Search Results (71,785)

Pyrethroids are pesticides used in agriculture, the textile industry, wood processing, and human and animal medicine. Pyrethroids inhibit voltage-sensitive sodium channels (VSSCs) in insects and mammals. It results in the premature opening and/or delayed closing of the channels, causing a prolonged influx of Na⁺ ions into the cell. Insects absorb pyrethroids throughout the entire body surface, while poisoning in humans most often occurs by inhalation and through the skin. In this study, 52 fragments of human skin taken from the eyelid fold were examined. A modified Ussing chamber was used to measure the active ion transport in epithelial tissue and quantify the tissue viability and integrity. Both permethrin and deltamethrin solutions induced changes in the transport of ions, mainly sodium, but by different mechanisms. Permethrin affected the transepithelial transport of sodium ions in a long-term mechanism, while deltamethrin affected the ability to respond to stimuli in an immediate mechanism. Contact with deltamethrin may cause a delay/slowness of sensation, inflammation, hypersensitivity, and/or allergy. The action of permethrin takes place in the intercellular spaces and is associated with the possibility of faster decomposition/metabolism, while deltamethrin interacts with receptors, channels, and the cell membrane, which translates into slower decomposition and longer action in the tissue. Full article

Fusarium oxysporum root rot (FORR) is an important disease threatening soybean production. The development of marker-assisted selection (MAS) molecular markers will help accelerate the disease resistance breeding process and achieve the breeding goal of improving soybean disease resistance. This study evaluated the FORR disease resistance of 356 soybean germplasm accessions (SGAs) and screened resistance-related loci using genome-wide association analysis (GWAS) to develop molecular markers for MAS. A total of 1,355,930 high-quality SNPs were analyzed, 150 SNP sites significantly associated with FORR resistance were identified, and these sites were distributed within 41 QTLs. Additionally, 240 candidate genes were screened near these QTL regions, involving multiple functions such as hormone metabolism, signal transduction, stress defense, and growth regulation. Cleaved amplified polymorphic sequence (CAPS) and Kompetitive Allele-Specific PCR (KASP) molecular markers were developed based on candidate genes with significant SNP loci and beneficial haplotypes. The CAPS markers, S15_50486939-CAPS1 and S15_50452626-CAPS2, can effectively distinguish resistant and sensitive genotypes through enzyme digestion. The KASP marker is based on S07_19078765-G/T and exhibits a genotype clustering pattern consistent with disease resistance, demonstrating its application value in breeding. The CAPS and KASP markers developed in this study can provide reliable tools for MAS in FORR disease-resistant varieties. The research results will help reveal the genetic structure of FORR disease resistance and provide support for efficient breeding. Full article

Heme, a complex iron-containing molecule, is traditionally recognized for its pivotal role in oxygen transport and cellular respiration. However, emerging research has illuminated its multifaceted functions in the nervous system, extending beyond its canonical roles. This review delves into the diverse roles of heme in the nervous system, highlighting its involvement in neural development, neurotransmission, and neuroprotection. We discuss the molecular mechanisms by which heme modulates neuronal activity and synaptic plasticity, emphasizing its influence on ion channels and neurotransmitter receptors. Additionally, the review explores the potential neuroprotective properties of heme, examining its role in mitigating oxidative stress, including mitochondrial oxidative stress, and its implications in neurodegenerative diseases. Furthermore, we address the pathological consequences of heme dysregulation, linking it to conditions such as Alzheimer’s disease, Parkinson’s disease, and traumatic brain injuries. By providing a comprehensive overview of heme’s multifunctional roles in the nervous system, this review underscores its significance as a potential therapeutic target and diagnostic biomarker for various neurological disorders. Full article

Background: A fundamental property of cancer cells is their metabolic reprogramming, allowing them to increase glucose uptake and glycolysis. Using a rat colon adenocarcinoma model, we previously showed that blood levels of free methylglyoxal (MG), a side-product of glycolysis, remained normal in animals grafted with a non-growing tumor cell clone, while MG levels were significantly increased and positively correlated with tumor growth in animals grafted with a tumorigenic cell clone issued from the same tumor. Methods: We measured free MG in the blood of cancerous non-diabetic patients and compared the results to healthy subjects and non-cancerous diabetic patients. We also measured free MG in tumors and in the corresponding non-cancer tissues, and the peripheral blood. Results: We show that free MG levels in the peripheral blood of cancer patients are significantly increased in comparison with free MG levels in the peripheral blood of healthy controls (p < 0.0001), and similar to those in the peripheral blood of hyperglycemic diabetic patients (p = 0.965). In addition, we show that repeated free MG level measurement could be used for the therapeutic monitoring of cancer patients. Moreover, we confirmed that free MG is produced by tumor cells at significantly higher levels than cells from their corresponding tissues (p < 0.0001), and is subsequently released in the peripheral blood. Conclusions: Free MG measured in the blood could be a new metabolic biomarker useful for the diagnostic, prognostic and follow-up of non-diabetic patients with cancers, such as bronchus carcinoma, pancreatic carcinoma and glioblastoma, for which there are presently no available useful biomarkers. Full article

Considerable studies have demonstrated that osteoarthritis (OA) is a risk factor for dementia. The precise mechanisms underlying the association between OA and increased risk for cognitive dysfunction, however, remain unclear. This study aimed at exploring the associations between pro-inflammatory cytokines/chemokines, biomarkers of Alzheimer’s disease (AD), pain intensity, and cognitive decline in knee joint OA patients. A total of 50 patients (26 in OA group and 24 in non-OA control group) were enrolled in this prospective, observational study. The visual analogue scale (VAS) score for pain intensity and Cognitive Abilities Screening Instrument (CASI) score for cognitive functions were examined in both groups. The plasma and cerebrospinal fluid (CSF) levels of pro-inflammatory molecules (IL-1β, IL-6, TNF-α, fractalkine, BDNF, MCP-1, and TGF-β), as well as biomarkers of AD (Aβ₄₀, Aβ₄₂, total-tau, and phospho-tau), were measured by multiplex immunoassay. Correlations among plasma or CSF biomarkers and questionnaire scores were assessed using Pearson’s correlation coefficient and simple linear regressions. There were more patients in the OA group whose CASI cutoff percentiles were <P5 or at P5 than in the control group. VAS pain scores were negatively correlated with cognitive domains, including total score, short term memory, attention, mental manipulation, abstract thinking, and judgment, of the CASI score. VAS scores were positively correlated with fractalkine, Aβ₄₀, and Aβ₄₂ in CSF of OA patients. The CSF levels of Aβ₄₀ and Aβ₄₂ in OA patients were negatively correlated with attention and abstract scores in CASI. The findings of this study suggest that knee OA is associated with poor cognitive performance, and this association is particularly pronounced in OA patients with chronic pain. Higher levels of brain AD biomarkers, such as Aβ₄₀ and Aβ₄₂, may partially mediate this relationship. Full article

Background: A new vitamin concept, termed vitamin A5, an umbrella term for vitamin A derivatives being direct nutritional precursors for 9-cis-13,14-dihydroretinoic acid and further induction of RXR-signaling, was recently identified with global importance for mental health and healthy brain and nerve functions. Dietary recommendations in the range of 1.1 (0.5–1.8) mg vitamin A5 / day were suggested by an international expert consortium. The ensuing question arises as to the current daily dietary intake amounts in Western civilization. Methods: Addressing this answer included calculating the intake based on known amounts of vitamin A5 in frequently consumed food items of the human diet that are high in this vitamin, as well as the known daily dietary intake amounts of those selected food components in Westernized countries. Results: Regarding food items, amounts of vitamin A5 in the form of provitamin A5 (i.e., 9-cis-beta-carotene (9CBC)), the predominant form in the diet, were found to range from 0.1 to 39 µg 9CBC / g for individual fruits and vegetables, with the highest concentrations being in leafy vegetables. The average intake amounts of vitamin A5 in adults of the general population following a Western lifestyle in Europe averaged 0.9, with a range from 0.5 (for Austria) to 1.3 (for Italy) mg 9CBC/day. Furthermore, based on our calculations, large parts, i.e., approximately two-thirds, of the population are low, even too low (<1.1 mg/day), in daily vitamin A5 intake. Conclusion: In addition to the importance of nudging the population toward a regrettably non-well-accepted higher intake of fruits and vegetables, an additional fortification and supplementation of vitamin A5 could be considered, similar to other micronutrients that are low in a Westernized diet. Full article

Obesity is one of the world’s major public health challenges. Its pathogenesis and comorbid metabolic disorders share common mechanisms, such as mitochondrial or endoplasmic reticulum dysfunction or oxidative stress, gut dysbiosis, chronic inflammation and altered autophagy. Numerous pro-autophagy dietary interventions are being investigated for their potential obesity-preventing or therapeutic effects. We summarize current data on the relationship between autophagy and obesity, and discuss various dietary interventions as regulators of autophagy-related genes in the prevention and ultimate treatment of obesity in humans, as available in scientific databases and published through July 2024. Lifestyle modifications (such as calorie restriction, intermittent fasting, physical exercise), including following a diet rich in flavonoids, antioxidants, specific fatty acids, specific amino acids and others, have shown a beneficial role in the induction of this process. The activation of autophagy through various nutritional interventions tends to elicit a consistent response, characterized by the induction of certain kinases (including AMPK, IKK, JNK1, TAK1, ULK1, and VPS34) or the suppression of others (like mTORC1), the deacetylation of proteins, and the alleviation of inhibitory interactions between BECN1 and members of the Bcl-2 family. Significant health/translational properties of many nutrients (nutraceuticals) can affect chronic disease risk through various mechanisms that include the activation or inhibition of autophagy. The role of nutritional intervention in the regulation of autophagy in obesity and its comorbidities is not yet clear, especially in obese individuals. Full article

Polyphenols are powerful natural antioxidants with numerous biological activities. They change cell membrane permeability, interact with receptors, intracellular enzymes, and cell membrane transporters, and quench reactive oxygen species (ROS). Yarrowia lipolytica yeast, being similar to mammalian cells, can be used as a model to study their survival ability upon long-lasting cultivation, assaying the effect of dihydroquercetin polyphenol (DHQ). The complex assessment of the physiological features of the population assaying cell respiration, survival, ROS detection, and flow cytometry was used. Y. lipolytica showed signs of chronological aging by eight weeks of growth, namely a decrease in the cell number, and size, increased ROS generation, a decrease in colony-forming unit (CFU) and metabolic activity, and decreased respiratory rate and membrane potential. An amount of 150 µM DHQ decreased ROS generation at the 6-week growth stage upon adding an oxidant of 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH). Moreover, it decreased CFU at 1–4 weeks of cultivation, inhibited cell metabolic activity of the 24-h-old culture and stimulated that on 14–56 days of growth, induced the cell respiration rate in the 24-h-old culture, and blocked alternative mitochondrial oxidase at growth late stages. DHQ serves as a mild pro-oxidant on the first day of age-stimulating anti-stress protection. In the deep stationary stage, it can act as a powerful antioxidant, stabilizing cell redox status and reducing free radical oxidation in mitochondria. It provides a stable state of population. The hormetic effects of DHQ using lower eukaryotes of Y. lipolytica have been previously discussed, which can be used as a model organism for screening geroprotective compounds of natural origin. Full article

Arbuscular mycorrhizal fungi (AMF) have been shown to play a major role in regulating the accumulation, transport, and toxicity of cadmium (Cd) in plant tissues. This review aims to highlight the current understanding of the mechanisms by which AMF alleviate Cd toxicity in plants. Cd accumulation in agricultural soils has become an increasing global concern due to industrial activities and the use of phosphatic fertilizers. Cd toxicity disrupts various physiological processes in plants, adversely affecting growth, photosynthesis, oxidative stress responses, and secondary metabolism. AMF alleviate Cd stress in plants through multiple mechanisms, including reduced Cd transport into plant roots, improved plant nutritional status, modulation of organic acid and protein exudation, enhanced antioxidant capacity, and maintenance of ion homeostasis. AMF colonization also influences Cd speciation, bioavailability, and compartmentalization within plant tissues. The expression of metal transporter genes, as well as the synthesis of phytochelatins and metallothioneins, are modulated by AMF during Cd stress. However, the efficacy of AMF in mitigating Cd toxicity depends on several factors, such as soil properties, plant species, AMF taxa, and experimental duration. Further knowledge of the intricate plant–AMF–Cd interactions is crucial for optimizing AMF-assisted phytoremediation strategies and developing Cd-tolerant and high-yielding crop varieties for cultivation in contaminated soils. Full article

Background and Objective: Diabetes Mellitus is a long-term, multifaceted metabolic condition that necessitates ongoing medical management. Hypogonadism is a syndrome that is a clinical and/or biochemical indicator of testosterone deficiency. Cross-sectional studies have reported that 20–80.4% of all men with Type 2 diabetes have hypogonadism, and Type 2 diabetes is related to low testosterone. This study presents an analysis of the use of ML and EL classifiers in predicting testosterone deficiency. In our study, we compared optimized traditional ML classifiers and three EL classifiers using grid search and stratified k-fold cross-validation. We used the SMOTE method for the class imbalance problem. Methods: This database contains 3397 patients for the assessment of testosterone deficiency. Among these patients, 1886 patients with Type 2 diabetes were included in the study. In the data preprocessing stage, firstly, outlier/excessive observation analyses were performed with LOF and missing value analyses were performed with random forest. The SMOTE is a method for generating synthetic samples of the minority class. Four basic classifiers, namely MLP, RF, ELM and LR, were used as first-level classifiers. Tree ensemble classifiers, namely ADA, XGBoost and SGB, were used as second-level classifiers. Results: After the SMOTE, while the diagnostic accuracy decreased in all base classifiers except ELM, sensitivity values increased in all classifiers. Similarly, while the specificity values decreased in all classifiers, F1 score increased. The RF classifier gave more successful results on the base-training dataset. The most successful ensemble classifier in the training dataset was the ADA classifier in the original data and in the SMOTE data. In terms of the testing data, XGBoost is the most suitable model for your intended use in evaluating model performance. XGBoost, which exhibits a balanced performance especially when the SMOTE is used, can be preferred to correct class imbalance. Conclusions: The SMOTE is used to correct the class imbalance in the original data. However, as seen in this study, when the SMOTE was applied, the diagnostic accuracy decreased in some models but the sensitivity increased significantly. This shows the positive effects of the SMOTE in terms of better predicting the minority class. Full article

Among various environmental factors, light is a crucial parameter necessary for the germination of some seeds. Seed germination is an important phase in the plant life cycle, when metabolic activity is resumed and reserves are mobilized to support initial plant development. Although all nutrients are extremely important for proper physiological and biochemical development of plants, phosphorus (P) seems to play a special role, as it is an essential component of all important structural and functional substances which compose the cells of plants. We believe that transformations of the forms of phosphorus accompanying metabolic activity of germinating seeds determine the efficiency of this process, and thus the seedling’s metabolic status. Therefore, we decided to study the changes in the major phosphorus-containing substances in radish sprouts during the first phase of growth. The effect of different colours of light on the quality parameters in radish, as a model plant, during germination, was evaluated. Contents of Pi, adenylates, antioxidants, pigments, phytase activity, and ³¹P NMR phosphorus profile were investigated. Based on the results of our study, we may propose the phosphoromic approach as an important metabolic parameter determining the physiological status of the plant. Full article

Trimethylaminuria (TMAU) is a rare metabolic syndrome caused by the accumulation of trimethylamine in the body, causing odor emissions similar to rotten fish in affected patients. This condition is determined by both genetic and environmental factors, especially gut dysbiosis. The multifactorial nature of this syndrome makes for a complex and multi-level diagnosis. To date, many aspects of this disease are still unclear. Recent research revealed the FMO3 haplotypes’ role on the enzyme’s catalytic activity. This could explain why patients showing only combined polymorphisms or heterozygous causative variants also manifest the TMAU phenotype. In addition, another research hypothesized that the behavioral disturbances showed by patients may be linked to gut microbiota alterations. Our review considers current knowledge about TMAU, clarifying its molecular aspects, the therapeutic approaches used to limit this condition, and the new therapies that are under study. Full article

Background/Objectives: Cholesterol is vital in various bodily functions, such as maintaining cell membranes, producing hormones, etc. However, imbalances, like hypercholesterolemia, can lead to diseases such as cancer, kidney disease, non-alcoholic fatty liver disease, and cardiovascular conditions. This study explores the impact of kiwifruit consumption, specifically Actinidia arguta cultivar Geneva and Actinidia deliciosa cultivar Hayward, on cholesterol and lipid metabolism in rat liver. Methods: Rats were divided into groups: a 1% cholesterol control group (Ch), a 5% Geneva kiwifruit-supplemented group (ChGENE), and a 5% Hayward kiwifruit-supplemented group (ChHAYW). Gene expression was analyzed using Gene Spring v.14. Gene ontology, pathway analysis, miRNA, and transcription factor prediction were performed using DAVID, Reactome, and miRNet. In addition, we used Agilent Literature Search software to gain further insights. Results: Statistical analysis identified 72 genes in ChGENE-Ch and 2 genes in ChHAYW-Ch comparison. Key genes involved in cholesterol metabolism pathways, including PCSK9, SCD1, SLC27A5, HMGCR, and DHCR24, showed lower expression in the kiwifruit-supplemented groups. The genes mentioned above showed lower expression in the kiwifruit-supplemented group, probably contributing to the liver lipid level reduction. Further analysis identified miRNA-26a, miRNA-29a/b/c, miRNA-33a/b, and miRNA-155 targeting hub genes. Conclusions: Our findings suggest that dietary supplementation with kiwifruit, particularly the Geneva cultivar, reduces fat accumulation in the liver of rats with hypercholesterolemia, likely through downregulation of critical genes involved in cholesterol metabolism. These studies highlight the potential of kiwifruit as a part of a dietary strategy to manage cholesterol levels. Full article

Aggressiveness is one of the personality traits of crustaceans, playing a crucial role in their growth, life history, and adaptability by influencing resource acquisition. However, the neuroregulatory mechanisms of aggressiveness in crustaceans remain poorly understood. The thoracic ganglion offers valuable insights into complementary aspects of aggression control. This study identified the aggressiveness of swimming crabs Portunus trituberculatus, conducted transcriptomic and metabolomic analyses of the thoracic ganglia, and confirmed the neural regulatory effects on aggressiveness. Behavioral analyses showed that highly aggressive individuals exhibited increased frequency and duration of chela extension, more frequent attacks, approaches and retreats, as well as extended movement distances. Omics analysis revealed 11 key candidate genes and three metabolites associated with aggressiveness, which were primarily enriched in pathways related to energy metabolism and neurodegeneration. Injection of an NMDAR activator significantly decreased aggressiveness in highly aggressive crabs, accompanied by a significant increase in NMDAR protein fluorescence intensity and downregulation of NR2B, CaMKII, and CREB genes. Conversely, when lowly aggressive crabs were injected with an NMDAR inhibitor, they showed increased aggressiveness alongside significantly decreased NMDAR protein fluorescence intensity, upregulated NR2B expression, and downregulated CaMKII and CREB genes. These results suggest that NMDAR within the thoracic ganglia serves as a key receptor in modulating aggressiveness in P. trituberculatus, potentially by influencing neural energy state via the NMDAR-CaMKII pathway, which in turn affects oxidative phosphorylation, cAMP, and FoxO pathways. Full article

Background: Regular physical activity plays a crucial role in modulating cellular metabolism and mitigating the progression of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. Objective: The objective of this review is to evaluate the molecular mechanisms by which exercise influences cellular metabolism, with a focus on its potential as a therapeutic intervention for neurological disorders. Methods: A comprehensive literature review was conducted using peer-reviewed scientific articles, with a focus on the period between 2015 and 2024, to analyze the effects of exercise on mitochondrial function, oxidative stress, and metabolic health. Results: The findings indicate that exercise promotes mitochondrial biogenesis, enhances oxidative phosphorylation, and reduces reactive oxygen species, contributing to improved energy production and cellular resilience. These metabolic adaptations are associated with delayed disease progression and reduced symptoms in patients with neurodegenerative conditions. Additionally, integrating exercise with nutritional strategies may further enhance therapeutic outcomes by addressing metabolic disturbances comprehensively. Conclusion: This review concludes that personalized exercise protocols should be developed to optimize metabolic benefits for patients with neurological diseases, while future research should focus on biomarker development for individualized treatment approaches. These findings highlight the importance of non-pharmacological interventions in managing neurodegenerative diseases. Full article