scholarly journals Sphingolipid-Transporting Proteins as Cancer Therapeutic Targets

2019 ◽  
Vol 20 (14) ◽  
pp. 3554 ◽  
Author(s):  
Doaa Samaha ◽  
Housam H. Hamdo ◽  
Max Wilde ◽  
Kevin Prause ◽  
Christoph Arenz
Keyword(s):  
Potential Role ◽  
Therapeutic Targets ◽  
Transport Proteins ◽  
Biochemical Data ◽  
Sphingolipid Metabolism ◽  
Potential Target ◽  
The Past ◽  
Essential Components ◽  
Rate Limiting

The understanding of the role of sphingolipid metabolism in cancer has tremendously increased in the past ten years. Many tumors are characterized by imbalances in sphingolipid metabolism. In many cases, disorders of sphingolipid metabolism are also likely to cause or at least promote cancer. In this review, sphingolipid transport proteins and the processes catalyzed by them are regarded as essential components of sphingolipid metabolism. There is much to suggest that these processes are often rate-limiting steps for metabolism of individual sphingolipid species and thus represent potential target structures for pharmaceutical anticancer research. Here, we summarize empirical and biochemical data on different proteins with key roles in sphingolipid transport and their potential role in cancer.

Acid ceramidase, a double-edged sword in cancer aggression: A minireview

2020 ◽  
Vol 20 ◽  
Author(s):  
Helen Shiphrah Vethakanraj ◽  
Niveditha Chandrasekaran ◽  
Ashok Kumar Sekar
Keyword(s):  
Cell Fate ◽  
Cancer Progression ◽  
Potential Role ◽  
Tumour Progression ◽  
Acid Ceramidase ◽  
The Core ◽  
The Past ◽  
Sphingosine 1 Phosphate ◽  
Key Enzyme

: Acid ceramidase (AC), the key enzyme of the ceramide metabolic pathway hydrolyzes pro-apoptotic ceramide to sphingosine, which by the action of sphingosine-1-kinase is metabolized to mitogenic sphingosine-1-phosphate. The intracellular level of AC determines ceramide/sphingosine-1-phosphate rheostat which in turn decides the cell fate. The upregulated AC expression during cancerous condition acts as a “double-edged sword” by converting pro-apoptotic ceramide to anti-apoptotic sphingosine-1-phosphate, wherein on one end, the level of ceramide is decreased and on the other end, the level of sphingosine-1-phosphate is increased, thus altogether aggravating the cancer progression. In addition, cancer cells with upregulated AC expression exhibited increased cell proliferation, metastasis, chemoresistance, radioresistance and numerous strategies were developed in the past to effectively target the enzyme. Gene silencing and pharmacological inhibition of AC sensitized the resistant cells to chemo/radiotherapy thereby promoting cell death. The core objective of this review is to explore AC mediated tumour progression and the potential role of AC inhibitors in various cancer cell lines/models.

scholarly journals Anti-phospholipid syndrome and COVID-19 thrombosis: connecting the dots

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Moon Ley Tung ◽  
Bryce Tan ◽  
Robin Cherian ◽  
Bharatendu Chandra
Keyword(s):  
Endothelial Dysfunction ◽  
Severe Acute Respiratory Syndrome ◽  
Potential Role ◽  
Molecular Mimicry ◽  
Thromboembolic Events ◽  
The Past ◽  
High Prevalence ◽  
Connecting The Dots ◽  
Anti Phospholipid Syndrome

Abstract As the coronavirus disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide, it has emerged as a leading cause of mortality, resulting in >1 million deaths over the past 10 months. The pathophysiology of COVID-19 remains unclear, posing a great challenge to the medical management of patients. Recent studies have reported an unusually high prevalence of thromboembolic events in COVID-19 patients, although the mechanism remains elusive. Several studies have reported the presence of aPLs in COVID-19 patients. We have noticed similarities between COVID-19 and APS, which is an autoimmune prothrombotic disease that is often associated with an infective aetiology. Molecular mimicry and endothelial dysfunction could plausibly explain the mechanism of thrombogenesis in acquired APS. In this review, we discuss the clinicopathological similarities between COVID-19 and APS, and the potential role of therapeutic targets based on the anti-phospholipid model for COVID-19 disease.

Nitric oxide: a new role in intensive care

2020 ◽  
Vol 22 (1) ◽  
pp. 72-79
Author(s):  
Alexandra Lee ◽  
◽  
Warwick Butt ◽  
◽  
◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Potential Role ◽  
Nitric Oxide Donors ◽  
Ischaemia Reperfusion Injury ◽  
Surface Receptors ◽  
The Past ◽  
Ischaemia Reperfusion ◽  
Human Experiments ◽  
Endogenous Nitric Oxide

Inhaled nitric oxide has been used for 30 years to improve oxygenation and decrease pulmonary vascular resistance. In the past 15 years, there has been increased understanding of the role of endogenous nitric oxide on cell surface receptors, mitochondria, and intracellular processes involving calcium and superoxide radicals. This has led to several animal and human experiments revealing a potential role for administered nitric oxide or nitric oxide donors in patients with systemic inflammatory response syndrome or ischaemia–reperfusion injury, and in patients for whom exposure of blood to artificial surfaces has occurred.

Fifty years ago: ‘The scope of occupational medicine in a university health service’

2020 ◽  
pp. 202-203
Author(s):  
Anthony Ryle
Keyword(s):  
Health Service ◽  
Physical Health ◽  
Occupational Medicine ◽  
Potential Role ◽  
Health And Safety ◽  
Academic Achievements ◽  
The Past ◽  
Selection Of

This series provides a selection of articles from the past. In Fifty years ago: The scope of occupational medicine in a university health service Anthony Ryle briefly explores the potential role of a University Health Service in relation to students’ academic achievements and failures, rather than their physical health and safety.

scholarly journals Sorting Mechanisms for MicroRNAs into Extracellular Vesicles and Their Associated Diseases

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1044 ◽  
Author(s):  
Michael Groot ◽  
Heedoo Lee
Keyword(s):  
Extracellular Vesicles ◽  
Potential Role ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Transport Proteins ◽  
Caveolin 1 ◽  
Argonaute 2 ◽  
Disease States ◽  
Mirna Content

Extracellular vesicles (EV) are secretory membranous elements used by cells to transport proteins, lipids, mRNAs, and microRNAs (miRNAs). While their existence has been known for many years, only recently has research begun to identify their function in intercellular communication and gene regulation. Importantly, cells have the ability to selectively sort miRNA into EVs for secretion to nearby or distant targets. These mechanisms broadly include RNA-binding proteins such as hnRNPA2B1 and Argonaute-2, but also membranous proteins involved in EV biogenesis such as Caveolin-1 and Neural Sphingomyelinase 2. Moreover, certain disease states have also identified dysregulated EV-miRNA content, shedding light on the potential role of selective sorting in pathogenesis. These pathologies include chronic lung disease, immune response, neuroinflammation, diabetes mellitus, cancer, and heart disease. In this review, we will overview the mechanisms whereby cells selectively sort miRNA into EVs and also outline disease states where EV-miRNAs become dysregulated.

scholarly journals Role of Histone Deacetylases in Carcinogenesis: Potential Role in Cholangiocarcinoma

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 780
Author(s):  
Kishor Pant ◽  
Estanislao Peixoto ◽  
Seth Richard ◽  
Sergio A. Gradilone
Keyword(s):  
Histone Deacetylases ◽  
Potential Role ◽  
Chemotherapy Resistance ◽  
Tumor Development ◽  
Therapeutic Targets ◽  
Cellular Proteins ◽  
Epigenetic Changes ◽  
Post Translational Modifications ◽  
Frequent Relapse

Cholangiocarcinoma (CCA) is a highly invasive and metastatic form of carcinoma with bleak prognosis due to limited therapies, frequent relapse, and chemotherapy resistance. There is an urgent need to identify the molecular regulators of CCA in order to develop novel therapeutics and advance diseases diagnosis. Many cellular proteins including histones may undergo a series of enzyme-mediated post-translational modifications including acetylation, methylation, phosphorylation, sumoylation, and crotonylation. Histone deacetylases (HDACs) play an important role in regulating epigenetic maintenance and modifications of their targets, which in turn exert critical impacts on chromatin structure, gene expression, and stability of proteins. As such, HDACs constitute a group of potential therapeutic targets for CCA. The aim of this review was to summarize the role that HDACs perform in regulating epigenetic changes, tumor development, and their potential as therapeutic targets for CCA.

scholarly journals Endocrine Significance of SARS-CoV-2’s Reliance on ACE2

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Eric Lazartigues ◽  
Mirza Muhammad Fahd Qadir ◽  
Franck Mauvais-Jarvis
Keyword(s):  
Potential Role ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Impact ◽  
The Past ◽  
And Function ◽  
Endocrine Tissues

Abstract The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and thyroid diseases.

PIG, TONE SANDHI AND WUMIN

1989 ◽  
Vol 18 (2) ◽  
pp. 163-182
Author(s):  
William L. Ballard
Keyword(s):  
Potential Role ◽  
Historical Linguistics ◽  
Tone Sandhi ◽  
Basic Principles ◽  
The Past ◽  
Language History ◽  
History Of ◽  
Chinese Dialects ◽  
Historical Relationship

Several scholars have made various remarks about the language history of the Wu and Min areas. Some of these remarks concern non-Chinese languages that may have been spoken in the area(s) and that may have left some traces in the forms of Chinese spoken there now (substrata). Other remarks concern the possible prehistory of what appear now to be transitional or mixed forms, or features that may be present due to some ancient influence or borrowing. In considering such matters it is important to keep in mind the basic principles (and biases) of historical linguistics, and of the potential role of philological materials in the discussion. My fieldwork in China this spring, as well as my research in the past, point to some special historical relationship between southern Wu and northern Min. This appears to mean that the boundaries between the northern and southern types of each of the two dialect groups are stronger than they have been portrayed in the past, and that the traditional boundary between Wu and Min is considerably weaker than has been supposed. The total sum of dialect facts cannot be ignored in trying to ascertain the language history of this area; it would appear that various elements of the traditional view of the history of the southern dialects are in error in various ways. In particular, it is at least possible that Wu and Min, in some sense, share a common ancestor not common to any other Chinese dialects.

scholarly journals Populações Celulares Periféricas (CD4+, CD8+ e CD19+) em Indivíduos Dislipidémicos

2013 ◽  
Vol 26 (6) ◽  
pp. 676
Author(s):  
Jose Pereira de Moura ◽  
Manuel Santos Rosa ◽  
Vera Alves ◽  
Anabela Mota Pinto ◽  
Victor Rodrigues ◽  
...  
Keyword(s):  
Potential Role ◽  
Inflammatory Cells ◽  
Control Group ◽  
Cd4 Cells ◽  
Reactive Protein ◽  
The Past ◽  
Markers Of Inflammation ◽  
The People ◽  
Risk Predictors

Introduction: The past decade has witnessed an increasing recognition that inflammatory mechanisms play a central role in the pathogenesis of atherosclerosis and its complications. Recently, attention was focused on the potential role of plasma markers of inflammation as risk predictors among those at risk for cardiovascular events. Of these potential markers, C-reactive protein (CRP), IL6, metalloproteinases, ICAM, VCAM and other molecules, have been extensively studied. On the other hand, to our knowledge, there are only a few studies on the role of inflammatory cells, like T and B lymphocytes in the atherosclerosis.Material and Methods: By Flow Cytrometry analysis we have determined on dyslipidemic people and on a control group, the percentage of some peripheral inflammatory cells, like CD3+, CD4+, CD8+, CD19+, CD56+, CD56CD8+, DN, CD25+, CD26+, CD25CD3+, CD26CD3+, CD25CD26CD3+, CCR5+, CCR5CD3+, CCR5CD4+, HLADR+, HLADRCD4+, HLADRCD8h+, HLADRCD8low+, HLADRCD8+, CD95+, CD95CD95L+, CD3CD95+, CD3CD95L+, CD62L+, CD3CD62L+, CD69+, CD69CD3+ e CD69CD4+.Results: In the present study we have particularly studied the percentage of CD4+, CD8+ and CD19+ cells. The CD4+ cells have been significantly reduced in the people with dyslipidemia.Discussion: We do not know the peripheral numbers of the subtype Th1 and Th2, neither the percentage of CD4+CD25+ cells (regulatory T cells). We have not find any differences on the percentage from the CD8+ and CD19+ cells.Conclusions: In spite of the identified limitations resulting from the small-sized samples, it was possible to show a reduction of some molecules after application of acetylsalicylic acid.

scholarly journals Environmental Degradation in Developing Countries: The Plight and Potential Role of Women

1970 ◽  
pp. 13
Author(s):  
Maya Abdel Rahim
Keyword(s):  
Developing Countries ◽  
Environmental Degradation ◽  
Potential Role ◽  
Environmental Problems ◽  
The Past ◽  
Role Of Women

The past two decades have witnessed a growing awareness of and concern with the ever-increasing magnitude of environmental problems, laying bare the societies and government's incomplete understanding of these problems and their inability to deal with them effectively.

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