Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has ...Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.展开更多
Acute kidney injury(AKI)is a serious kidney disease without specific medications currently except for expensive dialysis treatment.Some potential drugs are limited due to their high hydrophobicity,poor in vivo stabili...Acute kidney injury(AKI)is a serious kidney disease without specific medications currently except for expensive dialysis treatment.Some potential drugs are limited due to their high hydrophobicity,poor in vivo stability,low bioavailability and possible adverse effects.Besides,kidney-targeted drugs are not common and small molecules are cleared too quickly to achieve effective drug concentrations in injured kidneys.These problems limit the development of pharmacological therapy for AKI.Nanotherapeutics based on nanotechnology have been proved to be an emerging and promising treatment strategy for AKI,which may solve the pharmacological therapy dilemma.More and more nanotherapeutics with different physicochemical properties are developed to efficiently deliver drugs,increase accumulation and control release of drugs in injury kidneys and also directly as effective antioxidants.Here,we discuss the recent nanotherapeutics applied in the treatment and prevention of AKI with improved effectiveness and few side effects.展开更多
Hepatocellular carcinoma(HCC)is a life-threatening disease for which there is no effective treatment currently.Novel theranostics simultaneously having excellent imaging and therapeutic functions are highly desired in...Hepatocellular carcinoma(HCC)is a life-threatening disease for which there is no effective treatment currently.Novel theranostics simultaneously having excellent imaging and therapeutic functions are highly desired in cancer therapy.Herein,we develop the sialic acid(SA)modified polymeric micelles at an upper critical solution temperature(UCST)of 43℃(sialic acid-poly(ethylene glycol)-poly(acrylamide-co-acrylonitrile),SA-PEG-p(AAm-co-AN)),which further encapsulated with doxorubicin(DOX)and Gd-CuS nanoparticles(Gd-CuS NPs)for chemo-photothermal treatment of HCC guided by magnetic resonance(MR)/photoacoustic(PA)dual-mode imaging.The resultant SA-PEG-p(AAm-co-AN)/DOX/Gd-CuS(SPDG)had an excellent photothermal conversion efficiency,enabling SPDG with an instantaneous release behavior of DOX under near-infrared(NIR)irradiation.This study also revealed that SPDG could actively target to HCC,which was due to that SA had a high affinity with E-selectin overexpressed at the tumor site.Moreover,benefiting from the HCC-targeted ability and NIR light-controlled on-demand delivery of DOX,SPDG showed a superior potential in MR/PA dual-mode imaging-guided chemo-photothermal treatment.Overall,our study reveals that the designed SPDG may be used as an ideal multifunctional nanoplatform for cancer theranostics.展开更多
基金supported by the Beijing Nova Program,Nos.20230484436,Z211100002121038the Chinese Institutes for Medical Research,No.CX23YQ01+1 种基金the NationalNatural Science Foundation of China,Nos.32100925,82027802Beijing-Tianjin-Hebei Basic Research Cooperation Project,No.22JCZXJC00190(all to XJand JL).
文摘Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.
基金supported by New Century 151 Talent Project of Zhejiang ProvinceJoint Institute of Lishui Hospital and Zhejiang University for nanomaterials and nanotechnology。
文摘Acute kidney injury(AKI)is a serious kidney disease without specific medications currently except for expensive dialysis treatment.Some potential drugs are limited due to their high hydrophobicity,poor in vivo stability,low bioavailability and possible adverse effects.Besides,kidney-targeted drugs are not common and small molecules are cleared too quickly to achieve effective drug concentrations in injured kidneys.These problems limit the development of pharmacological therapy for AKI.Nanotherapeutics based on nanotechnology have been proved to be an emerging and promising treatment strategy for AKI,which may solve the pharmacological therapy dilemma.More and more nanotherapeutics with different physicochemical properties are developed to efficiently deliver drugs,increase accumulation and control release of drugs in injury kidneys and also directly as effective antioxidants.Here,we discuss the recent nanotherapeutics applied in the treatment and prevention of AKI with improved effectiveness and few side effects.
基金National Key Research and Development projects intergovernmental cooperation in science and technology of China(No.2018YFE0126900)Zhejiang Provincial Natural Science Foundation(Nos.LD21H300002,LY18H180005,and LQ21H180003).
文摘Hepatocellular carcinoma(HCC)is a life-threatening disease for which there is no effective treatment currently.Novel theranostics simultaneously having excellent imaging and therapeutic functions are highly desired in cancer therapy.Herein,we develop the sialic acid(SA)modified polymeric micelles at an upper critical solution temperature(UCST)of 43℃(sialic acid-poly(ethylene glycol)-poly(acrylamide-co-acrylonitrile),SA-PEG-p(AAm-co-AN)),which further encapsulated with doxorubicin(DOX)and Gd-CuS nanoparticles(Gd-CuS NPs)for chemo-photothermal treatment of HCC guided by magnetic resonance(MR)/photoacoustic(PA)dual-mode imaging.The resultant SA-PEG-p(AAm-co-AN)/DOX/Gd-CuS(SPDG)had an excellent photothermal conversion efficiency,enabling SPDG with an instantaneous release behavior of DOX under near-infrared(NIR)irradiation.This study also revealed that SPDG could actively target to HCC,which was due to that SA had a high affinity with E-selectin overexpressed at the tumor site.Moreover,benefiting from the HCC-targeted ability and NIR light-controlled on-demand delivery of DOX,SPDG showed a superior potential in MR/PA dual-mode imaging-guided chemo-photothermal treatment.Overall,our study reveals that the designed SPDG may be used as an ideal multifunctional nanoplatform for cancer theranostics.
