Upregulation of inducible NO synthase by exogenous adenosine in vascular smooth muscle cells activated by inflammatory stimuli in experimental diabetes

BACKGROUND: Adenosine has been shown to induce nitric oxide (NO) production via inducible NO synthase (iNOS) activation in vascular smooth muscle cells (VSMCs). Although this is interpreted as a beneficial vasodilating pathway in vaso-occlusive disorders, iNOS is also involved in diabetic vascular dysfunction. Because the turnover of and the potential to modulate iNOS by adenosine in experimental diabetes have not been explored, we hypothesized that both the adenosine system and control of iNOS function are impaired in VSMCs from streptozotocin-diabetic rats. METHODS: Male Sprague-Dawley rats were injected with streptozotocin once to induce diabetes. Aortic VSMCs from diabetic and nondiabetic rats were isolated, cultured and exposed to lipopolysaccharide (LPS) plus a cytokine mix for 24 h in the presence or absence of (1) exogenous adenosine and related compounds, and/or (2) pharmacological agents affecting adenosine turnover. iNOS functional expression was determined by immunoblotting and NO metabolite assays. Concentrations of adenosine, related compounds and metabolites thereof were assayed by HPLC. Vasomotor responses to adenosine were determined in endothelium-deprived aortic rings. RESULTS: Treatment with adenosine-degrading enzymes or receptor antagonists increased iNOS formation in activated VSMCs from nondiabetic and diabetic rats. Following treatment with the adenosine transport inhibitor NBTI, iNOS levels increased in nondiabetic but decreased in diabetic VSMCs. The amount of secreted NO metabolites was uncoupled from iNOS levels in diabetic VSMCs. Addition of high concentrations of adenosine and its precursors or analogues enhanced iNOS formation solely in diabetic VSMCs. Exogenous adenosine and AMP were completely removed from the culture medium and converted into metabolites. A tendency towards elevated inosine generation was observed in diabetic VSMCs, which were also less sensitive to CD73 inhibition, but inosine supplementation did not affect iNOS levels. Pharmacological inhibition of NOS abolished adenosine-induced vasorelaxation in aortic tissues from diabetic but not nondiabetic animals. CONCLUSIONS: Endogenous adenosine prevented cytokine- and LPS-induced iNOS activation in VSMCs. By contrast, supplementation with adenosine and its precursors or analogues enhanced iNOS levels in diabetic VSMCs. This effect was associated with alterations in exogenous adenosine turnover. Thus, overactivation of the adenosine system may foster iNOS-mediated diabetic vascular dysfunction

Estrogen, angiogenesis, immunity and cell metabolism: Solving the puzzle

Estrogen plays an important role in the regulation of cardiovascular physiology and the immune system by inducing direct effects on multiple cell types including immune and vascular cells. Sex steroid hormones are implicated in cardiovascular protection, including endothelial healing in case of arterial injury and collateral vessel formation in ischemic tissue. Estrogen can exert potent modulation effects at all levels of the innate and adaptive immune systems. Their action is mediated by interaction with classical estrogen receptors (ERs), ER\u3b1 and ER\u3b2, as well as the more recently identified G-protein coupled receptor 30/G-protein estrogen receptor 1 (GPER1), via both genomic and non-genomic mechanisms. Emerging data from the literature suggest that estrogen deficiency in menopause is associated with an increased potential for an unresolved inflammatory status. In this review, we provide an overview through the puzzle pieces of how 17\u3b2-estradiol can influence the cardiovascular and immune systems

Metabolic Syndrome, Inflammation and Atherosclerosis

The inflammatory component of atherogenesis has been increasingly recognized over the last decade. Inflammation participates in all stages of atherosclerosis, not only during initiation and during evolution of lesions, but also with precipitation of acute thrombotic complications. The metabolic syndrome is associated with increased risk for development of both cardiovascular disease and type-2 diabetes in humans. Central obesity and insulin resistance are thought to represent common underlying factors of the syndrome, which features a chronic low-grade inflammatory state. Diagnosis of the metabolic syndrome occurs using defined threshold values for waist circumference, blood pressure, fasting glucose and dyslipidemia. The metabolic syndrome appears to affect a significant proportion of the population. Therapeutic approaches that reduce the levels of proinflammatory biomarkers and address traditional risk factors are particularly important in preventing cardiovascular disease and, potentially, diabetes. The primary management of metabolic syndrome involves healthy lifestyle promotion through moderate calorie restriction, moderate increase in physical activity and change in dietary composition. Treatment of individual components aims to control atherogenic dyslipidemia using fibrates and statins, elevated blood pressure, and hyperglycemia. While no single treatment for the metabolic syndrome as a whole yet exists, emerging therapies offer potential as future therapeutic approaches

WordUp! at VaxxStance 2021: Combining Contextual Information with Textual and Dependency-Based Syntactic Features for Stance Detection.

In this paper we describe the participation of the WordUp! team in the VaxxStance shared task at IberLEF 2021. The goal of the competition is to determine the author's stance from tweets written both in Spanish and Basque on the topic of the Antivaxxers movement. Our approach, in the four different tracks proposed, combines the Logistic Regression classifier with diverse groups of features: stylistic, tweet-based, user-based, lexicon-based, dependency-based, and network-based. The outcomes of our experiments are in line with state-of-the-art results on other languages, proving the efficacy of combining methods derived from NLP and Network Science for detecting stance in Spanish and Basque

QUEEREOTYPES: A Multi-Source Italian Corpus of Stereotypes towards LGBTQIA+ Community Members

The paper describes a dataset composed of two sub-corpora from two different sources in Italian. The QUEEREOTYPES corpus includes social media texts regarding LGBTQIA+ individuals, behaviors, ideology and events. The texts were collected from Facebook and Twitter in 2018 and were annotated for the presence of stereotypes, and orthogonal dimensions (such as hate speech, aggressiveness, offensiveness, and irony in one sub-corpus, and stance in the other). The resource was developed by Natural Language Processing researchers together with activists from an Italian LGBTQIA+ not-for-profit organization. The creation of the dataset allows the NLP community to study stereotypes against marginalized groups, individuals and, ultimately, to develop proper tools and measures to reduce the online spread of such stereotypes. A test for the robustness of the language resource has been performed by means of 5-fold cross-validation experiments. Finally, text classification experiments have been carried out with a fine-tuned version of AlBERTo (a BERT-based model pre-trained on Italian tweets) and mBERT, obtaining good results on the task of stereotype detection, suggesting that stereotypes towards different targets might share common traits