Search Results (14)

Significant deviations between chronological and biological age can signal the early risk of chronic diseases, driving the need for tools that accurately determine biological age. While DNA methylation-based clocks have demonstrated strong predictive power for biological aging determination, their clinical application is limited by several barriers including high costs, the need to analyze hundreds of methylation sites using sophisticated platforms and the lack of standardized measurement tools and protocols. In this study, we developed a multivariate linear model using the analysis of eight CpGs within the promoter region of the very long chain fatty acid elongase 2 gene (ELOVL2). The model generated predicts biological age with a mean absolute error (MAE) of 5.04, providing a simplified, cost-effective alternative to more complex methylation-based clocks. Additionally, we identified sex-specific biological clocks, achieving MAEs of 4.37 for males and 5.38 for females, highlighting sex-related molecular differences in the methylation of this gene during aging. Our minimal CpG-based clock offers a practical solution for estimating biological age, with potential applications in clinical practice for assessing age-related disease risks and providing personalized healthcare interventions. Full article

Chronic hyperglycemia is a major driver of neurovascular damage in diabetic retinopathy (DR), a leading cause of preventable blindness in adults. DR progression is often undetected until its advanced stages, with oxidative stress recognized as a primary contributor. In diabetes, oxidative stress disrupts retinal cellular balance, damaging proteins, DNA, and lipids, and triggering photoreceptor degeneration. Pterostilbene (Pter), a polyphenol with antioxidant properties, has demonstrated protective effects in DR animal models and was assessed in a pilot clinical study. DR patients treated with 250 mg/day of oral Pter showed a reduction in the development of retinal vascular alterations characteristic of the disease. Urinary analyses confirmed Pter’s role in reducing the lipid peroxidation of polyunsaturated fatty acids (PUFAs), including arachidonic and adrenic acids, indicators of oxidative damage in DR. Pter also improved the GSH/GSSG ratio, reflecting a restored redox balance. However, after six months without treatment, retinal damage indicators reappeared, highlighting the importance of sustained intervention. These findings suggest that Pter may help slow the progression of DR by protecting against oxidative stress and highlight the importance of implementing antioxidant therapies from the diagnosis of diabetes, although its long-term impact and the development of consistent biomarkers deserve more research to optimize DR management. Full article

This paper presents a plantwide control strategy for optimizing a pressure-swing azeotropic distillation process used in tetrahydrofuran dehydration. Leveraging Skogestad’s methodology, this strategy focused on two distillation columns: a low-pressure column for water recovery at 20 psia and a high-pressure column that achieved 0.99 molar fraction purity of tetrahydrofuran at 115 psia. This study identified critical control variables through plant analysis by implementing PI controllers in the regulatory control layer to stabilize flows and pressures. In the supervisory control layer, a PI controller combined with MIMO MPC effectively enhanced the product purity and reduced the energy consumption by 36%. Stable inlet and outlet flow conditions (100 lbmol/hr inlet, 29.59 lbmol/hr outlet) were maintained without compromising the equipment integrity. The operational ranges for the process included variations in the tetrahydrofuran mole fraction from 0.25 to 0.35 at the inlet, which demonstrated a robust performance across perturbations. These achievements signify significant advancements in process efficiency and sustainability, offering substantial reductions in energy usage while ensuring consistent high purity levels in tetrahydrofuran production. The developed control structure sets a new standard for efficient azeotropic distillation processes, with implications for enhancing operational performance across industrial applications. Full article

Biological age, reflecting the cumulative damage in the body over a lifespan, is a dynamic measure more indicative of individual health than chronological age. Accelerated aging, when biological age surpasses chronological age, is implicated in poorer clinical outcomes, especially for breast cancer (BC) survivors undergoing treatments. This preliminary study investigates the impact of a 16-week online supervised physical activity (PA) intervention on biological age in post-surgery female BC patients. Telomere length was measured using qPCR, and the ELOVL2-based epigenetic clock was assessed via DNA methylation pyrosequencing of the ELOVL2 promoter region. Telomere length remained unchanged, but the ELOVL2 epigenetic clock indicated a significant decrease in biological age in the PA group, suggesting the potential of PA interventions to reverse accelerated aging processes in BC survivors. The exercise group showed improved cardiovascular fitness, highlighting PA’s health impact. Finally, the reduction in biological age, as measured by the ELOVL2 epigenetic clock, was significantly associated with improvements in cardiovascular fitness and handgrip strength, supporting improved recovery. Epigenetic clocks can potentially assess health status and recovery progress in BC patients, identifying at-risk individuals in clinical practice. This study provides potential and valuable insights into how PA benefits BC survivors’ health, supporting the immediate benefits of a 16-week exercise intervention in mitigating accelerated aging. The findings could suggest a holistic approach to improving the health and recovery of post-surgery BC patients. Full article

The advent of immune checkpoint inhibitors (ICIs) has represented a breakthrough in the treatment of many cancers, although a high number of patients fail to respond to ICIs, which is partially due to the ability of tumor cells to evade immune system surveillance. Non-coding microRNAs (miRNAs) have been shown to modulate the immune evasion of tumor cells, and there is thus growing interest in elucidating whether these miRNAs could be targetable or proposed as novel biomarkers for prognosis and treatment response to ICIs. We therefore performed an extensive literature analysis to evaluate the clinical utility of miRNAs with a confirmed direct relationship with treatment response to ICIs. As a result of this systematic review, we have stratified the miRNA landscape into (i) miRNAs whose levels directly modulate response to ICIs, (ii) miRNAs whose expression is modulated by ICIs, and (iii) miRNAs that directly elicit toxic effects or participate in immune-related adverse events (irAEs) caused by ICIs. Full article

In recent years, cancer treatment has undergone significant changes, predominantly in the shift towards immunotherapeutic strategies using immune checkpoint inhibitors. Despite the clinical efficacy of many of these inhibitors, the overall response rate remains modest, and immunotherapies for many cancers have proved ineffective, highlighting the importance of knowing the tumor microenvironment and heterogeneity of each malignancy in patients. Long non-coding RNAs (lncRNAs) have attracted increasing attention for their ability to control various biological processes by targeting different molecular pathways. Some lncRNAs have a regulatory role in immune checkpoints, suggesting they might be utilized as a target for immune checkpoint treatment. The focus of this review is to describe relevant lncRNAs and their targets and functions to understand key regulatory mechanisms that may contribute in regulating immune checkpoints. We also provide the state of the art on super-enhancers lncRNAs (selncRNAs) and circular RNAs (circRNAs), which have recently been reported as modulators of immune checkpoint molecules within the framework of human cancer. Other feasible mechanisms of interaction between lncRNAs and immune checkpoints are also reported, along with the use of miRNAs and circRNAs, in generating new tumor immune microenvironments, which can further help avoid tumor evasion. Full article

Gamification is a new methodological tool in the field of physical education and sports sciences, which seeks to generate a formative change in educational centers and in the training of future teachers. The aim of the research was to analyze the effect of gamification on motivation, basic psychological needs and cooperative learning of prospective physical education teachers. The sample consisted of 102 future teachers in the specific area of physical education and sport. Three measuring instruments were used: Motivational Situation Scale, Cooperative Learning Questionnaire and Basic Psychological Needs in Physical Education Scale. The significance level (p < 0.05) was determined according to the variables described. The results were analyzed with the Kruskal–Wallis test for the variables age and study group and the Mann–Whitney U-test for gender. The results show high values for basic psychological needs, motivation and cooperative learning. In the case of cooperative learning, gamification has a different behavior according to gender. By degree, gamification does not affect the degree of study in the same way. In conclusion, the results of the present study support the use of gamification in the training of future physical education teachers, as it is associated with increased levels of students’ intrinsic and self-determined motivation, basic psychological needs and cooperative learning. Full article

Extractive distillation with salts, unlike other dehydration technologies, is better due to the null toxicity that exists in the distillate, since salt cannot be evaporated. With this distillation technology, it is possible to obtain a high concentration of ethanol, however, there are still problems in the control of the distillation columns in the presence of disturbances. The present work deals with the simulation and control of an extractive distillation column using CaCl${}_2$ as a separating agent, for which the Aspen Dynamics^® simulator is used. The measurement and control of the ethanol composition are carried out by means of temperature, in addition, four control structures are evaluated and compared. These structures are L, D, LV, and DV, which are the most common in conventional distillation, and their performance is measured by means of deterministic indicators applying changes (disturbances) of composition and the flow rate in the main feed of the column. The most relevant results of this work lead to the fact that by applying a controller, it is possible to maintain the desired purity above the international purity standards (99% ethanol) that govern biofuels. Full article

In a prospective study, 48 fetuses were evaluated with Doppler ultrasound after 34 weeks and classified, according to the cerebroplacental ratio (CPR) and estimated fetal weight (EFW), into fetuses with normal growth and fetuses with late-onset fetal growth restriction (LO-FGR). Overexpression of miRNAs from neonatal cord blood belonging to LO-FGR fetuses, was validated by real-time PCR. In addition, functional characterization of overexpressed miRNAs was performed by analyzing overrepresented pathways, gene ontologies, and prioritization of synergistically working miRNAs. Three miRNAs: miR-25-3p, miR-185-5p and miR-132-3p, were significantly overexpressed in cord blood of LO-FGR fetuses. Pathway and gene ontology analysis revealed over-representation of certain molecular pathways associated with cardiac development and neuron death. In addition, prioritization of synergistically working miRNAs highlighted the importance of miR-185-5p and miR-25-3p in cholesterol efflux and starvation responses associated with LO-FGR phenotypes. Evaluation of miR-25-3p; miR-132-3p and miR-185-5p might serve as molecular biomarkers for the diagnosis and management of LO-FGR; improving the understanding of its influence on adult disease. Full article

The main epigenetic features in aging are: reduced bulk levels of core histones, altered pattern of histone post-translational modifications, changes in the pattern of DNA methylation, replacement of canonical histones with histone variants, and altered expression of non-coding RNA. The identification of epigenetic mechanisms may contribute to the early detection of age-associated subclinical changes or deficits at the molecular and/or cellular level, to predict the development of frailty, or even more interestingly, to improve health trajectories in older adults. Frailty reflects a state of increased vulnerability to stressors as a result of decreased physiologic reserves, and even dysregulation of multiple physiologic systems leading to adverse health outcomes for individuals of the same chronological age. A key approach to overcome the challenges of frailty is the development of biomarkers to improve early diagnostic accuracy and to predict trajectories in older individuals. The identification of epigenetic biomarkers of frailty could provide important support for the clinical diagnosis of frailty, or more specifically, to the evaluation of its associated risks. Interventional studies aimed at delaying the onset of frailty and the functional alterations associated with it, would also undoubtedly benefit from the identification of frailty biomarkers. Specific to the article yet reasonably common within the subject discipline. Full article

Oxidative stress generated by diabetes plays a key role in the development of diabetic retinopathy (DR), a common diabetic complication. DR remains asymptomatic until it reaches advanced stages, which complicate its treatment. Although it is known that good metabolic control is essential for preventing DR, knowledge of the disease is incomplete and an effective treatment with no side effects is lacking. Pterostilbene (Pter), a natural stilbene with good antioxidant activity, has proved to beneficially affect different pathologies, including diabetes. Therefore, our study aimed to analyse the protective and/or therapeutic capacity of Pter against oxidant damage by characterising early retinal alterations induced by hyperglycaemia, and its possible mechanism of action in a rabbit model of type 1 diabetes mellitus. Pter reduced lipid and protein oxidative damage, and recovered redox status and the main activities of antioxidant enzymes. Moreover, the redox regulation by Pter was associated with activation of the PI3K/AKT/GSK3β/NRF2 pathway. Our results show that Pter is a powerful protective agent that may delay early DR development. Full article

Teleost red blood cells (RBCs) are nucleated and therefore can propagate cellular responses to exogenous stimuli. RBCs can mount an immune response against a variety of fish viruses, including the viral septicemia hemorrhagic virus (VHSV), which is one of the most prevalent fish viruses resulting in aquaculture losses. In this work, RBCs from blood and head kidney samples of rainbow trout challenged with VHSV were analyzed via transcriptomic and proteomic analyses. We detected an overrepresentation of differentially expressed genes (DEGs) related to the type I interferon response and signaling in RBCs from the head kidney and related to complement activation in RBCs from blood. Antigen processing and presentation of peptide antigen was overrepresented in RBCs from both tissues. DEGs shared by both tissues showed an opposite expression profile. In summary, this work has demonstrated that teleost RBCs can modulate the immune response during an in vivo viral infection, thus implicating RBCs as cell targets for the development of novel immunomodulants. Full article

Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy. Full article

Metastases that are resistant to conventional therapies are the main cause of most cancer-related deaths in humans. Tumor cell heterogeneity, which associates with genomic and phenotypic instability, represents a major problem for cancer therapy. Additional factors, such as the attack of immune cells or organ-specific microenvironments, also influence metastatic cell behavior and the response to therapy. Interaction of cancer and endothelial cells in capillary beds, involving mechanical contact and transient adhesion, is a critical step in the initiation of metastasis. This interaction initiates a cascade of activation pathways that involves cytokines, growth factors, bioactive lipids and reactive oxygen and nitrogen species (ROS and RNS) produced by either the cancer cell or the endothelium. Vascular endothelium-derived NO and H₂O₂ are cytotoxic for the cancer cells, but also help to identify some critical molecular targets that appear essential for survival of invasive metastatic cell subsets. Surviving cancer cells that extravasate and start colonization of an organ or tissue can still be attacked by macrophages and be influenced by specific intraorgan microenvironment conditions. At all steps; from the primary tumor until colonization of a distant organ; metastatic cells undergo a dynamic process of constant adaptations that may lead to the survival of highly resistant malignant cell subsets. In this sequence of molecular events both ROS and RNS play key roles. Full article