Role of reactive oxygen species in epithelial-mesenchymal transition and apoptosis of human lens epithelial cells

AIM:To investigate the role of reactive oxygen species(ROS)in epithelial–mesenchymal transition(EMT)and apoptosis of human lens epithelial cells(HLECs).METHODS:Flow cytometry was used to assess ROS production after transforming growth factorβ2(TGF-β2)induction.Apoptosis of HLECs after H_(2)O_(2) and TGF-β2 interference with or without ROS scavenger N-acetylcysteine(NAC)were assessed by flow cytometry.The corresponding protein expression levels of the EMT markerα-smooth muscle actin(α-SMA),the extracellular matrix(ECM),marker fibronectin(Fn),and apoptosis-associated proteins were detected by using Western blotting in the presence of an ROS scavenger(NAC).Wound-healing and Transwell assays were used to assess the migration capability of HLECs.RESULTS:TGF-β2 stimulates ROS production within 8h in HLECs.Additionally,TGF-β2 induced HLECs cell apoptosis,EMT/ECM synthesis protein markers expression,and pro-apoptotic proteins production;nonetheless,NAC treatment prevented these responses.Similarly,TGF-β2 promoted HLECs cell migration,whereas NAC inhibited cell migration.We further determined that although ROS initiated apoptosis,it only induced the accumulation of the EMT markerα-SMA protein,but not COL-1 or Fn.CONCLUSION:ROS contribute to TGF-β2-induced EMT/ECM synthesis and cell apoptosis of HLECs;however,ROS alone are not sufficient for EMT/ECM synthesis.

Effect and mechanism of reactive oxygen species-mediated NOD-like receptor family pyrin domain-containing 3 inflammasome activation in hepatic alveolar echinococcosis

BACKGROUND The NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome is a significant component of the innate immune system that plays a vital role in the development of various parasitic diseases.However,its role in hepatic alveolar echinococcosis(HAE)remains unclear.AIM To investigate the NLRP3 inflammasome and its mechanism of activation in HAE.METHODS We assessed the expression of NLRP3,caspase-1,interleukin(IL)-1β,and IL-18 in the marginal zone and corresponding normal liver of 60 patients with HAE.A rat model of HAE was employed to investigate the role of the NLRP3 inflammasome in the marginal zone of HAE.Transwell experiments were conducted to investigate the effect of Echinococcus multilocularis(E.multilocularis)in stimulating Kupffer cells and hepatocytes.Furthermore,immunohistochemistry,Western blotting,and enzyme-linked immunosorbent assay were used to evaluate NLRP3,caspase-1,IL-1β,and IL-18 expression;flow cytometry was used to detect apoptosis and reactive oxygen species(ROS).RESULTS NLRP3 inflammasome activation was significantly associated with ROS.Inhibition of ROS production decreased NLRP3-caspase-1-IL-1βpathway activation and mitigated hepatocyte damage and inflammation.CONCLUSION E.multilocularis induces hepatocyte damage and inflammation by activating the ROS-mediated NLRP3-caspase-1-IL-1βpathway in Kupffer cells,indicating that ROS may serve as a potential target for the treatment of HAE.

Danlu Tongdu tablets treat lumbar spinal stenosis through reducing reactive oxygen species and apoptosis by regulating CDK2/CDK4/CDKN1A expression

Lumbar spinal stenosis is caused by the compression of the nerve root or cauda equina nerve by stenosis of the lumbar spinal canal or intervertebral foramen,and is manifested as chronic low back and leg pain.Danlu Tongdu(DLTD)tablets can relieve chronic pain caused by lumbar spinal stenosis,but the molecular mechanism remains largely unknown.In this study,the potential molecular mechanism of DLTD tablets in the treatment of lumbar spinal stenosis was first predicted by the network pharmacology method.Results showed that DLTD functions in regulating anti-oxidative,apoptosis,and inflammation signaling pathways.Furthermore,the flow cytometry results showed that DLTD tablets efficiently reduced reactive oxygen species content and inhibited rat neural stem cell apoptosis induced by hydrogen peroxide.DLTD also inhibited the mitochondrial membrane potential damage induced by hydrogen peroxide.Elisa analysis showed that DLTD induced cell cycle-related protein,CDK2 and CDK4,and reduced CDKN1A protein expression level.Taken together,our study provided new insights of DLTD in treating lumbar spinal stenosis through reducing reactive oxygen species content,decreasing apoptosis by inhibiting CDKN1A and promoting CDK2 and CDK4 expression levels.

The cell cycle related apoptotic susceptibility to arsenic trioxide is associated with the level of reactive oxygen species

Double staining flow cytometry was performed using 7-amino actinomycin D and 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate,to detect the level fluctuation of reactive oxygen species (ROS) during the cell cycle of normal NB4 cells. Our results showed that NB4 cells possessed higher level of ROS in G2/M phase than in G1 and S phases. Double staining flow cytometry,with TdT mediated dUTP nick end labeling (Tunel) and propidium iodide (PI),indicated that As2O3 (2 μM) could induce apoptosis in NB4 cells prevailingly from G2/M phase,and this efficacy was enhanced upon co-administration of 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) (2.5 μM) which could produce the endogenous ROS. These results suggested that different ROS level in different cell cycle phases of NB4 cells might determin the selective induction of G2/M apoptosis and the cells' susceptibility to apoptosis by As2O3.

Changes of NF-kB,p53,Bcl-2 and caspase in apoptosis induced by JTE-522 in human gastric adenocarcinoma cell line AGS cells:role of reactive oxygen species

AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process. METHODS: Cell culture, MTT, Electromicroscopy, agarose gel electrophoresis, lucigenin, Western blot and electrophoretic mobility shift assay (EMSA) analysis were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanisms. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Lucigenin assay showed the generation of ROS in cells under incubation with JTE-522. The increased ROS generation might contribute to the induction of AGS cells to apoptosis. EMSA and Western blot revealed that NF-kB activity was almost completely inhibited by preventing the degradation of IkBalpha. Additionally, by using Western blot we confirmed that the level of bcl-2 was decreased, whereas p53 showed a great increase following JTE-522 treatment. Their changes were in a dose-dependent manner. CONCLUSION: These findings suggest that reactive oxygen species, NF-kB, p53, bcl-2 and caspase-3 may play an important role in the induction of apoptosis in AGS cells after treatment with JTE-522.

Urotensin Ⅱ-induced insulin resistance is mediated by NADPH oxidase-derived reactive oxygen species in Hep G2 cells

AIM: To investigated the effects of urotensin Ⅱ(UII) on hepatic insulin resistance in Hep G2 cells and the potential mechanisms involved.METHODS: Human hepatoma Hep G2 cells were cultured with or without exogenous UII for 24 h, in the presence or absence of 100 nmol/L insulin for the last 30 min. Glucose levels were detected by the glucoseoxidase method and glycogen synthesis was analyzed by glycogen colorimetric/fluorometric assay. Reactive oxygen species(ROS) levels were detected with a multimode reader using a 2′,7′-dichlorofluorescein diacetate probe. The protein expression and phosphorylation levels of c-Jun N-terminal kinase(JNK), insulin signal essential molecules such as insulin receptor substrate-1(IRS-1), protein kinase B(Akt), glycogen synthase kinase-3β(GSK-3β), and glucose transporter-2(Glut 2), and NADPH oxidase subunits such as gp91 phox, p67 phox, p47 phox, p40 phox, and p22 phox were evaluated by Western blot.RESULTS: Exposure to 100 nmol/L UII reduced the insulin-induced glucose consumption(P < 0.05)and glycogen content(P < 0.01) in Hep G2 cells compared with cells without UII. UII also abolished insulin-stimulated protein expression(P < 0.01) and phosphorylation of IRS-1(P < 0.05), associated with down-regulation of Akt(P < 0.05) and GSK-3β(P < 0.05) phosphorylation levels, and the expression of Glut 2(P < 0.001), indicating an insulin-resistance state in Hep G2 cells. Furthermore, UII enhanced the phosphorylation of JNK(P < 0.05), while the activity of JNK, insulin signaling, such as total protein of IRS-1(P < 0.001), phosphorylation of IRS-1(P < 0.001) and GSK-3β(P < 0.05), and glycogen synthesis(P < 0.001) could be reversed by pretreatment with the JNK inhibitor SP600125. Besides, UII markedly improved ROS generation(P < 0.05) and NADPH oxidase subunit expression(P < 0.05). However, the antioxidant/NADPH oxidase inhibitor apocynin could decrease UII-induced ROS production(P < 0.05), JNK phosphorylation(P < 0.05), and insulin resistance(P < 0.05) in HepG 2 cells. CONCLUSION: UII induces insulin resistance, and this can be reversed by JNK inhibitor SP600125 and antioxidant/NADPH oxidase inhibitor apocynin targeting the insulin signaling pathway in HepG 2 cells.

High glucose induces myocardial cell injury through increasing reactive oxygen species production

Objective: To study the injury effect and molecular mechanism of high glucose on myocardial cells. Methods: Myocardial cells H9 c2 were cultured and divided into the control group treated with DMEM containing 5.5 mmol/L glucose, the high glucose group treated with DMEM containing 35 mmol/L glucose, and the N-acetylcysteine(NAC) group pre-treated with 1000μmol/L NAC and treated with DMEM containing 1000 μmol/L NAC and 35 mmol/L glucose.The production of ROS and the expression of mitochondria pathway apoptosis molecules in cells as well as the contents of collagen and collagen metabolism molecules were measured.Results: After 8 h, 16 h and 24 h of treatment, ROS RFU as well as Bax, CytC, Caspase-3 and Caspase-9 protein expression in cells and Col-I, Col-Ⅲ, PINP and PⅢNP protein levels in culture medium of high glucose group were higher than those of control group, Bcl-2 protein expression were lower than those of control group, but CTX-Ⅰ protein levels in culture medium were not significantly different from those of control group; after 24 h of treatment, Bax, CytC,Caspase-3 and Caspase-9 protein expression in cells as well as Col-Ⅰ, Col-Ⅲ, PINP and PIIINP protein levels in culture medium of NAC group were lower than those of high glucose group whereas Bcl-2 protein expression was higher than that of high glucose group. Conclusions:High glucose can induce myocardial cell apoptosis, increase collagen synthesis and accelerate interstitial fibrosis by increasing the production of reactive oxygen species.

Autophagic cell death induced by reactive oxygen species is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells

AIM To investigate whether autophagic cell death is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells, and to explore the underlying mechanism.METHODS Human hepatocellular carcinoma cells were treated with hyperthermia and ionizing radiation. MTT and clonogenic assays were performed to determine cell survival. Cell autophagy was detected using acridine orange staining and flow cytometric analysis, and the expression of autophagy-associated proteins, LC3 and p62, was determined by Western blot analysis. Intracellular reactive oxygen species(ROS) were quantified using the fluorescent probe DCFH-DA.RESULTS Treatment with hyperthermia and ionizing radiation significantly decreased cell viability and surviving fraction as compared with hyperthermia or ionizing radiation alone. Cell autophagy was significantly increased after ionizing radiation combined with hyperthermia treatment, as evidenced by increased formation of acidic vesicular organelles, increased expression of LC3 II and decreased expression of p62. Intracellular ROS were also increased after combined treatment with hyperthermia and ionizing radiation. Pretreatment with N-acetylcysteine, an ROS scavenger, markedly inhibited the cytotoxicity and cell autophagy induced by hyperthermia and ionizing radiation.CONCLUSION Autophagic cell death is involved in hyperthermic sensitization of cancer cells to ionizing radiation, and its induction may be due to the increased intracellular ROS.

Production of reactive oxygen species and expression of inducible nitric oxide synthase in rat isolated Kupffer cells stimulated by Leptospira interrogans and Borrelia burgdorfen

AIM： To evaluate the production of reactive oxygen species （ROS） and the expression of inducible nitric oxide synthase （iNOS） in rat isolated Kupffer cells （KCs） stimulated by Leptospira interrogans and Borrelia burgdorferi. METHODS： Rat Kupffer cells were separated by perfusion of the liver with 0.05% collagenase, and purified by Percoll gradients. Pudfied Kupffer cells were tested in vitro with alive L.interogans and B. burgdorferi preparations. The production of ROS was determined by chemiluminescence, whereas iNOS protein expression was evaluated by Western blot assay using anti-iNOS antibodies. RESULTS： B. burgdorferi and to a less extent L. interrogans induced ROS production with a peak 35 min after infection. The chemiluminescence signal progressively diminished and was undetectable by 180 min of incubation. Leptospirae and borreliae induced an increased iNOS expression in Kupffer cells that peaked at 6 hours and was still evident 22 h after infection. CONCLUSION： Both genera of spirochetes induced ROS and iNOS production in rat Kupffer cells. Since the cause of liver damage both in leptospiral as well as in borrelial infections are still unknown, we suggest that leptospira and borrelia damage of the liver can be initially mediated by oxygen radicals, and is then maintained at least in part by nitric oxide.

Reactive oxygen species are involved in cell death in wheat roots against powdery mildew

Inoculation of wheat(Triticum aestivum L.)leaves with wheat powdery mildew fungus(Blumeria graminis f.sp.tritici)induces the cell death in adventitious roots.Reactive oxygen species(ROS)play a key role in respond to biotic stress in plants.To study the involvement of ROS and the degree of cell death in the wheat roots following inoculation,ROS levels and microstructure of root cells were analyzed in two wheat cultivars that are susceptible(Huamai 8)and resistant(Shenmai 8)to powdery mildew fungus.At 18 d after powdery mildew fungus inoculation,only Huamai 8 displayed the leaf lesions,while root cell death occurred in both varieties.Huamai 8 had a high level of ROS accumulation,which is associated with increased root cell degradation,while in Shenmai 8,there was little ROS accumulation correlating with slight root cell degradation.The molecular study about the expression levels of ROS scavenging genes(MnSOD and CAT)in wheat roots showed that these genes expression decreased after the leaves of wheat was inoculated.The difference between Huamai 8 and Shenmai 8 on subcellular localization of H2 O2 and O2^–·was corresponded with the different down-regulation of the genes encoding for superoxide dismutase and catalase in two wheat cultivars.These results suggested that ROS were involved in the process by which powdery mildew fungus induced cell death in wheat roots.

Fluorescent intracellular imaging of reactive oxygen species and pH levels moderated by a hydrogenase mimic in living cells

The catalytic generation of H_(2) in living cells provides a method for antioxidant therapy.In this study,an[FeFe]-hydrogenase mimic[Ru+Fe_(2)S_(2)@F127(80)]was synthesized by self-assembling polymeric pluronic F-127,catalytic[Fe_(2)S_(2)]sites,and photosensitizer Ru(bpy)_(3)^(2+).Under blue light irradiation,hydrated protons were photochemically reduced to H2,which increased the local pH in living cells(HeLa cells).The generated H2 was subsequently used as an antioxidant to decrease reactive oxygen species(ROS)levels in living cells(HEK 293T,HepG2,MCF-7,and HeLa cells).Our findings revealed that the proliferation of HEK 293T cells increased by a factor of about six times,relative to that of other cells(HepG2,MCF-7,and HeLa cells).Intracellular ROS and pH levels were then monitored using fluorescent cell imaging.Our study showed that cell imaging can be used to evaluate the ability of Ru t Fe2S2@F127 to eliminate oxidative stress and prevent ROS-related diseases.

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

Photodynamic therapy(PDT)is an effective and promising cancer treatment.PDT directly generates reactive oxygen species(ROS)through photochemical reactions.This oxygen-dependent exogenous ROS has anti-cancer stem cell(CSC)effect.In addition,PDT may also increase ROS production by altering metabolism,endoplasmic reticulum stress,or potential of mitochondrial membrane.It is known that the half-life of ROS in PDT is short,with high reactivity and limited diffusion distance.Therefore,the main targeting position of PDT is often the subcellular localization of photosensitizers,which is helpful for us to explain how PDT affects CSC characteristics,including differentiation,selfrenewal,apoptosis,autophagy,and immunogenicity.Broadly speaking,excess ROS will damage the redox system and cause oxidative damage to molecules such as DNA,change mitochondrial permeability,activate unfolded protein response,autophagy,and CSC resting state.Therefore,understanding the molecular mechanism by which ROS affect CSCs is beneficial to improve the efficiency of PDT and prevent tumor recurrence and metastasis.In this article,we review the effects of two types of photochemical reactions on PDT,the metabolic processes,and the biological effects of ROS in different subcellular locations on CSCs.

Cell viability in the cadmium-stressed cell suspension cultures of tobacco is regulated by extracellular ATP,possibly by a reactive oxygen species-associated mechanism

Cadmium(Cd)is one of the most widespread and toxic heavy metals to plants.Extracellular ATP(exATP)is thought to be an extracellular effector in regulating the physiological responses of plant cells to environmental stresses.However,the function of exATP in Cd-stressed plant cells is much unknown.The present work showed that treating tobacco(Nicotiana tabacum L.cv.Bright Yellow-2)cell-suspension cultures with exogenous CdCl2 reduced the cell viability,exATP level,and Mg content.However,the production of reactive oxygen species(ROS),Cd content,and electrolyte leakage of the cells were enhanced by exogenous CdCl2.When the Cd-induced accumulation of ROS was decreased by the supplement with DMTU(dimethylthiourea,a scavenger of ROS),the Cd-induced increases of the electrolyte leakage and Cd content were alleviated,and the Cd-induced reductions of cell viability were partly rescued,suggesting that Cd-induced reduction of cell viability could be related to the ROS accumulation.Under the condition of Cd stress,when the reduction of exATP level was partly rescued by exogenous ATP(20μM),the increases of ROS production,electrolyte leakage,and Cd content were attenuated,and the reduction of cell viability was also alleviated.These observations indicate that exATP can regulate the cell viability in the Cd–stressed plant cells possibly by an ROS-associated mechanism.

Effect of Antioxidants on Endothelial Cell Reactive Oxygen Species (ROD Generation and Adhesion of Leukocytes to Endothelial Cells

Objective To investigatewhether antioxidants inhibit adhesion of leukocytes to endothelium and furthermore, whether all antioxidants regulate NF-KB activation through a redox sensitive mechanism. Methods The effect of the antioxidative substances pyrrolidin dithiocarbamat (PDTC), dichloroisocumarin (DCI), chrysin and probucol on the endothelial leukocyte adhesion were examined under near physiological flow conditions. The antioxidative activity of antioxidants was measured in a DCF fluorescence assay with flow cytometry. The activation of NF-kB in endothelial cells was investigated in a gel shift assay. Results PDTC and probucol did not show an inhibitory effect to the formation of intracellular H2O2 in TNFa activated human vascular endothelial cells (HUVEC) . Chrysin showed a moderate effect. DCI showed a strong antioxidative effect. In contrast, PDTC and chrysin inhibited the adhesion of HL 60 cells to TNFa-stimulated HUVEC. DCI and probucol did not have influence on the adhesion within the area of the examined shear stresses. Only PDTC inhibited the TNFa-induced activation of NF-KB in endothelial cells. Conclusion The inhibition of the endothelial leukocyte adhesion by antioxidative substances is not to be explained by its antioxidative characteristics only. The inhibitory effect of PDTC on NF-KB activation was probably not related to its antioxidative properties. Endothelial cell Antioxidants NF-kappa-B

Tamarind seed coat extract restores reactive oxygen species through attenuation of glutathione level and antioxidant enzyme expression in human skin fibroblasts in response to oxidative stress

Objective:To investigate the role and mechanism of tamarind seed coat extract(TSCE) on normal human skin fibroblast CCD-l064Sk cells under normal and oxidative stress conditions induced by hydrogen peroxide(H_2O_2).Methods:Tamarind seed coats were extracted with boiling water and then partitioned with ethyl acetate before the cell analysis.Effect of TSCE on intracellular reactive oxygen species(ROS),glutathione(GSH) level,antioxidant enzymes such as superoxide dismulase(SOU),glutathione peroxidase(CPx) and catalase activity including antioxidant protein expression was investigated.Results:TSCE significantly attenuated intracellular ROS in the absence and presence of H_1O_2by increasing GSH level In the absence of H_2O_2,TSCE significantly enhanced SOD and catalase activity but did not affected on CPx.Meanwhile,TSCE significantly increased the protein expression of SOD and CPx in H_2O_2-treated cells.Conclusions:TSCE exhibited antioxidant activities by scavenging ROS.attenuating GSll level that could protect human skin fibroblast cells from oxidative stress.Our results highlight the antioxidant mechanism of tamarind seed coat through an antioxidant enzyme system,the exlracl potentially benefits for health food and cosmeceutical application of tamarind seed coat.

Reactive oxygen species induced oxidative stress, neuronal apoptosis and alternative death pathways

Reactive oxygen species (ROS) are produced as a byproduct of cellular metabolic pathways and function as a critical second messenger in a variety of intracellular signaling pathways. The excessive intracellular generation of ROS on the other renders a cell oxidatively stressed. This involvement of ROS in numerous diseases has been documented and at different phases of the apoptotic pathway such as induction of mitochondrial permeability transition and release of mitochondrial death amplification factors, activetion of intracellular caspases and DNA damage has been clearly established. Cell death by apoptosis is a part of normal development and maintenance of tissue homeostasis. Polychlorinated biphenyls, one of the environmental pollutants which are widely used in electrical industries and lipophilic and resistant to biological decomposition accumulate through food chain. They are developmental neurotoxicants which induce neuronal apoptosis. Our studies proved that oxidative stress is induced promoting LPO and a decrease in all the antioxidant enzymes in testis, epididymis, ventral prostate, seminal vesicles, liver, kidney and brain regions. Neuronal damages were observed in all the brain regions after PCB exposure. PCB increased caspase8 mRNA/protein expression in hippocampus of adult rats. This upregulation results in Fas-FasL mediated induction of hippocampal apoptosis. Performin/granzyme induced apoptosis is the main pathway used by cytotoxic lymphocytes to eliminate virus-infected or transformed cells. The production of ROS is greatly increased during reperfusion phase when oxygen becomes available and the mitochondrial respiratory chain is impaired. Furthermore, this is exacerbated by reduced antioxidant defenses.

Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells

The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechanisms responsible for initiating spontaneous ATP release have not been determined.Our previous study revealed that telomerase reverse transcriptase(TERT)is expressed in the basilar membrane during the first postnatal week.Its role in cochlear development remains unclear.In this study,we investigated the expression and role of TERT in postnatal cochlea supporting cells.Our results revealed that in postnatal cochlear Kölliker’s organ supporting cells,TERT shifts from the nucleus into the cytoplasm over time.We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo.Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis,suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions.We observed increased ATP synthesis,release and activation of purine signaling systems in supporting cells during the first 10 postnatal days.The phenomenon that TERT translocation coincided with changes in ATP synthesis,release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system.Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.

Red light-driven generation of reactive oxygen species for the targeted oxidation of glioma cells and thiols over covalent organic framework

Reactive oxygen species(RoS)are essential for biological processes like cell signaling and chemical processes like organic oxidation.Moreover,the sufficient generation of RoS plays a significant role in targeted tumor treatments or oxidation of organics.Herein,a hydrazone-linked porphyrin covalent organic framework(Por-DETH-COF)is developed for red light-induced generation of ROS like singlet oxygen(^(1)O_(2))or superoxide(O_(2)·^(-))to undertake different but targeted oxidations.First,^(1)O_(2)is adopted in photodynamic therapy(PDT)for the oxidation of glioma cells.The PDT efficiency of Por-DETH-COF on the apoptosis of glioma cells is explored through flow cytometry and western blot assay.The apoptosis rate of glioma cells significantly increases over Por-DETH-COF under 660nm red light illumination,suggestive of the potency of^(1)O_(2).Second,O_(2)^(·-)is employed for the targeted oxidation of thiols.A series of thiols could be efficiently oxidized to corresponding disulfides over Por-DETH-COF under 660 nm red light illumination,indicative of the significance of O_(2)^(·-).This work highlights the potential of covalent organic frameworks in generating Ros for precise medical applications of complex chemical environments.