Ethanol-Induced Cell Damage Can Result in the Development of Oral Tumors

Alcohol consumption is an underestimated risk factor for the development of precancerous lesions in the oral cavity. Although alcohol is a well-accepted recreational drug, 26.4% of all lip and oral cavity cancers worldwide are related to heavy drinking. Molecular mechanisms underlying this carcinogenic effect of ethanol are still under investigation. An important damaging effect comes from the first metabolite of ethanol, being acetaldehyde. Concentrations of acetaldehyde detected in the oral cavity are relatively high due to the metabolization of ethanol by oral microbes. Acetaldehyde can directly damage the DNA by the formation of mutagenic DNA adducts and interstrand crosslinks. Additionally, ethanol is known to affect epigenetic methylation and acetylation patterns, which are important regulators of gene expression. Ethanol-induced hypomethylation can activate the expression of oncogenes which subsequently can result in malignant transformation. The recent identification of ethanol-related mutational signatures emphasizes the role of acetaldehyde in alcohol-associated carcinogenesis. However, not all signatures associated with alcohol intake also relate to acetaldehyde. This finding highlights that there might be other effects of ethanol yet to be discovered.

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Diabetes and Thrombosis: A Central Role for Vascular Oxidative Stress

Antioxidants ◽

10.3390/antiox10050706 ◽

2021 ◽

Vol 10 (5) ◽

pp. 706

Author(s):

Aishwarya R. Vaidya ◽

Nina Wolska ◽

Dina Vara ◽

Reiner K. Mailer ◽

Katrin Schröder ◽

...

Keyword(s):

Diabetes Mellitus ◽

Molecular Mechanisms ◽

Vascular System ◽

Cell Damage ◽

National Health System ◽

Vascular Damage ◽

Circulating Cells ◽

Environmental Causes ◽

Vascular Oxidative Stress

Diabetes mellitus is the fifth most common cause of death worldwide. Due to its chronic nature, diabetes is a debilitating disease for the patient and a relevant cost for the national health system. Type 2 diabetes mellitus is the most common form of diabetes mellitus (90% of cases) and is characteristically multifactorial, with both genetic and environmental causes. Diabetes patients display a significant increase in the risk of developing cardiovascular disease compared to the rest of the population. This is associated with increased blood clotting, which results in circulatory complications and vascular damage. Platelets are circulating cells within the vascular system that contribute to hemostasis. Their increased tendency to activate and form thrombi has been observed in diabetes mellitus patients (i.e., platelet hyperactivity). The oxidative damage of platelets and the function of pro-oxidant enzymes such as the NADPH oxidases appear central to diabetes-dependent platelet hyperactivity. In addition to platelet hyperactivity, endothelial cell damage and alterations of the coagulation response also participate in the vascular damage associated with diabetes. Here, we present an updated interpretation of the molecular mechanisms underlying vascular damage in diabetes, including current therapeutic options for its control.

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The Cardiovascular Phenotype in Fabry Disease: New Findings in the Research Field

International Journal of Molecular Sciences ◽

10.3390/ijms22031331 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1331

Author(s):

Daniela Sorriento ◽

Guido Iaccarino

Keyword(s):

Fabry Disease ◽

Molecular Mechanisms ◽

Cell Damage ◽

Research Field ◽

Cardiac Cell ◽

Lysosomal Storage ◽

Clinical Level ◽

New Findings ◽

Alpha Gene ◽

Alpha Galactosidase

Fabry disease (FD) is a lysosomal storage disorder, depending on defects in alpha-galactosidase A (GAL) activity. At the clinical level, FD shows a high phenotype variability. Among them, cardiovascular dysfunction is often recurrent or, in some cases, is the sole symptom (cardiac variant) representing the leading cause of death in Fabry patients. The existing therapies, besides specific symptomatic treatments, are mainly based on the restoration of GAL activity. Indeed, mutations of the galactosidase alpha gene (GLA) cause a reduction or lack of GAL activity leading to globotriaosylceramide (Gb3) accumulation in several organs. However, several other mechanisms are involved in FD’s development and progression that could become useful targets for therapeutics. This review discusses FD’s cardiovascular phenotype and the last findings on molecular mechanisms that accelerate cardiac cell damage.

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