The recent findings of circulating cell-free tissue specific microRNAs in the systemic circulation and the potential of their use as specific markers of disease highlight the need to make microRNAs testing a routine part of medical care. At the present time, microRNAs are detected by long and laborious techniques such as Northern blot, RT-PCR, and microarrays. The originality of our work consists in performing microRNAs detection through an electrochemical genosensor using a label-free method. We were able to directly detect microRNAs without the need of PCR and a labeling reaction. The test is simple, very fast and ultrasensitive, with a detection limit of 0.1 pmol. Particularly feasible for a routine microRNAs detection in serum and other biological samples, our technical approach would be of great scientific value and become a common method for simple miRNAs routine detection in both clinical and research settings.
Thyroid hormones (TH) are major modulators of energy metabolism and thermogenesis. It is generally believed that 3,5,3'-triiodo-l-thyronine (T3) is the only active form of TH, and that most of its effects are mediated by nuclear T3 receptors, which chiefly affect the transcription of target genes. Some of these genes encode for the proteins involved in energy metabolism. However, a growing volume of evidence now indicates that other iodothyronines may be biologically active. Several mechanisms have been proposed to explain the calorigenic effect of TH, but none has received universal acceptance. Cold acclimation/exposure and altered nutritional status are physiological conditions in which a modulation of energy expenditure is particularly important. TH seem to be deeply involved in this modulation, and this article will review some aspects of their possible influence in these conditions.
The COVID-19 pandemic is the major health crisis of our time. It bears the potential to create devastating social, economic, and political consequences in all the countries it touches. At the same time, it represents a great challenge for the entire scientific community. Indeed, the latter is currently making extraordinary efforts to increase knowledge on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2), and so helps in containing the pandemic and hopefully in eradicating it. The renin-angiotensin-aldosterone system (RAAS) has recently been put on the forefront as the angiotensin-converting enzyme (ACE) 2 is targeted by SARS-CoV 2. In parallel, obesity appears as the main risk factor for severe forms of COVID-19. The RAAS and obesity are closely related, leading to the aggravation of the disease. Here, we focus on the endogenous imbalance of RAAS in obesity.
Glioblastoma multiforme is the most common and aggressive primary brain cancer with only ∼3% of patients surviving more than 3 years from diagnosis. Several mechanisms are involved in drug and radiation resistance to anticancer treatments and among them one of the most important factors is the tumor microenvironment status, characterized by cancer cell hypersecretion of interleukins and cytokines. The aim of our research was the synthesis of a nanocarrier of quercetin combined with temozolomide, to enhance the specificity and efficacy of this anticancer drug commonly used in glioblastoma treatment. The nanohydrogel increased the internalization and cytotoxicity of quercetin in human glioblastoma cells and, when co-delivered with temozolomide, contribute to an improved anticancer effect. The nanohydrogel loaded with quercetin had the ability to recognize CD44 receptor, a brain cancer cell marker, through an energy and caveolae dependent mechanism of internalization. Moreover, nanohydrogel of quercetin was able to reduce significantly IL-8, IL-6, and VEGF production in pro-inflammatory conditions with interesting implications on the mechanism of glioblastoma cells drug resistance. In summary, novel CD44 targeted polymeric based nanocarriers appear to be proficient in mediating site-specific delivery of quercetin via CD44 receptor in glioblastoma cells. This targeted therapy lead to an improved therapeutic efficacy of temozolomide by modulating the brain tumor microenvironment.
Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis. Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis. Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronic liver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation. Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble, water-soluble vitamins and trace elements and should be supplemented appropriately. Diet, physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations. Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation. The risk of sarcopenia, micronutrient status, and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review. Furthermore, the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.
We evaluated the effects of fasting on the gene expression profile in rat gastrocnemius muscle using a combined cDNA array and RT-PCR approach. Of the 1176 distinct rat genes analyzed on the cDNA array, 114 were up-regulated more than twofold in response to fasting, including all 17 genes related to lipid metabolism present on the membranes and all 10 analyzed components of the proteasome machinery. Only 7 genes were down-regulated more than twofold. On the basis of our analysis of genes on the cDNA array plus the data from our RT-PCR assays, the metabolic adaptations shown by rat gastrocnemius muscle during fasting are reflected by i) increased transcription both of myosin heavy chain (MHC) Ib (associated with type I fibers) and of at least three factors involved in the shift toward type I fibers [p27kip1, muscle LIM protein (MLP), cystein rich protein-2], of which one (MLP) has been shown to enhance the activity of MyoD, which would explain the known increase in the expression of skeletal muscle uncoupling protein-3 (UCP3); ii) increased lipoprotein lipase (LPL) expression, known to trigger UCP3 transcription, which tends, together with the first point, to underline the suggested role of UCP3 in mitochondrial lipid handling (the variations under the first point and this one have not been observed in mice, indicating a species-specific regulation of these mechanisms); iii) reduced expression of the muscle-specific coenzyme Q (CoQ)7 gene, which is necessary for mitochondrial CoQ synthesis, together with an increased expression of mitochondrial adenylate kinase 3, which inactivates the resident key enzyme for CoQ synthesis, 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), the mRNA level for which fell during fasting; and iv) increased transcription of components of the proteasomal pathways involved in protein degradation/turnover.
Fasting is characterized by disrupted thyroid feedback, with suppressed levels of thyroid hormones and paraventricular thyrotropin releasing hormone (TRH). We found that third ventricle administration of the deiodinase inhibitor, iopanoic acid, dose-dependently reduced deiodinase type II (DII) activity selectively in the hypothalamus. This suppression of DII by iopanoic acid during fasting prevented elevated DII activity and blunted the decline in hypothalamic TRH mRNA levels. Because fasting-induced elevation in hypothalamic DII activity is paralleled by increased hypothalamic T3 concentration, our study suggests that T3 formation by DII in the hypothalamus is the cause of disrupted thyroid feedback during fasting.
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