To investigate the effect of Myocardin related transcription factor A(MRTF-A)on apoptosis induced by ischemic/reperfusion(I/R),middle cerebral artery occlusion/reperfusion(MCAO/R)in rats were applied to mimic I/R.The ...To investigate the effect of Myocardin related transcription factor A(MRTF-A)on apoptosis induced by ischemic/reperfusion(I/R),middle cerebral artery occlusion/reperfusion(MCAO/R)in rats were applied to mimic I/R.The neurological deficit score,cerebral infarct size,cortical neuron apoptosis and cleaved caspase 3 level were evaluated to determine the effect and the level of apoptosis by TTC straining,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)straining,Western blot and immunofuorescence staining.The myeloid cell leukemia-1(Mcl-1)expression,release of cytochrome C(Cyt C)and its colocalization with apoptotic pro-tease activating factor-1(Apaf-1)were analyzed by quantitative real-time PCR(qRT-PCR),Western blot,and immunofuorescence staining.The results showed that MRTF-A over-expression could decrease the neurological deficit score and reduce cerebral infarct size(P<0.01 versus Sham).In the MRTF-A-I/R group,TUNEL-positive cells and apoptosis ratio(%)(51.61±6.17%)were significantly decreased compared to the Neg-I/R group(76.45±8.77%)at 24 h reperfusion.Meanwhile,the cleaved caspase 3 expression revealed a similar trend while the expression of Mcl-1 was the opposite.Moreover,MRTF-A overexpression significantly enhanced Mcl-1 fAuorescence intensity,which up-regulated the mRNA and protein level(P<0.05or P<0.01 versus Neg-I/R).Furthermore,MRTF-A overexpression markedly inhibited the release of Cyt C,and decreased the colocalization with Apaf-1 in the cytoplasm(P<0.05 or P<0.01.versus Neg-I/R).All the data indicated that MRTF-A overexpression could improve the neu-rological function against cerebral I/R-induced apoptosis since underlying mechanism might be involved in the Mc-1/Cyt C/cleaved caspase 3 signaling pathway.展开更多
Recently,photodynamic therapy(PDT)has attracted wide attention due to its less susceptibility to drug resistance,broad-spectrum biocidal activity and biosafety in normal tissues.However,the traditional photosensitizer...Recently,photodynamic therapy(PDT)has attracted wide attention due to its less susceptibility to drug resistance,broad-spectrum biocidal activity and biosafety in normal tissues.However,the traditional photosensitizers(Ps)face the disadvantage of poor therapeutic efficacy due to the requirement of an aerobic environment to generate ^(1)O_(2) through Type Ⅱ pathway.Herein,we designed and synthesized a novel cationic conjugated oligomer oligo(phenylene vinylene)(OPV)and studied its antibacterial photodynamic activity against both Gram-negative Escherichia coli(E.coli)and Gram-positive bacteria methicillin-resistant Staphylococcus aureus(MRSA).Importantly,the OpV can rapidly produce reactive oxygen species(ROs)through double pathways,Type Ⅰ and Ⅱ mechanism under white light irradiation,and efficiently kill E.coli and MRSA at a nanomolar level.The dual type photosensitizing capability makes OPV promising for enhanced PDT to treat pathogens and tumors in complex environments.展开更多
Regulating antioxidative stress pathways to augment oxidative stress and enhance antitumor therapy is highly desirable but very challenging.Herein,we initiated a multifunctional nanoparticle to regulate the Keap1-Nrf2...Regulating antioxidative stress pathways to augment oxidative stress and enhance antitumor therapy is highly desirable but very challenging.Herein,we initiated a multifunctional nanoparticle to regulate the Keap1-Nrf2 antioxidative stress pathway to promote cancer cell apoptosis.The OPFV-SnMP@GE11 nanoparticles were assembled by enzyme-activated OPFV-TLQ,tin mesoporphyrin(SnMP),and DSPEPEG-GE11.OPFV-SnMP@GE11 accumulated at tumor sites through specific targeting with GE11.OPFV-TLQ was specifically reduced to a photosensitizer OPFVNH2 by endocellular NAD(P)H:quinone oxidoreductase 1(NQO1).Under irradiation,OPFV-NH2 greatly produced reactive oxygen species(ROS)through a type I mechanism,which activated the Keap1-Nrf2 signal pathway and enhanced the transcription of NQO1,resulting in a continuous and explosive generation of ROS.Additionally,SnMP inhibited the activity of heme oxygenase-1(HO-1),further depressing antioxidative stress.This strategy provides insight into the regulation of the signal pathway to amplify oxidative stress,paving the way to studying the molecular mechanisms of cellular activities to enhance cancer therapy.展开更多
In this study,we identified that a conserved circular RNA(circRNA)DICAR,which was downregulated in diabetic mouse hearts.DICAR had an inhibitory effect on diabetic cardiomyopathy(DCM),as the spontaneous cardiac dysfun...In this study,we identified that a conserved circular RNA(circRNA)DICAR,which was downregulated in diabetic mouse hearts.DICAR had an inhibitory effect on diabetic cardiomyopathy(DCM),as the spontaneous cardiac dysfunction,cardiac cell hypertrophy,and cardiac fibrosis occurred in DICAR deficiency(DICAR+/−)mice,whereas the DCM was alleviated in DICARoverexpressed DICARTg mice.At the cellular level,we found that overexpression of DICAR inhibited,but knockdown of DICAR enhanced the diabetic cardiomyocyte pyroptosis.At the molecular level,we identified that DICAR-VCP-Med12 degradation could be the underlying molecular mechanism in DICAR-mediated effects.The synthesized DICAR junction part(DICAR-JP)exhibited a similar effect to the entire DICAR.In addition,the expression of DICAR in circulating blood cells and plasma from diabetic patients was lower than that from health controls,which was consistent with the decreased DICAR expression in diabetic hearts.DICAR and the synthesized DICAR-JP may be drug candidates for DCM.展开更多
The conversion of N_(2)to NH_(3)holds great importance due to the essential role of NH_(3)in fertilizer production,energy storage and the synthesis of key industrial chemicals.Development of novel methods for N_(2)tra...The conversion of N_(2)to NH_(3)holds great importance due to the essential role of NH_(3)in fertilizer production,energy storage and the synthesis of key industrial chemicals.Development of novel methods for N_(2)transformation is a worthwhile goal and researchers have turned their attention to electrochemical N_(2)reduction as a potentially sustainable solution.The development of molecular electrocatalysts has gained considerable momentum over the last decades,and this review focuses on the advances and challenges in the field of molecular electrochemical nitrogen fixation and aims to inspire further research into the realm of nitrogen fixation chemistry from an electrochemical perspective.展开更多
Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis.Long non-coding RNAs(lncRNAs)are a group of protein ...Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis.Long non-coding RNAs(lncRNAs)are a group of protein expression regulators;however,the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear.The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis.We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis.In cultured monocytes,Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation.The differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown.Moreover,overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage differentiation.The role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice.We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression,whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation.To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease,we applied an acute atherosclerosis model in mice.The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice.The results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes,which is involved in atherogenesis.展开更多
基金supported by the National Nature Science Foundation of China(Nos.31171327 and 81770377)the Nature Science Foundation of Hubei Province(No.2017CFB448).
文摘To investigate the effect of Myocardin related transcription factor A(MRTF-A)on apoptosis induced by ischemic/reperfusion(I/R),middle cerebral artery occlusion/reperfusion(MCAO/R)in rats were applied to mimic I/R.The neurological deficit score,cerebral infarct size,cortical neuron apoptosis and cleaved caspase 3 level were evaluated to determine the effect and the level of apoptosis by TTC straining,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)straining,Western blot and immunofuorescence staining.The myeloid cell leukemia-1(Mcl-1)expression,release of cytochrome C(Cyt C)and its colocalization with apoptotic pro-tease activating factor-1(Apaf-1)were analyzed by quantitative real-time PCR(qRT-PCR),Western blot,and immunofuorescence staining.The results showed that MRTF-A over-expression could decrease the neurological deficit score and reduce cerebral infarct size(P<0.01 versus Sham).In the MRTF-A-I/R group,TUNEL-positive cells and apoptosis ratio(%)(51.61±6.17%)were significantly decreased compared to the Neg-I/R group(76.45±8.77%)at 24 h reperfusion.Meanwhile,the cleaved caspase 3 expression revealed a similar trend while the expression of Mcl-1 was the opposite.Moreover,MRTF-A overexpression significantly enhanced Mcl-1 fAuorescence intensity,which up-regulated the mRNA and protein level(P<0.05or P<0.01 versus Neg-I/R).Furthermore,MRTF-A overexpression markedly inhibited the release of Cyt C,and decreased the colocalization with Apaf-1 in the cytoplasm(P<0.05 or P<0.01.versus Neg-I/R).All the data indicated that MRTF-A overexpression could improve the neu-rological function against cerebral I/R-induced apoptosis since underlying mechanism might be involved in the Mc-1/Cyt C/cleaved caspase 3 signaling pathway.
基金financial support from the National Natural Science Foundation of China(Grants 21974084,22274095 and 22101310)Innovation Capability Support Program of Shaanxi(Program no.2021TD-42)Fundamental Research Funds for the Central Universities(No.GK202302004,GK202207013,and GK202101001).
文摘Recently,photodynamic therapy(PDT)has attracted wide attention due to its less susceptibility to drug resistance,broad-spectrum biocidal activity and biosafety in normal tissues.However,the traditional photosensitizers(Ps)face the disadvantage of poor therapeutic efficacy due to the requirement of an aerobic environment to generate ^(1)O_(2) through Type Ⅱ pathway.Herein,we designed and synthesized a novel cationic conjugated oligomer oligo(phenylene vinylene)(OPV)and studied its antibacterial photodynamic activity against both Gram-negative Escherichia coli(E.coli)and Gram-positive bacteria methicillin-resistant Staphylococcus aureus(MRSA).Importantly,the OpV can rapidly produce reactive oxygen species(ROs)through double pathways,Type Ⅰ and Ⅱ mechanism under white light irradiation,and efficiently kill E.coli and MRSA at a nanomolar level.The dual type photosensitizing capability makes OPV promising for enhanced PDT to treat pathogens and tumors in complex environments.
基金supported by the National Natural Science Foundation of China(grant nos.22274095 and 21974084)the Innovation Capability Support Program of Shaanxi(program no.2021TD-42)the Fundamental Research Funds for the Central Universities(program nos.GK202302004,2021TS030,and GK202101001).
文摘Regulating antioxidative stress pathways to augment oxidative stress and enhance antitumor therapy is highly desirable but very challenging.Herein,we initiated a multifunctional nanoparticle to regulate the Keap1-Nrf2 antioxidative stress pathway to promote cancer cell apoptosis.The OPFV-SnMP@GE11 nanoparticles were assembled by enzyme-activated OPFV-TLQ,tin mesoporphyrin(SnMP),and DSPEPEG-GE11.OPFV-SnMP@GE11 accumulated at tumor sites through specific targeting with GE11.OPFV-TLQ was specifically reduced to a photosensitizer OPFVNH2 by endocellular NAD(P)H:quinone oxidoreductase 1(NQO1).Under irradiation,OPFV-NH2 greatly produced reactive oxygen species(ROS)through a type I mechanism,which activated the Keap1-Nrf2 signal pathway and enhanced the transcription of NQO1,resulting in a continuous and explosive generation of ROS.Additionally,SnMP inhibited the activity of heme oxygenase-1(HO-1),further depressing antioxidative stress.This strategy provides insight into the regulation of the signal pathway to amplify oxidative stress,paving the way to studying the molecular mechanisms of cellular activities to enhance cancer therapy.
基金National Natural Science Foundation of China(#81770377,#82030007)Hubei Province Funds for Distinguished Young Scholars(#2020CFA076)+2 种基金High-level Hospital Construction Project(#DFJH201807)Scientific Research Plan Project of Hubei Provincial Department of Education(#D20211105)Health Commission of Hubei Province Scientific Research Project(#WJ2021M215).
文摘In this study,we identified that a conserved circular RNA(circRNA)DICAR,which was downregulated in diabetic mouse hearts.DICAR had an inhibitory effect on diabetic cardiomyopathy(DCM),as the spontaneous cardiac dysfunction,cardiac cell hypertrophy,and cardiac fibrosis occurred in DICAR deficiency(DICAR+/−)mice,whereas the DCM was alleviated in DICARoverexpressed DICARTg mice.At the cellular level,we found that overexpression of DICAR inhibited,but knockdown of DICAR enhanced the diabetic cardiomyocyte pyroptosis.At the molecular level,we identified that DICAR-VCP-Med12 degradation could be the underlying molecular mechanism in DICAR-mediated effects.The synthesized DICAR junction part(DICAR-JP)exhibited a similar effect to the entire DICAR.In addition,the expression of DICAR in circulating blood cells and plasma from diabetic patients was lower than that from health controls,which was consistent with the decreased DICAR expression in diabetic hearts.DICAR and the synthesized DICAR-JP may be drug candidates for DCM.
基金supported by the National Natural Science Foundation of China(21988101)。
文摘The conversion of N_(2)to NH_(3)holds great importance due to the essential role of NH_(3)in fertilizer production,energy storage and the synthesis of key industrial chemicals.Development of novel methods for N_(2)transformation is a worthwhile goal and researchers have turned their attention to electrochemical N_(2)reduction as a potentially sustainable solution.The development of molecular electrocatalysts has gained considerable momentum over the last decades,and this review focuses on the advances and challenges in the field of molecular electrochemical nitrogen fixation and aims to inspire further research into the realm of nitrogen fixation chemistry from an electrochemical perspective.
基金supported by the National Natural Science Foundation of China(Grant Nos.82030007,81670398,and 91639102)the Central Government Guides Local Science and Technology Development Project(Grant No.2022ZYD0057)+2 种基金the Sichuan Science and Technology Program(Grant Nos.2022YFS0578 and 2022YFS0614)the Start-up Research Fund of Southwest Medical University(Grant No.00040155)supported in part by the Start-up fund from the University of Alabama at Birmingham.
文摘Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis.Long non-coding RNAs(lncRNAs)are a group of protein expression regulators;however,the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear.The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis.We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis.In cultured monocytes,Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation.The differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown.Moreover,overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage differentiation.The role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice.We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression,whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation.To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease,we applied an acute atherosclerosis model in mice.The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice.The results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes,which is involved in atherogenesis.