COVID-19: is there a link between the course of infection and pharmacological agents in diabetes?

The Coronavirus disease 2019 (COVID-19) and type 2 diabetes (T2D) are two pandemics that share the dramatic impact on global mortality and economic resources. COVID-19 largely exhibits mild to moderate clinical manifestations. However, severe pneumonia with high fatality rate may occur, especially in the elderly and in patients with underlying conditions, such as diabetes and cardiovascular disease. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) binds to the angiotensin-converting enzyme 2 (ACE2), a ubiquitous trans-membrane carboxypeptidase, to enter the cells

Bisphenol A and phthalates in diet: an emerging link with pregnancy complications

Endocrine-disrupting chemicals (EDCs) are exogenous substances that are able to interfere with hormone action, likely contributing to the development of several endocrine and metabolic diseases. Among them, Bisphenol A (BPA) and phthalates contaminate food and water and have been largely studied as obesogenic agents. They might contribute to weight gain, insulin resistance and pancreatic β-cell dysfunction in pregnancy, potentially playing a role in the development of pregnancy complications, such as gestational diabetes mellitus (GDM), and adverse outcomes. Pregnancy and childhood are sensitive windows of susceptibility, and, although with not univocal results, preclinical and clinical studies have suggested that exposure to BPA and phthalates at these stages of life might have an impact on the development of metabolic diseases even many years later. The molecular mechanisms underlying this association are largely unknown, but adipocyte and pancreatic β-cell dysfunction are suspected to be involved. Remarkably, transgenerational damage has been observed, which might be explained by epigenetic changes. Further research is needed to address knowledge gaps and to provide preventive measure to limit health risks connected with exposure to EDCs

The phosphodiesterase 5 inhibitor sildenafil decreases the proinflammatory chemokine IL-8 in diabetic cardiomyopathy: in vivo and in vitro evidence

Purpose: Interleukin (IL)-8 is a proinflammatory C-X-C chemokine involved in inflammation underling cardiac diseases, primary or in comorbid condition, such diabetic cardiomyopathy (DCM). The phosphodiesterase type 5 inhibitor sildenafil can ameliorate cardiac conditions by counteracting inflammation. The study aim is to evaluate the effect of sildenafil on serum IL-8 in DCM subjects vs. placebo, and on IL-8 release in human endothelial cells (Hfaec) and peripheral blood mononuclear cells (PBMC) under inflammatory stimuli. Methods: IL-8 was quantified: in sera of (30) DCM subjects before (baseline) and after sildenafil (100 mg/day, 3-months) vs. (16) placebo and (15) healthy subjects, by multiplatform array; in supernatants from inflammation-challenged cells after sildenafil (1 µM), by ELISA. Results: Baseline IL-8 was higher in DCM vs. healthy subjects (149.14 ± 46.89 vs. 16.17 ± 5.38 pg/ml, p < 0.01). Sildenafil, not placebo, significantly reduced serum IL-8 (23.7 ± 5.9 pg/ml, p < 0.05 vs. baseline). Receiver operating characteristic (ROC) curve for IL-8 was 0.945 (95% confidence interval of 0.772 to 1.0, p < 0.01), showing good capacity of discriminating the response in terms of drug-induced IL-8 decrease (sensitivity of 0.93, specificity of 0.90). Sildenafil significantly decreased IL-8 protein release by inflammation-induced Hfaec and PBMC and downregulated IL-8 mRNA in PBMC, without affecting cell number or PDE5 expression. Conclusion: Sildenafil might be suggested as potential novel pharmacological tool to control DCM progression through IL-8 targeting at systemic and cellular level

Tissue and circulating microRNAs as biomarkers of response to obesity treatment strategies

Background: Obesity, characterized by an increased amount of adipose tissue, is a metabolic chronic alteration which has reached pandemic proportion. Lifestyle changes are the first line therapy for obesity and a large variety of dietary approaches have demonstrated efficacy in promoting weight loss and improving obesity-related metabolic alterations. Besides diet and physical activity, bariatric surgery might be an effective therapeutic strategy for morbid obese patients. Response to weight-loss interventions is characterised by high inter-individual variability, which might involve epigenetic factors. microRNAs have critical roles in metabolic processes and their dysregulated expression has been reported in obesity. Aim: The aim of this review is to provide a comprehensive overview of current studies evaluating changes in microRNA expression in obese patients undergoing lifestyle interventions or bariatric surgery. Results: A considerable number of studies have reported a differential expression of circulating microRNAs before and after various dietary and bariatric surgery approaches, identifying several candidate biomarkers of response to weight loss. Significant changes in microRNA expression have been observed at a tissue level as well, with entirely different patterns between visceral and subcutaneous adipose tissue. Interestingly, relevant differences in microRNA expression have emerged between responders and non-responders to dietary or surgical interventions. A wide variety of dysregulated microRNA target pathways have also been identified, helping to understand the pathophysiological mechanisms underlying obesity and obesity-related metabolic diseases. Conclusions: Although further research is needed to draw firm conclusions, there is increasing evidence about microRNAs as potential biomarkers for weight loss and response to intervention strategies in obesity

Cardiomyopathy associated with diabetes. the central role of the cardiomyocyte

The term diabetic cardiomyopathy (DCM) labels an abnormal cardiac structure and performance due to intrinsic heart muscle malfunction, independently of other vascular co-morbidity. DCM, accounting for 50%-80% of deaths in diabetic patients, represents a worldwide problem for human health and related economics. Optimal glycemic control is not sufficient to prevent DCM, which derives from heart remodeling and geometrical changes, with both consequences of critical events initially occurring at the cardiomyocyte level. Cardiac cells, under hyperglycemia, very early undergo metabolic abnormalities and contribute to T helper (Th)-driven inflammatory perturbation, behaving as immunoactive units capable of releasing critical biomediators, such as cytokines and chemokines. This paper aims to focus onto the role of cardiomyocytes, no longer considered as "passive" targets but as "active" units participating in the inflammatory dialogue between local and systemic counterparts underlying DCM development and maintenance. Some of the main biomolecular/metabolic/inflammatory processes triggered within cardiac cells by high glucose are overviewed; particular attention is addressed to early inflammatory cytokines and chemokines, representing potential therapeutic targets for a prompt early intervention when no signs or symptoms of DCM are manifesting yet. DCM clinical management still represents a challenge and further translational investigations, including studies at female/male cell level, are warranted

Type 1 diabetes, thyroid, gastric and adrenal humoral autoantibodies are present altogether in almost one third of adult celiac patients at diagnosis, with a higher frequency than children and adolescent celiac patients

Background: No data are available on the frequency of organ-specific humoral autoimmunity at diagnosis of adult celiac disease (CD). Aim: To evaluate the humoral immunoreactivities specific of type 1 diabetes (T1D), thyroid (THD), atrophic-gastritis (AG) and Addison’s (AD) diseases in 92 adult CD patients at diagnosis and 237 adult healthy subjects (CTRL). Methods: T1D, THD and AD specific autoantibodies were analyzed by radioimmunoprecipitation assays. AG autoantibodies were detected by enzyme-linked immunosorbent assay. Results: Of 92 CD patients, 31.5% were positive for at least one of the organ-specific autoantibodies investigated (p <.0001 vs CTRL). Thyroid, diabetes, gastric and adrenal-autoantibodies, that increase with age at diagnosis, were detected in 12.0%, 10.9%, 10.9%, 2.2% of CD patients, respectively. Gastric- and diabetes- rather than thyroid- and adrenal-autoimmunity seem to be specifically related to presence of CD. Conclusions: One third of adult CD patients at diagnosis is target of at least one organ-specific autoantibody. A systematic organ-specific autoantibody screening in these patients might be of value to promptly identify, prevent or treat the relative diseases

Rapid diversification and secondary sympatry in Australo-Pacific kingfishers (Aves: Alcedinidae: Todiramphus)

Todiramphus chloris is the most widely distributed of the Pacific's ‘great speciators’. Its 50 subspecies constitute a species complex that is distributed over 16 000 km from the Red Sea to Polynesia. We present, to our knowledge, the first comprehensive molecular phylogeny of this enigmatic radiation of kingfishers. Ten Pacific Todiramphus species are embedded within the T. chloris complex, rendering it paraphyletic. Among these is a radiation of five species from the remote islands of Eastern Polynesian, as well as the widespread migratory taxon, Todiramphus sanctus. Our results offer strong support that Pacific Todiramphus, including T. chloris, underwent an extensive range expansion and diversification less than 1 Ma. Multiple instances of secondary sympatry have accumulated in this group, despite its recent origin, including on Australia and oceanic islands in Palau, Vanuatu and the Solomon Islands. Significant ecomorphological and behavioural differences exist between secondarily sympatric lineages, which suggest that pre-mating isolating mechanisms were achieved rapidly during diversification. We found evidence for complex biogeographic patterns, including a novel phylogeographic break in the eastern Solomon Islands that separates a Northern Melanesian clade from Polynesian taxa. In light of our results, we discuss systematic relationships of Todiramphus and propose an updated taxonomy. This paper contributes to our understanding of avian diversification and assembly on islands, and to the systematics of a classically polytypic species complex.This project was funded in part by an American Museum of Natural History Chapman Fellowship (M.J.A.), an American Ornithologists' Union Research Award (M.J.A.), a University of Kansas Doctoral Student Research Fund (M.J.A.) and NSF DEB-1241181 and DEB-0743491 (R.G.M.

MicroRNA modulation by dietary supplements in obesity

The prevalence of obesity has dramatically increased over the last decades. Weight loss obtained through diet and exercise leads to a significant decrease in morbidity and mortality. Recently, there has been growing interest in the possible beneficial effects of dietary supplements (DSs), including polyphenols, fatty acids, and other plant-derived substances, as adjuvants in the management of obesity and metabolic diseases. Specifically, polyphenols, widely spread in vegetables and fruits, significantly modulate adipose tissue activities, contrasting inflammation and improving insulin sensitivity in preclinical and clinical studies. Remarkably, polyphenols are involved in complex microRNA networks, which play crucial roles in metabolic processes. The administration of different polyphenols and other plant-derived compounds led to significant changes in the microRNA expression profile in peripheral tissues in a growing number of preclinical studies. In particular, these compounds were able to revert obesity-induced microRNA dysregulation, leading to the inhibition of adipogenesis and the induction of weight loss. Furthermore, through microRNA modulation, they attenuated key metabolic alterations, including insulin resistance and lipid anomalies, in animal models of obesity. Some of them were also able to reduce proinflammatory cytokines in adipose tissue. The aim of this review is to summarize current evidence about the effect of plant-derived DSs on microRNA expression in obesity

Grizzly bear monitoring by the Heiltsuk people as a crucible for First Nation conservation practice

Guided by deeply held cultural values, First Nations in Canada are rapidly regaining legal authority to manage natural resources. We present a research collaboration among academics, tribal government, provincial and federal government, resource managers, conservation practitioners, and community leaders supporting First Nation resource authority and stewardship. First, we present results from a molecular genetics study of grizzly bears inhabiting an important conservation area within the territory of the Heiltsuk First Nation in coastal British Columbia. Noninvasive hair sampling occurred between 2006 and 2009 in the Koeye watershed, a stronghold for grizzly bears, salmon, and Heiltsuk people. Molecular demographic analyses revealed a regionally significant population of bears, which congregate at the Koeye each salmon-spawning season. There was a minimum of 57 individual bears detected during the study period. Results also pointed to a larger than expected source geography for salmon-feeding bears in the study area (\u3e 1000 km²), as well as early evidence of a declining trend in the bear population potentially explained by declining salmon numbers. Second, we demonstrate and discuss the power of integrating scientific research with a culturally appropriate research agenda developed by indigenous people. Guided explicitly by principles from Gvi’ilas or customary law, this research methodology is coupled with Heiltsuk culture, enabling results of applied conservation science to involve and resonate with tribal leadership in ways that have eluded previous scientific endeavors. In this context, we discuss the effectiveness of research partnerships that, from the outset, create both scientific programs and integrated communities of action that can implement change. We argue that indigenous resource management requires collaborative approaches like ours, in which science-based management is embedded within a socially and culturally appropriate context. We emerge not only with a set of guiding principles for resource management by the Heiltsuk, but a broadly applicable strategy that fosters intimacy with traditional lands and resources and provides a powerful engine for conservation

Otimização de pré-tratamento ácido do bagaço de cana-de-açúcar para obtenção de açúcares fermentecíveis.

O objetivo deste trabalho foi otimizar as condições de pré-tratamento ácido de bagaço de cana-de-açúcar visando obter maiores quantidades destes açúcares