and interactions. Stimuli, actions, interactions, and downstream effects of cytokines have been investigated in more depth in recent years, and clinical research has also been conducted to implicate cytokines in causal patterns in certain diseases. However, particular cutoffs of cytokines as biomarkers for disease processes have not been well studied, and this warrants future work to potentially improve diagnoses for diseases with inflammatory markers. A limited number of studies in this area are reviewed, considering diseases correlated with abnormal cytokine profiles, as well as specific cutoffs at which cytokines have been deemed clinically useful for diagnosing those diseases through Receiver Operator Characteristics modeling. In light of studies such as those discussed in this review, cytokine testing has the potential to support diagnosis due to its lack of invasiveness and low cost, compared to other common types of testing for infections and inflammatory diseases.

Functional linkage as a direction for studies in oxidative stress: α-adrenergic receptorsThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 220-232 ◽  
Author(s):  
Natalia Ziolkowski ◽  
Ashok K. Grover
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Arterial Blood Flow ◽  
Arterial Blood ◽  
Functional Linkage ◽  
Protein Kinase C Activity ◽  
Downstream Effects ◽  
Fine Regulation ◽  
Health And Disease ◽  
G Protein Coupled

The α-adrenergic receptors (adrenoceptors) are activated by the endogenous agonists epinephrine and norepinephrine. They are G protein-coupled receptors that may be broadly classified into α1 (subclasses α1A, α1B, α1D) and α2 (subclasses α2A, α2B, α2C). The α1-adrenoceptors act by binding to Gαq subunits of the G proteins, causing activation of phospholipase C (PLC). PLC converts phosphatidylinositol 4,5-bisphosphate into inositol trisphosphate (IP3) and diacylglycerol (DAG), which have downstream effects on cytosolic Ca2+ concentration. The α2-adrenoceptors bind to Gαi thus inhibiting adenylyl cyclase and decreasing cAMP levels. DAG alters protein kinase C activity and cAMP activates protein kinase A. The downstream pathways of the two receptors may also interact. Activation of α1- and α2-adrenoceptors in vascular smooth muscle results in vasoconstriction. However, the densities of individual receptor subclasses vary between vessel beds or between vessels of various sizes within the same bed. In vasculature, the densities of adrenoceptor subclasses differ between conduit arteries and arterioles. These differences, along with differences in coupling mechanisms, allow for fine regulation of arterial blood flow. This diversity is enhanced by interactions resulting from homo- and heterodimer formation of the receptors, metabolic pathways, and kinases. Reactive oxygen species generated in pathologies may alter α1- and α2-adrenoceptor cascades, change vascular contractility, or cause remodeling of blood vessels. This review emphasizes the need for understanding the functional linkage between α-adrenoceptor subtypes, coupling, cross talk, and oxidative stress in cardiovascular pathologies.

Sign in / Sign up

Export Citation Format

Share Document