scholarly journals A Putative Role of de-Mono-ADP-Ribosylation of STAT1 by the SARS-CoV-2 Nsp3 Protein in the Cytokine Storm Syndrome of COVID-19

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 646 ◽  
Author(s):  
Jean-Michel Claverie
Keyword(s):  
Inflammatory Response ◽  
Molecular Data ◽  
High Variability ◽  
Cytokine Storm ◽  
Therapeutic Approaches ◽  
Genomic Comparison ◽  
Adp Ribosylation ◽  
New Therapeutic Approaches ◽  
Variability Region

As more cases of COVID-19 are studied and treated worldwide, it had become apparent that the lethal and most severe cases of pneumonia are due to an out-of-control inflammatory response to the SARS-CoV-2 virus. I explored the putative causes of this specific feature through a detailed genomic comparison with the closest SARS-CoV-2 relatives isolated from bats, as well as previous coronavirus strains responsible for the previous epidemics (SARS-CoV and MERS-CoV). The high variability region of the nsp3 protein was confirmed to exhibit the most variations between closest strains. It was then studied in the context of physiological and molecular data available in the literature. A number of convergent findings suggest de-mono-ADP-ribosylation (de-MARylation) of STAT1 by the SARS-CoV-2 nsp3 as a putative cause of the cytokine storm observed in the most severe cases of COVID-19. This may suggest new therapeutic approaches and help in designing assays to predict the virulence of naturally circulating SARS-like animal coronaviruses.

scholarly journals The Likely Role of de-Mono-ADP-ribosylation of STAT1 by the SARS-CoV-2 nsp3 Protein in the Cytokine Storm Syndrome of COVID-19

2020 ◽  
Author(s):  
Jean-Michel CLAVERIE
Keyword(s):  
Inflammatory Response ◽  
World Wide ◽  
Molecular Data ◽  
High Variability ◽  
Cytokine Storm ◽  
Therapeutic Approaches ◽  
Genomic Comparison ◽  
New Therapeutic Approaches ◽  
Variability Region

As more cases of COVID-19 are studied and treated world-wide, it had become apparent that lethal and most severe cases of pneumonia are due to an out-of-control inflammatory response to the SARS-CoV2 virus. I explored the putative causes of this specific feature through a detailed genomic comparison with the closest SARS-CoV-2 relatives isolated from bats, as well as previous coronavirus strains responsible for the previous epidemics (SARS-CoV, and MERS-CoV). The high variability region of the nsp3 protein was confirmed to exhibit the most variations between closest strains. It was then studied in the context of physiological and molecular data available in the literature. A number of convergent findings point out de-mono-ADP-ribosylation (de-MARylation) of STAT1 by the SARS-CoV-2 nsp3 as a likely cause of the cytokine storm observed in the most severe cases of COVID-19. This may suggest new therapeutic approaches and an assay to predict the virulence of naturally circulating SARS-like animal coronaviruses.

scholarly journals The emerging role of mechanical and topographical factors in the development and treatment of nervous system disorders: dark and light sides of the force

2021 ◽  
Author(s):  
Natalia Bryniarska-Kubiak ◽  
Andrzej Kubiak ◽  
Małgorzata Lekka ◽  
Agnieszka Basta-Kaim
Keyword(s):  
Nervous System ◽  
Physical Factors ◽  
Nervous System Diseases ◽  
Therapeutic Approaches ◽  
System Disease ◽  
New Therapeutic Approaches ◽  
The Subject ◽  
Topographical Factors ◽  
New Treatment

AbstractNervous system diseases are the subject of intensive research due to their association with high mortality rates and their potential to cause irreversible disability. Most studies focus on targeting the biological factors related to disease pathogenesis, e.g. use of recombinant activator of plasminogen in the treatment of stroke. Nevertheless, multiple diseases such as Parkinson’s disease and Alzheimer’s disease still lack successful treatment. Recently, evidence has indicated that physical factors such as the mechanical properties of cells and tissue and topography play a crucial role in homeostasis as well as disease progression. This review aims to depict these factors’ roles in the progression of nervous system diseases and consequently discusses the possibility of new therapeutic approaches. The literature is reviewed to provide a deeper understanding of the roles played by physical factors in nervous system disease development to aid in the design of promising new treatment approaches. Graphic abstract

Insights into the role of components of the tumor microenvironment in oral carcinoma call for new therapeutic approaches

2014 ◽  
Vol 325 (2) ◽  
pp. 58-64 ◽  
Author(s):  
Tuula Salo ◽  
Marilena Vered ◽  
Ibrahim O. Bello ◽  
Pia Nyberg ◽  
Carolina Cavalcante Bitu ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Oral Carcinoma ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches

scholarly journals Clinical Significance of Circulating Tumor Cells in Gastrointestinal Carcinomas

Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 192
Author(s):  
Leonie Konczalla ◽  
Anna Wöstemeier ◽  
Marius Kemper ◽  
Karl-Frederik Karstens ◽  
Jakob Izbicki ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Clinical Application ◽  
Liquid Biopsy ◽  
Cancer Diagnostics ◽  
Therapeutic Approaches ◽  
Primary Tumors ◽  
New Therapeutic Approaches ◽  
Tumor Dissemination

The idea of a liquid biopsy to screen, surveil and treat cancer patients is an intensively discussed and highly awaited tool in the field of oncology. Despite intensive research in this field, the clinical application has not been implemented yet and further research has to be conducted. However, one component of the liquid biopsy is circulating tumor cells (CTCs) whose potential for clinical application is evaluated in the following. CTCs can shed from primary tumors to the peripheral blood at any time point during the progress of a malignant disease. Following, one single CTC can be the origin for distant metastasis at later cancer stage. Thus, CTCs have great potential to either be used in cancer diagnostics and patient stratification or to function as a target for new therapeutic approaches to stop tumor dissemination and metastasis at the very early beginning. Due to the biological fundamental role of CTCs in tumor progression, here, we provide an overview of CTCs in gastrointestinal cancers and their potential use in the clinical setting. In particular, we discuss the usage of CTC for screening and stratifying patients’ risk. Moreover, we will discuss the potential role of CTCs for treatment specification and treatment monitoring.

Corrigendum

2019 ◽  
Vol 26 (3) ◽  
pp. 235-235
Keyword(s):  
Review Article ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches

In the Review Article entitled “An Emerging Role of Endometrial Inflammasome in Reproduction: New Therapeutic Approaches” published in Protein & Peptides Letters, 2018, Vol. 26, No. 5, the affiliations of authors are revised due to recent restructuring that took place within the Institution for which the authors work for. The revised affiliation is as follows: </p><p> Fiorella Di Nicuoloa,b,*, Monia Specchiac, Lorenza Trentavizic, Alfredo Pontecorvid, Giovanni Scambiacc,e and Nicoletta Di Simoneb,c </p><p> aIstituto Scientifico Internazionale Paolo VI, ISI, Università Cattolica del Sacro Cuore, Rome, Italia; bFondazione Policlinico Universitario A. Gemelli IRCCS, U.O.C. di Ostetricia e Patologia Ostetrica, Dipartimento di Scienze della Salute della Donna e del Bambino, Roma, Italia; cUniversità Cattolica del Sacro Cuore, Istituto di Clinica Ostetrica e Ginecologica, Roma, Italia; dFondazione Policlinico Universitario A. Gemelli IRCCS, Dipartimento di Scienze Gastroenterologiche, Endocrino- Metaboliche e Nefro-Urologiche, Roma, Italia; eFondazione Policlinico Universitario A. Gemelli IRCCS, U.O.C. di Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna e del Bambino, Roma, Italia

scholarly journals Emerging role of circadian clock disruption in alcohol-induced liver disease

2018 ◽  
Vol 315 (3) ◽  
pp. G364-G373 ◽  
Author(s):  
Shannon M. Bailey
Keyword(s):  
Liver Disease ◽  
Circadian Clock ◽  
Therapeutic Approaches ◽  
Excessive Alcohol Consumption ◽  
Peripheral Tissues ◽  
New Therapeutic Approaches ◽  
Timing System ◽  
Excessive Alcohol ◽  
The Impact

The detrimental health effects of excessive alcohol consumption are well documented. Alcohol-induced liver disease (ALD) is the leading cause of death from chronic alcohol use. As with many diseases, the etiology of ALD is influenced by how the liver responds to other secondary insults. The molecular circadian clock is an intrinsic cellular timing system that helps organisms adapt and synchronize metabolism to changes in their environment. The clock also influences how tissues respond to toxic, environmental, and metabolic stressors, like alcohol. Consistent with the essential role for clocks in maintaining health, genetic and environmental disruption of the circadian clock contributes to disease. While a large amount of rich literature is available showing that alcohol disrupts circadian-driven behaviors and that circadian clock disruption increases alcohol drinking and preference, very little is known about the role circadian clocks play in alcohol-induced tissue injuries. In this review, recent studies examining the effect alcohol has on the circadian clock in peripheral tissues (liver and intestine) and the impact circadian clock disruption has on development of ALD are presented. This review also highlights some of the rhythmic metabolic processes in the liver that are disrupted by alcohol and potential mechanisms through which alcohol disrupts the liver clock. Improved understanding of the mechanistic links between the circadian clock and alcohol will hopefully lead to the development of new therapeutic approaches for treating ALD and other alcohol-related organ pathologies.

scholarly journals Biological bases of cancer immunotherapy

2021 ◽  
Vol 23 ◽  
Author(s):  
Maryanne M. Gonzales Carazas ◽  
Joseph A. Pinto ◽  
Fanny L. Casado
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Historical Review ◽  
Predictive Biomarkers ◽  
High Variability ◽  
Therapeutic Approaches ◽  
Cancer Treatments ◽  
Cancer Types

Abstract Immunotherapy has changed the landscape of cancer treatment and has significantly improved the outcome of several cancer types including breast, lung, colorectal and prostate. Neoantigen recognition and immune checkpoint inhibitors are nowadays the milestones of different immunotherapeutic regimes; however, high cost, primary and acquired resistance and the high variability of responses make their extensive use difficult. The development of better predictive biomarkers that represent tumour diversity shows promise because there is a significant body of clinical data showing a spectrum of immunotherapeutic responses that might be related back to their specific characteristics. This article makes a conceptual and historical review to summarise the main advances in our understanding of the role of the immune system in cancer, while describing the methodological details that have been successfully implemented on cancer treatments and that may hold the key to improved therapeutic approaches.

Comorbidity of Migraine and Epilepsy in Pediatrics: A Review

2018 ◽  
Vol 33 (12) ◽  
pp. 801-808 ◽  
Author(s):  
Jasna Jancic ◽  
Vesna Djuric ◽  
Boris Hencic ◽  
John N. van den Anker ◽  
Janko Samardzic
Keyword(s):  
Genetic Basis ◽  
Treatment Options ◽  
Dietary Therapy ◽  
Channel Blockers ◽  
Therapeutic Approaches ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled ◽  
New Therapeutic Approaches ◽  
Neurologic Disorders

Migraine and epilepsy are classified as chronic paroxysmal neurologic disorders sharing many clinical features, as well as possible treatment options. This review highlights the similarities between migraine and epilepsy in pediatrics, focusing on epidemiologic, pathophysiological, genetic, clinical, and pharmacologic aspects. Despite the fact that several syndromes share symptoms of both migraine and epilepsy, further research is needed to clarify the pathophysiological and genetic basis of their comorbidity. Drugs used for prophylactic therapy of migraine and epilepsy have similar pharmacologic properties. The role of epileptic pharmacotherapy in the prophylaxis of migraine is assessed, including the use of conventional antiepileptic drugs, calcium channel blockers, and nonpharmacologic methods such as dietary therapy, supplements, and vagal nerve stimulation. Further randomized, controlled clinical trials assessing pharmacologic and nonpharmacologic methods for the treatment of both disorders are essential, in order to initiate new therapeutic approaches.

scholarly journals The PI3K/AKT/mTOR pathway in the pathophysiology and treatment of pituitary adenomas

2014 ◽  
Vol 21 (4) ◽  
pp. R331-R344 ◽  
Author(s):  
Eric Monsalves ◽  
Kyle Juraschka ◽  
Toru Tateno ◽  
Sameer Agnihotri ◽  
Sylvia L Asa ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Human Cancer ◽  
Tumor Biology ◽  
Pituitary Tumors ◽  
Mass Effect ◽  
Therapeutic Approaches ◽  
Hormone Production ◽  
New Therapeutic Approaches ◽  
Wide Range

Pituitary adenomas are common intracranial neoplasms. Patients with these tumors exhibit a wide range of clinically challenging problems, stemming either from results of sellar mass effect in pituitary macroadenoma or the diverse effects of aberrant hormone production by adenoma cells. While some patients are cured/controlled by surgical resection and/or medical therapy, a proportion of patients exhibit tumors that are refractory to current modalities. New therapeutic approaches are needed for these patients. Activation of the AKT/phophotidylinositide-3-kinase pathway, including mTOR activation, is common in human neoplasia, and a number of therapeutic approaches are being employed to neutralize activation of this pathway in human cancer. This review examines the role of this pathway in pituitary tumors with respect to tumor biology and its potential role as a therapeutic target.

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