Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various disea...Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.展开更多
Theranostic agents that can be sensitively and specifically activated by the tumor microenvironment(TME)have recently attracted considerable attention.In this study,TME-activatable 3,3′,5,5′-tetramethylbenzidine(TMB...Theranostic agents that can be sensitively and specifically activated by the tumor microenvironment(TME)have recently attracted considerable attention.In this study,TME-activatable 3,3′,5,5′-tetramethylbenzidine(TMB)-copper peroxide(CuO_(2))@poly(lactic-co-glycolic acid)(PLGA)@red blood cell membrane(RBCM)(TCPR)nanoparticles(NPs)for second near-infrared photoacoustic imaging-guided tumor-specific photothermal therapy were developed by co-loading CuO_(2)NPs and TMB into PLGA camouflaged by RBCMs.As an efficient H_(2)O_(2)supplier,once exposed to a proton-rich TME,CuO_(2)NPs can generate H_(2)O_(2)and Cu^(2+),which are further reduced to Cu^(+) by endogenous glutathione.Subsequently,the Cu^(+)-mediated Fenton-like reaction produces cytotoxic·OH to kill the cancer cells and induce TMB-mediated photoacoustic and photothermal effects.Combined with the RBCM modification-prolonged blood circulation,TCPR NPs display excellent specificity and efficiency in suppressing tumor growth,paving the way for more accurate,safe,and efficient cancer theranostics.展开更多
Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-022-00900-8,published online 28 March 2022 The plate photo from Control in Figure 4c of the published work was mistakenly used when...Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-022-00900-8,published online 28 March 2022 The plate photo from Control in Figure 4c of the published work was mistakenly used when editing the photos,and the corrected version is demonstrated below.The results and conclusions of this paper were not affected by this error.展开更多
The current feasibility of nanocatalysts in clinical anti-infection therapy,especially for drug-resistant bacteria infection is extremely restrained because of the insufficient reactive oxygen generation.Herein,a nove...The current feasibility of nanocatalysts in clinical anti-infection therapy,especially for drug-resistant bacteria infection is extremely restrained because of the insufficient reactive oxygen generation.Herein,a novel Ag/Bi2MoO6(Ag/BMO)nanozyme optimized by charge separation engineering with photoactivated sustainable peroxidase-mimicking activities and NIR-II photodynamic performance was synthesized by solvothermal reaction and photoreduction.The Ag/BMO nanozyme held satisfactory bactericidal performance against methicillin-resistant Staphylococcus aureus(MRSA)(~99.9%).The excellent antibacterial performance of Ag/BMO NPs was ascribed to the corporation of peroxidase-like activity,NIR-II photodynamic behavior,and acidity-enhanced release of Ag^(+).As revealed by theoretical calculations,the introduction of Ag to BMO made it easier to separate photo-triggered electronhole pairs for ROS production.And the conduction and valence band potentials of Ag/BMO NPs were favorable for the reduction of O_(2) to·O_(2)^(−).Under 1064 nm laser irradiation,the electron transfer to BMO was beneficial to the reversible change of Mo^(5+)/Mo^(6+),further improving the peroxidase-like catalytic activity and NIR-II photodynamic performance based on the Russell mechanism.In vivo,the Ag/BMO NPs exhibited promising therapeutic effects towards MRSA-infected wounds.This study enriches the nanozyme research and proves that nanozymes can be rationally optimized by charge separation engineering strategy.展开更多
Cisplatin(CDDP)-based chemotherapy is substantially limited in the clinic due to its high postoperative recurrence rate.Synergy therapy has been proven as a potent approach to minimize recurrence and achieve enhanced ...Cisplatin(CDDP)-based chemotherapy is substantially limited in the clinic due to its high postoperative recurrence rate.Synergy therapy has been proven as a potent approach to minimize recurrence and achieve enhanced treatment effects.Herein,chemotherapy drug CDDP is assembled with the photothermal-Fenton agent of bovine serum albumin(BSA)stabilized gallic acid-functionalized iron nanoparticles(GA-Fe NPs)to achieve chemo/chemodynamic synergistic cascade oncotherapy.The Pt-GA-Fe NPs can be utilized to generate H_(2)O_(2) via the activation of nicotinamide adenine dinucleotide phosphate(NADPH)oxidases(NOXs)in the tumor microenvironment(TME),which would then greatly boost H2O2-depending chemodynamic therapy(CDT).The generated cytotoxic reactive oxygen species(hydroxyl radicals,·OH)and the depletion of glutathione(GSH)would further promote CDDP-induced DNA damage.Moreover,benefiting from the absorption in the near-infrared(NIR)region,Pt-GA-Fe NPs exhibit excellent photothermal conversion efficiency(η=45.5%)and allow photoacoustic imaging(PAI)guided photothermal therapy(PTT).In vitro and in vivo experiments show that synergy therapy can effectively kill cancer cells and successfully cure cancer without systemic toxicity.The work highlights a new type of therapeutic agent based on CDDP with the ability of H_(2)O_(2) self-generation,thermal responsiveness,and enhanced CDT effects for applications in cancer therapy.展开更多
基金supported by National Natural Science Foundation of China,No.32102745(to XL).
文摘Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.
基金This work was supported by the National Natural Science Foundation of China(62120106002,51803091,61935004,22175089)Jiangsu Province Policy Guidance Plan(BZ2019014)+3 种基金Jiangsu Provincial key research and development plan(BE2021711)Natural Science Foundation of Shandong Province(ZR2020KB018)Taishan scholars construction special fund of Shandong Province,Natural Science Foundation of Ningbo(202003N40448)the Jiangsu postgraduate research innovation program(KYCX21_1103).
文摘Theranostic agents that can be sensitively and specifically activated by the tumor microenvironment(TME)have recently attracted considerable attention.In this study,TME-activatable 3,3′,5,5′-tetramethylbenzidine(TMB)-copper peroxide(CuO_(2))@poly(lactic-co-glycolic acid)(PLGA)@red blood cell membrane(RBCM)(TCPR)nanoparticles(NPs)for second near-infrared photoacoustic imaging-guided tumor-specific photothermal therapy were developed by co-loading CuO_(2)NPs and TMB into PLGA camouflaged by RBCMs.As an efficient H_(2)O_(2)supplier,once exposed to a proton-rich TME,CuO_(2)NPs can generate H_(2)O_(2)and Cu^(2+),which are further reduced to Cu^(+) by endogenous glutathione.Subsequently,the Cu^(+)-mediated Fenton-like reaction produces cytotoxic·OH to kill the cancer cells and induce TMB-mediated photoacoustic and photothermal effects.Combined with the RBCM modification-prolonged blood circulation,TCPR NPs display excellent specificity and efficiency in suppressing tumor growth,paving the way for more accurate,safe,and efficient cancer theranostics.
文摘Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-022-00900-8,published online 28 March 2022 The plate photo from Control in Figure 4c of the published work was mistakenly used when editing the photos,and the corrected version is demonstrated below.The results and conclusions of this paper were not affected by this error.
基金NNSF of China(62120106002,52103166)Jiangsu Province Policy Guidance Plan(BZ2019014)+1 种基金Natural Science Foundation of Jiangsu Province(BK20200710)‘Taishan scholars’construction special fund of Shandong Province.
文摘The current feasibility of nanocatalysts in clinical anti-infection therapy,especially for drug-resistant bacteria infection is extremely restrained because of the insufficient reactive oxygen generation.Herein,a novel Ag/Bi2MoO6(Ag/BMO)nanozyme optimized by charge separation engineering with photoactivated sustainable peroxidase-mimicking activities and NIR-II photodynamic performance was synthesized by solvothermal reaction and photoreduction.The Ag/BMO nanozyme held satisfactory bactericidal performance against methicillin-resistant Staphylococcus aureus(MRSA)(~99.9%).The excellent antibacterial performance of Ag/BMO NPs was ascribed to the corporation of peroxidase-like activity,NIR-II photodynamic behavior,and acidity-enhanced release of Ag^(+).As revealed by theoretical calculations,the introduction of Ag to BMO made it easier to separate photo-triggered electronhole pairs for ROS production.And the conduction and valence band potentials of Ag/BMO NPs were favorable for the reduction of O_(2) to·O_(2)^(−).Under 1064 nm laser irradiation,the electron transfer to BMO was beneficial to the reversible change of Mo^(5+)/Mo^(6+),further improving the peroxidase-like catalytic activity and NIR-II photodynamic performance based on the Russell mechanism.In vivo,the Ag/BMO NPs exhibited promising therapeutic effects towards MRSA-infected wounds.This study enriches the nanozyme research and proves that nanozymes can be rationally optimized by charge separation engineering strategy.
基金National Natural Science Foundation(NNSF)of China(Nos.61775095,61935004,and 51803091)Jiangsu Province Policy Guidance Plan(No.BZ2019014)+2 种基金Natural Science Foundation of Jiangsu Province(No.BK20200092)Natural Science Foundation of Shandong Province(No.ZR2020KB018)“Taishan scholars”construction special fund of Shandong Province.
文摘Cisplatin(CDDP)-based chemotherapy is substantially limited in the clinic due to its high postoperative recurrence rate.Synergy therapy has been proven as a potent approach to minimize recurrence and achieve enhanced treatment effects.Herein,chemotherapy drug CDDP is assembled with the photothermal-Fenton agent of bovine serum albumin(BSA)stabilized gallic acid-functionalized iron nanoparticles(GA-Fe NPs)to achieve chemo/chemodynamic synergistic cascade oncotherapy.The Pt-GA-Fe NPs can be utilized to generate H_(2)O_(2) via the activation of nicotinamide adenine dinucleotide phosphate(NADPH)oxidases(NOXs)in the tumor microenvironment(TME),which would then greatly boost H2O2-depending chemodynamic therapy(CDT).The generated cytotoxic reactive oxygen species(hydroxyl radicals,·OH)and the depletion of glutathione(GSH)would further promote CDDP-induced DNA damage.Moreover,benefiting from the absorption in the near-infrared(NIR)region,Pt-GA-Fe NPs exhibit excellent photothermal conversion efficiency(η=45.5%)and allow photoacoustic imaging(PAI)guided photothermal therapy(PTT).In vitro and in vivo experiments show that synergy therapy can effectively kill cancer cells and successfully cure cancer without systemic toxicity.The work highlights a new type of therapeutic agent based on CDDP with the ability of H_(2)O_(2) self-generation,thermal responsiveness,and enhanced CDT effects for applications in cancer therapy.
