scholarly journals The Critical Role of PPARγin Human Malignant Melanoma

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-5 ◽  
Author(s):  
Christian Freudlsperger ◽  
Udo Schumacher ◽  
Siegmar Reinert ◽  
Jürgen Hoffmann
Keyword(s):  
Potential Role ◽  
Critical Role ◽  
Apoptosis Resistance ◽  
Human Malignant Melanoma ◽  
The Past ◽  
Anticancer Effects ◽  
Survival Capacity ◽  
Apoptotic Pathways ◽  
Melanoma Therapy

The past 30 years have only seen slight improvement in melanoma therapy. Despite a wide variety of therapeutic options, current survival for patients with metastatic disease is only 6–8 months. Part of the reason for this treatment failure is the broad chemoresistance of melanoma, which is due to an altered survival capacity and an inactivation of apoptotic pathways. Several targetable pathways, responsible for this survival/apoptosis resistance in melanoma, have been described and current research has focused on mechanism inactivating these pathways. As PPARγwas shown to be constitutively active in several tumour entities and PPARγagonists extent strong anticancer effects, the role of PPARγas a possible target for specific anticancer strategy was investigated in numerous studies. However, only a few studies have focused on the effects of PPARγagonists in melanoma, showing conflicting results. The use of PPARγagonists in melanoma therapy has to be carefully weighted against considerable, undesirable side effects, as their mode of action is not fully understood and even pro-proliferative effects have been described. In the current review, we discuss the role of PPARs, in particular PPARγin melanoma and their potential role as a molecular target for melanoma therapy.

scholarly journals The role of P53 up-regulated modulator of apoptosis (PUMA) in ovarian development, cardiovascular and neurodegenerative diseases

APOPTOSIS ◽  
2021 ◽  
Author(s):  
Mei Li
Keyword(s):  
Neurodegenerative Diseases ◽  
Ovarian Development ◽  
Critical Role ◽  
Ovary Development ◽  
Mitochondrial Apoptosis ◽  
The Past ◽  
Apoptotic Pathways ◽  
Extrinsic Apoptotic Pathways ◽  
Transcriptional Target

AbstractP53 up-regulated modulator of apoptosis (PUMA), a pro-apoptotic BCL-2 homology 3 (BH3)-only member of the BCL-2 family, is a direct transcriptional target of P53 that elicits mitochondrial apoptosis under treatment with radiation and chemotherapy. It also induces excessive apoptosis in cardiovascular and/or neurodegenerative diseases. PUMA has been found to play a critical role in ovarian apoptosis. In the present paper, we review the progress of the study in PUMA over the past two decades in terms of its inducement and/or amplification of programmed cell death and describe recent updates to the understanding of both P53-dependent and P53-independent PUMA-mediated apoptotic pathways that are implicated in physiology and pathology, including the development of the ovary and cardiovascular and neurodegenerative diseases. We propose that PUMA may be a key regulator during ovary development, provide a model for PUMA-mediated apoptotic pathways, including intrinsic and extrinsic apoptotic pathways.

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.

scholarly journals OX40L/OX40 Signal Promotes IL-9 Production by Mucosal MAIT Cells During Helicobacter pylori Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Siqi Ming ◽  
Mei Zhang ◽  
Zibin Liang ◽  
Chunna Li ◽  
Jianzhong He ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Potential Role ◽  
Critical Role ◽  
Underlying Mechanism ◽  
Mucosal Inflammation ◽  
Cross Linking ◽  
Mait Cells ◽  
H Pylori ◽  
Mait Cell

Mucosal associated invariant T (MAIT) cells play a critical role in Helicobacter pylori (H. pylori)-induced gastritis by promoting mucosal inflammation and aggravating mucosal injuries (1, 2). However, the underlying mechanism and key molecules involved are still uncertain. Here we identified OX40, a co-stimulatory molecule mainly expressed on T cells, as a critical regulator to promote proliferation and IL-9 production by MAIT cells and facilitate mucosal inflammation in H. pylori-positive gastritis patients. Serum examination revealed an increased level of IL-9 in gastritis patients. Meanwhile, OX40 expression was increased in mucosal MAIT cells, and its ligand OX40L was also up-regulated in mucosal dendritic cells (DCs) of gastritis patients, compared with healthy controls. Further results demonstrated that activation of the OX40/OX40L pathway promoted IL-9 production by MAIT cells, and MAIT cells displayed a highly-activated phenotype after the cross-linking of OX40 and OX40L. Moreover, the level of IL-9 produced by MAIT cells was positively correlated with inflammatory indexes in the gastric mucosa, suggesting the potential role of IL-9-producing MAIT cells in mucosal inflammation. Taken together, we elucidated that OX40/OX40L axis promoted mucosal MAIT cell proliferation and IL-9 production in H. pylori-induced gastritis, which may provide potential targeting strategies for gastritis treatment.

scholarly journals CUL4A ubiquitin ligase: a promising drug target for cancer and other human diseases

Open Biology ◽  
2014 ◽  
Vol 4 (2) ◽  
pp. 130217 ◽  
Author(s):  
Puneet Sharma ◽  
Alo Nag
Keyword(s):  
Ubiquitin Ligase ◽  
Drug Target ◽  
Critical Role ◽  
Cellular Transformation ◽  
Biological Processes ◽  
Molecular Architecture ◽  
The Past ◽  
Cullin 4A ◽  
Broad Overview

The ability of cullin 4A (CUL4A), a scaffold protein, to recruit a repertoire of substrate adaptors allows it to assemble into distinct E3 ligase complexes to mediate turnover of key regulatory proteins. In the past decade, a considerable wealth of information has been generated regarding its biology, regulation, assembly, molecular architecture and novel functions. Importantly, unravelling of its association with multiple tumours and modulation by viral proteins establishes it as one of the key proteins that may play an important role in cellular transformation. Considering the role of its substrate in regulating the cell cycle and maintenance of genomic stability, understanding the detailed aspects of these processes will have significant consequences for the treatment of cancer and related diseases. This review is an effort to provide a broad overview of this multifaceted ubiquitin ligase and addresses its critical role in regulation of important biological processes. More importantly, its tremendous potential to be exploited for therapeutic purposes has been discussed.

Potential Role of Darvyadi Kwatha in the Management of Diabetes

The Healer ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 80-86
Author(s):  
Shankar Gautam ◽  
Abhishek Upadhyay ◽  
Rashmi Mutha ◽  
BINOD KUMAR SINGH ◽  
Ram Kishor Joshi
Keyword(s):  
Causes Of Death ◽  
Potential Role ◽  
Critical Role ◽  
Animal Experiments ◽  
Safety Evaluation ◽  
New Drugs ◽  
Effective Management ◽  
The Individual ◽  
Glucose 6 Phosphate Dehydrogenase

Diabetes is a clinical condition characterized by a spike in blood glucose in plasma. It is one of the 21st century's greatest public health crises and is among the top 10 causes of death worldwide. Although new drugs and therapeutics are emerging for its management but the prevalence is increasing at an alarming pace; thus, every system must contribute for effective management. An effort is made to review the efficacy and safety evaluation of the individual herbs of Darvyadi Kwatha (DK), an Ayurvedic formulation mentioned in Charaka Samhita. The constituents of the DK has some strong efficient antidiabetic/hypoglycaemic chemical principle having insulin-triggering and insulin-like behaviors which increases the activity of glucose-6-phosphate dehydrogenase (G6PD) and glucokinase and decreases glucose-6-phosphatase activity, reduce oxidative stress and prevention of glutathione reductase, superoxide dismutase, and catalase activity play a critical role in glucose homeostasis. DK also improve biochemical parameters such as SGPT, SGOT, cholesterol and triglycerides and is found to be safe in animal experiments. The various evidences clearly indicates that DK has definite hypoglycemic potential as well as anti-diabetic activity.

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 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.

Sign in / Sign up

Export Citation Format

Share Document