Sensitization of Multidrug Resistant Cancer Cells to Doxorubicin Using Ebselen by Disturbing Cellular Redox Status.

Multidrug resistance (MDR) poses a significant problem in cancer treatment, often causing adverse effects during chemotherapy. Ebselen (Ebs), a synthetic organoselenium compound, affects cellular redox status in cancer cells. In the study, we observed that Ebs disrupted cellular redox balance and sensitized drug-resistant cells to doxorubicin (DOX) treatment. The combination of Ebs and DOX led to increased intracellular reactive oxygen species (ROS) levels and lipid peroxidation while decreasing the activity of thioredoxin reductase (TrxR) and cellular antioxidants in drug-resistant cells. Furthermore, this combination treatment demonstrated notable chemosensitizing effects by reducing cell viability and proliferation in MDR cells compared to DOX treatment alone. Additionally, the combination of Ebs and DOX induced DNA fragmentation and exhibited G2/M phase cell cycle arrest. Immunofluorescent analysis revealed that the Ebs and DOX combination upregulated the expression of p53 and p21, which activated the mitochondrial-dependent apoptotic pathway. The combination treatment also enhanced the upregulation of proapoptotic markers such as Bax, Caspase-3, -9, and cytochrome C, while downregulating the expression of the antiapoptotic marker Bcl-2. Therefore, the current discoveries suggest that Ebs could be employed as a drug candidate for reversing MDR in cancer cells by regulating cellular redox homeostasis.

Oat Beta-Glucan as a Metabolic Regulator in Early Stage of Colorectal Cancer-A Model Study on Azoxymethane-Treated Rats.

Factors that reduce the risk of developing colorectal cancer include biologically active substances. In our previous research, we demonstrated the anti-inflammatory, immunomodulatory, and antioxidant effects of oat beta-glucans in gastrointestinal disease models. The aim of this study was to investigate the effect of an 8-week consumption of a diet supplemented with low-molar-mass oat beta-glucan in two doses on the antioxidant potential, inflammatory parameters, and colonic metabolomic profile in azoxymethane(AOM)-induced early-stage colorectal cancer in the large intestine wall of rats. The results showed a statistically significant effect of AOM leading to the development of neoplastic changes in the colon. Consumption of beta-glucans induced changes in colonic antioxidant potential parameters, including an increase in total antioxidant status, a decrease in the superoxide dismutase (SOD) activity, and a reduction in thiobarbituric acid reactive substance (TBARS) concentration. In addition, beta-glucans decreased the levels of pro-inflammatory interleukins (IL-1α, IL-1ß, IL-12) and C-reactive protein (CRP) while increasing the concentration of IL-10. Metabolomic studies confirmed the efficacy of oat beta-glucans in the AOM-induced early-stage colon cancer model by increasing the levels of metabolites involved in metabolic pathways, such as amino acids, purine, biotin, and folate. In conclusion, these results suggest a wide range of mechanisms involved in altering colonic metabolism during the early stage of carcinogenesis and a strong influence of low-molar-mass oat beta-glucan, administered as dietary supplement, in modulating these mechanisms.

Analytical Methods for Assessing Thiol Antioxidants in Biological Fluids: A Review.

Redox metabolism is an integral part of the glutathione system, encompassing reduced and oxidized glutathione, hydrogen peroxide, and associated enzymes. This core process orchestrates a network of thiol antioxidants like thioredoxins and peroxiredoxins, alongside critical thiol-containing proteins such as mercaptoalbumin. Modifications to thiol-containing proteins, including oxidation and glutathionylation, regulate cellular signaling influencing gene activities in inflammation and carcinogenesis. Analyzing thiol antioxidants, especially glutathione, in biological fluids offers insights into pathological conditions. This review discusses the analytical methods for biothiol determination, mainly in blood plasma. The study includes all key methodological aspects of spectroscopy, chromatography, electrochemistry, and mass spectrometry, highlighting their principles, benefits, limitations, and recent advancements that were not included in previously published reviews. Sample preparation and factors affecting thiol antioxidant measurements are discussed. The review reveals that the choice of analytical procedures should be based on the specific requirements of the research. Spectrophotometric methods are simple and cost-effective but may need more specificity. Chromatographic techniques have excellent separation capabilities but require longer analysis times. Electrochemical methods enable real-time monitoring but have disadvantages such as interference. Mass spectrometry-based approaches have high sensitivity and selectivity but require sophisticated instrumentation. Combining multiple techniques can provide comprehensive information on thiol antioxidant levels in biological fluids, enabling clearer insights into their roles in health and disease. This review covers the time span from 2010 to mid-2024, and the data were obtained from the SciFinder® (ACS), Google Scholar (Google), PubMed®, and ScienceDirect (Scopus) databases through a combination search approach using keywords.

The effect of dietary administration of Saussurea lappa root on performance, blood biochemical indices, redox status, innate immune response, intestinal microbial population and resistance against A. hydrophila infections of Tilapia Fingerlings.

This experiment was performed to identify the influence of dietary Saussurea lappa root (SLR) on the performance and general health status of Nile Tilapia fingerlings (O. niloticus). Four formulated diets with different SLR levels of 0.0, 2.5, 5 and 10 g/kg, respectively, were afforded to fingerling fish (15.42 ± 0.05 g) for 8 weeks. The feed efficiency ratio (FER), feed intake (FI) and feed conversion ratio varied with dietary SLR level in a linear model and a high feed efficiency rate was recorded at the 10 g/kg group, while FI and FCR exhibited an opposite trend (P < 0.001). Dietary SLR level influenced serum protein constituents, liver and renal function enzymes, triglycerides, cholesterol and glucose (P < 0.001). Serum Catalase (CAT), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) remarkedly increased with dietary SLR level and attained a level at 10 g/kg. Furthermore, serum lysozyme, complement C3 (C3), IgA and IgD were stimulated by 10 g/kg SLR. Intestinal digestive enzymes (lipase and amylase) increased with SLR level up to 10 g/kg. As the dietary SLR level raised, the cumulative survival percentage aginst A. hydrophila challenge increased and then reached a maximum at 10 g/kg SLR group. Moreover, gene expression of pro-inflammation cytokines (TNF-2a, IL-1ß, and IL-10) in liver and kidney transcriptomes demonstrated effective immunostimulant capabilities of greater SLR inclusion levels in fish diet. Meanwhile, intestinal microbial investigation, revealed that high levels of SLR in tilapia fish feed significantly suppressed total bacterial count, and pathogenic bacterial count (such as, E. coli, Coliform, Aeromonas spp, Pseudomonas spp.), and stimulated lactic acid bacteria development. Finally, it is recommended to include a high level of SLR (5 or 10 g/kg) in the diet of O. niloticus fingerlings to enhance feed efficiency, antioxidant characteristics, and immunological response against bacterial infections.

Potential effects of probiotics (immunobacteryne; IMB) on growth performance, feed efficacy, blood biochemical, redox balance, nonspecific immunity and heat-shock protein expression of Nile tilapia (Oreochromis niloticus) fingerlings.

The supplementation of aquafeed with probiotics is recommended for feasible aquaculture activities. Therefore, the aim of current study was to investigate the potential effects of probiotics on growth performance, feed utilization, biochemical attributes, redox status and immunity response as well as the transcription of heat-shock protein 70 (HSP70) and insulin-like growth factor-1 (IGF-1) genes of Nile tilapia (Oreochromis niloticus; n = 120). Fish with an initial weight of 8.17 ± 0.02 g/fish were randomly divided into four treatment groups and were fed diets containing 0, 0.5, 1 and 1.5 mg immunobacteryne (IMB)/kg diet respectively. Dietary IMB at 1.5 g/kg diet significantly improved the growth performance, feed consumption and growth hormone secretion of the experimental fish (p < 0.05). The 1 or 1.5 g IMB/kg diet boosted phagocytic activities and innate immune response. Serum total protein, total cholesterol, triglycerides and glucose were significantly increased in the groups that were fed 1 and 1.5 mg IMB/kg diet compared to the control (p < 0.05). Meanwhile, the levels of uric acid, creatinine, liver enzymes (aspartate transaminase and alanine transaminase) and cortisol hormone were significantly reduced in the aforementioned treated groups compared to the control (p < 0.05). All fish fed IMB-supplemented diet showed a significant increase in the expression of IGF-1 gene, while the transcription of HSP70 was significantly decreased (p < 0.05). In conclusion, the dietary inclusion of IMB (1 g/kg diet) enhanced growth promoters, feed efficacy, blood biochemical, redox balance and nonspecific immune responses in Nile tilapia fingerlings.

Ethylene Renders Silver Nanoparticles Stress Tolerance in Rice Seedlings by Regulating Endogenous Nitric Oxide Accumulation.

Developments in the field of nanotechnology over the past few years have increased the prevalence of silver nanoparticles (AgNPs) in the environment, resulting in increased exposure of plants to AgNPs. Recently, various studies have reported the effect of AgNPs on plant growth at different concentrations. However, identifying the mechanisms and signaling molecules involved in plant responses against AgNPs stress is crucial to find an effective way to deal with the phytotoxic impacts of AgNPs on plant growth and development. Therefore, this study was envisaged to investigate the participation of ethylene in mediating the activation of AgNPs stress tolerance in rice (Oryza sativa L.) through a switch that regulates endogenous nitric oxide (NO) accumulation. Treatment of AgNPs alone hampered the growth of rice seedlings due to severe oxidative stress as a result of decline in sulfur assimilation, glutathione (GSH) biosynthesis and alteration in the redox status of GSH. These results are also accompanied by the higher endogenous NO level. However, addition of ethephon (a donor of ethylene) reversed the AgNP-induced effects. Though the application of silicon nanoparticles (SiNPs) alone promoted the growth of rice seedlings but, interestingly their application in combination with AgNPs enhanced the AgNP-induced toxicity in the seedlings through the same routes as exhibited in the case of AgNPs alone treatment. Interestingly, addition of ethephon reversed the negative effects of SiNPs under AgNPs stress. These results suggest that ethylene might act as a switch to regulate the level of endogenous NO, which in turn could be associated with AgNPs stress tolerance in rice. Furthermore, the results also indicated that addition of l-NG-nitro arginine methyl ester (l-NAME) (an inhibitor of endogenous NO synthesis) also reversed the toxic effects of SiNPs together with AgNPs, further suggesting that the low level of endogenous NO was associated with AgNPs stress tolerance. Overall, the results indicate that the low level of endogenous NO triggers AgNPs stress tolerance, while high level leads to AgNPs toxicity by regulating sulfur assimilation, GSH biosynthesis, redox status of GSH and oxidative stress markers. The results revealed that ethylene might act as a switch for regulating AgNPs stress in rice seedlings by controlling endogenous NO accumulation.

Plasma thiol levels and methylenetetrahydrofolate reductase gene c.665C > T and c.1286A > C variants affect fibrin clot properties in Polish venous thromboembolic patients.

BACKGROUND AND AIMS: Aminothiols, including cysteine (Cys) and glutathione (GSH) in relation to fibrin clot phenotype were not investigated in patients with venous thromboembolism (VTE) and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene variants. We aimed to explore the associations between MTHFR variants and plasma oxidative stress indicators including aminothiols as well as fibrin clot properties with plasma oxidative status and fibrin clot properties in this group of patients. METHODS: In 387 VTE patients the MTHFR c.665C > T and c.1286A > C variants were genotyped, together with chromatographic separation of plasma thiols. We also determined nitrotyrosine levels and fibrin clot properties, including clot permeability (Ks), lysis time (CLT), and fibrin fibers thickness. RESULTS: There were 193 patients with MTHFR c.665C > T (49.9%) and 214 (55.3%) with c.1286A > C variants. Both allele carriers with total homocysteine (tHcy) levels >15 µM (n = 71, 18.3%), compared to patients with tHcy ≤15 µM had 11.5% and 12.5% higher Cys levels, 20.6% and 34.3% higher GSH levels as well as 28.1% and 57.4% increased nitrotyrosine levels, respectively (all P < 0.05). The MTHFR c.665C > T carriers with tHcy levels >15 µM compared to tHcy ≤15 µM had 39.4% reduced Ks and 9% reduced fibrin fibers thickness (both P < 0.05) with no differences in CLT. In the MTHFR c.1286A > C carriers with tHcy levels >15 µM, Ks was decreased by 44.5%, CLT prolonged by 46.1%, and fibrin fibers thickness was reduced by 14.5% compared to patients with tHcy ≤15 µM (all P < 0.05). Nitrotyrosine levels in MTHFR variants carriers correlated with Ks (r = -0.38, P < 0.05) and fibrin fibers diameter (r = -0.50, P < 0.05). CONCLUSIONS: Our study indicates that patients with MTHFR variants and tHcy >15 µM are characterized by elevated Cys and nitrotyrosine levels associated with prothrombotic fibrin clot properties.

Effects of used and under-used doses of Transfluthrin-based insecticide on Caenorhabditis elegans metabolism.

Different classes of insecticide compounds have been employed to control insects and mosquitoes; Pyrethroids are one of the most common used in both urban and rural household environments. This study investigated the effects of exposure of two doses of commercial transfluthrin-based insecticide (T-BI) on behavior (body bends, pharyngeal pumping rate, and feeding attributes) and biochemical biomarkers (AChE, PolyQ40 aggregations, HSP, antioxidative SOD, CTL, and GST) following three different protocols (transgenerational, neonatal, and lifespan) in Caenorhabditis elegans model system. The relative calculated dose (RCD) and relative calculated half dose (RCHD) of T-BI were compared with those of the control (water). T-BI reduced the health span of worms treated during their whole life and changed biochemical and behavioral patterns due to progenitors' uterine (transgenerational) and neonatal exposures. It was inferred that the effects of T-BI are transgenerational and persistent and can be harmful to non-target species, including humans. In addition, our findings highlight that T-BI contact by progenitors accelerates the establishment of Huntington's disease and causes a cholinergic outbreak in offspring adulthood.

The role of O3 exposure and physical activity status on redox state, inflammation, and pulmonary toxicity of young men: A cross-sectional study.

The exposure to traffic-related air pollutants, such as NO2 and O3, are associated with detrimental health effects, becoming one of the greatest public health issues worldwide. Exercising in polluted environments could result in harmful outcomes for health and may blunt the physiological adaptations of exercise training. This study aimed to investigate the influence of physical activity and O3 exposure on redox status, an inflammatory marker, response to stress, and pulmonary toxicity of healthy young individuals. We performed a cross-sectional study with 100 individuals that, based on their exposure to O3 and physical fitness (PF) level, were distributed in four groups: Low PF + Low O3; Low PF + High O3; High PF + Low O3; High PF + High O3. We evaluated personal exposure to NO2 and O3, physical activity level, variables of oxidative stress (SOD, ROS, CAT, GSH, TBARS), pulmonary toxicity (CC16), and inflammatory mediators (IL-1ß, IL-4, IL-6, IL-10, TNF-α, HSP70). Spearman correlation test to check the association among the variables was used and to compare groups we used one-way ANOVA followed by Bonferroni's post hoc and Kruskal Wallis test followed by Dunn's post hoc. O3 levels correlated with physical activity (r = 0.25; p = 0.01) but not with age or markers of body composition (p > 0.05). The individuals with high physical fitness that were less exposed to O3 presented higher CAT activity (p < 0.001), lower TBARS (p < 0.01) and IL-1ß concentrations (p < 0.01), higher IL-6 (p < 0.05) and IL-10 concentrations (p < 0.05), lower IL-6:1L-10 ratio (p < 0.05), lower CC16 levels (p < 0.05), and higher HSP70 concentration (p < 0.05). Physical activity could result in higher exposure to O3 that could partially blunt some exercise adaptations, while high physical fitness improved the antioxidant defense system, systemic inflammatory mediators, and pulmonary toxicity.

Sublethal doses of glyphosate modulates mitochondria and oxidative stress in honeybees by direct feeding.

Honeybees are essential for the ecosystem maintenance and for plant production in agriculture. Glyphosate is a broad-spectrum systemic herbicide widely used in crops to control weeds and could affect honeybees' health in sublethal doses. Our aim was to study how sublethal doses of glyphosate affects to oxidative stress and mitochondrial homeostasis in honeybees. We exposed honeybees to glyphosate at 5 and 10 mg·l-1 for 2 and 10 h for the gene expression analysis by reverse transcription polymerase chain reaction and for 48 and 72 h for the antioxidant enzymes activity and lipid peroxidation determination. We observed a general increase in antioxidant- and mitochondrial-related genes expression in honeybees after 2 h of exposition to glyphosate, as well as a rise in catalase and superoxide dismutase enzymatic activity after 48 h and an increment in lipid peroxidation adducts generation after 72 h. These results suggest a direct effect of glyphosate on honeybees' health, with an insufficient response of the antioxidant system to the generated oxidative stress, resulting in an increase in lipid peroxidation and, therefore, oxidative damage. Altogether, results obtained in this work demonstrate that sublethal treatments of glyphosate could directly affect honeybee individuals under laboratory conditions. Therefore, it is necessary to investigate alternatives to glyphosate to determine if they are less harmful to non-target organisms.

Changes in salivary biomarkers of stress, inflammation, redox status, and muscle damage due to Streptococcus suis infection in pigs.

BACKGROUND: Streptococcus suis (S. suis) is a Gram-positive bacteria that infects pigs causing meningitis, arthritis, pneumonia, or endocarditis. This increases the mortality in pig farms deriving in severe economic losses. The use of saliva as a diagnostic fluid has various advantages compared to blood, especially in pigs. In this study, it was hypothesized that saliva could reflect changes in different biomarkers related to stress, inflammation, redox status, and muscle damage in pigs with S. suis infection and that changes in these biomarkers could be related to the severity of the disease. RESULTS: A total of 56 growing pigs from a farm were selected as infected pigs (n = 28) and healthy pigs (n = 28). Results showed increases in biomarkers related to stress (alpha-amylase and oxytocin), inflammation (haptoglobin, inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), total protein, S100A8-A9 and S100A12), redox status (advanced oxidation protein producs (AOPP)) and muscle damage (creatine kinase (CK), CK-MB, troponin I, lactate, aspartate aminotransferase, and lactate dehydrogenase). An increase in adenosine deaminase (ADA), procalcitonin, and aldolase in infected animals were also observed, as previously described. The grade of severity of the disease indicated a significant positive correlation with total protein concentrations, aspartate aminotransferase, aldolase, and AOPP. CONCLUSIONS: This report revealed that S. suis infection caused variations in analytes related to stress, inflammation, redox status, and muscle damage in the saliva of pigs and these can be considered potential biomarkers for this disease.

Auranofin sensitizes breast cancer cells to paclitaxel chemotherapy by disturbing the cellular redox system.

The intrinsic redox status of cancer cells limits the efficacy of chemotherapeutic drugs. Auranofin, a Food and Drug Administration-approved gold-containing compound, documented with effective pharmacokinetics and safety profiles in humans, has recently been repurposed for anticancer activity. This study examined the paclitaxel-sensitizing effect of auranofin by targeting redox balance in the MDA-MB-231 and MCF-7 breast cancer cell lines. Auranofin treatment depletes the activities of superoxide dismutase, catalase, and glutathione peroxidase and alters the redox ratio in the breast cancer cell lines. Furthermore, it has been noticed that auranofin augmented paclitaxel-mediated cytotoxicity in a concentration-dependent manner in both MDA-MB-231 and MCF-7 cell lines. Moreover, auranofin increased the levels of intracellular reactive oxygen species (observed using 2, 7-diacetyl dichlorofluorescein diacetate staining) and subsequently altered the mitochondrial membrane potential (rhodamine-123 staining) in a concentration-dependent manner. Further, the expression of apoptotic marker p21 was found to be higher in auranofin plus paclitaxel-treated breast cancer cells compared to paclitaxel-alone treatment. Thus, the present results illustrate the chemosensitizing property of auranofin in MDA-MB-231 and MCF-7 breast cancer cell lines via oxidative metabolism. Therefore, auranofin could be considered a chemosensitizing agent during cancer chemotherapy.

The Effect of Hypercapnia on Cortical Metabolic Rate and Mitochondrial Redox Status.

Hypercapnia is commonly used as a vasodilatory stimulus in both basic and clinical research. There have been conflicting reports about whether cerebral metabolic rate of oxygen (CMRO2) is maintained at normal levels during increases of cerebral blood flow (CBF) and oxygen delivery caused by hypercapnia.This study aims to provide insight into how hypercapnia may impact CMRO2 and brain mitochondrial function. We introduce data from mouse cortex collected with a novel multimodality system which combines MRI and near-infrared spectroscopy (NIRS). We quantify CBF, tissue oxygen saturation (StO2), oxidation state of the mitochondrial enzyme cytochrome c oxidase (CCO), and CMRO2.During hypercapnia, CMRO2 did not change while CBF, StO2, and the oxidation state of CCO increased significantly. This paper supports the conclusion that hypercapnia does not change CMRO2. It also introduces the application of a multimodal NIRS-MRI system which enables non-invasive quantification of CMRO2, and other physiological variables, in the cerebral cortex of mouse models.

Efficacy of creatine nitrate supplementation on redox status and mitochondrial function in pectoralis major muscle of preslaughter transported broilers.

This study was purposed to investigate the efficacy of dietary creatine nitrate (CrN) supplementation on redox status and mitochondrial function in pectoralis major (PM) muscle of broilers that experienced preslaughter transport. A total of 288 Arbor Acres broilers (28-day-old) were randomly assigned into five dietary treatments, including a basal diet or the basal diet supplemented with 600 mg/kg guanidinoacetic acid (GAA), 300, 600, or 900 mg/kg CrN for 14 days, respectively. On the transportation day, the basal diet group was divided into two groups on average, resulting in six groups. The control group was transported for 0.5 h and the other groups for 3 h (identified as Control, T3h, GAA600, CrN300, CrN600, and CrN900 group, respectively), and all crates were randomly placed on the truck travelling at an average speed of 80 km/h. Our results showed that GAA600 and CrN treatments decreased the muscle ROS level and MDA content (P < 0.05) and increased the mitochondrial membrane potential (P < 0.001), as well as a higher mRNA expression of avUCP (P < 0.001) and lower mRNA expressions of Nrf2 (P < 0.001), Nrf2 and PGC-1α (P < 0.05) compared with T3h group. Meanwhile, the mRNA and protein expressions of Nrf1, TFAM, and PGC-1α in CrN600 and CrN900 groups were lower than those in the T3h group (P < 0.05). Conclusively, dietary supplementation with GAA and CrN decreased muscle oxidative products and enhanced mitochondrial uncoupling mechanism and mtDNA copy number, which relieved muscle oxidative damage and maintained mitochondrial function.

Temporal analysis of paracetamol-induced hepatotoxicity.

Paracetamol-induced hepatotoxicity (APAP) causes severe damage that may be irreversible. Understanding the evolution of liver injury caused by overdose of the drug is important to assist in the treatment. In the present study, we evaluated the acute intoxication by APAP (500 mg/kg) in periods of 3 and 12 hours in C57BL/6 mice through biochemical, histological, inflammatory parameters, and the redox status. The results showed that in the 3-hour period there was an increase in creatinine dosage and lipid peroxidation (TBARS) compared to the control group. In the period of 12 hours after APAP intoxication all parameters evaluated were altered; there was an increase of ALT, AST, and necrosis, besides the increase of redox status biomarkers as carbonylated protein, TBARS, and MMP-9. We also observed activation of the inflammasome pathway as well as a reduction in the regenerative capacity of hepatocytes with a decrease in binucleated liver cells. In cytochrome gene expression, the mRNA level increased in CYP2E1 isoenzyme and reduced CYP1A2 expression. This study indicated that early treatment is necessary to mitigate APAP-induced acute liver injury, and alternative therapies capable of controlling the progression of intoxication in the liver are needed.

Redox Status and Telomere-Telomerase System Biomarkers in Patients with Acute Myocardial Infarction Using a Principal Component Analysis: Is There a Link?

In the present study, we examined redox status parameters in arterial and venous blood samples, its potential to predict the prognosis of acute myocardial infarction (AMI) patients assessed through its impact on the comprehensive grading SYNTAX score, and its clinical accuracy. Potential connections between common blood biomarkers, biomarkers of redox status, leukocyte telomere length, and telomerase enzyme activity in the acute myocardial infarction burden were assessed using principal component analysis (PCA). This study included 92 patients with acute myocardial infarction. Significantly higher levels of advanced oxidation protein products (AOPP), superoxide anion (O2•-), ischemia-modified albumin (IMA), and significantly lower levels of total oxidant status (TOS) and total protein sulfhydryl (SH-) groups were found in arterial blood than in the peripheral venous blood samples, while biomarkers of the telomere-telomerase system did not show statistical significance in the two compared sample types (p = 0.834 and p = 0.419). To better understand the effect of the examined biomarkers in the AMI patients on SYNTAX score, those biomarkers were grouped using PCA, which merged them into the four the most contributing factors. The "cholesterol-protein factor" and "oxidative-telomere factor" were independent predictors of higher SYNTAX score (OR = 0.338, p = 0.008 and OR = 0.427, p = 0.035, respectively), while the ability to discriminate STEMI from non-STEMI patients had only the "oxidative-telomere factor" (AUC = 0.860, p = 0.008). The results show that traditional cardiovascular risk factors, i.e., high total cholesterol together with high total serum proteins and haemoglobin, are associated with severe disease progression in much the same way as a combination of redox biomarkers (pro-oxidant-antioxidant balance, total antioxidant status, IMA) and telomere length.

Analysis of the Prognostic Potential of Schlafen 11, Programmed Death Ligand 1, and Redox Status in Colorectal Cancer Patients.

The Schlafen 11 (SLFN11) protein has recently emerged as pivotal in DNA damage conditions, with predictive potential for tumor response to cytotoxic chemotherapies. Recent discoveries also showed that the programmed death ligand 1 (PD-L1) protein can be found on malignant cells, providing an immune evasion mechanism exploited by different tumors. Additionally, excessive generation of free radicals, redox imbalance, and consequential DNA damage can affect intestinal cell homeostasis and lead to neoplastic transformation. Therefore, our study aimed to investigate the significance of SLFN11 and PD-L1 proteins and redox status parameters as prognostic biomarkers in CRC patients. This study included a total of 155 CRC patients. SLFN11 and PD-L1 serum levels were measured with ELISA and evaluated based on redox status parameters, sociodemographic and clinical characteristics, and survival. The following redox status parameters were investigated: spectrophotometrically measured superoxide dismutase (SOD), sulfhydryl (SH) groups, advanced oxidation protein products (AOPP), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), and superoxide anion (O2•-). The prooxidative score, antioxidative score, and OXY-SCORE were also calculated. The results showed significantly shorter survival in patients with higher OXY-SCOREs and higher levels of serum SLFN11, while only histopathology-analysis-related factors showed significant prognostic value. OXY-SCORE and SLFN11 levels may harbor prognostic potential in CRC patients.

Melatonin Role in Plant Growth and Physiology under Abiotic Stress.

Phyto-melatonin improves crop yield by mitigating the negative effects of abiotic stresses on plant growth. Numerous studies are currently being conducted to investigate the significant performance of melatonin in crops in regulating agricultural growth and productivity. However, a comprehensive review of the pivotal performance of phyto-melatonin in regulating plant morpho-physiological and biochemical activities under abiotic stresses needs to be clarified. This review focused on the research on morpho-physiological activities, plant growth regulation, redox status, and signal transduction in plants under abiotic stresses. Furthermore, it also highlighted the role of phyto-melatonin in plant defense systems and as biostimulants under abiotic stress conditions. The study revealed that phyto-melatonin enhances some leaf senescence proteins, and that protein further interacts with the plant's photosynthesis activity, macromolecules, and changes in redox and response to abiotic stress. Our goal is to thoroughly evaluate phyto-melatonin performance under abiotic stress, which will help us better understand the mechanism by which phyto-melatonin regulates crop growth and yield.

An Insight into the Impact of Serum Tellurium, Thallium, Osmium and Antimony on the Antioxidant/Redox Status of PCOS Patients: A Comprehensive Study.

Humans exploit heavy metals for various industrial and economic reasons. Although some heavy metals are essential for normal physiology, others such as Tellurium (Te), Thallium (TI), antimony (Sb), and Osmium (Os) are highly toxic and can lead to Polycystic Ovarian Syndrome (PCOS), a common female factor of infertility. The current study was undertaken to determine levels of the heavy metals TI, Te, Sb and Os in serum of PCOS females (n = 50) compared to healthy non-PCOS controls (n = 56), and to relate such levels with Total Antioxidant Capacity (TAC), activity of key antioxidant enzymes, oxidative stress marker levels and redox status. PCOS serum samples demonstrated significantly higher levels of TI, Te, Sb and Os and diminished TAC compared to control (p < 0.001). Furthermore, there was significant inhibition of SOD, CAT and several glutathione-related enzyme activities in sera of PCOS patients with concurrent elevations in superoxide anions, hydrogen and lipid peroxides, and protein carbonyls, along with disrupted glutathione homeostasis compared to those of controls (p < 0.001 for all parameters). Additionally, a significant negative correlation was found between the elevated levels of heavy metals and TAC, indicative of the role of metal-induced oxidative stress as a prominent phenomenon associated with the pathophysiology of the underlying PCOS. Data obtained in the study suggest toxic metals as risk factors causing PCOS, and thus protective measures should be considered to minimize exposure to prevent such reproductive anomalies.

Hormesis Responses of Photosystem II in Arabidopsis thaliana under Water Deficit Stress.

Since drought stress is one of the key risks for the future of agriculture, exploring the molecular mechanisms of photosynthetic responses to water deficit stress is, therefore, fundamental. By using chlorophyll fluorescence imaging analysis, we evaluated the responses of photosystem II (PSII) photochemistry in young and mature leaves of Arabidopsis thaliana Col-0 (cv Columbia-0) at the onset of water deficit stress (OnWDS) and under mild water deficit stress (MiWDS) and moderate water deficit stress (MoWDS). Moreover, we tried to illuminate the underlying mechanisms in the differential response of PSII in young and mature leaves to water deficit stress in the model plant A. thaliana. Water deficit stress induced a hormetic dose response of PSII function in both leaf types. A U-shaped biphasic response curve of the effective quantum yield of PSII photochemistry (ΦPSII) in A. thaliana young and mature leaves was observed, with an inhibition at MiWDS that was followed by an increase in ΦPSII at MoWDS. Young leaves exhibited lower oxidative stress, evaluated by malondialdehyde (MDA), and higher levels of anthocyanin content compared to mature leaves under both MiWDS (+16%) and MoWDS (+20%). The higher ΦPSII of young leaves resulted in a decreased quantum yield of non-regulated energy loss in PSII (ΦNO), under both MiWDS (-13%) and MoWDS (-19%), compared to mature leaves. Since ΦNO represents singlet-excited oxygen (1O2) generation, this decrease resulted in lower excess excitation energy at PSII, in young leaves under both MiWDS (-10%) and MoWDS (-23%), compared to mature leaves. The hormetic response of PSII function in both young and mature leaves is suggested to be triggered, under MiWDS, by the intensified reactive oxygen species (ROS) generation, which is considered to be beneficial for activating stress defense responses. This stress defense response that was induced at MiWDS triggered an acclimation response in A. thaliana young leaves and provided tolerance to PSII when water deficit stress became more severe (MoWDS). We concluded that the hormesis responses of PSII in A. thaliana under water deficit stress are regulated by the leaf developmental stage that modulates anthocyanin accumulation in a stress-dependent dose.