Stress-induced Damage Research Articles

Neuroprotective Effects of STAT3 Inhibitor on Hydrogen Peroxide-Induced Neuronal Cell Death via the ERK/CREB Signaling Pathway

This study investigates the neuroprotective potential of STAT3 inhibition in reducing oxidative stress-induced neuronal damage and apoptosis, a major factor contributing to the onset and progression of neurodegenerative diseases, including Alzheimer’s disease (AD). Our findings demonstrate that STAT3 inhibitors significantly enhance cell survival and reduce apoptosis in SH-SY5Y cells exposed to hydrogen peroxide. These protective effects are mediated through the ERK/CREB signaling pathway rather than direct suppression of STAT3 phosphorylation. Further analysis revealed that the ERK pathway is a critical mediator of CREB activation following STAT3 inhibition. The protective effects of STAT3 inhibitors were significantly reduced in the presence of the ERK inhibitor PD98059, underscoring the importance of the ERK/CREB axis in neuroprotection. We observed that STAT3 inhibitors promote CREB phosphorylation, leading to the upregulation of immediate early genes such as c-Fos, c-Jun, Arc, Egr-1, NR4A1, and Homer1a, as well as BDNF. These genes are crucial for synaptic plasticity and long-term memory formation, suggesting that STAT3 inhibition may ameliorate cognitive impairments in neurodegenerative conditions. Our results highlight the potential of STAT3 inhibitors to counteract oxidative stress and enhance cognitive functions by modulating the ERK/CREB signaling pathway. These findings provide valuable insights into the molecular mechanisms of STAT3 inhibition and support its therapeutic potential for treating neurodegenerative diseases.

Carnosic acid prevents heat stress-induced oxidative damage by regulating heat-shock proteins and apoptotic proteins in mouse testis.

Heat stress impacts male reproduction in animal husbandry. Carnosic acid (CA), a potent antioxidant, mitigates oxidative stress and apoptosis. αB-crystallin, a small heat shock protein, regulates apoptosis and oxidative stress. This study examines the protective effects of CA on the testis in wild-type and αB-crystallin knockout mice under heat stress. CA pretreatment increased testosterone levels and preserved testicular structure in wild-type mice, but no changes in knockout mice. CA reduced Hsp27, Hsp70, and cleaved caspase-3 levels, while knockout mice showed increased cleaved caspase-3. These results suggest that CA protects the testis by modulating heat shock and apoptosis-related proteins.

ROS-Induced Gingival Fibroblast Senescence: Implications in Exacerbating Inflammatory Responses in Periodontal Disease.

Periodontal disease is the pathological outcome of the overwhelming inflammation in periodontal tissue. Cellular senescence has been associated with chronic inflammation in several diseases. However, the role of cellular senescence in the pathogenesis of periodontal disease remained unclear. This study aimed to investigate the role and the mechanism of cellular senescence in periodontal disease. Using single-cell RNA sequencing, we first found the upregulated level of cellular senescence in fibroblasts and endothelial cells from inflamed gingival tissue. Subsequently, human gingival fibroblasts isolated from healthy and inflamed gingival tissues were labeled as H-GFs and I-GFs, respectively. Compared to H-GFs, I-GFs exhibited a distinct cellular senescence phenotype, including an increased proportion of senescence-associated β-galactosidase (SA-β-gal) positive cells, enlarged cell morphology, and significant upregulation of p16INK4A expression. We further observed increased cellular reactive oxygen species (ROS) activity, mitochondrial ROS, and DNA damage of I-GFs. These phenotypes could be reversed by ROS scavenger NAC, which suggested the cause of cellular senescence in I-GFs. The migration and proliferation assay showed the decreased activity of I-GFs while the gene expression of senescence-associated secretory phenotype (SASP) factors such as IL-1β, IL-6, TGF-β, and IL-8 was all significantly increased. Finally, we found that supernatants of I-GF culture induced more neutrophil extracellular trap (NET) formation and drove macrophage polarization toward the CD86-positive M1 pro-inflammatory phenotype. Altogether, our findings implicate that, in the inflamed gingiva, human gingival fibroblasts acquire a senescent phenotype due to oxidative stress-induced DNA and mitochondrial damage, which in turn activate neutrophils and macrophages through the secretion of SASP factors.

Trehalose: Neuroprotective Effects and Mechanisms-An Updated Review.

Trehalose is a naturally occurring disaccharide that has recently gained significant attention for its neuroprotective properties in various models of neurodegeneration. This review provides an overview of available experimental data on the beneficial properties of trehalose for central nervous system pathological conditions. Trehalose's impact on neuronal cell survival and function was also examined. As a result, we identified that trehalose's neuroprotection includes autophagy modulation as well as its capability to stabilize proteins and inhibit the formation of misfolded ones. Moreover, trehalose mitigates oxidative stress-induced neuronal damage by stabilizing cellular membranes and modulating mitochondrial function. Furthermore, trehalose attenuates excitotoxicity-induced neuroinflammation by suppressing pro-inflammatory cytokine release and inhibiting inflammasome activation. A possible connection of trehalose with the gut-brain axis was also examined. These findings highlight the potential therapeutic effects of trehalose in neurodegenerative diseases. According to the conclusions drawn from this study, trehalose is a promising neuroprotective agent as a result of its distinct mechanism of action, which makes this compound a candidate for further research and the development of therapeutic strategies to combat neuronal damage and promote neuroprotection in various neurological diseases.

Macrophage Dvl2 Deficiency Promotes NOD1-Driven Pyroptosis and Exacerbates Inflammatory Liver Injury

Dishevelled 2 (Dvl2) is a key mediator of the Wingless/Wnt signaling pathway that regulates cell proliferation, migration, and immune function. However, little is known about the role of macrophage Dvl2 in modulating NOD1-mediated pyroptosis and hepatocyte death in oxidative stress-induced inflammatory liver injury. In a mouse model of oxidative stress-induced liver inflammation, mice with myeloid-specific Dvl2 knockout (Dvl2M-KO) displayed exacerbated ischemia/reperfusion (IR) stress-induced hepatocellular damage with increased serum ALT levels, oxidative stress, and proinflammatory mediators. Unlike in Dvl2FL/FL controls, Dvl2M-KO enhanced NOD1, caspase-1, GSDMD, and NF-κB activation in liver macrophages after IR. Interestingly, IR stress enhanced YAP colocalized with HSF1 in Dvl2FL/FL macrophages, while macrophage Dvl2 deficiency reduced YAP and HSF1 colocalization in the nucleus under inflammatory conditions. Importantly, Dvl2 deletion diminished nuclear YAP interacted with HSF1 and augmented NOD1/caspase-1 and GSDMD activation in response to inflammatory stimulation. However, Dvl2 activation increased YAP interaction with HSF1 and activated HSF1 target gene eEF2, inhibiting NOD1/caspase-1, GSDMD, and NF-κB activity. Moreover, macrophage eEF2 deletion increased the NOD1-caspase-1 interaction, GSDMD activation, HMGB1 release, and hepatocyte LDH release after macrophage/hepatocyte co-culture. Adoptive transfer of eEF2-expressing macrophages in Dvl2M-KO mice alleviated IR-triggered liver inflammation and hepatocellular damage. Therefore, macrophage Dvl2 deficiency promotes NOD1-mediated pyroptosis and exacerbates IR-induced hepatocellular death by disrupting the YAP-HSF1 axis. eEF2 is crucial for modulating NOD1-driven pyroptosis, inflammatory response, and hepatocyte death. Our findings underscore a novel role of macrophage Dvl2 in modulating liver inflammatory injury and imply the therapeutic potential in organ IRI and transplant recipients.

Purification, characterization, and hypoglycemic activity of exopolysaccharides from Lactiplantibacillus plantarum MY04

As natural polymers, Lactiplantibacillus plantarum exopolysaccharides (EPS) possess a wide range of bioactivities but suffer from low yields and unclear relationships between functional activity and structure. To this end, the chemical structure and bioactive properties of EPS from Lactiplantibacillus plantarum MY04 were investigated. As a result, three polysaccharide fractions (EPS-1, EPS-2, EPS-3) were separated and purified, of which EPS-2 had better antioxidant activity and α-glucosidase inhibitory ability. More importantly, EPS-2 can significantly enhance insulin sensitivity in HepG2 cells by upregulating enzyme activities in the glycolytic pathway and mitigating oxidative stress-induced damage. In addition, the structural characterization of EPS-2 was also comprehensively elucidated. It was found that EPS-2 was mainly composed of mannose with a molecular weight of 2.3 × 106 Da, and its main chain structure is →3)-Manp-(1 → 2)-Manp-(1 → 2,6)-Manp-(1 → 2,6)-Manp-(1→, providing a theoretical basis for understanding the relationship between structure and function of polysaccharides.

Allium cepa L. as a natural antioxidant: Its efficacy in combating heat stress-induced physiological alterations

Heat stress (HS) is a major physiological stressor that induces oxidative damage, inflammation, and metabolic disruptions, all of which cause harm to health. This study investigates the potential protective effects of Allium cepa L. (AC), against the physiological alterations brought on by HS. Twenty male rats were utilized in this study and divided into 4 groups: Control, HS, AC, and HS + AC. Rats were exposed to 38–39 °C for 2 h each day for three weeks to induce HS while 1.0 ml/100 g body weight of ethanolic extract of AC was administered orally for three weeks. Hematological parameters, inflammatory markers, and lipid profiles were analyzed using blood samples obtained through heart puncture.The findings demonstrated that HS significantly lowered levels of hemoglobin (HB), red blood cell (RBC) counts, and antioxidant enzyme activity. However, there was a significant rise in the levels of inflammatory markers, platelet counts, LDL-c triglyceride (TG), total cholesterol (TC), and white blood cell (WBC). Many of these alterations were reversed by AC supplementation, by increasing RBC counts, HB levels, and antioxidant enzyme activities while decreasing LDL-c, TG and TC, MDA, and TNF-α (tumor necrosis factor-α). However, the positive benefits of AC were partially diminished in the HS + AC group, perhaps due to the severe oxidative stress caused by heat stress (HS).This study highlights the probable potential of AC as a natural antioxidant in modifying heat stress-induced oxidative damage, hematological changes, and lipid metabolism disruptions; however, its protective effects are insufficient to mitigate heat stress. Therefore, further research is required to explore the other possible underlying mechanisms.

Tumor-Specific Protein Induced in Situ Self-Assembly of Peptide Drugs for Synergistic Mitochondria Disruption.

Mitochondria-targeted cancer therapy is an effective method for controlling tumor growth. However, the presence of repair mechanisms in tumor cells in response to mitochondrial damage poses significant challenges for treatment. By taking advantage of intracellular self-assembly technology, a peptide nanomaterial, RC-K-FX, that enters tumor cells in a monomeric form is designed. After binding to MUC1-C inside the cell membrane, RC-K-FX assembles into a spherical structure that stably encapsulates MUC1-C, inhibiting its dimerization and blocking the repair of stress-induced mitochondrial damage in tumor cells. Moreover, the self-assembled mitochondrial toxic peptide effectively destroys the mitochondria, and the loss of mitochondrial repair significantly increases tumor cytotoxicity by disrupting the redox balance, enhancing reactive oxygen species (ROS), inhibiting the nuclear factor (NF)-κB pathway, and suppressing the epithelial-mesenchymal transition (EMT) process. After intravenous administration, RC-G-FX accumulated at the tumor site, exhibiting improved anti-tumor effects and extending the overall survival of tumor-bearing mice. Therefore, the integration of the in situ self-assembly of peptide drugs and damage to mitochondrial repair mechanisms provides effective therapeutic options for malignancy.

The fork protection complex generates DNA topological stress–induced DNA damage while ensuring full and faithful genome duplication

The fork protection complex (FPC), composed of Mrc1, Tof1, and Csm3, supports rapid and stable DNA replication. Here, we show that FPC activity also introduces DNA damage by increasing DNA topological stress during replication. Mrc1 action increases DNA topological stress during plasmid replication, while Mrc1 or Tof1 activity causes replication stress and DNA damage within topologically constrained regions. We show that the recruitment of Top1 to the fork by Tof1 suppresses the DNA damage generated in these loci. While FPC activity introduces some DNA damage due to increased topological stress, the FPC is also necessary to prevent DNA damage in long replicons across the genome, indicating that the FPC is required for complete and faithful genome duplication. We conclude that FPC regulation must balance ensuring full genome duplication through rapid replication with minimizing the consequential DNA topological stress-induced DNA damage caused by rapid replication through constrained regions.

Brown rice attenuates iron-induced Parkinson's disease phenotypes in male wild-type drosophila: insights into antioxidant and iron metabolism modulation.

Parkinson's disease (PD) is a progressive movement disorder associated with brain iron (Fe) accumulation and free radicals. Brown rice (BR) is antioxidant-rich and has been shown to ameliorate oxidative stress-induced damage. The aim of this study was to investigate the effects of BR compared to white rice (WR) on Fe-induced PD in a fruit fly model. Three-day-old male adult flies were divided into two groups: one on a normal diet and the other on Fe-diet (1 mmol/L) for 10 days to induce PD. After 10 days, the Fe-fed flies were redistributed into four groups: one on normal diet (Fe group), while the others were treated with BR (Fe+BR group), WR (Fe+WR group), or L-3,4-dihydroxyphenylalanine (L-dopa) (Fe+L-dopa group) for 5 days. Similarly, the flies initially on a normal diet were separated into four groups: one on normal diet (Control group), while the others were treated with BR (BR group), WR (WR group), or L-dopa (L-dopa group) for 5 days. Finally, Fe levels, dopamine, malonaldehyde (MDA), and antioxidant enzymes were measured, and the mRNA levels of antioxidant and Fe metabolism genes were assessed. BR significantly improved motor and cognitive functions, decreased fly head MDA and Fe levels, and increased antioxidant enzyme levels in comparison to the Fe and WR groups. Similarly, BR upregulated the mRNA levels of antioxidant genes: catalase, GPx, Nrf2, and DJ-1. The results suggest that BR could potentially reduce morbidities associated with PD possibly due to its bioactive compounds compared to WR.

An In Vitro Oxidative Stress Model of the Human Inner Ear Using Human-Induced Pluripotent Stem Cell-Derived Otic Progenitor Cells.

The inner ear organs responsible for hearing (cochlea) and balance (vestibular system) are susceptible to oxidative stress due to the high metabolic demands of their sensorineural cells. Oxidative stress-induced damage to these cells can cause hearing loss or vestibular dysfunction, yet the precise mechanisms remain unclear due to the limitations of animal models and challenges of obtaining living human inner ear tissue. Therefore, we developed an in vitro oxidative stress model of the pre-natal human inner ear using otic progenitor cells (OPCs) derived from human-induced pluripotent stem cells (hiPSCs). OPCs, hiPSCs, and HeLa cells were exposed to hydrogen peroxide or ototoxic drugs (gentamicin and cisplatin) that induce oxidative stress to evaluate subsequent cell viability, cell death, reactive oxygen species (ROS) production, mitochondrial activity, and apoptosis (caspase 3/7 activity). Dose-dependent reductions in OPC cell viability were observed post-exposure, demonstrating their vulnerability to oxidative stress. Notably, gentamicin exposure induced ROS production and cell death in OPCs, but not hiPSCs or HeLa cells. This OPC-based human model effectively simulates oxidative stress conditions in the human inner ear and may be useful for modeling the impact of ototoxicity during early pregnancy or evaluating therapies to prevent cytotoxicity.

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.

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.

Antioxidant activity of soybean peptides and Keap1 protein: A combined in vitro and in silico analysis

Antioxidant peptides can be obtained from diverse dietary protein sources with high safety. The Kelch-like ECH-associated protein 1(Keap1) is a key protein in the cellular oxidative stress signaling pathway and it plays an important role in the field of antioxidant. Soybeans are a vital source for the production of bioactive peptides. In this study, firstly, we screened 468 antioxidant peptides from soybean protein with low molecular weight, high hydrophobicity and non-toxicity. The top three antioxidant peptides were isolated and extracted from the fractions using UHPLC-QQQ/MS analysis. The free radical scavenging rate demonstrated significant antioxidant activity of PHHADS (EC50 = 4.26 mmol/L). In addition, peptide PHHADS was demonstrated significantly protects HepG2 cells from oxidative stress-induced damage. Lastly, 200 ns molecular dynamics simulations were performed between the peptides and Keap1. The results revealed that PHHADS closely interacts with the active site of Keap1. Moreover, the interaction of the antioxidant peptides with Keap1 led to the disruption of the β-sheet structure of Keap1 in residues380-390, transforming into an irregularly curved structure. This particular region in Keap1 is crucial for substrates binding, suggesting a potential inhibitory mechanism by the peptides. These findings contribute to the understanding of antioxidant peptide interactions and their potential application in developing functional foods for health benefits.

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.