Antioxidantes naturales y su efecto contra el estrés oxidante provocado por la contaminación por material particulado / Natural Antioxidants and their Effect Against Oxidative Stress Caused by Particulate Matter Pollution

Resumen La contaminación ambiental es uno de los factores que favorece el estrés oxidante, ya que expone al organismo a materiales diversos que generan radicales libres y afectan al sistema respiratorio, cardiovascular, inmunológico y nervioso de las personas más vulnerables como los niños, adultos mayores y personas con enfermedades crónicas. Para prevenir o reducir el estrés oxidante, el cual es un desequilibrio entre la producción de radicales libres y la capacidad del organismo de neutralizarlo, se recomienda consumir una dieta equilibrada y rica en antioxidantes naturales los cuales se encuentran diversos alimentos, especialmente en frutas y verduras con colores intensos, en las semillas y las especias. En las últimas décadas se ha demostrado la eficacia del consumo de antioxidantes naturales como: el resveratrol vino, el café, la curcumina, el ajo, la vitamina C, la vitamina E y el té verde que presentan efectos benéficos como: proteger membranas celulares, regular la expresión de genes relacionados con la inflamación, prevenir o reducir el daño endotelial, disminuir la frecuencia o severidad de enfermedades neurodegenerativas, hepáticas y pulmonares, así como estimular al sistema inmunológico.

Abstract Environmental pollution can promote oxidative stress by exposing the body to various elements and substances that generate free radicals, such as lead and vanadium. These free radicals can negatively impact the respiratory, cardiovascular, immune, and neurological systems of vulnerable populations, including children, the elderly, and those with chronic diseases. To prevent or reduce oxidative stress, it is recommended to consume a balanced diet rich in natural antioxidants. These antioxidants can be found in various foods, especially in fruits and vegetables with intense colors, seeds, and spices. In recent decades, the effectiveness of consuming natural antioxidants such as resveratrol found in wine, coffee, curcumin, garlic, vitamin C, vitamin E, and green tea has been demonstrated. These antioxidants have beneficial effects on the body, including the protection of cell membranes, regulation of gene expression associated with inflammation, prevention or reduction of endothelial damage, and the decrease or diminished severity of neurodegeneration, liver, and pulmonary disorders. Additionally, they stimulate the immune response.

Research progress on association between macrophages and ischemia-reperfusion injury / 器官移植

Ischemia-reperfusion injury (IRI) is an extremely complicated pathophysiological process, which may occur during the process of myocardial infarction, stroke, organ transplantation and temporary interruption of blood flow during surgery, etc. As key molecules of immune system, macrophages play a vital role in the pathogenesis of IRI. M1 macrophages are pro-inflammatory cells and participate in the elimination of pathogens. M2 macrophages exert anti-inflammatory effect and participate in tissue repair and remodeling and extracellular matrix remodeling. The balance between macrophage phenotypes is of significance for the outcome and treatment of IRI. This article reviewed the role of macrophages in IRI, including the balance between M1/M2 macrophage phenotype, the mechanism of infiltration and recruitment into different ischemic tissues. In addition, the potential therapeutic strategies of targeting macrophages during IRI were also discussed, aiming to provide reference for alleviating IRI and promoting tissue repair.

Quality Improvement Pathway of Cultivated Chinese Medicinal Materials Based on Physiological Ecology of Plants Under Adversity / 中国实验方剂学杂志

The quality of Chinese medicinal materials is related to the environment， with an optimal quality under adversity. The origin of Chinese medicinal materials has converted from wild collection to cultivation， and a better cultivation environment leads to a decline in their quality. At present， there are few effective methods to improve the quality of Chinese medicinal materials. Plants are bound to produce a large amount of reactive oxygen species （ROS） under adversity， and the quality improvement of Chinese medicinal materials under adversity may be achieved through ROS. This paper described the relationship between plant adversity-ROS-secondary metabolism： ROS can alter the structure of proteins （including enzymes） and regulate enzyme activities， thus affecting secondary metabolism to improve the adaptive capacity of plants. Therefore， ROS is the essential cause of adversity changing secondary metabolism. The cells of plants are omnipotent， and the medicinal parts of plants can independently complete the whole process of secondary metabolism， so regulation of secondary metabolism during the processing of fresh Chinese medicinal materials can significantly improve the quality of Chinese medicinal materials. Exogenous ROS can be used as inducible factors to stimulate medicinal parts， inducing a physiological state of fresh medicinal parts similar to that under adversity， thus enhancing secondary metabolism， and improving the contents of active ingredients in Chinese medicinal materials. In addition， the content and ratio of each ingredient in Chinese medicinal materials are closer to those of wild Chinese medicinal materials. The mechanism of plant adaptation to adversity is the mechanism of the quality formation of Chinese medicinal materials， and the application of ROS as inducible factors can provide a new pathway for the production of high-quality Chinese medicinal materials.

Prevention and Treatment of Alzheimer's Disease by Traditional Chinese Medicine via Regulating ROS： A Review / 中国实验方剂学杂志

The pathological mechanism of Alzheimer's disease （AD） is complex， and there are many hypotheses. The mainstream theory is the amyloid-beta protein （Aβ） and Tau protein phosphorylation. Oxidative stress （OS） is a bridge between other hypotheses and mechanisms and plays a key role in many hypotheses. Therefore， the treatment of OS in AD （ADOS） is beneficial in alleviating disease progression. Reactive oxygen species （ROS） is a kind of antioxidant and a kind of oxidation products， with Aβ and Tau protein interactions， activating microglia and astrocytes， triggering inflammation and mitochondrial dysfunction， leading to the deterioration of the environment in the brain， and accelerating the development of disease. ROS， as a signal messenger inducing OS， is widely involved in the progression of AD and may be a new target for the progression of AD. Traditional Chinese medicine （TCM） monomers and compounds play an increasingly important role in the prevention and treatment of AD. Recent studies have found that the effective prevention and treatment of AD by TCM is closely related to the regulation of ROS. There are many studies on the mechanism of TCM in the treatment of AD via regulating ROS， but there is a lack of systematic review. By analyzing and summarizing the literature in China and abroad in recent years， this paper reviewed the generation and physiology of ROS， the mechanism of action of AD， and the prevention of AD by TCM via regulating ROS through relevant ways， so as to provide references for the research on the regulation of ROS by TCM and provide new targets and new methods for the prevention and treatment of AD.

Effect of ceria nanoparticles on activity of DSS-induced colitis in mice by eliminating active oxygen species / 上海交通大学学报（医学版）

Objective·To investigate the effect of ceria nanoparticles-polyethylene glycol(CeNP-PEG)on scavenging reactive oxygen species(ROS)and alleviating disease activity in dextran sulphate sodium(DSS)-induced colitis mice.Methods·CeNP was synthesized with the hydrates of cerium acetate,oleamine,and xylene,which was modified with polyethylene glycol-stearyl phosphatidylethanolamine(mPEG-DPSE)to obtain CeNP-PEG.Then CeNP-PEG was purified.The particle size and zeta potential of CeNP-PEG were measured by using transmission electron microscopy(TEM)and dynamic light scattering(DLS).Mouse macrophages(Raw264.7)were cultured in vitro and induced to a pro-inflammatory phenotype(M1 phenotype).M1 macrophages were treated with 0.5 μg/mL and 1.0 μg/mL CeNP-PEG,respectively,and then Western blotting was used to detect the expression changes of the proteins related with nuclear factor-κB(NF-κB)signaling pathway.DSS-induced colitis mice models were constructed,and CeNP-PEG(1.0 mg/mL)was intravenously administrated for 3 times via tail vein during the modeling period.Meanwhile,the body weight,fecal characteristics,and frequency of rectal bleeding in mice were monitored in the normal control group(Normal group),the model group(DSS group),and the CeNP-PEG treatment group.The disease activity index(DAI)was calculated to evaluate the intestinal inflammation.The level of ROS in mouse intestinal tissues was detected by dihydroethidine(DHE)staining and the mRNA expression levels of inflammatory cytokines interferon-γ(Ifn-γ),interleukin-6(Il-6),Il-1β and tumor necrosis factor-α(Tnf-α)were detected by real-time quantitative PCR(RT-qPCR).Results·The hydrated particle size of synthesized CeNP-PEG was(6.96±0.27)nm,and the average zeta potential was(-6.02±1.31)mV.Western blotting results showed that the expression of p-P65 increased in the pro-inflammatory macrophages compared with the control group.The expression of NF-κB inhibitor-α(IκB-α)decreased,and their expressions tended to recover after the intervention of different concentrations of CeNP-PEG.In the DSS-induced colitis models,mice in the CeNP-PEG treatment group lost less weight than those in the DSS group(P= 0.000)and had lower DAI scores(P=0.000).The RT-qPCR results of intestinal tissues showed that the mRNA levels of Ifn-γ,Il-1β,Il-6 and Tnf-α in the DSS group were significantly up-regulated compared with those in the Normal group(P=0.000),and all of them significantly decreased in the CeNP-PEG treatment group.The results of DHE staining showed that the fluorescence intensity of intestinal tissues in the DSS group was significantly enhanced than that in the Normal group,and the fluorescence intensity decreased in the CeNP-PEG treatment group.Conclusion·CeNP-PEG can inhibit the expression of intestinal inflammatory factors and the activation of NF-κB-related inflammatory pathway of pro-inflammatory macrophages,eliminate intestinal ROS,improve the intestinal inflammatory microenvironment,and alleviate the disease activity of DSS-induced colitis in mice.

The role of reactive oxygen species in periodontitis and periodontal tissue regeneration / 中国组织工程研究

BACKGROUND:Reactive oxygen species is a double-edged sword in the development of periodontitis and the regeneration of periodontal tissue.Low concentration of reactive oxygen species induces the differentiation of periodontal fibroblasts,and excessive reactive oxygen species will cause damage to periodontal tissue.In the process of inflammation,the accumulation of reactive oxygen species in periodontal tissue induces damage to cells and tissues through a variety of signaling pathways or through redox reactions. OBJECTIVE:To review the double-edged sword effect of reactive oxygen species in periodontitis and periodontal tissue regeneration,thereby providing potential targets and treatment ideas for the clinical treatment of periodontitis and periodontal tissue regeneration. METHODS:Databases of CNKI and PubMed were searched for relevant articles published from April 1990 to April 2023 with the key words of"periodontal tissue engineering,periodontal defect,regeneration of periodontal tissue,chronic periodontitis,reactive oxygen species,oxidative stress,antioxidative stress,oxidative injuries,free radicals,reactive nitrogen species"in Chinese and English,respectively.By reading the titles and abstracts,repetitive studies or irrelevant literatures were excluded.Finally,77 articles were included for review. RESULTS AND CONCLUSION:Reactive oxygen species are a kind of free radicals with high reactivity.When bacteria invade,reactive oxygen species are released in large quantities by the respiratory explosion of neutrophils and play a double-edged sword role in the body through their redox reactions or as pleiotropic physiological signal transmitters.In periodontitis,low concentrations of reactive oxygen species can kill invading pathogenic bacteria,but high concentrations of reactive oxygen species promote the secretion of inflammatory factors through JNK,RANK,Wnt/β-Catenin and other pathways,promote immune damage or directly damage tissues through oxidative reactions or through other ways to aggravate periodontitis.In the process of periodontal tissue regeneration,low concentrations of reactive oxygen species can promote the proliferation and differentiation of periodontal ligament stem cells through Nrf2 and other pathways and can promote the secretion of vascular endothelial growth factor to promote vascular regeneration.This provides seeds and a nutrient environment for periodontal tissue regeneration,which is extremely important for promoting periodontal tissue regeneration.However,high concentrations of reactive oxygen species will reduce the activity of periodontal ligament stem cells and damage endothelial cells,which are not conducive to vascular regeneration.This will inhibit wound healing and periodontal tissue regeneration.Therefore,it is important to explore the role of reactive oxygen species in the development of periodontitis and periodontal tissue regeneration and to discover the potential mechanism of its action and to explore the appropriate concentration for its role in reducing periodontal inflammation and promoting periodontal tissue regeneration for the future treatment of periodontitis and periodontal tissue regeneration in clinical practice.Using reactive oxygen species as a target to explore ways to reduce periodontal inflammation and promote periodontal ligament stem cell activity and vascular regeneration may become a clinically effective method for treating periodontitis and promoting periodontal tissue regeneration.

The role of mitochondrial unfolded protein response in palmitic acid-induced lipid accumulation in renal tubule epithelium in vitro / 西安交通大学学报(医学版)

【Objective】 To investigate the effect of mitochondrial unfolded protein response (UPRmt) on lipid metabolism in human kidney 2 (HK-2) cells . 【Methods】 Lipid accumulation was induced by palmitic acid (PA) in HK-2 cells. The cells were pretreated with siRNA or CDDO respectively. The intracellular lipid accumulation was observed by oil red staining; mitochondrial membrane potential (MMP) was measured by JC-1.The contents of reactive oxygen species (ROS) in mitochondria were measured by Mito-SOX, and the expressions of HSP60, LONP1, CLPP, ACOX1, PPARα, PGC1α and CPT1α were detected by Western blotting. 【Results】 PA induced lipid aggregation, MMP decrease, ROS generation in mitochondria and the decreased expression of UPRmt proteins (e. g., HSP60 and LONP1) in HK-2 cells. Pretreatment of HK-2 cells with siRNA could aggravate lipid aggregation, MMP decrease and ROS generation induced by PA, and further decrease the expression of HSP 60and LONP1.Pretreatment of HK-2 cells with CDDO alleviated lipid aggregation, MMP decrease, ROS generation and decreased HSP60 and LONP1 expressions induced by PA. 【Conclusion】 Lipid aggregation in HK-2 cells induced by PA may be related to mitochondrial dysfunction and UPRmt has a protective effect on HK-2 cells in the process.

Treatment of Pulmonary Inflammatory Diseases by Traditional Chinese Medicine Through Regulating Mitochondrial Oxidative Stress： A Review / 中国实验方剂学杂志

Pulmonary fibrosis， chronic obstructive pulmonary disease， acute lung injury， asthma， and infectious pneumonia are common pulmonary inflammatory diseases worldwide. There is evidence that mitochondria produce a large amount of reactive oxygen species （ROS） when stimulated by inflammation， leading to oxidative stress that affects the onset and progression of pulmonary inflammatory diseases. With in-depth research， traditional Chinese medicine （TCM） has made significant progress in the treatment of pulmonary inflammatory diseases. An increasing amount of evidence indicates that single TCM and their active components， as well as TCM compound formulas， can improve mitochondrial oxidative stress status through multi-target and multi-pathway mechanisms， thereby effectively treating pulmonary inflammatory diseases. Currently， there is a lack of systematic review and summary of TCM research in this field both domestically and internationally. Therefore， this article aims to summarize and conclude the mechanisms by which TCM regulates mitochondrial oxidative stress to intervene in pulmonary inflammatory diseases， providing a scientific basis for its clinical application and offering new ideas and references for in-depth research on the prevention and treatment of pulmonary inflammatory diseases with TCM.

Induction of apoptosis in triple-negative breast cancer cells by petroleum ether extract of Sageretia thea / 药学实践与服务

Objective To investigate the effect of the petroleum ether extract of Sageretia thea on the proliferation and apoptosis of breast cancer cells. Methods After breast cancer cells were incubated with the petroleum ether extract for different times, cell viability was analyzed by CCK8 assay, cell proliferation was detected by plate cloning test, nuclear morphology was observed by DAPI staining, mitochondrial membrane potential（MMP）and reactive oxygen species（ROS）were determined by immunofluorescence, and the cell cycle and apoptosis were detected by flow cytometry. After incubating with the extract for 24 h, the CCK8 assay was used to observe the toxicity to normal human vascular endothelial cells. Results The IC50 of BT549 and MDA-MB-231 breast cancer cell lines treated with the petroleum ether extract for 24 h were 45.40 μg/ml and 12.23 μg/ml, respectively. The extract time and dose dependently inhibited breast cancer cell viability and clonal formation, induced cell apoptosis and cycle arrest in G1/S phase, decreased MMP and increased ROS levels. There was no toxic effect on normal endothelial cells. Conclusion The petroleum ether extract of Sageretia thea may induce apoptosis by increasing ROS to cause MMP collapse, followed by activating mitochondrial pathway, thereby hindering the growth of breast cancer cells. These results could support the application of Sageretia thea to anti-breast tumor in the folk.

The Catalytic Mechanism and Activity Modulation of Manganese Superoxide Dismutase / 生物化学与生物物理进展

Manganese superoxide dismutase catalyzes the dismutation of two molecules of superoxide radicals to one molecule of oxygen and one molecule of hydrogen peroxide. The oxidation of superoxide anion to oxygen by Mn3+SOD proceeds at a rate close to diffusion. The reduction of superoxide anion to hydrogen peroxide by Mn2+SOD can be progressed parallelly in either a fast or a slow cycle pathway. In the slow cycle pathway, Mn2+SOD forms a product inhibitory complex with superoxide anion, which is protonated and then slowly releases hydrogen peroxide out. In the fast cycle pathway, superoxide anion is directly converted into product hydrogen peroxide by Mn2+SOD, which facilitates the revival and turnover of the enzyme. We proposed for the first time that temperature is a key factor that regulates MnSOD into the slow- or fast-cycle catalytic pathway. Normally, the Mn2+ rest in the pent-coordinated state with four amino acid residues (His26, His74, His163 and Asp159) and one water (WAT1) in the active center of MnSOD. The sixth coordinate position on Mn (orange arrow) is open for water (WAT2, green) or O2• to coordinate. With the cold contraction in the active site as temperature decreases, WAT2 is closer to Mn, which may spatially interfere with the entrance of O2• into the inner sphere, and avoid O2•/Mn2+ coordination to reduce product inhibition. Low temperature compels the reaction into the faster outer sphere pathway, resulting in a higher gating ratio for the fast-cycle pathway. As the temperature increases in the physiological temperature range, the slow cycle becomes the mainstream of the whole catalytic reaction, so the increasing temperature in the physiological range inhibits the activity of the enzyme. The biphasic enzymatic kinetic properties of manganese superoxide dismutase can be rationalized by a temperature-dependent coordination model of the conserved active center of the enzyme. When the temperature decreases, a water molecule (or OH-) is close to or even coordinates Mn, which can interfere with the formation of product inhibition. So, the enzymatic reaction occurs mainly in the fast cycle pathway at a lower temperature. Finally, we describe the several chemical modifications of the enzyme, indicating that manganese superoxide dismutase can be rapidly regulated in many patterns (allosteric regulation and chemical modification). These regulatory modulations can rapidly and directly change the activation of the enzyme, and then regulate the balance and fluxes of superoxide anion and hydrogen peroxide in cells. We try to provide a new theory to reveal the physiological role of manganese superoxide dismutase and reactive oxygen species.

Berberine interferes with RSV infection of HEp-2 cells by inducing mitophagy autophagy / 中国药理学通报

Aim To explore the effect of berberine (B E) on RSV infected HEp-2 cells and the related mechanism. Methods HEp-2 cells were infected with RSV and treated with BE. Cell viability was assessed using the CCK-8 assay. Protein expression levels of NLRP3, ASC, caspase-1, PINK1, Parkin, Beclinl, p62, LC3 I,LC3 II,and BNIP3 in HEp-2 cells were detected by Western blot. The secretion level of IL-1 p in HEp-2 cells was measured using ELISA. Apoptosis rate and mitochondrial membrane potential of HEp-2 cells were examined by flow cytometry. Mitochondrial ROS (mtROS) in HEp-2 cells was detected through MitoSOX staining. Colocalization of mitochondria and autophagosomes in HEp-2 cells was investigated using immunofluorescence staining. Cyclosporin A was used for validation experiments. Results BE could significantly improve the activity of RSV-infected HEp-2 cells,reduce the apoptosis rate (P < 0. 05), and decrease the activation level of NLRP3 inflammasomes and IL-lp level (P <0. 05); BE improved mitochondrial function by increasing mitochondrial membrane potential and ATP levels,and reduced mtROS. BE significantly promoted the colocalization of mitochondria-autophagosome in RSV infected cells, inducing PINK1/ Parkin and BNIP3 to mediate mitochondrial autophagy; cyclosporine A aggravated RSV infection. Conclusions BE has protective effects on HEp-2 cells infected by RSV. The mechanism may be related to the inhibitory effect of BE on the production of mtROS and the activation of NLRP3 inflammasomes by inducing PINK1/ Parkin and BNIP3-mediated mitochondrial autophagy.

Mechanism of EGFR inhibitor AG1478 combined with oxaliplatin in inhibiting PI3K/AKT pathway and promoting autophagy in HI 975 cells / 中国药理学通报

Aim To explore the effect of oxaliplatin combined with epidermal growth factor receptor tyrosine kinase inhibitor AG1478 on autophagy in non-small cell lung cancer H1975 cells. Methods H1975 cells were cultured in vitro using gradient concentrations of AG1478 (0, 5, 10, 15, 20, 25, 30, 35, 40 jjimol • IT

Mechanism of action of formononetin in alleviating allergic asthma through DRP1-NLRP3 signaling pathway / 中国药理学通报

Aim To investigate the mechanism by which formononetin (FN) inhibits mitochondrial dynamic-related protein 1 (DRP1) -NLRP3 axis via intervening the generation of ROS to reduce allergic airway inflammation. Methods In order to establish allergic asthma mouse model, 50 BALB/c mice aged 8 weeks were divided into the control group, model group, FN treatment group and dexamethasone group after ovalbumin (OVA) induction. Airway inflammation and collagen deposition were detected by HampE and Masson staining. Th2 cytokines and superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and IgE levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA, ROS in BEAS-2B cells was assessed by DCFH-DA staining, DRP1 expression in lung tissue and BEAS-2B cells was detected by immunohistochemistry and immunofluorescence, and the DRP1-NLRP3 pathway was analyzed by immunoblotting. Results FN treatment could effectively ameliorate the symptoms of asthmatic mouse model, including reducing eosinophil accumulation, airway collagen deposition, decreasing Th2 cytokine and IgE levels, reducing ROS and MDA production, increasing SOD and CAT activities, and regulating DRP1-NLRP3 pathway-related protein expression, thereby relieving inflammation. Conclusion FN ameliorates airway inflammation in asthma by regulating DRP1-NLRP3 pathway.

Research progress on mitochondria regulating anti-tumor immunity / 浙江大学学报·医学版

Tumor cells adaptively reforge their metabolism to meet the demands of energy and biosynthesis. Mitochondria, pivotal organelles in the metabolic reprogramming of tumor cells, contribute to tumorigenesis and cancer progression significantly through various dysfunctions in both tumor and immune cells. Alterations in mitochondrial dynamics and metabolic signaling pathways exert crucial regulatory influence on the activation, proliferation, and differentiation of immune cells. The tumor microenvironment orchestrates the activation and functionality of tumor-infiltrating immune cells by reprogramming mitochondrial metabolism and inducing shifts in mitochondrial dynamics, thereby facilitating the establishment of a tumor immunosuppressive microenvironment. Stress-induced leakage of mitochondrial DNA contributes multifaceted regulatory effects on anti-tumor immune responses and the immunosuppressive microenvironment by activating multiple natural immune signals, including cGAS-STING, TLR9, and NLRP3. Moreover, mitochondrial DNA-mediated immunogenic cell death emerges as a promising avenue for anti-tumor immunotherapy. Additionally, mtROS, a crucial factor in tumorigenesis, drives the formation of tumor immunosuppressive microenvironment by changing the composition of immune cells within the tumor microenvironment. This review focuses on the intrinsic relationship between mitochondrial biology and anti-tumor immune responses from multiple angles. We expect to explore the core role of mitochondria in the dynamic interplay between the tumor and the host, in order to facilitate the development of targeted mitochondrial strategies for anti-tumor immunotherapy.

WNK2 delays the proliferation and invasion of hepatocellular carcinoma by inhibiting the ERK1/2/ROS/SHP2 signaling pathway / 中国实验动物学报

Objective To investigate the effect of WNK2 on the ERK1/2/ROS/SHP2 signaling pathway in hepatocellular carcinoma(HCC)and to explore its role in cell proliferation and migration in HCC.Methods HepG2 cells were transfected with WNK2-mimic,sh-RNA WNK2,and corresponding negative control.The effect of WNK2 on the proliferation of HCC was examined by subcutaneous tumorigenesis assay in BALB/c nude mice.The expressions of WNK2,p40,gp90,p-SHP2,p-AKT,and p-ERK1/2 in tumor tissues were detected by Western Blot.After treatment with SHP2 inhibitor PHPS1,the expressions of WNK2,P40,gp90,p-SHP2,p-AKT,and p-ERK1/2 in HepG2 cells were detected by Western Blot.The migration ability and invasion ability of HepG2 cells were detected by cell scratch assay and Transwell.The proliferation ability of HepG2 cells was detected by monoclonal proliferation assay.Results Compared with the sh-NC group,the tumor volume of nude mice in the sh-RNA WNK2 group was significantly increased(P＜0.01);Compared with the NC-mimic group,the tumor volume of nude mice in the WNK2-mimic group was significantly reduced(P＜0.01).Western Blot result showed that compared with the sh-NC group,the expression of WNK2 in the sh-RNA WNK2 group was significantly decreased(P＜0.01),while the expressions of p40,gp90,p-SHP2,p-AKT and p-ERK1/2 were significantly increased(P＜0.01).Compared with the NC-mimic group,the expression of WNK2 was significantly increased in the WNK2-mimic group(P＜0.01),and the expressions of p40,gp90,p-SHP2,p-AKT,and p-ERK1/2 were significantly decreased(P＜0.01).In vitro experiment,compared with the sh-NC group,the expression of WNK2 was significantly decreased in the sh-RNA WNK2 group(P＜0.01),while the expressions of p40,gp90,p-SHP2,p-AKT and p-ERK1/2 were significantly increased in the sh-RNA WNK2 group(P＜0.01).Compared with the sh-NC+PHPS1 group,the expression of WNK2 was significantly decreased in the sh-RNA WNK2+PHPS1 group(P＜0.01),while the expressions of p40,gp90,p-SHP2,p-AKT,and p-ERK1/2 were reversed and had no significant differences compared with the sh-NC+PHPS1 group(P＞0.05).The cell scratch assay and Transwell result showed that the migration and invasion ability of HepG2 cells in the sh-RNA WNK2 group was significantly increased compared with the sh-NC group(P＜0.01).The migration and invasion ability of HepG2 cells in the sh-NC+PHPS1 group and sh-RNA WNK2+PHPS1 group were significantly decreased with no significant difference(P＞0.05).The result of the monoclonal proliferation experiment showed that the proliferation capacity of HepG2 cells in the sh-RNA WNK2 group was significantly increased compared with the sh-NC group(P＜0.01),while the proliferation ability of HepG2 cells in the sh-NC+PHPS1 group and sh-RNA WNK2+PHPS1 group was significantly decreased with no significant difference(P＞0.05).Conclusions WNK2 can inhibit the ERK1/2/ROS/SHP2 signaling pathway,thereby inhibiting ERK1/2/Akt signaling and delaying the proliferation and migration of HCC.

Buzhong Yiqitang Regulates Apoptosis via Nrf2/ROS Pathway to Alleviate Cisplatin Resistance in A549/DDP Cells / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Buzhong Yiqitang-containing serum in alleviating the cisplatin resistance in human non-small cell lung cancer （A549/DDP） cells via regulating the nuclear factor E2-related factor 2 （Nrf2）/reactive oxygen species （ROS） signaling pathway. MethodThe serum containing Buzhong Yiqitang was prepared and A549/DDP cells were cultured and randomly grouped： blank （10% blank serum）， cisplatin （10% blank serum+20 mg·L-1 cisplatin）， Buzhong Yiqitang （10% Buzhong Yiqitang-containing serum+20 mg·L-1 cisplatin）， ML385 （10% blank serum+5 μmol·L-1 ML385+20 mg·L-1 cisplatin）， Buzhong Yiqitang+ML385 （10% Buzhong Yiqitang-containing serum+5 μmol·L-1 ML385+20 mg·L-1 cisplatin）， tertiary butylhydroquinone （TBHQ） （10% blank serum+5 μmol·L-1 TBHQ+20 mg·L-1 cisplatin）， and Buzhong Yiqitang+TBHQ （10% Buzhong Yiqitang-containing serum+5 μmol·L-1 TBHQ+20 mg·L-1 cisplatin）. The median inhibitory concentration （IC50） of cisplatin in each group was determined by the cell counting kit-8 （CCK-8） method and the resistance index （RI） was calculated. The apoptosis rate was detected by flow cytometry. The ROS content of each group was determined with the DCFH-DA fluorescence probe. Western blot was employed to determine the protein levels of Nrf2， cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3）， cytochrome C （Cyt C）， and B-cell lymphoma-2 （Bcl-2）. ResultCompared with those in the cisplatin group， the IC50 and RI of A549/DDP cells to cisplatin in Buzhong Yiqitang， ML385， and Buzhong Yiqitang+ML385 groups decreased （P˂0.05）. Compared with the blank group， the cisplatin， Buzhong Yiqitang， ML385， and Buzhong Yiqitang+ML385 groups showed increased apoptosis rate of A549/DDP cells （P˂0.05）. Compared with the blank group， cisplatin promoted the expression of Nrf2 （P˂0.05）. Compared with the cisplatin group， Buzhong Yiqitang， ML385， and Buzhong Yiqitang+ML385 inhibited the expression of Nrf2 （P<0.05）， elevated the ROS level （P˂0.05）， up-regulated the protein levels of cleaved Caspase-3 and Cyt C， and down-regulated the protein level of Bcl-2 （P<0.05）， which were the most significant in the Buzhong Yiqitang+ML385 group. Compared with the cisplatin group， the TBHQ group showed increased IC50 and RI of cisplatin （P<0.05）， decreased apoptosis rate of A549/DDP cells （P<0.05）， up-regulated protein levels of Nrf2 and Bcl-2 （P<0.05）， lowered level of ROS （P˂0.05）， and down-regulated protein levels of cleaved Caspase-3 and Cyt C （P<0.05）. Compared with the TBHQ group， Buzhong Yiqitang+TBHQ decreased the IC50 and RI of cisplatin in A549/DDP cells （P<0.05）， increased the apoptosis rate （P<0.05）， down-regulated the protein levels of Nrf2 and Bcl-2 （P<0.05）， increased ROS （P˂0.05）， and up-regulated the protein levels of cleaved Caspase-3 and Cyt C （P<0.05）. ConclusionBuzhong Yiqitang induced apoptosis by inhibiting Nrf2/ROS pathway to alleviate cisplatin resistance in A549/DDP cells.

Discovery of proqodine A derivatives with antitumor activity targeting NAD(P)H: quinone oxidoreductase 1 and nicotinamide phosphoribosyltransferase / 中国天然药物

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD+), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD+ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.

Effects of visible lights, photodermatoses and role of antioxidants in skin health

Visible light (VL) radiation poses potential risks to the skin, including solar urticaria, chronic actinic dermatitis (CAD), cutaneous porphyrias, and others. Photodermatoses, another skin condition, can be worsened by exposure to light. Involves the production of reactive oxygen and nitrogen species (ROS and RNS, respectively), which harms proteins, lipids, and DNA results in an inflammatory reaction and increased skin pigmentation. Studies show that plant-derived antioxidants can shield VIS-exposed skin from oxidative damage brought on by ROS. Both API (Active pharmaceutical ingredients) and BTC (Bis trichloromethyl carbonate) give protection against harm caused by VL and useful topical antioxidants that can be added to sunscreens in terms of sun protection techniques, whereas, vitamins A, C, and E are antioxidants that reduce the aging process by preventing free radicals from oxidizing sensitive biological components. With an emphasis on either VL blocking (tinted sunscreens) or production of reactive species and radical quenching (antioxidant sunscreens), availability of photoprotection products that contain VL protection is expanding. Promising advancements have been made in incorporating antioxidants and radical scavengers into sunscreen formulations to address the induction of ROS/RNS by visible light. Topical application of an antioxidant blend containing varying concentrations of a singlet oxygen quencher along with fixed concentrations of vitamin E (0.25%) and vitamin C (0.01%) has shown ability to inhibit erythema and reduce pigmentation in certain skin types. Recent advancements in understanding VL's ability to induce reactive species have paved the way for antioxidant-based formulations, which offer promising alternatives for photoprotection across all skin types.

Moisture Stress in Upland Rice (Oryza sativa L.) and Measures to Overcome It under Changing Climate: A Review

Low yields in upland rice (Oryza sativa L.) are frequently linked to poor crop management practices along with a lack of high yielding varieties, abiotic and biotic stressors. Drought (lack of water), overwatering (waterlogging/flooding), extreme temperatures (cold, frost, and heat), etc, all negatively impact crop and other plant growth, development, yield, and seed quality. Drought or moisture stress is the most important factor affecting upland rice under changing climate. Global climate change also exacerbates the vulnerability of upland rice production. Upland rice plants undergo physiological and biochemical alterations as well as morphological changes as a result of moisture stress. Different moisture stress affects the yield of upland rice ranging from 18-97% yield loss. As a result, crop management with broad, integrative and multi-disciplinary methodologies is required to increase productivity and profitability. Different mitigation strategies to overcome moisture stress and increase upland rice yields have been addressed in this review.

Metformin Inhibits ROS/TNF-alpha Axis-Mediated Chronic Kidney Disease Induced by TAA Independent of Leukocyte Infiltration in Association with the Inhibition of Kidney Injury Biomarkers / La Metformina Inhibe la Enfermedad Renal Crónica Mediada por el Eje ROS/TNF-alfa Inducida por TAA Independientemente de la Infiltración de Leucocitos en Asociación con la Inhibición de Biomarcadores de Lesión Renal

SUMMARY: The toxic effects of thioacetamide (TAA) and carbon tetrachloride on the human body are well recognized. In this study, we examined whether TAA intoxication can induce kidney leukocyte infiltration (measured as leukocyte common antigen CD45) associated with the augmentation of the reactive oxygen species (ROS)/tumor necrosis factor-alpha (TNF-α) axis, as well as biomarkers of kidney injury with and without metformin treatment. Rats were either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed after 10 weeks (experimental group) or were pre-treated with metformin (200 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment, at week 10 (protective group). Using basic histology staining, immunohistochemistry methods, and blood chemistry analysis, we observed profound kidney tissue injury such as glomerular and tubular damage in the experimental group, which were substantially ameliorated by metformin. Metformin also significantly (p0.05) increase in kidney expression of CD45 positive immunostaining cells. In conclusion, we found that TAA induces kidney injury in association with the augmentation of ROS/TNF-α axis, independent of leukocyte infiltration, which is protected by metformin.

Son bien conocidosos los efectos tóxicos de la tioacetamida (TAA) y el tetracloruro de carbono en el cuerpo humano. En este estudio, examinamos si la intoxicación por TAA puede inducir la infiltración de leucocitos renales (medida como antígeno leucocitario común CD45) asociada con el aumento de las especies reactivas de oxígeno (ROS)/factor de necrosis tumoral-alfa (TNF-α), así como biomarcadores de daño renal con y sin tratamiento con metformina. A las ratas se les inyectó TAA (200 mg/kg; dos veces por semana durante 8 semanas) antes de sacrificarlas a las 10 semanas (grupo experimental) o se les pretrató con metformina (200 mg/kg) diariamente durante dos semanas antes de las inyecciones de TAA y continuaron recibiendo ambos agentes hasta el final del experimento, en la semana 10 (grupo protector). Usando tinción histológica básica, métodos de inmunohistoquímica y análisis químico de la sangre, observamos una lesión profunda del tejido renal, como daño glomerular y tubular en el grupo experimental, que mejoraron sustancialmente con la metformina. La metformina también inhibió significativamente (p0,05) en la expresión renal de células de inmunotinción positivas para CD45. En conclusión, encontramos que el TAA induce la lesión renal en asociación con el aumento del eje ROS/TNF-α, independientemente de la infiltración de leucocitos, que está protegida por metformina.