Oxidative Stress Conditions Research Articles

Oxidative stress indices in apparently healthy blood donors in Ibadan

Background/Objective: Blood donors are life savers. They are also exposed to both exogenous and endogenous sources of free radical production. Therefore, this study aimed at investigating the oxidative stress status in apparently healthy blood donors in Ibadan. Method: This study was carried out in 100 urban and 67 rural male and female blood donors between the ages of 18 and 65 years after obtaining their consent. Ten (10) ml of venous blood was collected from each participant into heparinised bottles. The total plasma peroxides (TPP) and total antioxidant capacity (TAC) were determined using spectrophotometer and oxidative stress index (OSI) was calculated. All data were expressed as Mean ± SD. Results were analysed using one sample T-test to test the statistical significance between the variables. The level of significance was fixed at p ≤ 0.05. Result: In this study, the mean values of TPP and OSI were observed to be significantly higher in the urban blood donors (200±62.9µmol H2O2/L and 3.4±1.3%) compared with the rural blood donors (57.46±10.28µmol H2O2/L and 2.9±0.98%) (p < 0.001). Similarly, TAC (6388.7±1788.7 Vs 2133.99±708.1 p=0.000) was observed to be significantly higher in the urban blood donors compared with their rural counterparts. Conclusion: Significantly higher total plasma peroxides observed in urban blood donors is detrimental to the person receiving the blood. Therefore, intending blood donors should be educated on how to keep healthy feeding habits and life styles in order to improve their own health and the health of those they intend to save.

Para-Hydroxycinnamic Acid Mitigates Senescence and Inflammaging in Human Skin Models.

Para-hydroxycinnamic acid (pHCA) is one of the most abundant naturally occurring hydroxycinnamic acids, a class of chemistries known for their antioxidant properties. In this study, we evaluated the impact of pHCA on different parameters of skin aging in in vitro skin models after H2O2 and UV exposure. These parameters include keratinocyte senescence and differentiation, inflammation, and energy metabolism, as well as the underlying molecular mechanisms. Here we demonstrate that pHCA prevents oxidative stress-induced premature senescence of human primary keratinocytes in both 2D and 3D skin models, while improving clonogenicity in 2D. As aging is linked to inflammation, referred to as inflammaging, we analyzed the release of IL-6, IL-8, and PGE2, known to be associated with senescence. All of them were downregulated by pHCA in both normal and oxidative stress conditions. Mechanistically, DNA damage induced by oxidative stress is prevented by pHCA, while pHCA also exerts a positive effect on the mitochondrial and glycolytic functions under stress. Altogether, these results highlight the protective effects of pHCA against inflammaging, and importantly, help to elucidate its potential mechanisms of action.

Serum Metabolomics and NF-κB Pathway Analysis Revealed the Antipyretic Mechanism of Ellagic Acid on LPS-Induced Fever in Rabbits.

Fever is one of the most common clinical conditions and is characterized by pyrogenic infection, malignancy, inflammation, and tissue damage, among others. Ellagic acid (EA) can inhibit the expression of related proteins on the pathway by blocking the nuclear factor kappa-B(NF-κB) signaling pathway, inhibit the levels of pro-inflammatory factors interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), increase the level of anti-inflammatory factor IL-10, and effectively alleviate inflammatory symptoms. In addition, EA can also reduce the levels of malondialdehyde(MDA) and nitric oxide(NO) in the body, increase the activities of superoxide dismutase (SOD), glutathione (GSH), and catalase(CAT), scavenge oxidative free radicals, inhibit lipid oxidation, and achieve antipyretic and anti-inflammatory effects. The purpose of this study was to establish the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1β, prostaglandin E2(PGE2), and cyclic adenosine monophosphate(cAMP), and clarify the mechanism of the cyclooxidase-2(COX-2)/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism. Compared to lipopolysaccharide (LPS)- treated animals, subsequent administration of EA significantly lowered the LPS-induced rectal temperature increase (p < 0.05 or p < 0.01), significantly increased serum SOD and GSH levels (p < 0.05 or p < 0.01), and significantly decreased serum MDA, IL-1β, IL-6, and TNF-α levels (p < 0.05 or p < 0.01). In addition, compared to LPS-treated animals, subsequent administration of EA significantly decreased cerebrospinal fluid cAMP and PGE2 levels (p < 0.05 or p < 0.01), significantly decreased cAMP, significantly increased 5-HT levels (p < 0.05 or p < 0.01), and significantly down-regulated p-NF-κB p65 and COX-2 protein levels in the hypothalamus. Subsequent gas chromatography mass spectrometry(GC-MS) metabolite analysis indicated that 12 differential metabolites were detected in serum isolated 4 h after LPS treatment, and 10 differential metabolites were detected in serum collected 7 h after LPS treatment. Next, Pearson correlation analysis was used to systematically characterize the relationship between the identified metabolites and TNF-α, IL-6, MDA, SOD, PGE2, and cAMP. The levels of propionic acid, pyridine, and L-valine were up-regulated by EA, which inhibited the expression of MDA, IL-1β, and TNF-α and increased the activity of GSH. The levels of inositol, urea, and 2-monopalmitin were down-regulated by EA, which inhibited the expression of MDA, IL-1β, and TNF-α, increased the activity of SOD and GSH, reduced the inflammatory response, and alleviated the oxidative stress state. Combined with the results of the metabolic pathway analysis, we suggest that the pathways of the galactose metabolism, synthesis and degradation of ketone bodies, as well as ascorbic acid and aldehyde acid metabolism are closely related to the antipyretic and anti-inflammatory effects of EA. Our study established the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1β, PGE2, and cAMP, and clarified the mechanism of the COX-2/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism.

Chemical Composition, Antioxidant, and Cytotoxic Effects of Senna rugosa Leaf and Root Extracts on Human Leukemia Cell Lines.

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was carried out by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS•+ and DPPH• radical scavenging methods, protection against oxidative damage in proteins, and DNA. Cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extracts contained catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile showed obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with an IC50 of 4.86 ± 0.51 μg/mL and 8.33 ± 0.90 μg/mL in the ABTS assay for ELSR and ERSR, respectively. Furthermore, in the DPPH• assay, the IC50 was 19.98 ± 1.96 μg/mL for ELSR and 13.37 ± 1.05 μg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 μg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 h of treatment. After 48 h, results against the K562 cell line demonstrate an IC50 of 242.54 ± 2.38 μg/mL and 223.00 ± 2.34 μg/mL for ELSR and ERSR, respectively. While against the Jurkat cell line, these extracts showed an IC50 of 171.45 ± 2.25 μg/mL and 189.30 ± 2.27 μg/mL, respectively. The results pertaining to PBMC viability demonstrated that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions and expand their significant pharmacological potential in oxidative stress and leukemia conditions.

Unravelling the role of tumor microenvironment responsive nanobiomaterials in spatiotemporal controlled drug delivery for lung cancer therapy.

Design and development of efficient drug delivery technologies that impart site-specificity is the need of the hour for the effective treatment of lung cancer. The emergence of materials science and nanotechnology partially helped drug delivery scientists to achieve this objective. Various stimuli-responsive materials that undergo degradation at the pathological tumor microenvironment (TME) have been developed and explored for drug delivery applications using nanotechnological approaches. Nanoparticles (NPs), owing to their small size and high surface area to volume ratio, demonstrated enhanced cellular internalization, permeation, and retention at the tumor site. Such passive accumulation of stimuli-responsive materials helped to achieve spatiotemporally controlled and targeted drug delivery within the tumors. In this review, we discussed various stimuli-physical (interstitial pressure, temperature, and stiffness), chemical (pH, hypoxia, oxidative stress, and redox state), and biological (receptor expression, efflux transporters, immune cells, and their receptors or ligands)-that are characteristic to the TME. We mentioned an array of biomaterials-based nanoparticulate delivery systems that respond to these stimuli and control drug release at the TME. Further, we discussed nanoparticle-based combinatorial drug delivery strategies. Finally, we presented our perspectives on challenges related to scale-up, clinical translation, and regulatory approvals.

Graphene Quantum Dots Inhibit Lipid Peroxidation in Biological Membranes.

Excessive reactive oxygen species (ROS) in cellular environments leads to oxidative stress, which underlies numerous diseases, including inflammatory diseases, neurodegenerative diseases, cardiovascular diseases, and cancer. Oxidative stress can be particularly damaging to biological membranes such as those found in mitochondria, which are abundant with polyunsaturated fatty acids (PUFAs). Oxidation of these biological membranes results in concomitant disruption of membrane structure and function, which ultimately leads to cellular dysfunction. Graphene quantum dots (GQDs) have garnered significant interest as a therapeutic agent for numerous diseases that are linked to oxidative stress. Specifically, GQDs have demonstrated an ability to protect mitochondrial structure and function under oxidative stress conditions. However, the fundamental mechanisms by which GQDs interact with membranes in oxidative environments are poorly understood. Here, we used C11-BODIPY, a fluorescent lipid oxidation probe, to develop quantitative fluorescence assays that determine both the extent and rate of oxidation that occurs to PUFAs in biological membranes. Based on kinetics principles, we have developed a generalizable model that can be used to assess the potency of antioxidants that scavenge ROS in the presence of biological membranes. By augmenting our fluorescence assays with 1H NMR spectroscopy, the results demonstrate that GQDs scavenge nascent hydroxyl and peroxyl ROS that interact with membranes and that GQDs are potent inhibitors of ROS-induced lipid oxidation in PUFA-containing biological membranes. The antioxidant potency of GQDs is comparable to or even greater than established antioxidant molecules, such as ascorbic acid and Trolox. This work provides mechanistic insights into the mitoprotective properties of GQDs under oxidative stress conditions, as well as a quantitative framework for assessing antioxidant interactions in biological membrane systems.

The potential role of finerenone in patients with type 1 diabetes and chronic kidney disease.

Chronic kidney disease (CKD) represents a global health concern, associated with an increased risk of cardiovascular morbidity and mortality and decreased quality of life. Many patients with type 1 diabetes (T1D) will develop CKD over their lifetime. Uncontrolled glucose levels, which occur in patients with T1D as well as type 2 diabetes (T2D), are associated with substantial mortality and cardiovascular disease burden. T2D and T1D share common pathological features of CKD, which is thought to be driven by haemodynamic dysfunction, metabolic disturbances, and subsequently an influx of inflammatory and profibrotic mediators, both of which are major interrelated contributors to CKD progression. The mineralocorticoid receptor is also involved, and, under conditions of oxidative stress, salt loading and hyperglycaemia, it switches from homeostatic regulator to pathophysiological mediator by promoting oxidative stress, inflammation and fibrosis. Progressive glomerular and tubular injury leads to macroalbuminuria a progressive reduction in the glomerular filtration rate and eventually end-stage renal disease. Finerenone, a non-steroidal, selective mineralocorticoid receptor antagonist, is approved for treatment of patients with CKD associated with T2D; however, the benefit of finerenone in patients with T1D has yet to be determined. This narrative review will discuss treatment of CKD in T1D and the potential future role of finerenone in this setting.

Modulation of pulmonary oxidative status in methamphetamine-withdrawn rats, comparing the effects of continuous training and NBS superfood supplementation.

This study aimed to investigate the effects of six weeks of continuous training and Nutrition Bio-shield (NBS) Superfood Supplementation on the state of oxidative stress by the expression of Nrf2, NOX4, superoxide dismutase, and malondialdehyde genes in the lungs of rats after methamphetamine withdrawal. Forty male Wistar rats were randomly divided into five groups (n = 8, per group), undergoing methamphetamine administration (six weeks, 5 mg/kg ip, and once per day) followed by a 21-day withdrawal period. The rats were supplemented NBS superfood at a dosage of 25 g/kg per day for six weeks. The training protocol was 30 minutes of daily continuous training (treadmill running), five days a week for six weeks. The regimen escalated from a pace of 3 m/min for the initial 5 minutes, to 5 m/min for the following 5 minutes, culminating at 8 m/min for the remainder of the session, all at a 0° incline. A one-way analysis of variance was performed to analyze the gene expression of Nrf2, NOX4, MDA, and SOD in the lungs tissue of rats. The results indicated that, in the experimental groups which underwent continuous training and NBS Superfood supplementation, the expression of the Nrf2 gene exhibited a significant elevation compared to the control group (P < 0.05), while the NOX4, MDA, and SOD genes expression exhibited a significant decline in comparison to the control group (P < 0.05). In general, both exercise interventions and NBS superfood supplementation, when employed separately or in combination after methamphetamine withdrawal, can enhance the state of oxidative stress in the lung.

SerpinB3: A Multifaceted Player in Health and Disease-Review and Future Perspectives.

SerpinB3, a member of the serine-protease inhibitor family, has emerged as a crucial player in various physiological and pathological processes. Initially identified as an oncogenic factor in squamous cell carcinomas, SerpinB3's intricate involvement extends from fibrosis progression and cancer to cell protection in acute oxidative stress conditions. This review explores the multifaceted roles of SerpinB3, focusing on its implications in fibrosis, metabolic syndrome, carcinogenesis and immune system impairment. Furthermore, its involvement in tissue protection from oxidative stress and wound healing underscores its potential as diagnostic and therapeutic tool. Recent studies have described the therapeutic potential of targeting SerpinB3 through its upstream regulators, offering novel strategies for cancer treatment development. Overall, this review underscores the importance of further research to fully elucidate the mechanisms of action of SerpinB3 and to exploit its therapeutic potential across various medical conditions.

Near-infrared polarity fluorescent probe for wash-free imaging lipid droplets and the application in the diagnosis of non-alcoholic fatty liver tissue

Lipid droplets (LDs), as primary cellular energy storage organelles, play essential roles not only in energy conservation but also in inflammatory responses, apoptosis, and the progression of diseases such as non-alcoholic fatty liver disease (NAFLD). Studies indicate that alterations in the polarity of LDs are closely linked to pathological factors like oxidative stress, ferroptosis, and lipophagy. Therefore, developing biological probes for precisely monitoring LDs polarity is crucial for understanding these biological phenomena and devising new therapeutic strategies. In this context, we synthesized four fluorescent probes (CNL1-CNL4) to precisely monitor the polarity of LDs using triphenylamine and carbazole derivatives as electron donors and isophorone and benzopyranonitrile units as electron acceptors, employing intramolecular charge transfer (ICT) mechanism. Our findings demonstrated that all four probes exhibited high sensitivity and specificity for polarity changes. Probes CNL2 and CNL4 were sensitive to polarity, and their maximum fluorescence intensity and maximum emission wavelength demonstrated a good linear relationship with polarity parameters within a certain range. Biological experiments demonstrated that both CNL2 and CNL4 possess excellent wash-free imaging capabilities and superior LDs targeting abilities but also enable dynamic monitoring of LDs and respond well to changes in LDs polarity under varying concentrations of oleic acid stimulation. Due to its longer emission wavelength (>650 nm), boasting excellent photostability, and featuring a larger Stokes shift (≈168 nm in acetonitrile), probe CNL4 was selected for further studies. Furthermore, probe CNL4 effectively monitors changes in LDs polarity under conditions of ferroptosis and oxidative stress. It has shown potential in the diagnosis of NAFLD tissue and during the process of lipophagy, highlighting its value in disease diagnostics and biological research. These findings not only deepen our understanding of the mechanisms underlying NAFLD progression but also provide new tools for diagnosing and treating related diseases.

A novel hypovirulence-associated Hadaka virus 1 (HadV1-LA6) in Fusarium oxysporum f. sp. cubense.

Fusarium oxysporum f. sp. cubense (Foc) poses a significant threat to banana crops as a lethal fungal pathogen. The global spread of Foc underscores the formidable challenges associated with traditional management methods in combating this pathogen. This study delves into the hypovirulence-associated mycovirus in Foc. From Foc strain LA6, we isolated and characterized a novel member of the Hadakaviridae family, named Hadaka virus 1 strain LA6 (HadV1-LA6). HadV1-LA6 comprises 10 genomic RNA segments, with RNA1 to RNA7 sharing 80.9%-95.0% amino acid sequence identity with known HadV1-7n, while RNA8 to RNA10 display significantly lower identity. HadV1-LA6 demonstrates horizontal transmission capabilities in an all-or-none fashion between different Foc strains via coculturing. Phenotypic comparisons highlight that HadV1-LA6 significantly reduces the growth rates of its host fungus under cell wall stress and oxidative stress conditions. Importantly, HadV1-LA6 attenuates Foc's virulence in detached leaves and banana plants. This study represents the first introduction of a novel hypovirulence-associated Hadaka virus 1 in Foc.IMPORTANCEFusarium wilt of banana (FWB) is a severe fungal disease caused by soil-borne Fusarium oxysporum f. sp. cubense (Foc). Among various strategies, biocontrol emerges as a safe, ecologically friendly, and cost-effective approach to managing FWB. In this study, we focus on exploring the potential of a novel hypovirulent member of hadakavirid, HadV1-LA6. Previous reports suggest that HadV1 shows no apparent effect on the host. However, through phenotypic assessments, we demonstrate that HadV1-LA6 significantly impedes the growth rates of its host fungus under stress conditions. More importantly, HadV1-LA6 exhibits a remarkable capacity to attenuate Foc's virulence in detached leaves and banana plants. Furthermore, HadV1-LA6 could be horizontally transmitted between different Foc strains, presenting a promising resource for revealing the molecular mechanism of the interaction between Hadaka virus 1 and its host.

Impact of Intermittent Fasting and Dietary Restriction on Redox State, Energetic Metabolism, and Liver Injury in Common Bile Duct Ligation Model.

The aim of this work was to test whether we can treat cholestasis with dietary approaches applied after the onset of the disease. The effects of intermittent fasting and dietary restriction on liver damage caused by common bile duct ligation (BDL) in rats were studied, with particular attention paid to changes in the activity of enzymes of energy metabolism and antioxidant protection. Morphological changes in liver tissue and serum markers of liver damage were assessed in rats with BDL kept for one month on ad libitum diet, intermittent fasting, or 35% dietary restriction. We studied parameters of glucose metabolism (activity of glycolysis and gluconeogenesis enzymes), TCA cycle, and indicators of oxidative stress and redox status of the liver tissue. Dietary restriction resulted in an increase in gluconeogenesis activity, antioxidant capacity, and autophagy activation. When implemented after BDL, none of the dietary restriction protocols reduced the level of oxidative stress, detrimental morphological and biochemical alterations, or the fibrosis progression. Thus, under severe damage and oxidative stress developing in cholestasis, dietary restrictions are not hepatoprotective and can only be used in a pre-treatment mode.

Abscopal Effects, Clastogenic Effects and Bystander Effects: 70 Years of Non-Targeted Effects of Radiation.

In vitro and invivo observations accumulated over several decades have firmly shown that the biological effects of ionizing radiation can spread from irradiated cells/tissues to non-targeted cells/tissues. Redox-modulated intercellular communication mechanisms that include a role for secreted factors and gap junctions, can mediate these non-targeted effects. Clearly, the expression of such effects and their transmission to progeny cells has implications for issues related to radiation protection. Their elucidation is also relevant towards enhancing the efficacy of cancer radiotherapy and reducing its impact on the development of normal tissue toxicities. In addition, the study of non-targeted effects is pertinent to our basic understanding of intercellular communications under conditions of oxidative stress. This review will trace the history of non-targeted effects of radiation starting with early reports of abscopal effects which described radiation induced effects in tissues distant from the site of radiation exposure. A related effect involved the production of clastogenic factors in plasma following irradiation which can induce chromosome damage in unirradiated cells. Despite these early reports suggesting non-targeted effects of radiation, the classical paradigm that a direct deposition of energy in the nucleus was required still dominated. This paradigm was challenged by papers describing radiation induced bystander effects. This review will cover mechanisms of radiation-induced bystander effects and the potential impacts on radiation protection and radiation therapy.

Reproduction, growth and oxidative stress in earthworm Eisenia andrei exposed to conventional and biodegradable mulching film microplastics

Plastic contamination in agricultural soils has become increasingly evident. Plastic mulching films are widely used in agricultural practices. However, the increased use of biodegradable plastics has, to some extent, replaced their non-degradable counterparts. The fragmentation of plastics generates microplastics (MPs), posing risk to soil functions and organisms. In this study the effects of low-density polyethylene microplastics (PE-MP) and polybutylene adipate terephthalate biodegradable microplastics (PBAT-BD-MP) originating from mulching films on the earthworm Eisenia andrei were studied. The earthworms were exposed to seven concentrations (0, 0.005, 0.05, 0.1, 0.5, 1, and 5 % w/w) based on environmentally relevant levels and worst-case scenarios on soil contamination. Survival, growth, reproduction, and biomarkers for oxidative stress [superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione S-transferase (GST), glutathione (GSH), and lipid peroxidation (LPO)] were analysed. Additionally, the Integrated Biomarker Response Index (IBR) was calculated to assess the overall oxidative stress status of the earthworms. Results showed that PE-MP exposure slightly decreased the biomass of the earthworms towards higher concentrations, whereas PBAT-BD-MPs induced growth at lower concentrations. MPs did not have a significant effect on Eisenia andrei reproduction; however, a slight negative trend was observed in juvenile production with increasing PE-MP concentrations. Both PE-MP and PBAT-BD-MP affected antioxidant system, PE-MPs with changes in CAT and GR levels and PBAT-BD-MPs inducing effects on SOD and LPO levels. Additionally, both MPs exhibited effects on soil parameters, resulting in increased soil pH and water-holding capacity at 5 % concentration. Changes in soil parameters can further affect soil organisms such as earthworms. This study provides understanding of the ecotoxicological effects of conventional and biodegradable microplastics on the earthworm Eisenia andrei. It also shows that MP particles of both conventional and biodegradable mulching films induce oxidative stress, considered as an early-warning indicator for adverse ecological effects, in environmentally relevant concentrations.

Quantification of oxidative stress markers in the blood sera following subacute administration of different oximes in rats

Oxidative stress status, as a disruption of redox homeostasis, in the blood sera of Wistar rats caused by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Throughout this study, each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Then, seven days after the last oximes' application, markers of lipid peroxidation (malondialdehyde, MDA), and protein oxidation (advanced oxidation protein products, AOPP), as well as the activity of antioxidant enzymes (catalase, CAT, superoxide dismutase, SOD, reduced glutathione, GSH, and oxidized glutathione, GSSG), were determined. Oxidative stress parameters, MDA and AOPP were significantly highest in the K048-, K074- and K075-treated groups (p < 0.001). The activity of CAT was significantly elevated in the obidoxime-treated group (p < 0.05), while treatment with K027, K048, and K074 induced high elevation in SOD levels (p < 0.01, p < 0.001). Interestingly, the activity of GSH in each oxime-treated group was significantly elevated. Unlike, treatment with obidoxime caused elevation in GSSG levels (p < 0.01). As a continuation of our previously published data, these results assure that applied oximes following subacute treatment ameliorated the oxidative status and further adverse systemic toxic effects in rats.

Anxiolytic, Antidepression, and Memory-Enhancing Effects of the Novel Instant Soup RJ6601 in the Middle-Aged of Female Rats.

Due to the health benefits of polyphenols and dietary fiber in combating mental disorders, we hypothesized that a polyphenol- and dietary fiber-enriched soup (RJ6601) would improve mental wellness in a rat model of middle-aged women. To test this hypothesis, female Wistar rats aged 18 months (350-450 g) were orally administered RJ6601 at doses of 200 and 400 mg/kg BW for 28 days. The anxiolytic, antidepression, and memory-enhancing effects were assessed every 7 days throughout the study period. The neuron density and levels of activities of AChE, total MAO, MAO-A, MAO-B, MDA, SOD, CAT, GSH-Px, IL-1β, IL-6, and BDNF in the prefrontal cortex at the end of study were also investigated. Furthermore, the amounts of Lactobacillus spp. and Bifidobacterium spp. in their feces were also determined. The results revealed that the developed soup shows anxiolytic, antidepression, and memory-enhancing effects. An increased neuron density; reductions in AChE, total MAO, MAO-A, MAO-B, and MDA; and an elevation of serum BDNF, together with increased amounts of both bacterial species in feces, were also observed. Our results suggest that RJ6601 is a potential mental wellness promotion supplement that enhances BDNF levels, brain plasticity, neurotransmitter balance, and oxidative stress and inflammation status, along with improving microbiota.

Molecular and biochemical evaluation of oxidative effects of cord blood CD34+ MPs on hematopoietic cells

A graft source for allogeneic hematopoietic stem cell transplantation is umbilical cord blood, which contains umbilical cord blood mononuclear cells (MNCs and mesenchymal stem cells, both an excellent source of extracellular microparticles (MPs). MPs act as cell communication mediators, which are implicated in reactive oxygen species formation or detoxification depending on their origin. Oxidative stress plays a crucial role in both the development of cancer and its treatment by triggering apoptotic mechanisms, in which CD34+ cells are implicated. The aim of this work is to investigate the oxidative stress status and the apoptosis of HL-60 and mononuclear cells isolated from umbilical cord blood (UCB) following a 24- and 48-hour exposure to CD34 + microparticles (CD34 + MPs). The activity of superoxide dismutase, glutathione reductase, and glutathione S-transferase, as well as lipid peroxidation in the cells, were employed as oxidative stress markers. A 24- and 48-hour exposure of leukemic and mononuclear cells to CD34 + -MPs resulted in a statistically significant increase in the antioxidant activity and lipid peroxidation in both cells types. Moreover, CD34 + MPs affect the expression of BCL2 and FAS and related proteins and downregulate the hematopoietic differentiation program in both HL-60 and mononuclear cells. Our results indicate that MPs through activation of antioxidant enzymes in both homozygous and nonhomozygous cells might serve as a means for graft optimization and enhancement.

Does the frequency of hunting dogs’ activity influence their oxidative stress status subsequent to endurance?

Oxidative stress is implied in various pathological conditions in both humans and animals, and recent studies have suggested its role in performance, recovery, immunity, and health. This study’s objective was to investigate whether the higher frequency of activity by hunting dogs influences the oxidative stress indicators subsequent to endurance. The research involved forty-one hunting dogs, with equal representations of Alpine Brack Dachshund, Istrian Coarse-Haired Hound, and Posavina Hound. The dogs were categorized into higher frequency activity (n=22) and lower frequency activity (n=19) groups. Endurance was defined as a wild-boar hunt lasting for eight hours at an outside air temperature amounting to 10°C. Endurance had an impact on several parameters: an increased white blood cell count, neutrophils, and mean corpuscular hemoglobin concentration values, but decreased values of eosinophils and lymphocytes. Non-enzymatic biochemical indicators revealed higher energy expenditure (decreased glucose, total protein, and albumin concentration), hemoconcentration (decreased iron concentration), and elevated enzyme activity (AST, ALT, ALP, and CK-MB) but lower catalase activity. In terms of activity frequency, enzyme biomarker activity showed significant differences. ALT activity in both low- and high-frequency activity canines was notably higher (P&lt;0.05) post-endurance compared to pre-endurance levels. ALP activity was significantly higher (P&lt;0.05) post intense physical activity in higher frequency activity canines, yet lower (P&lt;0.05) in lower activity frequency canines compared to their pre-endurance status. In conclusion, both tested canine groups demonstrated notable signs of oxidative stress subsequent to endurance, without differences between activity frequencies.

Oxidative stress mediates nucleocytoplasmic shuttling of KPNA2 via AKT1-CDK1 axis-regulated S62 phosphorylation.

Karyopherin α 2 (KPNA2, importin α1), a transport factor shuttling between the nuclear and cytoplasmic compartments, is involved in the nuclear import of proteins and participates in cellular processes such as cell cycle regulation, apoptosis, and transcriptional regulation. However, it is still unclear which signaling regulates the nucleocytoplasmic distribution of KPNA2 in response to cellular stress. In this study, we report that oxidative stress increases nuclear retention of KPNA2 through alpha serine/threonine-protein kinase (AKT1)-mediated reduction of serine 62 (S62) phosphorylation. We first found that AKT1 activation was required for H2O2-induced nuclear accumulation of KPNA2. Immunoprecipitation and quantitative proteomic analysis revealed that the phosphorylation of KPNA2 at S62 was decreased under H2O2-induced oxidative stress. We showed that cyclin-dependent kinase 1 (CDK1), a kinase responsible for KPNA2 S62 phosphorylation, contributes to the localization of KPNA2 in the cytoplasm. AKT1 knockdown increased KPNA2 S62 phosphorylation and inhibited CDK1 activation. Furthermore, H2O2-induced AKT1 activation promoted nuclear KPNA2 interaction with nucleophosmin 1 (NPM1), resulting in attenuation of NPM1-mediated cyclin D1 gene transcription. Thus, we infer that the AKT1-CDK1 axis regulates the nucleocytoplasmic shuttling and function of KPNA2 through spatiotemporal regulation of KPNA2 S62 phosphorylation under oxidative stress conditions.

GC-MS/MS Analysis and Wound Repair Potential of Urtica dioica Essential Oil: In silico Modeling and In vivo Study in Rats.

The study aimed to assess the antioxidant and wound healing properties of Urtica dioica essential oil (UDEO) through a comprehensive evaluation involving in silico, in vitro, and in vivo analyses. The phytochemistry of UDEO was also investigated to identify trace compounds crucial. Various injection methods of the multimode inlet (MMI) in chromatography were investigated to attain lower instrumental detection limits. Subsequently, in silico studies were employed to delve deeper into the potential biological activities of the identified compounds. Standard antioxidative tests, encompassing ABTS•+ and TAC, were performed. In vivo tests centered on wound healing were implemented using rat models. The rats were randomly allocated to four groups: saline solution, vaseline vehicle, cytol centella, and 5% UDEO ointment. Wound healing progress was evaluated through a chromatic study. Gas chromatography combined with triple quadrupole mass spectrometry (GC-MS/MS) analysis revealed the presence of 97 thermolabile compounds in UDEO. Subsequent in silico studies unveiled the potential of identified compounds to inhibit COX-2, TNF-α, and IL-6, suggesting a possible enhancement of anti-inflammatory responses and healing processes. In vitro tests elucidated the notable antioxidant capacity of UDEO, a finding reinforced by wound healing data, revealing a substantial closure rate of 89% following the topical application of UDEO. Notably, fibrinogen and C-reactive protein (CRP) levels were significantly reduced, indicating minimized oxidative stress damage compared to control. Additionally, UDEO exhibited an increase in antioxidant enzyme activities compared to control. The study concludes that UDEO possesses significant antioxidant and wound-healing properties, supported by its rich phytochemical composition. The findings suggest its potential application in therapeutic interventions for oxidative stress and inflammatory conditions.