Reactive oxygen species(ROS),including singlet oxygen(^(1)O_(2)),hydroxyl radicals(·OH),and superoxide anions(O_(2)^(·-)),are highly reactive molecules that play central roles in many chemical,biological,and...Reactive oxygen species(ROS),including singlet oxygen(^(1)O_(2)),hydroxyl radicals(·OH),and superoxide anions(O_(2)^(·-)),are highly reactive molecules that play central roles in many chemical,biological,and environmental processes due to their strong oxidative power[1].Generating ROS in a controlled manner under mild conditions is essential for achieving selective oxidation reactions.Light-driven methods are especially appealing for this purpose,as they offer precise control over where and when ROS are produced.展开更多
Honglian type-cytoplasmic male sterility(HL-CMS)is caused by the inter-communication between the nucleus and mitochondria.However,the mechanisms by which sterility genes regulate metabolic alterations and changes in m...Honglian type-cytoplasmic male sterility(HL-CMS)is caused by the inter-communication between the nucleus and mitochondria.However,the mechanisms by which sterility genes regulate metabolic alterations and changes in mitochondrial morphology in the pollen of HL-CMS remain unclear.In this study,we compared the morphological differences between the pollen of the male sterile line YA and the near-isogenic line NIL-Rf6 using hematoxylin-eosin staining and 4ʹ,6-diamidino-2-phenylindole(DAPI)staining.HL-CMS is characterized by gametophytic sterility,where the aborted pollen grains are empty,and the tapetal layer remains intact.Transmission electron microscopy was employed to observe mitochondrial morphological changes at the microspore stage,revealing significant mitochondrial alterations,characterized by the formation of'large spherical mitochondria',occurred at the binucleate stage in the YA line.Additionally,metabolomics analysis revealed decreased levels of metabolites associated with the carbohydrate and flavonoid pathways.Notably,the decrease in flavonoids was found to contribute to an elevation in reactive oxygen species(ROS)levels.Therefore,we propose a model in which rice fertility is modulated by the levels of pollen carbohydrates and flavonoid metabolites,with impaired mitochondrial energy production and reduced flavonoid biosynthesis as the main causes of ROS accumulation and pollen abortion in rice.展开更多
BACKGROUND Sepsis is a life-threatening condition caused by a dysregulated host response to infection.Peripheral blood mononuclear cells(PBMCs)are critical mediators of the immune response and may exhibit redox imbala...BACKGROUND Sepsis is a life-threatening condition caused by a dysregulated host response to infection.Peripheral blood mononuclear cells(PBMCs)are critical mediators of the immune response and may exhibit redox imbalance during sepsis.Reactive oxygen species(ROS)are known to influence immune cell signaling,and excessive ROS accumulation may contribute to sepsis-associated immune alterations.AIM To assess intracellular ROS levels in PBMC subsets from septic patients and determine whether norepinephrine(NE)or N-acetylcysteine(NAC)modulate ROS levels following inflammatory stimulation in vitro.METHODS PBMCs were isolated from Department of Emergency patients meeting SEP-1/SEP-2 sepsis criteria and from healthy controls without signs of infection.Intracellular ROS levels were measured using a total ROS detection assay and analyzed by flow cytometry.PBMCs were also stimulated in vitro with lipopolysaccharide(LPS)or hydrogen peroxide(H2O2),with or without co-treatment with NE or NAC.RESULTS ROS levels were significantly elevated in CD3+and CD14+cells from septic patients compared to controls.In vitro stimulation of control PBMCs with LPS or H2O2 increased ROS in CD3+and CD14+cells,which was attenuated by cotreatment with NE or NAC.CONCLUSION ROS levels are elevated in specific PBMC subsets in sepsis,particularly CD3+T cells and CD14+monocytes.NE and NAC reduced ROS accumulation in vitro,supporting their potential role as redox modulators.These findings warrant further mechanistic investigation into immune redox regulation in sepsis.展开更多
Global warming poses a severe threat to rice production and food security.We identified a heat-sensitive mutant hs1 through largescale screening of an established rice mutant library,and subsequently cloned the corres...Global warming poses a severe threat to rice production and food security.We identified a heat-sensitive mutant hs1 through largescale screening of an established rice mutant library,and subsequently cloned the corresponding gene HS1,which confers thermotolerance in rice.HS1 is localized to the chloroplast and functions by preserving chloroplast integrity under elevated temperatures through stabilizing the photosystem I subunit protein PsaC.Loss of HS1 function in the hs1 mutant leads to severe structural damage to the chloroplast under heat stress,accompanied by intracellular accumulation of reactive oxygen species(ROS),which in turn triggers DNA damage and leaf albinism,ultimately manifesting as a heat-sensitive phenotype.展开更多
BACKGROUND Colon cancer is one of the most common malignancies worldwide,and chemo-therapy is a widely used strategy in colon cancer clinical therapy.Chemotherapy resistance is the main cause of recurrence and progres...BACKGROUND Colon cancer is one of the most common malignancies worldwide,and chemo-therapy is a widely used strategy in colon cancer clinical therapy.Chemotherapy resistance is the main cause of recurrence and progression in colon cancer.Thus,novel drugs for treatment are urgently needed.Tetramethylpyrazine(TMP),a component of the traditional Chinese medicine Chuanxiong Hort,has been proven to exhibit a beneficial effect in tumors.AIM To investigate the potential anticancer activity of TMP in colon cancer and the underlying mechanisms.METHODS Colon cancer cells were incubated with different concentrations of TMP.Cell viability was evaluated by crystal violet staining assay,and cell apoptosis was assessed by flow cytometry.Apoptosis-associated protein expression was measured using Western blot analysis.Intracellular reactive oxygen species(ROS)levels were assessed by flow cytometry using DCF fluorescence intensity.Xeno-grafts were established by the subcutaneous injection of colon cancer cells into nude mice;tumor growth was monitored and intracellular ROS was detected in tumors by malondialdehyde assay.RESULTS TMP induced apoptosis of colon cancer cells via the activation of the mitochon-drial pathway.TMP increased the generation of intracellular ROS and triggered mitochondria-mediated apoptosis in a caspase-dependent manner.CONCLUSION Our study demonstrates that TMP induces the apoptosis of colon cancer cells and increases the generation of intracellular ROS.TMP triggers mitochondria-mediated apoptosis in a caspase-dependent manner.The accumu-lation of intracellular ROS is involved in TMP-induced apoptosis.Our findings suggest that TMP may be a potential therapeutic drug for the treatment of colon cancer.展开更多
Reactive oxygen species(ROS)are closely related to cell death,proliferation and inflammation.However,excessive ROS levels may exceed the cellular oxidative capacity and cause irreversible damage.Organisms are often in...Reactive oxygen species(ROS)are closely related to cell death,proliferation and inflammation.However,excessive ROS levels may exceed the cellular oxidative capacity and cause irreversible damage.Organisms are often inadvertently exposed to nanomaterials(NMs).Therefore,elucidating the specific routes of ROS generation induced by NMs is crucial for comprehending the toxicity mechanisms of NMs and regulating their potential applications.This paper provides a comprehensive review of the toxicity mechanisms and applications of NMs from three perspectives:(1)Organelle perspective.Investigating the impact of NMmediated ROS onmitochondria,unravelingmechanisms at the organelle level.(2)NMs’perspective.Exploring the broad applications and biosafety considerations of Nanozymes,a unique class of NMs.(3)Cellular system.Examining the toxic effects and mechanisms of NMs in cells at a holistic cellular level.Expanding on these perspectives,the paper scrutinizes the regulation of Fenton reactions by NMs in organisms.Furthermore,it introduces diseases resulting fromNM-mediated ROS at the organism level.This comprehensive review aims to provide valuable insights for studying NM-mediated mechanisms at both cellular and organism levels,offering considerations for the safe design of nanomaterials.展开更多
BACKGROUND High levels of acetaminophen(APAP)consumption can result in significant liver toxicity.Mogroside V(MV)is a bioactive,plant-derived triterpenoid known for its various pharmacological activities.However,the i...BACKGROUND High levels of acetaminophen(APAP)consumption can result in significant liver toxicity.Mogroside V(MV)is a bioactive,plant-derived triterpenoid known for its various pharmacological activities.However,the impact of MV on acute liver injury(ALI)is unknown.AIM To investigate the hepatoprotective potential of MV against liver damage caused by APAP and to examine the underlying mechanisms.METHODS Mice were divided into three groups:Saline,APAP and APAP+MV.MV(10 mg/kg)was given intraperitoneally one hour before APAP(300 mg/kg)administration.Twenty-four hours after APAP exposure,serum transaminase levels,liver necrotic area,inflammatory responses,nitrotyrosine accumulation,and c-jun-N-terminal kinase(JNK)activation were assessed.Additionally,we analyzed reactive oxygen species(ROS)levels,JNK activation,and cell death in alpha mouse liver 12(AML12)cells.RESULTS MV pre-treatment in vivo led to a reduction in the rise of aspartate transaminase and alanine transaminase levels,mitigated liver damage,decreased nitrotyrosine accumulation,and blocked JNK phosphorylation resulting from APAP exposure,without affecting glutathione production.Similarly,MV diminished the APAP-induced increase in ROS,JNK phosphorylation,and cell death in vitro.CONCLUSION Our study suggests that MV treatment alleviates APAP-induced ALI by reducing ROS and JNK activation.展开更多
BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHO...BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHODS SW480 and DLD-1 CRC cell lines were used to investigate the mechanism of apoptosis by western blotting,flow cytometry,confocal microscopy,and other methods.RESULTS DCA significantly induced apoptosis,with rates increasing to 7.2%±1.5%in SW480 cells and 14.3%±0.6%in DLD-1 cells after treatment,compared to 4.7%±1.0%and 11.6%±0.8%in controls(P<0.05).Western blot analysis showed upregulation of pro-apoptotic proteins Bax and Cleaved-PARP,with a significant increase in the Cleaved-PARP/PARP ratio(P<0.001).DCA treatment also increased the intracellular reactive oxygen species(ROS)levels of SW480 and DLD-1 cells to 1.2-fold and 1.3-fold,respectively(P<0.01),while the increase of mitochondrial ROS levels in these cells was statistically significant under confocal microscopy.Additionally,cytosolic and mitochondrial Ca^(2+)levels increased 1.3-fold and 1.2-fold,respectively,in SW480 cells(P<0.01),and 1.1-fold and 1.1-fold,respectively,in DLD-1 cells compared with controls(P<0.05).p-CaMKII protein levels were also elevated(P<0.01),indicating activation of the Ca^(2+)-CaMKII signaling pathway.Pharmacological inhibition with BAPTAAM(1μM)reduced mitochondrial Ca^(2+)accumulation and ROS levels in SW480 cells(P<0.05),and suppressed apoptosis.CONCLUSION DCA activates the Ca^(2+)-CaMKII pathway,leading to ROS-mediated apoptosis in CRC cells,providing insights for potential therapeutic targets.展开更多
Light exposure can accelerate phase transformation of Schwertmannite(Sch)coexisting with lowmolecular-weight organic acids(LMWOAs),affecting the cycling of Fe in acid mine drainage(AMD).However,it is still unclear how...Light exposure can accelerate phase transformation of Schwertmannite(Sch)coexisting with lowmolecular-weight organic acids(LMWOAs),affecting the cycling of Fe in acid mine drainage(AMD).However,it is still unclear how this process relates to the fate of heavy metal contaminants.The study comprehensively reports the significant role and speciation redistribution of Cu(Ⅱ)during the photochemical transformation of a Sch/tartaric acid(TA)system.Based on X-ray diffractometer and Fourier transform infrared spectra results,the presence of TA in simulated AMD significantly promoted photoreductive dissolution and phase transformation of Sch to magnetite(Mt)and goethite(Gt)under anoxic and oxic conditions,respectively.With the addition of 10-30 mg/L Cu(Ⅱ),this transformation of Sch/TA system was significantly inhibited,i.e.,only Gt occurred as product under anoxic conditions and even no phase transformation under oxic conditions.The results of EPR and adsorbed Fe(Ⅱ)indicated that the coexistence of Cu(Ⅱ)suppressed the amount of adsorbed Fe(Ⅱ)available for the transformation of Sch via competitive adsorption with Fe(Ⅱ)and inhibition of ligand-to-metal charge transfer(LMCT)of Sch-TA complexes.Chemical speciation and X-ray photoelectron spectroscopy analysis revealed the proportions of adsorbed and structural Cu(Ⅱ)of Sch/TA system were observably enhanced due to an increase in pH and recrystallization/nucleation growth of newly formed Gt.Under anoxic conditions,62.7%-75.88%of Cu(Ⅱ)was adsorbed on the mineral surface,and during the nucleation and growth of secondary mineral phases,15.49%-17.01%of Cu(Ⅱ)was incorporated into their crystal structure.The changes in distribution of Cu(Ⅱ)further suggested the photochemical transformation of Sch facilitated the sequestration of heavy metals and reduced their bioavailability.These findings enhance the understanding of role and redistribution of Cu(Ⅱ)during the transformation of Sch/LMWOA system in euphotic zone of AMD and provid insights of exploring engineered strategies of AMD remediation.展开更多
To explore the mechanism of sperm dysfunction caused by dibutyl phthalate(DBP),the effects of DBP on intracellular[Ca^(2+)]and[pH],reactive oxygen species(ROS),lipid peroxidation(LPO),mitochondrial permeability transi...To explore the mechanism of sperm dysfunction caused by dibutyl phthalate(DBP),the effects of DBP on intracellular[Ca^(2+)]and[pH],reactive oxygen species(ROS),lipid peroxidation(LPO),mitochondrial permeability transition pore(mPTP)opening,mitochondrial membrane potential(MMP),adenosine triphosphate(ATP)levels,phosphorylation of protein kinase A(PKA)substrate proteins and phosphotyrosine(p-Tyr)proteins,sperm motility,spontaneous acrosome reaction,and tail bending were examined in mouse spermatozoa.At 100μg/mL,DBP significantly increased tail bending and[Ca^(2+)]i.Interestingly,DBP showed biphasic effects on[pH]i.DBP at 10–100μg/mL significantly decreased sperm motility.Similarly,Ca^(2+)ionophore A23187 decreased[pH]_(i)sperm motility,suggesting that DBP-induced excessive[Ca^(2+)]_(i)decreased sperm motility.DBP significantly increased ROS and LPO.DBP at 100μg/mL significantly decreased mPTP closing,MMP,and ATP levels in spermatozoa,as did H2O2,indicative of ROS-mediatedmitochondrial dysfunction caused by DBP.DBP as well as H2O2 increased p-Tyr sperm proteins and phosphorylated PKA substrate sperm proteins.DBP at 1–10μg/mL significantly increased the spontaneous acrosome reaction,suggesting that DBP can activate sperm capacitation.Altogether,DBP showed a biphasic effect on intracellular signaling in spermatozoa.At concentrations relevant to seminal ortho-phthalate levels,DBP activates[pH]i,protein tyrosine kinases and PKA via physiological levels of ROS generation,potentiating sperm capacitation.DBP at high doses excessively raises[Ca^(2+)]_(i)and ROS and disrupts[pH]i,impairing the mitochondrial function,tail structural integrity,and sperm motility.展开更多
Particulate matter(PM)can cause adverse health effects by overproducing reactive oxygen species(ROS).Although the ability of PM to induce ROS generation depends on its composi-tion and environmental factors.This study...Particulate matter(PM)can cause adverse health effects by overproducing reactive oxygen species(ROS).Although the ability of PM to induce ROS generation depends on its composi-tion and environmental factors.This study explores how photo-oxidation affects ROS gen-eration from aromatic compounds(ACs,including catechol(CAT),phthalic acid(PA),and 4,4-oxydibenzoic acid(4,4-OBA))and their mixtures with transition metals(TMs,includ-ing Fe(II),Mn(II),and Cu(II))using Fourier-transform infrared(FTIR)and Ultraviolet-visible spectroscopy(UV-Vis).Results showed that photo-oxidation facilitated ROS generation from ACs.CAT-Fe(II)/Cu(II)showed synergistic effects,but 4,4-OBA-Fe(II)/Cu(II)showed antag-onistic effects.ACs-Mn(II)and PA-Fe(II)/Cu(II)exhibited synergistic effects first and then showed antagonistic effects.The different interactions were due to complexation between ACs and TMs.The photo-oxidized ACs-TMs significantly enhanced ROS generation com-pared with ACs-TMs.The study suggested the photo-oxidation mechanism involved that the transfer ofπ-electrons from the ground to an excited state in benzene rings and func-tional groups,leading to the breakage and formation of chemical bonds or easierπ-electron transfer from ACs to TMs.The former could generate ROS directly or produce polymers that promoted ROS generation,while the latter promoted ROS generation by transferringπ-electrons to dissolved oxygen quickly.Our study revealed that both interactions among components and photo-oxidation significantly influenced ROS generation.Future studies should integrate broader atmospheric factors and PM components to fully assess oxidative potential and health impacts.展开更多
The anodic electrochemical ozone production(EOP)and the cathodic three-electron oxygen reduction reaction(3e^(-)ORR)are effective processes for generating active oxygen species(ROS).However,the activation of ozone(O_(...The anodic electrochemical ozone production(EOP)and the cathodic three-electron oxygen reduction reaction(3e^(-)ORR)are effective processes for generating active oxygen species(ROS).However,the activation of ozone(O_(3))by hydroxyl radical(OH)to form ROS poses significant challenges.The micelle balllike bimetallic La-Nb oxides(LNOx)have been developed as a bifunctional electrocatalyst for both the EOP and 3e^(-)ORR reactions.The LNO20 demonstrated a 9.8%of Faradaic efficiency(FE)in O_(3)production and a transfer number of 2.8 electrons in the 3e^(-)ORR.Theoretical calculations support the notion that the five-membered ring mechanism in LNO20 facilitates O_(3)production.Additionally,the incorporation of La provides active sites that enhance the activation of hydrogen peroxide(^(*)H_(2)O_(2))and the generation of OH.This innovative approach synergistically integrates EOP and 3e^(-)ORR,enhancing the activation of O_(3)to produce ROS,demonstrating exceptional efficacy in the degradation of organic pollutants and antimicrobial activity.The study paves the way for designing advanced electrocatalysts for EOP and 3e^(-)ORR and offers insights into utilizing electrochemical method to support other antibacterial strategies.展开更多
Although sonodynamic therapy(SDT)is a promising cancer treatment that induces DNA and macromolecular damage through the generation of reactive oxygen species(ROS),its therapeutic efficacy is limited by local hypoxia a...Although sonodynamic therapy(SDT)is a promising cancer treatment that induces DNA and macromolecular damage through the generation of reactive oxygen species(ROS),its therapeutic efficacy is limited by local hypoxia and ROS defense mechanisms in tumors.This study propose d a novel tumor treatment approach,focusing on ROS-mediated therapy by targ eting the nucleus and depleting glutathione(GSH)levels,which was achieved through a nanoplatform(Pt^(2+)-CDs@PpIX)with integrated functions including GSH detection and depletion,pH-responsive drug release,and nuclear targeting.The Pt^(2+)-CDs@PpIX nanoplatform effectively differentiated normal and cancer cells and also exhibited excellent biocompatibility.Depletion of GSH levels and increased ROS sensitivity of cells significantly improved the effectiveness of SDT,as demonstrated in vitro using Pt^(2+)-CDs@PpIX,which also exhibited significant cellular uptake.Pt^(2+)-CDs@PpIX exerted potent antitumor effects in both two-dimensional and three-dimensional tum or microenvironment models(3 DM-7721).Moreover,in 3 DM-7721 models,hepatoma cells(SMMC-7721)demonstrated significant inhibition of motility,invasion,and colony formation after exposure to Pt^(2+)-CDs@PpIX.Furthermore,intravenous administration of the Pt^(2+)-CDs@PpIX nanoplatform enabled precise and rapid tumor-targeting,followed by ultrasound-triggered therapy,without adverse effects in nude mice.Hence,this nanoplatform provides a promising strategy for designing cancer therapies and delivering nuclear-targeted drugs.展开更多
Prostate cancer(PCa)is a leading cause of cancer-related mortality among men.Radiotherapy is the cornerstone of PCa treatment.However,a major limitation of radiotherapy is the development of resistance,which compromis...Prostate cancer(PCa)is a leading cause of cancer-related mortality among men.Radiotherapy is the cornerstone of PCa treatment.However,a major limitation of radiotherapy is the development of resistance,which compromises treatment efficacy.Reactive oxygen species(ROS),which are generated by radiation,have a dual role in PCa by inducing DNA damage and apoptosis,while also promoting tumor progression and radioresistance.Elevated ROS levels enhance metabolic reprogramming,activate oncogenic pathways,and influence the tumor microenvironment by modulating immune responses and promoting the epithelial-mesenchymal transition(EMT).Key molecular mechanisms,including the Nrf2/Keap1 signaling axis,Bcl-2 mutations,and Speckle-type POZ protein alterations,contribute to radioresistance by enhancing antioxidant defenses and DNA repair capacity.Additionally,the interplay between hypoxia,androgen receptor variants(AR-Vs),and ferroptosis regulators further influence radiotherapy outcomes.Understanding these resistance mechanisms is crucial for developing targeted strategies to enhance radiosensitivity and improve therapeutic outcomes in PCa patients.展开更多
A geomagnetic field is a significant factor dur-ing the growth and development of trees.Changes in the magnetic field(MF)will result in reactions at the biochemi-cal,molecular,cellular and gene levels.However,it is no...A geomagnetic field is a significant factor dur-ing the growth and development of trees.Changes in the magnetic field(MF)will result in reactions at the biochemi-cal,molecular,cellular and gene levels.However,it is not clear how a magnetic field affects metabolism and home-ostasis under stressful conditions such as salinity.In this study,a novel method was developed of a static magnetic field(SMF)to investigate magnetobiological changes in trees.The results show that pre-treatment of poplar(Popu-lus×euramericana‘Neva’)cuttings with a static magnetic field significantly mitigated the negative effects of salinity stress on their growth and physiological activities.Bio-chemical assays revealed that several chemical messengers,including hydrogen peroxide(H2O2)and O_(2)^(·-),were sig-nificantly improved in roots treated with salt,implying an increase reactive oxygen species.A static magnetic field also significantly increased proline concentrations,soluble protein contents,and CAT and SOD activities.Electrophysiological experiments further revealed that pre-treatment with a static magnetic field remarkably decreased salt-induced Na^(+)influx and H^(+)efflux which control plant salt tolerance.In pharmacological experiments,because the Na^(+)/H^(+)cor-relation was closely related to the SMF-activated plasma membrane and Na^(+)antiporter activity alleviated the mas-sive accumulation of salt-induced reactive oxygen spe-cies(ROS)within the roots.In addition,a static magnetic field dramatically increased the transcriptional activity of stress-responsive genes,including PtrRBOHD and PtrHA5.Together,these results indicate that SMF reduced Na^(+)influx by activating Na^(+)/H^(+)antiporters and plasma membrane H^(+)-ATPase to effectively maintain homeostasis by regu-lating the reactive oxygen species system and cytoplasmic osmotic potential.Ultimately,these static magnetic field methods improved salt tolerance in poplar cuttings,and,for future research,similar methods could be applied to other plants.展开更多
Effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on the germination and metabolism of reactive oxygen species were surveyed in wheat (Triticum aestivum L.) seeds. Germination of wheat seeds and even t...Effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on the germination and metabolism of reactive oxygen species were surveyed in wheat (Triticum aestivum L.) seeds. Germination of wheat seeds and even the elongation of radicle and plumule were dramatically promoted by SNP treatments during the germination under osmotic stress. Meanwhile, activities of amylase and EP were enhanced, thus leading to the degradation of storage reserve in seeds. After osmotic stress was removed, higher viability of wheat seeds was also maintained. In addition, the activities of CAT, APX and the content of proline were increased by SNP treatment simultaneously, but activities of LOX were inhibited, and both of which were beneficial for improving the antioxidant capacity during the germination of wheat seeds under osmotic stress. It was also shown that the increase of the activity of amylase induced by SNP in embryoless half-seeds of wheat in the beginning period of germination (6 h) might be indirectly related to GA(3).展开更多
Objective: To evaluate the anti-tumor effects of SeO2 and its mechanisms on three human lung cancer cell lines. Methods: Three lung cancer cells A549, GLC-82 and PG were treated with 3-30 μmol/L SeO2. Flow cytometry ...Objective: To evaluate the anti-tumor effects of SeO2 and its mechanisms on three human lung cancer cell lines. Methods: Three lung cancer cells A549, GLC-82 and PG were treated with 3-30 μmol/L SeO2. Flow cytometry was used to detect apoptosis, and analyze the changes of expression of p53 and Bcl-2, as well as ROS and Ca2+ level within cells. Results:SeO2 markedly inhibited cell proliferation and viability, and prompted apoptosis after 48 h treatment. SeO2 at 10 μmol/L induced 47.8% apoptosis in A549 cells, 40.8% in GLC-82 cells, 18.2% in PG cells. SeO2 at 30 μmol/L induced 37.8% apoposis in PG cells,but did not increase apoptotic raes in other two cells. SeO2 could down-regulate the mean fluorescent intensity of Bcl-2 from 65.8 to 9.6 in A549, but not in GLC-82 and in PG cells, up-regulate wild type p53 level in all three cells. SeO2 decreased the ROS and Ca2+ level markedly within three tested cells. Conclusion: SeO2 showed anti-tumor effect via apoptosis pathway in three lung cancer cell lines. The decrease of ROS and Ca2+ level within cells as well as regulation of Bcl-2 and p53 expression may play important roles in above apoptotic procedure.展开更多
BACKGROUND In myelodysplastic syndrome(MDS),oxidative stress is closely related to iron overload and DNA damage.A recent study suggested the possibility that increased oxidative stress causes not only iron overload bu...BACKGROUND In myelodysplastic syndrome(MDS),oxidative stress is closely related to iron overload and DNA damage.A recent study suggested the possibility that increased oxidative stress causes not only iron overload but also disease progression of MDS with DNA damage.We present a case of MDS with decreased reactive oxygen species(ROS)production in peripheral white blood cells(WBCs)and decreased diacron-reactive oxygen metabolites(d-ROMs)in serum after azacitidine therapy.CASE SUMMARY A 74-year-old man presented to the hematological department with the chief complaint of anemia.His vital signs were within normal limits at admission with a heart rate of 80 bpm and blood pressure of 135/60 mmHg.Laboratory tests indicated pancytopenia,a WBC count of 2190 cells/μL,a hemoglobin level of 6.2 g/dL and a platelet count of 7.4×104/μL.The patient was diagnosed with MDS with fibrosis after a bone marrow examination.This case showed decreased ROS production in WBCs,d-ROMs in serum and Wilms’tumor 1 after azacitidine therapy,after which his hematopoiesis recovered.CONCLUSION Azacitidine therapy can improve hematopoiesis and decrease ROS and d-ROM production.展开更多
<abstract>Aim: To investigate the level of malondialdehyde (MDA), a direct indicator of lipid peroxidation-induced injury by reactive oxygen species (ROS), in testicular biopsy specimens from infertile patients....<abstract>Aim: To investigate the level of malondialdehyde (MDA), a direct indicator of lipid peroxidation-induced injury by reactive oxygen species (ROS), in testicular biopsy specimens from infertile patients. Methods: Levels of MDA were measured in testicular biopsy specimens from 29 consequent-randomized infertile men, aged 29.58±4.76 (21-45) years. All patients were evaluated by a complete medical and reproductive history, physical examination, semen analysis (at least two), serum follicle-stimulating hormone and free testosterone levels, testicular biopsy and contact imprint. Scrotal colour Doppler ultrasonography was used to confirm suspected varicocele. The testicular MDA level was measured using the thiobarbituric acid test and the results were expressed per unit tissue weight. Results: As a causal factor in infertility, varicocele was identified in 17 (58.6 %) patients, and idiopathic infertility, testicular failure and obstruction in 4 (13.8 %) patients each. The testicular MDA level was 13.56 (6.01), 49.56 (24.04), 58.53 (48.07), and 32.64 (21.51), 32.72 (13.61), 23.07 (7.82), 42,12 (34.76) pmol/mg tissue in the normal spermatogenesis (control), late maturation arrest, Sertoli cell only (SCO) and hypospermatogenesis (mild, moderete, severe) groups, respectively. The elevation of MDA levels was significant in the testicular tissue from SCO and maturation arrest groups compared with the controls (P<0.05). In addition, the elevation in testicular MDA levels between the SCO and the moderete hypospermatogenesis, and the moderate hypospermatogenesis and the maturation arrest groups was significant (P<0.05). Conclusion: Severe pathologic changes in the testicular tissue are associated with a high level of lipid peroxidation. These findings suggest that overproduction of ROS may play a role in the mechanism of testicular degeneration associated with infertility.展开更多
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,...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.展开更多
文摘Reactive oxygen species(ROS),including singlet oxygen(^(1)O_(2)),hydroxyl radicals(·OH),and superoxide anions(O_(2)^(·-)),are highly reactive molecules that play central roles in many chemical,biological,and environmental processes due to their strong oxidative power[1].Generating ROS in a controlled manner under mild conditions is essential for achieving selective oxidation reactions.Light-driven methods are especially appealing for this purpose,as they offer precise control over where and when ROS are produced.
基金supported by the National Natural Science Foundation of China(Grant No.32472185)the Key Research and Development Program of Hubei Province,China(Grant No.2022BFE003)the Hubei Agriculture Science and Technology Innovation Center program,and the National Rice Industry Technology System,China(Grant No.CARS-01-07).
文摘Honglian type-cytoplasmic male sterility(HL-CMS)is caused by the inter-communication between the nucleus and mitochondria.However,the mechanisms by which sterility genes regulate metabolic alterations and changes in mitochondrial morphology in the pollen of HL-CMS remain unclear.In this study,we compared the morphological differences between the pollen of the male sterile line YA and the near-isogenic line NIL-Rf6 using hematoxylin-eosin staining and 4ʹ,6-diamidino-2-phenylindole(DAPI)staining.HL-CMS is characterized by gametophytic sterility,where the aborted pollen grains are empty,and the tapetal layer remains intact.Transmission electron microscopy was employed to observe mitochondrial morphological changes at the microspore stage,revealing significant mitochondrial alterations,characterized by the formation of'large spherical mitochondria',occurred at the binucleate stage in the YA line.Additionally,metabolomics analysis revealed decreased levels of metabolites associated with the carbohydrate and flavonoid pathways.Notably,the decrease in flavonoids was found to contribute to an elevation in reactive oxygen species(ROS)levels.Therefore,we propose a model in which rice fertility is modulated by the levels of pollen carbohydrates and flavonoid metabolites,with impaired mitochondrial energy production and reduced flavonoid biosynthesis as the main causes of ROS accumulation and pollen abortion in rice.
文摘BACKGROUND Sepsis is a life-threatening condition caused by a dysregulated host response to infection.Peripheral blood mononuclear cells(PBMCs)are critical mediators of the immune response and may exhibit redox imbalance during sepsis.Reactive oxygen species(ROS)are known to influence immune cell signaling,and excessive ROS accumulation may contribute to sepsis-associated immune alterations.AIM To assess intracellular ROS levels in PBMC subsets from septic patients and determine whether norepinephrine(NE)or N-acetylcysteine(NAC)modulate ROS levels following inflammatory stimulation in vitro.METHODS PBMCs were isolated from Department of Emergency patients meeting SEP-1/SEP-2 sepsis criteria and from healthy controls without signs of infection.Intracellular ROS levels were measured using a total ROS detection assay and analyzed by flow cytometry.PBMCs were also stimulated in vitro with lipopolysaccharide(LPS)or hydrogen peroxide(H2O2),with or without co-treatment with NE or NAC.RESULTS ROS levels were significantly elevated in CD3+and CD14+cells from septic patients compared to controls.In vitro stimulation of control PBMCs with LPS or H2O2 increased ROS in CD3+and CD14+cells,which was attenuated by cotreatment with NE or NAC.CONCLUSION ROS levels are elevated in specific PBMC subsets in sepsis,particularly CD3+T cells and CD14+monocytes.NE and NAC reduced ROS accumulation in vitro,supporting their potential role as redox modulators.These findings warrant further mechanistic investigation into immune redox regulation in sepsis.
基金supported by the National Natural Science Foundation of China(Grant Nos.32372118 and 32188102)the Zhejiang Natural Science Foundation,China(Grant No.LZ25C130010)+1 种基金the Qian Qian Academician Workstation,and the specific research fund of the Innovation Platform for Academicians of Hainan Province,China(Grant No.YSPTZX202303)the Central Public-Interest Scientific Institution Basal Research Fund from Chinese Academy of Agricultural Sciences(Grant No.Y2025YC93)。
文摘Global warming poses a severe threat to rice production and food security.We identified a heat-sensitive mutant hs1 through largescale screening of an established rice mutant library,and subsequently cloned the corresponding gene HS1,which confers thermotolerance in rice.HS1 is localized to the chloroplast and functions by preserving chloroplast integrity under elevated temperatures through stabilizing the photosystem I subunit protein PsaC.Loss of HS1 function in the hs1 mutant leads to severe structural damage to the chloroplast under heat stress,accompanied by intracellular accumulation of reactive oxygen species(ROS),which in turn triggers DNA damage and leaf albinism,ultimately manifesting as a heat-sensitive phenotype.
文摘BACKGROUND Colon cancer is one of the most common malignancies worldwide,and chemo-therapy is a widely used strategy in colon cancer clinical therapy.Chemotherapy resistance is the main cause of recurrence and progression in colon cancer.Thus,novel drugs for treatment are urgently needed.Tetramethylpyrazine(TMP),a component of the traditional Chinese medicine Chuanxiong Hort,has been proven to exhibit a beneficial effect in tumors.AIM To investigate the potential anticancer activity of TMP in colon cancer and the underlying mechanisms.METHODS Colon cancer cells were incubated with different concentrations of TMP.Cell viability was evaluated by crystal violet staining assay,and cell apoptosis was assessed by flow cytometry.Apoptosis-associated protein expression was measured using Western blot analysis.Intracellular reactive oxygen species(ROS)levels were assessed by flow cytometry using DCF fluorescence intensity.Xeno-grafts were established by the subcutaneous injection of colon cancer cells into nude mice;tumor growth was monitored and intracellular ROS was detected in tumors by malondialdehyde assay.RESULTS TMP induced apoptosis of colon cancer cells via the activation of the mitochon-drial pathway.TMP increased the generation of intracellular ROS and triggered mitochondria-mediated apoptosis in a caspase-dependent manner.CONCLUSION Our study demonstrates that TMP induces the apoptosis of colon cancer cells and increases the generation of intracellular ROS.TMP triggers mitochondria-mediated apoptosis in a caspase-dependent manner.The accumu-lation of intracellular ROS is involved in TMP-induced apoptosis.Our findings suggest that TMP may be a potential therapeutic drug for the treatment of colon cancer.
基金supported by the National Natural Science Foundation of China(No.22176206).
文摘Reactive oxygen species(ROS)are closely related to cell death,proliferation and inflammation.However,excessive ROS levels may exceed the cellular oxidative capacity and cause irreversible damage.Organisms are often inadvertently exposed to nanomaterials(NMs).Therefore,elucidating the specific routes of ROS generation induced by NMs is crucial for comprehending the toxicity mechanisms of NMs and regulating their potential applications.This paper provides a comprehensive review of the toxicity mechanisms and applications of NMs from three perspectives:(1)Organelle perspective.Investigating the impact of NMmediated ROS onmitochondria,unravelingmechanisms at the organelle level.(2)NMs’perspective.Exploring the broad applications and biosafety considerations of Nanozymes,a unique class of NMs.(3)Cellular system.Examining the toxic effects and mechanisms of NMs in cells at a holistic cellular level.Expanding on these perspectives,the paper scrutinizes the regulation of Fenton reactions by NMs in organisms.Furthermore,it introduces diseases resulting fromNM-mediated ROS at the organism level.This comprehensive review aims to provide valuable insights for studying NM-mediated mechanisms at both cellular and organism levels,offering considerations for the safe design of nanomaterials.
基金Supported by Guangxi Natural Science Foundation of China,No.2024GXNSFAA010040Special Fund of the Central Government Guiding Local Scientific and Technological Development by Guangxi Science and Technology Department,No.GuikeZY21195024National Natural Science Foundation of China,No.82260499 and No.82460463.
文摘BACKGROUND High levels of acetaminophen(APAP)consumption can result in significant liver toxicity.Mogroside V(MV)is a bioactive,plant-derived triterpenoid known for its various pharmacological activities.However,the impact of MV on acute liver injury(ALI)is unknown.AIM To investigate the hepatoprotective potential of MV against liver damage caused by APAP and to examine the underlying mechanisms.METHODS Mice were divided into three groups:Saline,APAP and APAP+MV.MV(10 mg/kg)was given intraperitoneally one hour before APAP(300 mg/kg)administration.Twenty-four hours after APAP exposure,serum transaminase levels,liver necrotic area,inflammatory responses,nitrotyrosine accumulation,and c-jun-N-terminal kinase(JNK)activation were assessed.Additionally,we analyzed reactive oxygen species(ROS)levels,JNK activation,and cell death in alpha mouse liver 12(AML12)cells.RESULTS MV pre-treatment in vivo led to a reduction in the rise of aspartate transaminase and alanine transaminase levels,mitigated liver damage,decreased nitrotyrosine accumulation,and blocked JNK phosphorylation resulting from APAP exposure,without affecting glutathione production.Similarly,MV diminished the APAP-induced increase in ROS,JNK phosphorylation,and cell death in vitro.CONCLUSION Our study suggests that MV treatment alleviates APAP-induced ALI by reducing ROS and JNK activation.
基金Supported by the Key Discipline of Zhejiang Province in Medical Technology(First Class,Category A)Wenzhou Science&Technological Project,No.Y20240103.
文摘BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHODS SW480 and DLD-1 CRC cell lines were used to investigate the mechanism of apoptosis by western blotting,flow cytometry,confocal microscopy,and other methods.RESULTS DCA significantly induced apoptosis,with rates increasing to 7.2%±1.5%in SW480 cells and 14.3%±0.6%in DLD-1 cells after treatment,compared to 4.7%±1.0%and 11.6%±0.8%in controls(P<0.05).Western blot analysis showed upregulation of pro-apoptotic proteins Bax and Cleaved-PARP,with a significant increase in the Cleaved-PARP/PARP ratio(P<0.001).DCA treatment also increased the intracellular reactive oxygen species(ROS)levels of SW480 and DLD-1 cells to 1.2-fold and 1.3-fold,respectively(P<0.01),while the increase of mitochondrial ROS levels in these cells was statistically significant under confocal microscopy.Additionally,cytosolic and mitochondrial Ca^(2+)levels increased 1.3-fold and 1.2-fold,respectively,in SW480 cells(P<0.01),and 1.1-fold and 1.1-fold,respectively,in DLD-1 cells compared with controls(P<0.05).p-CaMKII protein levels were also elevated(P<0.01),indicating activation of the Ca^(2+)-CaMKII signaling pathway.Pharmacological inhibition with BAPTAAM(1μM)reduced mitochondrial Ca^(2+)accumulation and ROS levels in SW480 cells(P<0.05),and suppressed apoptosis.CONCLUSION DCA activates the Ca^(2+)-CaMKII pathway,leading to ROS-mediated apoptosis in CRC cells,providing insights for potential therapeutic targets.
基金financially supported by the National Natural Science Foundation of China(No.U21A2034)the Guangdong Special Support Plan for Innovation Teams(No.2019BT02L218).
文摘Light exposure can accelerate phase transformation of Schwertmannite(Sch)coexisting with lowmolecular-weight organic acids(LMWOAs),affecting the cycling of Fe in acid mine drainage(AMD).However,it is still unclear how this process relates to the fate of heavy metal contaminants.The study comprehensively reports the significant role and speciation redistribution of Cu(Ⅱ)during the photochemical transformation of a Sch/tartaric acid(TA)system.Based on X-ray diffractometer and Fourier transform infrared spectra results,the presence of TA in simulated AMD significantly promoted photoreductive dissolution and phase transformation of Sch to magnetite(Mt)and goethite(Gt)under anoxic and oxic conditions,respectively.With the addition of 10-30 mg/L Cu(Ⅱ),this transformation of Sch/TA system was significantly inhibited,i.e.,only Gt occurred as product under anoxic conditions and even no phase transformation under oxic conditions.The results of EPR and adsorbed Fe(Ⅱ)indicated that the coexistence of Cu(Ⅱ)suppressed the amount of adsorbed Fe(Ⅱ)available for the transformation of Sch via competitive adsorption with Fe(Ⅱ)and inhibition of ligand-to-metal charge transfer(LMCT)of Sch-TA complexes.Chemical speciation and X-ray photoelectron spectroscopy analysis revealed the proportions of adsorbed and structural Cu(Ⅱ)of Sch/TA system were observably enhanced due to an increase in pH and recrystallization/nucleation growth of newly formed Gt.Under anoxic conditions,62.7%-75.88%of Cu(Ⅱ)was adsorbed on the mineral surface,and during the nucleation and growth of secondary mineral phases,15.49%-17.01%of Cu(Ⅱ)was incorporated into their crystal structure.The changes in distribution of Cu(Ⅱ)further suggested the photochemical transformation of Sch facilitated the sequestration of heavy metals and reduced their bioavailability.These findings enhance the understanding of role and redistribution of Cu(Ⅱ)during the transformation of Sch/LMWOA system in euphotic zone of AMD and provid insights of exploring engineered strategies of AMD remediation.
基金supported by the National Research Foundation of Republic of Korea(NRF)grant funded by the Republic of Korea government(MSIT)(No.2022R1A2C1007831).
文摘To explore the mechanism of sperm dysfunction caused by dibutyl phthalate(DBP),the effects of DBP on intracellular[Ca^(2+)]and[pH],reactive oxygen species(ROS),lipid peroxidation(LPO),mitochondrial permeability transition pore(mPTP)opening,mitochondrial membrane potential(MMP),adenosine triphosphate(ATP)levels,phosphorylation of protein kinase A(PKA)substrate proteins and phosphotyrosine(p-Tyr)proteins,sperm motility,spontaneous acrosome reaction,and tail bending were examined in mouse spermatozoa.At 100μg/mL,DBP significantly increased tail bending and[Ca^(2+)]i.Interestingly,DBP showed biphasic effects on[pH]i.DBP at 10–100μg/mL significantly decreased sperm motility.Similarly,Ca^(2+)ionophore A23187 decreased[pH]_(i)sperm motility,suggesting that DBP-induced excessive[Ca^(2+)]_(i)decreased sperm motility.DBP significantly increased ROS and LPO.DBP at 100μg/mL significantly decreased mPTP closing,MMP,and ATP levels in spermatozoa,as did H2O2,indicative of ROS-mediatedmitochondrial dysfunction caused by DBP.DBP as well as H2O2 increased p-Tyr sperm proteins and phosphorylated PKA substrate sperm proteins.DBP at 1–10μg/mL significantly increased the spontaneous acrosome reaction,suggesting that DBP can activate sperm capacitation.Altogether,DBP showed a biphasic effect on intracellular signaling in spermatozoa.At concentrations relevant to seminal ortho-phthalate levels,DBP activates[pH]i,protein tyrosine kinases and PKA via physiological levels of ROS generation,potentiating sperm capacitation.DBP at high doses excessively raises[Ca^(2+)]_(i)and ROS and disrupts[pH]i,impairing the mitochondrial function,tail structural integrity,and sperm motility.
基金supported by the Weiqiao-UCAS Special Projects on Low-Carbon Technology Development(No.GYY-DTFZ-2022-007)the Fundamental Research Funds for the Central Universities(No.E0E48927×2)the National Natural Science Foundation of China(No.21677145).
文摘Particulate matter(PM)can cause adverse health effects by overproducing reactive oxygen species(ROS).Although the ability of PM to induce ROS generation depends on its composi-tion and environmental factors.This study explores how photo-oxidation affects ROS gen-eration from aromatic compounds(ACs,including catechol(CAT),phthalic acid(PA),and 4,4-oxydibenzoic acid(4,4-OBA))and their mixtures with transition metals(TMs,includ-ing Fe(II),Mn(II),and Cu(II))using Fourier-transform infrared(FTIR)and Ultraviolet-visible spectroscopy(UV-Vis).Results showed that photo-oxidation facilitated ROS generation from ACs.CAT-Fe(II)/Cu(II)showed synergistic effects,but 4,4-OBA-Fe(II)/Cu(II)showed antag-onistic effects.ACs-Mn(II)and PA-Fe(II)/Cu(II)exhibited synergistic effects first and then showed antagonistic effects.The different interactions were due to complexation between ACs and TMs.The photo-oxidized ACs-TMs significantly enhanced ROS generation com-pared with ACs-TMs.The study suggested the photo-oxidation mechanism involved that the transfer ofπ-electrons from the ground to an excited state in benzene rings and func-tional groups,leading to the breakage and formation of chemical bonds or easierπ-electron transfer from ACs to TMs.The former could generate ROS directly or produce polymers that promoted ROS generation,while the latter promoted ROS generation by transferringπ-electrons to dissolved oxygen quickly.Our study revealed that both interactions among components and photo-oxidation significantly influenced ROS generation.Future studies should integrate broader atmospheric factors and PM components to fully assess oxidative potential and health impacts.
基金the financial support from the National Key R&D Program of China(2022YFA1504200)the Zhejiang Provincial Natural Science Foundation(No.LR22B060003)+2 种基金the National Natural Science Foundation of China(22322810,22078293,22141001,and 22008211)the Fundamental Research Funds for the Provincial Universities of Zhejiang(RF-C2023004)the Midea Group-Zhejiang University of Technology Joint Development Funding(KYY-HX-20240263)。
文摘The anodic electrochemical ozone production(EOP)and the cathodic three-electron oxygen reduction reaction(3e^(-)ORR)are effective processes for generating active oxygen species(ROS).However,the activation of ozone(O_(3))by hydroxyl radical(OH)to form ROS poses significant challenges.The micelle balllike bimetallic La-Nb oxides(LNOx)have been developed as a bifunctional electrocatalyst for both the EOP and 3e^(-)ORR reactions.The LNO20 demonstrated a 9.8%of Faradaic efficiency(FE)in O_(3)production and a transfer number of 2.8 electrons in the 3e^(-)ORR.Theoretical calculations support the notion that the five-membered ring mechanism in LNO20 facilitates O_(3)production.Additionally,the incorporation of La provides active sites that enhance the activation of hydrogen peroxide(^(*)H_(2)O_(2))and the generation of OH.This innovative approach synergistically integrates EOP and 3e^(-)ORR,enhancing the activation of O_(3)to produce ROS,demonstrating exceptional efficacy in the degradation of organic pollutants and antimicrobial activity.The study paves the way for designing advanced electrocatalysts for EOP and 3e^(-)ORR and offers insights into utilizing electrochemical method to support other antibacterial strategies.
基金supported by the National Natural Science Foundation of China(No.62031022)the Sha nxi Provincial Basic Research Project(Nos.202103021221006 and 20210302123040)+2 种基金the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2021L044)the Key R&D Program of Shanxi Province(No.202302130501006)the Shanxi‒Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-TD026).
文摘Although sonodynamic therapy(SDT)is a promising cancer treatment that induces DNA and macromolecular damage through the generation of reactive oxygen species(ROS),its therapeutic efficacy is limited by local hypoxia and ROS defense mechanisms in tumors.This study propose d a novel tumor treatment approach,focusing on ROS-mediated therapy by targ eting the nucleus and depleting glutathione(GSH)levels,which was achieved through a nanoplatform(Pt^(2+)-CDs@PpIX)with integrated functions including GSH detection and depletion,pH-responsive drug release,and nuclear targeting.The Pt^(2+)-CDs@PpIX nanoplatform effectively differentiated normal and cancer cells and also exhibited excellent biocompatibility.Depletion of GSH levels and increased ROS sensitivity of cells significantly improved the effectiveness of SDT,as demonstrated in vitro using Pt^(2+)-CDs@PpIX,which also exhibited significant cellular uptake.Pt^(2+)-CDs@PpIX exerted potent antitumor effects in both two-dimensional and three-dimensional tum or microenvironment models(3 DM-7721).Moreover,in 3 DM-7721 models,hepatoma cells(SMMC-7721)demonstrated significant inhibition of motility,invasion,and colony formation after exposure to Pt^(2+)-CDs@PpIX.Furthermore,intravenous administration of the Pt^(2+)-CDs@PpIX nanoplatform enabled precise and rapid tumor-targeting,followed by ultrasound-triggered therapy,without adverse effects in nude mice.Hence,this nanoplatform provides a promising strategy for designing cancer therapies and delivering nuclear-targeted drugs.
基金supported by grants from Ningbo Yongjiang Talent programme-Project for Innovative Talents(Grant No.20240340)Jinhua Science and Technology Bureau(Grant No.2022-4-258)2022 Shandong Medical Association Clinical Research Special Fund for Dynamic Monitoring of Lymphocyte Subpopulations by Flow Cytometry(Grant No.YXH2022ZX03227)。
文摘Prostate cancer(PCa)is a leading cause of cancer-related mortality among men.Radiotherapy is the cornerstone of PCa treatment.However,a major limitation of radiotherapy is the development of resistance,which compromises treatment efficacy.Reactive oxygen species(ROS),which are generated by radiation,have a dual role in PCa by inducing DNA damage and apoptosis,while also promoting tumor progression and radioresistance.Elevated ROS levels enhance metabolic reprogramming,activate oncogenic pathways,and influence the tumor microenvironment by modulating immune responses and promoting the epithelial-mesenchymal transition(EMT).Key molecular mechanisms,including the Nrf2/Keap1 signaling axis,Bcl-2 mutations,and Speckle-type POZ protein alterations,contribute to radioresistance by enhancing antioxidant defenses and DNA repair capacity.Additionally,the interplay between hypoxia,androgen receptor variants(AR-Vs),and ferroptosis regulators further influence radiotherapy outcomes.Understanding these resistance mechanisms is crucial for developing targeted strategies to enhance radiosensitivity and improve therapeutic outcomes in PCa patients.
基金supported by the the National Natural Science Foundation of China(32071751).
文摘A geomagnetic field is a significant factor dur-ing the growth and development of trees.Changes in the magnetic field(MF)will result in reactions at the biochemi-cal,molecular,cellular and gene levels.However,it is not clear how a magnetic field affects metabolism and home-ostasis under stressful conditions such as salinity.In this study,a novel method was developed of a static magnetic field(SMF)to investigate magnetobiological changes in trees.The results show that pre-treatment of poplar(Popu-lus×euramericana‘Neva’)cuttings with a static magnetic field significantly mitigated the negative effects of salinity stress on their growth and physiological activities.Bio-chemical assays revealed that several chemical messengers,including hydrogen peroxide(H2O2)and O_(2)^(·-),were sig-nificantly improved in roots treated with salt,implying an increase reactive oxygen species.A static magnetic field also significantly increased proline concentrations,soluble protein contents,and CAT and SOD activities.Electrophysiological experiments further revealed that pre-treatment with a static magnetic field remarkably decreased salt-induced Na^(+)influx and H^(+)efflux which control plant salt tolerance.In pharmacological experiments,because the Na^(+)/H^(+)cor-relation was closely related to the SMF-activated plasma membrane and Na^(+)antiporter activity alleviated the mas-sive accumulation of salt-induced reactive oxygen spe-cies(ROS)within the roots.In addition,a static magnetic field dramatically increased the transcriptional activity of stress-responsive genes,including PtrRBOHD and PtrHA5.Together,these results indicate that SMF reduced Na^(+)influx by activating Na^(+)/H^(+)antiporters and plasma membrane H^(+)-ATPase to effectively maintain homeostasis by regu-lating the reactive oxygen species system and cytoplasmic osmotic potential.Ultimately,these static magnetic field methods improved salt tolerance in poplar cuttings,and,for future research,similar methods could be applied to other plants.
文摘Effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on the germination and metabolism of reactive oxygen species were surveyed in wheat (Triticum aestivum L.) seeds. Germination of wheat seeds and even the elongation of radicle and plumule were dramatically promoted by SNP treatments during the germination under osmotic stress. Meanwhile, activities of amylase and EP were enhanced, thus leading to the degradation of storage reserve in seeds. After osmotic stress was removed, higher viability of wheat seeds was also maintained. In addition, the activities of CAT, APX and the content of proline were increased by SNP treatment simultaneously, but activities of LOX were inhibited, and both of which were beneficial for improving the antioxidant capacity during the germination of wheat seeds under osmotic stress. It was also shown that the increase of the activity of amylase induced by SNP in embryoless half-seeds of wheat in the beginning period of germination (6 h) might be indirectly related to GA(3).
基金This project was partially supported by Science Foundation of Lanzhou Command of PLA(No.YZ-0106).
文摘Objective: To evaluate the anti-tumor effects of SeO2 and its mechanisms on three human lung cancer cell lines. Methods: Three lung cancer cells A549, GLC-82 and PG were treated with 3-30 μmol/L SeO2. Flow cytometry was used to detect apoptosis, and analyze the changes of expression of p53 and Bcl-2, as well as ROS and Ca2+ level within cells. Results:SeO2 markedly inhibited cell proliferation and viability, and prompted apoptosis after 48 h treatment. SeO2 at 10 μmol/L induced 47.8% apoptosis in A549 cells, 40.8% in GLC-82 cells, 18.2% in PG cells. SeO2 at 30 μmol/L induced 37.8% apoposis in PG cells,but did not increase apoptotic raes in other two cells. SeO2 could down-regulate the mean fluorescent intensity of Bcl-2 from 65.8 to 9.6 in A549, but not in GLC-82 and in PG cells, up-regulate wild type p53 level in all three cells. SeO2 decreased the ROS and Ca2+ level markedly within three tested cells. Conclusion: SeO2 showed anti-tumor effect via apoptosis pathway in three lung cancer cell lines. The decrease of ROS and Ca2+ level within cells as well as regulation of Bcl-2 and p53 expression may play important roles in above apoptotic procedure.
文摘BACKGROUND In myelodysplastic syndrome(MDS),oxidative stress is closely related to iron overload and DNA damage.A recent study suggested the possibility that increased oxidative stress causes not only iron overload but also disease progression of MDS with DNA damage.We present a case of MDS with decreased reactive oxygen species(ROS)production in peripheral white blood cells(WBCs)and decreased diacron-reactive oxygen metabolites(d-ROMs)in serum after azacitidine therapy.CASE SUMMARY A 74-year-old man presented to the hematological department with the chief complaint of anemia.His vital signs were within normal limits at admission with a heart rate of 80 bpm and blood pressure of 135/60 mmHg.Laboratory tests indicated pancytopenia,a WBC count of 2190 cells/μL,a hemoglobin level of 6.2 g/dL and a platelet count of 7.4×104/μL.The patient was diagnosed with MDS with fibrosis after a bone marrow examination.This case showed decreased ROS production in WBCs,d-ROMs in serum and Wilms’tumor 1 after azacitidine therapy,after which his hematopoiesis recovered.CONCLUSION Azacitidine therapy can improve hematopoiesis and decrease ROS and d-ROM production.
文摘<abstract>Aim: To investigate the level of malondialdehyde (MDA), a direct indicator of lipid peroxidation-induced injury by reactive oxygen species (ROS), in testicular biopsy specimens from infertile patients. Methods: Levels of MDA were measured in testicular biopsy specimens from 29 consequent-randomized infertile men, aged 29.58±4.76 (21-45) years. All patients were evaluated by a complete medical and reproductive history, physical examination, semen analysis (at least two), serum follicle-stimulating hormone and free testosterone levels, testicular biopsy and contact imprint. Scrotal colour Doppler ultrasonography was used to confirm suspected varicocele. The testicular MDA level was measured using the thiobarbituric acid test and the results were expressed per unit tissue weight. Results: As a causal factor in infertility, varicocele was identified in 17 (58.6 %) patients, and idiopathic infertility, testicular failure and obstruction in 4 (13.8 %) patients each. The testicular MDA level was 13.56 (6.01), 49.56 (24.04), 58.53 (48.07), and 32.64 (21.51), 32.72 (13.61), 23.07 (7.82), 42,12 (34.76) pmol/mg tissue in the normal spermatogenesis (control), late maturation arrest, Sertoli cell only (SCO) and hypospermatogenesis (mild, moderete, severe) groups, respectively. The elevation of MDA levels was significant in the testicular tissue from SCO and maturation arrest groups compared with the controls (P<0.05). In addition, the elevation in testicular MDA levels between the SCO and the moderete hypospermatogenesis, and the moderate hypospermatogenesis and the maturation arrest groups was significant (P<0.05). Conclusion: Severe pathologic changes in the testicular tissue are associated with a high level of lipid peroxidation. These findings suggest that overproduction of ROS may play a role in the mechanism of testicular degeneration associated with infertility.
基金National Natural Science Foundation of China,No.39770300,30070873the Overseas Chinese Affairs Office of the State Council Foundation,No.98-33
文摘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.
