PAF signaling plays a role in obesity-induced adipose tissue remodeling.

BACKGROUND/OBJECTIVES: Platelet-activating factor receptor (PAFR) activation controls adipose tissue (AT) expansion in animal models. Our objective was twofold: (i) to check whether PAFR signaling is involved in human obesity and (ii) investigate the PAF pathway role in hematopoietic or non-hematopoietic cells to control adipocyte size. MATERIALS/SUBJECTS AND METHODS: Clinical parameters and adipose tissue gene expression were evaluated in subjects with obesity. Bone marrow (BM) transplantation from wild-type (WT) or PAFR-/- mice was performed to obtain chimeric PAFR-deficient mice predominantly in hematopoietic or non-hematopoietic-derived cells. A high carbohydrate diet (HC) was used to induce AT remodeling and evaluate in which cell compartment PAFR signaling modulates it. Also, 3T3-L1 cells were treated with PAF to evaluate fat accumulation and the expression of genes related to it. RESULTS: PAFR expression in omental AT from humans with obesity was negatively correlated to different corpulence parameters and more expressed in the stromal vascular fraction than adipocytes. Total PAFR-/- increased adiposity compared with WT independent of diet-induced obesity. Differently, WT mice receiving PAFR-/--BM exhibited similar adiposity gain as WT chimeras. PAFR-/- mice receiving WT-BM showed comparable augmentation in adiposity as total PAFR-/- mice, demonstrating that PAFR signaling modulates adipose tissue expansion through non-hematopoietic cells. Indeed, the PAF treatment in 3T3-L1 adipocytes reduced fat accumulation and expression of adipogenic genes. CONCLUSIONS: Therefore, decreased PAFR signaling may favor an AT accumulation in humans and animal models. Importantly, PAFR signaling, mainly in non-hematopoietic cells, especially in adipocytes, appears to play a significant role in regulating diet-induced AT expansion.

Severe psychiatric disorders and general medical comorbidities: inflammation-related mechanisms and therapeutic opportunities.

Individuals with severe psychiatric disorders, such as mood disorders and schizophrenia, are at increased risk of developing other medical conditions, especially cardiovascular and metabolic diseases. These medical conditions are underdiagnosed and undertreated in these patients contributing to their increased morbidity and mortality. The basis for this increased comorbidity is not well understood, possibly reflecting shared risks factors (e.g. lifestyle risk factors), shared biological mechanisms and/or reciprocal interactions. Among overlapping pathophysiological mechanisms, inflammation and related factors, such as dysbiosis and insulin resistance, stand out. Besides underlying the association between psychiatric disorders and cardiometabolic diseases, these mechanisms provide several potential therapeutic targets.

The Involvement of Kynurenine Pathway in Neurodegenerative Diseases.

BACKGROUND: A growing body of evidence has shown the involvement of the kynurenine pathway (KP), the primary route of tryptophan (TRP) catabolism, in the pathophysiology of neuropsychiatric disorders. OBJECTIVE: The study aims to provide a comprehensive and critical overview of the clinical evidence on the KP involvement in the pathophysiology of Alzheimer's disease (AD) and Parkinson's disease (PD), discussing therapeutic opportunities. METHODS: We searched for studies investigating KP metabolites in human subjects with AD and/or PD. RESULTS: Postmortem studies showed altered levels of KP metabolites in the brain of AD and PD patients compared with controls. Cross-sectional studies have reported associations between peripheral levels (serum or plasma) of KP metabolites and cognitive function in these patients, but the results are not always concordant. CONCLUSION: Given the emerging evidence of the involvement of KP in the pathophysiology of neuropsychiatric/ neurodegenerative diseases and promising results from preclinical pharmacological studies, a better understanding of the KP involvement in AD and PD is warranted. Future longitudinal studies are needed to define the direction of the observed associations and specific therapeutic targets within the KP.

Accelerated epigenetic aging in older adults with HIV disease: associations with serostatus, HIV clinical factors, and health literacy.

The prevalence of older persons with HIV (PWH) disease has increased considerably in the last 20 years, but our understanding of biological factors of aging and their clinical correlates among PWH remains limited. Study participants were 149 persons aged 50 and older, including 107 PWH and 42 seronegatives. All participants completed a blood draw, research medical evaluation, structured psychiatric interview, neurocognitive assessment, questionnaires, and measures of health literacy. Four epigenetic clocks were generated from stored blood samples using standardized laboratory methods. In regression models adjusting for sex and smoking status, PWH had significantly higher epigenetic aging acceleration values than seronegatives on all four indicators. Within the PWH sample, higher levels of epigenetic aging acceleration were moderately associated with lower current CD4 count, AIDS diagnoses, higher scores on the Veterans Aging Cohort Study Index, and lower telomere values. Higher epigenetic aging acceleration indices were also associated with lower health literacy among PWH. PWH experience accelerated aging as measured by a series of epigenetic clocks, which may be linked to immune compromise and risk of all-cause mortality. Health literacy may be a modifiable target for mitigating the risk of accelerated aging among older PWH.

Genome-wide association study for morphological traits and resistance to Peryonella pinodes in the USDA pea single plant plus collection.

Peas (Pisum sativum) are the second most cultivated pulse crop in the world. They can serve as human food, fodder, and cover crop. The most serious foliar disease of pea cultivars worldwide is Ascochyta blight, which can be caused by several pathogens. Of these, Peyronella pinodes is the most aggressive and prevalent worldwide. Several traits, including resistance to Peyronella pinodes, stem diameter, internode length between nodes 2-3 and 5-6, and area of 7th leaf, were measured in 269 entries of the pea single plant plus collection. The heritability (H2) of the morphological traits was relatively high, while disease resistance had low heritability. Using 53,196 single-nucleotide polymorphism markers to perform a genome-wide association study to identify genomic loci associated with variation in all the traits measured, we identified 27 trait-locus associations, 5 of which were associated with more than 1 trait.

Factors Associated with Apathy in Alzheimer's Disease: A Cross-Sectional Analysis of the Texas Alzheimer's Research and Care Consortium (TARCC) Study.

BACKGROUND: Apathy is among the most frequent neuropsychiatric syndromes in Alzheimer's disease (AD). OBJECTIVE: To determine the prevalence of apathy and the associated clinical and laboratorial parameters (focus on inflammatory biomarkers) in patients with dementia enrolled at the Texas Alzheimer's Research and Care Consortium (TARCC) study. METHODS: This is a cross-sectional analysis of TARCC baseline. Participants were evaluated through different clinical tools, including the Mini-Mental State Examination (MMSE) and the Lawton-Brody Instrumental Activities of Daily Life (IADL)/Physical Self-Maintenance Scale (PSMS). Apathy was defined by a positive response to the respective item in the Neuropsychiatric Inventory-Questionnaire applied to caregivers. Serum levels of 16 biomarkers were determined by HumanMap multiplex immunoassay. Comparisons between apathy versus non-apathy groups were carried out with non-parametric tests. Logistic regression and the least absolute shrinkage and selection operator (LASSO) were used to separately model apathy as a function of each biomarker, adjusted for the potential confounders. RESULTS: From 1,319 patients with AD (M/F: 579/740, mean age ±â€ŠSD: 75.3 ±â€Š8.4), 373 (28.3%) exhibited apathy. When categorized according to the presence of apathy, the groups had significant differences in sex, diabetes diagnosis, and tobacco use. The apathy group also had worse cognitive performance and daily functioning than the non-apathy group as assessed, respectively, by MMSE and IADL/PSMS. Higher levels of interleukin-6, interleukin-10, and leptin were associated with higher odds of apathy. CONCLUSION: Apathy is associated with cognitive and functional status in AD. The association between apathy and peripheral inflammatory mediators deserves further investigation.

Nutrition-based interventions for mood disorders.

Introduction: 'Nutritional Psychiatry' is an emerging area of research that has great potential as an adjunctive tool for the prevention and treatment of diverse neuropsychiatric disorders. Several nutrition-related aspects, such as obesity, dietary patterns, gut microbiome composition and gut permeability, bioactive food compounds, and nutrients can influence pathways implicated in the pathophysiology of mood disorders.Areas covered: Here, the authors review the current evidence on nutrition-mood interaction and nutrition-based treatments for the two main mood disorders, i.e., major depressive disorder and bipolar disorder.Expert opinion: Consistent evidence from observational studies has pointed out the association between a 'healthy' diet, generally characterized by a higher intake of fruits, vegetables, legumes, nuts, whole grains, and good quality sources of protein (i.e. fish and/or seafood), and decreased risk of mood disorders and the parallel association between a 'Western' diet pattern and increased risk. However, only a few clinical trials have evaluated the effect of nutritional interventions on the treatment of these conditions. The bidirectional interaction between the brain and the gut, named 'brain-gut-microbiome axis' or 'gut-brain axis', plays a key role in the link between nutrition and mood disorders. Therefore, nutrition-based strategies for gut microbiota modulation are promising fields in mood disorders.

Validation and Characterization of Maize Multiple Disease Resistance QTL.

Southern Leaf Blight, Northern Leaf Blight, and Gray Leaf Spot, caused by ascomycete fungi, are among the most important foliar diseases of maize worldwide. Previously, disease resistance quantitative trait loci (QTL) for all three diseases were identified in a connected set of chromosome segment substitution line (CSSL) populations designed for the identification of disease resistance QTL. Some QTL for different diseases co-localized, indicating the presence of multiple disease resistance (MDR) QTL. The goal of this study was to perform an independent test of several of the MDR QTL identified to confirm their existence and derive a more precise estimate of allele additive and dominance effects. Twelve F2:3 family populations were produced, in which selected QTL were segregating in an otherwise uniform genetic background. The populations were assessed for each of the three diseases in replicated trials and genotyped with markers previously associated with disease resistance. Pairwise phenotypic correlations across all the populations for resistance to the three diseases ranged from 0.2 to 0.3 and were all significant at the alpha level of 0.01. Of the 44 QTL tested, 16 were validated (identified at the same genomic location for the same disease or diseases) and several novel QTL/disease associations were found. Two MDR QTL were associated with resistance to all three diseases. This study identifies several potentially important MDR QTL and demonstrates the importance of independently evaluating QTL effects following their initial identification.

Cytokines profile and its correlation with endothelial damage and oxidative stress in patients with type 1 diabetes mellitus and nephropathy.

The aim of the present study was to investigate the association between the presence of albuminuria and cytokines profile with biomarkers of endothelial damage and oxidative stress in patients with type 1 diabetes mellitus (DM1). The sample was composed by 35 healthy individuals, 63 DM1 patients with normoalbuminuria (<30 mg of albumin/g of creatinine) and 62 DM1 patients with micro- and macroalbuminuria (≥30 mg of albumin/g of creatinine). Plasma and urinary cytokines (TNF-α, IL-6 and IL-10) and thrombomodulin levels were determined by ELISA. Oxidative status was evaluated using the TBARS and MTT assays. Diabetic patients were characterized by elevated levels of urinary cytokines TNF-α, IL-6 and IL-10. Those with macroalbuminuria presented significantly higher TNF-α and IL-10 urinary levels when compared to other groups. Urinary and plasmatic levels of TNF-α were positively correlated with plasma levels of cystatin C, creatinine, urea and albuminuria, while they were negatively correlated with estimated glomerular filtration rate. Urinary IL-10 levels proved positive correlation with fasting glucose, HbA1c, thrombomodulin and TBARS, while IL-6 plasma levels were positively correlated with HbA1c and albuminuria. Only urinary TNF-α levels were associated with the presence and severity of macroalbuminuria, after logistic regression analysis. This finding suggests that measurement of urinary TNF-α level may be helpful to evaluate progression to nephropathy in DM1 patients.

Migraine is associated with altered levels of neurotrophins.

Neurotrophic factors have been implicated in hyperalgesia and peripheral levels of these molecules were altered in behavioral and neurological disorders. The objectives of this study were to assess neurotrophic factors levels in migraine patients in comparison with controls, and to investigate whether there was any association between them and clinical parameters. This was a cross-sectional study. We measured serum levels of neurotrophin family members - nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 and 4/5 (NT3 and NT4/5) - and glial cell line-derived factor (GDNF) in patients suffering from migraine and matched controls. One hundred forty-one people were enrolled in this study, seventy-one were migraine patients and seventy were controls. Migraine patients showed more depressive and anxiety symptoms than control individuals as assessed, respectively, by the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory. Chronic and episodic migraine patients showed higher NT4/5 levels than control individuals (P=0.001). Patients with chronic migraine had lower levels of BDNF that were not influenced by the presence of depressive symptoms (P=0.02). This is the first report to evaluate NT3 and NT-4/5 levels in migraine patients. Our findings suggest a possible role of neurotrophic factors in migraine pathophysiology.