State Of Imbalance Research Articles

Chelation Therapy Associated with Antioxidant Supplementation Can Decrease Oxidative Stress and Inflammation in Multiple Sclerosis: Preliminary Results.

An imbalance of oxy-inflammation status has been involved in axonal damage and demyelination in multiple sclerosis (MS). The aim of this study was to investigate the efficacy of an antioxidant treatment (calcium disodium ethylenediaminetetracetic acid-EDTA) chelation therapy associated with a micronutrient complex in MS patients. A total of 20 MS patients and 20 healthy subjects, enrolled as a control group (CTR), were recruited. We measured the plasma ROS production and total antioxidant capacity (TAC) by a direct assessment using Electron Paramagnetic Resonance; activities of the antioxidant system (thiols' redox status and enzymes); and the urinary presence of biomarkers of oxidative stress by immunoenzymatic assays. We also evaluated the levels of inflammation by plasmatic cytokines (TNFα, IL-1β, and IL-6) and assessed the sICAM levels, as well as the nitric oxide (NO) catabolism and transthyretin (TTR) concentration. Comparing CTR and MS, in the latter ROS production, oxidative damage, inflammatory biomarkers, and NO metabolite concentrations results were significantly higher, while TAC was significantly lower. Treatment in MS induced significant (p < 0.05) down-regulating of pro-inflammatory sICAM1, TNF-α, IL6, as well as biomarkers of lipid peroxidation and DNA damage production. The protective effect exhibited may occur by decreasing ROS production and increasing antioxidant capacity, turning into a more reduced thiols' status.

Subacute exposure to Roundup® changes steroidogenesis and gene expression of the glutathione-glutaredoxin system in rat ovaries: Implications for ovarian toxicity of this glyphosate-based herbicide

Studies have indicated that glyphosate induces endocrine disruption and may adversely affect the male reproductive system. However, evidence of its effects on ovarian function is poorly understood so far, making further studies necessary on the mechanisms of the glyphosate toxicity in the female reproductive system. The aim of this work was to evaluate the effect of a subacute exposure (28 days) to the glyphosate-based formulation Roundup® (1.05, 10.5 and 105 μg/kg b.w. of glyphosate) on steroidogenesis, oxidative stress, systems involved in cell redox control and histopathological parameters in rat ovaries. Hence we quantify plasma estradiol and progesterone by chemiluminescence; non-protein thiol levels, TBARS, superoxide dismutase and catalase activity by spectrophotometry; gene expression of steroidogenic enzymes and redox systems by real-time PCR; and ovarian follicles by optical microscopy. Our results demonstrated that oral exposure increased progesterone levels and the mRNA expression of 3β-hydroxysteroid dehydrogenase. Histopathological analysis revealed a decrease in the number of primary follicles and an increase in the number of corpus luteum in rats exposed to Roundup®. An imbalance of the oxidative status was also evidenced by decreasing the catalase activity at all groups exposed to the herbicide. Increased lipid peroxidation and gene expression of glutarredoxin and decreased of glutathione reductase were also observed. Our results indicate that Roundup® causes endocrine disruption of hormones related to female fertility and reproduction and changes the oxidative status by altering antioxidant activity, inducing lipid peroxidation, as well as changing the gene expression of the glutathione-glutarredoxin system in rat ovaries.

Mitochondrial dysfunction and calcium dyshomeostasis in the pectoralis major muscle of broiler chickens with wooden breast myopathy

The incidence of wooden breast (WB) meat of commercial broiler chicken has been increasing in recent years. Histological examination found that the occurrence of WB myopathy was accompanied by the pectoralis major (PM) muscle damage. So far, the potential mechanisms are not fully understood. This study aimed to explore the underlying mechanism of the damage of WB-affected PM muscle caused by changes in mitochondrial function, mitochondrial redox status and Ca2+ homeostasis. A total of 80 market-age Arbor Acres male broiler chickens were sampled and categorized into control (CON) and WB groups based on the evaluation of myopathic lesions. PM muscle samples were collected (n=8 in each group) for histopathological evaluation and biochemical analyses. Ultrastructural examination and histopathological changes suggested the occurrence of PM muscle damage in broiler chickens with WB myopathy. The WB group showed an increased level of reactive oxygen species and enhanced antioxidant capacities in mitochondria of PM muscle. These changes were related to impaired mitochondria morphology and mitochondrial dysfunction. In addition, abnormal expressions of Ca2+ channels led to substantial Ca2+ loss in SR and cytoplasmic Ca2+ overload, as well as Ca2+ accumulation in mitochondria, resulting in Ca2+ dyshomeostasis in PM muscle of broiler chickens with WB myopathy. Combined, these findings indicate that WB myopathy is related to mitochondrial dysfunction, mitochondrial redox status imbalance and Ca2+ dyshomeostasis, leading to WB-affected PM muscle damage.

Pathway-level multi-omics analysis of the molecular mechanisms underlying the toxicity of long-term tacrolimus exposure

Tacrolimus (TAC)-based treatment is associated with nephrotoxicity and hepatotoxicity; however, the underlying molecular mechanisms responsible for this toxicity have not been fully explored. This study elucidated the molecular processes underlying the toxic effects of TAC using an integrative omics approach. Rats were sacrificed after 4 weeks of daily oral TAC administration at a dose of 5 mg/kg. The liver and kidney underwent genome-wide gene expression profiling and untargeted metabolomics assays. Molecular alterations were identified using individual data profiling modalities and further characterized by pathway-level transcriptomics-metabolomics integration analysis. Metabolic disturbances were mainly related to an imbalance in oxidant-antioxidant status, as well as in lipid and amino acid metabolism in the liver and kidney. Gene expression profiles also indicated profound molecular alterations, including in genes associated with a dysregulated immune response, proinflammatory signals, and programmed cell death in the liver and kidney. Joint-pathway analysis indicated that the toxicity of TAC was associated with DNA synthesis disruption, oxidative stress, and cell membrane permeabilization, as well as lipid and glucose metabolism. In conclusion, our pathway-level integration of transcriptome and metabolome and conventional analyses of individual omics profiles, provided a more comprehensive picture of the molecular changes resulting from TAC toxicity. This study also serves as a valuable resource for subsequent investigations aiming to understand the mechanism underlying the molecular toxicology of TAC.

Association of Inflammatory and Oxidative Status Markers with Metabolic Syndrome and Its Components in 40-to-45-Year-Old Females: A Cross-Sectional Study.

Oxidative stress and sterile inflammation play roles in the induction and maintenance of metabolic syndrome (MetS). This study cohort included 170 females aged 40 to 45 years who were categorized according to the presentation of MetS components (e.g., central obesity, insulin resistance, atherogenic dyslipidemia, and elevated systolic blood pressure) as controls not presenting a single component (n = 43), those with pre-MetS displaying one to two components (n = 70), and females manifesting MetS, e.g., ≥3 components (n = 53). We analyzed the trends of seventeen oxidative and nine inflammatory status markers across three clinical categories. A multivariate regression of selected oxidative status and inflammatory markers on the components of MetS was performed. Markers of oxidative damage (malondialdehyde and advanced-glycation-end-products-associated fluorescence of plasma) were similar across the groups. Healthy controls displayed lower uricemia and higher bilirubinemia than females with MetS; and lower leukocyte counts, concentrations of C-reactive protein, interleukine-6, and higher levels of carotenoids/lipids and soluble receptors for advanced glycation end-products than those with pre-MetS and MetS. In multivariate regression models, levels of C-reactive protein, uric acid, and interleukine-6 were consistently associated with MetS components, although the impacts of single markers differed. Our data suggest that a proinflammatory imbalance precedes the manifestation of MetS, while an imbalance of oxidative status accompanies overt MetS. Further studies are needed to elucidate whether determining markers beyond traditional ones could help improve the prognosis of subjects at an early stage of MetS.

Transport Characteristics of Silicon Multi-Quantum-Dot Transistor Analyzed by Means of Experimental Parametrization Based on Single-Hole Tunneling Model.

The transport characteristics of a gate-all-around Si multiple-quantum-dot (QD) transistor were studied by means of experimental parametrization using theoretical models. The device was fabricated by using the e-beam lithographically patterned Si nanowire channel, in which the ultrasmall QDs were self-created along the Si nanowire due to its volumetric undulation. Owing to the large quantum-level spacings of the self-formed ultrasmall QDs, the device clearly exhibited both Coulomb blockade oscillation (CBO) and negative differential conductance (NDC) characteristics at room temperature. Furthermore, it was also observed that both CBO and NDC could evolve along the extended blockade region within wide gate and drain bias voltage ranges. By analyzing the experimental device parameters using the simple theoretical single-hole-tunneling models, the fabricated QD transistor was confirmed as comprising the double-dot system. Consequently, based on the analytical energy-band diagram, we found that the formation of ultrasmall QDs with imbalanced energetic natures (i.e., imbalanced quantum energy states and their imbalanced capacitive-coupling strengths between the two dots) could lead to effective CBO/NDC evolution in wide bias voltage ranges.

Carbon Emissions and National Sustainable Development Goals Coupling Coordination Degree Study from a Global Perspective: Characteristics, Heterogeneity, and Spatial Effects

While the environmental issues resulting from carbon emissions are widely recognized by the public, there is a lack of in-depth research on whether controlling carbon emissions will have an impact on social development at the national level. In this study, we used panel data from 166 countries worldwide from 2005 to 2020 to construct coupled coordination models, panel regression models, and spatial Durbin models to assess the impact of carbon emissions on the coupled coordinated development of sustainable development goals (SDGs) in different countries around the world. This study is the first to investigate the features, heterogeneity, and spatial effects of carbon emissions on the SDG coupling coordination degree. We found that: (1) Globally, the SDG coupling coordination degree was generally low from 2005 to 2020. Despite the slow improvement in the global SDG coupling coordination degree over the past 16 years, it has always been in a barely imbalanced transitional development state. At the same time, there was a phenomenon of “high-income &gt; high–middle-income &gt; low–middle-income &gt; low-income” difference in the SDG coupling coordination development level among countries of different income types. (2) Carbon emissions have a significant promoting effect on the SDG coupling coordination degree for low-income and low–middle-income countries while having a significant inhibitory effect on the SDG coupling coordination degree for high–middle-income and high-income countries. In addition, the impact of carbon emissions on the SDG coupling coordination degree also exhibits regional heterogeneity. (3) Carbon emissions have a significant spatial spillover effect on the SDG coupling coordination degree, with a positive promoting effect on the SDG coupling coordination degree in one’s own country and a significant inhibitory effect on the SDG coupling coordination degrees of neighboring countries. Our research can help decision-makers develop targeted carbon reduction plans to avoid social development losses caused by controlling carbon emissions in a crude manner. Our research findings provide crucial evidence for the formulation of international policies aimed at reducing carbon emissions, in order to avoid the inequities that may result from the adoption of extreme carbon reduction policies.

Benzophenone-3 causes oxidative stress in the brain and impairs aversive memory in adult zebrafish

Oxybenzone (BP-3) is an ultraviolet (UV) filter widely used in industries that is directly or indirectly released into the aquatic environment. However, little is known about its effects on brain performance. Here, we investigated whether BP-3 exposure affects the redox imbalance in zebrafish and how they respond to a task that requires memory of an aversive situation. Fish were exposed to BP-3 10 and 50 μg L−1 for 15 days and then tested using an associative learning protocol with electric shock as a stimulus. Brains were extracted for reactive oxygen species (ROS) measurement and qPCR analysis of antioxidant enzyme genes. ROS production increased for exposed animals, and catalase (cat) and superoxide dismutase 2 (sod 2) were upregulated. Furthermore, learning and memory were reduced in zebrafish exposed to BP-3. These results suggested that BP-3 may lead to a redox status imbalance, causing impaired cognition and reinforcing the need to replace the toxic UV filters with filters that minimize environmental effects.

Junction of the redox dynamic, orchestra of signaling, and altered metabolism in regulation of T- cell lymphoma.

T-cell lymphoma is a hematologic neoplasm derived from the lymphoid lineage. It belongs to a diverse group of malignant disorders, mostly affecting the young population worldwide, that vary with respect to molecular features as well as genetic and clinical complexities. Cancer cells rewire the cellular metabolism, persuading it to meet new demands of growth and proliferation. Furthermore, the metabolic alterations and heterogeneity are aberrantly driven in cancer by a combination of genetic and non-genetic factors, including the tumor microenvironment. New insight into cancer metabolism highlights the importance of nutrient supply to tumor development and therapeutic responses. Importantly, oxidative stress due to an imbalance in the redox status of reactive species via exogenous and/or endogenous factors is closely related to multiple aspects of cancer. This alters the signaling pathways governed through the multiple intracellular signal transduction and transcription factors, leading to tumor progression. These oncogenic signaling molecules are regulated through different redox sensors, including nuclear factor-erythroid 2 related factor 2 (Nrf2), phase-II antioxidant enzyme, and NQO1 (NADPH quinone oxidoreductase (1). The existing understanding of the molecular mechanisms of T-cell lymphoma regulation through the cross-talk of redox sensors under the influence of metabolic vulnerability is not well explored. This review highlights the role of the redox dynamics, orchestra of signaling, and genetic regulation involved in T-cell lymphoma progression in addition to the challenges to their etiology, treatment, and clinical response in light of recent updates.

Dietary Dityrosine Induces Oxidative Stress and Mitochondrial-Lipid Imbalance in Mouse Liver via MiR-144-3p-Mediated Downregulation of Nrf2.

Dityrosine (DT) is a protein oxidation marker present in many high-protein foods, such as dairy and meat products. Chronic dietary intake of DT induces oxidative stress damage in the liver and impairs energy metabolism. This study aims to investigate the mechanisms underlying the effects of DT on disrupted hepatic energy metabolism. The study investigates hepatic lipid accumulation, redox status imbalance, mitochondrial dysfunction, and energy metabolism disorders in 4-week-old C57BL/6J mice after 35 days of DT (420 µgkg-1 body weight) treatment. Transcriptome sequencing and quantitative real-time PCR in HepG2 cells show that DT mainly acted via miR-144-3p. miR-144-3p targets immune responsive gene 1 (IRG1) and decreases the fumaric acid level in the tricarboxylic acid (TCA) cycle, thereby decreasing nuclear factor erythroid 2-related factor 2 (Nrf2) expression and antioxidant activity. Administration of lycopene, a strong antioxidant, alleviates DT-induced damage in mice, confirming the involvement of the Nrf2 pathway in DT-induced abnormal hepatic lipid metabolism and energy homeostasis.

INTERNATIONAL AND RUSSIAN EXPERIENCE IN APPLYING EVIDENTIAL POLICY INSTRUMENTS IN THE SPHERE OF PUBLIC ADMINISTRATION: ISSUES OF CONTINUITY IN SECTORAL BALANCE

The article provides an analytical review of modern international practices in the development and practical implementation of an evidence-based approach in public administration. A brief description of the evidence-based approach, prerequisites, as well as the first (pioneer) practices of applying its elements to achieve sustainable development goals and leveling barriers in socially significant areas is given. The cases formed to date on the implementation of evidence-based public policy in a number of developed countries are considered. It is suggested that, given the accumulated international experience, there is a possibility of using evidence-based public policy tools for the purposes of sectoral balancing. Confirmation of this hypothesis is carried out through the prism of the industry. The Russian Federation is cited as a recipient country, as one of the largest world powers, the industrial sector of which, like in many other countries of the world, is in conditions of uncertainty and episodic imbalance. It is indicated that in view of the constantly changing conditions for the functioning of industrial enterprises, it is important to constantly evaluate the effectiveness and, as a result, adjust the measures of state support for industrial enterprises in order to maintain the "health" of the entire sector. It is postulated that for a long period of time in many countries of the world, in particular in Russia, there was a “rational-intuitive” approach to public administration, which is inappropriate in the new reality. The possibility of replacing this approach with an evidence-based approach is considered, examples of successful practices in the application of evidence-based policy tools in the field of public administration are presented, in particular, in the context of evaluation (audit) measures of the results obtained; special attention is paid to the approach adopted in the UK. The alternatives of their use for further improvement of state support for industrial enterprises that are forced to conduct their activities in conditions of uncertainty are specified.

Dosage balance acts as a time-dependent selective barrier to subfunctionalization

BackgroundGene duplication is an important process for genome expansion, sometimes allowing for new gene functions to develop. Duplicate genes can be retained through multiple processes, either for intermediate periods of time through processes such as dosage balance, or over extended periods of time through processes such as subfunctionalization and neofunctionalization.ResultsHere, we built upon an existing subfunctionalization Markov model by incorporating dosage balance to describe the interplay between subfunctionalization and dosage balance to explore selective pressures on duplicate copies. Our model incorporates dosage balance using a biophysical framework that penalizes the fitness of genetic states with stoichiometrically imbalanced proteins. These imbalanced states cause increased concentrations of exposed hydrophobic surface areas, which cause deleterious mis-interactions. We draw comparison between our Subfunctionalization + Dosage-Balance Model (Sub + Dos) and the previous Subfunctionalization-Only (Sub-Only) Model. This comparison includes how the retention probabilities change over time, dependent upon the effective population size and the selective cost associated with spurious interaction of dosage-imbalanced partners. We show comparison between Sub-Only and Sub + Dos models for both whole-genome duplication and small-scale duplication events.ConclusionThese comparisons show that following whole-genome duplication, dosage balance serves as a time-dependent selective barrier to the subfunctionalization process, by causing an overall delay but ultimately leading to a larger portion of the genome retained through subfunctionalization. This higher percentage of the genome that is ultimately retained is caused by the alternative competing process, nonfunctionalization, being selectively blocked to a greater extent. In small-scale duplication, the reverse pattern is seen, where dosage balance drives faster rates of subfunctionalization, but ultimately leads to a smaller portion of the genome retained as duplicates. This faster rate of subfunctionalization is because the dosage balance of interacting gene products is negatively affected immediately after duplication and the loss of a duplicate restores the stoichiometric balance. Our findings provide support that the subfunctionalization of genes that are susceptible to dosage balance effects, such as proteins involved in complexes, is not a purely neutral process. With stronger selection against stoichiometrically imbalanced gene partners, the rates of subfunctionalization and nonfunctionalization slow; however, this ultimately leads to a greater proportion of subfunctionalized gene pairs.

An Imbalance-Status-Enabled Autonomous Global Power-Sharing Scheme for Solid-State Transformer Interconnected Hybrid AC/DC Microgrids

This paper proposes a novel imbalance-status (IS)-enabled autonomous global power-sharing scheme for a solid-state transformer (SST) interconnected hybrid AC / DC microgrid system. Firstly, the proposed scheme globally estimates instantaneous active power imbalances according to the existing droop regulation characteristics of each sub-microgrid, and normalizes these imbalances by introducing the definition of IS. Next, three novel IS-enabled controllers are designed for the SST’s three core converters, to autonomously share the power imbalances in the entire system. Then, the control parameters of the proposed scheme are optimized through small-signal analysis. The control effectiveness and flexibility of the proposed scheme in realizing global power-sharing function are verified by controller hardware-in-loop experiments in RT-LAB platform.

Entropy-Optimized Fault Diagnosis Based on Unsupervised Domain Adaptation

In practice, the cross-domain transfer of data distribution and the sample imbalance of fault status are inevitable, but one or both are often ignored, which restricts the adaptability and classification accuracy of the generated fault diagnosis (FD) model. Accordingly, an entropy-optimized method is proposed in this paper based on an unsupervised domain-adaptive technique to enhance FD model training. For the training, pseudosamples and labels corresponding to the target samples are generated through data augmentation and self-training strategies to diminish the distribution discrepancy between the source and target domains. Meanwhile, an adaptive conditional entropy loss function is developed to improve the data quality of the semisupervised learning, with which reliable samples are generated for the training. According to the experiment results, compared with other state-of-the-art algorithms, our method can achieve significant accuracy improvement in rolling bearing FD. Typically, the accuracy improvement compared with the baseline Convolutional Neural Network (CNN) is achieved by over 13.23%.

Activity of respiratory chain cytochrome complexes and cytochromes content in the rat kidney mitochondria under different nutrients content in a diet

An important role in ensuring the functioning of the respiratory chain belongs to the cytochrome part, which includes complexes III (ubiquinol-cytochrome c oxidoreductase) and IV (cytochrome c oxidase). The key components of these enzymatic complexes are heme-containing cytochromes, the number of which depends on the balance of heme synthesis and catabolism. δ-Aminolevulinate synthase catalyzes the first step of the heme biosynthetic pathway, while heme oxygenase is the key enzyme of heme degradation. It is known that nutritional imbalances drive many risk factors for chronic kidney disease. That is why our research aimed to study the activity of ubiquinol-cytochrome c oxidoreductase and cytochrome oxidase complexes, the level of cytochromes a+a3, b, c, and c1, and the activity of key enzymes of heme metabolism in the mitochondria of rat kidneys under conditions of different content of protein and sucrose in animal diet. The obtained results showed a decreased activity of ubiquinol-cytochrome c oxidoreductase and cytochrome oxidase complexes and reduced levels of mitochondria cytochromes a+a3, b, c, and c1 in the kidney mitochondria under the conditions of nutrient imbalance, with the most pronounced changes found in animals kept on a low-protein/high-sucrose diet. A decrease in δ-aminolevulinate synthase activity with a simultaneous 2-fold increase in heme oxygenase activity was found in kidney mitochondria of animals kept on a low-protein/high-sucrose diet compared to those kept on full-value diet indicating an intensification of heme catabolism along with inhibition of its synthesis. The obtained results testify the energy imbalance under the conditions of low-protein/high-sucrose which in turn can lead to the progression of kidney injury. Keywords: cytochrome oxidase, cytochromes, heme oxygenase, nutrients, ubiquinol-cytochrome c oxidoreductase, δ-aminolevulinate synthase

Electric foot-shock induces neurobehavioral aberrations due to imbalance in oxidative status, stress hormone, neurochemical profile, and irregular cortical-beta wave pattern in rats: A validated animal model of anxiety

Neuropsychiatric disorders can be modeled on animals to investigate the neural mechanism underlying these disorders. Models of neuropsychiatric disorders, such as anxiety, basically aim to produce the signs and symptoms of human anxiety disorders in laboratory animals. Electric foot-shock is recommended to induce anxiety-like symptoms in rodents. For this purpose, however, a range of current intensities is available in the literature. The present study aims to modify the existing practices of generating anxiety-like symptoms through electric foot-shock by identifying an optimum current intensity and combining it with behavioral paradigms to produce a rat model of anxiety. Furthermore, the validity of the model was confirmed by checking the fulfillment of three validity criteria necessary for the development of any disease model including face validity, construct validity, and predictive validity. In the current study, after pre-testing, 1.0 mA electric intensity was selected to produce the model of anxiety. The results showed that the induction of 1.0 mA electric foot-shock induces abnormal behavioral effects which were similar to anxiety-like effects as evident by social interaction test, light-dark transition test, and open field test. Moreover, aberrations in the levels of the stress hormone, oxidative stress parameters, hippocampal neurotransmitter levels, and cortical-EEG wave pattern were also observed in the rat model of anxiety which were successfully overcome using diazepam. In conclusion, the outcome of our study suggests that electric foot-shock can be an adequate stressor to produce a validated animal model of anxiety and this model can be confidently used to identify and screen new and/or novel anxiolytics.

Phospholipase A2 regulates autophagy in gouty arthritis: proteomic and metabolomic studies

BackgroundAcute gouty arthritis is inflammatory joint arthritis. Gouty arthritis (GA) involves multiple pathological processes. Deposition of joints by monosodium urate (MSU) crystals has been shown to play a critical role in the injury process. Due to the different effects of MSU stimulation on the joints, the exact changes in the synovial fluid are unknown. We want to explore the changes in proteins and metabolites in the joints of gouty arthritis. Regulating various functional substances in the joint can reduce inflammation and pain symptoms.Methods10 patients with gouty knee arthritis and 10 normal controls were selected from clinical, surgical cases. The biological function of the metabolome was assessed by co-expression network analysis. A molecular network based on metabolomic and proteomic data was constructed to study critical molecules. The fundamental molecular changes in the relevant pathways were then verified by western blot.ResultsProteomic analysis showed that the expressions of proteases Cathepsin B, Cathepsin D, Cathepsin G, and Cathepsin S in synovial fluid patients with gouty arthritis were significantly increased. Enrichment analysis showed a positive correlation between lysosomal and clinical inflammatory cell shape changes. Untargeted metabolomic analysis revealed that lipids and lipoids accumulate, inhibit autophagic flux, and modulate inflammation and immunity in gouty arthritis patients. It was determined that the accumulation of lipid substances such as phospholipase A2 led to the imbalanced state of the autophagy-lysosome complex, and the differentially expressed metabolites of Stearoylcarnitine, Tetradecanoylcarnitine, Palmitoylcarnitine were identified (|log2 fold change|> 1.5, adjusted P value < 0.05 and variable importance in prediction (VIP) > 1.5). The autophagy-lysosomal pathway was found to be associated with gouty knee arthritis. Essential molecular alterations of multi-omics networks in gouty knee arthritis patients compared with normal controls involve acute inflammatory response, exosomes, immune responses, lysosomes, linoleic acid metabolism, and synthesis.ConclusionsComprehensive analysis of proteomic and untargeted metabolomics revealed protein and characteristic metabolite alterations in gouty arthritis, it mainly involves lipids and lipid like molecules, phospholipase A2 and autophagic lysosomes. This study describes the pathological characteristics, pathways, potential predictors and treatment goals of gouty knee arthritis.

Antioxidant Compounds from Edible Mushrooms as Potential Candidates for Treating Age-Related Neurodegenerative Diseases.

The last century has seen an increase in our life expectancy. As a result, various age-related diseases, such as neurodegenerative diseases (NDs), have emerged, representing new challenges to society. Oxidative stress (OS), a condition of redox imbalance resulting from excessive production of reactive oxygen species, represents a common feature that characterizes the brains of elderly people, thus contributing to NDs. Consequently, antioxidant supplementation or dietary intake of antioxidant-containing foods could represent an effective preventive and therapeutic intervention to maintain the integrity and survival of neurons and to counteract the neurodegenerative pathologies associated with aging. Food contains numerous bioactive molecules with beneficial actions for human health. To this purpose, a wide range of edible mushrooms have been reported to produce different antioxidant compounds such as phenolics, flavonoids, polysaccharides, vitamins, carotenoids, ergothioneine, and others, which might be used for dietary supplementation to enhance antioxidant defenses and, consequently, the prevention of age-related neurological diseases. In this review, we summarized the role of oxidative stress in age-related NDs, focusing on the current knowledge of the antioxidant compounds present in edible mushrooms, and highlighting their potential to preserve healthy aging by counteracting age-associated NDs.

Effects of eccentric-emphasized leg curl intervention on muscle strength imbalance markers in professional soccer players during pre-season

BackgroundThe effects of strength training on muscle strength imbalance are unclear in professional soccer players. As a result, this study examined the effects of an 8-week strength training program comprising eccentric-emphasized prone leg curl adjusted according to the individual strength imbalance status. MethodsTen professional soccer players (26.0 ± 3.6 yrs) participated in the study. Players who had a ≥ 10% contralateral imbalance in knee flexors eccentric peak torque (n = 6) performed two additional repetitions per set in the low-strength limb (high-volume, HV) compared to the high-strength limb (low-volume, LV). Isokinetic concentric knee extension and concentric and eccentric knee flexion peak torque (PT) and derived contralateral imbalances and conventional and functional hamstring-to-quadriceps ratios (H:Q) were assessed at baseline and after 8 weeks. Differences at baseline were assessed using paired-sample T-tests, and a two-way (limb x time) repeated measures analysis of covariance (ANCOVA) for changes over time. ResultsA significant improvement in the eccentric knee flexion PT was observed in both limbs after 8 weeks (P < 0.05), with greater effects observed in the HV limb (25.0 N m, 95% CI: 15.1–34.9 N m). Significant decreases were also observed in the contralateral imbalances from concentric knee extension and flexion and eccentric knee flexion PT (P < 0.05). Differences were not observed in concentric knee extension and flexion PT (P > 0.05). ConclusionsA short-term eccentric-emphasized leg curl intervention adjusted by the initial knee flexors eccentric strength was an efficient method to improve knee flexors strength imbalance in professional soccer players.

Common pathogenetic mechanisms in affective disorders and multiple sclerosis: role of interleukin imbalance in the progression of comorbid pathology

Relevance. Among many comorbid pathologies, it is of considerable interest to study and compare the pathogenetic mechanisms of neurological and mental disorders that combine the clinical manifestations of multiple sclerosis (MS) and affective disorders. The high MS prevalence, economic and social significance of the disease, heterogeneity of clinical symptoms, an unfavorable progressive course, as well as the frequent combination of this pathology with various forms of hypothymic disorders determine the relevance of studying the common pathogenetic mechanisms for the development of this comorbid pathology, which is necessary for the development of effective and safe preventive medical activities. The purpose of the review is to determine the common immunopathological mechanisms of affective disorders and multiple sclerosis, to analyze the role of cytokine status imbalance in the mutual increase in the severity of clinical symptoms in comorbid pathology, and to identify prognostic markers of disease progression. Materials and methods. On the basis of electronic Russian and foreign databases for the period 2017–2022, a theoretical analysis of the pathophysiological mechanisms of autoimmune CNS damage in MS and affective disorders was carried out. In order to search for literary sources, the following resources were used: https://elibrary.ru/, https://www.ncbi.nlm.nih.gov/pubmed/, https://cyberleninka.ru/. 10 Russian and 25 foreign sources were cited. Results. The mechanisms of development of mental affective disorders and multiple sclerosis have common pathogenetic features and are characterized by a violation of pro-inflammatory cytokine reactions and autoimmune nature of changes in the structures of the central nervous system (CNS). The similarity of immunological disorders underlying the pathogenesis of various forms of multiple sclerosis and affective disorders is of undoubted interest in terms of developing common approaches to the prevention and treatment of detectable interleukin status imbalance in neurological and mental diseases. Conclusion. Identification of mutually reinforcing changes in interleukin status and determination of the features of the course of immune imbalance in multiple sclerosis and hypothymic disorders in various pathologies of the mental sphere are necessary for a deeper understanding of neuroimmune interactions.