The Therapeutic Potential of Anthocyanins : Current Approaches Based on Their Molecular Mechanism of Action

Anthocyanins are natural phenolic pigments with biological activity. They are well-known to have potent antioxidant and antiinflammatory activity, which explains the various biological effects reported for these substances suggesting their antidiabetic and anticancer activities, and their role in cardiovascular and neuroprotective prevention. This review aims to comprehensively analyze different studies performed on this class of compounds, their bioavailability and their therapeutic potential. An in-depth look in preclinical, in vitro and in vivo, and clinical studies indicates the preventive effects of anthocyanins on cardioprotection, neuroprotection, antiobesity as well as their antidiabetes and anticancer effects

Pharmacological Properties of Chalcones: A Review of Preclinical Including Molecular Mechanisms and Clinical Evidence

Chalcones are among the leading bioactive flavonoids with a therapeutic potential implicated to an array of bioactivities investigated by a series of preclinical and clinical studies. In this article, different scientific databases were searched to retrieve studies depicting the biological activities of chalcones and their derivatives. This review comprehensively describes preclinical studies on chalcones and their derivatives describing their immense significance as antidiabetic, anticancer, anti-inflammatory, antimicrobial, antioxidant, antiparasitic, psychoactive, and neuroprotective agents. Besides, clinical trials revealed their use in the treatment of chronic venous insufficiency, skin conditions, and cancer. Bioavailability studies on chalcones and derivatives indicate possible hindrance and improvement in relation to its nutraceutical and pharmaceutical applications. Multifaceted and complex underlying mechanisms of chalcone actions demonstrated their ability to modulate a number of cancer cell lines, to inhibit a number of pathological microorganisms and parasites, and to control a number of signaling molecules and cascades related to disease modification. Clinical studies on chalcones revealed general absence of adverse effects besides reducing the clinical signs and symptoms with decent bioavailability. Further studies are needed to elucidate their structure activity, toxicity concerns, cellular basis of mode of action, and interactions with other molecules

A new threat from an old enemy: Re-emergence of coronavirus (Review)

The new outbreak of coronavirus from December 2019 has brought attention to an old viral enemy and has raised concerns as to the ability of current protection measures and the healthcare system to handle such a threat. It has been known since the 1960s that coronaviruses can cause respiratory infections in humans; however, their epidemic potential was understood only during the past two decades. © 2020 Spandidos Publications. All rights reserved

A mixture of routinely encountered xenobiotics induces both redox adaptations and perturbations in blood and tissues of rats after a long-term low-dose exposure regimen: The time and dose issue

Exposure of humans to xenobiotic mixtures is a continuous state during their everyday routine. However, the majority of toxicological studies assess the in vivo effects of individual substances rather than mixtures. Therefore, our main objective was to evaluate the impact of the 12- and 18-month exposure of rats to a mixture containing 13 pesticides, food, and life-style additives in three dosage levels (i.e. 0.0025 × NOAEL, 0.01 × NOAEL, and 0.05 × NOAEL), on redox biomarkers in blood and tissues. Our results indicate that the exposure to the mixture induces physiological adaptations by enhancing the blood antioxidant mechanism (i.e., increased glutathione, catalase and total antioxidant capacity and decreased protein carbonyls and TBARS) at 12 months of exposure. On the contrary, exposure to the 0.05 × NOAEL dose for 18 months induces significant perturbations in blood and tissue redox profile (i.e., increased carbonyls and TBARS). This study simulates a scenario of real-life risk exposure to mixtures of xenobiotics through a long-term low-dose administration regimen in rats. The results obtained could support, at least in part, the necessity of introducing testing of combined stimuli at reference doses and long term for the evaluation of the risk from exposure to chemicals. © 2019 Elsevier B.V

Unraveling the roles of Vitamin D status and melanin during COVID-19 (Review)

As the coronavirus disease 2019 (COVID- 19) continues to spread worldwide, it has become evident that the morbidity and mortality rates clearly vary across nations. Although several factors may account for this disparity, striking differences within and between populations indicate that ethnicity might impact COVID-19 clinical outcomes, reflecting the 'color of disease'. Therefore, the role of key biological variables that could interplay with viral spreading and severity indices has attracted increasing attention, particularly among non-C aucasian populations. Although the links between vitamin D status and the incidence and severity of COVID-19 remain elusive, several lines of emerging evidence suggest that vitamin D signaling, targeting several immune-mediated pathways, may offer potential benefits at different stages of SARS-CoV-2 infection. Given that the vitamin D status is modulated by several intrinsic and extrinsic factors, including skin type (pigmentation), melanin polymers may also play a role in variable COVID- 19 outcomes among diverse population settings. Moreover, apart from the well-known limiting effects of melanin on the endogenous production of vitamin D, the potential crosstalk between the pigmentary and immune system may also require special attention concerning the current pandemic. The present review article aimed to shed light on a range of mostly overlooked host factors, such as vitamin D status and melanin pigments, that may influence the course and outcome of COVID- 19. © This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License

A Mixture of Endocrine Disruptors and the Pesticide Roundup® Induce Oxidative Stress in Rabbit Liver When Administered under the Long-Term Low-Dose Regimen: Reinforcing the Notion of Real-Life Risk Simulation

Humans are exposed to xenobiotic mixtures daily through the long-term, low-dose regimen. Investigations designed to simulate this exposure profile approach the real-life risk simulation (RLRS) idea of modern toxicology. The purpose of the present study was to investigate the effects of 12-month exposure of New Zealand rabbits to a xenobiotic mixture comprising seven endocrine disruptors (EDs), which are chemical substances raising great concerns for human health, as well as the herbicide glyphosate, and its commercial formulation Roundup®, on blood and tissues redox status. It is reported herein that at the systemic level, the administration of the EDs mixture induced perturbations of blood redox homeostasis at 3 months, whereas at 6 and 12 months, it activated redox adaptations. Contrariwise, exposure to glyphosate and Roundup®, individually, caused mainly disturbances of blood redox equilibrium. At the tissue level, particularly in the liver, the administration of both the EDs mixture and Roundup® induced oxidative stress, whereas glyphosate did not affect it. The RLRS notion appears to be confirmed through these findings. Indeed, the administration of the EDs mixture and Roundup®, under the long-term, low-dose regimen, elicited detrimental effects on the redox status of the liver, a crucial tissue with a valuable biological role in the detoxification of organisms from xenobiotics. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Environmental exposure to organophosphorus nerve agents

Exposure to organophosphorus nerve agents, the most deadly chemical warfare agents, is possible in a variety of situations, such as destruction of chemical warfare agents, terrorist attacks, armed conflicts or accidents in research laboratories and storage facilities. Hundreds of thousands of tons of chemical munitions were disposed of at the sea in the post World War II period, with European, Russian, Japanese and US coasts being the most affected. Sulfur mustard, Lewisite and nerve agents appear to be the most frequently chemical warfare agents disposed of at the sea. Addressing the overall environmental risk, it has been one of the priorities of the world community since that time. Aside from confirming exposure to nerve agents in the alleged use for forensic purposes, the detection and identification of biological markers of exposure are also needed for the diagnosis and treatment of poisoning, in addition to occupational health monitoring for specific profiles of workers. When estimating detrimental effects of acute or potential chronic sub-lethal doses of organophosphorus nerve agents, released accidentally or intentionally into the environment, it is necessary to understand the wide spectra of physical, chemical and toxicological properties of these agents, and predict their ultimate fate in environmental systems. © 2017 Elsevier B.V

Chronic exposure to methylmercury induces puncta formation in cephalic dopaminergic neurons in Caenorhabditis elegans

The neurotransmitter dopamine is a neuromodulator in the positive and negative regulation of brain circuits. Dopamine insufficiency or overload has been implicated in aberrant activities of neural circuits that play key roles in the pathogenesis of neurological and psychiatric diseases. Dopaminergic neurons are vulnerable to environmental insults. The neurotoxin methylmercury (MeHg) produces dopaminergic neuron damage in rodent as well as in Caenorhabditis elegans (C. elegans) models. Previous studies have demonstrated the utility of C. elegans as an alternative and complementary experimental model in dissecting out mechanism of MeHg-induced dopaminergic neurodegeneration. However, a sensitive pathological change that marks early events in neurodegeneration induced by environmental level of MeHg, is still lacking. By establishing a chronic exposure C. elegans model, for the first time, we have shown the propensity of MeHg (5 μM, 10 days) to induce bright puncta of dat-1::mCherry aggreagtes in the dendrites of cephalic (2 CEPs) dopaminergic neurons in a dose- and time-dependent manner, while these changes were not found in other dopaminergic neurons: anterior deirids (2 ADEs) and posterior deirids (2 PDEs), cholinergic neurons (2 AIYs) or glutamatergic neurons (2 PVDs). The bright puncta appear as an aggregation of mCherry proteins accumulating in dendrites. Further staining shows that the puncta were not inclusions in lysosome, or amyloid protein aggregates. In addition, features of the puncta including enlarged sphere shape (0.5–2 μm diameters), bright and accompanying with the shrinkage of the dendrite suggest that the puncta are likely composed of homologous mCherry molecules packaged at the dendritic site for exportation. Moreover, in the glutathione S-transferase 4 (gst-4) transcriptional reporter strain and RT-PCR assay, the expression levels of gst-4 and tubulins (tba-1 and tba-2) genes were not significantly modified under this chronic exposure paradigm, but gst-4 did show significant changes in an one day exposure paradigm. Collectively, these results suggest that CEP dopaminergic neurons are a sensitive target of MeHg, and the current exposure paradigm could be used as a model to investigate mechanism of dopaminergic neurotoxicity. © 2020 Elsevier B.V

Back to basics in COVID-19: Antigens and antibodies—Completing the puzzle

The outbreak of the coronavirus disease 2019 (COVID-19) has gathered 1 year of scientific/clinical information. This informational asset should be thoroughly and wisely used in the coming year colliding in a global task force to control this infection. Epidemiology of this infection shows that the available estimates of SARS-CoV-2 infection prevalence largely depended on the availability of molecular testing and the extent of tested population. Within molecular diagnosis, the viability and infectiousness of the virus in the tested samples should be further investigated. Moreover, SARS-CoV-2 has a genetic normal evolution that is a dynamic process. The immune system participates to the counterattack of the viral infection by pathogen elimination, cellular homoeostasis, tissue repair and generation of memory cells that would be reactivated upon a second encounter with the same virus. In all these stages, we still have knowledge to be gathered regarding antibody persistence, protective effects and immunological memory. Moreover, information regarding the intense pro-inflammatory action in severe cases still lacks and this is important in stratifying patients for difficult to treat cases. Without being exhaustive, the review will cover these important issues to be acknowledged to further advance in the battle against the current pandemia. © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd