Polydatin is thought to protect mitochondria in different cell types in various diseases.Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury.To inve...Polydatin is thought to protect mitochondria in different cell types in various diseases.Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury.To investigate the protective effect of polydatin after traumatic brain injury,a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults.Rat models were intraperitoneally injected with polydatin(30 mg/kg)or the SIRT1 activator SRT1720(20 mg/kg,as a positive control to polydatin).At 6 hours post-traumatic brain injury insults,western blot assay was used to detect the expression of SIRT1,endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side.Flow cytometry was used to analyze neuronal mitochondrial superoxide,mitochondrial membrane potential and mitochondrial permeability transition pore opened.Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy.Our results showed that after treatment with polydatin,release of reactive oxygen species in neuronal mitochondria was markedly reduced;swelling of mitochondria was alleviated;mitochondrial membrane potential was maintained;mitochondrial permeability transition pore opened.Also endoplasmic reticulum stress related proteins were inhibited,including the activation of p-PERK,spliced XBP-1 and cleaved ATF6.SIRT1 expression and activity were increased;p38 phosphorylation and cleaved caspase-9/3 activation were inhibited.Neurological scores of treated rats were increased and the mortality was reduced compared with the rats only subjected to traumatic brain injury.These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria.The mechanisms may be linked to increased SIRT1 expression and activity,which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway.This study was approved by the Animal Care and Use Committee of the Southern Medical University,China(approval number:L2016113)on January 1,2016.展开更多
Atherosclerosis is the major contributor to cardiovascular mortality worldwide.Alternate day fasting(ADF)has gained growing attention due to its metabolic benefits.However,the effects of ADF on atherosclerotic plaque ...Atherosclerosis is the major contributor to cardiovascular mortality worldwide.Alternate day fasting(ADF)has gained growing attention due to its metabolic benefits.However,the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal models.The present study was designed to investigate the effects of ADF on atherosclerosis in apolipoprotein E-deficient(Apoe^(-/-))mice.Eleven-week-old male Apoe^(-/-)mice fed with Western diet(WD)were randomly grouped into ad libitum(AL)group and ADF group,and ADF aggravated both the early and advanced atherosclerotic lesion formation,which might be due to the disturbed cholesterol profiles caused by ADF intervention.ADF significantly altered cholesterol metabolism pathways and down-regulated integrated stress response(ISR)in the liver.The hepatic expression of activating transcription factor 3(ATF3)was suppressed in mice treated with ADF and hepatocyte-specific overexpression of Aft3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe^(-/-)mice.Moreover,the expression of ATF3 could be regulated by Krüppel-like factor 6(KLF6)and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR pathway.In conclusion,ADF aggravates atherosclerosis progression in Apoe^(-/-)mice fed on WD.ADF inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6,subsequently inhibiting ATF3 expression.The suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe^(-/-)mice.The findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.展开更多
The construction of biomimetic vasculatures within the artificial tissue models or organs is highly required for conveying nutrients,oxygen,and waste products,for improving the survival of engineered tissues in vitro....The construction of biomimetic vasculatures within the artificial tissue models or organs is highly required for conveying nutrients,oxygen,and waste products,for improving the survival of engineered tissues in vitro.In recent times,the remarkable progress in utilizing hydrogels and understanding vascular biology have enabled the creation of three-dimensional(3D)tissues and organs composed of highly complex vascular systems.In this review,we give an emphasis on the utilization of hydrogels and their advantages in the vascularization of tissues.Initially,the significance of vascular elements and the regeneration mechanisms of vascularization,including angiogenesis and vasculogenesis,are briefly introduced.Further,we highlight the importance and advantages of hydrogels as artificial microenvironments in fabricating vascularized tissues or organs,in terms of tunable physical properties,high similarity in physiological environments,and alternative shaping mechanisms,among others.Furthermore,we discuss the utilization of such hydrogels-based vascularized tissues in various applications,including tissue regeneration,drug screening,and organ-on-chips.Finally,we put forward the key challenges,including multifunctionalities of hydrogels,selection of suitable cell phenotype,sophisticated engineering techniques,and clinical translation behind the development of the tissues with complex vasculatures towards their future development.展开更多
Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices,leading to significant mortality in clinic.To address this issue,here,we report a biomim...Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices,leading to significant mortality in clinic.To address this issue,here,we report a biomimetic surface engineering strategy by the integration of mussel-inspired adhesive peptide,with bio-orthogonal click chemistry,to tailor the surface functionalities of tubing and catheters.Inspired by mussel adhesive foot protein,a bioclickable peptide mimic(DOPA)4-azidebased structure is designed and grafted on an aminated tubing robustly based on catechol-amine chemistry.Then,the dibenzylcyclooctyne(DBCO)modified nitric oxide generating species of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)chelated copper ions and the DBCO-modified antimicrobial peptide(DBCO-AMP)are clicked onto the grafted surfaces via bio-orthogonal reaction.The combination of the robustly grafted AMP and Cu-DOTA endows the modified tubing with durable antimicrobial properties and ability in long-term catalytically generating NO from endogenous snitrosothiols to resist adhesion/activation of platelets,thus preventing the formation of thrombosis.Overall,this biomimetic surface engineering technology provides a promising solution for multicomponent surface functionalization and the surface bioengineering of biomedical devices with enhanced clinical performance.展开更多
Thrombosis is the major stumbling block to the clinical application of blood-contacting devices.Herein,a quick and easy surface engineering strategy of hydrogel coating with the therapeutic gas nitric oxide(NO)generat...Thrombosis is the major stumbling block to the clinical application of blood-contacting devices.Herein,a quick and easy surface engineering strategy of hydrogel coating with the therapeutic gas nitric oxide(NO)generation was reported to realize up-regulation of cyclic guanosine monophosphate(c GMP)and improve hemocompatibility for diverse metal materials.We first introduce the active centre selenocysteine of glutathione peroxidase(GPx)to the self-assembling peptide(RADA)4,obtaining a functionalized hydrogel.Then the hydrogel is directly coated on the 316L stainless steel(SS)for catalytically generating NO from endogenous s-nitrosothiols(RSNO).The generated NO endows the coated surface with regulation of platelet behavior and reduction of plasmatic coagulation activation and complement system activation,hence improving antithrombotic ability in vitro and ex vivo.Overall,our NO-generating hydrogel coating surface engineering strategy provides a novel solution to remove the obstacle about thrombosis of blood-contacting devices in clinic.展开更多
The serum cholesterol level is an important indicator of healthy and there is a great necessity for frequent cholesterol monitoring to some cardiovascular-related diseases, which puts forward higher requirements for p...The serum cholesterol level is an important indicator of healthy and there is a great necessity for frequent cholesterol monitoring to some cardiovascular-related diseases, which puts forward higher requirements for point-of-care testing(POCT) of cholesterol. In this work, a cascade catalytic system of cholesterol is developed by encapsulation of cholesterol oxidase(Ch Ox) and Pd Cu Au nanoparticles into zeolitic imidazolate framework-L(Ch Ox/PCA@ZIF-L). Results indicate that ZIF-L carrier can significantly increase the catalytic activity of single or multiple enzymes, due to its high loading capacity and efficient molecular transport. Under the optimal conditions, the absorbance of reaction system performs linear relationships with the concentration of cholesterol in two intervals from 0.0005 mmol/L to 1.0000 mmol/L, with a limit of detection of 0.2176 μmol/L. The proposed colorimetric strategy based on Ch Ox/PCA@ZIF-L performs a good agreement with the results provided by chemiluminescence method for the serum cholesterol detection. Interestingly, a simple paper-based sensing system is constructed through a pre-reaction-transfer operation, which gets rid of the complex pre-processing requirements of traditional operations on filter paper. The presented strategy allows for the sensitive, convenient, costless assay of serum cholesterol,and paves a new way to design the POCT device for daily monitoring of healthy.展开更多
Bufalin is efficacious in treating various tumors, however, the clinical application of which is restricted by the myocardial toxicity. Developing a smart synergetic delivery system is widely considered as a promising...Bufalin is efficacious in treating various tumors, however, the clinical application of which is restricted by the myocardial toxicity. Developing a smart synergetic delivery system is widely considered as a promising therapeutic strategy. To address this issue, a black phosphorus hybrid polypeptides hydrogel was designed to highly load bufalin, and achieved near-infrared (NIR)-controllable drug release with synergistic photothermal-chemo therapeutic effect. Black phosphorus nanosheets (BPNSs) and bufalin were co-loaded in temperature-sensitive supramolecular hydrogel to receive smart hybridization (BP-bufalin@SH). With NIR irradiation (1 W·cm−2), BP-bufalin@SH exhibited a rapid and large temperature increase and released bufalin via light-controllable manner, with which the side effects of bufalin were greatly decreased. Combined with photothermal-chemo therapeutic effect, BP-bufalin@SH could collapse the mitochondrial transmembrane potential resulting in the irreversible apoptosis of tumor cells, and realize a highly efficient in vivo tumor elimination with good biosafety and biocompatibility. This work provides a new hydrogel platform for controlling bufalin release, and thus further promotes the practical application on antitumor therapy.展开更多
Upon the osteoporotic condition,sluggish osteogenesis,excessive bone resorption,and chronic inflammation make the osseointegration of bioinert titanium(Ti)implants with surrounding bone tissues difficult,often lead to...Upon the osteoporotic condition,sluggish osteogenesis,excessive bone resorption,and chronic inflammation make the osseointegration of bioinert titanium(Ti)implants with surrounding bone tissues difficult,often lead to prosthesis loosening,bone collapse,and implant failure.In this study,we firstly designed clickable mussel-inspired peptides(DOPA-N3)and grafted them onto the surfaces of Ti materials through robust catechol-TiO2 coordinative interactions.Then,two dibenzylcyclooctyne(DBCO)-capped bioactive peptides RGD and BMP-2 bioactive domain(BMP-2)were clicked onto the DOPA-N3-coated Ti material surfaces via bio-orthogonal reaction.We characterized the surface morphology and biocompatibility of the Ti substrates and optimized the osteogenic capacity of Ti surfaces through adjusting the ideal ratios of BMP-2/RGD at 3:1.In vitro,the dual-functionalized Ti substrates exhibited excellent promotion on adhesion and osteogenesis of mesenchymal stem cells(MSCs),and conspicuous immunopolarization-regulation to shift macrophages to alternative(M2)phenotypes and inhibit inflammation,as well as enhancement of osseointegration and mechanical stability in osteoporotic rats.In summary,our biomimetic surface modification strategy by bio-orthogonal reaction provided a convenient and feasible method to resolve the bioinertia and clinical complications of Ti-based implants,which was conducive to the long-term success of Ti implants,especially in the osteoporotic or inflammatory conditions.展开更多
Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease.Anti-fibrosis treatment is a significant therapy for heart disease,but there is still no thorough understanding of fibrotic mechanism...Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease.Anti-fibrosis treatment is a significant therapy for heart disease,but there is still no thorough understanding of fibrotic mechanisms.This study was carried out to ascertain the functions of cytokine receptor-like factor 1(CRLF1)in cardiac fibrosis and clarify its regulatory mechanisms.We found that CRLF1 was expressed predominantly in cardiac fibroblasts.Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction,but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-β1(TGF-β1).Gain-and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts(NMCFs)with or without TGF-β1 stimulation.CRLF1 overexpression increased cell viability,collagen production,cell proliferation capacity,and myofibroblast transformation of NMCFs with or without TGF-β1 stimulation,while silencing of CRLF1 had the opposite effects.An inhibitor of the extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway and different inhibitors of TGF-β1 signaling cascades,comprising mothers against decapentaplegic homolog(SMAD)-dependent and SMAD-independent pathways,were applied to investigate the mechanisms involved.CRLF1 exerted its functions by activating the ERK1/2 signaling pathway.Furthermore,the SMAD-dependent pathway,not the SMAD-independent pathway,was responsible for CRLF1 up-regulation in NMCFs treated with TGF-β1.In summary,activation of the TGF-β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression.CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway.CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.展开更多
Radiotherapy(RT)mediated tumor immunogenicity offers an opportunity for simultaneous RT and immunotherapy via immunogenic cell death(ICD),which releases damaged-associated molecular patterns and generates“eat me”sig...Radiotherapy(RT)mediated tumor immunogenicity offers an opportunity for simultaneous RT and immunotherapy via immunogenic cell death(ICD),which releases damaged-associated molecular patterns and generates“eat me”signals for the innate immune system to modulate the immunogenicity.However,tumor hypoxia significantly reduces the therapeutic efficacy of RT and hampers its mediation of ICD induction.Herein,Au@Bi_(2)Te_(3)-polyethylene glycol(PEG)was rationally constructed as theranostic nanozymes for mild photothermal therapy,tumor hypoxia modulation,and RT adjuvant cancer immunotherapy.The tumor-specific production of oxygen could not only augment the effects of RT by enhanced reactive oxygen species(ROS)generation,but also reduce hypoxia-related cytokines and downregulate programmed cell death-ligand 1(PD-L1)to unleash immune-enhancing T cells.Moreover,Au@Bi_(2)Te_(3)-PEG could act as an immune-blocking inhibitor by efficient ICD induction with the combination of mild-photothermal therapy+RT to inhibit the tumor immune escape and improve antitumor immune response.Increased amounts of CD^(4+) and CD^(8+) Tcells and elevated levels of cytokines could be observed that eventually led to effective post-medication inhibition of primary and abscopal tumors.Spectral computed tomography/photoacoustic imaging allowed noninvasive and real-time tracking of nanoparticle(NP)accumulation and oxygenation status at tumor sites.Collectively,Au@Bi_(2)Te_(3)-PEG NPs could serve as effective theranostic nanoregulators with remarkable synergistic mildphotothermal/RT/immunotherapy effects that helped reshape the immune microenvironment and had remarkable molecular imaging properties.展开更多
基金supported by the National Natural Science Foundation of China,No.81501690(to ZTG)the Scientific Research Staring Foundation for Talent Introduction for Southern Medical University(to MM)
文摘Polydatin is thought to protect mitochondria in different cell types in various diseases.Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury.To investigate the protective effect of polydatin after traumatic brain injury,a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults.Rat models were intraperitoneally injected with polydatin(30 mg/kg)or the SIRT1 activator SRT1720(20 mg/kg,as a positive control to polydatin).At 6 hours post-traumatic brain injury insults,western blot assay was used to detect the expression of SIRT1,endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side.Flow cytometry was used to analyze neuronal mitochondrial superoxide,mitochondrial membrane potential and mitochondrial permeability transition pore opened.Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy.Our results showed that after treatment with polydatin,release of reactive oxygen species in neuronal mitochondria was markedly reduced;swelling of mitochondria was alleviated;mitochondrial membrane potential was maintained;mitochondrial permeability transition pore opened.Also endoplasmic reticulum stress related proteins were inhibited,including the activation of p-PERK,spliced XBP-1 and cleaved ATF6.SIRT1 expression and activity were increased;p38 phosphorylation and cleaved caspase-9/3 activation were inhibited.Neurological scores of treated rats were increased and the mortality was reduced compared with the rats only subjected to traumatic brain injury.These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria.The mechanisms may be linked to increased SIRT1 expression and activity,which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway.This study was approved by the Animal Care and Use Committee of the Southern Medical University,China(approval number:L2016113)on January 1,2016.
基金supported by grants from the National Science Fund for Distinguished Young Scholars(82325011)the Joint Funds of the National Natural Science Foundation of China(U22A20288)+2 种基金the National Key Research and Development Project(2018YFA0800404)the National Natural Science Foundation of China(81970736)the Key-Area Clinical Research Program of Southern Medical University(LC2019ZD010 and 2019CR022).
文摘Atherosclerosis is the major contributor to cardiovascular mortality worldwide.Alternate day fasting(ADF)has gained growing attention due to its metabolic benefits.However,the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal models.The present study was designed to investigate the effects of ADF on atherosclerosis in apolipoprotein E-deficient(Apoe^(-/-))mice.Eleven-week-old male Apoe^(-/-)mice fed with Western diet(WD)were randomly grouped into ad libitum(AL)group and ADF group,and ADF aggravated both the early and advanced atherosclerotic lesion formation,which might be due to the disturbed cholesterol profiles caused by ADF intervention.ADF significantly altered cholesterol metabolism pathways and down-regulated integrated stress response(ISR)in the liver.The hepatic expression of activating transcription factor 3(ATF3)was suppressed in mice treated with ADF and hepatocyte-specific overexpression of Aft3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe^(-/-)mice.Moreover,the expression of ATF3 could be regulated by Krüppel-like factor 6(KLF6)and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR pathway.In conclusion,ADF aggravates atherosclerosis progression in Apoe^(-/-)mice fed on WD.ADF inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6,subsequently inhibiting ATF3 expression.The suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe^(-/-)mice.The findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.
基金This study received financial support from the High-level Talents Research and Development Program of Affiliated Dongguan Hospital,Southern Medical University(K202102)National Natural Science Foundation of China(NSFC,81971734,31771099,81871504)National Key R&D Program of China(2019YFE0113600),and Program for Innovative Research Team in Science and Technology in Fujian Province.
文摘The construction of biomimetic vasculatures within the artificial tissue models or organs is highly required for conveying nutrients,oxygen,and waste products,for improving the survival of engineered tissues in vitro.In recent times,the remarkable progress in utilizing hydrogels and understanding vascular biology have enabled the creation of three-dimensional(3D)tissues and organs composed of highly complex vascular systems.In this review,we give an emphasis on the utilization of hydrogels and their advantages in the vascularization of tissues.Initially,the significance of vascular elements and the regeneration mechanisms of vascularization,including angiogenesis and vasculogenesis,are briefly introduced.Further,we highlight the importance and advantages of hydrogels as artificial microenvironments in fabricating vascularized tissues or organs,in terms of tunable physical properties,high similarity in physiological environments,and alternative shaping mechanisms,among others.Furthermore,we discuss the utilization of such hydrogels-based vascularized tissues in various applications,including tissue regeneration,drug screening,and organ-on-chips.Finally,we put forward the key challenges,including multifunctionalities of hydrogels,selection of suitable cell phenotype,sophisticated engineering techniques,and clinical translation behind the development of the tissues with complex vasculatures towards their future development.
基金the National Natural Science Foundation of China(Project 82072072)(Z.Y)International Cooperation Project by Science and Technology Department of Sichuan Province(2021YFH0056 and 2019YFH0103)(Z.Y)the Fundamental Research Funds for the Central Universities(2682020ZT82 and 2682020ZT76)(Z.Y).
文摘Thrombosis and infections are the two major complications associated with extracorporeal circuits and indwelling medical devices,leading to significant mortality in clinic.To address this issue,here,we report a biomimetic surface engineering strategy by the integration of mussel-inspired adhesive peptide,with bio-orthogonal click chemistry,to tailor the surface functionalities of tubing and catheters.Inspired by mussel adhesive foot protein,a bioclickable peptide mimic(DOPA)4-azidebased structure is designed and grafted on an aminated tubing robustly based on catechol-amine chemistry.Then,the dibenzylcyclooctyne(DBCO)modified nitric oxide generating species of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)chelated copper ions and the DBCO-modified antimicrobial peptide(DBCO-AMP)are clicked onto the grafted surfaces via bio-orthogonal reaction.The combination of the robustly grafted AMP and Cu-DOTA endows the modified tubing with durable antimicrobial properties and ability in long-term catalytically generating NO from endogenous snitrosothiols to resist adhesion/activation of platelets,thus preventing the formation of thrombosis.Overall,this biomimetic surface engineering technology provides a promising solution for multicomponent surface functionalization and the surface bioengineering of biomedical devices with enhanced clinical performance.
基金financially supported by the National Natural Science Foundation of China(Nos.82072072,32171326 and 31800795)the International Cooperation Project by the Science and Technology Department of Sichuan Province(No.2021YFH0056)+1 种基金the Sichuan Science and Technology Program(No.2021JDRC0160)the High-level Talents Research and Development Program of Affiliated Dongguan Hospital(No.K202102)。
文摘Thrombosis is the major stumbling block to the clinical application of blood-contacting devices.Herein,a quick and easy surface engineering strategy of hydrogel coating with the therapeutic gas nitric oxide(NO)generation was reported to realize up-regulation of cyclic guanosine monophosphate(c GMP)and improve hemocompatibility for diverse metal materials.We first introduce the active centre selenocysteine of glutathione peroxidase(GPx)to the self-assembling peptide(RADA)4,obtaining a functionalized hydrogel.Then the hydrogel is directly coated on the 316L stainless steel(SS)for catalytically generating NO from endogenous s-nitrosothiols(RSNO).The generated NO endows the coated surface with regulation of platelet behavior and reduction of plasmatic coagulation activation and complement system activation,hence improving antithrombotic ability in vitro and ex vivo.Overall,our NO-generating hydrogel coating surface engineering strategy provides a novel solution to remove the obstacle about thrombosis of blood-contacting devices in clinic.
基金supported by the National Natural Science Foundation of China (Nos. 81971765, 31771099, 31671025 and 81871504)the Natural Science Foundation of Guangdong Province (No. 2020A1515011066)。
文摘The serum cholesterol level is an important indicator of healthy and there is a great necessity for frequent cholesterol monitoring to some cardiovascular-related diseases, which puts forward higher requirements for point-of-care testing(POCT) of cholesterol. In this work, a cascade catalytic system of cholesterol is developed by encapsulation of cholesterol oxidase(Ch Ox) and Pd Cu Au nanoparticles into zeolitic imidazolate framework-L(Ch Ox/PCA@ZIF-L). Results indicate that ZIF-L carrier can significantly increase the catalytic activity of single or multiple enzymes, due to its high loading capacity and efficient molecular transport. Under the optimal conditions, the absorbance of reaction system performs linear relationships with the concentration of cholesterol in two intervals from 0.0005 mmol/L to 1.0000 mmol/L, with a limit of detection of 0.2176 μmol/L. The proposed colorimetric strategy based on Ch Ox/PCA@ZIF-L performs a good agreement with the results provided by chemiluminescence method for the serum cholesterol detection. Interestingly, a simple paper-based sensing system is constructed through a pre-reaction-transfer operation, which gets rid of the complex pre-processing requirements of traditional operations on filter paper. The presented strategy allows for the sensitive, convenient, costless assay of serum cholesterol,and paves a new way to design the POCT device for daily monitoring of healthy.
基金Financial support from the National Natural Science Foundation of China (Nos. 31771099, 81871504, and31671025)Natural Science Foundation of Guangdong Province (No. 2020A1515011066)Pearl River S&T Nova Program of Guangzhou (No. 201806010170) are greatly acknowledged. The animal procedures were performed in according to the protocol approved by the Institutional Animal Care and Use Committee at Southern Medical University.
文摘Bufalin is efficacious in treating various tumors, however, the clinical application of which is restricted by the myocardial toxicity. Developing a smart synergetic delivery system is widely considered as a promising therapeutic strategy. To address this issue, a black phosphorus hybrid polypeptides hydrogel was designed to highly load bufalin, and achieved near-infrared (NIR)-controllable drug release with synergistic photothermal-chemo therapeutic effect. Black phosphorus nanosheets (BPNSs) and bufalin were co-loaded in temperature-sensitive supramolecular hydrogel to receive smart hybridization (BP-bufalin@SH). With NIR irradiation (1 W·cm−2), BP-bufalin@SH exhibited a rapid and large temperature increase and released bufalin via light-controllable manner, with which the side effects of bufalin were greatly decreased. Combined with photothermal-chemo therapeutic effect, BP-bufalin@SH could collapse the mitochondrial transmembrane potential resulting in the irreversible apoptosis of tumor cells, and realize a highly efficient in vivo tumor elimination with good biosafety and biocompatibility. This work provides a new hydrogel platform for controlling bufalin release, and thus further promotes the practical application on antitumor therapy.
基金This work was supported by the National Key Research and Development Program of China(2019YFA0112000)the National Natural Science Foundation of China(81972059,81772358,21875092)+1 种基金the key R&D programs of Jiangsu Province(BE2019668),China Postdoctoral Science Foundation(2020M671587)Jiangsu Provincial Clinical Orthopedic Center,Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the High-level Talents Research and Development Program of Affiliated Dongguan Hospital,Southern Medical University(K202102).
文摘Upon the osteoporotic condition,sluggish osteogenesis,excessive bone resorption,and chronic inflammation make the osseointegration of bioinert titanium(Ti)implants with surrounding bone tissues difficult,often lead to prosthesis loosening,bone collapse,and implant failure.In this study,we firstly designed clickable mussel-inspired peptides(DOPA-N3)and grafted them onto the surfaces of Ti materials through robust catechol-TiO2 coordinative interactions.Then,two dibenzylcyclooctyne(DBCO)-capped bioactive peptides RGD and BMP-2 bioactive domain(BMP-2)were clicked onto the DOPA-N3-coated Ti material surfaces via bio-orthogonal reaction.We characterized the surface morphology and biocompatibility of the Ti substrates and optimized the osteogenic capacity of Ti surfaces through adjusting the ideal ratios of BMP-2/RGD at 3:1.In vitro,the dual-functionalized Ti substrates exhibited excellent promotion on adhesion and osteogenesis of mesenchymal stem cells(MSCs),and conspicuous immunopolarization-regulation to shift macrophages to alternative(M2)phenotypes and inhibit inflammation,as well as enhancement of osseointegration and mechanical stability in osteoporotic rats.In summary,our biomimetic surface modification strategy by bio-orthogonal reaction provided a convenient and feasible method to resolve the bioinertia and clinical complications of Ti-based implants,which was conducive to the long-term success of Ti implants,especially in the osteoporotic or inflammatory conditions.
基金supported by the National Key Research and Development Project of China(No.2018YFA0800404)the National Natural Science Foundation of China(Nos.82100255 and 81970736)the China Postdoctoral Science Foundation(Nos.2021M691459 and 2022T150299).
文摘Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease.Anti-fibrosis treatment is a significant therapy for heart disease,but there is still no thorough understanding of fibrotic mechanisms.This study was carried out to ascertain the functions of cytokine receptor-like factor 1(CRLF1)in cardiac fibrosis and clarify its regulatory mechanisms.We found that CRLF1 was expressed predominantly in cardiac fibroblasts.Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction,but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-β1(TGF-β1).Gain-and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts(NMCFs)with or without TGF-β1 stimulation.CRLF1 overexpression increased cell viability,collagen production,cell proliferation capacity,and myofibroblast transformation of NMCFs with or without TGF-β1 stimulation,while silencing of CRLF1 had the opposite effects.An inhibitor of the extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway and different inhibitors of TGF-β1 signaling cascades,comprising mothers against decapentaplegic homolog(SMAD)-dependent and SMAD-independent pathways,were applied to investigate the mechanisms involved.CRLF1 exerted its functions by activating the ERK1/2 signaling pathway.Furthermore,the SMAD-dependent pathway,not the SMAD-independent pathway,was responsible for CRLF1 up-regulation in NMCFs treated with TGF-β1.In summary,activation of the TGF-β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression.CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway.CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.
基金This work was supported by the National Natural Science Foundation of China(Nos.81871334,81801764,82072056,and 51937010)the Guangdong Basic and Applied Basic Research Foundation(Nos.2017A050506011,2018030310343,2020B1515020008,2021A1515012542,and 2021A1515011882)+1 种基金the Medical Scientific Research Foundation of Guangdong Province(No.A2018014)the Pearl River Talented Young Scholar Program(No.2017GC010282).
文摘Radiotherapy(RT)mediated tumor immunogenicity offers an opportunity for simultaneous RT and immunotherapy via immunogenic cell death(ICD),which releases damaged-associated molecular patterns and generates“eat me”signals for the innate immune system to modulate the immunogenicity.However,tumor hypoxia significantly reduces the therapeutic efficacy of RT and hampers its mediation of ICD induction.Herein,Au@Bi_(2)Te_(3)-polyethylene glycol(PEG)was rationally constructed as theranostic nanozymes for mild photothermal therapy,tumor hypoxia modulation,and RT adjuvant cancer immunotherapy.The tumor-specific production of oxygen could not only augment the effects of RT by enhanced reactive oxygen species(ROS)generation,but also reduce hypoxia-related cytokines and downregulate programmed cell death-ligand 1(PD-L1)to unleash immune-enhancing T cells.Moreover,Au@Bi_(2)Te_(3)-PEG could act as an immune-blocking inhibitor by efficient ICD induction with the combination of mild-photothermal therapy+RT to inhibit the tumor immune escape and improve antitumor immune response.Increased amounts of CD^(4+) and CD^(8+) Tcells and elevated levels of cytokines could be observed that eventually led to effective post-medication inhibition of primary and abscopal tumors.Spectral computed tomography/photoacoustic imaging allowed noninvasive and real-time tracking of nanoparticle(NP)accumulation and oxygenation status at tumor sites.Collectively,Au@Bi_(2)Te_(3)-PEG NPs could serve as effective theranostic nanoregulators with remarkable synergistic mildphotothermal/RT/immunotherapy effects that helped reshape the immune microenvironment and had remarkable molecular imaging properties.
