Stress-associated Diseases Research Articles

Antioxidant Peptides and Protein Hydrolysates from Tilapia: Cellular and In Vivo Evidences for Human Health Benefits.

Antioxidant peptides derived from aquatic organisms have attracted tremendous research interest due to their potential applications in human health. Tilapia is one of the most widely farmed aquaculture species globally. The current understanding of tilapia-derived antioxidant peptides is gradually expanding. This review discusses the current knowledge of peptides and protein hydrolysates derived from tilapia muscle, skin, and scales, whose antioxidant capacity has been validated in various cellular and in vivo models. To date, at least 16 peptides and several hydrolysates have been identified from tilapia that protect human and non-human cell models against oxidative injury. Tilapia hydrolysates and peptide mixtures have also shown protective effects in animal models of oxidative stress-associated diseases and exercise-induced oxidative injury and fatigue. The key mechanisms of tilapia hydrolysates and peptide mixtures involve enhancing antioxidant enzyme activities and suppressing radical production. Notably, such hydrolysates also exerted additional in vivo functions, such as anti-inflammatory, anti-diabetic, wound healing, and antiaging properties. Taken together, tilapia-derived antioxidant peptides and hydrolysates represent a valuable source of functional ingredients for applications in functional food, dietary supplements, and therapeutic applications. Continued research into their health benefits is warranted in the future.

Exploring the cytoprotective potential of flavonoid fraction from Carica papaya L. Cultivar ‘Red Lady' Leaf: Insights into Nrf2 activation via in-vitro and in-silico approaches

Flavonoids play a significant role in mitigating the production of reactive oxygen species (ROS) and subsequent oxidative stress. In the present study we aimed to evaluate the cytoprotective and antioxidant defense mechanism of flavonoid fraction from Carica papaya L. (FFCP) leaf in human PBMC. For this investigation, the human PBMCs were lotted into three groups viz., negative control, positive control (treated with H2O2), and experiment group (pretreated with FFCP and challenged with H2O2). The cytoprotective mechanism was evaluated by assessing the intracellular ROS and Ca2+ mobilization, membrane and DNA damages, antioxidant enzymes, and Nrf2 activation. In-silico analysis was employed for assessing the interactions of flavonoids in FFCP with the Nrf2 binding pocket of Keap 1 protein. The results of the experiment unveiled that FFCP protected the human PBMCs from H2O2 induced oxidative damages such as lipid peroxidation, LDH leakage, DNA breakage, reduced the intracellular ROS and Ca2+ mobilization as compared to positive control. FFCP pretreatment effectively improved the activity of key antioxidant enzyme markers, such as SOD (1.66 ± 0.032-fold increase), CAT (2.24 ± 0.09-fold increase), GPx (1.94 ± 0.05-fold increase), and GR (1.81 ± 0.14-fold increase). Furthermore, the FFCP modulated the Nrf2 gene expression (a 2.38 ± 0.25 -fold) and its translocation into the nucleus as compared to the positive control. In-silico analysis enunciated that all flavonoids exhibited strong affinity with the Nrf2 binding pocket of Keap1 protein via stable hydrogen bonding and hydrophobic interactions. These observations suggest that FFCP is a natural source of bioactive compounds with nutraceutical benefits for combating oxidative stress-associated diseases by protecting the cells from oxidative stress induced damages as well as by instigating antioxidant defense mechanisms.

Exploring the synergistic potential of pomegranate fermented juice compounds against oxidative stress-induced neurotoxicity through computational docking and experimental analysis in human neuroblastoma cells

This study explored the neuroprotective potential of fermented pomegranate (PG-F) against hydrogen peroxide (H2O2)-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and elucidated the underlying molecular mechanisms. The fermentation process, involving probiotics, transforms the hydrolyzable tannins in pomegranate juice into ellagic acid (EA) and gallic acid (GA), which are believed to contribute to its health benefits. Molecular docking simulations confirmed the stable interactions between EA, GA, and proteins associated with the antioxidant and anti-apoptotic pathways. PG-F significantly enhanced the viability of H2O2-treated cells, as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, cell morphology observations, and Hoechst 33342 staining. PG-F mitigated the H2O2-induced intracellular reactive oxygen species (ROS) levels, restored mitochondrial membrane potential, and upregulated antioxidant gene expression. The PG-F treatment also attenuated the H2O2-induced imbalance in the Bax/Bcl-2 ratio and reduced the cleaved caspase-3, caspase-7, and caspase-9 levels, suppressing the apoptotic pathways. Further insights showed that PG-F inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and facilitated the nuclear translocation of nuclear factor-erythroid 2-related factor (Nrf2), highlighting its role in modulating the key signaling pathways. A combined treatment with equivalent concentrations of EA and GA, as found in PG-F, induced remarkable cellular protection. Drug combination analysis using the Chou–Talalay method revealed a synergistic effect between EA and GA, emphasizing their combined efficacy. In conclusion, PG-F has significant neuroprotective effects against H2O2-induced neurotoxicity by modulating the antioxidant and anti-apoptotic pathways. The synergistic action of EA and GA suggests the therapeutic potential of PG-F in alleviating oxidative stress-associated neurodegenerative diseases.

Biomimetic CaCO3 microspheres as a promising delivery system for catalase: Immobilization, kinetic studies and potential perspectives in oxidative stress diseases

Oxidative stress is implicated in the pathophysiology of several illnesses. Catalase (CAT), an antioxidant enzyme, remains a prime target for oxidative stress related therapies. Unfortunately, the labile nature, difficulty in recovering and reusing, and insufficient delivery systems limit its use in therapy. This study used a simple biomineralization process for the synthesis of vaterite porous calcium carbonate (CaCO3) microspheres (MS) for the development of cross-linked immobilized (CAT-MS). Scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), particle size analysis, and zeta-potential measurements were used for CaCO3-MS characterization. CAT was immobilized efficiently with a high immobilization yield (99 %). The immobilized enzyme had a higher Km than free CAT with a 1.7 fold increase in Vmax and Kcat. CAT-MS displayed a longer half-life, efficient reusability, enhanced storage stability, and excellent stability against various denaturants compared to free CAT. Furthermore, CAT-MS demonstrated negligible cytotoxicity in the fibroblast cell line (BJ1), where CAT-MS recorded higher cell viability than free CAT, (p< 0.05) indicating exceptional biocompatibility. This study raises the potential of an eco-friendly approach that enforces wide and safe catalase application in intracellular therapy for treating oxidative stress-associated diseases.

Metabolites of Culinary-medicinal Mushroom Hericium erinaceus Showed Anti-neuroinflammatory Activity in BV2 Cells and Anti-H2O2-induced Oxidative Stress Activity in SH-SY5Y Cells

Background: Hericium erinaceus is a versatile mushroom with potential therapeutic benefits. A variety of bioactive compounds have been found in this mushroom that have anti-ulcer, antiinflammatory, immunomodulatory, and blood sugar and lipid regulating effects. Objectives: The aim is to isolate and characterize compounds from the rice medium of H. erinaceus and evaluate their potential therapeutic effects on oxidative stress-associated diseases. Methods: Fifteen compounds were isolated and characterized using NMR spectra and ESI-MS. The effects of compounds 3 and 7 on LPS-induced nitric oxide (NO) generation in BV2 cells and H2O2- induced cytotoxicity in SH-SY5Y cells were investigated. The regulation of nitric oxide production and apoptosis-associated proteins Bcl-2 and Bax were also examined. Results: Compounds 3 and 7 exhibited potent inhibitory effects on LPS-induced NO generation in microglial cells and significant resistance to H2O2-induced cytotoxicity in neuronal cells. Molecular docking simulations demonstrated the interaction of compounds 3 and 7 with iNOS and Bax, respectively. Western blot analysis revealed that 7 inhibited NO production and regulated the expression of Bax and Bcl-2, suggesting a protective effect against H2O2-induced apoptosis. Conclusion: Compounds 3 and 7 isolated from H. erinaceus are potential therapeutic candidates for oxidative stress-associated diseases, possibly through their regulation of nitric oxide production and apoptosis-related proteins. Further investigations are warranted to elucidate their mechanisms of action and therapeutic potential.

Вікові особливості трансформації психофізіологічних функцій операторів безпілотних авіаційних комплексів зі стресогенними захворюваннями органів травлення

The purpose of the study is to identify age-related changes in the psychophysiological parameters of operators of unmanned aircraft systems who have stress-associated diseases of the digestive organs. Research materials and methods. In the course of the conducted research, 58 operators of unmanned aircraft complexes aged from 21 to 50 years old who had stress-related diseases of the digestive organs were examined. The investigated operators were divided into 2 groups based on their age. The examination was carried out using blank questionnaires and modern modified methods implemented on the basis of the «PFI-2» software and hardware complex for psychophysiological research. The results. According to the research data, it was established that the probability of diseases of the digestive organs in operators ˂40 years old is 0.78, and in operators ≥40 years old – 0.22 (p=0.00001). Such a large probability gap can be explained by the fact that the young population is particularly prone to the occurrence and development of diseases of the digestive organs. The comparative analysis also demonstrated the fact that most of the psychophysiological parameters of operators with stress-related diseases worsen with age. Correlation analysis showed that according to speed psychophysiological parameters, there is an unreliable shift in the system of ensuring professional activity with age (p=0.53), аccording to the psychological functions, there is a tendency towards the transformation of changes (p=0.0653), and when studying the structure of cognitive characteristics, it weakens quite a lot (p=0.001). Conclusions. It is shown that most of the listed psychophysiological parameters in operators who have stress-associated diseases reliably worsen with age (p&lt;0.05). It was found that the number of positive and negative correlations in the operators of unmanned aircraft systems aged ≥40 years old is significantly reduced between psychological and cognitive parameters. According to the number of negative correlations between both age groups of operators, their decrease was sufficient between psychological (p=0,014) and cognitive (p=0.05) parameters. That is, in operators who have stress-associated diseases of the digestive organs, the system of connections between individual psychological and cognitive functions weakens with age. A hypothesis was formulated: stress-associated diseases cause an increase in the life support system of the operator, but with age, this system gradually breaks down, unable to withstand the effects of stress loads.

Impact of the biomass pretreatment and simulated gastrointestinal digestion on the digestibility and antioxidant activity of microalgae Chlorella vulgaris and Tetraselmis chuii

Chlorella vulgaris and Tetraselmis chuii are two microalgae species already marketed because of their richness in high-value and health-beneficial compounds. Previous studies have demonstrated the biological properties of compounds isolated from both microalgae, although data are not yet available on the impact that pre-treatment and gastrointestinal digestion could exert on these properties. The aim of the present study was to analyze the impact of the biomass pre-treatment (freeze/thaw cycles plus ultrasounds) and simulated gastrointestinal digestion in the bioaccessibility and in vitro antioxidant activity (ABTS, ORAC, Q-FRAP, Q-DPPH) of the released digests. The cell wall from microalgae were susceptible to the pre-treatment and the action of saliva and gastric enzymes, releasing bioactive peptides and phenolic compounds that contributed to the potent antioxidant activity of digests through their radical scavenging and iron reduction capacities. Our findings suggest the potential of these microalgae against oxidative stress-associated diseases at both, intestinal and systemic level.

THE IMPACT OF STRESS-ASSOCIATED DISEASES OF THE DIGESTIVE ORGANS ON THE PSYCHOPHYSIOLOGICAL STATE OF OPERATORS OF UNMANNED AIRCRAFT SYSTEMS

Introduction. In the conditions of martial law, an important role belongs to modern military equipment, which includes unmanned aircraft systems (UAS). Оperators of UAS in the course of combat missions are significantly affected by the stress factor. It provokes the occurrence of stress-associated diseases in them, therefore, studying the specifics of the impact of stress-associated diseases on the psychophysiological state of operators determines the relevance of this study. The purpose of the study. To establish the patterns of influence of stress-associated diseases of the digestive organs on the psychophysiological state of the operators of unmanned aircraft systems. Materials and methods. In the course of the research, 94 operators of UAS under the age of 40 were examined, who were then divided into groups based on their health status. The examination was carried out using modern modified methods implemented on the basis of the software and hardware complex for psychophysiological research «PFI-2». The results. It has been proven that stress-associated diseases of the digestive organs significantly worsen (p&lt;0,05) the psychophysiological state of operators of UAS in a sufficiently large number of professionally important psychophysiological qualities. The reliable influence of the «state of health» factor on the indicators of simple and complex visual-motor reaction of operators of UAS is shown. The analysis of correlation constellations according to cognitive parameters showed that 6 of them are observed in healthy operators, 2 in mildly ill patients, and 1 in severely ill patients, that is, the system of connections between cognitive functions breaks down quite strongly with the development of stress-associated diseases of the digestive organs. There is a natural decrease in the number of connections in the series «healthy (13) – mildly ill (10) – severely ill (5)». It is shown that the stress that causes the disease fundamentally destroys the system of ensuring professional activity. Conclusions. It was established that stress-associated diseases of the digestive organs negatively affect the psychophysiological state of operators. The degree of degradation of the structure of correlation relations (р=0,0491) as a result of the influence of the stress factor on the operators was revealed. A hypothesis regarding the destruction of the system of connections between cognitive psychophysiological parameters depending on the «severity of the disease» is proposed. The need to develop a set of measures to prevent the development of stress-related diseases among operators of UAS has been established.

Repeated social defeat stress differently affects arthritis-associated hypersensitivity in male and female mice

Chronic stress enhances the risk of neuropsychiatric disorders and contributes to the aggravation and chronicity of pain. The development of stress-associated diseases, including pain, is affected by individual vulnerability or resilience to stress, although the mechanisms remain elusive. We used the repeated social defeat stress model promoting susceptible and resilient phenotypes in male and female mice and induced knee mono-arthritis to investigate the impact of stress vulnerability on pain and immune system regulation. We analyzed different pain-related behaviors, measured blood cytokine and immune cell levels, and performed histological analyses at the knee joints and pain/stress-related brain areas. Stress susceptible male and female mice showed prolonged arthritis-associated hypersensitivity. Interestingly, hypersensitivity was exacerbated in male but not female mice. In males, stress promoted transiently increased neutrophils and Ly6Chigh monocytes, lasting longer in susceptible than resilient mice. While resilient male mice displayed persistently increased levels of the anti-inflammatory interleukin (IL)-10, susceptible mice showed increased levels of the pro-inflammatory IL-6 at the early- and IL-12 at the late arthritis stage. Although joint inflammation levels were comparable among groups, macrophage and neutrophil infiltration was higher in the synovium of susceptible mice. Notably, only susceptible male mice, but not females, presented microgliosis and monocyte infiltration in the prefrontal cortex at the late arthritis stage. Blood Ly6Chigh monocyte depletion during the early inflammatory phase abrogated late-stage hypersensitivity and the associated histological alterations in susceptible male mice.Thus, recruitment of blood Ly6Chigh monocytes during the early arthritis phase might be a key factor mediating the persistence of arthritis pain in susceptible male mice. Alternative neuro-immune pathways that remain to be explored might be involved in females.

Regulation of hepatocyte phospholipid peroxidation signaling by a Chinese patent medicine against psychological stress-induced liver injury

BackgroundPsychological stress is associated with various diseases including liver dysfunction, yet effective intervention strategies remain lacking due to the unrevealed pathogenesis mechanism. PurposeThis study aims to explore the relevance between BMAL1-controlled circadian rhythms and lipoxygenase 15 (ALOX15)-mediated phospholipids peroxidation in psychological stress-induced liver injury, and to investigate whether hepatocyte phospholipid peroxidation signaling is involved in the hepatoprotective effects of a Chinese patent medicine, Pien Tze Huang (PZH). MethodsRestraint stress models were established to investigate the underlying molecular mechanisms of psychological stress-induced liver injury and the hepatoprotective effects of PZH. Redox lipidomics based on liquid chromatography-tandem mass spectrometry was applied for lipid profiling. ResultsThe present study discovered that acute restraint stress could induce liver injury. Notably, lipidomic analysis confirmed that phospholipid peroxidation was accumulated in the livers of stressed mice. Additionally, the essential core circadian clock gene Brain and Muscle Arnt-like Protein-1 (Bmal1) was altered in stressed mice. Circadian disruption in mice, as well as BMAL1-overexpression in human HepaRG cells, also appeared to have a significant increase in phospholipid peroxidation, suggesting that stress-induced liver injury is closely related to circadian rhythm and phospholipid peroxidation. Subsequently, arachidonate 15-lipoxygenase (ALOX15), a critical enzyme that contributed to phospholipid peroxidation, was screened as a potential regulatory target of BMAL1. Mechanistically, BMAL1 promoted ALOX15 expression via direct binding to an E-box-like motif in the promoter. Finally, this study revealed that PZH treatment significantly relieved pathological symptoms of psychological stress-induced liver injury with a potential mechanism of alleviating ALOX15-mediated phospholipid peroxidation. ConclusionOur findings illustrate the critical role of BMAL1-triggered phospholipid peroxidation in psychological stress-induced liver injury and provide new insight into treating psychological stress-associated liver diseases by TCM intervention.

Capsosiphon fulvescens suppresses LPS-stimulated inflammatory responses by suppressing TLR4/NF-κB activation in RAW264.7 murine macrophages

Objective: To evaluate the effects of Capsosiphon fulvescens (C. fulvescens) ethanolic extract on inflammation in lipopolysaccharide (LPS)-induced RAW296.7 macrophages. Methods: The protective effects of C. fulvescens ethanolic extract on LPS-induced inflammation in RAW264.7 macrophages were assessed using biochemical analysis, including enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, and Western blot analysis. To examine reactive oxygen species (ROS) production, flow cytometry analysis, and immunofluorescence staining were used. Furthermore, the modulatory effect of C. fulvescens ethanolic extract on NF-κB activation was investigated. Results: C. fulvescens ethanolic extract significantly attenuated LPS-induced levels of pro-inflammatory cytokines and notably reduced the secretion and mRNA levels of LPS-mediated matrix metalloproteinases. In addition, C. fulvescens ethanolic extract decreased ROS production and suppressed the TLR4/NF-κB signaling pathway. Conclusions: C. fulvescens ethanolic extract alleviates inflammation as well as oxidative stress by modulating the TLR4/NF-κB signaling in LPS-induced RAW264.7 macrophages. C. fulvescens can be used as a potential therapeutic agent to suppress inflammation and oxidative stress-associated diseases.

4,5-Diamino-2-Thiouracil-Powered Dual-Mode Biosensor for Sensitive, Nonenzymatic Determination of Saliva Uric Acid Levels.

Nonenzymatic and rapid monitoring of uric acid levels is of great value for early diagnosis, prevention, and management of oxidative stress-associated diseases. However, fast, convenient, and low-cost uric acid detection remains challenging, especially in resource-limited settings. In this study, a novel and rapid biosensing approach was developed for the simultaneous visualization and quantification of uric acid levels by using the unique surface plasmon resonance and photothermal property of 4,5-diamino-2-thiouracil (DT)-capped gold nanoparticles (AuNPs). With the presence of uric acid, DT-capped AuNPs rapidly aggregated, and a visible color/photothermal change was used for uric acid quantification within 15 min. The limit of detection was determined to be 11.3 and 6.6 μM for the dual-mode biosensor, leveraging the unique structure of DT to optimize reaction kinetics. Moreover, the sensor exhibited excellent anti-interference capabilities and demonstrated potential for detecting a wide range of uric acid concentrations in complex samples, thereby reducing the need for extensive sample dilution and complex material synthesis procedures. Furthermore, validation against gold standard testing indicates that this biosensor could serve as a highly sensitive assay for quantifying uric acid levels in point-of-care applications, particularly in resource-limited settings.

Structural modification of C2-substituents on 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N′-diacetic acid derivatives as potent inhibitors of the Keap1-Nrf2 protein-protein interaction

The Keap1-Nrf2-ARE signaling pathway is an attractive therapeutic target for the prevention and treatment of oxidative stress-associated diseases by activating the cellular expression of cytoprotective enzymes and proteins. Small molecule inhibitors can directly disrupt the Keap1-Nrf2 protein-protein interaction (PPI), resulting in elevated levels of Nrf2 protein and subsequent stimulation of related antioxidant responses. Previously, we found that 1,4-bis(arylsulfonamido)benzene or naphthalene-N,N′-diacetic acid derivatives with an ether type C2-substituent on the benzene or naphthalene core exhibited potent inhibitory activities with IC50's in the submicromolar or nanomolar range. We here describe a more detailed structure-activity relationship study around the C2 substituents containing various polar linkers shedding new insight on their binding interactions with the Keap1 Kelch domain. The key observation from our findings is that the substituents at the C2-position of the benzene or naphthalene scaffold impact their inhibitory potencies in biochemical assays as well as activities in cell culture. The biochemical FP and TR-FRET assays revealed that the naphthalene derivatives 17b and 18 with an additional carboxylate at the C2 were the most active inhibitors against Keap1-Nrf2 PPI. In the cell-based assay, the two compounds were shown to be potent Nrf2 activators of the transcription of the Nrf2-dependent genes, such as HMOX2, GSTM3, and NQO1.

Індикатори змін рівня функціональних резервів організму операторів при розвитку вікових змін, втоми та асоційованих зі стресом захворювань

In the condition of war on the territory of our country, the intensity of the development of events that surround a person has changed significantly. In this regard, the need to apply simple and quick methods of assessing the functional state has increased. This especially applies to operators of unmanned aircraft systems, whose professional activity is associated with a large informational and physical load. The purpose of study was to study the possibilities of the stabilometry methods in assessing functional changes in the body of operators associated with the loss of their functional reserves. This affects the psychophysiological age, fatigue and deviations in operators of unmanned aircraft systems, which have a stress-associated diseases. The presence of unidirectionality of psychophysiological processes that occur with age changed, during the development of fatigue and diseases, caused by the influence of a stress factor is shown. A linear multiple regression model was built, which can be used to determine the level and rate of aging of operators, and a nonlinear multiple regression model that can estimate the degree of fatigue that develops during the year in the operator while performing official duties. With help of the method of discriminant analysis, special solving rules have been developed, according to which it is possible to determine whether the operator belongs to a group of healthy persons or those suffering from stress-associated diseases.

Probing Tyrosine Nitration with a Small TbIII -Metallopeptide.

Tyrosine nitration, a post-translational modification (PTM) that takes place under nitrosative stress conditions, occurs through a non-enzymatic peroxynitrite-mediated reaction. Although protein nitration has long been considered an irreversible PTM involved in nitrosative stress-associated diseases, it has also been suggested to be a regulatory mechanism of signal transduction. Therefore, the development of tools that help to understand this protein modification is of great interest. Herein, we explore a TbIII -chelating metallopeptide to monitor tyrosine nitration. The luminescence of this probe decreases significantly between its non-nitrated and nitrated states, and this reduction in the luminescence intensity is directly related to the degree of tyrosine nitration after treatment with peroxynitrite. Remarkably, the luminescence intensity changes after nitration are not affected in the presence of complex biological media, which makes it a promising tool for understanding this protein modification.

Comparative characteristics of professionally important psychophysiological parameters of operators of unmanned aircraft complexes, practically healthy and patients with stress-associated diseases

Annotation. The article is devoted to the study and comparison of the professionally important psychophysiological parameters of the operators of unmanned aerial systems (UAVs), practically healthy (40 people) and those suffering from stress-related diseases (80 people), who are serving in the Armed Forces of Ukraine. In patients with stress-associated diseases of UAVs operators, we found the significance of the changes in the indicators of the latent period of simple and complex visual-motor reaction, balance during the study of the reaction to a moving object, and the number of false marks when performing a concentration test with a reliability of p&lt;0.05. The structure of the correlations of practically healthy and patients with stress-related diseases of UAVs operators in the parameters of concentration of attention, orientation in space and short-term visual memory are definitely different, which indicates a major restructuring of the functional system of the operators' professional activity in these aspects. Therefore, in order to prevent the occurrence of such changes, it is necessary to develop a set of organizational and medical measures to compensate for the negative impact of stress-associated diseases on the functional state of UAVs operators.

Potential of Nutmeg (&lt;em&gt;Myristica fragrans&lt;/em&gt; Houtt) Leaf Extracts as a Source of Functional Ingredients with Antibacterial, Antifungal and Antioxidant Activities

Purpose: The objectives of this study were to evaluate inhibition activities of acetone, chloroform, ethanol and hot water extracts of nutmeg (Myristica fragrans Houtt.) leaves against Salmonella enterica, Listeria monocytogenes, Shigella dysenteriae, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Aspergillus niger and, to assess the in vitro antioxidant activities and to discover the active compound profile of chloroform extract of nutmeg leaf. Research Method: Agar well diffusion and agar disc diffusion methods were used to evaluate the antibacterial activity and the antifungal activity of the extracts respectively. Antioxidant activities of the acetone extract were evaluated through DPPH, FRAP, ABTS+ radical scavenging and Ferrous Iron Chelating assays. The total phenolic content (TPC) of the acetone extract was determined using the Folin-Ciocalteu assay. Findings: All the extracts showed inhibitory activity for the tested bacteria at different intensities and it was found that the selection of the extraction solvent is important to get the maximum inhibition against different bacterium. Acetone and chloroform extract (20%) showed the highest inhibition against A. niger (49.42% and 51.52% respectively). Acetone extract showed strong antioxidant activities, 715.78 ±51.09 in FRAP (mg of Trolox /g of leaves), 65.56±0.93 in DPPH (mg of Ascorbic acid /g of leaves), 31.67± 0.49 in ABTS+ (mg of Trolox equivalent/g of leaves), 10.87±1.85 in Ferrous Ion chelating (mg of EDTA/g of leaves) and, higher percentages of total phenolic content of 895.12 ±44.24 TPC (mg GAE /g of leaves). Myristic acid was detected as the major compound (57.36%) in GC-MS analysis and that may be the major compound responsible that offers a great potential to use as antibacterial, antifungal and antioxidant agent of nutmeg leaf. Originality/ Value: Results revealed that the nutmeg leaf possesses marked biological activities and showed a great potential to use for the management of human pathogenic bacteria, plant pathogenic fungi, and oxidative stress-associated chronic diseases.

Irisin at the Crossroad of Autophagy and BNDF Signaling for Neuroplasticity Regulation

Neuroplasticity is an integral feature of both the developing brain and the brain maintaining functional homeostasis and implementing adaptive changes at normal conditions and upon compensation for pathology. Support of neuroplasticity mechanisms of is one of the targets for therapeutic intervention in the treatment of neurodegenerative and stress-associated diseases. Progress in understanding the mechanisms of interaction between the muscular system and the brain points to the role of the myokine irisin in mediating the procognitive and antidepressant activity of physical exercises. Irisin being released upon myocytes activation in the periphery can cross the blood-brain barrier and is thought to stimulate cellular autophagy. Autophagy-mediated activation of protein and macromolecule recycling promotes adaptive restructuring of synaptic contacts, and the release of proteases, including matrix metalloproteinase 9, which are determining the reformatting of the extracellular matrix, maturation of brain-derived neurotrophic factor (BDNF), and, therefore, the positive regulation of BDNF signaling. Recent findings allow one to consider factors stimulating autophagy as prerequisites for successful treatment of neurological and psychiatric disorders, as well as age-related dementia. Therefore, irisin, as a physiological regulator of autophagy, appears as a prototype molecule for the creation of new therapeutic agents for the correction of neurodegenerative conditions and stress-associated brain disorders.

Iridoids and oxidative stress-associated diseases

Iridoids and oxidative stress-associated diseases

Dual-omics reveals temporal differences in acute sympathetic stress-induced cardiac inflammation following α1 and β-adrenergic receptors activation.

Sympathetic stress is prevalent in cardiovascular diseases. Sympathetic overactivation under strong acute stresses triggers acute cardiovascular events including myocardial infarction (MI), sudden cardiac death, and stress cardiomyopathy. α1-ARs and β-ARs, two dominant subtypes of adrenergic receptors in the heart, play a significant role in the physiological and pathologic regulation of these processes. However, little is known about the functional similarities and differences between α1- and β-ARs activated temporal responses in stress-induced cardiac pathology. In this work, we systematically compared the cardiac temporal genome-wide profiles of acute α1-AR and β-AR activation in the mice model by integrating transcriptome and proteome. We found that α1- and β-AR activations induced sustained and transient inflammatory gene expression, respectively. Particularly, the overactivation of α1-AR but not β-AR led to neutrophil infiltration at one day, which was closely associated with the up-regulation of chemokines, activation of NF-κB pathway, and sustained inflammatory response. Furthermore, there are more metabolic disorders under α1-AR overactivation compared with β-AR overactivation. These findings provide a new therapeutic strategy that, besides using β-blocker as soon as possible, blocking α1-AR within one day should also be considered in the treatment of acute stress-associated cardiovascular diseases.