Antioxidant, Anti-Inflammatory and Anti-Obesity Potential of Extracts Containing Phenols, Chlorophyll and Carotenoids from Mexican Wild Populations of Bacopa monnieri (L.) Wettst.

Some of the species of the genus Bacopa have been used in Pharmacopoeia worldwide. However, in Mexico, Bacopa monnieri has neither been extensively cultivated nor studied, nor has their use in traditional medicine been reported. The aim of this work was to assess the taxonomic verification of the four wild populations of B. monnieri, the chemical content of their pigments and phenols and to provide an analysis of their potential bioactivity. B. monnieri wild populations from Mexico were validated using molecular markers. Chromatographic profiling using HPLC-PDA revealed 21 compounds comprising 12 chlorophylls and nine carotenoids; of the latter, the major ones were lutein (0.921 ± 0.031 µg/mg of dry extract) and ß-carotene (0.095 ± 0.003 µg/mg of dry extract). The total phenolic content, determined using the Folin-Ciocalteu assay, ranged from 54.8 ± 5.8 to 70.3 ± 2.2 µg of gallic acid equivalents (GAE)/mg. Plant extracts scavenged from the free radical DPPH in IC50 ranged from 130.6 ± 3.0 to 249.9 ± 12.1 µg dry extract/mL. In terms of the anti-inflammatory potential, the most effective extract was from a soil-based plant from Jalisco (BS), reduced from nitric oxide in a RAW 264.7 culture medium, with an IC50 value of 134 µg of dry extract/mL. The BS extract showed a significant neutral lipid-reducing activity in the zebrafish model, ranging from 3.13 µg/mL p < 0.05 to 100 µg/mL p < 0.0001. Overall, the extracts analyzed here for the first time seem promising for future use because of their antioxidant, anti-inflammatory and anti-obesity potential.

Irisin enhances longevity by boosting SIRT1, AMPK, autophagy and telomerase.

Ageing is characterised by the accumulation of molecular and cellular damage through time, leading to a decline in physical and mental abilities. Currently, society has experienced a rapid increase in life expectancy, which has led to an increase in age-associated diseases. Therefore, it is crucial to study the process of ageing to guarantee the best conditions in the final stages of life. In recent years, interest has increased in a myokine known as irisin, which is secreted during physical exercise. This polypeptide hormone is produced by various organs, mainly muscle, and once it is released into the blood, it performs a wide variety of functions that are involved in metabolic control and may be relevant during some of the diseases associated with ageing. The aim of this review is to highlight the recent studies of irisin, such as its mechanism of expression, blood release, distribution, tissue target and participation in various cellular metabolic reactions and the relationship with key anti-ageing pathways such as adenosine monophosphate-activated protein kinase, silent information regulator T 1, autophagy and telomerase. In conclusion, irisin is a key player during the ageing process and it could be a novel target molecule for the therapeutic approach to boost longevity pathways. However, more research will be necessary to use this promising hormone for this gain.

Inflammasome Activation: A Keystone of Proinflammatory Response in Obstructive Sleep Apnea.

Rationale: As the mechanism that links obstructive sleep apnea (OSA) with the regulation of inflammatory response is not well known, it is important to understand the inflammasome activation, mainly of NLRP3 (nucleotide-binding oligomerization domain-like receptor 3). Objectives: To assess the NLRP3 activity in patients with severe OSA and to identify its role in the systemic inflammatory response of patients with OSA. Methods: We analyzed the NLRP3 activity as well as key components of the inflammasome cascade, such as adaptor molecule apoptosis-associated speck-like protein, caspase-1, Gasdermin D, IL-1ß, IL-18, and tissue factor, in monocytes and plasma from patients with severe OSA and control subjects without sleep apnea. We explored the association of the different key markers with inflammatory comorbidities. Measurements and Main Results: Monocytes from patients with severe OSA presented higher NLRP3 activity than those from control subjects, which directly correlated with the apnea-hypopnea index and hypoxemic indices. NLRP3 overactivity triggered inflammatory cytokines (IL-1ß and IL-18) via caspase-1 and increased Gasdermin D, allowing for tissue factor to be released. In vitro models confirmed that monocytes increase NLRP3 signaling under intermittent hypoxia in a hypoxia-inducible factor-1α-dependent manner, and/or in combination with plasma from patients with OSA. Plasma concentrations of tissue factor were higher in patients with OSA with systemic inflammatory comorbidities than in those without them. Conclusions: In patients with severe OSA, NLRP3 activation might be a linking mechanism between intermittent hypoxia and other OSA-induced immediate changes with the development of systemic inflammatory response.

Procoagulant State of Sleep Apnea Depends on Systemic Inflammation and Endothelial Damage.

INTRODUCTION: Growing evidence shows a hypercoagulable state in obstructive sleep apnea (OSA) that could be a risk factor for thromboembolic disease. OBJECTIVES: We aimed to elucidate mechanisms involved in the procoagulant profile observed in patients with OSA and to investigate the potential utility of global tests in its characterization. METHODS: Thirty-eight patients with severe OSA without previous history of thrombosis and nineteen healthy age- and sex-matched controls were included. Kinetic of clot formation was determined using rotational thromboelastometry. Haemostatic capacity of plasma and microparticles was determined by Calibrated Automated Thrombinography. Platelet surface receptors, activation markers and formation of platelet/leukocytes aggregates were analyzed by flow cytometry. RESULTS: Thromboelastometry showed a procoagulant state in patients with OSA that did not seem to be related to a basal activation of platelets but by the increased existence of platelet/leukocyte aggregates. Patients with OSA presented many signs of endothelial damage such as increased plasma levels of E-selectin and cfDNA and enhanced thrombin generation due to the presence of microparticles rich in tissue-factor, which is related to OSA severity. CONCLUSIONS: OSA induces an enhancement in the dynamics of clot formation which appears to be caused by at least two pathological mechanisms. First, a greater formation of platelet-leukocyte aggregates; secondly, endothelial damage which provokes a greater procoagulant potential due to the increase in tissue factor-rich microparticles. Moreover, this study has identified thromboelastometry and thrombin generation assay as useful tools to evaluate the prothrombotic state in these patients.

Intermittent Hypoxia Mediates Paraspeckle Protein-1 Upregulation in Sleep Apnea.

As some evidence suggests that hypoxia might be an inducer of nuclear paraspeckle formation, we explore whether intermittent hypoxia (IH)-mediated paraspeckle protein-1 (PSPC1) overexpression might contribute to the activation of tumor growth factor (TGF)ß-SMAD pathway in patients with obstructive sleep apnea (OSA). This activation would promote changes in intracellular signaling that would explain the increased cancer aggressiveness reported in these patients. Here, we show that patients with OSA exhibit elevated PSPC1 levels both in plasma and in monocytes. Our data suggest that PSPC1 is ultimately delivered to the plasma through its cleavage from OSA monocytes by matrix metalloproteinase-2 (MMP2). In addition, IH promotes PSPC1, TGFß, and MMP2 expression in monocytes through the hypoxia-inducible factor. Lastly, both PSPC1 and TGFß induce increased expression of genes that drive the epithelial-to-mesenchymal transition. Our study details the mechanism by which hypoxemia upmodulates the extracellular release of PSPC1 by means of MMP2, such that plasma PSPC1 together with TGFß activation signaling further promotes tumor metastasis and supports cancer aggressiveness in patients with OSA.

Contribution of sleep characteristics to the association between obstructive sleep apnea and dyslipidemia.

OBJECTIVES/BACKGROUND: Little information is available about the association of obstructive sleep apnea (OSA) with atherogenic dyslipidemia and the contribution of sleep characteristics to lipid alterations. We compare dyslipidemia prevalence among non-apneic subjects and mild-severe OSA patients to identify the sleep characteristics that are independently associated with dyslipidemia and serum lipid levels in OSA patients. PATIENTS/METHODS: We recruited 809 consecutive patients who had been referred for polysomnography study by OSA suspicion. Anthropometric characteristics, body composition and comorbidities were recorded. Spirometry and 24-h ambulatory blood pressure monitoring were performed the same day of the sleep study. The day after attended polysomnography, fasting blood samples were drawn to measure the lipid profile. RESULTS: Dyslipidemia prevalence increased with the presence of OSA, from non-OSA subjects to mild, moderate and severe OSA patients (31%, 33%, 42% and 51%, respectively; p < 0.001). After adjusting for sex, age, body mass index and smoking habit, only severe OSA had an independent association with dyslipidemia when compared to non-OSA subjects (adjusted odds ratio 1.71, 95%CI 1.09 to 2.69, p = 0.019). In OSA patients, multivariate logistic regression identified active smoking, apnea-hypopnea index (AHI) and mean nocturnal saturation as variables independently associated with dyslipidemia. However, in these patients, arousal index, slow wave sleep duration and REM latency were also independently associated with cholesterol and low-density lipoprotein levels. CONCLUSIONS: The association between dyslipidemia and OSA is limited to severe patients, with high AHI and nocturnal hypoxemia. However, sleep fragmentation and increased sympathetic activity could also contribute to OSA-related lipid dysregulation.

Inhibition of Intestinal Lipid Absorption by Cyanobacterial Strains in Zebrafish Larvae.

Obesity is a complex metabolic disease, which is increasing worldwide. The reduction of dietary lipid intake is considered an interesting pathway to reduce fat absorption and to affect the chronic energy imbalance. In this study, zebrafish larvae were used to analyze effects of cyanobacteria on intestinal lipid absorption in vivo. In total, 263 fractions of a cyanobacterial library were screened for PED6 activity, a fluorescent reporter of intestinal lipases, and 11 fractions reduced PED6 activity > 30%. Toxicity was not observed for those fractions, considering mortality, malformations or digestive physiology (protease inhibition). Intestinal long-chain fatty acid uptake (C16) was reduced, but not short-chain fatty acid uptake (C5). Alteration of lipid classes by high-performance thin-layer chromatography (HPTLC) or lipid processing by fluorescent HPTLC was analyzed, and 2 fractions significantly reduced the whole-body triglyceride level. Bioactivity-guided feature-based molecular networking of LC-MS/MS data identified 14 significant bioactive mass peaks (p < 0.01, correlation > 0.95), which consisted of 3 known putative and 11 unknown compounds. All putatively identified compounds were known to be involved in lipid metabolism and obesity. Summarizing, some cyanobacterial strains repressed intestinal lipid absorption without any signs of toxicity and could be developed in the future as nutraceuticals to combat obesity.

A policy response to workplace innovation for the rail sector.

The rail sector is a sector with a significant impact on European industry and it is therefore important that it follows the current innovative trends. We live in an increasingly digitised society but, until now, digitisation has not been a priority issue for the sector as the rules that apply to the entire value chain have hindered the digitisation process. Even so, technologies are not enough, and innovation must be implemented in companies at the organisational and employee level. The RailActivation project has experimented with workplace innovation to foster innovation capabilities in the railway sector, providing elements for companies to remain as innovative and competitive as possible, as well as to have additional tools to adapt to these challenges. In order to help in this process, this article proposes a series of recommendations based on the lessons learnt during the implementation of the project. These recommendations establish a link between policy and workplace innovation practices and could be a reference framework for further research and policy. The suggested policy recommendations are focused on companies and policy makers and are based on the results obtained from the different consultations with the stakeholders involved in this research.

SMAD4 Overexpression in Patients with Sleep Apnoea May Be Associated with Cardiometabolic Comorbidities.

Obstructive sleep apnoea (OSA) is associated with several diseases related to metabolic and cardiovascular risk. Although the mechanisms involved in the development of these disorders may vary, OSA patients frequently present an increase in transforming growth factor beta (TGFß), the activity of which is higher still in patients with hypertension, diabetes or cardiovascular morbidity. Smad4 is a member of the small mother against decapentaplegic homologue (Smad) family of signal transducers and acts as a central mediator of TGFß signalling pathways. In this study, we evaluate Smad4 protein and mRNA expression from 52 newly diagnosed OSA patients, with an apnoea-hypopnoea index (AHI) ≥30 and 26 healthy volunteers. These analyses reveal that OSA patients exhibit high levels of SMAD4 which correlates with variation in HIF1α, mTOR and circadian genes. Moreover, we associated high concentrations of Smad4 plasma protein with the presence of diabetes, dyslipidaemia and hypertension in these patients. Results suggest that increased levels of SMAD4, mediated by intermittent hypoxaemia and circadian rhythm deregulation, may be associated with cardiometabolic comorbidities in patients with sleep apnoea.

Activating inclusive growth in railway SMEs by workplace innovation.

The digital revolution is happening, transforming the way we move and produce. Success in the digital revolution means that the rail industries need to use the best available technologies focusing on people. The managerial and organizational practices adopted by railway entities have considerable significance for Railway's ability to succeed in global competition. One of the challenges for railway entities is to deliver innovative products, offering quickness and flexibility to respond to changing demands from their customers. Non-technological innovations and especially Workplace innovation, have a key role to play in the digitalization and acceleration of technological developments, therefore in the railway sector competitiveness. This draws attention to the importance of innovation climate and employees' commitment aiming at improving staff motivation and working conditions, thereby enhancing labor productivity, organizational performance, innovation capability, reactivity to market change, and consequently business competitiveness. As with any emerging opportunity, there is no established path to follow to activate inclusive growth in railway SMEs to uptake Workplace innovation. To address these issues, this paper develops and tests a research model that covers individual behavior, organizational practices, and process practices of innovation among employees, analyzing the impact of Workplace Innovation on firm performance.

Amiloidosis derivada del factor quimiotáctico de leucocitos 2 (ALECT2): a propósito de un caso / LECT2-associated renal amyloidosis (ALECT2): A case report

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Tratamiento congestivo: diuréticos, resistencia diurética y alternativas Papel de la ultrafiltración / Tratamento congestivo: diuréticos, resistência diurética e alternativas Papel da ultrafiltração / Congestive treatment: diuretic treatment, diuretic resistance and alternatives Ultrafiltration role

Los pacientes con insuficiencia cardíaca descompensada presentan un estado congestivo. La inmensa mayoría de las veces es debido a la activación de mecanismos neurohormonales que provocan la retención de sodio y agua a nivel renal. Esta activación y la congestión pueden devenir en la alteración de la función renal (síndrome cardio-renal). El tratamiento de la congestión se basa en el uso de diuréticos, pero la inmensa mayoría de estos pacientes presentan resistencia a los mismos, además de sufrir diferentes efectos secundarios por su uso, como las alteraciones hidroelectrolíticas. Terapias como la ultrafiltración o la diálisis peritoneal se han valorado en el tratamiento de la insuficiencia cardíaca congestiva. Nuestro objetivo es hacer una aproximación al lector de las alternativas al tratamiento diurético en el paciente congestivo, centrándonos, prioritariamente, en la ultrafiltración.

Patients with decompensated heart failure have a congestive state. Volume overloaded state is due to neurohormonal mechanisms activation that cause the retention of sodium and water by the kidney. This activation and congestion can lead to impaired renal function (cardio-renal syndrome). Congestive treatment is based on use of diuretics but the vast majority of these patients have diuretic resistance, as well as suffering from different side effects due to their use such as hydroelectrolytic alterations. Therapies such ultrafiltration or peritoneal dialysis have been evaluated in the treatment of congestive heart failure. Our objective is to make an approximation of other therapeutic strategies specially on ultrafiltration to resolve congestive state.

Pacientes com insuficiência cardíaca descompensada apresentam um estado congestivo. A grande maioria é devido à ativação de mecanismos neuro-hormonais que causam a retenção de sódio e água nos rins. Essa ativação e congestão podem resultar em comprometimento da função renal (síndrome cardio-renal). O tratamento da congestão baseia-se no uso de diuréticos, mas a grande maioria destes pacientes têm a mesma resistência, e sofrem de diversos efeitos colaterais por utilização, como perturbações electrolíticas. Terapias como ultrafiltração ou diálise peritoneal foram avaliadas no tratamento da insuficiência cardíaca congestiva. Nosso objetivo é aproximar o leitor das alternativas ao tratamento diurético no paciente congestivo, enfocando, principalmente, a ultrafiltração.

The effect of treatment for sleep apnoea on determinants of blood pressure control.

Our aim was to assess the effect of continuous positive airway pressure (CPAP) on the nocturnal evolution of peripheral chemosensitivity, renin-angiotensin-aldosterone system activity, sympathetic tone and endothelial biomarkers in obstructive sleep apnoea (OSA) patients with isolated nocturnal hypertension (INH) or day-night sustained hypertension (D-NSH).In a crossover randomised trial, 32 OSA patients newly diagnosed with hypertension and without antihypertensive treatment were randomly assigned to 12 weeks of CPAP or sham CPAP. Peripheral chemosensitivity was evaluated before and after sleep using the hypoxic withdrawal test (%ΔVI).At baseline, D-NSH patients showed higher %ΔVI before sleep and higher levels of aldosterone and diurnal catecholamines. CPAP only reduced the nocturnal increase of %ΔVI in INH patients (6.9%, 95% CI 1.0-12.8%; p=0.026). CPAP-induced change from baseline in %ΔVI after sleep was 7.5% (95% CI 2.6-12.2%, p=0.005) in the INH group and 5.7% (95% CI 2.2-9.3%, p=0.004) in the D-NSH group. In contrast, %ΔVI before sleep only decreased with CPAP in the D-NSH patients (3.0%, 95% CI 0.5-5.6%; p=0.023).In conclusion, CPAP reduces the nocturnal increase of peripheral chemosensitivity experienced by INH patients and corrects the high daytime sensitivity of patients with D-NSH. Differences in response to CPAP between these patients can help better understand the mechanisms of perpetuation of hypertension in sleep apnoea.

Alpha lipoic acid efficacy in burning mouth syndrome. A controlled clinical trial.

BACKGROUND: A double-blind placebo-controlled trial was conducted in order to evaluate the efficacy of alpha lipoic acid (ALA) and determine the statistical significance of the outcome variables. Burning mouth syndrome (BMS) is defined as an oral burning sensation in the absence of clinical signs which could justify the syndrome. Recent studies suggest the existence of neurological factors as a possible cause of the disease. MATERIAL AND METHODS: 60 patients with BMS, in two groups: case group with 600 mg/day and placebo as control group; with follow up of 2 months. RESULTS: 64% of ALA patients reported some level of improvement, with a level of maintenance of 68.75% one month after treatment. 27.6% of the placebo group also demonstrated some reduction in BMS symptoms. CONCLUSIONS: Long-term evolution and the intensity of symptoms are variables that reduce the probability of improvement with ALA treatment.

Cyclin D3 promotes pancreatic ß-cell fitness and viability in a cell cycle-independent manner and is targeted in autoimmune diabetes.

Type 1 diabetes is an autoimmune condition caused by the lymphocyte-mediated destruction of the insulin-producing ß cells in pancreatic islets. We aimed to identify final molecular entities targeted by the autoimmune assault on pancreatic ß cells that are causally related to ß cell viability. Here, we show that cyclin D3 is targeted by the autoimmune attack on pancreatic ß cells in vivo. Cyclin D3 is down-regulated in a dose-dependent manner in ß cells by leukocyte infiltration into the islets of the nonobese diabetic (NOD) type 1 diabetes-prone mouse model. Furthermore, we established a direct in vivo causal link between cyclin D3 expression levels and ß-cell fitness and viability in the NOD mice. We found that changes in cyclin D3 expression levels in vivo altered the ß-cell apoptosis rates, ß-cell area homeostasis, and ß-cell sensitivity to glucose without affecting ß-cell proliferation in the NOD mice. Cyclin D3-deficient NOD mice exhibited exacerbated diabetes and impaired glucose responsiveness; conversely, transgenic NOD mice overexpressing cyclin D3 in ß cells exhibited mild diabetes and improved glucose responsiveness. Overexpression of cyclin D3 in ß cells of cyclin D3-deficient mice rescued them from the exacerbated diabetes observed in transgene-negative littermates. Moreover, cyclin D3 overexpression protected the NOD-derived insulinoma NIT-1 cell line from cytokine-induced apoptosis. Here, for the first time to our knowledge, cyclin D3 is identified as a key molecule targeted by autoimmunity that plays a nonredundant, protective, and cell cycle-independent role in ß cells against inflammation-induced apoptosis and confers metabolic fitness to these cells.

Tratamiento por teléfono del tabaquismo. Factores predictivos de éxito / Telephone-based smoking cessation. Predictors of success

Fundamento y objetivo: Evaluar los factores predictivos de éxito del tratamiento telefónico del tabaquismo. Pacientes y métodos: Estudio observacional realizado en el contexto de la práctica clínica en una Unidad de Tabaquismo. Programa de tratamiento por teléfono durante 3 meses y seguimiento hasta los seis meses. Se analizaron variables sociodemográficas, de dependencia y comorbilidad, y como variable principal la abstinencia continua a las 24 semanas. Resultados: Se incluyeron 743 sujetos (43% varones y 57% mujeres), con edad media (DE) de 41,9 (9,8) años. La abstinencia continua fue del 37,3% (intervalo de confianza del 95% [IC 95%] 34,9-40,0). El modelo multivariable mostró tres variables con valor predictivo: no padecer trastorno psiquiátrico, vivir en pareja y el primer ítem del test de Fagerström. Conclusiones: El resultado del programa de tratamiento estuvo condicionado por las siguientes variables del fumador: la dependencia a la nicotina, la patología psiquiátrica y el soporte social (AU)

Background and objective: To identify the predictors of successful outcome in a telephone smoking cessation program. Patients and methods: Observational study in the context of clinical practice in a smoking cessation clinic. The smoking cessation program was carried out by phone over a period of 3 months and follow-up for 6 months. Sociodemographic variables were analyzed, dependence, and comorbidity and the main variable was continuous abstinence at 24 weeks. Results: 743 smokers, 43% male and 57% female, mean (SD) age: 41.9 (9.8) years. The continuous abstinence rate at 24 weeks was 37.3% (IC 95% 34.9-40.0).The multivariable model showed three variables with predictive value: no current psychiatric diagnosis, social support and the first item of Fagerström test (time to first cigarette in the morning). Conclusions: Treatment outcomes of this smoking cessation program was influenced by the following variables: nicotine dependence, psychiatric disorders and social support (AU)

[Telephone-based smoking cessation. Predictors of success]. / Tratamiento por teléfono del tabaquismo. Factores predictivos de éxito.

BACKGROUND AND OBJECTIVE: To identify the predictors of successful outcome in a telephone smoking cessation program. PATIENTS AND METHODS: Observational study in the context of clinical practice in a smoking cessation clinic. The smoking cessation program was carried out by phone over a period of 3 months and follow-up for 6 months. Sociodemographic variables were analyzed, dependence, and comorbidity and the main variable was continuous abstinence at 24 weeks. RESULTS: 743 smokers, 43% male and 57% female, mean (SD) age: 41.9 (9.8) years. The continuous abstinence rate at 24 weeks was 37.3% (IC 95% 34.9-40.0).The multivariable model showed three variables with predictive value: no current psychiatric diagnosis, social support and the first item of Fagerström test (time to first cigarette in the morning). CONCLUSIONS: Treatment outcomes of this smoking cessation program was influenced by the following variables: nicotine dependence, psychiatric disorders and social support.