scholarly journals Secretory Phospholipase A2s in Insulin Resistance and Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Michael S. Kuefner
Keyword(s):  
Insulin Resistance ◽  
Clinical Trials ◽  
Distribution Function ◽  
Substrate Specificity ◽  
Tissue Distribution ◽  
Mouse Models ◽  
Insulin Action ◽  
The Past ◽  
Mammalian Tissues ◽  
Phospholipases A

The phospholipases A2 (PLA2) superfamily encompasses enzymes commonly found in mammalian tissues and snake venom. Many of these enzymes have unique tissue distribution, function, and substrate specificity suggesting distinct biological roles. In the past, much of the research on secretory PLA2s has analyzed their roles in inflammation, anti-bacterial actions, and atherosclerosis. In recent studies utilizing a variety of mouse models, pancreatic islets, and clinical trials, a role for many of these enzymes in the control of metabolism and insulin action has been revealed. In this review, this research, and the unique contributions of the PLA2 enzymes in insulin resistance and metabolism.

scholarly journals Mitochondrial dysfunction and insulin resistance: an update

2015 ◽  
Vol 4 (1) ◽  
pp. R1-R15 ◽  
Author(s):  
Magdalene K Montgomery ◽  
Nigel Turner
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Insulin Action ◽  
Intervention Studies ◽  
Human Populations ◽  
Genetic Manipulations ◽  
The Past ◽  
Mitochondrial Capacity

Mitochondrial dysfunction has been implicated in the development of insulin resistance (IR); however, a large variety of association and intervention studies as well as genetic manipulations in rodents have reported contrasting results. Indeed, even 39 years after the first publication describing a relationship between IR and diminished mitochondrial function, it is still unclear whether a direct relationship exists, and more importantly if changes in mitochondrial capacity are a cause or consequence of IR. This review will take a journey through the past and summarise the debate about the occurrence of mitochondrial dysfunction and its possible role in causing decreased insulin action in obesity and type 2 diabetes. Evidence is presented from studies in various human populations, as well as rodents with genetic manipulations of pathways known to affect mitochondrial function and insulin action. Finally, we have discussed whether mitochondria are a potential target for the treatment of IR.

scholarly journals ANCA Status or Clinical Phenotype — What Counts More?

2021 ◽  
Vol 23 (6) ◽  
Author(s):  
Martin Windpessl ◽  
Erica L. Bettac ◽  
Philipp Gauckler ◽  
Jae Il Shin ◽  
Duvuru Geetha ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Granulomatosis With Polyangiitis ◽  
Clinical Phenotype ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Cardiovascular Death ◽  
Genetic Associations ◽  
Ongoing Debate ◽  
The Past ◽  
Anca Associated Vasculitis

Abstract Purpose of Review There is ongoing debate concerning the classification of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. That is, whether classification should be based on the serotype (proteinase 3 (PR3)- or myeloperoxidase (MPO)-ANCA) or on the clinical phenotype (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)). To add clarity, this review focused on integration of the most recent literature. Recent Findings Large clinical trials have provided evidence that a serology-based risk assessment for relapses is more predictive than distinction based on the phenotype. Research conducted in the past decade indicated that a serology-based approach more closely resembles the genetic associations, the clinical presentation (i.e., lung involvement), biomarker biology, treatment response, and is also predicting comorbidities (such as cardiovascular death). Summary Our review highlights that a serology-based approach could replace a phenotype-based approach to classify ANCA-associated vasculitides. In future, clinical trials and observational studies will presumably focus on this distinction and, as such, translate into a “personalized medicine.”

scholarly journals Mesenchymal stem cells and oncolytic viruses: joining forces against cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001684
Author(s):  
Rafael Moreno
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Oncolytic Viruses ◽  
Immunogenic Cell Death ◽  
The Past ◽  
Physical Barriers ◽  
Immunogenic Properties ◽  
New Strategies

The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic ‘cold’ tumors into inflamed immunogenic ‘hot’ tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.

scholarly journals How I treat pediatric venous thromboembolism

Blood ◽  
2017 ◽  
Vol 130 (12) ◽  
pp. 1402-1408 ◽  
Author(s):  
Guy Young
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Large Scale ◽  
Central Venous Catheters ◽  
Rare Disorder ◽  
Central Venous ◽  
Management Decisions ◽  
Logical Approach ◽  
The Past ◽  
Medical Disorders

Abstract The incidence of pediatric venous thromboembolism (VTE) has been increasing significantly over the past decade in part as a result of increased recognition of this serious disorder but more so because of the increased use of central venous catheters and other technological advancements involved in the care of ill children. Management of pediatric VTE is a complex undertaking, considering that the vast majority of children who develop this complication have serious underlying medical disorders. Although the incidence is rising, in comparison with adults, this remains a relatively rare disorder, and as such, large-scale clinical trials have not been completed, rendering management decisions to be based on extrapolation from adult data and the experience of the treating physician. Clearly, both are fraught with problems. Thus, day-to-day management remains more art than science until such time that the results from clinical trials (many of which are under way) become available. This edition of “How I Treat” describes the author’s experience in managing 3 common scenarios that one may encounter in pediatric thrombosis and suggests a logical approach to such situations. Furthermore, the author provides 3 algorithms to help guide management decisions.

scholarly journals Leprechaunism: In Vitro Insulin Action Despite Genetic Insulin Resistance

1987 ◽  
Vol 22 (3) ◽  
pp. 286-291 ◽  
Author(s):  
Mitchell E Geffner ◽  
Solomon A Kaplan ◽  
Noelle Bersch ◽  
Barbara M Lippe ◽  
Wesley G Smith ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Action

scholarly journals Virus Eradication and Synthetic Biology: Changes with SARS-CoV-2?

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 569
Author(s):  
Jean-Nicolas Tournier ◽  
Joseph Kononchik
Keyword(s):  
Clinical Trials ◽  
Synthetic Biology ◽  
Viral Disease ◽  
Virus Eradication ◽  
Disease Eradication ◽  
The Public ◽  
The Past ◽  
The World ◽  
Significant Effort

The eradication of infectious diseases has been achieved only once in history, in 1980, with smallpox. Since 1988, significant effort has been made to eliminate poliomyelitis viruses, but eradication is still just out of reach. As the goal of viral disease eradication approaches, the ability to recreate historically eradicated viruses using synthetic biology has the potential to jeopardize the long-term sustainability of eradication. However, the emergence of the severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 pandemic has highlighted our ability to swiftly and resolutely respond to a potential outbreak. This virus has been synthetized faster than any other in the past and is resulting in vaccines before most attenuated candidates reach clinical trials. Here, synthetic biology has the opportunity to demonstrate its truest potential to the public and solidify a footing in the world of vaccines.

scholarly journals Immunocompetent Mouse Models in the Search for Effective Immunotherapy in Glioblastoma

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 19
Author(s):  
Roxanne Wouters ◽  
Sien Bevers ◽  
Matteo Riva ◽  
Frederik De Smet ◽  
An Coosemans
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Mouse Models ◽  
Standard Of Care ◽  
Preclinical Studies ◽  
Success Rates ◽  
Immunocompetent Mouse ◽  
Full Spectrum ◽  
Effective Immune Response ◽  
Radio Chemotherapy

Glioblastoma (GBM) is the most aggressive intrinsic brain tumor in adults. Despite maximal therapy consisting of surgery and radio/chemotherapy, GBM remains largely incurable with a median survival of less than 15 months. GBM has a strong immunosuppressive nature with a multitude of tumor and microenvironment (TME) derived factors that prohibit an effective immune response. To date, all clinical trials failed to provide lasting clinical efficacy, despite the relatively high success rates of preclinical studies to show effectivity of immunotherapy. Various factors may explain this discrepancy, including the inability of a single mouse model to fully recapitulate the complexity and heterogeneity of GBM. It is therefore critical to understand the features and limitations of each model, which should probably be combined to grab the full spectrum of the disease. In this review, we summarize the available knowledge concerning immune composition, stem cell characteristics and response to standard-of-care and immunotherapeutics for the most commonly available immunocompetent mouse models of GBM.

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