The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzin...The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzing APIP5-RNAi transgenic plants.To further investigate the biological functions of OsbZIP53,we generated osbzip53 mutants using CRISPR/Cas9 editing and also constructed OsbZIP53 over-expression transgenic plants.Comprehensive analysis of phenotypical,physiological,and transcriptional data showed that knocking-out OsbZIP53 not only improved disease resistance by inducing a hypersensitivity response in plants,but also regulated the immune response through the salicylic acid pathway.Specifically,disrupting OsbZIP53 increased H2O2 accumulation by promoting reactive oxygen species generation through up-regulation of several respiratory burst oxidase homologs(Osrboh genes)and weakened H2O2 degradation by directly targeting OsMYBS1.In addition,the growth of osbzip53 mutants was seriously impaired,while OsbZIP53 over-expression lines displayed a similar phenotype to the wild type,suggesting that OsbZIP53 has a balancing effect on rice immune response and growth.展开更多
Conventional blood sampling for glucose detection is prone to cause pain and fails to continuously record glucose fluctuations in vivo.Continuous glucose monitoring based on implantable electrodes could induce pain an...Conventional blood sampling for glucose detection is prone to cause pain and fails to continuously record glucose fluctuations in vivo.Continuous glucose monitoring based on implantable electrodes could induce pain and potential tissue inflammation,and the presence of reactive oxygen species(ROS)due to inflammationmay affect glucose detection.Microneedle technology is less invasive,yet microneedle adhesion with skin tissue is limited.In this work,we developed a microarrow sensor array(MASA),which provided enhanced skin surface adhesion and enabled simultaneous detection of glucose and H_(2)O_(2)(representative of ROS)in interstitial fluid in vivo.The microarrows fabricated via laser micromachining were modified with functional coating and integrated into a patch of a three-dimensional(3D)microneedle array.Due to the arrow tip mechanically interlocking with the tissue,the microarrow array could better adhere to the skin surface after penetration into skin.The MASA was demonstrated to provide continuous in vivo monitoring of glucose and H_(2)O_(2) concentrations,with the detection of H_(2)O_(2) providing a valuable reference for assessing the inflammation state.Finally,the MASA was integrated into a monitoring system using custom circuitry.This work provides a promising tool for the stable and reliable monitoring of blood glucose in diabetic patients.展开更多
Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a ...Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.展开更多
The role of reactive oxygen species(ROS)in ischemic and reperfusion(I/R)injury of the heart has been discussed for more than 40 years.It has been demonstrated that reperfusion triggers a multiple increase in free radi...The role of reactive oxygen species(ROS)in ischemic and reperfusion(I/R)injury of the heart has been discussed for more than 40 years.It has been demonstrated that reperfusion triggers a multiple increase in free radical generation in the isolated heart.Antioxidants were found to have the ability to mitigate I/R injury of the heart.However,it is unclear whether their cardioprotective effect truly depends on the decrease of ROS levels in myocardial tissues.Since high doses and high concentrations of antioxidants were experimentally used,it is highly likely that the cardioprotective effect of antioxidants depends on their interaction not only with free radicals but also with other molecules.It has been demonstrated that the antioxidant N-2-mercaptopropionyl glycine or NDPH oxidase knockout abolished the cardioprotective effect of ischemic preconditioning.Consequently,there is evidence that ROS protect the heart against the I/R injury.展开更多
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.Howe...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.展开更多
Neurite degeneration,a major component of many neurodegenerative diseases,such as Parkinson’s disease,Alzheimer’s disease,and amyotrophic lateral sclerosis,is not part of the typical apoptosis signaling mechanism,bu...Neurite degeneration,a major component of many neurodegenerative diseases,such as Parkinson’s disease,Alzheimer’s disease,and amyotrophic lateral sclerosis,is not part of the typical apoptosis signaling mechanism,but rather it appears that a self-destructive process is in action.Oxidative stress is a well-known inducer of neurodegenerative pathways:neuronal cell death and neurite degeneration.Although oxidative stress exerts cytotoxic effects leading to neuronal loss,the pathogenic mechanisms and precise signaling pathways by which oxidative stress causes neurite degeneration have remained entirely unknown.We previously reported that reactive oxygen species generated by NADPH oxidases induce activation of the E3 ubiquitin ligase ZNRF1 in neurons,which promotes neurite degeneration.In this process,the phosphorylation of an NADPH oxidase subunit p47-phox at the 345serine residue serves as an important checkpoint to initiate the ZNRF1-dependent neurite degeneration.Evidence provides new insights into the mechanism of reactive oxygen species-mediated neurodegeneration.In this review,we focus specifically on reactive oxygen species-induced neurite degeneration by highlighting a phosphorylation-dependent regulation of the molecular interaction between ZNRF1 and the NADPH oxidase complex.展开更多
The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/re...The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1/mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6/mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1/cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factorkappa B(NF-kB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-kB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-kB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca^(2+) influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-kB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.展开更多
Objective:To investigate the effects of different concentrations of N-acetylcysteine on follicular growth and morphology,as well as on viability,levels of reactive oxygen species(ROS)and meiotic progression of oocytes...Objective:To investigate the effects of different concentrations of N-acetylcysteine on follicular growth and morphology,as well as on viability,levels of reactive oxygen species(ROS)and meiotic progression of oocytes from in vitro cultured bovine early antral follicles.Methods:Isolated early antral follicles(about 500μm)were cultured in TCM-199+alone or supplemented with 1.0,5.0 or 25.0 mM N-acetylcysteine at 38.5℃with 5%CO_(2) for 8 days.Follicle diameters were evaluated at day 0,4 and 8 of culture.At the end of culture,the levels of ROS,chromatin configuration and viability(calcein-AM and ethidium homodimer-1 staining)were investigated in the cumulus-oocyte complexes.Comparisons of follicle diameters between treatments were performed.Data on percentages of morphologically normal follicles,growth rates and chromatin configuration in different treatments were compared.Results:An increase in follicular diameters after culture in all treatments was observed,except for follicles cultured with 25.0 mM N-acetylcysteine.Fluorescence microscopy showed that oocytes cultured in all treatments were stained positively with calcein AM,and that 5.0 mM N-acetylcysteine reduced fluorescence for ethidium homodimer-1.Intracellular levels of ROS in oocytes from follicles cultured with 1.0 mM N-acetylcysteine showed a significant reduction compared to other treatments.The presence of N-acetylcysteine in culture medium did not influence the rates of oocyte at the germinal vesicle stage.Conclusions:N-acetylcysteine at concentrations of 1.0 and 5.0 mM reduces ROS levels and staining for ethidium homodimer-1 in in vitro cultured follicles,respectively,while 25.0 mM N-acetylcysteine decreases follicular growth and the percentages of continuously growing follicles.展开更多
Recently, we found some errors in Fig. 3 of the article Chin. Phys. B 24 085201 (2015). Upon a thorough examination of the raw data materials, we confirm that the image error did not impact any of the findings and con...Recently, we found some errors in Fig. 3 of the article Chin. Phys. B 24 085201 (2015). Upon a thorough examination of the raw data materials, we confirm that the image error did not impact any of the findings and conclusions of the paper. Based on this, we have made corrections to the original article.展开更多
Senescence is the last developmental process in plant,which has an important impact on crop yield and quality.In this study,a stable hereditary early-senescence line BC64 was isolated from the high-generation recombin...Senescence is the last developmental process in plant,which has an important impact on crop yield and quality.In this study,a stable hereditary early-senescence line BC64 was isolated from the high-generation recombinant inbred lines of 93-11 and Wuyunjing7(W7).Genetic analysis showed that the premature aging phenotype was controlled by a dominant gene derived from 93-11.By linkage analysis,the gene was primarily mapped in the region between marker B4 and B5 near the centromere of chromosome 4,described as ES(4).Through multiple backcrossing with W7,the near-isogenic line of ES(4)(NIL-ES(4))was obtained.Compared with wild-type W7,NIL-ES(4)plants showed more sever senescence phenotype in both nature and dark conditions.In NIL plants,leaves turned yellow at the fully tillering stage;photosynthetic rate,pollen fertility and seed setting rate were decreased.Moreover,the malondialdehyde,proline content and relative conductivity in NIL-ES(4)were significantly higher than those in W7;both transcript level and activities of reactive oxygen species scavenging enzymes were repressed;H2O2 and O^(2−)were significantly accumulated.This study provides a basis for further cloning and function identification of ES(4).展开更多
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 t...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.展开更多
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 Ton...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.展开更多
In recent years,because of the growing desire to improve the noninvasiveness and safety of tumor treatments,sonodynamic therapy has gradually become a popular research topic.However,due to the complexity of the therap...In recent years,because of the growing desire to improve the noninvasiveness and safety of tumor treatments,sonodynamic therapy has gradually become a popular research topic.However,due to the complexity of the therapeutic process,the relevant mechanisms have not yet been fully elucidated.One of the widely accepted possibilities involves the effect of reactive oxygen species.In this review,the mechanism of reactive oxygen species production by sonodynamic therapy(SDT)and ways to enhance the sonodynamic production of reactive oxygen species are reviewed.Then,the clinical application and limitations of SDT are discussed.In conclusion,current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen,exhibit biological safety,and promote the clinical transformation of sonodynamic therapy.展开更多
The antibacterial activity of copper is well-known from an ancient civilization, however, its biocidal mechanism has not been necessarily elucidated. Notwithstanding up to now, mainly 4 processes have been proposed. A...The antibacterial activity of copper is well-known from an ancient civilization, however, its biocidal mechanism has not been necessarily elucidated. Notwithstanding up to now, mainly 4 processes have been proposed. Among them, it is cleared that 4 kinds of reactive oxygen species (ROS): hydroxyl radical ·OH, hydrogen per oxide H<sub>2</sub>O<sub>2</sub>, superoxide anion ·O<sup>-</sup>2</sub></sub> and singlet oxygen <sup>1</sup>O<sub>2</sub>, play an important role for contact-killing of bacteria, viruses and fungi. In this paper, generation of ROS on the surfaces of copper plates heated from room temperature to 673 K for 4.2 × 10<sup>2</sup> s in air, was investigated using the chemiluminescence. ROS have been evaluated by selecting the most suitable scavengers, such as 2-propanol for ·OH, sodium pyruvate for H<sub>2</sub>O<sub>2</sub>, nitro blue tetrazolium for ·O<sup>-</sup>2</sub></sub>, and sodium azide NaN<sub>3</sub> for <sup>1</sup>O<sub>2</sub>. At the same time the outermost surface of copper, on which thin film of cuprous oxide Cu<sub>2</sub>O was first formed and then cupric oxide CuO was laminated on Cu<sub>2</sub>O, was examined by thin-film XRD and TEM analysis to estimate the amounts and kinds of copper oxides. It was found that the most amounts of ROS were obtained for the 573 K-heated Cu plate and they were composed of ·OH, H<sub>2</sub>O<sub>2</sub>, and ·O<sup>-</sup>2.</sub></sub>.展开更多
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 diab...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.展开更多
Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Re...Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.展开更多
Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the m...Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains unclear.Protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum stress.Parkin is regulated by PERK and is a target of the unfolded protein response.It is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh Parkin.In this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s disease.We used adeno-associated virus to knockdown PHB2 expression.Our res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s disease.Ove rexpression of PHB2 inhibited these abnormalities.We also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s disease.We found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted mitophagy.In addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of PERK.These findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.展开更多
As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative str...As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.展开更多
Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism ...Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats.The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane,with histological score decreasing from 3.12±0.27 to 2.20±0.22 and anti-adhesion effectiveness increasing from 21.61%to 44.72%.Mechanistically,the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively;thus,the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited.Consequently,excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)is largely reduced.For biocompatibility evaluation,PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes.Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds,which further delays the fibrosis process.It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.展开更多
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 mechani...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.展开更多
基金the Zhejiang Natural Science Foundation,China(Grant No.LY21C130004)the Key Research and Development Program of Zhejiang Province,China(Grant No.2021C02056-3)+1 种基金the Central Public-Interest Scientific Institution Basal Research Fund,China(Grant No.CPSIBRF-CNRRI-202202)the Agricultural Science and Technology Innovation Program,China(Grant No.CAASASTIP-2021-CNRRI).
文摘The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzing APIP5-RNAi transgenic plants.To further investigate the biological functions of OsbZIP53,we generated osbzip53 mutants using CRISPR/Cas9 editing and also constructed OsbZIP53 over-expression transgenic plants.Comprehensive analysis of phenotypical,physiological,and transcriptional data showed that knocking-out OsbZIP53 not only improved disease resistance by inducing a hypersensitivity response in plants,but also regulated the immune response through the salicylic acid pathway.Specifically,disrupting OsbZIP53 increased H2O2 accumulation by promoting reactive oxygen species generation through up-regulation of several respiratory burst oxidase homologs(Osrboh genes)and weakened H2O2 degradation by directly targeting OsMYBS1.In addition,the growth of osbzip53 mutants was seriously impaired,while OsbZIP53 over-expression lines displayed a similar phenotype to the wild type,suggesting that OsbZIP53 has a balancing effect on rice immune response and growth.
基金This work was financially supported by the National Key R&D Program of China(Nos.2021YFF1200700 and 2021YFA0911100)the National Natural Science Foundation of China(Nos.32171399,32171456,and T2225010)+6 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515012261)the Science and Technology Program of Guangzhou,China(No.202103000076)the Fundamental Research Funds for the Central Universities,Sun Yat-Sen University(No.22dfx02),and Pazhou Lab,Guangzhou(No.PZL2021KF0003)FML would like to thank the National Natural Science Foundation of China(Nos.32171335 and 31900954)JL would like to thank the National Natural Science Foundation of China(No.62105380)the China Postdoctoral Science Foundation(No.2021M693686)QQOY would like to thank the China Postdoctoral Science Foundation(No.2022M713645).
文摘Conventional blood sampling for glucose detection is prone to cause pain and fails to continuously record glucose fluctuations in vivo.Continuous glucose monitoring based on implantable electrodes could induce pain and potential tissue inflammation,and the presence of reactive oxygen species(ROS)due to inflammationmay affect glucose detection.Microneedle technology is less invasive,yet microneedle adhesion with skin tissue is limited.In this work,we developed a microarrow sensor array(MASA),which provided enhanced skin surface adhesion and enabled simultaneous detection of glucose and H_(2)O_(2)(representative of ROS)in interstitial fluid in vivo.The microarrows fabricated via laser micromachining were modified with functional coating and integrated into a patch of a three-dimensional(3D)microneedle array.Due to the arrow tip mechanically interlocking with the tissue,the microarrow array could better adhere to the skin surface after penetration into skin.The MASA was demonstrated to provide continuous in vivo monitoring of glucose and H_(2)O_(2) concentrations,with the detection of H_(2)O_(2) providing a valuable reference for assessing the inflammation state.Finally,the MASA was integrated into a monitoring system using custom circuitry.This work provides a promising tool for the stable and reliable monitoring of blood glucose in diabetic patients.
基金supported by grants from Jiangsu Commission of Health,No.Z2021086(to XL)Science and Technology Program of Suzhou,Nos.SYSD2020008(to XL),SKYD2022012(to XL)+1 种基金Suzhou Municipal Health Commission,No.KJXW2020058(to XL)Science and Technology Program of Zhangjiagang,No.ZKS2018(to XL)。
文摘Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.
文摘The role of reactive oxygen species(ROS)in ischemic and reperfusion(I/R)injury of the heart has been discussed for more than 40 years.It has been demonstrated that reperfusion triggers a multiple increase in free radical generation in the isolated heart.Antioxidants were found to have the ability to mitigate I/R injury of the heart.However,it is unclear whether their cardioprotective effect truly depends on the decrease of ROS levels in myocardial tissues.Since high doses and high concentrations of antioxidants were experimentally used,it is highly likely that the cardioprotective effect of antioxidants depends on their interaction not only with free radicals but also with other molecules.It has been demonstrated that the antioxidant N-2-mercaptopropionyl glycine or NDPH oxidase knockout abolished the cardioprotective effect of ischemic preconditioning.Consequently,there is evidence that ROS protect the heart against the I/R injury.
基金Supported by the National Major Research and Development Project of“Precision Medicine Research”,No.2017YFC0909900Qinghai Province Science and Technology Department Programme,No.2019-SF-131the Qinghai Province Health and Family Planning Commission Programme,No.2016-wjzd-04.
文摘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.
文摘Neurite degeneration,a major component of many neurodegenerative diseases,such as Parkinson’s disease,Alzheimer’s disease,and amyotrophic lateral sclerosis,is not part of the typical apoptosis signaling mechanism,but rather it appears that a self-destructive process is in action.Oxidative stress is a well-known inducer of neurodegenerative pathways:neuronal cell death and neurite degeneration.Although oxidative stress exerts cytotoxic effects leading to neuronal loss,the pathogenic mechanisms and precise signaling pathways by which oxidative stress causes neurite degeneration have remained entirely unknown.We previously reported that reactive oxygen species generated by NADPH oxidases induce activation of the E3 ubiquitin ligase ZNRF1 in neurons,which promotes neurite degeneration.In this process,the phosphorylation of an NADPH oxidase subunit p47-phox at the 345serine residue serves as an important checkpoint to initiate the ZNRF1-dependent neurite degeneration.Evidence provides new insights into the mechanism of reactive oxygen species-mediated neurodegeneration.In this review,we focus specifically on reactive oxygen species-induced neurite degeneration by highlighting a phosphorylation-dependent regulation of the molecular interaction between ZNRF1 and the NADPH oxidase complex.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81970245,82270357,and 81770432)the Scientific Research Project of Shaanxi Administration of Traditional Chinese Medicine,China(Grant Nos.:2021-04-ZZ-001,2021-QYPT-003,and 2022-SLRH-YQ-004)+1 种基金the Project of Science and Technology Department of Shaanxi Province in China(Project No.:2022YWZX-PG-01)the Natural Science Basic Research Program of Shaanxi Province in China(Grant No.:2023-JC-JQ-61).
文摘The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1/mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6/mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1/cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factorkappa B(NF-kB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-kB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-kB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca^(2+) influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-kB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.
基金supported by grants from the National Council for Scientific and Technological Development(CNPq,Brazil,grant number 308737/2018-0).
文摘Objective:To investigate the effects of different concentrations of N-acetylcysteine on follicular growth and morphology,as well as on viability,levels of reactive oxygen species(ROS)and meiotic progression of oocytes from in vitro cultured bovine early antral follicles.Methods:Isolated early antral follicles(about 500μm)were cultured in TCM-199+alone or supplemented with 1.0,5.0 or 25.0 mM N-acetylcysteine at 38.5℃with 5%CO_(2) for 8 days.Follicle diameters were evaluated at day 0,4 and 8 of culture.At the end of culture,the levels of ROS,chromatin configuration and viability(calcein-AM and ethidium homodimer-1 staining)were investigated in the cumulus-oocyte complexes.Comparisons of follicle diameters between treatments were performed.Data on percentages of morphologically normal follicles,growth rates and chromatin configuration in different treatments were compared.Results:An increase in follicular diameters after culture in all treatments was observed,except for follicles cultured with 25.0 mM N-acetylcysteine.Fluorescence microscopy showed that oocytes cultured in all treatments were stained positively with calcein AM,and that 5.0 mM N-acetylcysteine reduced fluorescence for ethidium homodimer-1.Intracellular levels of ROS in oocytes from follicles cultured with 1.0 mM N-acetylcysteine showed a significant reduction compared to other treatments.The presence of N-acetylcysteine in culture medium did not influence the rates of oocyte at the germinal vesicle stage.Conclusions:N-acetylcysteine at concentrations of 1.0 and 5.0 mM reduces ROS levels and staining for ethidium homodimer-1 in in vitro cultured follicles,respectively,while 25.0 mM N-acetylcysteine decreases follicular growth and the percentages of continuously growing follicles.
文摘Recently, we found some errors in Fig. 3 of the article Chin. Phys. B 24 085201 (2015). Upon a thorough examination of the raw data materials, we confirm that the image error did not impact any of the findings and conclusions of the paper. Based on this, we have made corrections to the original article.
基金supported by grants from the Science Foundation of Jiangxi Province(Grant No.20212ACB215003)the National Natural Science Foundation of China(Grant No.31960403).
文摘Senescence is the last developmental process in plant,which has an important impact on crop yield and quality.In this study,a stable hereditary early-senescence line BC64 was isolated from the high-generation recombinant inbred lines of 93-11 and Wuyunjing7(W7).Genetic analysis showed that the premature aging phenotype was controlled by a dominant gene derived from 93-11.By linkage analysis,the gene was primarily mapped in the region between marker B4 and B5 near the centromere of chromosome 4,described as ES(4).Through multiple backcrossing with W7,the near-isogenic line of ES(4)(NIL-ES(4))was obtained.Compared with wild-type W7,NIL-ES(4)plants showed more sever senescence phenotype in both nature and dark conditions.In NIL plants,leaves turned yellow at the fully tillering stage;photosynthetic rate,pollen fertility and seed setting rate were decreased.Moreover,the malondialdehyde,proline content and relative conductivity in NIL-ES(4)were significantly higher than those in W7;both transcript level and activities of reactive oxygen species scavenging enzymes were repressed;H2O2 and O^(2−)were significantly accumulated.This study provides a basis for further cloning and function identification of ES(4).
基金Supported by the National Natural Science Foundation of China(No.82201163,No.81800812)Natural Science Foundation Youth Foundation of Shaanxi Province(No.2023-JC-QN-0861)Shaanxi Province Key Research and Development Program(No.2023-YBSF-483).
文摘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.
基金financially supported by the National Science Foundation of China(No.32271440).
文摘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.
基金the National Natural Science Foundation of China,No.82272004 and No.81974470the Nature Science Foundation of Zhejiang Province,No.LZ22H180001.
文摘In recent years,because of the growing desire to improve the noninvasiveness and safety of tumor treatments,sonodynamic therapy has gradually become a popular research topic.However,due to the complexity of the therapeutic process,the relevant mechanisms have not yet been fully elucidated.One of the widely accepted possibilities involves the effect of reactive oxygen species.In this review,the mechanism of reactive oxygen species production by sonodynamic therapy(SDT)and ways to enhance the sonodynamic production of reactive oxygen species are reviewed.Then,the clinical application and limitations of SDT are discussed.In conclusion,current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen,exhibit biological safety,and promote the clinical transformation of sonodynamic therapy.
文摘The antibacterial activity of copper is well-known from an ancient civilization, however, its biocidal mechanism has not been necessarily elucidated. Notwithstanding up to now, mainly 4 processes have been proposed. Among them, it is cleared that 4 kinds of reactive oxygen species (ROS): hydroxyl radical ·OH, hydrogen per oxide H<sub>2</sub>O<sub>2</sub>, superoxide anion ·O<sup>-</sup>2</sub></sub> and singlet oxygen <sup>1</sup>O<sub>2</sub>, play an important role for contact-killing of bacteria, viruses and fungi. In this paper, generation of ROS on the surfaces of copper plates heated from room temperature to 673 K for 4.2 × 10<sup>2</sup> s in air, was investigated using the chemiluminescence. ROS have been evaluated by selecting the most suitable scavengers, such as 2-propanol for ·OH, sodium pyruvate for H<sub>2</sub>O<sub>2</sub>, nitro blue tetrazolium for ·O<sup>-</sup>2</sub></sub>, and sodium azide NaN<sub>3</sub> for <sup>1</sup>O<sub>2</sub>. At the same time the outermost surface of copper, on which thin film of cuprous oxide Cu<sub>2</sub>O was first formed and then cupric oxide CuO was laminated on Cu<sub>2</sub>O, was examined by thin-film XRD and TEM analysis to estimate the amounts and kinds of copper oxides. It was found that the most amounts of ROS were obtained for the 573 K-heated Cu plate and they were composed of ·OH, H<sub>2</sub>O<sub>2</sub>, and ·O<sup>-</sup>2.</sub></sub>.
基金supported by the Projects of the National Key R&D Program of China,Nos.2021YFC2400803(to YO),2021YFC2400801(to YQ)the National Natural Science Foundation of China,Nos.82002290(to YQ),82072452(to YO),82272475(to YO)+5 种基金the Young Elite Scientist Sponsorship Program by Cast,No.YESS20200153(to YQ)the Sino-German Mobility Programme,No.M-0699(to YQ)the Excellent Youth Cultivation Program of Shanghai Sixth People’s Hospital,No.ynyq202201(to YQ)the Shanghai Sailing Program,No.20YF1436000(to YQ)the Medical Engineering Co-Project of University of Shanghai for Science and Technology,10-22-310-520(to YO)a grant from Shanghai Municipal Health Commission,No.202040399(to YO).
文摘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.
基金supported by the National Natural Science Foundation of China,Nos.82071382(to MZ),81601306(to HS)The Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(to MZ)+5 种基金Jiangsu 333 High-Level Talent Training Project(2022)(to HS)The Jiangsu Maternal and Child Health Research Key Project,No.F202013(to HS)Jiangsu Talent Youth Medical Program,No.QNRC2016245(to HS)Shanghai Key Lab of Forensic Medicine,No.KF2102(to MZ)Suzhou Science and Technology Development Project,No.SYS2020089(to MZ)The Fifth Batch of Gusu District Health Talent Training Project,No.GSWS2019060(to HS)。
文摘Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.
基金supported by the Key Science and Technology Research of Henan Province,No.222102310351(to JW)Luoyang 2022 Medical and Health Guiding Science and Technology Plan Project,No.2022057Y(to JY)Henan Medical Science and Technology Research Program Province-Ministry Co-sponsorship,No.SBGJ202002099(to JY)。
文摘Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains unclear.Protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum stress.Parkin is regulated by PERK and is a target of the unfolded protein response.It is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh Parkin.In this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s disease.We used adeno-associated virus to knockdown PHB2 expression.Our res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s disease.Ove rexpression of PHB2 inhibited these abnormalities.We also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s disease.We found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted mitophagy.In addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of PERK.These findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.
基金National Natural Science Foundation of China[82274366]The National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine:Multi-dimensional Evaluation and Multidisciplinary Innovation Team of Southwest Traditional Chinese Medicine Resources[ZYYCXTD-D-202209]+2 种基金The Youth Talent Promotion Project of China Association of Chinese Medicine[2021-QNRC2-A09]The Major Project of Sichuan Provincial Administration of Traditional Chinese Medicine(2023ZD01)the financial support from the Indian Council of Medical Research(ICMR),New Delhi,India,through Extramural Research Grants.
文摘As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.
基金supported by the National Natural Science Foundation of China(No.82172408,81772314,and 81922045)the Original Exploration project(22ZR1480300)+5 种基金Outstanding Academic Leaders(Youth)project(21XD1422900)of Shanghai Science and Technology Innovation Action PlanPrinciple Investigator Innovation Team of Both Shanghai Sixth People’s Hospital and Shanghai Institute of Nutrition and Health,Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program(No.20191829)The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang(No.SHDC2020CR4032)Shanghai Excellent Academic Leader ProgramShanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration(No.20DZ2254100)China Postdoctoral Science Foundation(2023M742347).
文摘Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats.The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane,with histological score decreasing from 3.12±0.27 to 2.20±0.22 and anti-adhesion effectiveness increasing from 21.61%to 44.72%.Mechanistically,the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively;thus,the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited.Consequently,excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)is largely reduced.For biocompatibility evaluation,PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes.Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds,which further delays the fibrosis process.It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.
基金supported by the National Natural Science Foundation of China,Nos.81870732(to DZ),82171161(to DZ),81900933(to YS),and 82000978(to ZL).
文摘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.