Phytochemical Profiling and Bioactive Properties of Essential Oils from Endemic Palestinian Satureja thymbrifolia.

Despite several studies on the Satureja L. genus, the chemical composition and biological activities of the traditional medicinal plant Satureja thymbrifolia (White Thyme), a Palestinian endemic species, are still unknown. It grows in arid regions and is used by Bedouins as a traditional medicinal herb. This study aimed to investigate S. thymbrifolia essential oils (EOs), mainly from its phytochemical pattern and biological properties. The GC-MS study identified p-cymene (48.53%) and thymol (23.27%) as the leading EOs components. Compared to Trolox, the EOs showed potential anti-DPPH free radical activity and had broad-spectrum antimicrobial potentials, with MIC values ranging from 0.13 ± 0.05 to 25 ± 0.00 µL/mL. They were most effective against Candida albicans species. The S. thymbrifolia EOs most effectively eliminated cancer cells when tested against CaCo-2 and HeLa cell lines (IC50 values of 192.15 ± 2.47 and 194.80 ± 1.87 µg/mL, respectively). The present investigation is the first documented study of S. thymbrifolia EOs' phytochemical composition and bioactivities. The results revealed that S. thymbrifolia EOs have potential antioxidant, antimicrobial, and cytotoxic effects. These outcomes emphasized S. thymbrifolia EO's potential dietary, pharmacological, and cosmetic applications.

Focused starvation of tumor cells using glucose oxidase: A comprehensive review.

Starvation therapy targets the high metabolic demand of tumor cells. It primarily leans over the consumption of intracellular glucose and simultaneous blockade of alternative metabolic pathways. The strategy involves the use of glucose oxidase (GOx) for catalyzing the conversion of glucose into gluconic acid and hydrogen peroxide. Under these conditions, metabolic re-programming of tumor cells enables the utilization of substrates such as amino acids, fatty acids and lipids. This can be overcome by co-administration of chemo-, photo- and immuno-therapeutics together with glucose oxidase. Targeted delivery of glucose oxidase at tumor site can be enabled with the use of nanoformulations. In this review, we highlight that the outcomes of starvation therapy can be improved using rationally developed nano-formulations. It is possible to load synergistically acting bioactives in these formulations and deliver in site-specific manner and hence achieve the elimination of tumors cells with greater efficacy.

Reno-protective potential of sudachitin to mitigate paraquat instigated renal toxicity via regulating Nrf2/Keap1 pathway: An inflammatory, apoptotic and histopathological assessment.

This investigation was executed to assess the protective effects of SCN to counteract PQ instigated renal damage in albino rats (Rattus norvegicus). Twenty-four rats were apportioned in 4 different groups i.e., a control group, PQ (5mg/kg) intoxicated, PQ (5mg/kg) + SCN (20mg/kg) exposed & SCN (20mg/kg) only administrated group. Our findings explored that exposure to PQ lessened the expressions of Nrf2 and its cytoprotective genes while escalating the expression of keap1. Furthermore, PQ intoxication reduced the enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR), & glutathione (GSH), while upregulating the levels of malondialdehyde (MDA) & reactive oxygen species (ROS). Moreover, intoxication to PQ significantly increased the levels of neutrophil gelatinous-associated lipocalin (NGAL), urea, kidney injury molecule-1(KIM-1) as well as creatine while reducing creatine clearance. Additionally, exposure to PQ upregulated the levels of inflammatory markers including interleukin-6 (IL-6), tumor necrosis- α (TNF- α), nuclear factor- κB (NF-κB), interleukin 1beta (IL-1ß), & cyclo-oxygenase-2 (COX-2). Moreover, PQ administration upregulated the expression of Bax and Caspase-3 while downregulating the expressions of Bcl-2. Besides, PQ exposure prompted various histopathological damages in renal tissues. Nonetheless, SCN substantially restored aforementioned alterations in renal tissues owing to its anti-oxidative, anti-inflammatory and anti-apoptotic potential.

BMP receptor 2 inhibition regulates mitochondrial bioenergetics to induce synergistic cell death with BCL-2 inhibitors in leukemia and NSLC cells.

Background: Bone morphogenetic protein (BMP) signaling cascade is a phylogenetically conserved stem cell regulator that is aberrantly expressed in non-small cell lung cancer (NSLC) and leukemias. BMP signaling negatively regulates mitochondrial bioenergetics in lung cancer cells. The impact of inhibiting BMP signaling on mitochondrial bioenergetics and the effect this has on the survival of NSLC and leukemia cells are not known. Methods: Utilizing the BMP type 2 receptor (BMPR2) JL189, BMPR2 knockout (KO) in cancer cells, and BMP loss of function mutants in C elegans, we determined the effects of BMPR2 inhibition (BMPR2i) on TCA cycle metabolic intermediates, mitochondrial respiration, and the regulation of mitochondrial superoxide anion (SOA) and Ca++ levels. We also examined whether BMPR2i altered the threshold cancer therapeutics induce cell death in NSLC and leukemia cell lines. KO of the mitochondria uniporter (MCU) was used to determine the mechanism BMPR2i regulates the uptake of Ca++ into the mitochondria, mitochondrial bioenergetics, and cell death. Results: BMPR2i increases mtCa++ levels and enhances mitochondrial bioenergetics in both NSLC and leukemia cell lines that is conserved in C elegans. BMPR2i induced increase in mtCa++ levels is regulated through the MCU, effecting mitochondria mass and cell survival. BMPR2i synergistically induced cell death when combined with BCL-2 inhibitors or microtubule targeting agents in both NSLC and leukemia cells. Cell death is caused by synergistic increase in mitochondrial ROS and Ca++ levels. BMPR2i enhances Ca++ uptake into the mitochondria induced by reactive oxygen species (ROS) produced by cancer therapeutics. Both acute myeloid leukemia (AML) and T-cell lymphoblastic leukemia cells lines were more responsive to the JL189 alone and when combined with venetoclax or navitoclax compared to NSLC.

Investigating In Silico and In Vitro Therapeutic Potential of Diosmetin as the Anti-Parkinson Agent.

AIM: This study aimed to investigate how diosmetin interacts with seven target receptors associated with oxidative stress (OS) and validate its antioxidant properties for the potential management of Parkinson's disease (PD). BACKGROUND: In PD, the degeneration of dopaminergic cells is strongly influenced by OS. This stressor is intricately connected to various mechanisms involved in neurodegeneration, such as mitochondrial dysfunction, neuroinflammation, and excitotoxicity induced by nitric oxide. OBJECTIVE: The aim of this research was to establish a molecular connection between diosmetin and OS-associated target receptors was the goal, and it investigated how this interaction can lessen PD. MATERIAL AND METHODS: Seven molecular targets - Adenosine A2A (AA2A), Peroxisome Proliferator- Activated Receptor Gamma (PPARγ), Protein Kinase AKT1, Nucleolar Receptor NURR1, Liver - X Receptor Beta (LXRß), Monoamine Oxidase - B (MAO-B) and Tropomyosin receptor kinase B (TrkB) were obtained from RCSB. Molecular docking software was employed to determine molecular interactions, while antioxidant activity was assessed through in-vitro assays against various free radicals. RESULTS: Diosmetin exhibited interactions with all seven target receptors at their binding sites. Notably, it showed superior interaction with AA2A and NURR1 compared to native ligands, with binding energies of -7.55, and -6.34 kcal/mol, respectively. Additionally, significant interactions were observed with PPARγ, AKT1, LXRß, MAO-B, and TrkB with binding energies of -8.34, -5.42, -7.66, -8.82, -8.45 kcal/mol, respectively. Diosmetin also demonstrated antioxidant activity against various free radicals, particularly against hypochlorous acid (HOCl) and nitric oxide (NO) free radicals. CONCLUSION: Diosmetin possibly acts on several target receptors linked to the pathophysiology of PD, demonstrating promise as an OS inhibitor and scavenger.

Phototransformation of tetrabromobisphenol A bis (allyl ether) in an aqueous solution: Role of environmentally persistent free radicals.

Tetrabromobisphenol A bis (allyl ether) (TBBPA-BAE) represents an extensively used brominated flame retardant (BFRs) in the production of many fields and their phototransformation in natural water is still unclear. The environmentally persistent free radicals (EPFRs) with preserved activities could exist in the environment for a long time and involve in the phototransformation of many organic pollutants. Here, the photodegradation of TBBPA-BAE with the degradation rate constant (k = 0.060 h-1) under simulate sunlight and the promoting effect of EPFRs on TBBPA-BAE photodegradation (k = 0.135 h-1) were investigated. According to the detected photogenerated electrons (e-) and singlet oxygen (1O2) rather than hydroxyl radicals (•OH) by the electron paramagnetic resonance (EPR), the effect mechanism may not be related to the typical •OH induced by EPFRs. The possible transformation pathways of the ether cleavage, hydrolysis and hydroxylation of propenyl bond and the debromination were proposed by the primary byproducts identified by UPLC-Q-Exactive Orbitrap MS. EPFRs caused a further debromination and ether cleavage and probably be due to EPFRs directly providing electrons to TBBPA-BAE which promoted the photodegradation of TBBPA-BAE, and their reaction mechanism needed further attention. Overall, this study provided useful information to understand the role of EPFRs on phototransformation of TBBPA-BAE in water.

Effect of UV Radiation and Temperature on Radical Scavenging Activity of Hippophaë rhamnoides L. and Vaccinium oxycoccos L. Fruit Extracts.

New active ingredients, including those of plant origin, which could protect the skin against various harmful factors, such as UV radiation and free radicals responsible for skin ageing, are still being sought. The present study was focused on the antioxidant activity of Hippophaë rhamnoides L. and Vaccinium oxycoccos L. fruit glycolic extracts. Investigations were also carried out to evaluate the effect of UVA radiation and the storage of the sea buckthorn and European cranberry extracts at an elevated temperature of 50 °C on their interactions with free radicals. The kinetics of the interactions of the extracts with DPPH were assessed using electron paramagnetic resonance (EPR) spectroscopy. The sea buckthorn and European cranberry extracts quench the EPR signal of DPPH free radicals, which indicates their antioxidant potential. The EPR method further showed that a mixture of sea buckthorn and cranberry extracts in a volume ratio of 2:1 was more potent in quenching free radicals compared to a mixture of these extracts in a ratio of 1:2. Our findings demonstrate that long-term UVA radiation exposure reduces the ability of sea buckthorn and cranberry extracts to interact with free radicals. Moreover, storage at elevated temperatures does not affect the interaction of sea buckthorn extract with free radicals, while it alters the ability of cranberry extract to interact with free radicals. This study has demonstrated that an important factor in maintaining the ability to scavenge radicals is the storage of raw materials under appropriate conditions. H. rhamnoides and V. oxycoccos extracts can be used as valuable raw materials with antioxidant properties in the pharmaceutical and cosmetic industries.

Selective synergistic effects of oxalic acid and salicylic acid in enhancing amino acid levels and alleviating lead stress in Zea mays L.

Lead is one of the major environmental pollutants which is highly toxic to plants and living beings. The current investigation thoroughly evaluated the synergistic effects of oxalic acid (OA) and salicylic acid (SA) on Zea mays L. plants subjected to varying durations (15, 30, 30, and 45 days) of lead (Pb) stress. Besides, the effects of oxalic acid (OA) combined with salicylic acid (SA) for different amino acids at various periods of Pb stress were also investigated on Zea mays L. The soil was treated with lead nitrate Pb (NO3)2 (0.5 mM) to induce Pb stress while the stressed plants were further treated using oxalic acid (25 mg/L), salicylic acid (25 mg/L), and their combination OA + SA (25 mg/L each). Measurements of protein content, malondialdehyde (MDA) levels, guaiacol peroxidase (GPOX) activity, catalase (CAT) activity, GSH content, and Pb concentration in maize leaves were done during this study. MDA levels increased by 71% under Pb stress, while protein content decreased by 56%, GSH content by 35%, and CAT activity by 46%. After treatment with SA, OA, and OA+SA, there was a significant reversal of these damages, with the OA+SA combination showing the highest improvement. Specifically, OA+SA treatment led to a 45% increase in protein content and a 39% reduction in MDA levels compared to Pb treatment alone. Moreover, amino acid concentrations increased by 68% under the Pb+OA+SA treatment, reflecting the most significant recovery (p < 0.0001).

Phytochemical composition, simulated digestive bioaccessibility and cytotoxicity of Ficus auriculata Lour. fruits: In vitro and in silico insights.

Ficus auriculata Lour. (Moraceae) is an underutilized wild edible fruit widely consumed for its nutritional properties. The present study aimed to determine the phytochemical composition and in vitro antioxidant, enzyme inhibitory, anti-inflammatory and anti-cancerous properties of the F. auriculata fruit extracts through in vitro digestion (oral, gastric and intestinal phases). The extracts were obtained by hot extraction and cold maceration methods using aqueous and methanolic solvents. Major phytoconstituents identified through LC-MS was subjected to molecular docking against the target proteins. The elemental analysis shows the presence of major elements; high levels of total phenolics (124.61 ± 0.82 mg gallic acid equivalent/g), flavonoids (76.38 ± 0.82 mg quercetin equivalent/g), vitamin E (32.48 ± 0.09 mg alpha-tocopherol equivalent/g), and carbohydrate (34.59 ± 0.45 mg glucose equivalent/g) in hot extracted methanolic undigested extract (HEM UD) and high level of total protein (124.71 ± 0.34 mg bovine serum albumin equivalent/g) in cold extracted methanolic undigested fruit extract were found. HEM UD showed high antioxidant activity in 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), 2,2-diphenyl-1-picryl-hydrazyl, and superoxide radical scavenging assays with IC50 of 53.30 ± 0.57, 80.69 ± 0.12, and 65.47 ± 1.13 µg/mL, respectively. The HEM UD extract also potentially inhibited the enzyme activity of α-amylase, α-glucosidase, tyrosinase, and protein denaturation (IC50 of 67.76 ± 1.22, 83.18 ± 1.23, 87.24 ± 1.15, and 65.76 ± 0.60 µg/mL). The most potent extract (HEM UD) was studied for its anticancer effects by MTT assay against the MCF-7 and HeLa cell lines and showed the IC50 of 89.80 ± 0.56 and 60.76 ± 0.04 µg/mL, respectively. The LC-MS analysis elucidated ten phytoconstituents. Based on the molecular docking study, querciturone could potentially be an effective constituent in treating diabetes and inflammation-related issues. The findings indicated the ability of F. auriculata fruits as a promising functional food.

Efficacy of propolis and royal jelly in attenuating cadmium-induced spermatogenesis and steroidogenesis dysregulation, causing infertility in rats.

Bee-derived pharmaceutical products, including propolis (PRO) and royal jelly (ROJ), possess outstanding pharmacological properties. However, their efficiency in counteracting the deleterious influences of cadmium (Cd) in testes and the relevant mechanisms entail further investigations. Therefore, this study sheds light on the therapeutic efficacy of PRO and ROJ against testicular dysfunction and infertility induced by Cd. Toward this end, 30 mature male Wistar albino rats were randomly divided into six groups (5 animals/group), including (I) control, (II) Cd, (III) PRO, (IV) ROJ, (V) PRO + Cd, and (VI) ROJ + Cd groups. Furthermore, antioxidant factors, semen quality, hormonal levels, steroidogenic enzymes, and genotoxicity were assessed. Moreover, histopathological and ultrastructural attributes and offspring rates were investigated. The Cd-treated group revealed marked reductions in reduced glutathione (GSH), total antioxidant capacity (TAC), and superoxide dismutase (SOD) with an amplification of lipid peroxidation in testes, indicating disruption of the antioxidant defense system. Furthermore, myeloperoxidase (MPO) activity and DNA damage were significantly heightened, implying inflammation and genotoxicity, respectively. Moreover, steroidogenic enzymes, including 17ß-Hydroxy Steroid Dehydrogenase 3 (HSD17b3), 3ß-Hydroxy Steroid Dehydrogenase 2 (HSD3b2), 17α-hydroxylase/17,20-lyase (CYP17A1), and steroid 5α-reductase 2 (SRD5A2) were markedly diminished accompanied with disorders in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Besides, spermatozoa quality was reduced, associated with a diminution in the diameter of seminiferous tubules. By contrast, PRO or ROJ significantly protected and/or counteracted the Cd-induced pathophysiological consequences, ameliorating antioxidant and inflammatory biomarkers, steroidogenic enzymes, hormonal levels, and sperm properties, along with lessening DNA impairments. Critically, histological and ultrastructural analyses manifested several anomalies in the testicular tissues of the Cd-administered group, including the Leydig and Sertoli cells and spermatozoa. Conversely, PRO or ROJ sustained testicular tissues' structure, enhancing spermatozoa integrity and productivity. Interestingly, treatment with PRO or ROJ improved fertility indices through offspring rates compared to the Cd-animal group. Our data suggest that PRO is a more effective countermeasure than ROJ against Cd toxicity for securing the delicate testicular microenvironment for spermatogenesis and steroidogenesis.

Tobacco cigarette smoking induces cerebrovascular dysfunction followed by oxidative neuronal injury with the onset of cognitive impairment.

While chronic smoking triggers cardiovascular disease, controversy remains regarding its effects on the brain and cognition. We investigated the effects of long-term cigarette smoke (CS) exposure (CSE) on cerebrovascular function, neuronal injury, and cognition in a novel mouse exposure model. Longitudinal studies were performed in CS or air-exposed mice, 2 hours/day, for up to 60 weeks. Hypertension and carotid vascular endothelial dysfunction (VED) occurred by 16 weeks of CSE, followed by reduced carotid artery blood flow, with oxidative stress detected in the carotid artery, and subsequently in the brain of CS-exposed mice with generation of reactive oxygen species (ROS) and secondary protein and DNA oxidation, microglial activation and astrocytosis. Brain small vessels exhibited decreased levels of endothelial NO synthase (eNOS), enlarged perivascular spaces with blood brain barrier (BBB) leak and decreased levels of tight-junction proteins. In the brain, amyloid-ß deposition and phosphorylated-tau were detected with increases out to 60 weeks, at which time mice exhibited impaired spatial learning and memory. Thus, long-term CSE initiates a cascade of ROS generation and oxidative damage, eNOS dysfunction with cerebral hypoperfusion, as well as cerebrovascular and BBB damage with intracerebral inflammation, and neuronal degeneration, followed by the onset of impaired cognition and memory.

Optimization and characterization of brown seaweed alginate for antioxidant, anticancer, antimicrobial, and antiviral properties.

Alginate is a natural polysaccharide obtained from brown seaweeds and having advantageous health usefulness, was employed extensively in nutraceutical sectors and the pharmaceutical industry. This research was devoted for optimization of alginate extraction from different brown seaweeds. A Box-Behnken Design (BBD) was used for the optimization of alginate extraction from Padina pavonica by analyzing the influence of temperature (30, 40, and 50 °C), time (60, 120, and 180 min), and alkaline concentration (1 %, 2 %, and 3 %) on extraction yield and uronic acid content. The optimal conditions recorded to maximize the alginate yield and its uronic content were an alkali concentration of 2.5 % and a temperature of 39.95 °C for 102.5 min. The optimized parameters achieved from BBD were used to compare alginate extraction from P. pavonica, Sargassum cinereum, Turbinaria turbinata, and Dictyota dichotoma. FTIR, 1H NMR, and HPLC were used to characterize the extracted alginate. The bioactivity of alginate against free radicals, breast cancer cells (MCF-7), some pathogenic microbes, and SARS-CoV-2 viruses was tested. Under the optimized conditions, alginate was extracted from P. pavonica at a rate of 21.13 ± 2.47 % DW, S. cinereum at 24.08 ± 0.33 % DW g/L, T. turbinata at 17.47 ± 0.26 % DW, and D. dichotoma at a rate of 19.57 ± 3.60 % DW. The alginate extracted from D. dichotoma showed the highest antioxidant, anticancer, and antiviral activity.

Acute inhibitory effects of tire wear particles on the removal of biological phosphorus：The critical role of aging in improving environmentally persistent free radicals.

A comparative study explored how photoaging, ozonation aging, and Fenton aging affect tire wear particles (TWPs) and their phosphorus (P) removal in activated sludge. Aging altered TWPs' properties, increasing surface roughness, porosity, and generating more small particles, especially environmental persistent free radicals (EPFRs) in ozonation and Fenton aging. Post-aging TWPs (50 mg/L) inhibited sludge P removal significantly (p < 0.05), with rates of 44.3% and 59.6% for ozonation and Fenton aging, respectively. In addition, the metabolites involved in P cycling (poly-ß-hydroxyalkanoates: PHA and glycogen) and essential enzymes (Exopolyphosphatase: PPX and Polyphosphate kinase: PPK) were significantly inhibited (p < 0.05). Moreover, TWPs led to a decrease in microbial cells within the sludge and altered the community structure, a situation exacerbated by the aging of TWPs. P-removing bacteria decreased (e.g., Burkholderia, Candidatus), while extracellular polymeric substance-secreting bacteria increased (e.g., Pseudomonas, Novosphingobium). Pearson correlation analysis highlighted EPFRs' role in TWPs' acute toxicity to microbial cells, yet, emphasizing particle size's impact on the sludge system's purification and community structure.

Nicotine inhalation and metabolism triggers AOX-mediated superoxide generation with oxidative lung injury.

With the increasing use of vaping devices that deliver high levels of nicotine (NIC) to the lungs, sporadic lung injury has been observed. Commercial vaping solutions can contain high NIC concentrations of 150 mM or more. With high NIC levels, its metabolic products may induce toxicity. NIC is primarily metabolized to form NIC iminium (NICI) which is further metabolized by aldehyde oxidase (AOX) to cotinine. We determine that NICI in the presence of AOX is a potent trigger of superoxide generation. NICI stimulated superoxide generation from AOX with Km = 2.7 µM and Vmax = 794 nmol/min/mg measured by cytochrome-c reduction. EPR spin-trapping confirmed that NICI in the presence of AOX is a potent source of superoxide. AOX is expressed in the lungs and chronic e-cigarette exposure in mice greatly increased AOX expression. NICI or NIC stimulated superoxide production in the lungs of control mice with an even greater increase after chronic e-cigarette exposure. This superoxide production was quenched by AOX inhibition. Furthermore, e-cigarette-mediated NIC delivery triggered oxidative lung damage that was blocked by AOX inhibition. Thus, NIC metabolism triggers AOX-mediated superoxide generation that can cause lung injury. Therefore, high uncontrolled levels of NIC inhalation, as occur with e-cigarette use, can induce oxidative lung damage.

Residential Wood Burning and Vehicle Emissions as Major Sources of Environmentally Persistent Free Radicals in Fairbanks, Alaska.

Environmentally persistent free radicals (EPFRs) play an important role in aerosol effects on air quality and public health, but their atmospheric abundance and sources are poorly understood. We measured EPFRs contained in PM2.5 collected in Fairbanks, Alaska, in winter 2022. We find that EPFR concentrations were enhanced during surface-based inversion and correlate strongly with incomplete combustion markers, including carbon monoxide and elemental carbon (R2 > 0.75). EPFRs exhibit moderately good correlations with PAHs, biomass burning organic aerosols, and potassium (R2 > 0.4). We also observe strong correlations of EPFRs with hydrocarbon-like organic aerosols, Fe and Ti (R2 > 0.6), and single-particle mass spectrometry measurements reveal internal mixing of PAHs, with potassium and iron. These results suggest that residential wood burning and vehicle tailpipes are major sources of EPFRs and nontailpipe emissions, such as brake wear and road dust, may contribute to the stabilization of EPFRs. Exposure to the observed EPFR concentrations (18 ± 12 pmol m-3) would be equivalent to smoking ∼0.4-1 cigarette daily. Very strong correlations (R2 > 0.8) of EPFR with hydroxyl radical formation in surrogate lung fluid indicate that exposure to EPFRs may induce oxidative stress in the human respiratory tract.

Unlocking peak performance: The role of Nrf2 in enhancing exercise outcomes and training adaptation in humans.

Since the discovery of the nuclear factor erythroid-derived 2-like 2 (Nrf2) transcription factor thirty years ago, it has been shown that it regulates more than 250 genes involved in a multitude of biological processes, including redox balance, mitochondrial biogenesis, metabolism, detoxification, cytoprotection, inflammation, immunity, autophagy, cell differentiation, and xenobiotic metabolism. In skeletal muscle, Nrf2 signalling is primarily activated in response to perturbation of redox balance by reactive oxygen species or electrophiles. Initial investigations into human skeletal muscle Nrf2 responses to exercise, dating back roughly a decade, have consistently indicated that exercise-induced ROS production stimulates Nrf2 signalling. Notably, recent studies employing Nrf2 knockout mice have revealed impaired skeletal muscle contractile function characterised by reduced force output and increased fatigue susceptibility compared to wild-type counterparts. These deficiencies partially stem from diminished basal mitochondrial respiratory capacity and an impaired capacity to upregulate specific mitochondrial proteins in response to training, findings corroborated by inducible muscle-specific Nrf2 knockout models. In humans, baseline Nrf2 expression in skeletal muscle correlates with maximal oxygen uptake and high-intensity exercise performance. This manuscript delves into the mechanisms underpinning Nrf2 signalling in response to acute exercise in human skeletal muscle, highlighting the involvement of ROS, antioxidants and Keap1/Nrf2 signalling in exercise performance. Furthermore, it explores Nrf2's role in mediating adaptations to chronic exercise and its impact on overall exercise performance. Additionally, the influence of diet and certain supplements on basal Nrf2 expression and its role in modulating acute and chronic exercise responses are briefly addressed.

Preventing free radical damage: The significance of including antioxidants in diet to strengthen immunity.

Free radicals (FRs), also known as reactive oxygen species (ROS), are usually established in the body when adequate oxygen depletion occurs. Oxidative stress and the establishment of FRs in the body are mainly caused by high metabolic activity, the need for rapid growth, inadequate flock management, exposure to viral and bacterial microorganisms, and adverse environmental conditions. Furthermore, FRs can also be produced during the activity of phagocytes when they depend on the action of ROS to kill the engulfed pathogen. FRs have very adverse effects on all cells, particularly the cells of the immune system. They are extremely erratic and reactive molecules that directly harm DNA, cellular proteins, lipids, and carbohydrates within cells. Antioxidants are substances that can eliminate and neutralize FRs within the body and free the body from the oxidative stress that occurs due to the accumulation of FRs. Many vitamins and minerals support the activity and effect of the immune system in fighting against microbes and cancer, which mostly depend on their antioxidant elements to diminish the negative impact of FRs in the body. Examples are vitamin C, vitamin E, superoxide dismutase, selenium, glycine, cofactors of glutathione peroxidase, manganese, essential oils, and phenolic compounds.

Rod-Shaped Au@Ce Nano-Platforms for Enhancing Photodynamic Tumor Collaborative Therapy.

Tumor photodynamic therapy (PDT) relies on intratumoral free radicals, while the limited oxygen source and the depletion of tissue oxygen may exacerbate the hypoxia. As the treatment progresses, there will eventually be a problem of insufficient free radicals. Here, it is found that Au@CeO2 nano-rods (Au@Ce NRs), assembled by gold nano-rods (Au NRs) and ceria nanoparticles (CeO2 NPs), can efficaciously absorb near-infrared light (NIR) to promote the release of oxygen and free radicals. Au@Ce NRs exhibit a higher proportion of Ce3+ (Ce2O3) after oxygen release, while Ce3+ is subsequently oxidized to Ce4+ (CeO2) by trace H2O2. Interestingly, Au@Ce NRs re-oxidized by trace H2O2 can re-releasing oxygen and free radicals again upon NIR treatment, achieving oxygenation/oxygen evolution, similar to charging/discharging. This loop maximizes the conversion of limited oxygen source into highly cytotoxic free radicals. As a result, when B16-F10 cells are treated by NIR/Au@Ce NRs, more tumor cells undergo apoptosis, consistent with the higher level of free radicals. Importantly, NIR/Au@Ce NRs successfully suppresses tumor growth and promotes the generation of epidermal collagen fibers in the transplanted tumor model. Therefore, the rod-shaped Au@Ce NRs provide an ideal platform for maximizing the utilization of intratumoral oxygen sources and improving the treatment of melanoma.

Theoretical study of the antioxidant mechanism and structure-activity relationships of 1,3,4-oxadiazol-2-ylthieno[2,3-d]pyrimidin-4-amine derivatives: a computational approach.

A theoretical thermodynamic study was conducted to investigate the antioxidant activity and mechanism of 1,3,4-oxadiazol-2-ylthieno[2,3-d]pyrimidin-4-amine derivatives (OTP) using a Density Functional Theory (DFT) approach. The study assessed how solvent environments influence the antioxidant properties of these derivatives. With the increasing prevalence of diseases linked to oxidative stress, such as cancer and cardiovascular diseases, antioxidants are crucial in mitigating the damage caused by free radicals. Previous research has demonstrated the remarkable scavenging abilities of 1,3,4-oxadiazole derivatives, prompting this investigation into their potential using computational methods. DFT calculations were employed to analyze key parameters, including bond dissociation enthalpy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), and electron transfer enthalpy (ETE), to delineate the antioxidant mechanisms of these compounds. Our findings indicate that specific electron-donating groups such as amine on the phenyl rings significantly enhance the antioxidant activities of these derivatives. The study also integrates global and local reactivity descriptors, such as Fukui functions and HOMO-LUMO energies, to predict the stability and reactivity of these molecules, providing insights into their potential as effective synthetic antioxidants in pharmaceutical applications.

Biomarker dosimetry of acute low level of thermal neutrons and radiation adaptive response effect on rats.

In this paper, we demonstrated the biological effects of acute low-dose neutrons on the whole body of rats and investigated the impact of that level of neutron dose to induce an in vivo radio-adaptive response. To understand the radio-adaptive response, the examined animals were exposed to acute neutron radiation doses of 5 and 10 mSv, followed by a 50 mSv challenge dose after 14 days. After irradiation, all groups receiving single and double doses were kept in cages for one day before sampling. The electron paramagnetic resonance (EPR) method was used to estimate the radiation-induced radicals in the blood, and some hematological parameters and lipid peroxidation (MDA) were determined. A comet assay was performed beside some of the antioxidant enzymes [catalase enzyme (CAT), superoxide dismutase (SOD), and glutathione (GSH)]. Seven groups of adult male rats were classified according to their dose of neutron exposure. Measurements of all studied markers are taken one week after harvesting, except for hematological markers, within 2 h. The results indicated lower production of antioxidant enzymes (CAT by 1.18-5.83%, SOD by 1.47-17.8%, and GSH by 11.3-82.1%). Additionally, there was an increase in red cell distribution width (RDW) (from 4.61 to 25.19%) and in comet assay parameters such as Tail Length, (from 6.16 to 10.81 µm), Tail Moment, (from 1.17 to 2.46 µm), and percentage of DNA in tail length (DNA%) (from 9.58 to 17.32%) in all groups exposed to acute doses of radiation ranging from 5 to 50 mSv, respectively. This emphasizes the ascending harmful effect with the increased acute thermal neutron doses. The values of the introduced factor of radio adaptive response for all markers under study reveal that the lower priming dose promotes a higher adaptation response and vice versa. Ultimately, the results indicate significant variations in DNA%, SOD enzyme levels, EPR intensity, total Hb concentration, and RDWs, suggesting their potential use as biomarkers for acute thermal neutron dosimetry. Further research is necessary to validate these measurements as biodosimetry for radiation exposure, including investigations involving the response impact of RAR with varied challenge doses and post-irradiation behavior.