The Intrinsic Virtues of EGCG, an Extremely Good Cell Guardian, on Prevention and Treatment of Diabesity Complications

The pandemic proportion of diabesity—a combination of obesity and diabetes—sets a worldwide health issue. Experimental and clinical studies have progressively reinforced the pioneering epidemiological observation of an inverse relationship between consumption of polyphenol-rich nutraceutical agents and mortality from cardiovascular and metabolic diseases. With chemical identification of epigallocatechin-3-gallate (EGCG) as the most abundant catechin of green tea, a number of cellular and molecular mechanisms underlying the activities of this unique catechin have been proposed. Favorable effects of EGCG have been initially attributed to its scavenging effects on free radicals, inhibition of ROS-generating mechanisms and upregulation of antioxidant enzymes. Biologic actions of EGCG are concentration-dependent and under certain conditions EGCG may exert pro-oxidant activities, including generation of free radicals. The discovery of 67-kDa laminin as potential EGCG membrane target has broaden the likelihood that EGCG may function not only because of its highly reactive nature, but also via receptor-mediated activation of multiple signaling pathways involved in cell proliferation, angiogenesis and apoptosis. Finally, by acting as epigenetic modulator of DNA methylation and chromatin remodeling, EGCG may alter gene expression and modify miRNA activities. Despite unceasing research providing detailed insights, ECGC composite activities are still not completely understood. This review summarizes the most recent evidence on molecular mechanisms by which EGCG may activate signal transduction pathways, regulate transcription factors or promote epigenetic changes that may contribute to prevent pathologic processes involved in diabesity and its cardiovascular complication

The war against bacteria, from the past to present and beyond

Introduction: : The human defense against microorganisms dates back to the ancient civilizations, with attempts to use substances from vegetal, animal or inorganic origin to fight infections. Today, the emerging threat of multidrug-resistant bacteria highlights the consequences of antibiotics inappropriate use, and the urgent need of novel effective molecules. Methods and materials: We extensively researched on more recent data within the databases PubMed, Medline, Web of Science, Elsevier's EMBASE, Cochrane Review for the modern pharmacology in a period ranging from 1987 until 2021. Furthermore, the historical evolution was defined through a detailed analysis of past studies on the significance of medical applications in the ancient therapeutic field. Areas covered: To examine history of antibiotics development and discovery, the most relevant biochemical aspects of their mode of action, and the biomolecular mechanisms conferring bacterial resistance to antibiotics. Expert opinion: : The list of pathogens showing low sensitivity or full resistance to most currently available antibiotics is growing worldwide. Long after the "golden age" of antibiotic discovery, the most novel molecules should be carefully reserved to treat serious bacterial infections of susceptible bacteria. A correct diagnostic and therapeutic procedure can slow down the spreading of nosocomial and community infections sustained by multidrug-resistant bacterial strains

Epigallocatechin Gallate, a Green Tea Polyphenol, Mediates NO-dependent Vasodilation Using Signaling Pathways in Vascular Endothelium Requiring Reactive Oxygen Species and Fyn

Green tea consumption is associated with reduced cardiovascular mortality in some epidemiological studies. Epigallocatechin gallate (EGCG), a bioactive polyphenol in green tea, mimics metabolic actions of insulin to inhibit gluconeogenesis in hepatocytes. Because signaling pathways regulating metabolic and vasodilator actions of insulin are shared in common, we hypothesized that EGCG may also have vasodilator actions to stimulate production of nitric oxide (NO) from endothelial cells. Acute intra-arterial administration of EGCG to mesenteric vascular beds isolated ex vivo from WKY rats caused dose-dependent vasorelaxation. This was inhibitable by L-NAME (NO synthase inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), or PP2 (Src family kinase inhibitor). Treatment of bovine aortic endothelial cells (BAEC) with EGCG (50 microm) acutely stimulated production of NO (assessed with NO-specific fluorescent dye DAF-2) that was inhibitable by l-NAME, wortmannin, or PP2. Stimulation of BAEC with EGCG also resulted in dose- and time-dependent phosphorylation of eNOS that was inhibitable by wortmannin or PP2 (but not by MEK inhibitor PD98059). Specific knockdown of Fyn (but not Src) with small interfering RNA inhibited both EGCG-stimulated phosphorylation of Akt and eNOS as well as production of NO in BAEC. Treatment of BAEC with EGCG generated intracellular H(2)O(2) (assessed with H(2)O(2)-specific fluorescent dye CM-H(2)DCF-DA), whereas treatment with N-acetylcysteine inhibited EGCG-stimulated phosphorylation of Fyn, Akt, and eNOS. We conclude that EGCG has endothelial-dependent vasodilator actions mediated by intracellular signaling pathways requiring reactive oxygen species and Fyn that lead to activation of phosphatidylinositol 3-kinase, Akt, and eNOS. This mechanism may explain, in part, beneficial vascular and metabolic health effects of green tea consumption

Release of {DNA} from Dermanyssus gallinae during the Biting Process

: Dermanyssus gallinae is a hematophagous ectoparasitic mite that usually infests poultry, but is also known for occasionally attacking other animals and humans. It represents a major problem for poultry systems all over the world, with detrimental effects for both production and animal welfare. Despite the significance of D. gallinae, very little is known about the biting process to date. Therefore, this study has aimed to verify if mite DNA is injected into the host skin during the blood meal. Mite DNA has been detected by seminested PCR from infested chicken skin and quantified by real-time PCR. Furthermore, its localization within the host tissue has been checked by fluorescent in situ hybridization. Results showed that a very little amount of D. gallinae DNA can be released by mites, suggesting that the latter do not introduce whole or partially destroyed cells into the host, but rather it injects traces of nucleic acids, possibly together with merocrine secretions

Release of DNA from Dermanyssus gallinae during the Biting Process

none10noDermanyssus gallinae is a hematophagous ectoparasitic mite that usually infests poultry, but is also known for occasionally attacking other animals and humans. It represents a major problem for poultry systems all over the world, with detrimental effects for both production and animal welfare. Despite the significance of D. gallinae, very little is known about the biting process to date. Therefore, this study has aimed to verify if mite DNA is injected into the host skin during the blood meal. Mite DNA has been detected by seminested PCR from infested chicken skin and quantified by real-time PCR. Furthermore, its localization within the host tissue has been checked by fluorescent in situ hybridization. Results showed that a very little amount of D. gallinae DNA can be released by mites, suggesting that the latter do not introduce whole or partially destroyed cells into the host, but rather it injects traces of nucleic acids, possibly together with merocrine secretions.Pugliese, Nicola; Raele, Donato Antonio; Schiavone, Antonella; Cafiero, Maria Assunta; Potenza, Lucia; Samarelli, Rossella; Circella, Elena; Vasco, Ilaria; Pennuzzi, Germana; Camarda, AntonioPugliese, Nicola; Raele, Donato Antonio; Schiavone, Antonella; Cafiero, Maria Assunta; Potenza, Lucia; Samarelli, Rossella; Circella, Elena; Vasco, Ilaria; Pennuzzi, Germana; Camarda, Antoni

Botulinum Neurotoxins (BoNTs) and Their Biological, Pharmacological, and Toxicological Issues: A Scoping Review

Botulinum toxins or neurotoxins (BoNTs) are the most potent neurotoxins known, and are currently extensively studied, not only for their potential lethality, but also for their possible therapeutic and cosmetic uses. Currently, seven types of antigenically distinct toxins are known and characterized, produced by a rod‐shaped bacterium, Clostridium botulinum. Human poisoning by botulism (presenting with severe neuromuscular paralytic disease) is usually caused by toxins A, B, E, and F type. Poisoning from contaminated food preparations is the most common cause of noniatrogenic botulism. The spores are highly resistant to heat but are easily destroyed at 80 °C for thirty minutes. Type A and B toxins are resistant to digestion by the enzymes of the gastrointestinal system. After their entry, BoNTs irreversibly bind to cholinergic nerve endings and block the release of acetylcholine from the synapses. In contrast, in wound botulism, the neurotoxin is instead product by the growth of C.botulium in infected tissues. The contamination by BoNT inhalation does not occur by a natural route but it is certainly the most dangerous. It can be caused by the dispersion of the botulinum toxin in the atmosphere in the form of an aerosol and therefore can be deliberately used for bioterrorist purposes (e.g., during CBRN (chemical, biological, radiological, and nuclear) unconventional events). In addition, BoNTs are currently used to treat a variety of diseases or alleviate their symptoms, such as the onabotulinumtoxinA for migraine attacks and for cosmetic use. Indeed, this paper aims to report on updated knowledge of BoNTs, both their toxicological mechanisms and their pharmacological action

Ruolo del sistema L-Arg/NO nell'iporeattivita del letto mesenterico vascolare di ratto in corso di shock endotossico: effetti modulanti del desametasone e dell'endotelina-1

Dottorato di ricerca in farmacologia clinica e terapia medica. 8. ciclo. A.a. 1992-95. Coordinatore V. CuomoConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Determinants of evolving cardiovascular benefit/risk profile of rosiglitazone during the natural hystory of diabetes

Rosiglitazone is a thiazolidinedione (TZD), a synthetic PPARγ receptor agonist with insulin-sensitizing properties that is used as an anti-diabetic drug. In addition to improving glycemic control through actions in metabolic target tissues, rosiglitazone has numerous biological actions that impact on cardiovascular homeostasis. Some of these actions are helpful (e.g., improving endothelial function) while others are potentially harmful (e.g., promoting fluid retention). Since cardiovascular morbidity and mortality are major endpoints for diabetes, it is essential to understand how the natural history of diabetes alters the net benefits and risks of rosiglitazone therapy. This complex issue is an important determinant of optimal use of rosiglitazone and is critical for understanding cardiovascular safety issues. We give special attention to the effects of rosiglitazone in diabetic patients with stable coronary artery disease (CAD) and the impact of rosiglitazone actions on atherosclerosis and plaque instability. This provides a rational conceptual framework for predicting evolving benefit/risk profiles that inform optimal use of rosiglitazone in the clinical setting and help explaining results of recent large clinical intervention trials where rosiglitazone had disappointing cardiovascular outcomes. Thus, in this review, we describe what is known about the molecular mechanisms of action of rosiglitazone on cardiovascular targets in the context of the evolving pathophysiology of diabetes over its natural history