Decreased Reactive Oxygen Species Levels Research Articles

Effect of zinc on sperm recovered by swim-up.

Zinc is known to influence chromatin stability, motility and protection against oxidative stress. While swim-up remains the preferred method for selecting sperm in Assisted Reproductive Technologies (ART), concerns arise regarding sperm DNA fragmentation associated with this procedure. Given zinc's significant role in protecting sperm DNA integrity and motility, we aimed to investigate the impact of zinc supplementation during the swim-up process on sperm quality. Semen samples from 203 normozoospermic men were used. Samples were divided into fractions and swim-up procedure was applied using human tubal fluid (mHTF) supplemented with three different concentrations of zinc or medium without supplementation as control. DNA fragmentation, chromatin maturity, reactive oxygen species (ROS) levels, motility and protein phosphorylation levels analyses were addressed to each fraction. The sperm DNA fragmentation was reduced in sperm recovered by swim-up in media with all concentrations of zinc assayed with respect to the control (p < 0.0001). Aniline blue staining showed better chromatin maturity in sperm recovered with 2.5- and 3.5-mM zinc (p = 0.045; p = 0.021). Kinematic parameters such as curvilinear velocity and beat-cross frequency showed improvement with 2.5mM zinc (p = 0.0080 and p = 0.0400), whereas straightness, linearity, and hypermotility showed improvement with 5mM zinc (p = 0.0075, p = 0.0069, and p = 0.0244). Protein phosphorylation patterns showed changes associated with treatment with zinc, and only 5mM zinc treatment showed a decrease in ROS levels. The addition of zinc to mHTF provided optimal physiological conditions for sperm recovered through swim-up. This supplementation should be considered for selecting sperm for use in ART.

Upregulation of CD244 promotes CD8+ T cell exhaustion in patients with alveolar echinococcosis and a murine model

BackgroundIn patients with alveolar echinococcosis (AE), CD8+ T cells undergo functional exhaustion, which accelerates the malignant progression of AE. However, the role of inhibitory receptor CD244 in mediating CD8+ T cell exhaustion remains elusive.MethodsCD244 expression on exhausted CD8+ T cells in the close liver tissue (CLT) of AE patients was analyzed using single-cell RNA sequencing data. Immunohistochemistry and immunofluorescence were employed to detect CD244 expression. Flow cytometry was used to assess the impact of CD244 on differentiation and effector function of CD8+ T cells in patients with AE, in vitro and in vivo models. Reactive oxygen species (ROS) and oxygen consumption rate (OCR) were measured to evaluate the influence of CD244 on mitochondrial function of CD8+ T cells.ResultsCD244+CD8+ T cells in the CLT of AE patients exhibit a more terminal differentiation phenotype, with reduced secretion of IFN-γ and TNF-α. In vitro studies revealed that CD8+ T cells from CD244-deficient mice produced higher levels of IFN-γ, TNF-α and Granzyme B. In vivo studies revealed that CD244 deficiency enhanced the secretion capacity of IFN-γ and TNF-α by CD8+ T cells, inhibiting the growth of metacestodes. Moreover, CD244 deficiency leads to a decrease in ROS levels in liver CD8+ T cells, while significantly increasing their adenosine triphosphate (ATP)-linked oxygen consumption rate.ConclusionsCD244 facilitates AE disease progression by mediating immune exhaustion in CD8+ T cells.Graphical abstract

Revealing the Therapeutic Potential: Investigating the Impact of a Novel Witch Hazel Formula on Anti-Inflammation and Antioxidation.

Skin barrier health is crucial for preventive and corrective skincare across all skin types. Witch hazel (Hamamelis virginiana) extracts show potential in addressing skin issues, but their efficacy in treating chronic inflammation, improving skin barrier function, and combating UV-induced oxidation requires further investigation. To evaluate the efficacy of a novel formula containing witch hazel extracts in treating chronic inflammation, improving skin barrier function, and combating UV-induced oxidation. We employed a novel exvivo chronic inflammation model to assess anti-inflammatory effects, measuring key pro-inflammatory cytokines. Barrier function markers, such as loricrin and transglutaminase-1, were analyzed. An exvivo model with UV-induced Reactive Oxygen Species (ROS) elevation was used to evaluate antioxidant properties, measuring specific ROS markers like 4-Hydroxynonenal and carbonylated protein. The novel witch hazel formula significantly reduced pro-inflammatory cytokines in both 2D and exvivo models, including IL-6 and IL-8, demonstrating potent anti-inflammatory effects. Barrier function markers showed notable improvements compared to the inflamed condition. In the UV-induced ROS model, the formula remarkably decreased ROS levels, specifically 4-Hydroxynonenal and carbonylated protein, indicating strong antioxidant properties. Our findings demonstrate that the novel witch hazel formula exhibits potent anti-inflammatory and antioxidant properties while enhancing skin barrier function. This natural, well-tolerated ingredient offers a promising treatment option for improving overall skin health, presenting new opportunities in skincare formulation and treatment strategies.

Flavonoids attenuate inflammation of HGF and HBMSC while modulating the osteogenic differentiation based on microfluidic chip

BackgroundWhen inflammation occurs in periodontal tissues, a dynamic cellular crosstalk interacts between gingival fibroblasts and bone marrow mesenchymal stem cells (BMSCs), which plays a crucial role in the biological behaviour and differentiation of the cells. Recently, flavonoids are increasingly recognized for their therapeutic potential in modulating inflammation and osteogenic differentiation. Owing to their varied molecular structures and mechanisms, there are more needs that flavonoid compounds should be identified by extensive screening. However, current drug research mostly relies on static, single-type cell cultures. In this study, an innovative bionic microfluidic chip system tailored for both soft and hard tissues was developed to screen for flavonoids suitable for treating periodontitis.MethodsThis study developed a microfluidic system that bionically simulates the soft and hard structures of periodontal tissues. Live/dead staining, reactive oxygen species (ROS) staining, and RT-qPCR analysis were employed. These techniques evaluated the effects of flavonoid compounds on the levels of inflammatory factors and ROS contents in HGF and HBMSC under LPS stimulation. Additionally, the impact of these compounds on osteogenic induction in HBMSC and the exploration of the underlying mechanisms were assessed.ResultsThe microfluidic chip used in this study features dual chambers separated by a porous membrane, allowing cellular signal communication via bioactive factors secreted by cells in both layers under perfusion. The inflammatory response within the chip under LPS stimulation was lower compared to individual static cultures of HGF and HBMSC. The selected flavonoids-myricetin, catechin, and quercetin-significantly reduced cellular inflammation, decreased ROS levels, and enhanced osteogenic differentiation of BMSCs. Additionally, fisetin, silybin, and icariside II also demonstrated favorable outcomes in reducing inflammation, lowering ROS levels, and promoting osteogenic differentiation through the Wnt/β-catenin pathway.ConclusionsThe bionic microfluidic chip system provides enhanced capabilities for drug screening and evaluation, delivering a more precise assessment of drug efficacy and safety compared to traditional in vitro methods. This study demonstrates the efficacy of flavonoids in influencing osteogenic processes in BMSCs primarily through the Wnt/β-catenin pathway. These results uncover the potential of flavonoids as therapeutic medicine for treating periodontitis, meriting further research and development.Graphical

Study on PINK1 Expression and Its Clinical Value in Diabetic Nephropathy.

To explore PTEN-induced putative kinase 1 (PINK1) expression and its clinical value in diabetic nephropathy. Ninety patients with diabetic nephropathy were recruited and divided into metformin hydrochloride monotherapy group, telmisartan monotherapy group and combination therapy (metformin and telmisartan) group. Renal function indices and PINK1 expression, inflammatory factors, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) levels were detected. The correlation between PINK1 and inflammatory factors, renal function indicators including estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR) and serum creatinine (SCr)] were analyzed by Pearson correlation. Following treatments, the combination therapy group exhibited increased PINK1 expression levels and decreased ROS levels compared to the groups receiving metformin hydrochloride or telmisartan monotherapy. The combination therapy group showed significant improvements in renal function indices and inflammatory markers. Additionally, the MMP ratio in the combination therapy group was higher compared to the two monotherapy groups. Furthermore, PINK1 was negatively correlated with UACR, SCr, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), while positively correlated with eGFR and interleukin-2 (IL-2). PINK1 exhibits low expression levels in patients with diabetic nephropathy and its expression is strongly associated with the inhibition of disease progression, thereby offering significant clinical diagnostic value. Additionally, it may serve as a potential biological marker for clinical diagnosis and treatment of diabetic nephropathy.

Zhachong Shisanwei pill drug-containing serum protects H2O2-Induced PC12 cells injury by suppressing apoptosis, oxidative stress via regulating the MAPK signaling pathway.

Zhachong Shisanwei Pill (ZSP) is a classical Mongolian formula that combines 13 types of Chinese medicinal materials and has been used for treating ischemic stroke (IS) for centuries. However, the underlying molecular mechanisms have yet to be fully elucidated. The aim of this study is to explore potential mechanism of ZSP on nerve cells in cerebral ischemic injury. To simulate the pathological process of oxidative stress following IS, an injury model using PC12 cells was induced with hydrogen peroxide (H2O2). Afterward, PC12 cells were treated with ZSP medicated serum at low, medium, and high doses. Various assays were conducted to assess cell viability and oxidative stress indicators, including lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reactive oxygen species (ROS), and mitochondrial membrane potential (MMP). Cell apoptosis was evaluated through morphological assessment and flow cytometry. Additionally, the expression levels of apoptosis-related proteins (Bcl-2, Bax, Caspase-9, Caspase-3, PARP) and signaling pathway proteins (JNK, phosphorylated JNK, ERK, phosphorylated ERK, p38, and phosphorylated p38) were measured using automated Western blotting. Our findings indicate that ZSP medicated serum preconditioning improves the condition of PC12 cells injured by H2O2. Specifically, it increased cell survival rates and reduced LDH release. Additionally, ZSP treatment decreased ROS levels and MDA content, while enhancing the activity of SOD and CAT in the injured PC12 cells. ZSP also reversed the depolarization of mitochondrial membrane potential and protected cells from apoptosis by modulating the expression of apoptosis-related proteins, including Bcl-2, Bax, Caspase-9, Caspase-3, and PARP. Furthermore, the overactivation of the MAPK signaling pathway due to H2O2-induced injury was inhibited, as evidenced by the downregulation of phosphorylated JNK, ERK, and p38 levels. Mongolian medicine ZSP demonstrates protective effects against H2O2-induced oxidative stress and apoptosis in PC12 cells. The underlying mechanism may involve the inhibition of the MAPK signaling pathway, enhancement of antioxidant enzyme activity, reduction of intracellular peroxidation levels, and suppression of intrinsic apoptosis pathways.

Effects of astaxanthin supplementation during vitrification and liquid nitrogen vapor freezing on motility, morphology, survival, reactive oxygen species (ROS), and DNA fragmentation of post-cryopreserved human sperm.

To investigate the effect of astaxanthin supplementation in cryopreservation media on post-thawed sperm motility, viability, morphology, reactive oxygen species (ROS), and DNA fragmentation in two cryopreservation techniques using vitrification and liquid nitrogen vapor freezing. Thirty normozoospermic semen samples were used in the study. Post-prepared semen samples were divided into 1) non-cryopreserved control, 2) and 3) vitrified without (V) and with astaxanthin 0.5 µM (V+ATX), 4) and 5) frozen in liquid nitrogen vapor without (L) and with astaxanthin 0.5 µM (L+ATX). Cryopreservation using vitrification and liquid nitrogen vapor freezing significantly decreased sperm motility and viability and increased ROS levels. However, no changes were seen in sperm morphology or DNA fragmentation. The addition of astaxanthin in cryopreservation media significantly increased post-thawed motility in both vitrification (77.6±8.9% vs. 69.0±9.5% in V+ATX and V) and vapor freezing (57.0±13.3% vs. 47.7±14.6% in L+ATX and L); it significantly increased sperm viability in vitrification (75.0±11.9% vs. 65.9±11.1% in V+ATX and V), and significantly decreased ROS level in both vitrification (4.7 (2.6-8.3) RLU/sec/106 vs. 10.6 (9.4-16.0) RLU/sec/106 in V+ATX and V) and vapor freezing (4.6 (3.3-10.5) RLU/sec/106 vs. 10.3 (7.9-18.6) RLU/ sec/106 in L+ATX and L). Astaxanthin supplementation in cryopreservation media did not affect sperm morphology or DNA fragmentation. Astaxanthin supplementation improved post-cryopreserved sperm motility, decreased ROS levels in both vitrification and liquid nitrogen vapor freezing and improved sperm viability only in the vitrification technique.

Gamma-butyrobetaine hydroxylase (BBOX1) exerts suppressive effects on HepG2 hepatoblastoma cells.

Gamma-butyrobetaine hydroxylase (BBOX1) plays a pivotal role in catalyzing the final stage of L-carnitine biosynthesis. Recently, increasing number of studies have reported that BBOX1 is weakly expressed in tumor cells and exhibits antitumor activity. The role of BBOX1 in Hepatoblastoma (HB) has yet to be determined. To substantiate this, we have investigated BBOX1 expression and its clinical relevance in HB, and explored how BBOX1 might inhibit the occurrence and development of HB. The GSE104766 and GSE131329 datasets were used to screen for the core gene BBOX1 in HB and to analyze differences in expression between hepatoblastoma and normal tissues. Based on the clinicopathological features of the GSE131329 dataset, the connections between the expression of BBOX1 and the clinicopathological feature of HB patients were determined. After BBOX1 was overexpressed, CCK-8 and colony formation assays were employed to assess cell proliferation and wound healing experiments were utilized to assess cell migration. The presence of cell apoptosis, cell cycle changes, and reactive oxygen species (ROS) was assayed using flow cytometry. Compared with normal tissues, the expression of BBOX1 in hepatoblastoma tissues was notably decreased. Dysregulated expression of BBOX1 was indicated as a prognostic risk factor closely linked to clinical stag of patients with HB. Furthermore, following BBOX1 overexpression, cell proliferation and migration are decreased, the cell cycle is arrested, and ROS are attenuated. BBOX1 has suppressive effects on HepG2 cells, potentially through its ability to hinder cancer cell proliferation, arrest cell cycle progression, and decrease ROS levels, suggesting its potential as a novel prognostic biomarker and therapeutic candidate for hepatoblastoma.

Salidroside prevents cadmium chloride-induced DNA damage in human fetal lung fibroblasts

BackgroundCadmium (Cd) is an environmental pollutant and a heavy metal known for its genotoxic effects, which can lead to cancer and other related diseases. Preventing Cd-induced genotoxicity is crucial; however, there is limited research on this topic. Salidroside (SAL), a phenylpropanoid glycoside isolated from Rhodiola rosea L., is a popular medicinal compound with several health benefits. Nevertheless, its therapeutic effect on Cd-induced genotoxicity remains unexplored. MethodsHuman fetal lung fibroblasts were treated with 20 μM Cd2+ (CdCl2) for 12 h and 5–20 μM SAL was used to test the anti-DNA damage effect. DNA damage was evaluated using γH2AX expression and the alkaline comet assay. Intracellular reactive oxygen species (ROS) levels were measured using flow cytometry. ResultsExposure to 20 μM Cd2+ for 12 h induced significant DNA damage in human fetal lung fibroblasts, and this effect was notably attenuated by SAL treatment. SAL treatment did not decrease ROS levels in cells treated with Cd2+. ConclusionSAL effectively prevented Cd2+-induced DNA damage in human fetal lung fibroblasts. However, the underlying mechanism requires further investigation.

Protective Effect of Corilagin on Alcoholic Liver Injury

Objectives The herbal product corilagin is renowned for its liver-protecting benefits and antioxidant properties. However, the protective role of corilagin in alcoholic liver injury remains unexplored. The objective of this study is to delve into the protective effects of corilagin on alcoholic liver injury, both in HepG2 cells and a mouse model. Methods To assess the antioxidant capacity of corilagin in vitro, DPPH and ABTS assays were conducted. HepG2 cells were pretreated with 800 mM ethanol for 24 hours, followed by corilagin treatment for another 24 hours, to evaluate its liver-protecting activity. For in vivo studies, ICR mice, with and without corilagin treatment, were given ethanol for 4 weeks to induce alcoholic liver injury. At the end of the study, serum and liver tissue samples were collected to analyze liver function, enzymatic antioxidants, reactive oxygen species (ROS) levels, alcohol dehydrogenase, and liver tissue histology. Results The findings reveal that corilagin exhibits remarkable free radical scavenging ability and alleviates alcohol-induced cell damage in vitro. In vivo, corilagin significantly reduced liver index and serum levels of aminotransferase aspartate, alanine transaminase, total cholesterol, and triglyceride in mice with alcoholic liver injury. Additionally, corilagin decreased ROS levels in liver tissue and increased the activities of antioxidant enzymes CAT, SOD, and GSH-Px. GSH content increased, while lipid peroxide MDA decreased in liver tissue. Conclusion Our data strongly suggests that corilagin possesses protective effects on alcoholic liver injury, both in vitro and in vivo, which is likely attributed to its exceptional antioxidant capacity. In summary, corilagin holds promise as a potential preventive or therapeutic agent for alcoholic liver injury.

Defect in Migration of HSPCs in Nox-2 Deficient Mice Explained by Impaired Activation of Nlrp3 Inflammasome and Impaired Formation of Membrane Lipid Rafts.

NADPH oxidase 2 (Nox2), a superoxide-generating enzyme, is a source of reactive oxygen species (ROS) that regulate the intracellular redox state, self-renewal, and fate of hematopoietic stem/progenitor cells (HSPCs). Nox2 complex expressed on HSPCs associated with several activated cell membrane receptors increases the intracellular level of ROS. In addition, ROS are also released from mitochondria and, all together, are potent activators of intracellular pattern recognition receptor Nlrp3 inflammasome, which regulates the trafficking, proliferation, and metabolism of HSPCs. In the current study, we noticed that Nox2-deficient mice, despite the increased number of HSPCs in the bone marrow (BM), show hematopoietic defects illustrated by delayed recovery of peripheral blood (PB) hematopoietic parameters after sublethal irradiation and mobilize fewer HSPCs after administration of G-CSF and AMD3100. Moreover, Nox2-deficient HSPCs engraft poorly after transplantation into normal syngeneic recipients. To explain these defects at the molecular level, we hypothesized that Nox2-KO decreased ROS level does not efficiently activate Nlrp3 inflammasome, which plays a crucial role in regulating the trafficking of HSPCs. Herein, we report Nox2-deficient HSPCs display i) defective migration to major chemoattractant, ii) impaired intracellular activation of Nlrp3 inflammasome, and iii) a defect in membrane lipid raft (MLRs) formation that is required for a proper chemotactic response to pro-migratory factors. We conclude that Nox2-derived ROS enhances in Nlrp3 inflammasome-dependent manner HSPCs trafficking by facilitating MLRs assemble on the outer cell membranes, and defect in Nox2 expression results in impaired activation of Nlrp3 inflammasome, which affects HSPCs migration.

Role of Quercetin in DNA Repair: Possible Target to Combat Drug Resistance in Diabetes.

Diabetes Mellitus (DM) is referred to as hyperglycemia in either fasting or postprandial phases. Oxidative stress, which is defined by an excessive amount of reactive oxygen species (ROS) production, increased exposure to external stress, and an excessive amount of the cellular defense system against them, results in cellular damage. Increased DNA damage is one of the main causes of genomic instability, and genetic changes are an underlying factor in the emergence of cancer. Through covalent connections with DNA and proteins, quercetin has been demonstrated to offer protection against the creation of oxidative DNA damage. It has been found that quercetin shields DNA from possible oxidative stress-related harm by reducing the production of ROS. Therefore, Quercetin helps to lessen DNA damage and improve the ability of DNA repair mechanisms. This review mainly focuses on the role of quercetin in repairing DNA damage and compensating for drug resistance in diabetic patients. Data on the target topic was obtained from major scientific databases, including SpringerLink, Web of Science, Google Scholar, Medline Plus, PubMed, Science Direct, and Elsevier. In preclinical studies, quercetin guards against DNA deterioration by regulating the degree of lipid peroxidation and enhancing the antioxidant defense system. By reactivating antioxidant enzymes, decreasing ROS levels, and decreasing the levels of 8-hydroxydeoxyguanosine, Quercetin protects DNA from oxidative damage. In clinical studies, it was found that quercetin supplementation was related to increased antioxidant capacity and decreased risk of type 2 diabetes mellitus in the experimental group as compared to the placebo group. It is concluded that quercetin has a significant role in DNA repair in order to overcome drug resistance in diabetes.

Health-Promoting Effects, Phytochemical Constituents and Molecular Genetic Profile of the Purple Carrot 'Purple Sun' (Daucus carota L.).

The purple carrot cultivar 'Purple Sun' (Daucus carota L.) is characterized by a relevant content of phenolic compounds and anthocyanins, which may play an important role in reducing the risk of chronic diseases and in the treatment of metabolic syndrome. In the present study, the genetic diversity, phytochemical composition, and bioactivities of this outstanding variety were studied for the first time. Genetic analysis by molecular markers estimated the level of genetic purity of this carrot cultivar, whose purple-pigmented roots were used for obtaining the purple carrot ethanol extract (PCE). With the aim to identify specialized metabolites potentially responsible for the bioactivities, the analysis of the metabolite profile of PCE by LC-ESI/LTQ Orbitrap/MS/MS was carried out. LC-ESI/HRMS analysis allowed the assignment of twenty-eight compounds, putatively identified as isocitric acid (1), phenolic acid derivatives (2 and 6), hydroxycinnamic acid derivatives (9, 10, 12-14, 16, 17, 19, 22, and 23), anthocyanins (3-5, 7, 8, 11, and 18), flavanonols (15 and 21), flavonols (20 and 24), oxylipins (25, 26, and 28), and the sesquiterpene 11-acetyloxytorilolone (27); compound 26, corresponding to the primary metabolite trihydroxyoctanoic acid (TriHOME), was the most abundant compound in the LC-ESI/HRMS analysis of the PCE, and hydroxycinnamic acid derivatives followed by anthocyanins were the two most represented groups. The antioxidant activity of PCE, expressed in terms of reactive oxygen species (ROS) level and antioxidant enzymes activity, and its pro-metabolic effect were evaluated. Moreover, the antibacterial activity on Gram (-) and (+) bacterial strains was investigated. An increase in the activity of antioxidant enzymes (SOD, CAT, and GPx), reaching a maximum at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL), was observed. PCE induced an initial decrease in ROS levels at 0.1 and 0.25 mg/mL concentrations, reaching the ROS levels of control at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL). Moreover, significant antioxidant and pro-metabolic effects of PCE on myoblasts were shown by a reduction in ROS content and an increase in ATP production linked to the promotion of mitochondrial respiration. Finally, the bacteriostatic activity of PCE was shown on the different bacterial strains tested, while the bactericidal action of PCE was exclusively observed against the Gram (+) Staphylococcus aureus. The bioactivities of PCE were also investigated from cellular and molecular points of view in colon and hematological cancer cells. The results showed that PCE induces proliferative arrest and modulates the expression of important cell-cycle regulators. For all these health-promoting effects, also supported by initial computational predictions, 'Purple Sun' is a promising functional food and an optimal candidate for pharmaceutical and/or nutraceutical preparations.

In Vitro Protective Effect of Pea-Derived Peptides (PPs) via the Keap1/Nrf2 Signaling Pathway on Alpha-Gliadin-Sensitizing Peptide Induced Cacao-2 Cells.

Celiac disease (CD) is an allergic intestinal disease caused mainly by gliadin in wheat, which is widespread in the population and currently lacks effective treatment. α-Gliadin peptides cause cellular damage by substantially increasing cellular reactive oxygen species (ROS) levels. This study investigates the protective effect of 11 pea-derived peptides (PPs) on ɑ-gliadin peptide (P31-43) treated Caco-2 cells. Results show that cells treated with PP2, PP5, and PP6 peptides significantly reduce the cell mortality caused by P31-43. Three PPs significantly reduce the P31-43-induced decrease in ROS levels to control levels, and there is no difference between them and the vitamin C (Vc) group. The results in terms of antioxidant-related enzymes show that PPs significantly decrease superoxide dismutase activity (SOD), glutathione reductases (GR), and glutathione (GSH)/oxidized glutathione (GSSG) levels, thus significantly enhancing the antioxidant level of cells. By studying the key proteins of the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2) pathway, it is found that PPs activate the Keap1/Nrf2 signaling pathway. The study finds that peptides from peas can effectively alleviate ɑ-gliadin peptide-induced cell damage. The discovery of these food-derived peptides provides novel potential solutions for the prevention and treatment of CD.

The effects of simvastatin-loaded nanoliposomes on human multilineage liver fibrosis microtissue.

In this invitro study, for the first time, we evaluate the effects of simvastatin-loaded liposome nanoparticles (SIM-LipoNPs) treatment on fibrosis-induced liver microtissues, as simvastatin (SIM) has shown potential benefits in the non-alcoholic fatty liver disease process. We developed multicellular liver microtissues composed of hepatic stellate cells, hepatoblastoma cells and human umbilical vein endothelial cells. The microtissues were supplemented with a combination of palmitic acid and oleic acid to develop fibrosis models. Subsequently, various groups of microtissues were exposed to SIM and SIM-LipoNPs at doses of 5 and 10 mg/mL. The effectiveness of the treatments was evaluated by analysing cell viability, production of reactive oxygen species (ROS) and nitric oxide (NO), the expression of Kruppel-like factor (KLF) 2, and pro-inflammatory cytokines (interleukin(IL)-1 α, IL-1 β, IL-6 and tumour necrosis factor-α), and the expression of collagen I. Our results indicated that SIM-LipoNPs application showed promising results. SIM-LipoNPs effectively amplified the SIM-klf2-NO pathway at a lower dosage compatible with a high dosage of free SIM, which also led to reduced oxidative stress by decreasing ROS levels. SIM-LipoNPs administration also resulted in a significant reduction in pro-inflammatory cytokines and Collagen I mRNA levels, as a marker of fibrosis. In conclusion, our study highlights the considerable therapeutic potential of using SIM-LipoNPs to prevent liver fibrosis progress, underscoring the remarkable properties of SIM-LipoNPs in activating the KLF2-NO pathway and anti-oxidative and anti-inflammatory response.

Transcription factor GmAlfin09 regulates endoplasmic reticulum stress in soybean via peroxidase GmPRDX6.

Soybean (Glycine max [L.] Merr.) is a valuable oil crop but is also highly susceptible to environmental stress. Thus, developing approaches to enhance soybean stress resistance is vital to soybean yield improvement. In previous studies, transcription factor Alfin has been shown to serve as an epigenetic regulator of plant growth and development. However, no studies on Alfin have yet been reported in soybean. In this study, the endoplasmic reticulum (ER) stress- and reactive oxygen species (ROS)-related GmAlfin09 was identified. Screening of genes co-expressed with GmAlfin09 unexpectedly led to the identification of soybean peroxidase 6 (GmPRDX6). Further analyses revealed that both GmAlfin09 and GmPRDX6 were responsive to ER stress, with GmPRDX6 localizing to the ER under stress. Promoter binding experiments confirmed the ability of GmAlfin09 to bind to the GmPRDX6 promoter directly. When GmAlfin09 and GmPRDX6 were overexpressed in soybean, enhanced ER stress resistance and decreased ROS levels were observed. Together, these findings suggest that GmAlfin09 promotes the upregulation of GmPRDX6, and GmPRDX6 subsequently localizes to the ER, reduces ROS levels, promotes ER homeostasis, and ensures the normal growth of soybean even under ER stress. This study highlights a vital target gene for future molecular breeding of stress-resistant soybean lines.

Mitigation of Surface Browning in Fresh-Cut Banana Blossom by Tamarind (Tamarindus indica L.) Pulp Extract: A Role in Regulating ROS Metabolism

T he surface browning of fresh-cut products not only diminishes their nutritional content but also lowers their market value. Fresh-cut banana blossom (FBB), an increasingly popular vegan food, is prone to browning on the cut surface, which poses a significant challenge for this fresh-cut produce. Chemicals and natural extracts are commonly used to address this issue in fresh-cut produce, offering alternatives to synthetic chemicals. Tamarind (Tamarindus indica L.) pulp extract (TPE), derived from the tamarind fruit, contains compounds such as polyphenols with antioxidant properties, making it an intriguing choice as an anti-browning agent. Therefore, this study investigated the effects of TPE on surface browning and reactive oxygen species (ROS) metabolism in FBB during storage at 30 ± 1 °C. FBB was immersed in 0 % (the control) and 2.5 % TPE for 5 min, then rinsed with distilled water, air-dried, and stored at 30 ± 1 °C for 60 h. The control group showed increasing surface browning and declining overall quality during storage. TPE immersion significantly enhanced antioxidant defense systems during storage compared to the control. The heightened activity of antioxidant enzymes and increased non-enzymatic antioxidant levels corresponded with decreased ROS levels, oxidative membrane damage, and surface browning. These findings suggest that TPE has the potential to effectively reduce browning in FBB and may serve as an effective anti-browning agent for other fresh-cut products.

ZmmiR398b negatively regulates maize resistance to sugarcane mosaic virus infection by targeting ZmCSD2/4/9.

MicroRNAs (miRNAs) are widely involved in various biological processes of plants and contribute to plant resistance against various pathogens. In this study, upon sugarcane mosaic virus (SCMV) infection, the accumulation of maize (Zea mays) miR398b (ZmmiR398b) was significantly reduced in resistant inbred line Chang7-2, while it was increased in susceptible inbred line Mo17. Degradome sequencing analysis coupled with transient co-expression assays revealed that ZmmiR398b can target Cu/Zn-superoxidase dismutase2 (ZmCSD2), ZmCSD4, and ZmCSD9 invivo, of which the expression levels were all upregulated by SCMV infection in Chang7-2 and Mo17. Moreover, overexpressing ZmmiR398b (OE398b) exhibited increased susceptibility to SCMV infection, probably by increasing reactive oxygen species (ROS) accumulation, which were consistent with ZmCSD2/4/9-silenced maize plants. By contrast, silencing ZmmiR398b (STTM398b) through short tandem target mimic (STTM) technology enhanced maize resistance to SCMV infection and decreased ROS levels. Interestingly, copper (Cu)-gradient hydroponic experiments demonstrated that Cu deficiency promoted SCMV infection while Cu sufficiency inhibited SCMV infection by regulating accumulations of ZmmiR398b and ZmCSD2/4/9 in maize. These results revealed that manipulating the ZmmiR398b-ZmCSD2/4/9-ROS module provides a prospective strategy for developing SCMV-tolerant maize varieties.

Puerarin mitigated LPS-ATP or HG-primed endothelial cells damage and diabetes-associated cardiovascular disease via ROS-NLRP3 signalling.

The occurrence and development of diabetic vascular diseases are closely linked to inflammation-induced endothelial dysfunction. Puerarin (Pue), the primary component of Pueraria lobata, possesses potent anti-inflammatory properties. However, its vasoprotective role remains elusive. Therefore, we investigated whether Pue can effectively protect against vascular damage induced by diabetes. In the study, Pue ameliorated lipopolysaccharide-adenosine triphosphate (LPS-ATP) or HG-primed cytotoxicity and apoptosis, while inhibited reactive oxygen species (ROS)-mediated NLR family pyrin domain containing 3 (NLRP3) inflammasome in HUVECs, as evidenced by significantly decreased ROS level, NOX4, Caspase-1 activity and expression of NLRP3, GSDMD, cleaved caspase-1, IL-1β and IL-18. Meanwhile, ROS inducer CoCI2 efficiently weakened the effects of Pue against LPS-ATP-primed pyroptosis. In addition, NLRP3 knockdown notably enhanced Pue's ability to suppress pyroptosis in LPS-ATP-primed HUVECs, whereas overexpression of NLRP3 reversed the inhibitory effects of Pue. Furthermore, Pue inhibited the expression of ROS and NLRP3 inflammasome-associated proteins on the aorta in type 2 diabetes mellitus rats. Our findings indicated that Pue might ameliorate LPS-ATP or HG-primed damage in HUVECs by inactivating the ROS-NLRP3 signalling pathway.

The impact of sestrin2 on reactive oxygen species in diabetic retinopathy.

Diabetic retinopathy (DR) is a significant complication of diabetes that often leads to blindness, impacting Müller cells, the primary retinal macroglia involved in DR pathogenesis. Reactive oxygen species (ROS) play a crucial role in the development of DR. The objective of this study was to investigate the involvement of sestrin2 in DR using a high-glucose (HG)-induced Müller cell model and assessing cell proliferation with 5-ethynyl-2-deoxyuridine (EdU) labeling. Following this, sestrin2 was upregulated in Müller cells to investigate its effects on ROS, tube formation, and inflammation both in vitro and in vivo, as well as its interaction with the nuclear factor erythroid2-related factor 2 (Nrf2) signaling pathway. The findings demonstrated a gradual increase in the number of EdU-positive cells over time, with a subsequent decrease after 72 h of exposure to high glucose levels. Additionally, the expression of sestrin2 exhibited a progressive increase over time, followed by a decrease at 72 h. The rh-sestrin2 treatment suppressed the injury of Müller cells, decreased ROS level, and inhibited the tube formation. Rh-sestrin2 treatment enhanced the expression of sestrin2, Nrf2, heme oxygenase-1 (HO-1), and glutamine synthetase (GS); however, the ML385 treatment reversed the protective effect of rh-sestrin2. Finally, we evaluated the effect of sestrin2 in a DR rat model. Sestrin2 overexpression treatment improved the pathological injury of retina and attenuated the oxidative damage and inflammatory reaction. Our results highlighted the inhibitory effect of sestrin2 in the damage of retina, thus presenting a novel therapeutic sight for DR.