Stress Markers Research Articles

Safflower Yellow Alleviates Cognitive Impairment in Mice by Modulating Cholinergic System Function, Oxidative Stress, and CREB/BDNF/TrkB Signaling Pathway

Ethnopharmacological relevanceCarthamus tinctorius L. (Safflower) was believed to have multiple benefits, including antioxidant effects, enhanced learning and memory, and improving neuronal injury. Safflower Yellow(SY) are the main active ingredients of Safflower, displays strong pharmacological potential treatment of Alzheimer's disease(AD). However, its effect on memory impairments remains insufficiently investigated. Aim of the study:The study aims to investigate the effects of SY on cognitive functions in memory impairments model and to explore the mechanism of its action. Materials and methodsWe utilized the Morris Water Maze, Step-Through Test, Step-Down Test to assess the potential of SY in ameliorating learning and memory dysfunction caused by SCOP, NaNO2 and ethanol in mice. Bioinformatic analysis and molecular biological approaches were used to study the related mechanisms of SY on anti-memory impairments. ResultsThe results of the Morris Water Test suggested that SY could shorten the escape latency and the time of the first crossing platform in the mice with memory acquisition and memory consolidation impairments, and increase the platform crossing times. The results of the Step-Though test and Step-Down test showed that the escape latency in the mice was prolonged and the number of errors was reduced after SY treatment. ELISA experiments indicated that SY decreased the AChE activities, increased the ChAT activities, and modulated oxidative stress markers (SOD, MDA, and GSH-PX) in scopolamine-induced mice. Western Blot and Nissl staining showed that SY could activated BDNF/TrkB/CREB signaling pathway and reduced neuronal damage. ConclusionThe findings present that SY can restore the function of the cholinergic system, inhibit oxidative stress, regulate the expression of upstream and downstream proteins in the CREB/BDNF/TrkB pathway, and alleviate brain tissue damage to improve memory impairment in mice.

Evaluation of oxidative stress biomarkers for differentiating bacterial and viral infections: a comparative study of glutathione disulfide (GSSG) and reduced glutathione (GSH)

Background and aims. This study evaluates the potential of oxidative stress biomarkers, specifically glutathione disulfide (GSSG) and reduced glutathione (GSH), for differentiating bacterial and viral infections. Oxidative stress plays a crucial role in the immune response, and glutathione is a key regulator of cellular redox balance. The aim was to assess whether differences in GSH and GSSG levels could be used as diagnostic markers for infection type. Methods. A chemiluminescence-based method evaluated GSH and GSSG as potential biomarkers for distinguishing between bacterial and viral infections. The GSH and GSSG concentrations were analyzed across bacterial, viral, and control groups. Results. Our data revealed significant differences in the GSH/GSSG ratio between the analyzed groups, with bacterial infections showing higher oxidative stress markers compared to viral infections. A combined analysis of GSH and GSSG concentrations, visualized through heatmaps and ROC curves, improved diagnostic accuracy, with clustering patterns distinguishing infection types. Conclusions. These findings suggest that the GSH/GSSG ratio could be used as a biomarker in distinguishing between bacterial and viral infections, offering potential clinical applications for more accurate diagnosis. Further research is required to validate these results in larger cohorts and to explore the underlying mechanisms of oxidative stress in pathogen-specific immune responses.

Transcriptome-wide analysis reveal dynamic expression changes during endoplasmic reticulum stress in tomato

Endoplasmic reticulum (ER) stress is a cellular condition induced by environmental stressors. Transcriptomic approaches reveal the response of plants to ER stress and provide a broadened view. Tomato plants were treated with tunicamycin, and total RNA isolated from the tomato leaves was sequenced on an RNA-sequencing platform to be analyzed for differential expressions. A total of 856 differentially expressed genes (DEGs) were discovered in tunicamycin-treated tomato leaves. Upregulation of ER stress marker gene expressions was detected after 2h, while a prolonged ER stress downregulated most of the protein-coding genes. Pathways such as: response to stress, jasmonic acid mediated signaling, signal transduction regulation, plant hormone signal transduction, and protein processing in ER were enriched. Prolonged stress mostly resulted in reduced transcript levels, possibly related to a mechanism functioning to lower the load of nascent transcripts in the ER. Our findings emphasize the key role of JA-regulated signaling in tomato ER stress responses due to the differential expressions of the pathway components, along with other plant hormones and signaling-related or regulatory genes. ER stress being a common response to many stressors in plants, transcriptome data obtained here will provide for further studies of understanding plant stress tolerance or generating stress-resistant tomato plants.

L-arginine, aminoguanidine and mesenchymal stem cells reduce the level of endoplasmic reticulum stress markers and D-dimer in the lungs of mice with antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by damage to the intima of the microcirculatory blood vessels as a result of the formation of autoimmune antibodies to phospholipids of cell membranes. Recent data indicate a possible link between the occurrence of autoimmune diseases and endoplasmic reticulum stress, impaired nitric oxide availability, high plasma D-dimer level. The aim of the study was to estimate the effect of nitric oxide synthesis modulators L-arginine and aminoguanidine, and mesenchymal stem cells on the level of inositol-requiring enzyme-1a (IRE-1a), glucose-regulated protein 78 (GRP-78) as ER stress markers, and the level of D-dimer in the lung tissue of female BALB/c line mice with experimental APS induced with cardiolipin administration. 30 experimental animals were divided into five groups: 1 – control animals; 2 – mice with APS; 3 – mice with APS, injected intraperitoneally with L-arginine hydrochloride (25 mg/kg) and aminoguanidine (10 mg/kg); 4 – mice with APS, injected intraperitoneally with stem cells (5×106/kg); 5 – mice with APS, injected with L-arginine hydrochloride, aminoguanidine and stem cells in combination. After 10 days post APS formation animals were removed from the experiment, proteins were extracted from the lung tissue and their level was determined with Western blotting. It was established that in group with APS the levels of IRE-1, GRP-78 and D-dimer were substantially increased as compared to the control group. After separate administration of both arginine with aminoguanidine and MSC, as well as with their combined use, the level of IRE-1, GRP-78 and D-dimer decreased compared to the indices in animals with induced APS. The obtained data indicated that this effect is probably due to the reduction of ER stress through iNOS inhibition and the anti-inflammatory action of MSCs. Keywords: aminoguanidine, antiphospholipid syndrome, D-dimer, endoplasmic reticulume stress, GRP-78, IRE-1, L-arginine, lung, mesenchymal stem cells

Correlation of screen exposure to stress, learning, cognitive and language performance in children.

The omnipresence of mobile screens and convenience to operate them has led to increased screen time for young children whereas the sequelae of prolonged exposure are not known yet. 70 refugee children (RG) and 111 children of a clinical comparison group (CG) from a help-seeking population (age: M = 5.10; SD = 1.11; range 3.00-6.97years) were assessed concerning their amount of daily screen exposure time in relation to parental education and distress. Salivary cortisol was collected as a marker for biological stress and children were tested concerning learning performance, non-verbal IQ and vocabulary with the Kaufmann Assessment Battery for Children (KABC-II). Language skills were assessed in educator rating. The amount of children's screen exposure was negatively related to parental education and positively to distress. In the CG, higher amounts of screen time were associated with elevated cortisol levels and lower learning scores. On both measures, the RG and CG only differed in the condition of screen time less than one hour/day, for higher amounts of screen time the CG approached the more problematic scores of the RG. Whereas in the whole sample the amount of screen time was negatively correlated to language performance, it was not correlated to non-verbal IQ-scores. As a higher amount of media exposure in our clinical comparison group is associated with elevated biological stress, decreased learning and lower language performance, it should be classified as a relevant environmental factor and regularly considered in clinical assessments of children and therapeutical interventions, especially in vulnerable subgroups. German clinical trials register, registration number: DRKS00025734, date: 07-23-2021.

Dietary Restriction of Advanced Glycation End-Products (AGEs) in Patients with Diabetes: A Systematic Review of Randomized Controlled Trials.

Advanced Glycation End Products (AGEs) are formed through non-enzymatic reactions between reducing sugars and proteins, nucleic acids or lipids (for example through hyperoxidation). In diabetes, elevated glucose levels provide more substrate for AGEs formation. AGEs can also be ingested through the diet from foods cooked at high temperatures, or containing much sugar. The present work aimed to review all published randomized controlled trials (RCT) on low-dietary AGE (L-dAGEs) interventions in patients with diabetes. Pubmed, Scopus and Cochrane databases were searched (until 29 February 2024) with appropriate keywords (inclusion criteria: RCT, patients with diabetes, age > 18 years, outcomes related to inflammation, glucose, and lipids; exclusion criteria: non-RCTs, case-series, case reports and Letter to the Editor, or animal studies). The present review was registered to the Open Science Framework (OSF). From 7091 studies, seven were ultimately included. Bias was assessed with the updated Cochrane Risk of Bias tool. A reduction in circulating AGEs was documented in 3/3 studies. No particular differences were documented in glycemic parameters after a L-dAGEs diet. Reductions in glucose levels were observed in one out of six studies (1/6), while HbA1c and HOMA did not change in any study (0/6 and 0/3, correspondingly). Lipid profile also changed in one out of four studies (1/4). More consistent results were observed for oxidative stress (beneficial effects in 3/3 studies) and inflammatory markers (beneficial effects in 4/4 studies). Other athero-protective effects, such as adiponectin increases, were reported. Limitations included the small sample size and the fact that dietary and physical activity habits were not considered in most studies. In conclusion, a L-dAGEs pattern may minimize AGEs accumulation and have beneficial effects on oxidative stress and inflammation indices, while its effects on glycemic and lipemic parameters are inconsistent and modest in patients with diabetes.

Curcumin alleviates arsenic trioxide-induced neural damage in the murine striatal region.

Arsenic-induced neurotoxicity, with dose-dependent effects, is well-documented in rodents. Curcumin (CUR), a cost-effective plant polyphenol, shows neuroprotective effects by modulating oxidative stress, apoptosis, and neurochemistry. This study evaluates curcumin's neuroprotective potential against arsenic trioxide (As2O3) in the mouse striatal region. Healthy adult male mice were chronically administered with varying concentrations of As2O3 (2, 4 and 8mg/kg bw) alone and along with CUR (100mg/kg bw) orally for 45days.Towards the end of the experimental period, the animals were subjected to behavioural paradigms including open field task, novel object recognition, rota-rod, and Morris water maze. Striatal tissues were freshly collected from the animals on day 46 for biochemical analyses (MDA, GPx, and GSH). Additionally, perfusion-fixed brains were processed for morphological observations. Behavioural study showed an apparent decrease in certain cognitive functions (learning and memory) and locomotor activity in mice exposed to As2O3 compared to controls. Simultaneous treatment of As2O3 (2, 4 and 8mg/kg bw) and curcumin (100mg/kg bw) alleviated the As-induced locomotor and cognitive deficits. As2O3 alone exposure also exhibited a significant increase in oxidative stress marker (MDA) and a decrease in antioxidant enzyme levels (GPx, GSH). Morphological alterations were noted in mice subjected to elevated doses of As2O3 (4 and 8mg/kg bw). However, these changes were reversed in mice who received As2O3 + CUR co-treatment. Collectively, our findings indicate that curcumin offers neuroprotection to the striatal region against As2O3-induced behavioral deficits, as well as biochemical and morphological alterations.

Evaluating Inclusion of Commercial Pistachio By-Product as a Functional Ingredient in Rainbow Trout Fishmeal and Plant Meal-Based Diets

To meet the growing demand for sustainable aquaculture, plant proteins are being explored as alternative sources in fish diets. However, some plant proteins can have adverse health effects on fish, prompting research into functional feed ingredients to mitigate these issues. This study investigated pistachio shell powder (PSP), rich in antioxidants, as a functional feed ingredient for rainbow trout (Oncorhynchus mykiss). The effects of PSP inclusion (0%, 0.5%, 1%, 2%) on growth performance, intestinal health, and gut microbiota were assessed in fish fed either a fishmeal (FM) or plant meal (PM) diet over a 12-week feeding period. The results indicated that PSP inclusion at 1% significantly (p < 0.05) improved weight gain and growth performance in FM treatments, with no impact on growth in PM treatments. No significant differences were observed in other growth parameters, intestinal morphology, or oxidative stress markers, although a trend toward the downregulation of inflammatory genes was noted in PM treatments at 2% PSP inclusion. PSP inclusion did not significantly alter gut microbiota alpha diversity but affected beta diversity at the 0.5% level in the FM treatments (p < 0.05). Differential abundance analysis of gut microbiota revealed taxa-specific responses to PSP, particularly the genus Candidatus arthromitus, increasing in relative abundance with PSP inclusion in both the FM- and PM-based treatments. Overall, PSP inclusion up to 2% did not have significant adverse effects on the growth, intestinal health, or antioxidant status of rainbow trout.

Antimutagenic and anticoagulant therapeutic effects of Ag/Ag2O nanoparticles from Olea europaea leaf extract: mitigating metribuzin-induced hepato-and nephrotoxicity.

Silver nanoparticles (Ag/Ag₂O NPs) have garnered attention for their potent antioxidant, antimicrobial, and anti-inflammatory properties, showing promise for therapeutic applications, particularly in mitigating chemical-induced toxicity. This study aimed to synthesize Ag/Ag₂O NPs using Olea europaea (olive) leaf extract as a green, eco-friendly reducing agent and evaluate their protective effects against metribuzin-induced toxicity in Wistar rats, focusing on oxidative stress, hematological parameters, and lipid profiles, with specific dose optimization. Ag/Ag₂O NPs were synthesized using Olea europaea leaf extract, and their properties were confirmed via XRD, FTIR, SEM, EDS, and UV-visible spectroscopy. Wistar rats exposed to metribuzin (110mg/kg/day) were treated with two doses of Ag/Ag₂O NPs (0.062mg/kg and 0.125mg/kg). Hematological and biochemical markers were assessed to evaluate the NPs' protective effects. Physicochemical characterization confirmed the successful formation of Ag/Ag₂O NPs loaded with phytochemicals, exhibiting crystallite sizes of 23nm and 19nm, a particle size of 25nm, and significant peaks in XRD, FTIR, and UV-Vis spectra indicating the formation of Ag/Ag₂O. Metribuzin exposure led to significant hematological disruptions (elevated WBC, reduced RBC and hemoglobin) and worsened lipid profiles (increased cholesterol, LDL, and triglycerides). The lower NP dose (0.062mg/kg) improved WBC, RBC, hemoglobin, and platelet counts, normalized lipid levels, and positively influenced biochemical markers such as serum creatinine and uric acid. In contrast, the higher NP dose (0.125mg/kg) showed mixed results, with some improvements but an increase in triglycerides and continued elevation of ASAT and ALAT enzyme levels. Ag/Ag₂O NPs synthesized via green methods using olive leaf extract effectively mitigated metribuzin-induced toxicity, especially at lower doses, by improving oxidative stress markers and hematological and biochemical profiles. Dose optimization is crucial to maximize therapeutic benefits and minimize adverse effects, underscoring their potential in treating chemical-induced toxicity.

Bacterial Cellulose Membrane Experimentally Implanted in the Peritoneum of Wistar Rats—Inflammatory Immunoreactivity and Oxidative Stress

Bacterial cellulose (BC) has been used for various applications; however, studies investigating the immunohistochemical characteristics of the inflammatory and scarring component in BC implanted in the peritoneum in vivo have not yet been fully described. This study aimed to evaluate the systemic and organic safety of BC through oxidative stress, blood, and serum biochemical markers, as well as the late inflammatory response in rats, using histopathology and immunohistochemistry. Forty-three rats (26 males; 17 females) received BC in the peritoneal cavity (implanted group—IG), while twenty-seven rats (12 males; 15 females) served as the control (sham group—SG). Sixty days after surgery, oxidative stress in tissues, blood biochemical markers, and histopathological and immunohistochemical analyses for lymphocytes, macrophages, collagen, and vascular response around the BC were assessed. Only one oxidative stress marker, glutathione peroxidase, was elevated in the liver of IG rats. Creatine kinase MB and lactate dehydrogenase levels were significantly lower in IG animals. Histopathological analysis showed granulomatous inflammation in 93% of IG rats, with 74% of mild intensity. Immunohistochemistry revealed a significant macrophage presence (F4/80), with CD3, CD20, and F4/80 markers indicating differences favoring macrophages. In conclusion, BC implantation in the peritoneum induces a foreign body granulomatous response with prominent macrophage presence (F4/80). Type I and III collagen were observed around the membrane, and vascularization was intense 60 days post-implantation. From a biochemical and oxidative stress perspective, BC seems to be a safe material to be used in the peritoneal cavity.

The Impact of COVID-19 Vaccination on Oxidative Stress and Cardiac Fibrosis Biomarkers in Patients with Acute Myocardial Infarction (STEMI), a Single-Center Experience Analysis

The relationship between the classical cardiac biomarker and acute myocardial infarction (STEMI) in patients with COVID-19 is far from being elucidated. Furthermore, superoxide dismutase (SOD), a marker for oxidative stress, was associated with cardiac ischemia. Also, Galectin-3 is significant for defining the relationship between cardiac fibrosis and COVID-19. There are no studies on the effect of SARS-CoV-2 virus infection and vaccination on patients with STEMI and biomarkers above-mentioned. Aim: our single-center prospective study assesses the relationship between COVID-19 infection with/without vaccination and the value of SOD and Galectin-3 in STEMI patients. Material and methods: In total, 93 patients with STEMI and SARS-CoV-2 virus infection were included in the analysis, patients were divided in two groups based on COVID-19 vaccination status. Echocardiographic and laboratory investigations for cardiac ischemia, oxidative stress, and cardiac fibrosis biomarkers were investigated. Results: In total, 93 patients were included, the majority of which were male (72.0%), 45.2% (n = 42) were vaccinated against SARS-CoV-2; the mean age of vaccinated patients is 62 years, and 57% (n = 53) are smokers; blood pressure is found with a higher frequency in unvaccinated people (62.7%) compared to 28.6% in vaccinated people (p = 0.015), and 90.5% of the vaccinated people presented STEMI, compared with 96.1% of the unvaccinated ones. Revascularization with one stent was achieved in 47.6% of the vaccinated people and 72.5% for the unvaccinated people (p = 0.015). Galectin-3 was slightly more reduced in the vaccinated patients compared to the unvaccinated patients (0.73 vs. 0.99; p = 0.202), and the average level of Cu/ZnSOD was slightly more reduced in vaccinated patients compared to the unvaccinated patients (0.84 vs. 0.91; p = 0.740). Conclusions: Regarding patient’s SARS-CoV-2 infection functional status, the results from our single-center analysis did not find a statistically significant decrease in oxidative stress and cardiac fibrosis biomarkers along with cardiovascular complication following STEMI treated with percutaneous coronary angioplasty (PCI) in the case of patients with COVID-19 vaccination compared with patients who did not receive COVID-19 vaccine. Anyway, our data suggest that contemporary PCI techniques may offer an alternative revascularization strategy that enables complex CAD COVID-19 patients to be safely discharged from hospital.

Brivaracetam and rufinamide combination increased seizure threshold and improved neurobehavioral deficits in corneal kindling model of epilepsy.

Besides seizures, a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy, which further debilitates their quality of life. This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses, respectively, on corneal kindling-induced generalized seizures and behavioral alterations. Furthermore, observed convulsive frequency and behavioral changes were correlated to post-kindling-induced changes in the activity of markers of oxidative stress. Adult C57BL/6 mice were kindled via twice-daily transcorneal 50-Hz electrical stimulations (3 mA) for 3 s for 12 days until animals reached a fully kindled state. After the kindling procedure, animals were tested using a set of behavioral tests, and neurochemical alterations were assessed. Corneal-kindled animals exhibited intense generalized convulsions, altered behavioral phenotypes typified by positive symptoms (hyperlocomotion), negative symptoms (anxiety and anhedonia), and deficits in semantic and working memory. BRV 10 + RFM 20 dual regime increased convulsive threshold and propensity toward the start of stage 4-5 seizures and improved phenotypical deficits, that is, anxiety, depression, and memory impairments. Moreover, this combination therapy mitigated kindling-induced redox impairments as evidenced by reduced malondialdehyde and acetylcholinesterase levels and increased glutathione antioxidant activity in the brain of animals subjected to repetitive brain insult. Based on our outcomes, this dual therapy provides supporting evidence in alleviating epilepsy-induced neurobehavioral comorbidities and changes in redox homeostasis.

Oxidative stress markers in canine parvovirus infection

Parvovirus infections are among the deadly viral diseases in dogs and sick puppies. Young dogs are more prone to the virus. Antioxidants are important components of the defense system which prevent cell damage by neutralizing reactive oxygen species. Malondialdehyde is a reliable and commonly used marker of oxidative stress. The present study was performed to determine the role of oxidative stress markers in canine parvovirus disease. Thirty Cane Corso male dogs with an average age of 3-6 months were enrolled in this study out of which 10 animals were spontaneously infected with the parvovirus and the other 10 were healthy. The activity of superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde were measured by colorimetric methods whereas the enzymatic activity of glutathione peroxidase (GPX) was measured. Catalase was measured by means of rapid spectrophotometry and chromography was used for obtaining the concentrations of vitamin D and vitamin E. The increase in malondialdehyde in infected dogs demonstrates that oxidative stress plays a role in the pathogenesis of the parvovirus. The significant elevation in TAC, and lack of important changes in superoxide dismutase and catalase are indicative of a good response by the antioxidant system against oxidative stress induced by the parvovirus. In conclusion, oxidative stress is involved in the pathogenesis of parvovirus. Thus, strengthening the antioxidant system can be effective in the prevention and treatment of canine parvovirus infection.

Molecular mechanisms of endoplasmic reticulum stress-mediated acute kidney injury in juvenile rats and the protective role of mesencephalic astrocyte-derived neurotrophic factor.

This study examined the role of endoplasmic reticulum stress in pediatric acute kidney injury and the therapeutic effect of midbrain astrocyte-derived neurotrophic factor. Two-week-old Sprague-Dawley rats were divided into: Sham, ischemia-reperfusion injury-induced acute kidney injury (AKI), mesencephalic astrocyte-derived neurotrophic factor (MANF)-treated, tauroursodeoxycholic acid (TUDCA)-treated. Analyses were conducted 24h post-treatment. Serum creatinine, cystatin C, Albumin, MANF levels were measured, cytokine concentrations in serum and renal tissues were determined using a Luminex assay. Histopathology was assessed via light and electron microscopy. Western blotting and RT-qPCR analyzed markers for oxidative stress, apoptosis, endoplasmic reticulum (ER) stress, and autophagy. HK-2 cells underwent hypoxia/reoxygenation (H/R) to simulate AKI and were treated with MANF or TUDCA. AKI rats had increased serum creatinine, cystatin C, and inflammatory cytokines, along with significant renal damage, and showed loose and swollen ER structures, reduced cell proliferation, and elevated levels of IRE1, PERK, ATF6, CHOP, LC3-II/I, KIM-1, TLR4, JNK, and NF-κB. MANF treatment reduced these biomarkers and protein levels, improved ER structure and cell proliferation, alleviated oxidative stress, apoptosis, ER stress, and inhibited JNK/TLR4/NF-κB signaling. In HK-2 cells, MANF reduced ER stress and inflammation post-H/R exposure. MANF treatment alleviates ER stress, oxidative stress, apoptosis, and inflammation in pediatric AKI, improving renal function and morphology.

Acute and sub-acute toxicity study of aqueous and methanol root extract of Tetracera alnifolia in male albino rats

The aim of this study was to assess the acute and sub-acute toxicity of aqueous and methanol extracts of the root of Tetracera alnifolia as well as the effects on some biochemical parameters in albino rats as many plants used in traditional medicine lack scientific and clinical evidence to support a better understanding of their safety and efficacy. Phytochemical screening and proximate analysis of the pulverised root of Tetracera alnifolia was carried out using previously reported protocol. Sub-acute toxicity study of each extract was done for 28 days followed by organs function tests and histopathology studies of the liver, kidney and heart. Evaluation of lipid profile and oxidative stress marker to ascertain the effect of each extract on lipid peroxidation and their antioxidant property was done after administration of 200 mg/Kg body weight of each extract for a period of thirty-five days. Acute toxicity study of each extract gave oral LD50 (rat) of greater than 5000 mg/kg body weight with no signs of toxicity. Sub-acute toxicity study showed both extracts were non-toxic to the liver, kidney, heart and blood at doses between 200 and 3000 mg/Kg body weight assessed by the respective organ function tests, hematological parameters, and histopathology study. However, higher doses seem toxic to the liver particularly at 5000 mg/kg B. W due to increase in plasma AST, ALT and ALP activities accompanied with reduced protein and albumin concentrations. Effects of each extracts at 200 mg/Kg body weight on some biochemical parameters revealed no significant difference in lipid profile parameters and no lipid peroxidation. Each extract may possess antioxidant property due to increase in catalase activity. The result from this research may help validate the safety of the oral use of this plant in traditional medicine.

Effects of smoking on local and systemic oxidative stress markers in individuals with periodontitis

Aim: This study aimed to assess the effects of smoking on systemic and local oxidative stress markers in patients with periodontitis. Methods: A total of 72 patients with periodontitis [38 smokers (S +P+), 34 non-smokers (S-P+)] and 54 periodontally healthy individuals [28 smokers (S+P-), 26 non-smokers (S-P-, control)] were included. After clinical measurements and samplings, the cotinine level, total antioxidant capacity (TAOC), total oxidative status (TOS), and malondialdehyde (MDA) level in the serum and saliva were determined, and the oxidative stress index (OSI) was calculated. Kruskal-Wallis and Mann-Whitney U tests were used for multiple and pairwise comparisons. Correlations were analyzed using Pearson correlation coefficient. P<0.05 was considered statistically significant. Results: Smoking and periodontitis decreased the serum and salivary TAOCs and increased the TOS, MDA level, and OSI. The smokers with periodontitis had the lowest TAOC and the highest TOS, MDA level, and OSI, while the controls had the highest TAOC and the lowest TOS, MDA level, and OSI. The systemic and local effects of smoking seemed more pronounced than those of periodontitis in the oxidative stress study, but no significant difference was identified between the smoking (S+P-) and periodontitis (S-P+) groups. The clinical parameters and oxidative stress markers showed both substantial positive and negative relationships in all groups (p<0.01). Conclusions: It can be concluded that smoking and periodontitis (S+P+) are associated with a decrease in serum and salivary TAOCs and an increase in TOS, MDA levels, and OSI. Smoking has a similar effect as periodontitis on local and systemic oxidative stress, and oxidative stress caused by smoking may be a significant factor in the pathophysiology of periodontitis.

Effects of WN1703 on Cardiovascular Function in Chronic Hyperuricemia Rats and Myocardial Injury Mechanism Exploration in H9C2 Cells.

Hyperuricemia, a prevalent condition, is typically preceded by disturbances in purine metabolism and is frequently associated with hyperlipidemia and other dysfunctions of metabolism. WN1703 demonstrated an inhibitory activity against xanthine oxidoreductase (XOR) that was comparable to febuxostat in our prior investigation. In this study, we assessed the cardiovascular safety of WN1703 in a chronic hyperuricemia rat model induced by potassium oxonate in combination with hypoxanthine. We investigated the changes in cardiovascular biomarkers in chronic hyperuricemia rats treated with febuxostat and WN1703, including creatine kinase (CK), CK-MB, B type natriuretic peptide (BNP), Corin protein (CRN), Neprilysin (NEP), myeloperoxidase (MPO), 8-hydroxy-2-deoxyguanosine (8-OHdG), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-8 (IL-8). Additionally, we validated the potential mechanism of cardiac injury induced by WN1703 in H9C2 cells, guided by cardiotoxicity predictions from the cardioToxCSM database and network pharmacology. We observed that excessively rapid urate-lowering, oxidative stress, and inflammation could disrupt myocardial functional homeostasis and increase the risk of cardiovascular injury in hyperuricemia rats, and WN1703 treatment effectively reduced the levels oxidative stress marker 8-OHdG and inflammatory factor TNF-α. Despite the absence of organic damage to the heart with prolonged treatment of febuxostat and WN1703, potential hazard of cardiovascular injury could be associated with the modulation of the TGFβ and RHO/ROCK signaling pathways by febuxostat and WN1703. This could offer new insights into the mechanisms underlying the adverse effects caused by XOR inhibitors.

Raga Bhairavi in virtual reality reduces stress-related psychophysiological markers

The effects of classical music on psychophysiological parameters are not well understood. This study aimed to investigate the impact of listening to raga Bhairavi, an Indian Classical Music for six days on anxiety, stress, depression, and heart rate variability (HRV) parameters. Forty-four individuals were randomly assigned to either the intervention group (VR-raga), where they listened to raga Bhairavi via 360° video in a virtual reality environment, or the control group, where there was no exposure to raga Bhairavi for six days. Before allocation, the HRV baselines (relax-baseline and stress-baseline) were recorded on the first day. On the first and sixth days of the intervention, HRV was monitored, and the Depression, Anxiety, and Stress Scale (DASS-21) questionnaire was administered before and after the intervention. After six days, all DASS-21 subscales were significantly reduced in the VR-raga group. A similar trend was observed in the seven HRV parameters evaluated in this study, which demonstrated reduced physiological stress and enhanced autonomic balance following the six-day intervention. The findings collectively indicated the efficacy of the VR-based raga Bhairavi intervention in reducing psychological stress markers and highlighted the potential applications of utilizing the VR-based raga intervention for improving mental well-being in the real-world context.

Phillyrin inhibits oxidative stress and neutrophil extracellular trap formation through the KEAP1/NRF2 pathway in gouty arthritis.

Gouty arthritis (GA) is an inflammatory disorder characterized by deposition of monosodium urate (MSU) crystal in joints. Phillyrin, a natural compound with anti-inflammatory properties, shows promise in mitigating inflammatory responses. This study investigates the therapeutic potential of phillyrin in GA and explores its mechanisms of action. GA was induced in mice via intraarticular MSU injection, and joint inflammation, inflammatory cell infiltration, and their level in serum/tissue were assessed. Key proteins in the NF-κB and NLRP3 pathways were examined using western blot analysis. The impact of phillyrin on oxidative stress, neutrophil extracellular trap (NET) formation, and neutrophil accumulation was evaluated by measuring CD11b + Ly6G + cells, MPO, CitH3, extracellular DNA ratio, and oxidative stress markers. In vitro studies assessed the effects of phillyrin on oxidative stress, cell viability, cytokine production, and NET formation in MSU-treated neutrophils. The KEAP1/NRF2 pathway's role was analyzed using ML385, an NRF2 inhibitor. Phillyrin significantly reversed MSU-induced ankle swelling and inflammatory cell infiltration in joint tissues. It suppressed pro-inflammatory cytokines and proteins in the NF-κB and NLRP3 pathways. Phillyrin reduced neutrophil infiltration, evidenced by lower MPO activity and NET formation, marked by reduced CitH3 expression. In vitro, phillyrin inhibited inflammatory marker expression and NET formation without affecting cell viability. It also restored antioxidant enzyme levels and reduced ROS production, regulating the KEAP1/NRF2 pathway, enhancing NRF2 expression and stability. These effects were reversed by NRF2 inhibition with ML385. Phillyrin alleviates GA by reducing joint inflammation, inhibiting NET formation, and suppressing oxidative stress through NRF2 modulation.

Evaluation of Bioactive Compounds, Antioxidant Capacity, and Anti-Inflammatory Effects of Lipophilic and Hydrophilic Extracts of the Pericarp of Passiflora tripartita var. mollissima at Two Stages of Ripening.

Chronic disease inflammation requires safe complementary treatments. The pericarp of Passiflora tripartita var. mollissima (PTM) contains potential anti-inflammatory metabolites. This study aimed to evaluate the bioactive components, antioxidant capacity, and anti-inflammatory effects of PTM extracts at two ripening stages. The bioactive compounds in the hydrophilic and lipophilic extracts of mature and green pericarps were identified by GC-MS and UV-VIS, while the antioxidant capacity was measured by free radical reduction. Anti-inflammatory effects were tested using a rat paw edema model with carrageenan-induced edema, indomethacin, or PTM extracts (100, 250, and 500 mg/kg). The effect of mature hydrophilic extract was further evaluated in an air pouch model, where rats received the placebo, carrageenan, indomethacin, or the extract (500 and 1000 mg/kg). Leukocytes, cytokines, and markers of oxidative stress were evaluated. The results showed the presence of organic compounds, total phenols, and flavonoids. The mature hydrophilic extract exhibited the highest antioxidant activity. At 500 mg/kg, it reduced edema, leukocyte migration, and levels of IL-1β, IL-6, and TNF-α while managing oxidative stress and preventing histological damage. In conclusion, PTM contains bioactive compounds with potential pharmacological properties. The hydrophilic extract of the mature pericarp, at a dose of 500 mg/kg, exhibits an enhanced antioxidant and anti-inflammatory effect.