Mini Mental State

EVOLUTION: Of Mice . . .

MicroRNAs (miRNAs) are a class of small noncoding RNAs, which function in posttranscriptional regulation of gene expression. They are powerful regulators of various cellular activities including cell growth, differentiation, development, and apoptosis. They have been linked to many diseases, and currently miRNA-mediated clinical trial has shown promising results for treatment of cancer and viral infection. This review provides an overview and update on miRNAs biogenesis, regulation of miRNAs expression, their biological functions, and role of miRNAs in epigenetics and cell-cell communication. In addition, alteration of miRNAs following exercise, their association with diseases, and therapeutic potential will be explained. Finally, miRNA bioinformatics tools and conventional methods for miRNA detection and quantification will be discussed.

An overview of microRNAs: Biology, functions, therapeutics, and analysis methods

Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzyme (IDE)s such as neprilysin or insulin IDE. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action.

https://cyberleninka.org/article/n/324193.pdf

Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases

Cardiovascular Benefits and Diabetes Risks of Statin Therapy in Primary Prevention: An Analysis From the JUPITER Trial

Hypoglycemia represents a dark and tormented side of diabetes mellitus therapy. Patients treated with insulin or drug inducing hypoglycemia, consider hypoglycemia as a harmful element, which leads to their resistance and lack of acceptance of the pathology and relative therapies. Severe hypoglycemia, in itself, is a risk for patients and relatives. The possibility to have novel strategies and scientific knowledge concerning hypoglycemia could represent an enormous benefit. Novel available glucagon formulations, even now, allow clinicians to deal with hypoglycemia differently with respect to past years. Novel scientific evidence leads to advances concerning physiopathological mechanisms that regulated glycemic homeostasis. In this review, we will try to show some of the important aspects of this field.

Glucagon as a Therapeutic Approach to Severe Hypoglycemia: After 100 Years, Is It Still the Antidote of Insulin?

Glycemic homeostasis is an essential mechanism for the proper working of an organism. However, balance in blood lipid and protein levels also plays an important role. The discovery of the hormone insulin and the description of its function for glycemic control made fundamental scientific progress in this field. However, since then our view of the problem has been deeply influenced only in terms of glucose and insulin (in an insulin-centric and glucose-centric way). Based on recent scientific discoveries, a fine and sophisticated network of hormonal and metabolic interactions, involving almost every apparatus and tissue of the human body, has been theorized. Efficient metabolic homeostasis is founded on these intricate interactions. Although it is still not fully defined, this complex network can undergo alterations that lead to metabolic disorders such as diabetes mellitus (DM). The endocrine pancreas plays a crucial role in the metabolic balance of an organism, but insulin is just one of the elements involved and each single pancreatic islet hormone is worthy of our concern. Moreover, pancreatic hormones need to be considered in a general view, concerning both their systemic function as direct mediators and as hormones, which, in turn, are regulated by other hormones or other substances. This more complex scenario should be taken into account for a better understanding of the pathophysiology and the therapeutic algorithms of DM. As a consequence, improvements in modern medicine could help to contemplate this new perspective. This review is focused on some aspects of gutpancreas interaction, aiming to integrate this synergy into a wider context involving other organs and tissues.

/pdf/the-entero-insular-axis-a-journey-in-the-physiopathology-of-3xc60vupls.pdf

The entero-insular axis: a journey in the physiopathology of diabetes

Alterations of glucose homeostasis are associated with subclinical vascular damage; however, the role of platelet reactivity in this process has not been fully investigated. In this cross-sectional study, we evaluated the correlation between markers of platelet reactivity and inflammation and markers of vascular disease in subjects with prediabetes. Markers of platelet reactivity such as 11-dehydro-thromboxane B2 urinary levels (11-dh-TXB2) and mean platelet volume (MPV) and inflammatory indexes such as platelet-to-lymphocyte ratio (PLR) were evaluated in subjects with prediabetes (n = 48), new-onset type 2 diabetes (NODM, n = 60) and controls (n = 62). Furthermore, we assessed the cardiovascular risk profile of the study population with arterial stiffness and quality intima–media thickness (qIMT). Subjects with prediabetes and NODM exhibited higher 11-dh-TXB2 urinary levels and MPV and a proinflammatory profile with an increased PLR, high-sensitivity C-reactive protein, ferritin and fibrinogen. Furthermore, after multiple regression analyses, we found that urinary 11-dh-TXB2 was one of the major determinants of IMT and arterial stiffness parameters. In conclusion, subjects with prediabetes exhibit increased platelet reactivity as well as a proinflammatory profile. Furthermore, this condition is associated with early markers of cardiovascular disease.

/pdf/increased-platelet-reactivity-and-proinflammatory-profile-2n5joa2n.pdf

Increased Platelet Reactivity and Proinflammatory Profile Are Associated with Intima–Media Thickness and Arterial Stiffness in Prediabetes

Metformin, a molecule belonging to the biguanide family, represents one of the most commonly prescribed medications for the treatment of diabetes mellitus in the world. Over the sixty years during which it has been used, many benefits have been described, which are not limited to the treatment of diabetes mellitus. However, since metformin is similar to other members of the same drug family, there is still much concern regarding the risk of lactic acidosis. This article aims to highlight the correlation between the use of metformin and the onset of renal damage or lactic acidosis. Metformin-associated lactic acidosis exists; however, it is rare. The appropriate use of the drug, under safe conditions, induces benefits without risks.

https://www.mdpi.com/1422-0067/23/15/8320/pdf?version=1658990621

Metformin: When Should We Fear Lactic Acidosis?

Intestinal cell dysfunctions involved in obesity and associated diabetes could be correlated with impaired intestinal cell development. To date, the molecular mechanisms underlying these dysfunctions have been poorly investigated because of the lack of a good model for studying obesity. The main aim of this study was to investigate the effects of lipotoxicity on intestinal cell differentiation in small intestinal organoid platforms, which are used to analyze the regulation of cell differentiation. Mouse intestinal organoids were grown in the presence/absence of high palmitate concentrations (0.5 mM) for 48 h to simulate lipotoxicity. Palmitate treatment altered the expression of markers involved in the differentiation of enterocytes and goblet cells in the early (Hes1) and late (Muc2) phases of their development, respectively, and it modified enterocytes and goblet cell numbers. Furthermore, the expression of enteroendocrine cell progenitors (Ngn3) and I cells (CCK) markers was also impaired, as well as CCK-positive cell numbers and CCK secretion. Our data indicate, for the first time, that lipotoxicity simultaneously influences the differentiation of specific intestinal cell types in the gut: enterocytes, goblet cells and CCK cells. Through this study, we identified novel targets associated with molecular mechanisms affected by lipotoxicity that could be important for obesity and diabetes therapy.

https://www.mdpi.com/1422-0067/23/14/7751/pdf?version=1657785194

Stefania Di Mauro

Papers

Glucagon as a Therapeutic Approach to Severe Hypoglycemia: After 100 Years, Is It Still the Antidote of Insulin?

The entero-insular axis: a journey in the physiopathology of diabetes

Increased Platelet Reactivity and Proinflammatory Profile Are Associated with Intima–Media Thickness and Arterial Stiffness in Prediabetes

Metformin: When Should We Fear Lactic Acidosis?

Molecular Effects of Chronic Exposure to Palmitate in Intestinal Organoids: A New Model to Study Obesity and Diabetes