Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavio...Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice.Mice were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein groups.In the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse brain.These changes resulted in improved neurological function compared with controlled cortical impact mice.Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein.Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral outcomes.Furthermore,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control.Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways.展开更多
The center was first established in 2013 and affiliated to the Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine.In 2015,the center was entitled as 3D Bioprinting Clinical Transformati...The center was first established in 2013 and affiliated to the Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine.In 2015,the center was entitled as 3D Bioprinting Clinical Transformation Collaborative Innovation Center.In 2016,the center was renamed as Medical 3D Printing Innovation Research Center of Shanghai Jiao Tong University School of Medicine.Although the center was established in 2013,the clinical application of 3D printing in Shanghai Ninth People’s Hospital can be traced back to the 1990s.As early as 30 years ago,Prof.Kerong Dai had tried to rebuild patients pelvic by manually cutting the foam boards and layering them together based on the theory of 3D printing for preoperative planning model of abnormal skeleton structures and development of personalized prosthesis.That was the first application of 3D printing in the area of medicine in China.Now,The Research Center of 3D Bioprinting in Shanghai Ninth People’s Hospital comprised of subcenters including the outpatient department of 3D printing,medical 3D printing innovation research center and Shanghai key laboratory of orthopedic implant.展开更多
Recent studies have shown that microglia/macrophages and astrocytes can mediate synaptic phagocytosis through the MER proto-oncokinase in developmental or stroke models,but it is unclear whether the same mechanism is ...Recent studies have shown that microglia/macrophages and astrocytes can mediate synaptic phagocytosis through the MER proto-oncokinase in developmental or stroke models,but it is unclear whether the same mechanism is also active in traumatic brain injury.In this study,we established a mouse model of traumatic brain injury and found that both microglia/macrophages and astrocytes phagocytosed synapses and expression of the MER proto-oncokinase increased 14 days after injury.Specific knockout of MER in microglia/macrophages or astrocytes markedly reduced injury volume and greatly improved neurobehavioral function.In addition,in both microglia/macrophages-specific and astrocytes-specific MER knock-out mice,the number of microglia/macrophage and astrocyte phagocytosing synapses was markedly decreased,and the total number of dendritic spines was increased.Our study suggested that MER proto-oncokinase expression in microglia/macrophages and astrocytes may play an important role in synaptic phagocytosis,and inhibiting this process could be a new strategy for treating traumatic brain injury.展开更多
Three-dimensional(3D)tumor models prepared from patient-derived cells have been reported to imitate some of the biological development processes of in situ tumors in vitro.These 3D tumor models share several important...Three-dimensional(3D)tumor models prepared from patient-derived cells have been reported to imitate some of the biological development processes of in situ tumors in vitro.These 3D tumor models share several important characteristics with their in vivo tumor counterparts.Accordingly,their applications in tumor modeling,drug screening,and precision-targeted treatment are promising.However,the establishment of tumormodels is subject to several challenges,including advancements in scale size,repeatability,structural precision in time and space,vascularization,and the tumor microenvironment.Recently,bioprinting technologies enabling the editorial arrangement of cells,factors,and materials have improved the simulation of tumormodels in vitro.Among the 3D bioprinted tumor models,the organoidmodel has been widely appreciated for its advantages of maintaining high heterogeneity and capacity for simulating the developmental process of tumor tissues.In this review,we outline approaches and potential prospects for tumor model bioprinting and discuss the existing bioprinting technologies and bioinks in tumor model construction.The multidisciplinary combination of tumor pathology,molecular biology,material science,and additive manufacturing will help overcome the barriers to tumor model construction by allowing consideration of the structural and functional characteristics of in vitro models and promoting the development of heterogeneous tumor precision therapies.展开更多
The fuorescence-based in vivo flow cytometry(IVFC)is an emerging tool to monitor eirculating cells in vivo.As a noninvasive and real-timne diagnostic technology,the fluorescence based IVFC allows long-term monitoring ...The fuorescence-based in vivo flow cytometry(IVFC)is an emerging tool to monitor eirculating cells in vivo.As a noninvasive and real-timne diagnostic technology,the fluorescence based IVFC allows long-term monitoring of circulating cells without changing their native biological environment.It has been applied for various biological applications(eg,monitoring circulating tumor cells).In this work,we will review our recent works on fluorescence-based IVFC.The operation principle and typical biological applications will be introduced.In addition,the recent advances in IVFC flow cytometry based on photoacoustic effects and other label free detection methods such as imaging based methods,difuse-light methods,hybrid multimodality methods and multispectral methods are also summarized.展开更多
Alzheimers disease(AD)is a chronic neurodegenerative disease.The symptoms include memoryand spatial learning dificulties,language disorders,and loss of motivation,which get worse overtime,eventually ending in death.No...Alzheimers disease(AD)is a chronic neurodegenerative disease.The symptoms include memoryand spatial learning dificulties,language disorders,and loss of motivation,which get worse overtime,eventually ending in death.No ffective treatments are available for AD,currently.Currenttreatments only attenuate symptoms temporarily and are associated with severe side ffects.Nearinfra-red(NIR)light has been studied for a long time.We investigated the effect of NIR on ADusing a transgenic mouse model,which was obtained by co-injecting two vectors carrying ADmutations in amyloid precursor protein(APP)and presenilin-i(PSEN1)into C57BL/6J mice.The irradiation equipment consisted of an accommodating box and an LED array.The wave-length of NIR light emitted from LED was between 1040 nm and 1090 nm.The power densitydelivered at the level of the mice was approximately 15 mW/cm^(2),Firstly,we treated the micewith NIR for 40 days,Then,the irradiation was suspended for 28 days.Finally,another 15 daystreatment was brought to mice.We conducted Morris water maze and immunofluorescenceanalysis to evaluate the effects of treatment.Immunofuorescence analysis was based on mea-suring the quantity of plaques in mouse brain slices,Our results show that NIR light improvesmemory and spatial learning ability and reduces plaques moderately.NIR light represents apotential treatment for AD.展开更多
Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation ...Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.展开更多
Nutriology relies on advanced analytical tools to study the molecular compositions of food and provide key information on sample quality/safety. Small nutrients detection is challenging due to the high diversity and b...Nutriology relies on advanced analytical tools to study the molecular compositions of food and provide key information on sample quality/safety. Small nutrients detection is challenging due to the high diversity and broad dynamic range of molecules in food samples, and a further issue is to track low abundance toxins. Herein, we developed a novel plasmonic matrix-assisted laser desorption/ionization mass spectrometry(MALDI MS)approach to detect small nutrients and toxins in complex biological emulsion samples. Silver nanoshells(SiO_2@-Ag) with optimized structures were used as matrices andachieved direct analysis of ~ 6 n L of human breast milk without any enrichment or separation. We performed identification and quantitation of small nutrients and toxins with limit-of-detection down to 0.4 pmol(for melamine) and reaction time shortened to minutes, which is superior to the conventional biochemical method currently in use. The developed approach contributes to the near-future application of MALDI MS in a broad field and personalized design of plasmonic materials for real-case bio-analysis.展开更多
Catalysis-based chemodynamic therapy(CDT)is an emerging cancer treatment strategy which uses a Fenton-like reaction to kill tumor cells by catalyzing endogenous hydrogen peroxide(H_(2)O_(2))into a toxic hydroxyl radic...Catalysis-based chemodynamic therapy(CDT)is an emerging cancer treatment strategy which uses a Fenton-like reaction to kill tumor cells by catalyzing endogenous hydrogen peroxide(H_(2)O_(2))into a toxic hydroxyl radical(·OH).The performance of CDT is greatly dependent on PDT agent.Herein,mitochondria-targeting Pt nanoclusters were synthesized using cytochrome c aptamer(CytcApt)as template.The obtained CytcApt-PtNCs can produce.OH by H_(2)O_(2)under the acidic conditions.Moreover,CytcApt-PtNCs could kill 4T1 tumor cells in a pH-dependent manner,but had no side effect on normal 293T cells.Therefore,CytcApt-PtNCs possess excellent therapeutic effect and good biosafety,indicating their great potential for CDT.展开更多
Endothelial cell (EC) morphology can be regulated by the micro/nano topography in engineered vascular grafts and by hemodynamic forces in the native blood vessels. However, how EC morphology affects miRNA and thus EC ...Endothelial cell (EC) morphology can be regulated by the micro/nano topography in engineered vascular grafts and by hemodynamic forces in the native blood vessels. However, how EC morphology affects miRNA and thus EC functions is not well understood. In this study, we addressed this question by using human umbilical vein endothelial cells (HUVECs) cultured on microgrooves as a model. HUVECs were grown on either microgrooved (with 10 μm width/spacing and 3 μm depth) or smooth surfaces. HUVECs on microgrooved surface had elongated and bipolar morphology, while HUVECs on smooth surface showed cobble stone shape or non-polar morphology. EdU staining indicated that HUVECs with elongated morphology had lower proliferation rate compared to their counterpart cultured on smooth surface. Quantitative PCR analysis demonstrated that the expression of the specific microRNAs (miR-10a, miR-19a, miR-221) that targeted proliferation-related genes was all up-regulated. Consistently, the mRNA levels of their respective target genes, mitogen-activated protein kinase kinase kinase 7, Cyclin D1 and c-kit were significantly reduced by a fold change of 0.12 ± 0.01 (p < 0.01), 0.70 ± 0.23 (p 0.05) and 0.76 ± 0.21 (p < 0.05). Other miRNAs such as miR-126 and miR-181a were up-regulated as well, leading to the repression of their targets vascular cell adhesion molecule-1 and prospero homeobox-1. Our results suggested that microgrooved surface may regulate microRNA levels and thus EC functions. These results provide insight into the modulation of EC functions by microtopographic cues, and will facilitate the rational design of microstructured materials for cell and tissue engineering.展开更多
Metastasis is a very complicated multi-step process and accounts for the low survival rate of the cancerous patients.To metastasize,t he malignant cells must detach from the primary tumor and migrate to secondary site...Metastasis is a very complicated multi-step process and accounts for the low survival rate of the cancerous patients.To metastasize,t he malignant cells must detach from the primary tumor and migrate to secondary sites in the body through either blood or lymph circulation.Macrophages appear to be directly involved in tumor progression and metastasis.However,the role of macrophages in affecting cancer metast asis has not been fully elucidated.Here,we have utilized an emerging technique,namely in vivo flow cytometry(IVFC)to study the depletion kinetics of circulating prostate cancer cells in mice and determine how depletion of macrophages by the liposome encapsulated clodronate affects the depletion kinetics.Our results show diferent depletion kinetics of PC-3 cells between the macrophagedeficient group and the control group.The number of circulating tumor cells(CTCs)in the macrophage-deficient group decreases in a slower manner compared to the control mice group.The differences in depletion kinetics indicate that the absence of macrophages facilitates the stay of prostate cancer cells in circulation.In addition,our imaging data suggest that macrophages might be able to arrest,phagocytose and digest PC-3 cells.Therefore,phagocy tosis may mainly contribute to the de-pletion kinetic diferences.The developed methods elaborated here would be useful to study the relationship between macr ophages and tumor metastasis in small animal cancer models.展开更多
In this paper,a model-based reconstruction technique is proposed to simultaneously measure the relative deoxyhemoglobin concentration and the relative blood flow velocity in cerebral cortex.With the help of this model...In this paper,a model-based reconstruction technique is proposed to simultaneously measure the relative deoxyhemoglobin concentration and the relative blood flow velocity in cerebral cortex.With the help of this model-based reconstruction technique,artifacts due to nonuniform laser illumination and curvature of cortex are efficiently corrected.The results of relative deoxyhemoglobin concentration and relative blood flow velocity are then used to detect and distinguish cerebral arteries and veins.In an experimental study on rat,cerebral blood vessels are segmented from the reconstructed blood flow image by Otsu multiple threshold method.Afterwards,arteries and veins are distinguished by a simple fuzzy criterion based on the information of relative deoxyhemoglobin concentration.展开更多
Cancer stem cells (CSCs) are a rare subpopulation of phenotypically distinct cancer cells exhibiting stem cell characteristics. They are tumourigenic, meanwhile capable of self-renewal and forming differentiated pro...Cancer stem cells (CSCs) are a rare subpopulation of phenotypically distinct cancer cells exhibiting stem cell characteristics. They are tumourigenic, meanwhile capable of self-renewal and forming differentiated progenies. CSCs are believed to be resistant to the standard therapeutics, and provide the cell reservoir for tumour initiation.1 Understanding CSCs or in another word, tumour-initiating cells, is of critical therapeutic importance.展开更多
Electrospun porous films doped with the green-synthesized CdSe quantum dots were synthesized. Glycerol was chosen to prepare the quantum dots ( QDs), with the highest quantum yield of 78.28%. Polycaprolactone (PCL...Electrospun porous films doped with the green-synthesized CdSe quantum dots were synthesized. Glycerol was chosen to prepare the quantum dots ( QDs), with the highest quantum yield of 78.28%. Polycaprolactone (PCL) was electrospun with CdSe QDs to avoid the QDs' toxicity and improve the QDs' cytocompatibility. The electrospun QDs-doped films preserve the original QDs' fluorescence. Pores can be detected from the SEM of the films, predicting the possibility of loading drugs in the cancer therapy. The cell proliferation assay shows excellent cytocompatibility of the eletrospun CdSe-QDs-doped films. The present eletrospun CdSe- QDs-doped porous films are cytocompatibale, highly-fluorescent and ootential to load drugs in cancer therapy.展开更多
In biomedical research fields,the in vio Aow cytometry(IVFC)is a widely used technology which is able to monitor target cells dynamically in living animals.Although the setup of IVFC system has been well established,b...In biomedical research fields,the in vio Aow cytometry(IVFC)is a widely used technology which is able to monitor target cells dynamically in living animals.Although the setup of IVFC system has been well established,baseline drift is still a challenge in the process of quantifying circulating cells.Previous methods,i.e.,the dynamic peak picking method,counted cells by setting a static threshold without considering the baseline drift,leading to an inaccurate cell quantification.Here,we developed a method of cell counting for IVFC data with baseline drift by interpolation fitting,automatic segmentation and wavelet-based denoising.We demonstrated its performance for IVFC signals with three types of representative baseline drift.Compared with non-baseline correction methods,this method showed a higher sensitivity and specificity,as well as a better result in the Pearson's correlation coefficient and the mean-squared error(MSE).展开更多
Separation of arteries and veins in the cerebral cortex is of significant importance in the studies of cortical hemodynamics,such as the changes of cerebral blood flow,perfusion or oxygen con-centration in arteries an...Separation of arteries and veins in the cerebral cortex is of significant importance in the studies of cortical hemodynamics,such as the changes of cerebral blood flow,perfusion or oxygen con-centration in arteries and veins under different pathological and physiological conditions.Yet the cerebral vessel segmentation and vessel-type separation are challenging due to the complexity of cortical vessel characteristics and low spatial signal-to-noise ratio.In this work,we presented an effective full-field method to differentiate arteries and veins in cerebral cortex using dual-modal optical imaging technology including laser speckle imaging(LSI)and optical intrinsic signals(OIS)imaging.The raw contrast images were acquired by LSI and processed with enhanced laser speckle contrast analysis(eLASCA),algorithm.The vascular pattern was extracted and seg-mented using region growing algorithm from the eLASCA-based LSI.Meanwhile,OIS imageswere acquired altermatively with 630 and 870 nm to obtain an oxy hemoglobin concentration mapover cerebral cortex.Then the separation of arteries and veins was accomplished by Otsuthreshold segmentation algorithm based on the OIS information and segmentation of LSI.Finally,the segmentation and separation performances were assessed using area overlap measure(AOM).The segmentation and separation of cerebral vessels in cortical optical imaging have great potential applications in full-field cerebral hemodynamics monitoring and pathological study of cerebral vascular diseases,as well as in clinical intraoperative monitoring.展开更多
Recent studies in oncology have addressed the importance of detecting circulating tumor cell clusters because circulating tumor cell clusters might survive and metastasize more easily than single circulating tumor cel...Recent studies in oncology have addressed the importance of detecting circulating tumor cell clusters because circulating tumor cell clusters might survive and metastasize more easily than single circulating tumor cells.Signals with larger peak widths detected by in vivo flow cytometer(IVFC)have been used to identify cell clusters in previous studies.However,the accuracy of this criterion might be greatly degraded by variance in blood°ow and the rolling behaviors of circulating tumor cells.Here,we propose a criterion and algorithm to distinguish cell clusters from single cells.In this work,we first used area-based and volume-based models for single°uorescent cells.Simulating each model,we analyzed the corresponding morphology of IVFC signals from cell clusters.According to the Rayleigh criterion,the valley between two adjacent peak signals from two distinguishable cells should be lower than 73.5%of the peak values.A novel signal processing algorithm for IVFC was developed based on this criterion.The results showed that cell clusters can be reliably identied using our proposed algorithm.Intravital imaging was also performed to further support our algorithm.With enhanced accuracy,IVFC is a powerful tool to study circulating cell clusters.展开更多
Vascular inflammation is an important process which contributes to the pathogenesis of many cardiovascular diseases, such as atherosclerosis. MicroRNAs (miRNAs) have been revealed as novel regulators of vascular infla...Vascular inflammation is an important process which contributes to the pathogenesis of many cardiovascular diseases, such as atherosclerosis. MicroRNAs (miRNAs) have been revealed as novel regulators of vascular inflammation. Prior researches had shown that alterations in gene expression of human umbilical vein endothelial cells (HUVECs) associated with topo-graphic cues. Here, we showed that poly (dimethyl siloxane) (PDMS) substrate of 10 μm width and 3 μm depth parallel microgrooves on the surface could significantly upregulate the expression of anti-inflammatory microRNAs, miR-146a and miR-181b. In addition, the results also showed that TRAF6 and importin-α3, target of miR-146a and miR-181b, respectively, were both down-regulated (P < 0.05 and P < 0.001, respectively). The expression levels of the inflammation related proteins were all significantly decreased, including VCAM-1 (P < 0.05), ICAM-1 (P < 0.001), E-selectin (P < 0.001), and MCP-1 (P < 0.05). The adhesion of the mononuclear cell line, THP-1, was significantly decreased (P < 0.05). The results revealed that morphology modified HUVEC can modulate miR-146a and miR-181b and their downstream biological functions such as decreasing inflammation, suggesting that surface microtopology may affect vascular inflammation in the setting of cardiovascular disease. These interesting findings will facilitate the optimal design of microstructured materials in tissue engineering.展开更多
Aim: Periodontitis is caused by chronic gingival inflammation and affects a large population in the world. Although guided tissue regeneration (GTR) therapy has been proven to be an effective treatment, the deficiency...Aim: Periodontitis is caused by chronic gingival inflammation and affects a large population in the world. Although guided tissue regeneration (GTR) therapy has been proven to be an effective treatment, the deficiency in the symmetrical design of all the GTR membrane in the market leaves large space for improvement. Therefore, we designed a novel asymmetrical bi-layer PLA/gelatin composite membrane for treating periodontitis. Methods: The PLA side was fabricated by electrospinning with metronidazole (MNA) pre-mixed with the PLA solution. The gelatin side containing bioglass (BG) 45S5 was fabricated with freeze-drying process and cross-linked with PLA membrane. The bio-compatibility of the membrane was evaluated in vitro using NIH3T3 cells. The releasing of MNA was measured by spectrophotometer. The bioactivity of the membrane was evaluated by hydroxyapatite (HA) deposit and determined by FTIR spectrometer. The ionic concentration of Ca2+ and was measured by ICPOES. The expression of the osteogenesis makers was determined by qRT-PCR. Results: The bi-layer PLA/gelatin composite membrane is biocompatible and bioactive. The releasing of MNA can rapidly reach the anti-bacterial effective concentration. Interestingly, the incorporation of MNA modulated the degradation rate of PLA scaffold to meet the requirement of tissue regeneration. Meanwhile, the embedding of the BG powder in the gelatin porous layer provided a favorable Ca2+ and ion environment for the regeneration of the alveolar bone tissue. Conclusions: Taken together, this bi-layer GTR membrane is closer to the physiological structure of the periodontal. The addition of MNA and BG makes it more powerful in treating periodontitis. Moreover, this research provides an example of biomimetic design in fabricating biomaterial for clinical applications.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81801236(to ZX),81974189(to HT)a grant from Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.ynlc201719(to QZ).
文摘Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice.Mice were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein groups.In the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse brain.These changes resulted in improved neurological function compared with controlled cortical impact mice.Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein.Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral outcomes.Furthermore,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control.Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways.
文摘The center was first established in 2013 and affiliated to the Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine.In 2015,the center was entitled as 3D Bioprinting Clinical Transformation Collaborative Innovation Center.In 2016,the center was renamed as Medical 3D Printing Innovation Research Center of Shanghai Jiao Tong University School of Medicine.Although the center was established in 2013,the clinical application of 3D printing in Shanghai Ninth People’s Hospital can be traced back to the 1990s.As early as 30 years ago,Prof.Kerong Dai had tried to rebuild patients pelvic by manually cutting the foam boards and layering them together based on the theory of 3D printing for preoperative planning model of abnormal skeleton structures and development of personalized prosthesis.That was the first application of 3D printing in the area of medicine in China.Now,The Research Center of 3D Bioprinting in Shanghai Ninth People’s Hospital comprised of subcenters including the outpatient department of 3D printing,medical 3D printing innovation research center and Shanghai key laboratory of orthopedic implant.
基金supported by the National Key R&D Program of China,No.2019YFA0112000(to YHT)the National Natural Science Foundation of China,Nos.82071284(to YHT),81974179(to ZJZ)+4 种基金Shanghai Rising-Star Program,No.21QA1405200(to YHT)the Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY)the Notional Research Foundation of Korea,Nos.2020M3E5D9079912(to WSC),2021R1A2C3005704(to WSC),2022M3E5E8081188(to WSC)the Korea Health Technology R&D Project,No.HU20C0290(to WSC)。
文摘Recent studies have shown that microglia/macrophages and astrocytes can mediate synaptic phagocytosis through the MER proto-oncokinase in developmental or stroke models,but it is unclear whether the same mechanism is also active in traumatic brain injury.In this study,we established a mouse model of traumatic brain injury and found that both microglia/macrophages and astrocytes phagocytosed synapses and expression of the MER proto-oncokinase increased 14 days after injury.Specific knockout of MER in microglia/macrophages or astrocytes markedly reduced injury volume and greatly improved neurobehavioral function.In addition,in both microglia/macrophages-specific and astrocytes-specific MER knock-out mice,the number of microglia/macrophage and astrocyte phagocytosing synapses was markedly decreased,and the total number of dendritic spines was increased.Our study suggested that MER proto-oncokinase expression in microglia/macrophages and astrocytes may play an important role in synaptic phagocytosis,and inhibiting this process could be a new strategy for treating traumatic brain injury.
基金The authors appreciated the financial support from the National Key R&D Program of China(No.2018YFA0703000)the National Natural Science Foundation of China(No.82072412)+2 种基金the Translation Medicine National Key Science and Technology Infrastructure(Shanghai)Open Project(No.TMSK-2020-118)the Lingang Laboratory“Seeking Outstanding Youth Program”Open Project(No.LG-QS-202206-04)the Shanghai Municipal Natural Science Foundation(No.19ZR1429100).
文摘Three-dimensional(3D)tumor models prepared from patient-derived cells have been reported to imitate some of the biological development processes of in situ tumors in vitro.These 3D tumor models share several important characteristics with their in vivo tumor counterparts.Accordingly,their applications in tumor modeling,drug screening,and precision-targeted treatment are promising.However,the establishment of tumormodels is subject to several challenges,including advancements in scale size,repeatability,structural precision in time and space,vascularization,and the tumor microenvironment.Recently,bioprinting technologies enabling the editorial arrangement of cells,factors,and materials have improved the simulation of tumormodels in vitro.Among the 3D bioprinted tumor models,the organoidmodel has been widely appreciated for its advantages of maintaining high heterogeneity and capacity for simulating the developmental process of tumor tissues.In this review,we outline approaches and potential prospects for tumor model bioprinting and discuss the existing bioprinting technologies and bioinks in tumor model construction.The multidisciplinary combination of tumor pathology,molecular biology,material science,and additive manufacturing will help overcome the barriers to tumor model construction by allowing consideration of the structural and functional characteristics of in vitro models and promoting the development of heterogeneous tumor precision therapies.
文摘The fuorescence-based in vivo flow cytometry(IVFC)is an emerging tool to monitor eirculating cells in vivo.As a noninvasive and real-timne diagnostic technology,the fluorescence based IVFC allows long-term monitoring of circulating cells without changing their native biological environment.It has been applied for various biological applications(eg,monitoring circulating tumor cells).In this work,we will review our recent works on fluorescence-based IVFC.The operation principle and typical biological applications will be introduced.In addition,the recent advances in IVFC flow cytometry based on photoacoustic effects and other label free detection methods such as imaging based methods,difuse-light methods,hybrid multimodality methods and multispectral methods are also summarized.
基金supported by grants awarded by the National Major Scientic Research Program of China(Grant No.2011CB910404)the National Nature Science Foundation of China(Grant No.61227017)+1 种基金the State Key Basic Research Development Program of China(2012CB518103)National Outstanding Young Scientist Award of China(61425006).
文摘Alzheimers disease(AD)is a chronic neurodegenerative disease.The symptoms include memoryand spatial learning dificulties,language disorders,and loss of motivation,which get worse overtime,eventually ending in death.No ffective treatments are available for AD,currently.Currenttreatments only attenuate symptoms temporarily and are associated with severe side ffects.Nearinfra-red(NIR)light has been studied for a long time.We investigated the effect of NIR on ADusing a transgenic mouse model,which was obtained by co-injecting two vectors carrying ADmutations in amyloid precursor protein(APP)and presenilin-i(PSEN1)into C57BL/6J mice.The irradiation equipment consisted of an accommodating box and an LED array.The wave-length of NIR light emitted from LED was between 1040 nm and 1090 nm.The power densitydelivered at the level of the mice was approximately 15 mW/cm^(2),Firstly,we treated the micewith NIR for 40 days,Then,the irradiation was suspended for 28 days.Finally,another 15 daystreatment was brought to mice.We conducted Morris water maze and immunofluorescenceanalysis to evaluate the effects of treatment.Immunofuorescence analysis was based on mea-suring the quantity of plaques in mouse brain slices,Our results show that NIR light improvesmemory and spatial learning ability and reduces plaques moderately.NIR light represents apotential treatment for AD.
基金supported by the National Natural Science Foundation of China,Nos.81802232(to JXW),81801170(to YHT),82071284(to YHT),2019YFA0112000(to YHT)the Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)+1 种基金Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY)Science and Technology Commission of Shanghai,No.19441907900(to JFS).
文摘Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.
基金the financial support from Project 81771983, 81750110544, 81750410695, 81650110523, and 81471096 (to LXQ) by National Natural Science Foundation of China (NSFC)Project 16441909300 by Shanghai Science and Technology Commission+2 种基金Project 2017YFC0909000 by Ministry of Science and Technology of Chinasponsored by the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (TP2015015)supported by 14DZ2272400 Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition (to WC)
文摘Nutriology relies on advanced analytical tools to study the molecular compositions of food and provide key information on sample quality/safety. Small nutrients detection is challenging due to the high diversity and broad dynamic range of molecules in food samples, and a further issue is to track low abundance toxins. Herein, we developed a novel plasmonic matrix-assisted laser desorption/ionization mass spectrometry(MALDI MS)approach to detect small nutrients and toxins in complex biological emulsion samples. Silver nanoshells(SiO_2@-Ag) with optimized structures were used as matrices andachieved direct analysis of ~ 6 n L of human breast milk without any enrichment or separation. We performed identification and quantitation of small nutrients and toxins with limit-of-detection down to 0.4 pmol(for melamine) and reaction time shortened to minutes, which is superior to the conventional biochemical method currently in use. The developed approach contributes to the near-future application of MALDI MS in a broad field and personalized design of plasmonic materials for real-case bio-analysis.
基金This work is supported by the Cross Research Fund of Biomedical Engineering of Shanghai Jiao Tong University(YG2019QNA43).
文摘Catalysis-based chemodynamic therapy(CDT)is an emerging cancer treatment strategy which uses a Fenton-like reaction to kill tumor cells by catalyzing endogenous hydrogen peroxide(H_(2)O_(2))into a toxic hydroxyl radical(·OH).The performance of CDT is greatly dependent on PDT agent.Herein,mitochondria-targeting Pt nanoclusters were synthesized using cytochrome c aptamer(CytcApt)as template.The obtained CytcApt-PtNCs can produce.OH by H_(2)O_(2)under the acidic conditions.Moreover,CytcApt-PtNCs could kill 4T1 tumor cells in a pH-dependent manner,but had no side effect on normal 293T cells.Therefore,CytcApt-PtNCs possess excellent therapeutic effect and good biosafety,indicating their great potential for CDT.
文摘Endothelial cell (EC) morphology can be regulated by the micro/nano topography in engineered vascular grafts and by hemodynamic forces in the native blood vessels. However, how EC morphology affects miRNA and thus EC functions is not well understood. In this study, we addressed this question by using human umbilical vein endothelial cells (HUVECs) cultured on microgrooves as a model. HUVECs were grown on either microgrooved (with 10 μm width/spacing and 3 μm depth) or smooth surfaces. HUVECs on microgrooved surface had elongated and bipolar morphology, while HUVECs on smooth surface showed cobble stone shape or non-polar morphology. EdU staining indicated that HUVECs with elongated morphology had lower proliferation rate compared to their counterpart cultured on smooth surface. Quantitative PCR analysis demonstrated that the expression of the specific microRNAs (miR-10a, miR-19a, miR-221) that targeted proliferation-related genes was all up-regulated. Consistently, the mRNA levels of their respective target genes, mitogen-activated protein kinase kinase kinase 7, Cyclin D1 and c-kit were significantly reduced by a fold change of 0.12 ± 0.01 (p < 0.01), 0.70 ± 0.23 (p 0.05) and 0.76 ± 0.21 (p < 0.05). Other miRNAs such as miR-126 and miR-181a were up-regulated as well, leading to the repression of their targets vascular cell adhesion molecule-1 and prospero homeobox-1. Our results suggested that microgrooved surface may regulate microRNA levels and thus EC functions. These results provide insight into the modulation of EC functions by microtopographic cues, and will facilitate the rational design of microstructured materials for cell and tissue engineering.
基金supported by the National Basic Research Program of China(973Program,2011CB910404 and 2012CB966800)China National Natural Science Foundation(30901432 and 30972949)+2 种基金the Chinese Ministry of Education(109056)Program for New Century Excellent Talents in University Award(NCET-08-0131)Shanghai Science and Tech-nology Committee(11DZ2211000).
文摘Metastasis is a very complicated multi-step process and accounts for the low survival rate of the cancerous patients.To metastasize,t he malignant cells must detach from the primary tumor and migrate to secondary sites in the body through either blood or lymph circulation.Macrophages appear to be directly involved in tumor progression and metastasis.However,the role of macrophages in affecting cancer metast asis has not been fully elucidated.Here,we have utilized an emerging technique,namely in vivo flow cytometry(IVFC)to study the depletion kinetics of circulating prostate cancer cells in mice and determine how depletion of macrophages by the liposome encapsulated clodronate affects the depletion kinetics.Our results show diferent depletion kinetics of PC-3 cells between the macrophagedeficient group and the control group.The number of circulating tumor cells(CTCs)in the macrophage-deficient group decreases in a slower manner compared to the control mice group.The differences in depletion kinetics indicate that the absence of macrophages facilitates the stay of prostate cancer cells in circulation.In addition,our imaging data suggest that macrophages might be able to arrest,phagocytose and digest PC-3 cells.Therefore,phagocy tosis may mainly contribute to the de-pletion kinetic diferences.The developed methods elaborated here would be useful to study the relationship between macr ophages and tumor metastasis in small animal cancer models.
基金supported by NIH/NIA1R01AG 029681supported by the New Century Talent Program by the Ministry of Education of China,and Shanghai Shuguang Program(07SG13)supported by the China Scholarship Council.
文摘In this paper,a model-based reconstruction technique is proposed to simultaneously measure the relative deoxyhemoglobin concentration and the relative blood flow velocity in cerebral cortex.With the help of this model-based reconstruction technique,artifacts due to nonuniform laser illumination and curvature of cortex are efficiently corrected.The results of relative deoxyhemoglobin concentration and relative blood flow velocity are then used to detect and distinguish cerebral arteries and veins.In an experimental study on rat,cerebral blood vessels are segmented from the reconstructed blood flow image by Otsu multiple threshold method.Afterwards,arteries and veins are distinguished by a simple fuzzy criterion based on the information of relative deoxyhemoglobin concentration.
文摘Cancer stem cells (CSCs) are a rare subpopulation of phenotypically distinct cancer cells exhibiting stem cell characteristics. They are tumourigenic, meanwhile capable of self-renewal and forming differentiated progenies. CSCs are believed to be resistant to the standard therapeutics, and provide the cell reservoir for tumour initiation.1 Understanding CSCs or in another word, tumour-initiating cells, is of critical therapeutic importance.
基金Shanghai Leading Academic Discipline Project,China,Shanghai Key Laboratory Project,China,Doctoral Fund of Ministry of Education of China,National Natural Science Foundation of China
文摘Electrospun porous films doped with the green-synthesized CdSe quantum dots were synthesized. Glycerol was chosen to prepare the quantum dots ( QDs), with the highest quantum yield of 78.28%. Polycaprolactone (PCL) was electrospun with CdSe QDs to avoid the QDs' toxicity and improve the QDs' cytocompatibility. The electrospun QDs-doped films preserve the original QDs' fluorescence. Pores can be detected from the SEM of the films, predicting the possibility of loading drugs in the cancer therapy. The cell proliferation assay shows excellent cytocompatibility of the eletrospun CdSe-QDs-doped films. The present eletrospun CdSe- QDs-doped porous films are cytocompatibale, highly-fluorescent and ootential to load drugs in cancer therapy.
基金the grants of the National Major Scientific Research Program of China(Grant Nos.2011CB910404 and 2012CB966801)the National N ature Science Foundation of China(Grant No.61227017)the National Science Fund for Distinguished Young Scholars(Grant No.61425006).
文摘In biomedical research fields,the in vio Aow cytometry(IVFC)is a widely used technology which is able to monitor target cells dynamically in living animals.Although the setup of IVFC system has been well established,baseline drift is still a challenge in the process of quantifying circulating cells.Previous methods,i.e.,the dynamic peak picking method,counted cells by setting a static threshold without considering the baseline drift,leading to an inaccurate cell quantification.Here,we developed a method of cell counting for IVFC data with baseline drift by interpolation fitting,automatic segmentation and wavelet-based denoising.We demonstrated its performance for IVFC signals with three types of representative baseline drift.Compared with non-baseline correction methods,this method showed a higher sensitivity and specificity,as well as a better result in the Pearson's correlation coefficient and the mean-squared error(MSE).
文摘Separation of arteries and veins in the cerebral cortex is of significant importance in the studies of cortical hemodynamics,such as the changes of cerebral blood flow,perfusion or oxygen con-centration in arteries and veins under different pathological and physiological conditions.Yet the cerebral vessel segmentation and vessel-type separation are challenging due to the complexity of cortical vessel characteristics and low spatial signal-to-noise ratio.In this work,we presented an effective full-field method to differentiate arteries and veins in cerebral cortex using dual-modal optical imaging technology including laser speckle imaging(LSI)and optical intrinsic signals(OIS)imaging.The raw contrast images were acquired by LSI and processed with enhanced laser speckle contrast analysis(eLASCA),algorithm.The vascular pattern was extracted and seg-mented using region growing algorithm from the eLASCA-based LSI.Meanwhile,OIS imageswere acquired altermatively with 630 and 870 nm to obtain an oxy hemoglobin concentration mapover cerebral cortex.Then the separation of arteries and veins was accomplished by Otsuthreshold segmentation algorithm based on the OIS information and segmentation of LSI.Finally,the segmentation and separation performances were assessed using area overlap measure(AOM).The segmentation and separation of cerebral vessels in cortical optical imaging have great potential applications in full-field cerebral hemodynamics monitoring and pathological study of cerebral vascular diseases,as well as in clinical intraoperative monitoring.
基金the National Science Fund for Distinguished Young Scholars(Grant No.61425006)Program of Shanghai Technology Research Leader(Grant No.17XD1402200).
文摘Recent studies in oncology have addressed the importance of detecting circulating tumor cell clusters because circulating tumor cell clusters might survive and metastasize more easily than single circulating tumor cells.Signals with larger peak widths detected by in vivo flow cytometer(IVFC)have been used to identify cell clusters in previous studies.However,the accuracy of this criterion might be greatly degraded by variance in blood°ow and the rolling behaviors of circulating tumor cells.Here,we propose a criterion and algorithm to distinguish cell clusters from single cells.In this work,we first used area-based and volume-based models for single°uorescent cells.Simulating each model,we analyzed the corresponding morphology of IVFC signals from cell clusters.According to the Rayleigh criterion,the valley between two adjacent peak signals from two distinguishable cells should be lower than 73.5%of the peak values.A novel signal processing algorithm for IVFC was developed based on this criterion.The results showed that cell clusters can be reliably identied using our proposed algorithm.Intravital imaging was also performed to further support our algorithm.With enhanced accuracy,IVFC is a powerful tool to study circulating cell clusters.
文摘Vascular inflammation is an important process which contributes to the pathogenesis of many cardiovascular diseases, such as atherosclerosis. MicroRNAs (miRNAs) have been revealed as novel regulators of vascular inflammation. Prior researches had shown that alterations in gene expression of human umbilical vein endothelial cells (HUVECs) associated with topo-graphic cues. Here, we showed that poly (dimethyl siloxane) (PDMS) substrate of 10 μm width and 3 μm depth parallel microgrooves on the surface could significantly upregulate the expression of anti-inflammatory microRNAs, miR-146a and miR-181b. In addition, the results also showed that TRAF6 and importin-α3, target of miR-146a and miR-181b, respectively, were both down-regulated (P < 0.05 and P < 0.001, respectively). The expression levels of the inflammation related proteins were all significantly decreased, including VCAM-1 (P < 0.05), ICAM-1 (P < 0.001), E-selectin (P < 0.001), and MCP-1 (P < 0.05). The adhesion of the mononuclear cell line, THP-1, was significantly decreased (P < 0.05). The results revealed that morphology modified HUVEC can modulate miR-146a and miR-181b and their downstream biological functions such as decreasing inflammation, suggesting that surface microtopology may affect vascular inflammation in the setting of cardiovascular disease. These interesting findings will facilitate the optimal design of microstructured materials in tissue engineering.
文摘Aim: Periodontitis is caused by chronic gingival inflammation and affects a large population in the world. Although guided tissue regeneration (GTR) therapy has been proven to be an effective treatment, the deficiency in the symmetrical design of all the GTR membrane in the market leaves large space for improvement. Therefore, we designed a novel asymmetrical bi-layer PLA/gelatin composite membrane for treating periodontitis. Methods: The PLA side was fabricated by electrospinning with metronidazole (MNA) pre-mixed with the PLA solution. The gelatin side containing bioglass (BG) 45S5 was fabricated with freeze-drying process and cross-linked with PLA membrane. The bio-compatibility of the membrane was evaluated in vitro using NIH3T3 cells. The releasing of MNA was measured by spectrophotometer. The bioactivity of the membrane was evaluated by hydroxyapatite (HA) deposit and determined by FTIR spectrometer. The ionic concentration of Ca2+ and was measured by ICPOES. The expression of the osteogenesis makers was determined by qRT-PCR. Results: The bi-layer PLA/gelatin composite membrane is biocompatible and bioactive. The releasing of MNA can rapidly reach the anti-bacterial effective concentration. Interestingly, the incorporation of MNA modulated the degradation rate of PLA scaffold to meet the requirement of tissue regeneration. Meanwhile, the embedding of the BG powder in the gelatin porous layer provided a favorable Ca2+ and ion environment for the regeneration of the alveolar bone tissue. Conclusions: Taken together, this bi-layer GTR membrane is closer to the physiological structure of the periodontal. The addition of MNA and BG makes it more powerful in treating periodontitis. Moreover, this research provides an example of biomimetic design in fabricating biomaterial for clinical applications.