Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarge...Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally enlarged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its novel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Further studies showed that siRNA-directed ARPC 2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 complex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregulated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specific Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of cardiomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regulates pathological cardiac hypertrophy.展开更多
Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its im...Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its implications for carbon sequestration.A large number of experiments have proved that CO_(2) interaction time(T),saturation pressure(P)and other parameters have significant effects on coal strength.However,accurate evaluation of CO_(2)-induced alterations in coal strength is still a difficult problem,so it is particularly important to establish accurate and efficient prediction models.This study explored the application of advancedmachine learning(ML)algorithms and Gene Expression Programming(GEP)techniques to predict CO_(2)-induced alterations in coal strength.Sixmodels were developed,including three metaheuristic-optimized XGBoost models(GWO-XGBoost,SSA-XGBoost,PO-XGBoost)and three GEP models(GEP-1,GEP-2,GEP-3).Comprehensive evaluations using multiple metrics revealed that all models demonstrated high predictive accuracy,with the SSA-XGBoost model achieving the best performance(R2—Coefficient of determination=0.99396,RMSE—Root Mean Square Error=0.62102,MAE—Mean Absolute Error=0.36164,MAPE—Mean Absolute Percentage Error=4.8101%,RPD—Residual Predictive Deviation=13.4741).Model interpretability analyses using SHAP(Shapley Additive exPlanations),ICE(Individual Conditional Expectation),and PDP(Partial Dependence Plot)techniques highlighted the dominant role of fixed carbon content(FC)and significant interactions between FC and CO_(2) saturation pressure(P).Theresults demonstrated that the proposedmodels effectively address the challenges of CO_(2)-induced strength prediction,providing valuable insights for geological storage safety and environmental applications.展开更多
The problem of water and sulfur poisoning in flue gas atmosphere remains a significant obstacle for low-temperature deNO_(x) catalysts.This study investigated the sulfation mechanism of the CoMn_(2)O_(4)/CeTiO_(x)(CMC...The problem of water and sulfur poisoning in flue gas atmosphere remains a significant obstacle for low-temperature deNO_(x) catalysts.This study investigated the sulfation mechanism of the CoMn_(2)O_(4)/CeTiO_(x)(CMCT)catalyst during the selective catalytic reduction of NO_(x) with NH3 under conditions containing H2O and SO_(2) at 150℃.Employing a comprehensive suite of time-resolved analysis and characterization techniques,the evolution of sulfate species was systematically categorized into three stages:initial rapid surface sulfate accumulation,the transformation of surface sulfates to bulk metal sulfates,and partial sulfates decomposition after the removal of H2O and SO_(2).These findings indicate that bulk metal sulfates irreversibly deactivate the catalyst by distorting active component lattices and consuming oxygen vacancies,whereas surface sulfates(including ammonium sulfates and surface-coordinated metal sulfates)cause reversible performance loss through decomposition.Furthermore,the competitive adsorption of H2O and SO_(2) significantly influences the catalytic efficiency,with H2O suppressing SO_(2) adsorption while simultaneously enhancing the formation of Brönsted acid sites.This research underscores the critical role of sulfate dynamics on catalyst performance,revealing the enhanced SO_(2) resistance of the Eley-Rideal mechanism facilitated by the Ce-Ti support relative to the Langmuir-Hinshelwood pathway.Collectively,the study unravels the complex interplay of sulfate dynamics influencing catalyst performance and provides potential approaches to mitigate deactivation in demanding atmospheric conditions.展开更多
The aim of this study was to investigate the possible protective effects and mechanisms of 20-hydroxyecdysone, an insect steroid hormone, on HEO2-induced cytotoxicity in human neuroblastoma SH-SYSY cells. Pretreatment...The aim of this study was to investigate the possible protective effects and mechanisms of 20-hydroxyecdysone, an insect steroid hormone, on HEO2-induced cytotoxicity in human neuroblastoma SH-SYSY cells. Pretreatment with 20-hydroxyecdysone significantly elevated the cell viability and decreased LDH leakage in H2O2-treated SH-SY5Y cells. 20-Hydroxyecdysone also dramatically reduced malondialdehyde （MDA） contents and enhanced the superoxide dismutase （SOD） activities under oxidative stress conditions. Furthermore, 20-hydroxyecdysone pretreatment inhibited apoptosis by decreasing the Bax/Bcl-2 ratio and attenuating the activation of caspase-3. These results suggest that 20-hydroxyecdysone can protect SH-SYSY cells against H2O2-induced cytotoxicity and might potentially be used to treat neurodegenerative diseases induced by oxidative stress and anontosis.展开更多
Objective Stroke is a leading cause of death and disability worldwide,with ischemic stroke accounting for 80%-85%of cases.Despite the prevalence,effective treatments remain scarce.The compelling evidence suggest that ...Objective Stroke is a leading cause of death and disability worldwide,with ischemic stroke accounting for 80%-85%of cases.Despite the prevalence,effective treatments remain scarce.The compelling evidence suggest that high concentrations of ATP in the brain post-stroke can trigger irreversible neuronal damage and necrosis,contributing to a range of neurocellular dysfunctions.Pyroptosis,a recently identified form of programmed cell death,is characterized by caspase-1 activation and the action of the Gasdermin D(GSDMD)protein family,leading to cell perforation and inflammatory death.Methods In this study,human neuroblastoma SH-SY5Y cells were used to investigate the mechanisms of ATP-induced neurotoxicity and the protective effects of hydrogen sulfide(H_(2)S)against this toxicity through the antagonization of pyroptosis.We employed CCK-8 and LDH assays to assess cell viability.YO-PRO-1 fluorescent dyes and flow cytometry were conducted for detecting changes in cell membrane permeability.Western blot analysis was used to measure protein levels associated with cellular dysfunction.Results Our results indicate that high concentrations of ATP enhance cytotoxicity and increase cell membrane permeability in SH-SY5Y cells,that are mitigated by the H_(2)S donor NaHS.Furthermore,ATP was found to promote the activation of the NOD-like receptor pyrin domain-containing 1(NLRP-1),caspase-1,and the cleavage of GSDMD,with NaHS significantly attenuating these effects.Conclusion Our research suggests that H2S protects SH-SY5Y cells from ATP-induced neurotoxicity through a mechanism mediated by the NLRP1,caspase-1,and GSDMD pathway.展开更多
To investigate and compare the inhibitory properties of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes (alpha-amylase & alpha-glucosidase) and Fe2+-induced lipid peroxidatio...To investigate and compare the inhibitory properties of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes (alpha-amylase & alpha-glucosidase) and Fe2+-induced lipid peroxidation in rat pancreas in vitro. Methods: The free phenolics were extracted with 80% (v/v) acetone, while bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate. Then, the interaction of the extracts with alpha-amylase and alpha-glucosidase was subsequently assessed. Thereafter, the total phenolic contents and antioxidant activities of the extracts were determined. Results: The result revealed that both extracts inhibited alpha-amylase and alpha-glucosidase in a dose-dependent manner. However, the alpha-glucosidase inhibitory activity of the extracts were significantly (P<0.05) higher than their alpha-amylase inhibitory activity. The free phenolics (31.67 mg/g) and flavonoid (17.28 mg/g) contents were significantly (P<0.05) higher than bound phenolic (23.52 mg/g) and flavonoid (13.70 mg/g) contents. Both extracts also exhibited high antioxidant activities as typified by their high reducing power, 1,1 diphenyl-2- picrylhydrazyl (DPPH) and 2, 2-azinobis-3-ethylbenzo-thiazoline-6-sulfonate (ABTS) radical scavenging abilities, as well as inhibition of Fe2+-induced lipid peroxidation in rat pancreas in vitro. Conclusions: This study provides a biochemical rationale by which clove elicits therapeutic effect on type 2 diabetes.展开更多
The aim of the present study was to explore the effects of annexin A1(ANXA1) mimetic peptide AC2-26 on sepsis-induced cardiomyocyte apoptosis in vivo and in vitro and the underlying mechanisms.In the in vivo study,a r...The aim of the present study was to explore the effects of annexin A1(ANXA1) mimetic peptide AC2-26 on sepsis-induced cardiomyocyte apoptosis in vivo and in vitro and the underlying mechanisms.In the in vivo study,a rat septic model was established by the cecal ligation and puncture (CLP).The rats were divided into control group,sepsis group and AC2-26 group.The rats in the AC2-26 group were intraperitoneally injected with AC2-26(1mg/kg)2h before CLP,and those in the control group and sepsis group were injected with the same volume of normal saline.The myocardial tissue was examined by hematoxylin and eosin (HE)staining and transmission electron microscopy (TEM).Furthermore,myocardial apoptosis was measured by terminal dUTP nick end-labeling (TUNEL)assay.In the in vitro study,H9C2cells were cultured and divided into three groups:control group,in which cells were only given the basic culture medium;LPS group,in which cells were treated with 10μg/mL LPS;AC2-26 group,in which cells were treated with 0.5μmol/L AC2-262h before 10μg/mL LPS was given.The apoptosis of H9C2 cells was detected by flow cytometry.The levels of lipoxin A4 receptor (LXA4),phosphoinositide3-kinase (PI3K)and protein kinase B (PKB or AKT)protein were measured by Western blotting, the activity of NF-KB and the level of TNF-α by ELISA and the activities of caspase-3/8by using the caspase activity kits.The in vivo study showed that the myocardial pathological damage and myocardial ultrastructural damage were significantly alleviated and the myocardial apoptosis significantly decreased in the AC2-26 group as compared with the sepsis group (P<0.05 for all). The in vivo study revealed that the apoptosis of H9C2 cells was profoundly ameliorated in the AC2-26 group relative to the sepsis group (P<0.05).The protein expression levels of LXA4 were significantly up-regulated,and those of PI3K and AKT prominently down-regulated in the AC2-26 group when compared with those in the LPS group (P<0.05 for all).The activity of NF-κB was greatly inhibited and the level of TNF-α markedly decreased in the AC2-26 group as compared with those in the LPS group (P<0.05 for all).AC2-26 treatment also significantly suppressed the activities of caspase-3/8 in H9C2 cells.In conclusion,these findings suggest that AC2-26 may alleviate the sepsis-induced cardiomyocyte apoptosis in vivo and in vivo through the LXA4/PI3K/ AKT signaling pathway.展开更多
The inflammatory response is involved in the pathogenesis of the most common types of heart disease. Sanguinarine （SAN） has various pharmacological properties such as anti-inflammatory, antioxidant, antibacterial, a...The inflammatory response is involved in the pathogenesis of the most common types of heart disease. Sanguinarine （SAN） has various pharmacological properties such as anti-inflammatory, antioxidant, antibacterial, antitumor, and immune-enhancing properties. However, few studies have investigated the effects of SAN on lipopolysaceharide （LPS）-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes. Therefore, in this study, H9c2 cells were co-treated with SAN and LPS, and the mRNA levels of pro-inflammation markers and the apoptosis rate were measured to clarify the effect of SAN on cardiac inflammation. The underlying mechanism was further investigated by detecting the activation of Toll-like receptor （TLR）4/nuclear faetor-κB （NF-κB） signaling pathways. As a result, increased mRNA expression of interleukin （IL）-1β, IL-6, and TNFα induced by LPS was attenuated after SAN treatment; LPS-induced apoptosis ofHge2 cardiomyocytes and cleaved-caspase 8, 9, 3 were all significantly reduced by SAN. Further experiments showed that the beneficial effect of SAN on blocking the inflammation and apoptosis of H9c2 cardiomyocytes induced by LPS was associated with suppression of the TLR4/NF-κB signaling pathway. It was suggested that SAN suppressed the LPS-induced inflammation and apoptosis of H9c2 cardiomyocytes, which may be mediated by inhibition of the TLR4/NF-κB signaling pathway. Thus, SAN may be a feasible therapy to treat sepsis patients with cardiac dysfunction.展开更多
This study aimed to investigate the protective effects of astragaloside IV(AS IV) on lipopolysaccharide(LPS)-induced injury in H9C2 cardiomyocytes. H9C2 Cardiomyocytes were cultured with LPS(10 μg·mL-1) for 4 h ...This study aimed to investigate the protective effects of astragaloside IV(AS IV) on lipopolysaccharide(LPS)-induced injury in H9C2 cardiomyocytes. H9C2 Cardiomyocytes were cultured with LPS(10 μg·mL-1) for 4 h and treated with AS IV at 50, 100, and 150 μmol·L-1 for various durations. Cell viability was determined by MTT. The content of released TNF-α and IL-6 from cardiomyocytes were evaluated by enzyme-linked immunosorbent assay(ELISA). The levels of superoxidase dismutase(SOD), malondialdehyde(MDA), lactate dehydrogenase(LDH), and creatine phosphate kinase(CK) were measured by using commercial available kits. The mR NA and protein expression levels of NF-κB p65 were measured by RT-PCR and Western blotting, respectively. And the NF-κB p65 activity was measured by ELISA. Our results demonstrated that AS IV at 50, 100, and 150 μmol·L-1 markedly inhibited the release of TNF-α and IL-6 and decreased NF-κB expression, compared with the model group. Moreover, the improved SOD activity and decreased MDA, LDH and CK levels were detected after AS IV treatment. In summary, AS IV could increase the activities of antioxidant enzymes, inhibite lipid peroxidation, and down-regulate the inflammatory mediators involved in the inflammatory responses. These results demonstrated that AS IV could prevent LPS-induced injury in cardiomyocytes.展开更多
In this study,an acid-induced assembly strategy for a rutile TiO2 photocatalyst was proposed on the basis of the treatment of lamellar protonated titanate with a concentrated HNO3 solution.Nitrate groups were successf...In this study,an acid-induced assembly strategy for a rutile TiO2 photocatalyst was proposed on the basis of the treatment of lamellar protonated titanate with a concentrated HNO3 solution.Nitrate groups were successfully grafted onto a TiO2 surface and induced the assembly of rutile TiO2 nanorods into uniform spindle-like nanobundles.The resulting TiO2 product achieved a photocatalytic hydrogen evolution rate of 402.4μmol h^?1,which is 3.1 times higher than that of Degussa P25-TiO2.It was demonstrated that nitrate group grafting caused the rutile TiO2 surface to become negatively charged,which is favorable for trapping positive protons and improving charge carrier separation,thereby enhancing photocatalytic hydrogen production.Additionally,surface charges were crucial to structural stability based on electrostatic repulsion.This study not only developed a facile surface modification strategy for fabricating efficient H2 production photocatalysts but also identified an influence mechanism of inorganic acids different from that reported in the literature.展开更多
Benzene is an established leukotoxin and leukemogen in humans. We have previously re- ported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein k...Benzene is an established leukotoxin and leukemogen in humans. We have previously re- ported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit （DNA-PKcs） to mediate the cellular response to DNA double strand break （DSB） caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-（morpholin-4-yl）-benzo[h]chomen-4-one （NU7026）, as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phos- phorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apop- tosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.展开更多
Eucommia ulmoides Oliv.(EuO),also known as Duzhong,native to China,has been reported to have antioxidative function,but its cellular mechanism is not fully examined yet.We investigated inhibitory effects of EuO leaf e...Eucommia ulmoides Oliv.(EuO),also known as Duzhong,native to China,has been reported to have antioxidative function,but its cellular mechanism is not fully examined yet.We investigated inhibitory effects of EuO leaf ethanol extracts on H2O2-induced apoptosis in rat osteoblastic MC3T3-E1 cells and underlying mechanisms.Locally-grown Duzhong leaves were extracted with ethanol.MC3T3-E1 cells were treated with EuO (6.25,12.5,25,50,and 100 μg/ml) for 24 h,and then H2O2 (800 μmol/L) for an additional 24 h.Cell survival rate,percentage of apoptosis,and expressions of caspases 3,6,7,and 9 were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay,microscopic analysis,Western blotting,and reverse transcription polymerase chain reaction (RT-PCR).The final EuO leaf ethanol extract powder was detected to contain caffeotannic acid at 58 mg/g and geniposide at 3.45 mg/g by high performance liquid chromatography (HPLC).EuO remarkably restrained cell oxidative damage and increased cell survival rate in a dose-dependent manner: 0 μg/ml,0.21;6.25 μg/ml,0.28;12.5 μg/ml,0.31;25 μg/ml,0.48;50 μg/ml,0.54;and 100 μg/ml,0.66 (P<0.05),with the half-effective concentration being around 25 μg/ml.MTT results were confirmed by microscopic analysis.Western blotting and RT-PCR analyses showed that the expressions of caspases 3,6,7,and 9 were significantly decreased in the EuO-treated cells compared with the control (EuOand H2O2-free) (P<0.05),with the half-effective concentration of EuO ranging from 12.5 to 25 μg/ml.We conclude that the ethanol-extracted EuO leaf extracts promoted the growth of MC3T3-E1 cells,and suppressed the H2O2-induced apoptosis in a rat MC3T3-E1 osteogenic cell model,likely due to the inhibition of caspases’ activities.The results indicate that EuO is a potent antioxidant,which may contribute to its many cellular protective functions,including the promotion of bone growth.展开更多
Jasmonic acid(JA)plays an important role in regulating leaf senescence.However,the molecular mechanisms of leaf senescence in apple(Malus domestica)remain elusive.In this study,we found that MdZAT10,a C2H2-type zinc f...Jasmonic acid(JA)plays an important role in regulating leaf senescence.However,the molecular mechanisms of leaf senescence in apple(Malus domestica)remain elusive.In this study,we found that MdZAT10,a C2H2-type zinc finger transcription factor(TF)in apple,markedly accelerates leaf senescence and increases the expression of senescence-related genes.To explore how MdZAT10 promotes leaf senescence,we carried out liquid chromatography/mass spectrometry screening.We found that MdABI5 physically interacts with MdZAT10.MdABI5,an important positive regulator of leaf senescence,significantly accelerated leaf senescence in apple.MdZAT10 was found to enhance the transcriptional activity of MdABI5 for MdNYC1 and MdNYE1,thus accelerating leaf senescence.In addition,we found that MdZAT10 expression was induced by methyl jasmonate(MeJA),which accelerated JA-induced leaf senescence.We also found that the JA-responsive protein MdBT2 directly interacts with MdZAT10 and reduces its protein stability through ubiquitination and degradation,thereby delaying MdZAT10-mediated leaf senescence.Taken together,our results provide new insight into the mechanisms by which MdZAT10 positively regulates JA-induced leaf senescence in apple.展开更多
The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson’s disease (PD). Notably, the VA receives direct innervation from t...The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson’s disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K^(+) channels, or Ca^(2+)-activated K+ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.展开更多
Gastric mucosal inflammatory responses to H. pylori lipopolysaccharide (LPS), are characterized by the excessive NO and prostaglandin (PGE2) generation due to the disturbances in nitric oxide synthase (NOS) and cycloo...Gastric mucosal inflammatory responses to H. pylori lipopolysaccharide (LPS), are characterized by the excessive NO and prostaglandin (PGE2) generation due to the disturbances in nitric oxide synthase (NOS) and cyclooxygenase (COX) systems. Here, we report that the LPS-induced enhancement in gastric mucosal inducible (i) iNOS) activity and up-regulation in PGE2 production was associated with the suppression in Akt kinase activity and the impairment in constitutive (c) cNOS activation. The stimulatory effect of the LPS on PGE2 production, furthermore, was susceptible to suppression by COX-2 inhibitor, NS-398, and iNOS inhibitor, 1400 W. Further, we show that the countering effect of peptide hormone, ghrelin, on the LPS-induced changes was reflected in up-regu- lation in Akt activity and the increase in cNOS activation through phosphorylation, and accompanied by the suppression in iNOS expression and the reduction in COX-2 activity associated with the loss in COX-2 protein S-nitrosylation. Moreover, the effect of ghre-lin on the LPS-induced COX-2 S-nitrosylation was subject to repression by Akt inhibition. Our findings demonstrate that induction in iNOS with H. pylori in- fection leads to COX-2 activation through S-nitro- sylation and up-regulation in PGE2 generation, and that ghrelin counters these untoward consequences of the LPS through Akt-mediated up-regulation in cNO- S activation required for the iNOS gene repression.展开更多
The activation of adsorbed CO is an important step in CO hydrogenation. The results from TPSR of pre-adsorbed CO with H2 and syngas suggested that the presence of H2 increased the amount of CO adsorption and accelerat...The activation of adsorbed CO is an important step in CO hydrogenation. The results from TPSR of pre-adsorbed CO with H2 and syngas suggested that the presence of H2 increased the amount of CO adsorption and accelerated CO dissociation. The H2 was adsorbed first, and activated to form H＊ over metal sites, then reacted with carbonaceous species. The oxygen species for CO2 formation in the presence of hydrogen was mostly OH^＊, which reacted with adsorbed CO subsequently via CO^＊＋OH^＊ → CO2^＊＋H^＊; however, the direct CO dissociation was not excluded in CO hydrogenation. The dissociation of C-O bond in the presence of H2 proceeded by a concerted mechanism, which assisted the Boudourd reaction of adsorbed CO on the surface via CO^＊＋2H^＊ → CH^＊＋OH^＊. The formation of the surface species （CH） from adsorbed CO proceeded as indicated with the participation of surface hydrogen, was favored in the initial step of the Fischer-Tropsch synthesis.展开更多
Rho kinase （ROCK） was the first downstream Rho effector found to mediate RhoA-induced actin cytoskeletal changes through effects on myosin light chain phosphorylation. There is abundant evidence that the ROCK pathwa...Rho kinase （ROCK） was the first downstream Rho effector found to mediate RhoA-induced actin cytoskeletal changes through effects on myosin light chain phosphorylation. There is abundant evidence that the ROCK pathway participates in the pathogenesis of retinal endothelial injury and proliferative epiretinal membrane traction. In this study, we investigated the effect of the ROCK pathway inhibitor Y-27632 on retinal Müller cells subjected to hypoxia or oxidative stress. Müller cells were subjected to hypoxia or oxidative stress by exposure to CoCl2 or H2O2. After a 24-hour treatment with Y-27632, the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide assay was used to assess the survival of Müller cells. Hoechst 33258 was used to detect apoptosis, while 2′,7′-dichlorodihydrofluorescein diacetate was used to measure reactive oxygen species generation. A transwell chamber system was used to examine the migration ability of Müller cells. Western blot assay was used to detect the expression levels of α-smooth muscle actin, glutamine synthetase and vimentin. After treatment with Y-27632, Müller cells subjected to hypoxia or oxidative stress exhibited a morphology similar to control cells. Y-27632 reduced apoptosis, α-smooth muscle actin expression and reactive oxygen species generation under oxidative stress, and it reduced cell migration under hypoxia. Y-27632 also upregulated glutamine synthetase expression under hypoxia but did not impact vimentin expression. These findings suggest that Y-27632 protects Müller cells against cellular injury caused by oxidative stress and hypoxia by inhibiting the ROCK pathway.展开更多
Pathological cardiac hypertrophy induced by angiotensin Ⅱ （Ang Ⅱ ） can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the r...Pathological cardiac hypertrophy induced by angiotensin Ⅱ （Ang Ⅱ ） can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the roots ofNardostachys chinensis, a well-known traditional Chinese medicine. In order to investigate the effects of nardosinone on Ang Ⅱ-induced cardiac cell hypertrophy and the related mechanisms, the myoblast cell line H9c2, derived from embryonic rat heart, was treated with nardosi- none （25, 50, 100, and 200μmol/L） or Ang Ⅱ （1 μmol/L）. Then cell surface area and mRNA expression of classical markers of hypertrophy were detected. The related protein levels in PI3K/Akt/mTOR and MEK/ERK signaling pathways were examined by Western blotting. It was found that pretreatment with nardosinone could significantly inhibit the enlargement of cell surface area induced by Ang Ⅱ. The mRNA expression of ANP, BNP and 13-MHC was obviously elevated in Ang Ⅱ-treated H9c2 cells, which could be effectively blocked by nardosinone at the concentration of 100μmol/L. Further study revealed that the protective effects of nardosinone might be mediated by repressing the phosphorylation of related proteins in PI3K/Akt and MEK/ERK signaling pathways. It was suggested that the inhibitory effect of nardosinone on Ang Ⅱ-induced hypertrophy in H9c2 cells might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways.展开更多
Objective To investigate the role of H1 and H2 receptors in the locus ceruleus （LC） in carotid sinus baroreceptor reflex （CSR） resetting induced by intracerebroventricular （i.c.v.） injection of histamine （HA）....Objective To investigate the role of H1 and H2 receptors in the locus ceruleus （LC） in carotid sinus baroreceptor reflex （CSR） resetting induced by intracerebroventricular （i.c.v.） injection of histamine （HA）. Methods The left and right carotid sinus regions were isolated from the systemic circulation in 18 male Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure （ISP） was altered in a stepwise manner in vivo. ISP-mean arterial pressure （MAP） relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CSR performance induced by i.c.v. HA and the effects of pretreatment with H1 or H2 receptors selective antagonist, chlorpheniramine （CHL） or cimetidine （CIM） into the LC, on the responses of CSR to HA were examined. Results I.c.v. HA （100 ng in 5 μl） significantly shifted the ISP-MAP relationship curve upwards （P 〈 0.05） and obviously decreased the value of the reflex parameters such as MAP range and maximum gain （P 〈 0.05）, but increased the threshold pressure, saturation pressure and ISP at maximum gain （P 〈 0.05）. The pretreatment with CHL （0.5 μg in 1 μl） or CIM （1.5 μg in 1 μl） into the LC could obviously attenuate the changes mentioned above in CSR performance induced by HA, but the alleviative effect of CIM was less remarkable than that of CHL （P 〈 0.05）. Respective microinjection of CHL or CIM alone into the LC with the corresponding dose and volume did not change CSR performance significantly （P 〉 0.05）. Conclusion Intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the responses of CSR to HA may be mediated, at least in part, by H1 and H2 receptors activities in the LC, especially by H1 receptors. Moreover, the effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to LC.展开更多
文摘Pathological cardiac hypertrophy is an early and significant cardiac structural characteristic that contributes to the onset and progression of heart failure(HF).Its mainly structural feature is the abnormally enlarged cardiomyocyte.Effective intervention targets for abnormally enlarged cardiomyocyte remain to be identified.Previous studies have shown that the cellular shape and size can be regulated by the actin related protein 2/3(Arp2/3)complex,which is an actin-binding protein complex involved in the actin nucleation and assembly.However,the roles of the Arp2/3 complex in cardiomyocyte hypertrophy remain unknown.Here our study identifies its novel roles in the occurrence and development of cardiomyocyte hypertrophy.We found that mRNA levels of all subunits from the Arp2/3 complex are significantly upregulated(P<0.05)in the angiotensin Ⅱ(Ang Ⅱ)-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy.Further studies showed that siRNA-directed ARPC 2 silencing inhibits the reactivation of fetal genes and enlargement of cardiomyocyte area induced by Ang Ⅱ in neonatal rat primary cardiomyocytes(NRCMs)and H9c2 cells(P<0.05).In addition,the upstream activators of the Arp2/3 complex including SH3 protein interacting with Nck,90 kD(SPIN90)and Ras-related C3 botulinum toxin substrate 1(Rac1)/WASp family Verprolin-homologous protein-2(WAVE-2)are upregulated(P<0.05)in Ang Ⅱ-induced neonatal rat primary and H9c2 cardiomyocyte hypertrophy,indicating the excessive activation of the Arp2/3 complex.We further show that CK666,a specific Arp2/3 complex inhibitor,prevents the reactivation of fetal genes and the enlargement of cardiomyocyte area induced by Ang Ⅱ in NRCMs and H9c2 cells(P<0.05).Our results reveal that the Arp2/3 complex plays a crucial role in Ang Ⅱ-induced cardiomyocyte hypertrophy,which is beneficial to further studies about the molecular mechanisms by which the Arp2/3 complex regulates pathological cardiac hypertrophy.
基金partially supported by the National Natural Science Foundation of China(42177164,52474121)the Outstanding Youth Project of Hunan Provincial Department of Education(23B0008).
文摘Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its implications for carbon sequestration.A large number of experiments have proved that CO_(2) interaction time(T),saturation pressure(P)and other parameters have significant effects on coal strength.However,accurate evaluation of CO_(2)-induced alterations in coal strength is still a difficult problem,so it is particularly important to establish accurate and efficient prediction models.This study explored the application of advancedmachine learning(ML)algorithms and Gene Expression Programming(GEP)techniques to predict CO_(2)-induced alterations in coal strength.Sixmodels were developed,including three metaheuristic-optimized XGBoost models(GWO-XGBoost,SSA-XGBoost,PO-XGBoost)and three GEP models(GEP-1,GEP-2,GEP-3).Comprehensive evaluations using multiple metrics revealed that all models demonstrated high predictive accuracy,with the SSA-XGBoost model achieving the best performance(R2—Coefficient of determination=0.99396,RMSE—Root Mean Square Error=0.62102,MAE—Mean Absolute Error=0.36164,MAPE—Mean Absolute Percentage Error=4.8101%,RPD—Residual Predictive Deviation=13.4741).Model interpretability analyses using SHAP(Shapley Additive exPlanations),ICE(Individual Conditional Expectation),and PDP(Partial Dependence Plot)techniques highlighted the dominant role of fixed carbon content(FC)and significant interactions between FC and CO_(2) saturation pressure(P).Theresults demonstrated that the proposedmodels effectively address the challenges of CO_(2)-induced strength prediction,providing valuable insights for geological storage safety and environmental applications.
文摘The problem of water and sulfur poisoning in flue gas atmosphere remains a significant obstacle for low-temperature deNO_(x) catalysts.This study investigated the sulfation mechanism of the CoMn_(2)O_(4)/CeTiO_(x)(CMCT)catalyst during the selective catalytic reduction of NO_(x) with NH3 under conditions containing H2O and SO_(2) at 150℃.Employing a comprehensive suite of time-resolved analysis and characterization techniques,the evolution of sulfate species was systematically categorized into three stages:initial rapid surface sulfate accumulation,the transformation of surface sulfates to bulk metal sulfates,and partial sulfates decomposition after the removal of H2O and SO_(2).These findings indicate that bulk metal sulfates irreversibly deactivate the catalyst by distorting active component lattices and consuming oxygen vacancies,whereas surface sulfates(including ammonium sulfates and surface-coordinated metal sulfates)cause reversible performance loss through decomposition.Furthermore,the competitive adsorption of H2O and SO_(2) significantly influences the catalytic efficiency,with H2O suppressing SO_(2) adsorption while simultaneously enhancing the formation of Brönsted acid sites.This research underscores the critical role of sulfate dynamics on catalyst performance,revealing the enhanced SO_(2) resistance of the Eley-Rideal mechanism facilitated by the Ce-Ti support relative to the Langmuir-Hinshelwood pathway.Collectively,the study unravels the complex interplay of sulfate dynamics influencing catalyst performance and provides potential approaches to mitigate deactivation in demanding atmospheric conditions.
文摘The aim of this study was to investigate the possible protective effects and mechanisms of 20-hydroxyecdysone, an insect steroid hormone, on HEO2-induced cytotoxicity in human neuroblastoma SH-SYSY cells. Pretreatment with 20-hydroxyecdysone significantly elevated the cell viability and decreased LDH leakage in H2O2-treated SH-SY5Y cells. 20-Hydroxyecdysone also dramatically reduced malondialdehyde （MDA） contents and enhanced the superoxide dismutase （SOD） activities under oxidative stress conditions. Furthermore, 20-hydroxyecdysone pretreatment inhibited apoptosis by decreasing the Bax/Bcl-2 ratio and attenuating the activation of caspase-3. These results suggest that 20-hydroxyecdysone can protect SH-SYSY cells against H2O2-induced cytotoxicity and might potentially be used to treat neurodegenerative diseases induced by oxidative stress and anontosis.
文摘Objective Stroke is a leading cause of death and disability worldwide,with ischemic stroke accounting for 80%-85%of cases.Despite the prevalence,effective treatments remain scarce.The compelling evidence suggest that high concentrations of ATP in the brain post-stroke can trigger irreversible neuronal damage and necrosis,contributing to a range of neurocellular dysfunctions.Pyroptosis,a recently identified form of programmed cell death,is characterized by caspase-1 activation and the action of the Gasdermin D(GSDMD)protein family,leading to cell perforation and inflammatory death.Methods In this study,human neuroblastoma SH-SY5Y cells were used to investigate the mechanisms of ATP-induced neurotoxicity and the protective effects of hydrogen sulfide(H_(2)S)against this toxicity through the antagonization of pyroptosis.We employed CCK-8 and LDH assays to assess cell viability.YO-PRO-1 fluorescent dyes and flow cytometry were conducted for detecting changes in cell membrane permeability.Western blot analysis was used to measure protein levels associated with cellular dysfunction.Results Our results indicate that high concentrations of ATP enhance cytotoxicity and increase cell membrane permeability in SH-SY5Y cells,that are mitigated by the H_(2)S donor NaHS.Furthermore,ATP was found to promote the activation of the NOD-like receptor pyrin domain-containing 1(NLRP-1),caspase-1,and the cleavage of GSDMD,with NaHS significantly attenuating these effects.Conclusion Our research suggests that H2S protects SH-SY5Y cells from ATP-induced neurotoxicity through a mechanism mediated by the NLRP1,caspase-1,and GSDMD pathway.
文摘To investigate and compare the inhibitory properties of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes (alpha-amylase & alpha-glucosidase) and Fe2+-induced lipid peroxidation in rat pancreas in vitro. Methods: The free phenolics were extracted with 80% (v/v) acetone, while bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate. Then, the interaction of the extracts with alpha-amylase and alpha-glucosidase was subsequently assessed. Thereafter, the total phenolic contents and antioxidant activities of the extracts were determined. Results: The result revealed that both extracts inhibited alpha-amylase and alpha-glucosidase in a dose-dependent manner. However, the alpha-glucosidase inhibitory activity of the extracts were significantly (P<0.05) higher than their alpha-amylase inhibitory activity. The free phenolics (31.67 mg/g) and flavonoid (17.28 mg/g) contents were significantly (P<0.05) higher than bound phenolic (23.52 mg/g) and flavonoid (13.70 mg/g) contents. Both extracts also exhibited high antioxidant activities as typified by their high reducing power, 1,1 diphenyl-2- picrylhydrazyl (DPPH) and 2, 2-azinobis-3-ethylbenzo-thiazoline-6-sulfonate (ABTS) radical scavenging abilities, as well as inhibition of Fe2+-induced lipid peroxidation in rat pancreas in vitro. Conclusions: This study provides a biochemical rationale by which clove elicits therapeutic effect on type 2 diabetes.
基金the Hubei Provincial Natural Science Foundation(No.2018CFC847)the Hubei Cancer Hospital Foundation(No.2015C11).
文摘The aim of the present study was to explore the effects of annexin A1(ANXA1) mimetic peptide AC2-26 on sepsis-induced cardiomyocyte apoptosis in vivo and in vitro and the underlying mechanisms.In the in vivo study,a rat septic model was established by the cecal ligation and puncture (CLP).The rats were divided into control group,sepsis group and AC2-26 group.The rats in the AC2-26 group were intraperitoneally injected with AC2-26(1mg/kg)2h before CLP,and those in the control group and sepsis group were injected with the same volume of normal saline.The myocardial tissue was examined by hematoxylin and eosin (HE)staining and transmission electron microscopy (TEM).Furthermore,myocardial apoptosis was measured by terminal dUTP nick end-labeling (TUNEL)assay.In the in vitro study,H9C2cells were cultured and divided into three groups:control group,in which cells were only given the basic culture medium;LPS group,in which cells were treated with 10μg/mL LPS;AC2-26 group,in which cells were treated with 0.5μmol/L AC2-262h before 10μg/mL LPS was given.The apoptosis of H9C2 cells was detected by flow cytometry.The levels of lipoxin A4 receptor (LXA4),phosphoinositide3-kinase (PI3K)and protein kinase B (PKB or AKT)protein were measured by Western blotting, the activity of NF-KB and the level of TNF-α by ELISA and the activities of caspase-3/8by using the caspase activity kits.The in vivo study showed that the myocardial pathological damage and myocardial ultrastructural damage were significantly alleviated and the myocardial apoptosis significantly decreased in the AC2-26 group as compared with the sepsis group (P<0.05 for all). The in vivo study revealed that the apoptosis of H9C2 cells was profoundly ameliorated in the AC2-26 group relative to the sepsis group (P<0.05).The protein expression levels of LXA4 were significantly up-regulated,and those of PI3K and AKT prominently down-regulated in the AC2-26 group when compared with those in the LPS group (P<0.05 for all).The activity of NF-κB was greatly inhibited and the level of TNF-α markedly decreased in the AC2-26 group as compared with those in the LPS group (P<0.05 for all).AC2-26 treatment also significantly suppressed the activities of caspase-3/8 in H9C2 cells.In conclusion,these findings suggest that AC2-26 may alleviate the sepsis-induced cardiomyocyte apoptosis in vivo and in vivo through the LXA4/PI3K/ AKT signaling pathway.
文摘The inflammatory response is involved in the pathogenesis of the most common types of heart disease. Sanguinarine （SAN） has various pharmacological properties such as anti-inflammatory, antioxidant, antibacterial, antitumor, and immune-enhancing properties. However, few studies have investigated the effects of SAN on lipopolysaceharide （LPS）-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes. Therefore, in this study, H9c2 cells were co-treated with SAN and LPS, and the mRNA levels of pro-inflammation markers and the apoptosis rate were measured to clarify the effect of SAN on cardiac inflammation. The underlying mechanism was further investigated by detecting the activation of Toll-like receptor （TLR）4/nuclear faetor-κB （NF-κB） signaling pathways. As a result, increased mRNA expression of interleukin （IL）-1β, IL-6, and TNFα induced by LPS was attenuated after SAN treatment; LPS-induced apoptosis ofHge2 cardiomyocytes and cleaved-caspase 8, 9, 3 were all significantly reduced by SAN. Further experiments showed that the beneficial effect of SAN on blocking the inflammation and apoptosis of H9c2 cardiomyocytes induced by LPS was associated with suppression of the TLR4/NF-κB signaling pathway. It was suggested that SAN suppressed the LPS-induced inflammation and apoptosis of H9c2 cardiomyocytes, which may be mediated by inhibition of the TLR4/NF-κB signaling pathway. Thus, SAN may be a feasible therapy to treat sepsis patients with cardiac dysfunction.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Nanjing University of Chinese Medicine Natural Science Foundation for the Youth(No.12XZR06)+1 种基金Anhui Province Natural Science Foundation(No.1408085MH146)Anhui University of Chinese Medicine Natural Science Foundation(No.2015qn023)
文摘This study aimed to investigate the protective effects of astragaloside IV(AS IV) on lipopolysaccharide(LPS)-induced injury in H9C2 cardiomyocytes. H9C2 Cardiomyocytes were cultured with LPS(10 μg·mL-1) for 4 h and treated with AS IV at 50, 100, and 150 μmol·L-1 for various durations. Cell viability was determined by MTT. The content of released TNF-α and IL-6 from cardiomyocytes were evaluated by enzyme-linked immunosorbent assay(ELISA). The levels of superoxidase dismutase(SOD), malondialdehyde(MDA), lactate dehydrogenase(LDH), and creatine phosphate kinase(CK) were measured by using commercial available kits. The mR NA and protein expression levels of NF-κB p65 were measured by RT-PCR and Western blotting, respectively. And the NF-κB p65 activity was measured by ELISA. Our results demonstrated that AS IV at 50, 100, and 150 μmol·L-1 markedly inhibited the release of TNF-α and IL-6 and decreased NF-κB expression, compared with the model group. Moreover, the improved SOD activity and decreased MDA, LDH and CK levels were detected after AS IV treatment. In summary, AS IV could increase the activities of antioxidant enzymes, inhibite lipid peroxidation, and down-regulate the inflammatory mediators involved in the inflammatory responses. These results demonstrated that AS IV could prevent LPS-induced injury in cardiomyocytes.
基金supported by the National Natural Science Foundation of China (21771070, 21571071)the Fundamental Research Funds for the Central Universities (2018KFYYXJJ120, 2019KFYRCPY104)~~
文摘In this study,an acid-induced assembly strategy for a rutile TiO2 photocatalyst was proposed on the basis of the treatment of lamellar protonated titanate with a concentrated HNO3 solution.Nitrate groups were successfully grafted onto a TiO2 surface and induced the assembly of rutile TiO2 nanorods into uniform spindle-like nanobundles.The resulting TiO2 product achieved a photocatalytic hydrogen evolution rate of 402.4μmol h^?1,which is 3.1 times higher than that of Degussa P25-TiO2.It was demonstrated that nitrate group grafting caused the rutile TiO2 surface to become negatively charged,which is favorable for trapping positive protons and improving charge carrier separation,thereby enhancing photocatalytic hydrogen production.Additionally,surface charges were crucial to structural stability based on electrostatic repulsion.This study not only developed a facile surface modification strategy for fabricating efficient H2 production photocatalysts but also identified an influence mechanism of inorganic acids different from that reported in the literature.
文摘Benzene is an established leukotoxin and leukemogen in humans. We have previously re- ported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit （DNA-PKcs） to mediate the cellular response to DNA double strand break （DSB） caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-（morpholin-4-yl）-benzo[h]chomen-4-one （NU7026）, as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phos- phorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apop- tosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.
基金Project (No.2007C33030) supported by the Science and Technology Program of Zhejiang Province,China
文摘Eucommia ulmoides Oliv.(EuO),also known as Duzhong,native to China,has been reported to have antioxidative function,but its cellular mechanism is not fully examined yet.We investigated inhibitory effects of EuO leaf ethanol extracts on H2O2-induced apoptosis in rat osteoblastic MC3T3-E1 cells and underlying mechanisms.Locally-grown Duzhong leaves were extracted with ethanol.MC3T3-E1 cells were treated with EuO (6.25,12.5,25,50,and 100 μg/ml) for 24 h,and then H2O2 (800 μmol/L) for an additional 24 h.Cell survival rate,percentage of apoptosis,and expressions of caspases 3,6,7,and 9 were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay,microscopic analysis,Western blotting,and reverse transcription polymerase chain reaction (RT-PCR).The final EuO leaf ethanol extract powder was detected to contain caffeotannic acid at 58 mg/g and geniposide at 3.45 mg/g by high performance liquid chromatography (HPLC).EuO remarkably restrained cell oxidative damage and increased cell survival rate in a dose-dependent manner: 0 μg/ml,0.21;6.25 μg/ml,0.28;12.5 μg/ml,0.31;25 μg/ml,0.48;50 μg/ml,0.54;and 100 μg/ml,0.66 (P<0.05),with the half-effective concentration being around 25 μg/ml.MTT results were confirmed by microscopic analysis.Western blotting and RT-PCR analyses showed that the expressions of caspases 3,6,7,and 9 were significantly decreased in the EuO-treated cells compared with the control (EuOand H2O2-free) (P<0.05),with the half-effective concentration of EuO ranging from 12.5 to 25 μg/ml.We conclude that the ethanol-extracted EuO leaf extracts promoted the growth of MC3T3-E1 cells,and suppressed the H2O2-induced apoptosis in a rat MC3T3-E1 osteogenic cell model,likely due to the inhibition of caspases’ activities.The results indicate that EuO is a potent antioxidant,which may contribute to its many cellular protective functions,including the promotion of bone growth.
基金This research was supported by the National Natural Science Foundation of China(31772288)Shandong Natural Science Major Basic Research Foundation(ZR2020ZD43).
文摘Jasmonic acid(JA)plays an important role in regulating leaf senescence.However,the molecular mechanisms of leaf senescence in apple(Malus domestica)remain elusive.In this study,we found that MdZAT10,a C2H2-type zinc finger transcription factor(TF)in apple,markedly accelerates leaf senescence and increases the expression of senescence-related genes.To explore how MdZAT10 promotes leaf senescence,we carried out liquid chromatography/mass spectrometry screening.We found that MdABI5 physically interacts with MdZAT10.MdABI5,an important positive regulator of leaf senescence,significantly accelerated leaf senescence in apple.MdZAT10 was found to enhance the transcriptional activity of MdABI5 for MdNYC1 and MdNYE1,thus accelerating leaf senescence.In addition,we found that MdZAT10 expression was induced by methyl jasmonate(MeJA),which accelerated JA-induced leaf senescence.We also found that the JA-responsive protein MdBT2 directly interacts with MdZAT10 and reduces its protein stability through ubiquitination and degradation,thereby delaying MdZAT10-mediated leaf senescence.Taken together,our results provide new insight into the mechanisms by which MdZAT10 positively regulates JA-induced leaf senescence in apple.
基金supported by grants from the National Natural Science Foundation of China(32030044,32171012,82101332,32200948,and 323B1008)the Natural Science Foundation of Jiangsu Province,China(BK20240168+3 种基金BK20190008)the grant from the State Key Laboratory of Pharmaceutical Biotechnology(LNSN-202402)the Fundamental Research Funds for the Central Universities(020814380197,020814380208)Nanjing University Integrated Research Platform of the Ministry of Education-Top Talents Program(2024300475).
文摘The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson’s disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K^(+) channels, or Ca^(2+)-activated K+ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
文摘Gastric mucosal inflammatory responses to H. pylori lipopolysaccharide (LPS), are characterized by the excessive NO and prostaglandin (PGE2) generation due to the disturbances in nitric oxide synthase (NOS) and cyclooxygenase (COX) systems. Here, we report that the LPS-induced enhancement in gastric mucosal inducible (i) iNOS) activity and up-regulation in PGE2 production was associated with the suppression in Akt kinase activity and the impairment in constitutive (c) cNOS activation. The stimulatory effect of the LPS on PGE2 production, furthermore, was susceptible to suppression by COX-2 inhibitor, NS-398, and iNOS inhibitor, 1400 W. Further, we show that the countering effect of peptide hormone, ghrelin, on the LPS-induced changes was reflected in up-regu- lation in Akt activity and the increase in cNOS activation through phosphorylation, and accompanied by the suppression in iNOS expression and the reduction in COX-2 activity associated with the loss in COX-2 protein S-nitrosylation. Moreover, the effect of ghre-lin on the LPS-induced COX-2 S-nitrosylation was subject to repression by Akt inhibition. Our findings demonstrate that induction in iNOS with H. pylori in- fection leads to COX-2 activation through S-nitro- sylation and up-regulation in PGE2 generation, and that ghrelin counters these untoward consequences of the LPS through Akt-mediated up-regulation in cNO- S activation required for the iNOS gene repression.
基金The National Key Project for Basic Research of China(973 Project)(No.2005CB221402)China National Petroleum Corporation
文摘The activation of adsorbed CO is an important step in CO hydrogenation. The results from TPSR of pre-adsorbed CO with H2 and syngas suggested that the presence of H2 increased the amount of CO adsorption and accelerated CO dissociation. The H2 was adsorbed first, and activated to form H＊ over metal sites, then reacted with carbonaceous species. The oxygen species for CO2 formation in the presence of hydrogen was mostly OH^＊, which reacted with adsorbed CO subsequently via CO^＊＋OH^＊ → CO2^＊＋H^＊; however, the direct CO dissociation was not excluded in CO hydrogenation. The dissociation of C-O bond in the presence of H2 proceeded by a concerted mechanism, which assisted the Boudourd reaction of adsorbed CO on the surface via CO^＊＋2H^＊ → CH^＊＋OH^＊. The formation of the surface species （CH） from adsorbed CO proceeded as indicated with the participation of surface hydrogen, was favored in the initial step of the Fischer-Tropsch synthesis.
基金financially supported by the Scientific and Technological Project of Shaanxi Province of China,No.2016SF-010
文摘Rho kinase （ROCK） was the first downstream Rho effector found to mediate RhoA-induced actin cytoskeletal changes through effects on myosin light chain phosphorylation. There is abundant evidence that the ROCK pathway participates in the pathogenesis of retinal endothelial injury and proliferative epiretinal membrane traction. In this study, we investigated the effect of the ROCK pathway inhibitor Y-27632 on retinal Müller cells subjected to hypoxia or oxidative stress. Müller cells were subjected to hypoxia or oxidative stress by exposure to CoCl2 or H2O2. After a 24-hour treatment with Y-27632, the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide assay was used to assess the survival of Müller cells. Hoechst 33258 was used to detect apoptosis, while 2′,7′-dichlorodihydrofluorescein diacetate was used to measure reactive oxygen species generation. A transwell chamber system was used to examine the migration ability of Müller cells. Western blot assay was used to detect the expression levels of α-smooth muscle actin, glutamine synthetase and vimentin. After treatment with Y-27632, Müller cells subjected to hypoxia or oxidative stress exhibited a morphology similar to control cells. Y-27632 reduced apoptosis, α-smooth muscle actin expression and reactive oxygen species generation under oxidative stress, and it reduced cell migration under hypoxia. Y-27632 also upregulated glutamine synthetase expression under hypoxia but did not impact vimentin expression. These findings suggest that Y-27632 protects Müller cells against cellular injury caused by oxidative stress and hypoxia by inhibiting the ROCK pathway.
基金supported by the grants from the National Natural Science Foundation of China(No.30971245 and No.81000112)
文摘Pathological cardiac hypertrophy induced by angiotensin Ⅱ （Ang Ⅱ ） can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the roots ofNardostachys chinensis, a well-known traditional Chinese medicine. In order to investigate the effects of nardosinone on Ang Ⅱ-induced cardiac cell hypertrophy and the related mechanisms, the myoblast cell line H9c2, derived from embryonic rat heart, was treated with nardosi- none （25, 50, 100, and 200μmol/L） or Ang Ⅱ （1 μmol/L）. Then cell surface area and mRNA expression of classical markers of hypertrophy were detected. The related protein levels in PI3K/Akt/mTOR and MEK/ERK signaling pathways were examined by Western blotting. It was found that pretreatment with nardosinone could significantly inhibit the enlargement of cell surface area induced by Ang Ⅱ. The mRNA expression of ANP, BNP and 13-MHC was obviously elevated in Ang Ⅱ-treated H9c2 cells, which could be effectively blocked by nardosinone at the concentration of 100μmol/L. Further study revealed that the protective effects of nardosinone might be mediated by repressing the phosphorylation of related proteins in PI3K/Akt and MEK/ERK signaling pathways. It was suggested that the inhibitory effect of nardosinone on Ang Ⅱ-induced hypertrophy in H9c2 cells might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways.
文摘Objective To investigate the role of H1 and H2 receptors in the locus ceruleus （LC） in carotid sinus baroreceptor reflex （CSR） resetting induced by intracerebroventricular （i.c.v.） injection of histamine （HA）. Methods The left and right carotid sinus regions were isolated from the systemic circulation in 18 male Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure （ISP） was altered in a stepwise manner in vivo. ISP-mean arterial pressure （MAP） relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CSR performance induced by i.c.v. HA and the effects of pretreatment with H1 or H2 receptors selective antagonist, chlorpheniramine （CHL） or cimetidine （CIM） into the LC, on the responses of CSR to HA were examined. Results I.c.v. HA （100 ng in 5 μl） significantly shifted the ISP-MAP relationship curve upwards （P 〈 0.05） and obviously decreased the value of the reflex parameters such as MAP range and maximum gain （P 〈 0.05）, but increased the threshold pressure, saturation pressure and ISP at maximum gain （P 〈 0.05）. The pretreatment with CHL （0.5 μg in 1 μl） or CIM （1.5 μg in 1 μl） into the LC could obviously attenuate the changes mentioned above in CSR performance induced by HA, but the alleviative effect of CIM was less remarkable than that of CHL （P 〈 0.05）. Respective microinjection of CHL or CIM alone into the LC with the corresponding dose and volume did not change CSR performance significantly （P 〉 0.05）. Conclusion Intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the responses of CSR to HA may be mediated, at least in part, by H1 and H2 receptors activities in the LC, especially by H1 receptors. Moreover, the effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to LC.
