Benzbromarone as adjuvant therapy for cystic fibrosis lung disease: a pilot clinical trial.

Objective: Cystic fibrosis (CF) affects multiple organs, the most severe consequences being observed in the lungs. Despite significant progress in developing CF transmembrane conductance regulator-specific treatments for CF lung disease, exploring alternative CF-targeted medications seems reasonable. We sought to evaluate the potential beneficial effects of oral benzbromarone as an adjuvant therapy in CF patients with reduced lung function.

Excess of body weight is associated with accelerated T-cell senescence in hospitalized COVID-19 patients.

Background: Several risk factors have been involved in the poor clinical progression of coronavirus disease-19 (COVID-19), including ageing, and obesity. SARS-CoV-2 may compromise lung function through cell damage and paracrine inflammation; and obesity has been associated with premature immunosenescence, microbial translocation, and dysfunctional innate immune responses leading to poor immune response against a range of viruses and bacterial infections. Here, we have comprehensively characterized the immunosenescence, microbial translocation, and immune dysregulation established in hospitalized COVID-19 patients with different degrees of body weight.

Eotaxin-1/CCL11 promotes cellular senescence in human-derived fibroblasts through pro-oxidant and pro-inflammatory pathways.

Introduction: Eotaxin-1/CCL11 is a pivotal chemokine crucial for eosinophil homing to the lungs of asthmatic patients. Recent studies also suggest that CCL11 is involved in the aging process, as it is upregulated in elderly, and correlated with shorter telomere length in leukocytes from asthmatic children. Despite its potential pro-aging effects, the precise contribution of CCL11 and the underlying mechanisms involved in the promotion of cellular senescence remains unclear.

Characterization of purinergic signaling in tumor-infiltrating lymphocytes from lower- and high-grade gliomas.

Malignant gliomas are highly heterogeneous glia-derived tumors that present an aggressive and invasive nature, with a dismal prognosis. The multi-dimensional interactions between glioma cells and other tumor microenvironment (TME) non-tumoral components constitute a challenge to finding successful treatment strategies. Several molecules, such as extracellular purines, participate in signaling events and support the immunosuppressive TME of glioma patients.

Bioinformatic Analysis of Human Cumulus Cells to Unravel Cellular's Processes that Could Be Used to Establish Oocyte Quality Biomarkers with Clinical Application.

Metadata analysis of public microarray datasets using bioinformatics tools has been successfully used in several biomedical fields in the search for biomarkers. In reproductive science, there is an urgent need for the establishment of oocyte quality biomarkers that could be used in the clinical environment to increase the chances of successful outcomes in treatment cycles. Adaptive cellular processes observed in cumulus oophorus cells reflect the conditions of the follicular microenvironment and may thus bring relevant information of oocyte's conditions.

Telomere length in healthy newborns is not affected by adverse intrauterine environments.

Different intrauterine exposures are associated with different metabolic profiles leading to growth and development characteristics in children and also relate to health and disease patterns in adult life. The objective of this work was to evaluate the impact of four different intrauterine environments on the telomere length of newborns. This is a longitudinal observational study using a convenience sample of 222 mothers and their term newborns (>37 weeks of gestational age) from hospitals in Porto Alegre, Rio Grande do Sul (Brazil), from September 2011 to January 2016.

Telomere length and epigenetic age acceleration in adolescents with anxiety disorders.

Evidence on the relationship between genetics and mental health are flourishing. However, few studies are evaluating early biomarkers that might link genes, environment, and psychopathology. We aimed to study telomere length (TL) and epigenetic age acceleration (AA) in a cohort of adolescents with and without anxiety disorders (N = 234).

Arundic acid (ONO-2526) inhibits stimulated-S100B secretion in inflammatory conditions.

Astrocytes respond to injury by modifying the expression profile of several proteins, including the S100 calcium-binding protein B (S100B), assumed to be a marker as well as a mediator of brain injury. AA is an inhibitor of S100B synthesis and plays a protective role in different models of brain injury, as decreases in S100B expression cause decreases in extracellular S100B. However, S100B mRNA expression, S100B protein content and S100B secretion do not always occur in association; as such, we herein investigated the effect of AA on S100B secretion, using different approaches with three stimulating conditions for S100B secretion, namely, low potassium medium, TNF-α (in hippocampal slices) and LPS exposure (in astrocyte cultures).

Shorter telomeres in children with severe asthma, an indicative of accelerated aging.

Severe therapy-resistant asthma (STRA) is closely associated with distinct clinical and inflammatory pheno-endotypes, which may contribute to the development of age-related comorbidities. Evidence has demonstrated a contribution of accelerated telomere shortening on the poor prognosis of respiratory diseases in adults. Eotaxin-1 (CCL11) is an important chemokine for eosinophilic recruitment and the progression of asthma.

Methoxyeugenol regulates the p53/p21 pathway and suppresses human endometrial cancer cell proliferation.

Ethnopharmacological Relevance: Plant-derived compounds are a reservoir of natural chemicals and can act as drug precursors or prototypes and pharmacological probes. Methoxyeugenol is a natural compound found in plant extracts, such as nutmeg (Myristica fragrans), and it presents anthelmintic, antimicrobial, anti-inflammatory activities. Recently, interest in the anticancer activity of plant extracts is increasing and the therapeutic activity of methoxyeugenol against cancer has not yet been explored.

Retinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin.

Recent studies have investigated the use of retinoic acid (RA) molecule in combined chemotherapies to cancer cells as an attempt to increase treatment efficiency and circumvent cell resistance. Positive results were obtained in clinical trials from lung cancer patients treated with RA and cisplatin. Meanwhile, the signalling process that results from the interaction of both molecules remains unclear.

TRF1 as a major contributor for telomeres' shortening in the context of obesity.

Obesity is a prevalent multifactorial chronic disorder characterized by metabolic dysregulation. Sustained pro-oxidative mediators trigger harmful consequences that reflect at systemic level and contribute for the establishment of a premature senescent phenotype associated with macromolecular damage (DNA, protein, and lipids). Telomeres are structures that protect chromosome ends and are associated with a six-protein complex called the shelterin complex and subject to regulation.

Immunosenescence Induced by Plasma from Individuals with Obesity Caused Cell Signaling Dysfunction and Inflammation.

Objective: To evaluate the consequences of plasma from individuals with obesity on parameters associated with immunosenescence in unrelated healthy peripheral blood mononuclear cells (PBMC).

Methods: Freshly isolated PBMC were incubated in media supplemented with 10% of plasma from individuals with obesity or control subjects for the first 4 hours of 24 to 120 hours of culture.

Results: Plasma from individuals with obesity modulated the phenotype of healthy PBMC, leading to a higher rate of apoptosis, lower amounts of phospho-γH2AX and -p53, and mitochondrial dysfunction.

Arterial stiffness by oscillometric device and telomere lenght in juvenile idiopathic artrhitis with no cardiovascular risk factors: a cross-sectional study.

Background: Advances in juvenile idiopathic arthritis (JIA) treatment is promoting free disease survival. Cardiovascular disease (CVD) may emerge as an important cause of morbidity and mortality. Pulse wave velocity (PWV), a surrogate marker of arterial stiffness, and telomere length (TL) are considered as potential predictors of CVD and its outcomes.

Telomere Length, Oxidative Stress, Inflammation and BDNF Levels in Siblings of Patients with Bipolar Disorder: Implications for Accelerated Cellular Aging.

Background: Growing evidence supports the existence of neurobiological trait abnormalities in individuals at genetic risk for bipolar disorder. The aim of this study was to examine potential differences in brain-derived neurotrophic factor, cytokines, oxidative stress, and telomere length markers between patients with bipolar disorder, their siblings, and healthy controls.

Methods: Thirty-six patients with bipolar disorder type I, 39 siblings, and 44 healthy controls were assessed.

Telomere Length and CCL11 Levels are Associated With Gray Matter Volume and Episodic Memory Performance in Schizophrenia: Evidence of Pathological Accelerated Aging.

Schizophrenia (SZ) is associated with increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, which may suggest that pathological accelerated aging occurs in SZ. Therefore, we aim to evaluate the relationships of age, telomere length (TL), and CCL11 (aging and inflammatory biomarkers, respectively), gray matter (GM) volume and episodic memory performance in individuals with SZ compared to healthy controls (HC). One hundred twelve participants (48 SZ and 64 HC) underwent clinical and memory assessments, structural MRI, and had their peripheral blood drawn for biomarkers analysis.

Effects of previous physical exercise to chronic stress on long-term aversive memory and oxidative stress in amygdala and hippocampus of rats.

Since stressful situations are considered risk factors for the development of depression and there are few studies evaluating prevention therapies for this disease, in the present study we evaluated the effect of previous physical exercise in animals subjected to chronic variable stress (CVS), an animal model of depression, on behavior tasks. We also investigated some parameters of oxidative stress and Na, K-ATPase activity, immunocontent and gene expression of alpha subunits in amygdala and hippocampus of rats. Young male rats were randomized into four study groups (control, exercised, stressed, exercised+stressed).

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease.

Objective:: Bipolar disorder (BD) has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age- and gender-matched healthy controls.

Telomere length in subjects with schizophrenia, their unaffected siblings and healthy controls: Evidence of accelerated aging.

Schizophrenia (SZ) is associated with broad burden. The clinical manifestations of SZ are related to pathophysiological alterations similar to what is seen in normal aging. Our aim was to evaluate the differences in telomere length (TL), a biomarker of cellular aging, in subjects with SZ (n=36), unaffected siblings (SB, n=36) and healthy controls (HC, n=47).