The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events.Thus,timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the ...The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events.Thus,timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the clinical management of atherosclerosis.In this work,a targeting theranostic strategy on early-stage vulnerable plaques in atherosclerosis is realized by a LAID nanoplatform with X-CT and fluorescent dual-mode imaging and lipid-inflammation integrated regulation abilities.The iodinated contrast agents(ICA),phenylboronic acid modified astaxanthin and oxidized-dextran(oxDEX)jointly construct the nanoparticles loaded with the lipid-specific probe LFP.LAID indicates an active targeting to plaques along with the dual-responsive disassembly in oxidative stress and acidic microenvironment of atherosclerosis.The X-CT signals of ICA execute the location of early-stage plaques,while the LFP combines with lipid cores and realizes the recognition of vulnerable plaques.Meanwhile,the treatment based on astaxanthin is performed for restraining the progression of plaques.Transcriptome sequencing suggests that LAID can inhibit the lipid uptake and block NF-κB pathway,which synergistically demonstrates a lipid-inflammation integrated regulation to suppression the plaques growing.The in vivo investigations suggest that LAID delivers a favorable theranostics to the early-stage vulnerable plaques,which provides an impressive prospect for reducing the adverse prognosis of atherosclerosis.展开更多
Osteoporosis harms human health and has a variety of causes,among which the imbalance of bone metabolism caused by menopause is an important one.Studies have shown that sea cucumbers have a variety of physiological ac...Osteoporosis harms human health and has a variety of causes,among which the imbalance of bone metabolism caused by menopause is an important one.Studies have shown that sea cucumbers have a variety of physiological activities such as anti-inflammation.Sea cucumber enzymatic hydrolysates(SCEH)were prepared and characterized for peptides and polysaccharides,and then the effects on relieving osteoporosis were explored by feeding ovariectomized Sprague-Dawley rats for 90 days.Bone density and microstructure were measured using micro-CT and pathological sectioning.Serum markers for bone metabolism,and inflammation were measured using ELISA kits.Gene transcription and expression of the OPG/RANKL system in bone were measured using qRT-PCR and western blots.Results showed that SCEH could improve the bone density,strength,microstructure and mass,and inhibit the generation of osteoclasts.The abnormally elevated markers for bone resorption,formation and inflammation were reduced with the intake of SCEH.The mRNA and protein expressions of RANKL were also decreased by feeding SCEH,thereby up-regulating the ratio of OPG to RANKL.These results suggested that SCEH could inhibit the bone resorption by inhibiting the NF-κB pathway related to osteoclast generation via the down-regulation of both the RANKL level and inflammatory response,and also improve the balance of bone metabolism,thus obtaining the effects of increasing bone density and relieving osteoporosis.SCEH with a medium-dose(1000 mg/kg body weight)had the best remission effect and could be used as a potential starting material to develop healthy foods that can assist in treating osteoporosis.展开更多
Vascular diseases seriously threaten human life and health.Exogenous delivery of nitric oxide(NO)represents an effective approach for maintaining vascular homeostasis during pathological events.However,the overproduct...Vascular diseases seriously threaten human life and health.Exogenous delivery of nitric oxide(NO)represents an effective approach for maintaining vascular homeostasis during pathological events.However,the overproduction of reactive oxygen species(ROS)at vascular injury sites would react with NO to produce damaging peroxynitrite(ONOO)species and limit the therapeutic effect of NO.Hence,we design a ROS-responsive NO nanomedicine(t-PBA&NO NP)with ROS scavenging ability to solve the dilemma of NO-based therapy.t-PBA&NO NP targets NO and anti-oxidant ethyl caffeate(ECA)to the injury sites via collagen IV homing peptide.The ROS-triggered ROS depletion and ECA release potently alleviate local oxidative stress via ROS scavenging,endoplasmic reticulum and mitochondrial regulation.It subsequently maximizes vascular modulation effects of NO,without production of harmful compounds,reactive nitrogen species(RNS).Therefore,it significantly increases competitiveness of human umbilical vein endothelial cells(HUVECs)over human aortic smooth muscle cells(HASMCs)both in vitro and in vivo.The strategy proved effective in inducing faster re-endothelialization,inhibiting neointimal formation and restoring vascular homeostasis.The synergy between ROS depletion and NO therapy served as a new inspiration for the treatment of cardiovascular diseases and other ROS-associated illnesses.展开更多
基金supported by National Natural Science Foundation of China (No.32201128,No.82270262,and No.82070408)Zhejiang TCM Science and Technology Program TCM modernization Special project,China (No.2022ZX012).
文摘The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events.Thus,timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the clinical management of atherosclerosis.In this work,a targeting theranostic strategy on early-stage vulnerable plaques in atherosclerosis is realized by a LAID nanoplatform with X-CT and fluorescent dual-mode imaging and lipid-inflammation integrated regulation abilities.The iodinated contrast agents(ICA),phenylboronic acid modified astaxanthin and oxidized-dextran(oxDEX)jointly construct the nanoparticles loaded with the lipid-specific probe LFP.LAID indicates an active targeting to plaques along with the dual-responsive disassembly in oxidative stress and acidic microenvironment of atherosclerosis.The X-CT signals of ICA execute the location of early-stage plaques,while the LFP combines with lipid cores and realizes the recognition of vulnerable plaques.Meanwhile,the treatment based on astaxanthin is performed for restraining the progression of plaques.Transcriptome sequencing suggests that LAID can inhibit the lipid uptake and block NF-κB pathway,which synergistically demonstrates a lipid-inflammation integrated regulation to suppression the plaques growing.The in vivo investigations suggest that LAID delivers a favorable theranostics to the early-stage vulnerable plaques,which provides an impressive prospect for reducing the adverse prognosis of atherosclerosis.
基金This study was partly supported by the National Natural Science Foundation of China(31901613)the Fundamental Research Funds for the Central University(JUSRP121077)the Innovation and Exploration Project of the State Key Laboratory of Food Science and Technology of Jiangnan University(SKLF-ZZA-202004).
文摘Osteoporosis harms human health and has a variety of causes,among which the imbalance of bone metabolism caused by menopause is an important one.Studies have shown that sea cucumbers have a variety of physiological activities such as anti-inflammation.Sea cucumber enzymatic hydrolysates(SCEH)were prepared and characterized for peptides and polysaccharides,and then the effects on relieving osteoporosis were explored by feeding ovariectomized Sprague-Dawley rats for 90 days.Bone density and microstructure were measured using micro-CT and pathological sectioning.Serum markers for bone metabolism,and inflammation were measured using ELISA kits.Gene transcription and expression of the OPG/RANKL system in bone were measured using qRT-PCR and western blots.Results showed that SCEH could improve the bone density,strength,microstructure and mass,and inhibit the generation of osteoclasts.The abnormally elevated markers for bone resorption,formation and inflammation were reduced with the intake of SCEH.The mRNA and protein expressions of RANKL were also decreased by feeding SCEH,thereby up-regulating the ratio of OPG to RANKL.These results suggested that SCEH could inhibit the bone resorption by inhibiting the NF-κB pathway related to osteoclast generation via the down-regulation of both the RANKL level and inflammatory response,and also improve the balance of bone metabolism,thus obtaining the effects of increasing bone density and relieving osteoporosis.SCEH with a medium-dose(1000 mg/kg body weight)had the best remission effect and could be used as a potential starting material to develop healthy foods that can assist in treating osteoporosis.
基金supported by the National Key Research and Development Program of China (2022YFB3807300)the National Natural Science Foundation of China (51933009,82370427,22305219)+3 种基金the Fundamental Research Funds for the Central Universities,China (26-2023-00074)the Natural Science Foundation of Zhejiang Province,China (No.LY20H020005)The Zhejiang Provincial Traditional Chinese Medicine Science and Technology Plan,China (2022ZX012)The Province and Central Administration-Zhejiang Provincial Health Commission,China (WKJ-ZJ-2209).
文摘Vascular diseases seriously threaten human life and health.Exogenous delivery of nitric oxide(NO)represents an effective approach for maintaining vascular homeostasis during pathological events.However,the overproduction of reactive oxygen species(ROS)at vascular injury sites would react with NO to produce damaging peroxynitrite(ONOO)species and limit the therapeutic effect of NO.Hence,we design a ROS-responsive NO nanomedicine(t-PBA&NO NP)with ROS scavenging ability to solve the dilemma of NO-based therapy.t-PBA&NO NP targets NO and anti-oxidant ethyl caffeate(ECA)to the injury sites via collagen IV homing peptide.The ROS-triggered ROS depletion and ECA release potently alleviate local oxidative stress via ROS scavenging,endoplasmic reticulum and mitochondrial regulation.It subsequently maximizes vascular modulation effects of NO,without production of harmful compounds,reactive nitrogen species(RNS).Therefore,it significantly increases competitiveness of human umbilical vein endothelial cells(HUVECs)over human aortic smooth muscle cells(HASMCs)both in vitro and in vivo.The strategy proved effective in inducing faster re-endothelialization,inhibiting neointimal formation and restoring vascular homeostasis.The synergy between ROS depletion and NO therapy served as a new inspiration for the treatment of cardiovascular diseases and other ROS-associated illnesses.
