Oxidative Stress-induced Damage Research Articles

Nuclear respiratory factor 1 regulates super enhancer-controlled SPIDR to protect hepatocellular carcinoma cells from oxidative stress

BackgroundCellular response to oxidative stress plays significant roles in hepatocellular carcinoma (HCC) development, yet the exact mechanism by which HCC cells respond to oxidative stress remains poorly understood. This study aimed to investigate the role and mechanism of super enhancer (SE)-controlled genes in oxidative stress response of HCC cells.MethodsThe GSE112221 dataset was used to identify SEs by HOMER. Functional enrichment of SE-controlled genes was performed by Metascape. Transcription factors were predicted using HOMER. Prognosis analysis was conducted using the Kaplan-Meier Plotter website. Expression correlation analysis was performed using the Tumor Immune Estimation Resource web server. NRF1 and SPIDR expression in HCC and normal liver tissues was analyzed based on the TCGA-LIHC dataset. ChIP-qPCR was used to detect acetylation of lysine 27 on histone 3 (H3K27ac) levels of SE regions of genes, and the binding of NRF1 to the SE of SPIDR. To mimic oxidative stress, HepG2 and Hep3B cells were stimulated with H2O2. The effects of NRF1 and SPIDR on the oxidative stress response of HCC cells were determined by the functional assays.ResultsA total of 318 HCC-specific SE-controlled genes were identified. The functions of these genes was significant association with oxidative stress response. SPIDR and RHOB were enriched in the “response to oxidative stress” term and were chosen for validation. SE regions of SPIDR and RHOB exhibited strong H3K27ac modification, which was significantly inhibited by JQ1. JQ1 treatment suppressed the expression of SPIDR and RHOB, and increased reactive oxygen species (ROS) levels in HCC cells. TEAD2, TEAD3, NRF1, HINFP and TCFL5 were identified as potential transcription factors for HCC-specific SE-controlled genes related to oxidative stress response. The five transcription factors were positively correlated with SPIDR expression, with the highest correlation coefficient for NRF1. NRF1 and SPIDR expression was up-regulated in HCC tissues and cells. NRF1 activated SPIDR transcription by binding to its SE. Silencing SPIDR or NRF1 significantly promoted ROS accumulation in HCC cells. Under oxidative stress, silencing SPIDR or NRF1 increased ROS, malondialdehyde (MDA) and γH2AX levels, and decreased superoxide dismutase (SOD) levels and cell proliferation of HCC cells. Furthermore, overexpression of SPIDR partially offset the effects of NRF1 silencing on ROS, MDA, SOD, γH2AX levels and cell proliferation of HCC cells.ConclusionNRF1 driven SPIDR transcription by occupying its SE, protecting HCC cells from oxidative stress-induced damage. NRF1 and SPIDR are promising biomarkers for targeting oxidative stress in the treatment of HCC.

A Sustainable Retinal Drug Co-Delivery for Boosting Therapeutic Efficacy in wAMD: Unveiling Multifaceted Evidence and Synergistic Mechanisms.

Sustainable retinal codelivery poses significant challenges technically, although it is imperative for synergistic treatment of wet age-related macular degeneration (wAMD). Here, a microemulsion-doped hydrogel (Bor/PT-M@TRG) is engineered as an intravitreal depot composing of temperature-responsive hydrogel (TRG) and borneol-decorated paeoniflorin (PF) & tetramethylpyrazine (TMP)-coloaded microemulsions (Bor/PT-M). Bor/PT-M@TRG, functioning as the "ammunition depot", resides in the vitreous and continuously releases Bor/PT-M as the therapeutic "bullet", enabling deep penetration into the retina for 21 days. A single intravitreal injection of Bor/PT-M@TRG yields substantial reductions in choroidal neovascularization (CNV, a hallmark feature of wAMD) progression and mitigates oxidative stress-induced damage in vivo. Combinational PF&TMP regulates the "reactive oxygen species/nuclear factor erythroid-2-related factor 2/heme oxygenase-1" pathway and blocks the "hypoxia inducible factor-1α/vascular endothelial growth factor" signaling in retina, synergistically cutting off the loop of CNV formation. Utilizing fluorescence resonance energy transfer and liquid chromatography-mass spectrometry techniques, they present compelling multifaceted evidence of sustainable retinal codelivery spanning formulations, ARPE-19 cells, in vivo eye balls, and ex vivo section/retina-choroid complex cell levels. Such codelivery approach is elucidated as the key driving force behind the exceptional therapeutic outcomes of Bor/PT-M@TRG. These findings highlight the significance of sustainable retinal drug codelivery and rational combination for effective treatment of wAMD.

The mechanism of curcumin to protect mouse ovaries from oxidative damage by regulating AMPK/mTOR mediated autophagy

BackgroundOxidative stress is considered the main cause of granulosa cell apoptosis in ovarian disease. Curcumin has various biological roles, but its potential role in protecting granulosa cells from oxidative damage remains unidentified. PurposeThe study revealed the protective effect of curcumin on granulosa cell survival under oxidative stress, and explored its mode of action. Study designThe protective effect of curcumin on oxidative stress-induced ovarian cell apoptosis was evaluated in vivo and in vitro, and the role of autophagy and AMPK/mTOR signaling pathway in this process was also demonstrated. MethodsFirst, mice were injected to 3-nitropropionic acid (3-NPA, 20 mg/kg/day) for 14 consecutive days to establish the ovarian oxidative stress model, at same time, curcumin (50, 100, 200 mg/kg/day) was given orally. Thereafter, functional changes, cell apoptosis, and autophagy in ovarian tissue were evaluated by hematoxylin-eosin staining, enzyme-linked immunosorbent assay, western blotting, TUNEL assays, and transmission electron microscopy. Finally, oxidative stress model of granulosa cells was established with H2O2in vitro and treated with curcumin. The underlying mechanisms of curcumin to protect the apoptosis under oxidative stress in vitro were determined using western blotting and TUNEL assays. ResultsIn our study, after curcumin treatment, the mouse ovarian function disorder under 3-nitropropionic acid-induced oxidative stress recovered significantly, and ovarian cell apoptosis decreased. H2O2 induced granulosa cell apoptosis in vitro, and curcumin antagonized this process. Autophagy contributes to tissue and cell survival under stress. We therefore examined the role of autophagy in this process. According to the in vivo and in vitro results, curcumin restored autophagy under oxidative stress. The autophagy inhibitor (chloroquine) exhibited the same effect as curcumin, whereas the autophagy activator (rapamycin) antagonized the effect of curcumin. In addition, the study found that the AMPK/mTOR pathway plays a crucial role in curcumin- mediated autophagy to protect against oxidative stress-induced apoptosis. ConclusionOur findings for the first time systematically revealed a new mechanism through which curcumin protects ovarian granulosa cells from oxidative stress-induced damage through AMPK/mTOR-mediated autophagy and suggested that it can be a new therapeutic direction for female ovarian diseases.

Long-lasting bioactive compounds production from Malus x domestica Borkh var. Mela Rosa Marchigiana pulp callus culture with antioxidant activity: In vitro, ex vivo and in vivo validation

The Mela Rosa Marchigiana (MRM) pulp callus, kept alive since 2017 by monthly sub-cultures, was investigated and morphologically described. In the present paper, the MRM callus ethanolic Extract (MRME) was prepared from one of the 2022 callus sub-cultures and analysed by GC-MS and GC-FID. The investigation was carried out to test whether a long-term culture could affect either the amount or the bioactivity (or both) of the triterpenes produced by the callus. To this aim, the 2022 extract (MRME 2022) was compared to the extract prepared a few years ago (i.e., MRME 2019). Obtained results showed that the composition of both extracts was almost the same, thus revealing that the callus culture efficiency of triterpenes production was nearly unchanged over time. When analysing the biological effect of the extract, all experimental tests, including cell-free, in vitro, ex vivo, and in vivo assays, confirmed that MRME 2022 significantly protected cells, tissues, or whole organisms from oxidative stress-induced damage. Present results could lead to future studies to test MRME as a possible ingredient of a nutraceutical formulation for healthy aging or for the prevention of oxidative stress-associated pathologies.

Garcinol prevents oxidative stress-induced bone loss and dysfunction of BMSCs through NRF2-antioxidant signaling

There are multiple published data showing that excessive oxidative stress contributes to bone loss and even bone tissue damage, and it is also correlated with the pathophysiology of bone degenerative diseases, including osteoporosis (OP). Garcinol, a polyisoprenylated benzophenone derivative, has been recently established as an anti-oxidant agent. However, it remains elusive whether Garcinol protects bone marrow mesenchymal stem cells (BMSCs) and bone tissue from oxidative stress-induced damage. Here, we explored the potential effects of Garcinol supplementation in ameliorating oxidative stimulation-induced dysfunction of BMSCs and bone loss in osteoporotic mice. In this study, we verified that Garcinol exerted potent protective functions in the hydrogen peroxide (H2O2)-induced excessive oxidative stress and dysfunction of BMSCs. Besides, Garcinol was also identified to improve the reduced bone mass and abnormal lineage commitment of BMSCs in the condition of OP by suppressing the oxidative stimulation. Subsequent analysis revealed that nuclear factor erythroid 2-related factor 2 (NRF2) might be a key regulator in the sheltering effects of Garcinol on the H2O2-regulated oxidative stress, and the protective functions of Garcinol was mediated by NRF2-antioxidant signaling. Collectively, Garcinol prevented oxidative stress-related BMSC damage and bone loss through the NRF2-antioxidant signaling, which suggested the promising therapeutic values of Garcinol in the treatment of oxidative stress-related bone loss. Therefore, Garcinol might contribute to treating OP.

Effect of sulfate on the osmoregulatory and physio-biochemical responses of GIFT (Oreochromis niloticus) juveniles reared in potassium-deficient medium saline waters.

The inland saline waters were continuously observed to have low potassium concentrations compared to their seawater counterpart of the same salinity. We hypothesize that the toxic effect of sulfate may manifest in low potassium saline (LPSW) waters compared to brackish water of the same salinity. Thus, LC50 trials were performed in GIFT (genetically improved farmed tilapia) fry (0.5 ± 0.02 g) to determine the acute sulfate toxicity in freshwater (FW, 0.5 g L-1), artificial seawater (ASW, 10 g L-1), and LPSW (10 g L-1). The median lethal concentrations (96h LC50) of sulfate ion in FW, LPSW, and ASW for the GIFT were 5.30 g L-1, 2.56 g L-1, and 2.98 g L-1, respectively. A second experiment was conducted for 21 days, exposing fish to a sub-lethal level of sulfate ion (SO42-) concentration (1000 mg L-1, one-fifth of FW LC50) with different types of waters (FW, freshwater, 0.5 g L-1; ASW, artificial seawater, 10 g L-1; LPSW, low potassium saline water, 10 g L-1) with and without sulfate inclusion to constitute the treatments as follows, (FW, FW + SO4, ASW, ASW + SO4, LPSW, LPSW + SO4). The effect of sulfate on GIFT reared in sulfate-rich potassium-deficient medium saline water was evaluated by focusing on the hematological adjustments, stress-induced oxidative damage, and osmoregulatory imbalances. The survival was not altered due to the sulfate concentration and K+ deficiency; however, there were significant changes in branchial NKA (Na+/K+-ATPase) activity and osmolality. The increase in NKA was highest in LPSW treatment, suggesting that internal ionic imbalance was triggered due to an interactive effect of sulfate and K+ deficiency. The cortisol levels showed a pronounced increase due to sulfate inclusion irrespective of K+ deficiency. The antioxidant enzymes, i.e., SOD (superoxide dismutase), catalase, GST (glutathione-S-transferase), and GPX (glutathione peroxidase), reflected a similar pattern of increment in the gills and liver of the LPSW + SO4 groups, suggesting a poor antioxidant status of the exposed group. The hepatic peroxidation status, i.e. TBARS (thiobarbituric acid reactive substances), and the peroxide values were enhanced due to both K+ deficiency and sulfate inclusion, suggesting a possible lipid peroxidation in the liver due to handling the excess sulfate anion concentration. The hematological parameters, including haemoglobin, total erythrocyte count, and hematocrit level, reduced significantly in the LPSW + SO4 group, indicating a reduced blood oxygen capacity due to the sulfate exposure and water potassium deficiency. The hepatic acetylcholine esterase activity was suppressed in all the treatments with sulfate inclusion, while the highest suppression was observed in the LPSW + SO4 group. Thus, it is concluded that sulfate-induced physiological imbalances manifest more in potassium-deficient water, indicating that environmental sulfate is more detrimental to inland saline water than freshwater or brackish water of the same salinity.

Chronic exposure to 2,2′-azobis-2-amidinopropane that induces intestinal damage and oxidative stress in larvae of Drosophila melanogaster

Embryonic development is exceptionally susceptible to pathogenic, chemistry and mechanical stressors as they can disrupt homeostasis, causing damage and impacted viability. Oxidative stress has the capacity to induce alterations and reshape the environment. However, the specific impacts of these oxidative stress-induced damages in the gastrointestinal tract of Drosophila melanogaster larvae have been minimally explored. This study used 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH), a free radical generator, to investigate oxidative stress effects on Drosophila embryo development. The results showed that exposing Drosophila eggs to 30 mM AAPH during 1st instar larva, 2nd instar larva and 3rd instar larva stages significantly reduced hatching rates and pupal generation. It increased the activity of antioxidant enzymes and increased oxidative damage to proteins and MDA content, indicating severe oxidative stress. Morphological changes in 3rd individuals included decreased brush borders in enterocytes and reduced lipid vacuoles in trophocytes, essential fat bodies for insect metabolism. Immunostaining revealed elevated cleaved caspase 3, an apoptosis marker. This evidence validates the impact of oxidative stress toxicity and cell apoptosis following exposure, offering insights into comprehending the chemically induced effects of oxidative stress by AAPH on animal development.

The optimization of gold nanoparticles–horseradish peroxidase as peroxidase mimic using central composite design for the detection of hydrogen peroxide

The oxidizing agent, hydrogen peroxide (H2O2), which is a part of reactive oxygen species (ROS) is well-known to contribute to oxidative stress-induced damage to biological molecules. An excess of free radicals can harm health and is associated with human diseases. Gold nanotechnology, a highly relevant nanomaterial, has been utilized as a new material in advanced sensor detection. In this study, colorimetric methods based on peroxidase enzymes were developed for measuring H2O2. The synthesized gold nanoparticles (AuNPs) showed a concentration of approximately 1.73 nM at a wavelength of 520 nm. The average diameter displayed a uniform size distribution, estimated at 18 nm, and an increase in the shell thickness of AuNPs-horseradish peroxidase (HRP) was observed in the TEM images. The AuNPs-HRP system demonstrated remarkable catalytic activity in the reaction of the chromogenic substrate tetramethylbenzidine (TMB) with H2O2, resulting in the production of an oxide product. The optimal conditions for the AuNPs-HRP system, as determined by central composite design (CCD), were a temperature of 25 °C and a pH of 7 within an 8 h period. A strong linear relationship was observed between different absorbance values and the H2O2 concentration, with a coefficient of determination of 0.9956. A portable platform was successfully used to determine H2O2 levels in beverages with recoveries ranging from 95.51% to 118.85%. These findings suggest that the AuNPs-HRP system could be applied to detect H2O2 in beverages.

Trimethylamine N-Oxide Improves Exercise Performance by Reducing Oxidative Stress through Activation of the Nrf2 Signaling Pathway.

Trimethylamine N-oxide (TMAO) has attracted interest because of its association with cardiovascular disease and diabetes, and evidence for the beneficial effects of TMAO is accumulating. This study investigates the role of TMAO in improving exercise performance and elucidates the underlying molecular mechanisms. Using C2C12 cells, we established an oxidative stress model and administered TMAO treatment. Our results indicate that TMAO significantly protects myoblasts from oxidative stress-induced damage by increasing the expression of Nrf2, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase (NQO1), and catalase (CAT). In particular, suppression of Nrf2 resulted in a loss of the protective effects of TMAO and a significant decrease in the expression levels of Nrf2, HO-1, and NQO1. In addition, we evaluated the effects of TMAO in an exhaustive swimming test in mice. TMAO treatment significantly prolonged swimming endurance, increased glutathione and taurine levels, enhanced glutathione peroxidase activity, and increased the expression of Nrf2 and its downstream antioxidant genes, including HO-1, NQO1, and CAT, in skeletal muscle. These findings underscore the potential of TMAO to counteract exercise-induced oxidative stress. This research provides new insights into the ability of TMAO to alleviate exercise-induced oxidative stress via the Nrf2 signaling pathway, providing a valuable framework for the development of sports nutrition supplements aimed at mitigating oxidative stress.

Investigating the therapeutic potential of Allium cepa extract in combating pesticide exposure induced ocular damage

The ocular surface is subject to a range of potentially hazardous environmental factors and substances, owing to its anatomical location, sensitivity, and physiological makeup. Xenobiotic stress exerted by chronic pesticide exposure on the cornea is primarily responsible for ocular irritation, excessive tear production (hyper-lacrimation), corneal abrasions and decreased visual acuity. Traditional medicine hails the humble onion (Allium cepa) for its multi-faceted properties including but not limited to anti-microbial, antioxidant, anti-inflammatory and wound healing. However, there is a lacuna regarding its impact on the ocular surface.Thereby, the current study investigated whether topical application of crude extract of Allium cepa aided in mitigating pesticide-induced damage to the ocular surface. The deleterious effects of pesticide exposure and their mitigation through the topical application of herbal extract of Allium cepa were analysed initially through in vitro evaluation on cell lines and then on the ocular surface via various in-vivo and ex-vivo techniques. Pathophysiological alterations to the ocular surface that impacted vision were explored through detailed neurophysiological screening with special emphasis on visual acuity wherein it was observed that the murine group treated with topical application of Allium cepa extract had comparable visual capacity to the non-pesticide exposed group. Additionally, SOD2 was utilized as an oxidative stress marker along with the expression of cellular apoptotic markers such as Bcl-xL to analyse the impact of pesticide exposure and subsequent herbal intervention on oxidative stress-induced corneal damage. The impact on the corneal epithelial progenitor cell population (ABCG2 and TERT positive cells) was also flowcytometrically analysed. Therefore, from our observations, it can be postulated that the topical application of Allium cepa extract might serve as an effective strategy to alleviate pesticide exposure related ocular damage.

Sodium butyrate alleviates heat stress-induced damage to morphology, anti-oxidant status, inflammatory response and barrier integrity in jejunum of broilers

To evaluate the protective effects of sodium butyrate (SB) on intestinal morphology, anti-oxidant status, inflammatory response and barrier integrity in male broilers under heat stress. A total of 180 21-d-old male Arbour Acres broilers with similar body weight were used for this 21-d experiment. Broilers were randomly allocated to three groups: CON group, basal diet and raised under 24 °C; HS group, basal diet and raised under heat stress condition (34 °C from 10:00 to 18:00 and 24 °C for the rest time); HS-SB group, basal diet with 1200 mg/kg SB and raised under heat stress condition. Compared to the HS group, SB supplementation increased average daily gain (ADG), villus height: crypt depth ratio (VH: CD), VH, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity, and interleukin-10 (IL-10) level, decreased feed conversion ratio (FCR), CD, reactive oxygen species (ROS), IL-1β and tumour necrosis factor-alpha (TNF-α) level, up-regulated the mRNA expression of nuclear factor erythroid 2-related factor 2, haem oxygenase 1, GSH 1 (GPX1), SOD and CAT, down-regulated the mRNA expression of toll-like receptor 4 (TLR4), nuclear transcription factors, IL-1β, and TNF-α in jejunum of heat-stressed broilers. Furthermore, SB supplementation up-regulated the mRNA expression of occluding, claudin-1 and zona occludens-1 (ZO-1) in jejunum of heat-stressed broilers, accompanied with decreasing serum endotoxin and D-lactic acid concentration, and diamine oxidase (DAO) activity. There results suggested that SB supplementation could alleviate heat stress-induced jejunal tight junction structure dysfunction by up-regulated the expression of occluding, claudin-1 and ZO-1, presumably through alleviating oxidative stress and inflammatory response. HIGHLIGHTS Sodium butyrate alleviated heat stress-induced jejunal morphology damage. Sodium butyrate alleviated heat stress-induced jejunal oxidative damage. Sodium butyrate alleviated heat stress-induced jejunal inflammatory response. Sodium butyrate alleviated heat stress-induced tight junction structure dysfunction.

Molecular Insights into the Interaction of Vitamin C (Ascorbic Acid) with Glutathione Peroxidase: A Comprehensive Computational Study

This research investigates the molecular interaction between vitamin C (ascorbic acid) and glutathione peroxidase (GPX), a key enzyme in the antioxidant defense system. Oxidative stress-induced damage, caused by an imbalance in reactive oxygen species (ROS) production, is implicated in various health issues. Vitamin C, a potent antioxidant, is known for its ability to neutralize free radicals and support overall cellular health. Despite numerous studies on the protective effects of vitamin C, the molecular details of its interaction with GPX remain unclear. In this study, we employ computational methods, including molecular docking and dynamics simulations, to predict and visualize the molecular-level interaction between vitamin C and GPX. Our results reveal a favorable binding affinity, supported by negative free energy values, suggesting strong interactions. Detailed analyses of various parameters provide insights into the structural flexibility of the ligand, vibrational dynamics, and clustering characteristics. Overall, this study enhances our understanding of the molecular mechanisms underlying the beneficial effects of vitamin C in combating oxidative stress, with potential implications for therapeutic interventions.

Mycorrhizal colonization and calcium spraying modulate physiological and antioxidant responses to improve pepper growth and yield under salinity stress

Abiotic stresses, such as salt and drought, limit plant growth, reduce crop production, and pose the greatest challenge to the sustainability of agricultural development in arid and semi-arid countries. Arbuscular mycorrhizal fungi (AMF) and calcium can play an important role in alleviating the adverse effects of abiotic stresses on plants. Therefore, this study was conducted to evaluate the effect of two levels of mycorrhizal inoculation (inoculated seedlings and non-inoculated seedlings) and three levels of foliar spraying with calcium (0, 0.5%, and 1%), separately or in combination, on growth, physiology, and yield of salt-stressed pepper (Capsicum annuum L.). The experiment was conducted in an open field with saline soil and irrigation water, in a randomized complete block design with split plot arrangement. Mycorrhizal inoculation and calcium spray have been shown to facilitate nutrient uptake, modulate physiological responses, and activate the antioxidant system, enhancing salt stress tolerance and improving the growth and yield of salt-stressed pepper. Combined treatment plants grown from inoculated seedlings and sprayed with 1% Ca recorded the best results, alleviating salt stress-induced oxidative damage by activating the antioxidant system including antioxidant enzymes [Superoxide dismutase (SOD) and catalase (CAT)], and non-enzymatic antioxidants (ascorbic acid and phenols), reducing H2O2 and malondialdehyde (MDA) accumulation, enhancing physiological activities (relative water content (RWC %) and chlorophyll content), and improving nutrient balance (increasing N, P, K and reducing Na content), leading to increased pepper growth and yield parameters. Our results indicated that mycorrhizal inoculation and calcium spray can be recommended as a practical alternative and environmentally friendly approach to enhance plant tolerance to salt stress by improving nutritional status, physiological processes, and antioxidant activities, thus increasing the morphological and yield traits of stressed plants.

Structure characterization of polysaccharides from Cistanche deserticola and their neuroprotective effects against oxidative stress in slow transit constipation mice

Oxidative stress-induced enteric neuropathy is an important factor in slow transit constipation (STC). Cistanche deserticola crude polysaccharides (CDCP) are natural antioxidants with various biological activities. We prepared CDCP through water-extract and alcohol-precipitation methods. The structural characteristics of CDCP were analyzed by infrared spectroscopy and methylation analysis. The results showed that CDCP was primarily composed of (1 → 4)-linked glucans with minor amounts of pectic polysaccharides. Different doses of CDCP (100, 200, and 400 mg/kg) were administered to loperamide-induced STC mice to explore the therapeutic effects of CDCP. Compared with the untreated group, CDCP treatment significantly improved constipation symptoms, relevant gut-regulating peptides levels, colonic pathological damage, and colonic myenteric nerons injury. CDCP enhanced the antioxidant capacity by decreasing Malondialdehyde (MDA) content, increasing Superoxide Dismutase (SOD) activity and Reduced Glutathione (GSH) content. CDCP significantly reduced oxidative stress-induced injury by preserving mitochondrial function in the colonic myenteric plexus. Furthermore, the neuroprotective effects of CDCP might be associated with the Nrf2/Keap1 pathway. Thus, our findings first revealed the potential of CDCP to protect the colonic myenteric plexus against oxidative stress-induced damage in STC, establishing CDCP as promising candidates for natural medicine in the clinical management of STC.

Bilayer nanofibers loaded with Malva sylvestris extract for enhanced wound healing applications

Addressing the challenges of wound care requires accurate dressing selection. The combination of collagen with nanofibers (NFs) enhances its properties, improving cellular recognition. Multi-layered nanofibrous systems, particularly those with Polycaprolactone (PCL), offer higher mechanical attributes and prolonged substance release. We fabricated four types of nanofibrous bilayer mats (NBMs) using electrospinning (EN), each composed of an active layer containing a mixture of PCL and collagen loaded with and without Malva sylvestris (MS) extract, and an inactive layer with only PCL. The resulting bilayers were neat PCL/PCL-Collagen (PCLC), PCL/PCLC-5% MS, PCL/PCLC-10% MS, and PCL/PCLC-15% MS. Morphological and mechanical properties, porosity, water vapor transmission rate (WVTR), swelling rates, drug release profiles, cytotoxicity, cell attachment, and cytoprotective effect of bilayers were evaluated. FE-SEM imaging revealed smooth and filamentous mats without any beads, with Fiber diameter average (FDA) ranging from 128 ± 41 nm to 140 ± 51 nm. WVTR values of the NFs were comparable to commercial dressings like Tegaderm, Bioclusive, and Op Site. The mats demonstrated significant liquid uptake capacity, indicating their potential to handle wound exudate. They exhibited prolonged extract release, ensuring a sustained supply. All mats showed excellent blood compatibility, with our MS-loaded NBMs displaying rapid blood clotting times, essential for effective wound closure. FE-SEM images confirmed robust cell adhesion and spreading on both loaded and unloaded mats. The study underscored the potent cytoprotective effects of MS extract, in both free and encapsulated forms. The dose-dependent increase in cell viability suggests its potential in mitigating oxidative stress-induced cellular damage. The MTT (4,5-dimethyl- 2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay revealed that encapsulating MS extract in bilayer NFs significantly improved cell viability at 48 and 72 h, surpassing free MS extract treatment.

Post-exposure self-recovery reverses oxidative stress, ameliorates pathology and neurotransmitters imbalance and rescues spatial memory after time-dependent aluminum exposure in rat brain.

Aluminum is a potent neurotoxin, responsible for memory impairment and cognitive dysfunction. The neurotoxic effect of aluminum on cognitive impairment is well documented, however, exposure to aluminum in a time-dependent manner and post-exposure self-recovery still needs to be elaborated. This research aimed to (1) study the time-dependent effect of aluminum exposure by administering a total dose of 5850mg/kg of Al over two different time periods: 30 and 45days (130 and 195mg/kg of AlCl3 respectively), and (2) study 20days post-exposure self-recovery effect in both aluminum-exposed groups by giving distilledwater. Cognitive abilities were investigated through Morris water maze test and hole board test and compared in both exposure and recovery groups. Oxidative stress markers and neurotransmitter levels were measured for both exposure and recovery groups. To understand the mechanism of aluminum exposure and recovery, immunohistochemical analysis of synaptophysin (Syp) and glial fibrillary acidic protein (GFAP) was performed. Results showed cognitive dysfunction, oxidative stress-induced damage, reduced neurotransmitter levels, decreased immunoreactivity of Syp, and increased GFAP. However, these parameters showed a larger improvement in the recovery group where rats were given aluminum for 30days period in comparison to recovery group followed by 45days of aluminum exposure. These results suggest that restoration of cognitive ability is affected by the duration of aluminum exposure. The study findings provide us with insight into the adverse effects of aluminum exposure and can be utilized to guide future preventive and therapeutic strategies against aluminum neurotoxicity.

Inactivation of Mst/Nrf2/Keap1 signaling flexibly mitigates MAPK/NQO-HO1 activation in the reproductive axis of experimental fluorosis

Fluoride induced reprotoxicity through oxidative stress-mediated reproductive cell death. Hence, the current study evaluated the importance of the MST/Nrf2/MAPK/NQO-HO1 signaling pathway in fluorosis-induced reproductive toxicity. For this purpose, the reproductive toxicity of sodium fluoride (NaF) at physiological, biochemical, and intracellular levels was evaluated. In-vivo, NaF at 100 mg/L instigated physiological dysfunction, morphological, stereological, and structural injuries in the gut-gonadal axis of fluorosis mice through weakening the antioxidant signaling, Nrf2/HO-1/NQO1signaling pathway, causing the gut-gonadal barrier disintegrated via oxidative stress-induced inflammation, mitochondrial damage, apoptosis, and autophagy. Similar trends were also observed in-vitro in the isolated Leydig cells (LCs) challenging with 20 mg/L NaF. Henceforth, activating the cellular antioxidant signaling pathway, Nrf2/HO-1/NQO1, inactivating autophagy and apoptosis, or attenuating lipopolysaccharide (LPS) can be the theoretical basis and valuable therapeutic targets for coping with NaF-induced reproductive toxicity.

Management of excessive soil H+ ion induced toxicities by application of organic seaweed amendment enhances photosynthesis and resource use efficiencies in rice (Oryza sativa)

Globally, soil acidification is a serious environmental issue that reduces commercial agricultural production. Rice is subjected to nutritional stress due to acidic soil, which is a major impediment to rice production. Since acid soil threatens rice plants with soil compaction, nutrient loss, and plant stress-induced oxidative cell damage that results in affecting the photosynthetic system, restricting the availability of water, and reducing overall plant growth and productivity. Since contemporary soil acidification management strategies provide mediocre results, the use of Sargassum wightii seaweed-based biostimulants (BS) and soil amendments is sought as an environmentally friendly alternative strategy, and therefore its potential isevaluated in this study. BS was able to mediate soil quality by improving soil pH and structure along with facilitating nitrogen phytoavailability. BS also increased the activity of the antioxidant enzyme system, superoxide dismutase ((48%), peroxidase (76.6%), and ascorbate peroxidase (63.5%), aggregating the monaldehyde-mediating accumulation of osmoprotective proline in roots, that was evident from rapid initiation of root hair growth in treated seedlings. BS was also able to physiologically modulate photosynthetic activities and chlorophyll production (24.31%) in leaves, maintaining the efficiency of plant water use by regulating the stomatal conductance (0.91 mol/m/s) and the transpiration rate (13.2 mM/m/s). The BS compounds were also successful in facilitating nitrogen uptake resulting in improved plant growth (59%), tiller-panicle number, and yield (52.57%), demonstrating a resourceful nitrogen use efficiency (71.96%) previously affected by stress induced by acid soil. Therefore, the study affirms the competent potential of S. wightii-based soil amendment to be applied not only to improve soil quality, but also to increase plant production and yield.

Post-translational modifications of Keap1: the state of the art.

The Keap1-Nrf2 signaling pathway plays a crucial role in cellular defense against oxidative stress-induced damage. Its activation entails the expression and transcriptional regulation of several proteins involved in detoxification and antioxidation processes within the organism. Keap1, serving as a pivotal transcriptional regulator within this pathway, exerts control over the activity of Nrf2. Various post-translational modifications (PTMs) of Keap1, such as alkylation, glycosylation, glutathiylation, S-sulfhydration, and other modifications, impact the binding affinity between Keap1 and Nrf2. Consequently, this leads to the accumulation of Nrf2 and its translocation to the nucleus, and subsequent activation of downstream antioxidant genes. Given the association between the Keap1-Nrf2 signaling pathway and various diseases such as cancer, neurodegenerative disorders, and diabetes, comprehending the post-translational modification of Keap1 not only deepens our understanding of Nrf2 signaling regulation but also contributes to the identification of novel drug targets and biomarkers. Consequently, this knowledge holds immense importance in the prevention and treatment of diseases induced by oxidative stress.

DNA damage signaling in Drosophila macrophages modulates systemic cytokine levels in response to oxidative stress

Environmental factors, infection, or injury can cause oxidative stress in diverse tissues and loss of tissue homeostasis. Effective stress response cascades, conserved from invertebrates to mammals, ensure reestablishment of homeostasis and tissue repair. Hemocytes, the Drosophila blood-like cells, rapidly respond to oxidative stress by immune activation. However, the precise signals how they sense oxidative stress and integrate these signals to modulate and balance the response to oxidative stress in the adult fly are ill-defined. Furthermore, hemocyte diversification was not explored yet on oxidative stress. Here, we employed high-throughput single nuclei RNA-sequencing to explore hemocytes and other cell types, such as fat body, during oxidative stress in the adult fly. We identified distinct cellular responder states in plasmatocytes, the Drosophila macrophages, associated with immune response and metabolic activation upon oxidative stress. We further define oxidative stress-induced DNA damage signaling as a key sensor and a rate-limiting step in immune-activated plasmatocytes controlling JNK-mediated release of the pro-inflammatory cytokine unpaired-3. We subsequently tested the role of this specific immune activated cell stage during oxidative stress and found that inhibition of DNA damage signaling in plasmatocytes, as well as JNK or upd3 overactivation, result in a higher susceptibility to oxidative stress. Our findings uncover that a balanced composition and response of hemocyte subclusters is essential for the survival of adult Drosophila on oxidative stress by regulating systemic cytokine levels and cross-talk to other organs, such as the fat body, to control energy mobilization.