Stress-induced Damage Research Articles

Moisturizing and antioxidant factors of skin barrier restoring cream with shea butter, silkflo and vitamin E in human keratinocyte cells.

Moisturizers are integral to daily skincare routines, reflecting the increasing trend among people towards cosmetic products, particularly for skin care. They significantly contribute to preserving skin health, particularly by regulating the epidermal barrier and moisture levels within the skin. This study aims to explore the moisturizing and antioxidant effect of skin barrier restoring cream Moiz MM (MZ) with shea butter, silkflo and vitamin E by investigating its protective effect against oxidative stress-induced cellular damage and therapeutic mechanisms in human keratinocytes cells (HaCaT). The invitro antioxidant activity of MZ was evaluated by DPPH, ABTS and NO assays. For the cell culture study, HaCaT cells were cultured and stimulated using H2O2 and then treated with different concentrations of MZ. Then, it was subjected to DCFH-DA staining, reverse transcriptase PCR and western blot analysis for the evaluation of various skin-moisture-related components in human keratinocyte cells. Type I procollagen was examined using ELISA technique. The results highlighted that oxidative stress in HaCaT cells decreased type I procollagen synthesis, while MZ treatment significantly increased the synthesis. Moreover, the viability of HaCaT cells was not affected in the presence of MZ, which demonstrates its non-toxic effect. Furthermore, MZ can counteract H2O2-mediated oxidative stress by enhancing the antioxidant enzyme activity such as superoxide dismutase and catalase, and decrease reactive oxygen species generation in skin cells. Additionally, MZ greatly promotes hyaluronic acid production by enhancing the expression of the hyaluronic acid synthase-1 gene and Aquaporin 3 protein. This study suggests that MZ has the potential to serve as a moisturizing and antioxidant skincare formula.

Ameliorative effect of rutecarpine supplementation against cisplatin-induced nephrotoxicity in rats via inhibition of monocyte chemoattractant protein-1, intercellular adhesion molecule-1, high-mobility group box 1, and nuclear factor kappa B.

Cisplatin, the pioneering heavy metal compound, stands out as a potent drug for the treatment of various solid tumors. However, its clinical utility is hampered by notable toxicity and adverse effects, particularly nephrotoxicity. The potency of rutecarpine, a phytochemical, in mitigating cisplatin-induced nephrotoxicity was assessed in the present study. In this experimental setup, healthy male Wistar rats were grouped into four and Group I rats served as the control group, receiving only vehicle control. Group II rats were subjected to cisplatin treatment alone, administered intraperitoneally at a dosage of 7mg/kg body weight on the 19th, 20th, and 21st days. Group III and IV rats were orally administered with rutecarpine at doses of 10 and 20mg/kg body weight, respectively, starting from Day 1 and continuing daily for 21 days. Additionally, they were injected intraperitoneally with cisplatin at the same dosage and schedule as Group II. Relative kidney weight and renal biochemical markers blood urea nitrogen, lactate dehydrogenase, serum urea, and creatinine were measured to assess rutecarpine inhibitory potency against cisplatin toxicity. Markers of oxidative damage and antioxidants levels were quantified in the ruteacarpine- and cisplatin-treated rats. The study investigated the anti-inflammatory property of rutecarpine in cisplatin-induced nephrotoxicity by analyzing inflammatory cytokines. Renal tissue levels of monocyte chemoattractant protein-1, intercellular adhesion molecule-1, high-mobility group box 1, and nuclear factor kappa B, key markers of nephrotoxicity, were quantified to assess rutecarpine's potential to mitigate cisplatin-triggered damage. Histopathological examinations were performed to confirm the impact of rutecarpine against cisplatin-induced nephrotoxicity. Treatment with rutecarpine notably reduced renal biochemical markers, prevented renal edema, and attenuated oxidative stress-induced damage in cisplatin-treated rats. Both inflammatory and nephrotoxicity markers showed significant decreases in rats treated with rutecarpine along with cisplatin. Histological analysis affirmed that rutecarpine pretreatment effectively prevented cisplatin-induced nephrotoxicity. The study findings demonstrate that rutecarpine ameliorates cisplatin-triggered nephrotoxicity through its antioxidant and anti-inflammatory properties, suggesting that rutecarpine supplementation alongside cisplatin treatment could potentially reduce nephrotoxicity in cancer patients.

Therapeutic Effect of Shikimic Acid on Heat Stress-Induced Myocardial Damage: Assessment via Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Experiments

Abstract: Background: Rising global temperatures have been linked to an increased incidence of heat stress (HS)-induced myocardial damage. Methods: This study aimed to investigate the therapeutic potential of shikimic acid (SA) on HS-induced myocardial damage using network pharmacology, molecular docking, molecular dynamics (MD) simulations, and in vitro experiments. Results: Network pharmacology analysis indicated that SA significantly attenuates the inflammatory response to HS by modulating 60 targets, including TNF, IL-6, and STAT3, which are enriched in the PI3K/AKT signaling pathway. Molecular docking and MD simulation analyses demonstrated that SA forms stable complexes with TNF (−6.642 kcal/mol) and IL-6 (−7.261 kcal/mol), with no significant conformational changes over a 100 ns simulation period. In vitro experiments demonstrated that SA, within the concentration range of 250 μM to 31.25 μM, significantly promoted the proliferation of normal HL-1 cells by an average of 31.0%. Moreover, it enhanced the survival rate of HL-1 cells exposed to 43 °C for 3 h by approximately 59.9% and downregulated the expression of Hsp90 and Hsp70. Additionally, this concentration range of SA reduced the expression of TNF-α, IL-6, TLR2, and COL1A1. Conclusions: These findings offer evidence for the therapeutic potential of SA in HS-induced myocardial damage.

N-glycosylation Modification Reveals Insights into the Oxidative Reactions of Liver in Wuzhishan Pigs

Although porcine liver contributes to their growth and development by nutrition production and energy supply, oxidative stress-induced hepatocyte damage is inevitable during metabolism. N-glycosylation is a common modification in oxidation; nevertheless, the effects of N-glycosylation on pig liver oxidative reactions remain undefined. In this study, liver proteins with N-glycosylation were detected in Wuzhishan (WZS) pigs between 4 and 8 months old and Large White (LW) pigs at 4 months old based on LC-MS/MS. The results showed that the number of differentially expressed proteins (DEPs) was larger between different pig cultivars than that between WZS pigs at various growth periods. The enriched pathways of DEPs were mainly related to oxidative reactions, and 10 proteins were finally selected that primarily consisted of CYPs, GSTs and HSPs with expressions significantly correlating to liver size and weight. The oxidative genes shared N-glycosylation-modified models of N-x-S and N-G. Five out of 10 proteins were upregulated in WZS pigs compared to LW pigs at 4 months old, while five proteins increased in WZS pigs from 4 to 8 months old. In conclusion, this research provides valuable information on the N-glycosylation motifs in liver oxidation genes of WZS pigs.

Protective effect of apelin-13 in lens epithelial cells via inhibiting oxidative stress-induced apoptosis

BackgroundIt is widely accepted that glaucoma-induced oxidative stress expedites cataracts’ process. Therefore, we examined the effects of apelin-13 against oxidative stress-induced damage in human lens epithelial cells (HLECs) and investigated the potential pathogenic mechanism of acute primary angle-closure glaucoma.MethodsThis experiment included five groups: control, H2O2, apelin-13 + H2O2, ML221 + H2O2, and apelin-13 + ML221 + H2O2. ML221 was employed in rescue experiments as an APJ antagonist. HLECs were pretreated with or without apelin-13 and subsequently exposed to H2O2. HLECs’ viability was assessed by CCK8. Cell apoptosis was determined using Annexin V-FITC/PI staining. The mitochondrial membrane potential was assessed by fluorescent probe JC-1. Intracellular G6PD activity, NADPH/NADP+, and GSH/GSSG ratios were detected to assess the cells’ oxidative damage.ResultApelin-13 reversed the H2O2-induced decrease in cell viability. The increased expression of G6PD and GLTU1, the G6PD, GSH/GSSG and NADPH/NADP + levels showed that apelin-13 can mitigate the H2O2-induced inhibition of the pentose phosphate pathway and dysregulation of cell redox status in the apelin-13 + H2O2 group compared with the H2O2 group. In H2O2-treated HLECs, apelin-13 can mitigate cell apoptosis, promote Bcl-2 expression, and suppress the Bax and Caspase-3 expression. In addition, H2O2 substantially reduced the mitochondrial membrane potential in HLECs, which was reversed by apelin-13. Notably, the inhibition of APJ intensified oxidative damage in H2O2-induced HLECs, demonstrating that the effects of apelin-13 were hindered by ML221.ConclutionsApelin-13 reduced oxidative damage and apoptosis in HLECs through APJ. These results demonstrate that apelin-13 can be employed as a potential drug for glaucoma with cataracts to delay the progression of cataracts.

Rivaroxaban as a protector of Oxidative Stress-induced Vascular Endothelial Glycocalyx Damage via The IQGAP1/PAR1-2/PI3K/Akt Pathway.

The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a FXa inhibitor, on the glycocalyx under oxidative stress condition. We examined the impact of rivaroxaban on human umbilical vein endothelial cells (HUVECs) exposed to acute and chronic H₂O₂-induced oxidative stress. Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/ phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx. We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention.

Pickering Emulsion of Curcumin Stabilized by Cellulose Nanocrystals/Chitosan Oligosaccharide: Effect in Promoting Wound Healing

Background: The stabilization of droplets in Pickering emulsions using solid particles has garnered significant attention through various methods. Cellulose and chitin derivatives in nature offer a sustainable source of Pickering emulsion stabilizers. Methods: In this study, medium-chain triglycerides were used as the oil phase for the preparation of emulsion. This study explores the potential of cellulose nanocrystals (CNC) and shell oligosaccharides (COS) as effective stabilizers for achieving stable Pickering emulsions. Optical microscopy, CLSM, and Cyro-SEM were employed to analyze CNC/COS–Cur, revealing the formation of bright and uniform yellow spherical emulsions. Results: CLSM and SEM results confirmed that CNC/COS formed a continuous and compact shell at the oil–water interface layer, enabling a stable 2~3 microns Pickering emulsion with CNS/COS–Cur as an oil-in-water emulsion stabilizer. Based on FTIR, XRD, and SEM analyses of CNC/COS, along with zeta potential measurements of the emulsion, we found that CNC and COS complexed via electrostatic adsorption, forming irregular rods measuring approximately 200–300 nm in length. An evaluation of the DPPH radical-scavenging ability demonstrated that the CNC/ COS–Cur Pickering emulsion performed well in vitro. In vivo experiments involving full-thickness skin excision surgery in rats revealed that CNC/COS–Cur facilitated wound repair processes. Measurements of the MDA and SOD content in healing tissues indicated that the CNC/COS–Cur Pickering emulsion increased SOD levels and reduced MDA content, effectively countering oxidative stress-induced damage. An assessment based on wound-healing rates and histopathological examination showed that CNC/COS-Cur promoted granulation tissue formation, fibroblast proliferation, angiogenesis, and an accelerated re-epithelialization process within the wound tissue, leading to enhanced collagen deposition and facilitating rapid wound-healing capabilities. An antibacterial efficacy assessment conducted in vitro demonstrated antibacterial activity.

The Acetylated 2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-Glucoside Improved Pharmacokinetics and Enhanced Anti-Osteoporosis Effects

Background: Osteoporosis has emerged as a significant global public health concern, predominantly affecting postmenopausal women. Its pathogenesis is intricate and the disease course is protracted, imposing substantial medical burden on both society and individuals. Objective: To investigate the effects of 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside (TSG) and acetylated-TSG (Ac-TSG) on osteoblast viability, in vivo pharmacokinetics in rats and anti-osteoporotic effects in ovariectomized rat model. Methods: Ac-TSG was obtained by acetylation of TSG, and the purity and structure of Ac-TSG were determined by HPLC and 1H NMR. The effects of TSG and Ac-TSG on MC3T3-E1 cell viability, pharmacokinetics in rats, blood biochemical indexes of OVX model rats were detected. Hematoxylin–eosin (HE) staining was used to observe bone tissue morphology, tartrate-resistant acid phosphatase (TRAP) staining was used to observe osteoclast morphology, micro-CT was used to perform three-dimensional reconstruction of femur, and femur parameters were analyzed. Results: The structure of the compound is Ac-TSG and the purity is more than 98%. Both TSG and Ac-TSG could reduce the damage of oxidative stress to MC3T3-E1 cells and effectively improve the levels of Ca, P, ALP and BGP in serum of OVX rats. Compared with TSG, Ac-TSG has a longer action time in vivo and can improve the femoral structure, the number of trabecular bone and the number of osteoclasts in rats. Conclusion: Ac-TSG conferred protection to MC3T3-E1 cells against oxidative stress-induced damage and enhanced their bioavailability. Simultaneously, Ac-TSG ameliorated abnormal bone metabolism and mitigated bone microstructural changes in OVX rats, exhibiting a protective effect against osteoporosis.

An Innovative Approach: Alleviating Cadmium Toxicity in Grapevine Seedlings Using Smoke Solution Derived from the Burning of Vineyard Pruning Waste.

Although plant-derived smoke solutions (SSs) have exhibited growth-promoting properties in various plant species, their potential role in mitigating heavy metal stress, specifically in grapevines, has remained unexplored and unreported. This knowledge gap prompted the present study to evaluate the efficacy of foliar application of SSs derived from vineyard pruning waste at concentrations of 0%, 0.5%, 1%, and 2% in mitigating Cadmium (Cd) phytotoxicity in grape saplings. In our study, cadmium stress was induced by applying 10 mg/kg CdCl2 to the root area of the saplings, in conjunction with fertilizers. Our findings showed that exposure to Cd toxicity impeded the growth of grapevine saplings, adversely affecting shoot and root length, as well as fresh weight. Furthermore, it resulted in a reduction in chlorophyll content, stomatal conductance, and leaf water content while significantly increasing membrane damage and lipid peroxidation. Notably, the application of 0.5% SS enhanced grapevine sapling growth and alleviated Cd stress-induced damage by more effectively regulating physiological and biochemical responses compared to the control and other concentrations. Based on our results, under Cd stress conditions, the application of 0.5% SS effectively increased chlorophyll content, relative water content (RWC), stomatal conductance (1.79 mmol.m-2.sn-1), and total phenolic content (1.89 mg.g-1), whereas it significantly reduced malondialdehyde (MDA) levels and membrane damage (1.35 nmol.g-1). Additionally, it significantly elevated the activities of antioxidant enzymes, including superoxide dismutase (SOD) (2.16 U.mg-1), catalase (CAT) (1.55 U.mg-1), and ascorbate peroxidase (APX) (3.03 U.mg-1). The study demonstrated that plant-derived SS mitigates Cd stress in grapevines by enhancing antioxidative defence mechanisms.

Bioactive proteins and antioxidant peptides from Litsea cubeba fruit meal: Preparation, characterization and ameliorating function on high-fat diet-induced NAFLD through regulating lipid metabolism, oxidative stress and inflammatory response

Non-alcoholic fatty liver disease (NAFLD) plays an increasingly significant threat to human health. In this study, the processing by-products of Litsea cubeba fruit meal were defatted by ultrasound-assisted methods, then the acetone-precipitated protein of L. cubeba (LCP) was obtained and structural analysis was performed. LCP was hydrolyzed by a two-step sequential hydrolysis method using alcalase and papain. Subsequently, antioxidant peptide fraction (IV2) was isolated and identified from the resultant hydrolysate through membrane ultrafiltration, Sephadex G-15 chromatography, and liquid chromatograph mass spectrometer (LC-MS). Animal experimentation indicated the potential of IV2 to mitigate hepatic steatosis. Moreover, IV2 could effectively reduce oxidative stress-induced damage by modulating the Keap1-Nrf2 pathway to activate downstream heme oxygenase-1 (HO-1) and NAD(P) H quinone oxidoreductase 1 (NQO1). Integrating metabolomics and transcriptomics revealed enrichment in pathways associated with glycerolipid metabolism and fatty acid β-oxidation, suggesting the principal mechanisms underlying IV2's ameliorative effects on NAFLD. Transcriptome sequencing identified 3092 up-regulated and 3010 down-regulated genes following IV2 treatment. Interaction analyses based on different lipid compositions (DELs) and differentially expressed genes (DEGs) indicated that IV2 primarily alleviated hepatic steatosis by modulating peroxisome proliferator-activated receptor α (PPAR-α) related pathways, thereby augmenting fatty acid β-oxidation within liver cells. These results indicate that IV2 shows potential in improving high-fat diet (HFD)-induced NAFLD, with improved fatty acid β-oxidation and reduced triglyceride biosynthesis emerging as underlying mechanisms.

Monitoring stress-induced brittle rock mass damage for preventative support maintenance

Stress-induced brittle fracturing near an excavation boundary results in a volume increase, known as bulking. Excessive bulking places added demand on the rock support, which, if not detected and addressed through preventative support maintenance (i.e., proactively added reinforcement), can cause the support to fail, leading to a safety hazard and costly production delays for underground mining operations. For caving mines, these project risks are exacerbated during cave establishment due to the large abutment stress from undercutting that redistributes and concentrates stresses near excavations critical for production. This paper reports the findings from research conducted to develop and improve geotechnical monitoring practices to support preventative support maintenance in deep mining operations. This research uses a unique geotechnical monitoring database collected for the Deep Mill Level Zone panel cave mine. The data was collected across a large footprint during the mine's ramp-up period and represents an initial step toward best practices for data collection at cave mines operating in high-stress environments. Borehole camera surveys supplemented by multi-point borehole extensometers have been used to determine the depth of stress fracturing in pillar walls as a function of the distance away from the undercut. Convergence measurements and LiDAR scanning are used to characterize the corresponding rock mass bulking. The results show that the interpretation of monitoring data can be used to identify the long-term depth of stress fracturing and bulking trends in response to undercut advances. These show that direct measures of stress-induced fracturing damage provide an early indication of excavations vulnerable to bulking and that LiDAR scanning is an effective method for capturing the onset of bulking and anticipating local areas likely to experience greater deformation demand as bulking progresses. Proactive and strategic geotechnical monitoring based on the long-term depth of stress-induced fracturing trends is proposed to assist with preventative support maintenance practices.

GdVO4:Eu3+ and LaVO4:Eu3+ Nanoparticles Exacerbate Oxidative Stress in L929 Cells: Potential Implications for Cancer Therapy.

The therapeutic potential of redox-active nanoscale materials as antioxidant- or reactive oxygen species (ROS)-inducing agents was intensely studied. Herein, we demonstrate that the synthesized and characterized GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles, which have been already shown to have redox-active, anti-inflammatory, antibacterial, and wound healing properties, both in vitro and in vivo, worsen oxidative stress of L929 cells triggered by hydrogen peroxide or tert-butyl hydroperoxide (tBuOOH) at the concentrations that are safe for intact L929 cells. This effect was observed upon internalization of the investigated nanosized materials and is associated with the cleavage of caspase-3 and caspase-9 without recruitment of caspase-8. Such changes in the caspase cascade indicate activation of the intrinsic caspase-9-dependent mitochondrial but not the extrinsic death, receptor-mediated, and caspase-8-dependent apoptotic pathway. The GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticle-induced apoptosis of oxidatively compromised L929 cells is mediated by ROS overgeneration, Ca2+ overload, endoplasmic reticulum stress-associated JNK (c-Jun N-terminal kinase), and DNA damage-inducible transcript 3 (DDIT3). Our findings demonstrate that GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles aggravate the oxidative stress-induced damage to L929 cells, indicating that they might potentially be applied as anti-cancer agents.

Activation of protein kinase B rescues against thapsigargin-elicited cardiac dysfunction through regulation of NADPH oxidase and ferroptosis

Endoplasmic reticulum (ER) stress is a known contributor to cardiac remodeling and contractile dysfunction. Although NADPH oxidase has been implicated in ER stress-induced organ damage, its specific role in myocardial complications resulting from ER stress remains unclear. This study aimed to investigate the possible involvement of NADPH oxidase in ER stress-induced myocardial abnormalities and to evaluate the impact of Akt constitutive activation on these myocardial defects. Mice with cardiac-specific overexpression of active mutant of Akt (Myr-Akt) and their wild-type (WT) littermates were treated with ER stress instigator thapsigargin (1 mg/kg, i. p. 72 hrs) before evaluating myocardial morphology and function. Our results noted that thapsigargin significantly impaired echocardiographic parameters and cell shortening indices, including elevated LVESD, decreased ejection fraction, fractional shortening, peak shortening, electrically-stimulated intracellular Ca2+ release, and cardiomyocyte survival. These functional deteriorations were accompanied by upregulation of NADPH oxidase, O2− production, mitochondrial damage, carbonyl formation, lipid peroxidation, apoptosis, and interstitial fibrosis, with unchanged myocardial size. Constitutive Akt hyperactivation did not generate any response on myocardial morphology and function, although it greatly suppressed or nullified thapsigargin-induced myocardial remodeling and dysfunction. Thapsigargin also triggered dephosphorylation of Akt and its downstream signal GSK3β, along with development of ferroptosis, all of which were nullified by Akt hyperactivation. In vitro studies further revealed that thapsigargin provoked cardiomyocyte mechanical anomalies and lipid peroxidation, similar to in vivo results. These effects were reverted by inhibitors of NADPH oxidase and ferroptosis (apocynin and LIP1). Collectively, our data denote an important protective role for Akt hyperactivation in thapsigargin-evoked myocardial anomalies, likely through NADPH oxidase-mediated regulation of ferroptosis.

Alda-1 Ameliorates Oxidative Stress-Induced Cardiomyocyte Damage by Inhibiting the Mitochondrial ROS/TXNIP/NLRP3 Pathway.

Alda-1 functions as an agonist of aldehyde dehydrogenase (ALDH2) within the mitochondria, contributing to the preservation of mitochondrial structure and function. This study aimed to determine whether Alda-1 inhibited the accumulation of mitochondrial reactive oxygen species (mtROS) and improved cardiomyocyte damage under oxidative stress. Cardiomyocytes derived from human induced pluripotent embryonic stem cells (iPSC-CMs) and human AC16 cardiomyocytes were chosen for the experiments. Oxidative stress was induced in both cardiomyocyte types using hydrogen peroxide (H2O2), a commonly employed agent. The mtROS accumulation and mitochondrial functional status were assessed by measuring the ROS content, mitochondrial membrane potential, and mitochondrial respiratory chain function. Co-IP experiments were used to analyze whether mtROS promoted protein interactions between TXNIP and NLRP3 and induced NLRP3 inflammasome activation. The results showed that Alda-1 mitigated damage to mitochondrial structure and function under oxidative stress, concurrently reducing the accumulation of mtROS. Co-IP experiments revealed that elevated mtROS levels attenuated the protein interaction between TXNIP and TRX while intensifying the interaction between TXNIP and NLRP3. Consequently, this triggers activation of the NLRP3 inflammasome, leading to cardiomyocyte damage. In contrast, TXNIP knockdown inhibited H2O2-induced myocardial injury and enhanced the therapeutic effects of Alda-1. Collectively, the results show that, in an H2O2 environment, Alda-1 increased the production of ALDH2 activity in cardiomyocytes, hindered the production of mtROS, disrupted the interaction between TXNIP and NLRP3, and alleviated myocardial damage during oxidative stress.

Camel Whey Protein Attenuates Acute Heat Stress-Induced Kidney Injury in Rats by Up-Regulating CYP2J Activity and Activating PI3K/AKT/eNOS to Inhibit Oxidative Stress

Camel whey protein (CWP) is a potent natural antioxidant, noted for its abundance of antioxidant amino acids. Despite its promising properties, the precise mechanisms underlying its effects remain inadequately explored. This study aims to investigate the impact of CWP on kidney damage induced by acute heat stress in rats, as well as to elucidate its mechanism of action. We assessed CWP’s influence on cytochrome P450 2J (CYP2J) activity during heat stress, measured oxidative stress levels, and evaluated renal injury using CYP2J knockout rats. Our findings indicate that acute heat stress reduces CYP2J expression, while CWP administration restores CYP2J activity and enhances PI3K/Akt signaling. However, CWP did not mitigate oxidative stress-induced kidney damage in CYP2J−/− rats, suggesting the necessity of CYP2J for its protective effects.

Spraying KH2PO4 Alleviates the Damage of Spring Low-Temperature Stress by Improving the Physiological Characteristics of Wheat Flag Leaves.

The low-temperature stress (LTS) in spring results in tremendous yield loss in wheat production, and the application of potassium dihydrogen phosphate (KH2PO4) can alleviate stress-induced damage. However, the underlying effect of spraying KH2PO4 on the physiological characteristics of wheat flag leaves under spring LTS remains unclear. In this study, we investigated the effect of spraying KH2PO4 on flag leaf physiological traits and yield under spring LTS, including treatments at 15 °C and spraying H2O (CK), treatment at -4 °C and spraying H2O (LT1), and treatment at -4 °C and spraying KH2PO4 (LT2). The results showed that spraying KH2PO4 significantly increased the activities of the superoxide dismutase (SOD), the peroxidase (POD), and the catalase (CAT), and reduced malondialdehyde (MDA) content in the flag leaves. Compared to LT1, the SOD, POD, and CAT activities in the flag leaves of the Yangnong19 (YN19) and Xinmai26 (XM26) via LT2 increased by 5.5%, 10.9%, and 3.9%, and 5.4%, 9.2%, and 4.4%, respectively, and the MDA content of the YN19 and XM26 decreased by 10.5% and 9.1%, respectively, at 0-12 d after low temperature treatment (DALTT). Spraying KH2PO4 appreciably alleviated damage to the leaf cell morphology and tissue integrity, and increased the accumulation of proline and soluble protein, the chlorophyll content, and the activities of Ribulose-1,5-bisphosphate carboxylase and phosphoenolpyruvate carboxykinase. The net photosynthetic rate in the flag leaves of the YN19 and XM26 via LT2 increased by 37.9% and 35.9%, respectively, at 0-12 DALTT, compared to LT1. Moreover, spraying KH2PO4 reduced the yield loss rate of the YN19 and XM26 by 13.06% and 16.72%, respectively. The present study demonstrates that spraying KH2PO4 can enhance wheat resistance to spring LTS and maintain the photosynthetic capacity of flag leaves, alleviating the negative effects of LTS on grain yield.

Nanozyme Hydrogels Promote Nerve Regeneration in Spinal Cord Injury by Reducing Oxidative Stress.

Inhibiting secondary cell death and promoting neuronal regeneration are critical for nerve repair after spinal cord injury (SCI). The excessive accumulation of reactive oxygen species (ROS) after SCI causes cell death and induces apoptosis. These reactions further increase the level of ROS production, leading to a vicious cycle of spinal cord tissue damage. Therefore, intervention targeting ROS is a potential therapeutic approach to improve the recovery of locomotor function after SCI. In this study, we designed and synthesized a nanozyme hydrogel delivery system loaded with multiple drugs, LA/Me/Se NPs-h. LA/Me/Se NPs-h exhibited a satisfactory size distribution and excellent stability, enhancing the bioavailability of therapeutic drugs. Moreover, we explored the antioxidant and protective effects of LA/Me/Se NPs-h against oxidative stress-induced cell damage caused by ROS production after SCI in vitro. In the mice SCI model, the Basso mouse scale and gait analysis showed that LA/Me/Se NPs-h significantly promoted the recovery of locomotor function after SCI. The histological and immunofluorescence results of the injury site revealed that LA/Me/Se NPs-h upregulated the expression of GFAP, NF-200, and superoxide dismutase in spinal cord lesion, reduced caspase-3 expression, improved spinal cord continuity, reduced lesion cavity, and inhibited the axonal demyelination. Consequently, LA/Me/Se NPs-h increased the activity of antioxidant enzymes and reduced neuronal apoptosis by reducing oxidative stress and ultimately promoted nerve regeneration. Taken together, this study demonstrated promising nanozyme hydrogels and provided an effective therapeutic strategy for SCI and other ROS-related diseases.

IKKα affects the susceptibility of primary human osteoarthritis chondrocytes to oxidative stress-induced DNA damage by tuning autophagy

The functional derangement affecting human chondrocytes during osteoarthritis (OA) onset and progression is sustained by the failure of major homeostatic mechanisms. This makes them more susceptible to oxidative stress (OS), which can induce DNA damage responses and exacerbate stress-induced senescence. The knockdown (KD) of IκB kinase α (IKKα), a dispensable protein in healthy articular cartilage physiology, was shown to increase the survival and replication potential of human primary OA chondrocytes. Our recent findings showed that the DNA Mismatch Repair pathway only partially accounts for the reduced susceptibility to OS of IKKαKD cells. Here we therefore investigated other ROS-mediated DNA damage and repair mechanisms. We exposed IKKαWT and IKKαKD chondrocytes to sub-cytotoxic hydrogen peroxide and evaluated the occurrence of double-strand breaks (DSB), 8-oxo-2′-deoxyguanosine (8-oxo-dG) and telomere shortening. ROS exposure was able to significantly increase the number of γH2AX foci (directly related to the number of DSB) in both cell types, but IKKα deficient cells undergoing cell division were able to better recover compared to their IKKα proficient counterpart. 8-oxo-dG signal proved to be the highest DNA damage signal among those investigated, located in the mitochondria and with a slightly higher intensity in IKKα proficient cells immediately after OS exposure. Furthermore, ROS significantly reduced telomere length both in IKKαWT and IKKαKD, with the former showing more pervasive effects, especially in dividing cells. Assessment of the HIF-1α>Beclin-1>LC3B axis after recovery from OS showed that IKKα deficient cells exhibited a more efficient autophagic machinery that allowed them to better cope with oxidative stress, possibly through the turnover of damaged mitochondria. Higher Beclin-1 levels likely helped in rescuing dividing cells (identified by coupled cell cycle analysis) because of Beclin-1's involvement in both autophagy and mitotic spindle organization. Therefore, our data further confirm the higher capacity of IKKαKD chondrocytes to cope with oxidative stress-induced DNA damage.

The Protective Effects of Polygala tenuifolia and Tenuifolin on Corticosterone-Evoked Ferroptosis, Oxidative Stress, and Neuroinflammation: Insights from Molecular Dynamics Simulations and In Vitro Experiments.

Excessive stress is a well-established contributor to neurological damage, insomnia, and depression, imposing a significant burden on individuals and society. This underscores the urgent need for effective stress-relief strategies. The main purpose of this study was to explore the protective effects of Polygala tenuifolia (PT) and its bioactive compound, tenuifolin, against corticosterone-induced neurotoxicity, with a focus on ferroptosis, oxidative stress, and neuroinflammation. Both PT extracts and tenuifolin mitigated corticosterone-induced cellular damage. Tenuifolin reversed the corticosterone-induced dysregulation of ferroptosis-associated proteins, such as SLC7A11, GPX4, and Nrf2, leading to a marked reduction in ferroptosis levels. Molecular dynamics simulations revealed that corticosterone significantly altered the conformation and binding energy of the SLC7A11/SLC3A2 complex, critical for ferroptosis regulation. These changes were reversed by tenuifolin. Additionally, tenuifolin alleviated corticosterone-induced oxidative stress and neuroinflammation, both of which accelerated ferroptosis. In conclusion, these results indicate that tenuifolin attenuates corticosterone-induced neurotoxicity by modulating ferroptosis, oxidative stress, and neuroinflammation. This study provides a theoretical foundation for the application of PT and tenuifolin in stress-induced nerve damage.

Acyclic sesquiterpenes nerolidol and farnesol: mechanistic insights into their neuroprotective potential.

Sesquiterpenes are a class of organic compounds found in plants, fungi, and some insects. They are characterized by the presence of three isoprene units, resulting in a molecular formula that typically contains 15 carbon atoms (C₁₅H₂₄). Nerolidol and farnesol are both sesquiterpene alcohols present in the essential oils of numerous plants. They have drawn attention due to their potential neuroprotective properties. Nerolidol and farnesol are structural isomers, specifically geometric isomers, haring the same molecular formula (C₁₅H₂₄O) but differing in the spatial arrangement of their atoms. This variation in structure may contribute to their distinct biological activities. Scientific evidence suggests that nerolidol and farnesol exhibit antioxidant and anti-inflammatory characteristics which are crucial for neuroprotection. Nerolidol has been specifically noted for its ability to alleviate conditions such as Alzheimer's disease, Parkinson's disease, encephalomyelitis, depression, and anxiety by modulating inflammatory and oxidative stress pathways. Moreover, research indicates that both nerolidol and farnesol may modulate the Nrf-2/HO-1 antioxidant signaling pathway to mitigate oxidative stress-induced neurological damage. Activation of Nrf-2/HO-1 signaling cascade promotes cell survival and enhances the brain's ability to resist various insults. Nerolidol has also been reported to alleviate neuroinflammation by inhibiting the TLR-4/NF-κB and COX-2/NF-κB inflammatory signaling pathway. Besides, this nerolidol also modulates BDNF/TrkB/CREB signaling pathway to improve neuronal health. To date, limited research has delved into the anti-inflammatory properties of farnesol concerning neurodegenerative diseases. Further investigation is warranted to comprehensively elucidate the mechanisms underlying its action and potential therapeutic uses in neuroprotection. Initial observations indicate that farnesol exhibits promising prospects as a natural agent for safeguarding brain functions. Henceforth, drawing upon existing literature elucidating the neuroprotective attributes of nerolidol and farnesol, the current review endeavors to provide a detailed analysis of their mechanistic underpinnings in neuroprotection.