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Pulmonary arterial hypertension (PAH) is a rare and progressive disorder that affects the pulmonary vasculature. Although recent developments in pharmacotherapy have extended the life expectancy of PAH patients, their 5-year survival remains unacceptably low, underscoring the need for multitarget and more comprehensive approaches to managing the disease. This should incorporate not only medical, but also lifestyle interventions, including dietary changes and the use of nutraceutical support. Among these strategies, n-3 polyunsaturated fatty acids (n-3 PUFAs) are emerging as promising agents able to counteract the inflammatory component of PAH. In this narrative review, we aim at analysing the preclinical evidence for the impact of n-3 PUFAs on the pathogenesis and the course of PAH. Although evidence for the role of n-3 PUFAs deficiencies in the development and progression of PAH in humans is limited, preclinical studies suggest that these dietary components may influence several aspects of the pathobiology of PAH. Further clinical research should test the efficacy of n-3 PUFAs on top of approved clinical management. These studies will provide evidence on whether n-3 PUFAs can genuinely serve as a valuable tool to enhance the efficacy of pharmacotherapy in the treatment of PAH.
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Ácidos Graxos Ômega-3 , Hipertensão Arterial Pulmonar , Humanos , Ácidos Graxos Ômega-3/uso terapêutico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Suplementos Nutricionais , Animais , Hipertensão Pulmonar/tratamento farmacológicoRESUMO
We investigated the extent to which adherence to the Mediterranean diet (MD) in combination with Mediterranean lifestyle factors influenced students' perceptions of subjective well-being (SWB) and distress. 939 undergraduates completed a survey to assess sociodemographic and lifestyle characteristics, including adherence to the MD, depression, anxiety, stress, and SWB. Data were analysed with correlation, logistic, and multiple linear regression models. Higher adherence to MD correlated with better SWB. Fruit, red meat, sweet and caffeinated beverages contributed significantly. However, it was the combination of adherence to MD with other factors, including quality of social relationships, income, smoking, sleep, and physical activity that better predicted SWB. Our results confirm the positive influence of MD on SWB. However, they also suggest the need to consider perceptions of well-being by a more holistic approach that considers physical and social factors simultaneously to improve the development of more effective educational and motivational programmes.
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Dieta Mediterrânea , Estilo de Vida , Humanos , Universidades , Estudantes , Itália , PercepçãoRESUMO
The natural environment represents an important source of drugs that originates from the terrestrial and, in minority, marine organisms. Indeed, the marine environment represents a largely untapped source in the process of drug discovery. Among all marine organisms, sponges with algae represent the richest source of compounds showing anticancer activity. In this study, the two secondary metabolites pelorol (PEL) and 5-epi-ilimaquinone (EPI), purified from Dactylospongia elegans were investigated for their anti-melanoma activity. PEL and EPI induced cell growth repression of 501Mel melanoma cells in a concentration- and time-dependent manner. A cell cycle block in the G1 phase by PEL and EPI was also observed. Furthermore, PEL and EPI induced significant accumulation of DNA histone fragments in the cytoplasmic fraction, indicating a pro-apoptotic effect of both compounds. At the molecular level, PEL and EPI induced apoptosis through the increase in pro-apoptotic BAX expression, confirmed by the decrease in its silencing miR-214-3p and the decrease in the anti-apoptotic BCL-2, MCL1, and BIRC-5 mRNA expression, attested by the increase in their silencing miRNAs, i.e., miR-193a-3p and miR-16-5p. In conclusion, our data indicate that PEL and EPI exert cytotoxicity activity against 501Mel melanoma cells promoting apoptotic signaling and inducing changes in miRNA expression and their downstream effectors. For these reasons could represent promising lead compounds in the anti-melanoma drug research.
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Melanoma , MicroRNAs , Poríferos , Animais , Apoptose , Organismos Aquáticos/metabolismo , Linhagem Celular Tumoral , Humanos , Melanoma/tratamento farmacológico , MicroRNAs/genética , MicroRNAs/metabolismo , Poríferos/metabolismo , Quinonas , SesquiterpenosRESUMO
Chronic pain is a major public health problem and an economic burden worldwide. However, its underlying pathological mechanisms remain unclear. MicroRNAs (miRNAs) are a class of small noncoding RNAs that post-transcriptionally regulate gene expression and serve key roles in physiological and pathological processes. This review aims to synthesize the human studies examining miRNA expression in the pathogenesis of chronic primary pain and chronic secondary pain. Additionally, to understand the potential pathophysiological impact of miRNAs in these conditions, an in silico analysis was performed to reveal the target genes and pathways involved in primary and secondary pain and their differential regulation in the different types of chronic pain. The findings, methodological issues and challenges of miRNA research in the pathophysiology of chronic pain are discussed. The available evidence suggests the potential role of miRNA in disease pathogenesis and possibly the pain process, eventually enabling this role to be exploited for pain monitoring and management.
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Dor Crônica , MicroRNAs , Dor Crônica/genética , Humanos , MicroRNAs/metabolismoRESUMO
PURPOSE: The aim of the study was to evaluate the vascular health properties of extracts from biofortified bread, obtained by adding different durum wheat milling by-products rich in phenolic compounds, by analyzing their effects on overwhelming inflammatory response in endothelial cells and monocytes, two main players of atherogenesis. METHODS: Human umbilical vein endothelial cells or U937 monocytes were incubated with increasing concentrations (1, 5, 10 µg/mL) of biofortified bread polyphenol extracts or corresponding pure phenolic acids before stimulation with lipopolysaccharide (LPS). We analyzed the endothelial-monocyte adhesion and related endothelial adhesion molecules. The expression of chemokines and pro-inflammatory cytokines was also measured in LPS-stimulated endothelial cells and monocytes as well as intracellular oxidative stress. RESULTS: Biofortified bread extracts inhibited monocyte adhesion to LPS-stimulated endothelial cells, in a concentration-dependent manner by reducing mainly endothelial VCAM-1 expression. Phenolic acid extracts contained in 10 mg biofortified bread downregulated the LPS-induced expression of chemokines MCP-1, M-CSF, and CXCL-10 as well as pro-inflammatory cytokines TNF-α and IL-1ß, in endothelial cells and monocytes, with CXCL-10 as the most reduced inflammatory mediator. Among phenolic acids of biofortified bread, ferulic, sinapic, and p-coumaric acids significantly inhibited the LPS-stimulated CXCL-10 expression in vascular cells. The reduced pro-inflammatory response was related to a slightly but significant reduction of intracellular oxidative stress. CONCLUSIONS: Our findings suggest the bread biofortified with selected durum wheat milling by-products as a source of phenolic acids with multiple anti-inflammatory and anti-atherosclerotic properties, which could help to counteract or prevent inflammatory vascular diseases.
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Pão , Quimiocina CXCL10 , Alimentos Fortificados , Células Endoteliais da Veia Umbilical Humana , Monócitos , Polifenóis , Molécula 1 de Adesão de Célula Vascular , Adesão Celular , Humanos , Hidroxibenzoatos , Inflamação , Triticum , Molécula 1 de Adesão de Célula Vascular/genéticaRESUMO
PURPOSE: The quality of the study design and data reporting in human trials dealing with the inter-individual variability in response to the consumption of plant bioactives is, in general, low. There is a lack of recommendations supporting the scientific community on this topic. This study aimed at developing a quality index to assist the assessment of the reporting quality of intervention trials addressing the inter-individual variability in response to plant bioactive consumption. Recommendations for better designing and reporting studies were discussed. METHODS: The selection of the parameters used for the development of the quality index was carried out in agreement with the scientific community through a survey. Parameters were defined, grouped into categories, and scored for different quality levels. The applicability of the scoring system was tested in terms of consistency and effort, and its validity was assessed by comparison with a simultaneous evaluation by experts' criteria. RESULTS: The "POSITIVe quality index" included 11 reporting criteria grouped into four categories (Statistics, Reporting, Data presentation, and Individual data availability). It was supported by detailed definitions and guidance for their scoring. The quality index score was tested, and the index demonstrated to be valid, reliable, and responsive. CONCLUSIONS: The evaluation of the reporting quality of studies addressing inter-individual variability in response to plant bioactives highlighted the aspects requiring major improvements. Specific tools and recommendations favoring a complete and transparent reporting on inter-individual variability have been provided to support the scientific community on this field.
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Variação Biológica da População/fisiologia , Confiabilidade dos Dados , Dieta Vegetariana/métodos , Compostos Fitoquímicos/farmacologia , Projetos de Pesquisa , Dieta Vegetariana/tendências , Humanos , Compostos Fitoquímicos/administração & dosagem , Plantas Comestíveis , Reprodutibilidade dos TestesRESUMO
Adipose tissue inflammation is a mechanistic link between obesity and its related sequelae, including insulin resistance and type 2 diabetes. Dual ligands of peroxisome proliferator activated receptor (PPAR)α and γ, combining in a single molecule the metabolic and inflammatory-regulatory properties of α and γ agonists, have been proposed as a promising therapeutic strategy to antagonize adipose tissue inflammation. Here we investigated the effects of the dual PPARα/γ agonist aleglitazar on human adipocytes challenged with inflammatory stimuli. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were treated with aleglitazar or - for comparison - the selective agonists for PPARα or γ fenofibrate or rosiglitazone, respectively, for 24h before stimulation with TNF-α. Aleglitazar, at concentrations as low as 10nmol/L, providing the half-maximal transcriptional activation of both PPARα and PPARγ, reduced the stimulated expression of several pro-inflammatory mediators including interleukin (IL)-6, the chemokine CXC-L10, and monocyte chemoattractant protein (MCP)-1. Correspondingly, media from adipocytes treated with aleglitazar reduced monocyte migration, consistent with suppression of MCP-1 secretion. Under the same conditions, aleglitazar also reversed the TNF-α-mediated suppression of insulin-stimulated ser473 Akt phosphorylation and decreased the TNF-α-induced ser312 IRS1 phosphorylation, two major switches in insulin-mediated metabolic activities, restoring glucose uptake in insulin-resistant adipocytes. Such effects were similar to those obtainable with a combination of single PPARα and γ agonists. In conclusion, aleglitazar reduces inflammatory activation and dysfunction in insulin signaling in activated adipocytes, properties that may benefit diabetic and obese patients. The effect of aleglitazar was consistent with dual PPARα and γ agonism, but with no evidence of synergism.
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Adipócitos/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Oxazóis/farmacologia , PPAR alfa/agonistas , PPAR gama/agonistas , Tiofenos/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Adipócitos/metabolismo , Adipócitos/fisiologia , Adiponectina/genética , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CCL2/genética , Quimiocina CXCL10/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Humanos , Inflamação/genética , Inflamação/metabolismo , Resistência à Insulina , Interleucina-6/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
PURPOSE: The aim of the study was to evaluate the vascular anti-inflammatory effects of polyphenolic extracts from two typical South Italy red wines, the specific contribution of individual polyphenols and the underlying mechanisms of action. METHODS: Human endothelial cells were incubated with increasing concentrations (1-50 µg/mL) of Primitivo and Negroamaro polyphenolic extracts (PWPE and NWPE, respectively) or pure polyphenols (1-25 µmol/L), including hydroxycinnamic acids (p-coumaric, caffeic and caftaric acids), flavonols (kaempferol, quercetin, myricetin) or stilbenes (trans-resveratrol, trans-piceid) before stimulation with lipopolysaccharide. Through multiple assays, we analyzed the endothelial-monocyte adhesion, the endothelial expression of adhesion molecules (ICAM-1, VCAM-1 and E-Selectin), monocyte chemoattractant protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF), as well as ROS intracellular levels and the activation of NF-κB and AP-1. RESULTS: Both PWPE and NWPE, already at 1 µg/mL, inhibited monocyte adhesion to stimulated endothelial cells, a key event in triggering vascular inflammation. They down-regulated the expression of adhesion molecules, ICAM-1, VCAM-1, E-Selectin, as well as MCP-1 and M-CSF, at mRNA and protein levels. All polyphenols reduced intracellular ROS, and everything, except caftaric acid, inhibited the endothelial expression of adhesion molecules and MCP-1, although with different potency. Flavonols and resveratrol significantly reduced also the endothelial expression and release of M-CSF. The decrease in endothelial inflammatory gene expression was related to the inhibition of NF-κB and AP-1 activation but not to intracellular oxidative stress. CONCLUSIONS: This study showed multiple anti-inflammatory and anti-atherosclerotic properties of red wine polyphenolic extracts and indentified specific bioactive polyphenols which could counteract inflammatory diseases including atherosclerosis.
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Anti-Inflamatórios/farmacologia , Ácidos Cumáricos/farmacologia , Flavonóis/farmacologia , Polifenóis/farmacologia , Estilbenos/farmacologia , Vinho/análise , Anti-Inflamatórios/análise , Aterosclerose/tratamento farmacológico , Adesão Celular/efeitos dos fármacos , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Ácidos Cumáricos/análise , Selectina E/genética , Selectina E/metabolismo , Células Endoteliais/efeitos dos fármacos , Flavonóis/análise , Humanos , Inflamação/tratamento farmacológico , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Itália , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/análise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estilbenos/análise , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep disorder associated with severe cardiovascular events, morbidity and mortality. Recent evidence has highlighted OSAS as an independent risk factor for an excessive platelet activation and arterial thrombosis, but the underlying mechanisms have not yet been determined. Studies in cell culture and animal models have significantly increased our understanding of the mechanisms of inflammation in OSAS. Hypoxia is a critical pathophysiological element that leads to an intense sympathetic activity, in association with systemic inflammation, oxidative stress and procoagulant activity. While platelet dysfunction and/or hypercoagulability play an important role in the pathogenesis of vascular disease, there are limited studies on the potential role of blood viscosity in the development of vascular disease in OSAS. CONCLUSION: Further studies are required to determine the precise role of hypercoagulability in the cardiovascular pathogenesis of OSAS, particularly its interaction with oxidative stress, thrombotic tendency and endothelial dysfunction. Nasal continuous positive airway pressure (nCPAP), the gold standard treatment for OSAS, not only significantly reduced apnea-hypopnoea indices but also markers of hypercoagulability, thus representing a potential mechanisms by which CPAP reduces the rate of cardiovascular morbidity and mortality in OSAS patients.
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Pressão Positiva Contínua nas Vias Aéreas , Ativação Plaquetária/fisiologia , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/terapia , Trombose/sangue , Trombose/terapia , Viscosidade Sanguínea/fisiologia , Humanos , Fatores de Risco , Apneia Obstrutiva do Sono/epidemiologia , Trombose/epidemiologiaRESUMO
Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases' activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5-25 µg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5-25 µmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases.
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Frutas/química , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/enzimologia , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Modelos Biológicos , Polifenóis , Vasculite/tratamento farmacológico , Vitis/química , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Polifenóis/química , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Remodelação Vascular/efeitos dos fármacos , Vasculite/enzimologia , Vasculite/patologiaRESUMO
The liver is central in regulating glucose homeostasis, being the major contributor to endogenous glucose production and the greatest reserve of glucose as glycogen. It is both a target and regulator of the action of glucoregulatory hormones. Hepatic metabolic functions are altered in and contribute to the highly prevalent steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). In this Review, we describe the dysregulation of hepatic glucose metabolism in MASLD and MASH and associated metabolic comorbidities, and how advances in techniques and models for the assessment of hepatic glucose fluxes in vivo have led to the identification of the mechanisms related to the alterations in glucose metabolism in MASLD and comorbidities. These fluxes can ultimately increase hepatic glucose production concomitantly with fat accumulation and alterations in the secretion and action of glucoregulatory hormones. No pharmacological treatment has yet been approved for MASLD or MASH, but some antihyperglycaemic drugs approved for treating type 2 diabetes have shown positive effects on hepatic glucose metabolism and hepatosteatosis. A deep understanding of how MASLD affects glucose metabolic fluxes and glucoregulatory hormones might assist in the early identification of at-risk individuals and the use or development of targeted therapies.
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Fígado Gorduroso , Glucose , Fígado , Humanos , Glucose/metabolismo , Fígado/metabolismo , Fígado Gorduroso/metabolismoRESUMO
Background/Objectives: Over time, the scientific community has developed a growing interest in the effects of mixtures of different compounds, for which there is currently no established evidence or knowledge, in relation to certain categories of xenobiotics. It is well known that exposure to pollutants causes oxidative stress, resulting in the overproduction of reactive oxygen species (ROS), which can affect signaling pathways that regulate the cell cycle, apoptosis, energy balance, and cellular metabolism. The aim of this study was to investigate the effects of sub-lethal concentrations of mixtures of emerging pollutants and pharmaceuticals on the modulation of biomarkers related to toxicity, oxidative stress, and cancer. Methods: In this study, the hepatoma cell line HepG2 was exposed to increasing concentrations of polybrominated diphenyl ether 47 (BDE-47), cadmium chloride (CdCl2), and carbamazepine (CBZ), both individually and in mixtures, for 72 h to assess cytotoxicity using the MTT assay. The subsequent step, following the identification of the sub-lethal concentration, was to investigate the effects of exposure at the gene expression level, through the evaluation of molecular markers related to cell cycle and apoptosis (p53), oxidative stress (NRF2), conjugation and detoxification of xenobiotics (CYP2C9 and GST), DNA damage (RAD51 and γH2AFX), and SUMOylation processes (SUMO1 and UBC9) in order to identify any potential alterations in pathways that are normally activated at the cellular level. Results: The results showed that contaminants tend to affect the enzymatic detoxification and antioxidant system, influencing DNA repair defense mechanisms involved in resistance to oxidative stress. The combined effect of the compounds at sub-lethal doses results in a greater activation of these pathways compared to exposure to each compound alone, thereby exacerbating their cytotoxicity. Conclusions: The biomarkers analyzed could contribute to the definition of early warning markers useful for environmental monitoring, while simultaneously providing insight into the toxicity and hazard levels of these substances in the environment and associated health risks.
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The COVID-19 outbreak has led to relevant changes in everyday life worldwide. One of these changes has been a rapid transition to and an increasing implementation of working from home (WH) modality. This study aimed to evaluate the impact of mandatory WH during the COVID-19 pandemic on lifestyle behaviors, Mediterranean diet adherence, body weight, and depression. An online cross-sectional survey was conducted in the early 2022 at the National Research Council of Italy using ad hoc questions and validated scales collecting information on physical activity, sedentary behavior, hobbies/pastimes, dietary habits including adherence to the Mediterranean diet, body weight, and depression during WH compared with before WH. 748 respondents were included in the study. An increased sedentary lifetime was reported by 48% of respondents; however, the subsample of workers who previously performed moderate physical activity intensified this activity. Body weight gain during WH was self-reported in 39.9% of respondents. Mediterranean diet adherence increased (pâª0.001) during WH compared with before WH. The average level of mental health did not record an overall variation; however, the proportion of subjects with mild and moderate depression increased (p = 0.006), while workers who reported values indicative of depression before the transition declared an improvement. These findings highlight health-related impact of WH during the COVID-19 pandemic that may inform future strategies and policies to improve employees' health and well-being.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Saúde Mental , Estudos Transversais , Estilo de Vida , Peso Corporal , Inquéritos e QuestionáriosRESUMO
Polyphenols are secondary plant metabolites derived from the shikimate/phenylpropanoid pathway, protecting plants from physical, chemical and biological stress [...].
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Fenômenos Bioquímicos , Polifenóis , Polifenóis/farmacologia , Polifenóis/metabolismo , Plantas/metabolismo , Disponibilidade BiológicaRESUMO
The endothelium, an essential component of the vascular system, plays a critical role in the inflammatory response. Under pro-inflammatory stimuli, endothelial cells undergo activation and dysfunction, leading to the release of inflammatory mediators and upregulation of cell adhesion molecules. These changes facilitate the adhesion, rolling, and transmigration of leukocytes into the subendothelial space. Emerging evidence suggests that epigenetic mechanisms, including nucleic acid methylation, post-translational histone modifications, and non-coding RNA, contribute significantly to the regulation of vascular inflammation and expression of cell adhesion molecules. Understanding the epigenetic molecular signatures that govern these processes may provide new insights into the development of therapeutic strategies to combat vascular inflammation and associated diseases. This review aims to summarize the current knowledge on the epigenetic mechanisms involved in modulating the intricate processes underlying vascular inflammation, with a specific focus on the expression of endothelial adhesion molecules and endothelium-leukocyte adhesion.
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Células Endoteliais , Molécula 1 de Adesão de Célula Vascular , Humanos , Células Endoteliais/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Adesão Celular/genética , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Endotélio/metabolismo , Leucócitos , Epigênese Genética , Inflamação/genética , Inflamação/metabolismo , Endotélio VascularRESUMO
Sea urchins have emerged as an important source of bioactive compounds with anti-inflammatory and antioxidant properties relevant to human health. Since inflammation is a crucial pathogenic process in the development and progression of atherosclerosis, we here assessed the potential anti-inflammatory and vasculoprotective effects of coelomic red-cell methanolic extract of the black sea urchin Arbacia lixula in an in vitro model of endothelial cell dysfunction. Human microvascular endothelial cells (HMEC-1) were pretreated with A. lixula red-cell extract (10 and 100 µg/mL) before exposure to the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. The extract was non-toxic after 24 h cell treatment and was characterized by antioxidant power and phenol content. The TNF-α-stimulated expression of adhesion molecules (VCAM-1, ICAM-1) and cytokines/chemokines (MCP-1, CCL-5, IL-6, IL-8, M-CSF) was significantly attenuated by A. lixula red-cell extract. This was functionally accompanied by a reduction in monocyte adhesion and chemotaxis towards activated endothelial cells. At the molecular level, the tested extract significantly counteracted the TNF-α-stimulated activation of the pro-inflammatory transcription factor NF-κB. These results provide evidence of potential anti-atherosclerotic properties of A. lixula red-cell extract, and open avenues in the discovery and development of dietary supplements and/or drugs for the prevention or treatment of cardiovascular diseases.
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Arbacia , Animais , Humanos , Arbacia/metabolismo , Células Endoteliais/metabolismo , Extratos Celulares/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , NF-kappa B/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Citocinas/metabolismo , Ouriços-do-Mar/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Adesão CelularRESUMO
INTRODUCTION: Increasing evidence suggests that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have emerged as attractive targets in viral infections, including Human immunodeficiency virus (HIV). OBJECTIVE: To deepen the understanding of the molecular mechanisms that lead to HIV and provide potential targets for the future development of molecular therapies for its treatment. METHODS: Four miRNAs were selected as candidates based on a previous systematic review. A combination of bioinformatic analyses was performed to identify their target genes, lncRNAs and biological processes that regulate them. RESULTS: In the constructed miRNA-mRNA network, 193 gene targets are identified. These miRNAs potentially control genes from several important processes, including signal transduction and cancer. LncRNA-XIST, lncRNA-NEAT1 and lncRNA-HCG18 interact with all four miRNAs. CONCLUSION: This preliminary result forms the basis for improving reliability in future studies to fully understand the role these molecules and their interactions play in HIV.
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Infecções por HIV , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Infecções por HIV/genética , Reprodutibilidade dos Testes , MicroRNAs/genética , Biologia ComputacionalRESUMO
Objective: The study aimed to investigate perceptions and determinants of the overall impact on life and work domains among a community of knowledge workers after 18 months of forced work from home due to the pandemic. Methods: A cross-sectional study with a retrospective assessment was conducted early in 2022 at the National Research Council of Italy. Five single-item questions explored the perceived impact on life domain while a 7-item scale the impact on the work domain. Bivariate analyses and multivariate regressions were used to evaluate the associations between impacts and some key factors defined by 29 ad hoc closed questions. Results: More than 95% of the 748 respondents reported a perceived change in at least one item of the life domain. For each of these items, although a large group of subjects has reported that working from home had no impact (from 27 to 55%), in the rest of the sample the positive evaluation (from 30 to 60%) clearly prevailed over the negative one. Overall, most of the subjects (64%) rated the impact on the work experience positively. Relationship with colleagues and participation in the work context were the items where the greatest number of negative rates was concentrated (27 and 25%, respectively). On the other hand, positive perceptions prevailed over both negative perceptions and lack of impact perceptions on the subjects of organizational flexibility and quality of work. The frequency of work-room sharing, home-work commute time and changes in sedentary lifestyle, have been identified as common explanatory factors of perceived impacts on both domains. Conclusion: Overall, respondents reported positive rather than negative perceived impacts of forced work from home in both their lives and work. The obtained results suggest that policies to promote the physical and mental health of employees, strengthen inclusion and maintain a sense of community are necessary to improve workers' health and prevent the effects of perceived isolation on research activities.
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COVID-19 , Estados Unidos , Humanos , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Estudos Retrospectivos , Teletrabalho , Itália/epidemiologia , National Academy of Sciences, U.S. , Inquéritos e QuestionáriosRESUMO
[This corrects the article DOI: 10.3389/fpubh.2023.1151009.].
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INTRODUCTION: Minimal erythema dose (MED) remains a parameter of paramount importance to orient narrow-band (NB)-UVB phototherapy in psoriatic (PsO) patients. Recently, circadian rhythm and diet were recognized as potential MED modulators, but their mutual interaction remains understudied. Thus, we aimed to evaluate the potential diet modulation of MED circadian oscillations. METHODS: In the first phase, a cohort study was performed comparing potential MED oscillations (morning, afternoon, and evening) among omnivorous psoriatic patients before and after a phototherapy cycle and omnivorous healthy controls. The two groups were age-, gender-, skin-type-, MED-, and diet-matched. Then, in the second phase, another cohort study was carried out comparing MED oscillations 24 h after the last phototherapeutic session only in psoriatic patients cleared with NB-UVB and undergoing different diets (vegan, vegetarian, paleo , ketogenic, intermittent circadian fasting, and omnivore). Patients with different diets were age-, gender-, and skin-type matched. RESULTS: In the first phase, we enrolled only omnivores, specifically 54 PsO patients and 54 healthy individuals. Their MED before and after NB-UVB therapy changed significantly among the three different time-points (morning, afternoon, and evening) (p < 0.001). The time effect was statistically significant in both groups before and after phototherapy. In the second phase, we enrolled 144 PsO patients (vegan, vegetarian, paleo, ketogenic, intermittent circadian fasting, and omnivore). MED circadian oscillations preserved a significant difference also after clearance and were influenced by diet type and time of day (p < 0.001). In particular, vegans displayed the lowest MED values, whilst Ramadan fasting showed the highest values in morning, afternoon, and evening. CONCLUSIONS: Diet, like other ongoing therapies, should be reported in the medical records of patients with psoriasis undergoing NB-UVB and patients with lower MEDs should be preferentially treated in the morning when the MED is higher.