scholarly journals The Role of Natural Products in Targeting Cardiovascular Diseases via Nrf2 Pathway: Novel Molecular Mechanisms and Therapeutic Approaches

2018 ◽  
Vol 9 ◽  
Author(s):  
Bee Kee Ooi ◽  
Kok-Gan Chan ◽  
Bey Hing Goh ◽  
Wei Hsum Yap
Keyword(s):  
Natural Products ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Therapeutic Approaches ◽  
Nrf2 Pathway

scholarly journals Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 979 ◽  
Author(s):  
Valeria De Pasquale ◽  
Anna Moles ◽  
Luigi Michele Pavone
Keyword(s):  
Molecular Mechanisms ◽  
Protein Processing ◽  
Lysosomal Storage ◽  
Therapeutic Approaches ◽  
Kidney Dysfunction ◽  
Nuclear Membranes ◽  
Intracellular Organelles ◽  
Primary Focus ◽  
Storage Disorders

Cathepsins (CTSs) are ubiquitously expressed proteases normally found in the endolysosomal compartment where they mediate protein degradation and turnover. However, CTSs are also found in the cytoplasm, nucleus, and extracellular matrix where they actively participate in cell signaling, protein processing, and trafficking through the plasma and nuclear membranes and between intracellular organelles. Dysregulation in CTS expression and/or activity disrupts cellular homeostasis, thus contributing to many human diseases, including inflammatory and cardiovascular diseases, neurodegenerative disorders, diabetes, obesity, cancer, kidney dysfunction, and others. This review aimed to highlight the involvement of CTSs in inherited lysosomal storage disorders, with a primary focus to the emerging evidence on the role of CTSs in the pathophysiology of Mucopolysaccharidoses (MPSs). These latter diseases are characterized by severe neurological, skeletal and cardiovascular phenotypes, and no effective cure exists to date. The advance in the knowledge of the molecular mechanisms underlying the activity of CTSs in MPSs may open a new challenge for the development of novel therapeutic approaches for the cure of such intractable diseases.

scholarly journals Insight into Salivary Gland Aquaporins

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1547 ◽  
Author(s):  
Claudia D’Agostino ◽  
Osama A. Elkashty ◽  
Clara Chivasso ◽  
Jason Perret ◽  
Simon D. Tran ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Physiological Role ◽  
Main Role ◽  
Osmotic Gradient ◽  
Therapeutic Approaches ◽  
Potential Therapeutic Target ◽  
Transmembrane Channel ◽  
Saliva Secretion ◽  
Insight Into

The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren’s syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia.

scholarly journals Therapeutic Approaches and Role of ncRNAs in Cardiovascular Disorders and Insulin Resistance

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Kalupahana Irushi Pamodya Liyanage ◽  
Gamage Upeksha Ganegoda
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Cardiovascular Diseases ◽  
Gene Expression Regulation ◽  
Therapeutic Approaches ◽  
Gene Expressions ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Regulatory Functions

Diseases resulting from alterations in gene expressions through mutations in the genes or through changes in the gene expression regulation could be identified through the analysis of RNA expressions. ncRNAs play a significant role in regulation of the gene expression by controlling the expression levels of the coding RNAs and other cellular processes. Discoveries have shown that the human genome is encoded with sequences responsible for the transcription of thousands of ncRNAs. Even though the studies conducted on ncRNAs are still at initial stages, facts established so far display biomarkers that confirm their relationship with certain diseases such as cancers, cardiovascular diseases, and insulin resistance. These studies have been facilitated with high throughput modern sequencing techniques such as microarrays and RNA sequencing. The data obtained through the above analysis are processed with the aid of existing databases, to deduce conclusions on different diagnostic biomarkers and therapeutic targets for specific diseases. This review focuses on the association of ncRNAs in disease prediction, focusing mainly on cardiovascular diseases and disorders caused by insulin resistance. The report also analyzes regulatory functions of ncRNAs and novel approaches used in disease therapeutics.

scholarly journals The Role of Oxidative Stress in Cardiovascular Aging and Cardiovascular Diseases

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 60
Author(s):  
Carmine Izzo ◽  
Paolo Vitillo ◽  
Paola Di Pietro ◽  
Valeria Visco ◽  
Andrea Strianese ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Stress Theory ◽  
Age Related ◽  
Theory Of Aging ◽  
Cardiovascular Aging ◽  
Primary Risk Factor ◽  
Structure And Functions

Aging can be seen as process characterized by accumulation of oxidative stress induced damage. Oxidative stress derives from different endogenous and exogenous processes, all of which ultimately lead to progressive loss in tissue and organ structure and functions. The oxidative stress theory of aging expresses itself in age-related diseases. Aging is in fact a primary risk factor for many diseases and in particular for cardiovascular diseases and its derived morbidity and mortality. Here we highlight the role of oxidative stress in age-related cardiovascular aging and diseases. We take into consideration the molecular mechanisms, the structural and functional alterations, and the diseases accompanied to the cardiovascular aging process.

scholarly journals The Role of Histone Acetylation-/Methylation-Mediated Apoptotic Gene Regulation in Hepatocellular Carcinoma

2020 ◽  
Vol 21 (23) ◽  
pp. 8894
Author(s):  
Pradeep Kumar Rajan ◽  
Utibe-Abasi Udoh ◽  
Juan D. Sanabria ◽  
Moumita Banerjee ◽  
Gary Smith ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Histone Modification ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Epigenetic Alterations ◽  
Therapeutic Approaches ◽  
Nuclear Changes ◽  
New Perspective ◽  
Effective Diagnosis

Epigenetics, an inheritable phenomenon, which influences the expression of gene without altering the DNA sequence, offers a new perspective on the pathogenesis of hepatocellular carcinoma (HCC). Nonalcoholic steatohepatitis (NASH) is projected to account for a significant share of HCC incidence due to the growing prevalence of various metabolic disorders. One of the major molecular mechanisms involved in epigenetic regulation, post-translational histone modification seems to coordinate various aspects of NASH which will further progress to HCC. Mounting evidence suggests that the orchestrated events of cellular and nuclear changes during apoptosis can be regulated by histone modifications. This review focuses on the current advances in the study of acetylation-/methylation-mediated histone modification in apoptosis and the implication of these epigenetic regulations in HCC. The reversibility of epigenetic alterations and the agents that can target these alterations offers novel therapeutic approaches and strategies for drug development. Further molecular mechanistic studies are required to enhance information governing these epigenetic modulators, which will facilitate the design of more effective diagnosis and treatment options.

scholarly journals Galectin-3 in Cardiovascular Diseases

2020 ◽  
Vol 21 (23) ◽  
pp. 9232
Author(s):  
Valeria Blanda ◽  
Umberto Marcello Bracale ◽  
Maria Donata Di Taranto ◽  
Giuliana Fortunato
Keyword(s):  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Cellular Adhesion ◽  
Cellular Growth ◽  
Cardiac Inflammation ◽  
Galectin 3 ◽  
Diagnostic Applications

Galectin-3 (Gal-3) is a β-galactoside-binding protein belonging to the lectin family with pleiotropic regulatory activities and several physiological cellular functions, such as cellular growth, proliferation, apoptosis, differentiation, cellular adhesion, and tissue repair. Inflammation, tissue fibrosis and angiogenesis are the main processes in which Gal-3 is involved. It is implicated in the pathogenesis of several diseases, including organ fibrosis, chronic inflammation, cancer, atherosclerosis and other cardiovascular diseases (CVDs). This review aims to explore the connections of Gal-3 with cardiovascular diseases since they represent a major cause of morbidity and mortality. We herein discuss the evidence on the pro-inflammatory role of Gal-3 in the atherogenic process as well as the association with plaque features linked to lesion stability. We report the biological role and molecular mechanisms of Gal-3 in other CVDs, highlighting its involvement in the development of cardiac fibrosis and impaired myocardium remodelling, resulting in heart failure and atrial fibrillation. The role of Gal-3 as a prognostic marker of heart failure is described together with possible diagnostic applications to other CVDs. Finally, we report the tentative use of Gal-3 inhibition as a therapeutic approach to prevent cardiac inflammation and fibrosis.

scholarly journals The Role of Androgen Receptor Signaling in Ovarian Cancer

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 176 ◽  
Author(s):  
Taichi Mizushima ◽  
Hiroshi Miyamoto
Keyword(s):  
Ovarian Cancer ◽  
Androgen Receptor ◽  
Molecular Mechanisms ◽  
Receptor Activation ◽  
Receptor Signaling ◽  
Therapeutic Approaches ◽  
Androgen Receptor Signaling ◽  
Ovarian Carcinogenesis ◽  
Androgen Receptor Activity

Emerging evidence has suggested that androgen receptor signaling plays an important role in ovarian cancer outgrowth. Specifically, androgen receptor activation appears to be associated with increased risks of developing ovarian cancer and inducing tumor progression. However, conflicting findings have also been reported. This review summarizes and discusses the available data indicating the involvement of androgens as well as androgen receptor and related signals in ovarian carcinogenesis and cancer growth. Although the underlying molecular mechanisms for androgen receptor functions in ovarian cancer remain far from being fully understood, current observations may offer effective chemopreventive and therapeutic approaches, via modulation of androgen receptor activity, against ovarian cancer. Indeed, several clinical trials have been conducted to determine the efficacy of androgen deprivation therapy in patients with ovarian cancer.

scholarly journals Nitric Oxide: Exploring the Contextual Link with Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Nicholas Asiimwe ◽  
Seung Geun Yeo ◽  
Min-Sik Kim ◽  
Junyang Jung ◽  
Na Young Jeong
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
The Body ◽  
Bioactive Molecules ◽  
Therapeutic Approaches ◽  
Cellular Debris ◽  
And Oxidative Stress ◽  
Proinflammatory Factors

Neuronal inflammation is a systematically organized physiological step often triggered to counteract an invading pathogen or to rid the body of damaged and/or dead cellular debris. At the crux of this inflammatory response is the deployment of nonneuronal cells: microglia, astrocytes, and blood-derived macrophages. Glial cells secrete a host of bioactive molecules, which include proinflammatory factors and nitric oxide (NO). From immunomodulation to neuromodulation, NO is a renowned modulator of vast physiological systems. It essentially mediates these physiological effects by interacting with cyclic GMP (cGMP) leading to the regulation of intracellular calcium ions. NO regulates the release of proinflammatory molecules, interacts with ROS leading to the formation of reactive nitrogen species (RNS), and targets vital organelles such as mitochondria, ultimately causing cellular death, a hallmark of many neurodegenerative diseases. AD is an enervating neurodegenerative disorder with an obscure etiology. Because of accumulating experimental data continually highlighting the role of NO in neuroinflammation and AD progression, we explore the most recent data to highlight in detail newly investigated molecular mechanisms in which NO becomes relevant in neuronal inflammation and oxidative stress-associated neurodegeneration in the CNS as well as lay down up-to-date knowledge regarding therapeutic approaches targeting NO.

Two Sides of the Same Coin: Wnt Signaling in Neurodegeneration and Neuro-Oncology

2005 ◽  
Vol 25 (5-6) ◽  
pp. 309-327 ◽  
Author(s):  
A. Caricasole ◽  
A. Bakker ◽  
A. Copani ◽  
F. Nicoletti ◽  
G. Gaviraghi ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Molecular Mechanisms ◽  
Signal Transduction Pathways ◽  
Common Theme ◽  
Therapeutic Approaches ◽  
Recent Developments ◽  
Intracellular Signal ◽  
Canonical Wnt ◽  
Two Sides

Wnts function through the activation of at least three intracellular signal transduction pathways, of which the canonical β-catenin mediated pathway is the best understood. Aberrant canonical Wnt signaling has been involved in both neurodegeneration and cancer. An impairment of Wnt signals appears to be associated with aspects of neurodegenerative pathologies while overactivation of Wnt signaling is a common theme in several types of human tumors. Therefore, although therapeutic approaches aimed at modulating Wnt signaling in neurodegenerative and hyperproliferative diseases might impinge on the same molecular mechanisms, different pharmacological outcomes are required. Here we review recent developments on the understanding of the role of Wnt signaling in Alzheimer's disease and CNS tumors, and identify possible avenues for therapeutic intervention within a complex and multi-faceted signaling pathway.

Mass spectrometry for the evaluation of cardiovascular diseases based on proteomics and lipidomics

2011 ◽  
Vol 106 (07) ◽  
pp. 20-33 ◽  
Author(s):  
Aurélien Thomas ◽  
Sébastien Lenglet ◽  
Pierre Chaurand ◽  
Julien Déglon ◽  
Patrice Mangin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Medical Community ◽  
Cardiovascular Disorders ◽  
Recent Developments ◽  
Novel Biomarkers ◽  
Analytical Platforms ◽  
Broad Interest

SummaryThe identification and quantification of proteins and lipids is of major importance for the diagnosis, prognosis and understanding of the molecular mechanisms involved in disease development. Owing to its selectivity and sensitivity, mass spectrometry has become a key technique in analytical platforms for proteomic and lipidomic investigations. Using this technique, many strategies have been developed based on unbiased or targeted approaches to highlight or monitor molecules of interest from biomatrices. Although these approaches have largely been employed in cancer research, this type of investigation has been met by a growing interest in the field of cardiovascular disorders, potentially leading to the discovery of novel biomarkers and the development of new therapies. In this paper, we will review the different mass spectrometry- based proteomic and lipidomic strategies applied in cardiovascular diseases, especially atherosclerosis. Particular attention will be given to recent developments and the role of bioinformatics in data treatment. This review will be of broad interest to the medical community by providing a tutorial of how mass spectrometric strategies can support clinical trials.

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