Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean ...diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet.
A randomized trial (two MedDiet intervention groups and a control group) with 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for cardiovascular events.
The TCF7L2-rs7903146 polymorphism was associated with type 2 diabetes (odds ratio 1.87 95% CI 1.62-2.17 for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004). When adherence to the MedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 95% CI 1.36-6.19; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjusted HR 0.96 95% CI 0.49-1.87; P = 0.892 for TT compared with CC).
Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence.
Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a heterogeneous state of chronic intestinal inflammation with no exact known cause. Intestinal innate ...immunity is enacted by neutrophils, monocytes, macrophages, and dendritic cells (DCs), and innate lymphoid cells and NK cells, characterized by their capacity to produce a rapid and nonspecific reaction as a first-line response. Innate immune cells (IIC) defend against pathogens and excessive entry of intestinal microorganisms, while preserving immune tolerance to resident intestinal microbiota. Changes to this equilibrium are linked to intestinal inflammation in the gut and IBD. IICs mediate host defense responses, inflammation, and tissue healing by producing cytokines and chemokines, activating the complement cascade and phagocytosis, or presenting antigens to activate the adaptive immune response. IICs exert important functions that promote or ameliorate the cellular and molecular mechanisms that underlie and sustain IBD. A comprehensive understanding of the mechanisms underlying these clinical manifestations will be important for developing therapies targeting the innate immune system in IBD patients. This review examines the complex roles of and interactions among IICs, and their interactions with other immune and non-immune cells in homeostasis and pathological conditions.
Review of natural products with hepatoprotective effects Eduardo Madrigal-Santillán Eduardo Madrigal-Bujaidar Isela álvarez-González María Teresa Sumaya-Martínez José Gutiérrez-Salinas Mirandeli Bautista ángel Morales-González Manuel García-Luna y González-Rubio J Leopoldo Aguilar-Faisal José A Morales-González
World journal of gastroenterology,
10/2014, Letnik:
20, Številka:
40
Journal Article
Odprti dostop
The liver is one of the most important organs in the body,performing a fundamental role in the regulationof diverse processes,among which the metabolism,secretion,storage,and detoxification of ...endogenous and exogenous substances are prominent.Due to these functions,hepatic diseases continue to be among the main threats to public health,and they remain problems throughout the world.Despite enormous advances in modern medicine,there are no completely effective drugs that stimulate hepatic function,that offer complete protection of the organ,or that help to regenerate hepatic cells.Thus,it is necessary to identify pharmaceutical alternatives for the treatment of liver diseases,with the aim of these alternatives being more effective and less toxic.The use of some plants and the consumption of different fruits have played basic roles in human health care,and diverse scientific investigations have indicated that,in those plants and fruits so identified,their beneficial effects can be attributed to the presence of chemical compounds that are called phytochemicals.The present review had as its objective the collecting of data based on research conducted into some fruits(grapefruit,cranberries,and grapes)and plantscactus pear(nopal)and cactus pear fruit,chamomile,silymarin,and spirulina,which are consumed frequently by humans and which have demonstrated hepatoprotective capacity,as well as an analysis of a resin(propolis)and some phytochemicals extracted from fruits,plants,yeasts,and algae,which have been evaluated in different models of hepatotoxicity.
Aims
To contrast functional connectivity on ventral and dorsal striatum networks in cocaine dependence relative to pathological gambling, via a resting‐state functional connectivity approach; and to ...determine the association between cocaine dependence‐related neuroadaptations indexed by functional connectivity and impulsivity, compulsivity and drug relapse.
Design
Cross‐sectional study of 20 individuals with cocaine dependence (CD), 19 individuals with pathological gambling (PG) and 21 healthy controls (HC), and a prospective cohort study of 20 CD followed‐up for 12 weeks to measure drug relapse.
Setting and Participants
CD and PG were recruited through consecutive admissions to a public clinic specialized in substance addiction treatment (Centro Provincial de Drogodependencias) and a public clinic specialized in gambling treatment (AGRAJER), respectively; HC were recruited through community advertisement in the same area in Granada (Spain).
Measurements
Seed‐based functional connectivity in the ventral striatum (ventral caudate and ventral putamen) and dorsal striatum (dorsal caudate and dorsal putamen), the Kirby delay‐discounting questionnaire, the reversal‐learning task and a dichotomous measure of cocaine relapse indicated with self‐report and urine tests.
Findings
CD relative to PG exhibit enhanced connectivity between the ventral caudate seed and subgenual anterior cingulate cortex, the ventral putamen seed and dorsomedial pre‐frontal cortex and the dorsal putamen seed and insula (P ≤ 0.001, kE = 108). Connectivity between the ventral caudate seed and subgenual anterior cingulate cortex is associated with steeper delay discounting (P ≤ 0.001, kE = 108) and cocaine relapse (P ≤ 0.005, kE = 34).
Conclusions
Cocaine dependence‐related neuroadaptations in the ventral striatum of the brain network are associated with increased impulsivity and higher rate of cocaine relapse.
Abstract Background The aim of this study was to compare the cognitive performance of cocaine dependent individuals (CDI) with that of pathological gamblers (PG). Cocaine dependence and pathological ...gambling share neurobiological vulnerabilities related to addiction, but PG are relatively free of the toxic consequences, such that any additional deficits observed in CDI may be interpreted as pertaining to specific drug effects. Methods We used a case–control observational design contrasting multiple measures of impulsivity (UPPS-P trait impulsivity, delay discounting) and executive measures of response inhibition (Stroop) and working memory performance ( N -back) between groups of CDI ( n = 29), PG ( n = 23), and healthy controls ( n = 20). We conducted one-way ANOVAs, followed by planned pairwise tests and calculations of Cohen's d to estimate significant differences between the groups. Results CDI, as compared to PG, had elevated scores on UPPS-P Negative Urgency and poorer performance on working memory (2-back). PG had steeper delay-discounting rates. Both groups had elevated Positive Urgency and poorer Stroop inhibition compared to controls. Peak amount of cocaine use was negatively correlated with working memory and response inhibition performance. Conclusion We found cocaine-related specific elevations in Negative Urgency and working memory deficits, putatively identified as cocaine neurotoxicity effects. Other aspects of impulsivity (Positive Urgency, Stroop inhibition) were increased across CDI and PG groups and may reflect vulnerability factors for addiction.
The impact of the mitochondria‐targeted antioxidant MitoQ was evaluated in the metabolic alterations and the adipose tissue remodeling associated with obesity. Male Wistar rats were fed either a ...high‐fat diet (HFD; 35% fat) or a standard diet (3.5% fat) for 7 wk and treated with MitoQ (200 μM). A proteomic analysis of visceral adipose tissue from patients with obesity and patients without obesity was performed. MitoQ partially prevented the increase in body weight, adiposity, homeostasis model assessment index, and adipose tissue remodeling in HFD rats. It also ameliorated protein level changes of factors involved in insulin signaling observed in adipose tissue of obese rats: reductions in adiponectin and glucose transporter 4 (GLUT 4) and increases in dipeptidylpeptidase 4, suppressor of cytokine signaling 3 (SOCS3), and insulin receptor substrate 1 phosphorylation. MitoQ prevented down‐regulation of adiponectin and GLUT 4 and increases in SOCS3 levels in a TNF‐α‐induced insulin‐resistant 3T3‐L1 adipocyte model. MitoQ also ameliorated alterations in mitochondrial proteins observed in obese rats: increases in cyclophylin F and carnitine palmitoyl transferase 1A and reductions in mitofusin1, peroxiredoxin 4, and fumarate hydratase. The proteomic analysis of the visceral adipose tissue from patients with obesity show alterations in mitochondrial proteins similar to those observed in obese rats. Therefore, the data show the beneficial effect of MitoQ in the metabolic dysfunction induced by obesity.—Marín‐Royo, G., Rodríguez, C., Le Pape, A., Jurado‐Lopez, R., Luaces, M., Antequera, A., Martinez‐Gonzalez, J., Souza‐Neto, F. V., Nieto, M. L., Martínez‐Martínez, E., Cachofeiro, V. The role of mitochondrial oxidative stress in the metabolic alterations in diet‐induced obesity in rats. FASEB J. 33, 12060‐12072 (2019). www.fasebj.org
Familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data on attainment of treatment ...targets; large registries that reflect real-life clinical practice can uniquely provide this information.
We sought to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients enrolled in a large national registry.
The SAFEHEART study (Spanish Familial Hypercholesterolemia Cohort Study) is a large, ongoing registry of molecularly defined patients with heterozygous FH treated in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was investigated in relation to use of lipid-lowering therapy (LLT).
The study recruited 4,132 individuals (3,745 of whom were ≥18 years of age); 2,752 of those enrolled were molecularly diagnosed FH cases. Mean follow-up was 5.1 ± 3.1 years; 71.8% of FH cases were on maximal LLT, and an LDL-C treatment target <100 mg/dl was reached by only 11.2% of patients. At follow-up, there was a significant increase in the use of ezetimibe, drug combinations with statins, and maximal LLT. The presence of type 2 diabetes mellitus, a defective allele mutation, ezetimibe use, and the absence of previous ASCVD were predictors of the attainment of LDL-C goals.
Despite the use of intensified LLT, many FH patients continue to experience high plasma LDL-C levels and, consequently, do not achieve recommended treatment targets. Type of LDL-receptor mutation, use of ezetimibe, coexistent diabetes, and ASCVD status can bear significantly on the likelihood of attaining LDL-C treatment goals.
Solid polymer electrolytes (SPEs) comprising lithium bis(fluorosulfonyl)imide (LiN(SO2F)2, LiFSI) and poly(ethylene oxide) (PEO) have been studied as electrolyte material and binder for the Li–S ...polymer cell. The LiFSI-based Li–S all solid polymer cell can deliver high specific discharge capacity of 800 mAh gsulfur –1 (i.e., 320 mAh gcathode –1), high areal capacity of 0.5 mAh cm–2, and relatively good rate capability. The cycling performances of Li–S polymer cell with LiFSI are significantly improved compared with those with conventional LiTFSI (LiN(SO2CF3)2) salt in the polymer membrane due to the improved stability of the Li anode/electrolyte interphases formed in the LiFSI-based SPEs. These results suggest that the LiFSI-based SPEs are attractive electrolyte materials for solid-state Li–S batteries.
Inflammatory bowel disease (IBD) is an umbrella term for the chronic immune-mediated idiopathic inflammation of the gastrointestinal tract, manifesting as Crohn's disease (CD) or ulcerative colitis ...(UC). IBD is characterized by exacerbated innate and adaptive immunity in the gut in association with microbiota dysbiosis and the disruption of the intestinal barrier, resulting in increased bacterial exposure. In response to signals from microorganisms and damaged tissue, innate immune cells produce inflammatory cytokines and factors that stimulate T and B cells of the adaptive immune system, and a prominent characteristic of IBD patients is the accumulation of inflammatory T-cells and their proinflammatory-associated cytokines in intestinal tissue. Upon antigen recognition and activation, CD4 T-cells differentiate towards a range of distinct phenotypes: T helper(h)1, Th2, Th9, Th17, Th22, T follicular helper (Tfh), and several types of T-regulatory cells (Treg). T-cells are generated according to and adapt to microenvironmental conditions and participate in a complex network of interactions among other immune cells that modulate the further progression of IBD. This review examines the role of the CD4 T-cells most relevant to IBD, highlighting how these cells adapt to the environment and interact with other cell populations to promote or inhibit the development of IBD.
Multiple sclerosis (MS) is a multifaceted neurological condition characterized by challenges in timely diagnosis and personalized patient management. The application of Artificial Intelligence (AI) ...to MS holds promises for early detection, accurate diagnosis, and predictive modeling. The objectives of this study are: 1) to propose new MS trajectory descriptors that could be employed in Machine Learning (ML) regressors and classifiers to predict patient evolution; 2) to explore the contribution of ML models in discerning MS trajectory descriptors using only baseline Magnetic Resonance Imaging (MRI) studies. This study involved 446 MS patients who had a baseline MRI, at least two measurements of Expanded Disability Status Scale (EDSS), and a 1-year follow-up. Patients were divided into two groups: 1) for model development and 2) for evaluation. Three descriptors: beta.sub.1, beta.sub.2, and EDSS(t), were related to baseline MRI parameters using regression and classification XGBoost models. Shapley Additive Explanations (SHAP) analysis enhanced model transparency by identifying influential features. The results of this study demonstrate the potential of AI in predicting MS progression using the proposed patient trajectories and baseline MRI scans, outperforming classic Multiple Linear Regression (MLR) methods. In conclusion, MS trajectory descriptors are crucial; incorporating AI analysis into MRI assessments presents promising opportunities to advance predictive capabilities. SHAP analysis enhances model interpretation, revealing feature importance for clinical decisions.
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