Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs sur...Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus.^(Sox2)is an important factor for NSCs to maintain proliferation.Therefore,^(Sox2)-overexpressing NSCs(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.展开更多
The restoration of nerve dysfunction after traumatic brain injury(TBI)faces huge challenges due to the limited self-regenerative abilities of nerve tissues.In situ inductive recovery can be achieved utilizing biologic...The restoration of nerve dysfunction after traumatic brain injury(TBI)faces huge challenges due to the limited self-regenerative abilities of nerve tissues.In situ inductive recovery can be achieved utilizing biological scaffolds combined with endogenous human umbilical cord mesenchymal stem cells(HUCMSCs)-derived exosomes(MExos).In this study,brain-derived neurotrophic factor-stimulated HUCMSCs-derived exosomes(BMExos)were composited with collagen/chitosan by 3D printing technology.3D-printed collagen/chitosan/BMExos(3D-CC-BMExos)scaffolds have excellent mechanical properties and biocompatibility.Subsequently,in vivo experiments showed that 3D-CC-BMExos therapy could improve the recovery of neuromotor function and cognitive function in a TBI model in rats.Consistent with the behavioural recovery,the results of histomorphological tests showed that 3D-CC-BMExos therapy could facilitate the remodelling of neural networks,such as improving the regeneration of nerve fibres,synaptic connections and myelin sheaths,in lesions after TBI.展开更多
A 12-wk trial was conducted to compare the tolerance of tilapia to high carbohydrate and high lipid diets.Three isonitrogenous and isoenergetic diets,whose carbohydrate and lipid levels were the following:35.0%and 8%(...A 12-wk trial was conducted to compare the tolerance of tilapia to high carbohydrate and high lipid diets.Three isonitrogenous and isoenergetic diets,whose carbohydrate and lipid levels were the following:35.0%and 8%(control),44.2%and 4%(D1,high carbohydrate),and 25.8%and 12%(D2,high lipid),respectively.Three hundred tilapias(27±0.11 g)were fed the diets for 10 wk(4 replicates per group);72 fish from the D1 group were continually fed the D1(D1D1)and 72 fish from the D2 were continually fed the D2(D2D2)diet for 2 wk(3 replicates each group)to evaluate the tilapia's capacity to tolerate high carbohydrate and high lipid diets,respectively.Another 36 fish from D1 group were continually fed D2(D1D2)for comparison with D1D1 and D2D2 groups.In phase 1,hepatosomatic index,liver triglycerides(TG),glucose tolerance(GT)and crude protein in the whole body in D1 group were higher than those in D2 group(P<0.05).During phase 2,D1D1 group had lower feed intake and weight gain,as well as lower serum total protein and albumin than that of D2D2 group(P<0.05),while its liver glycogen was significantly higher than that in D1D2 and D2D2 groups(P<0.05).Moreover,serum glucose and GT were higher in D1D1 and D1D2 groups than those in D2D2 group(P<0.05).By contrast,D2D2 group had significantly higher intraperitoneal fat,subcutaneous adipose tissue(SCAT)and liver TG than those in D1D1 group(P<0.05).The mRNA expression of brain npy,hepatic nrf2,gst1 and hepatic transcriptomic data showed that immune-related genes(gama,mrc2,mhc2 and cd163),were downregulated in D1D1 group compared to D2D2 and D1D2 groups.Taken together:1)tilapia have higher tolerance to a high lipid diet than high carbohydrate diet;2)despite retention of glucose tolerance,the continuous feeding of D1 diet impaired tilapia's appetite,weight gain rate and host immune response;3)specific distri-bution of fat in intraperitoneal regions,SCAT and liver may be a risk-avoidance strategy in tilapia in response to a continuous D2 diet.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82473334(to LZ),82401629(to XL)the Major Scientific and Technological Achievements Transformation Project of Ningxia Hui Autonomous Region,No.2022CJE09013(to LZ)+4 种基金Mianyang Science and Technology Bureau(Mianyang Science and Technology Program),No.2023ZYDF097(to LZ)NHC Key Laboratory of Nuclear Technology Medical Transformation(Mianyang Central Hospital),No.2023HYX001(to LZ)Spinal Cord Diseases Clinical Medical Center of Yunnan Province,No.2024JSKFKT-16(to BG)the Natural Science Foundation of Sichuan Province,No.2024NSFSC1646(to XL)the China Postdoctoral Science Foundation,Nos.GZC20231811(to XL),2024T170601(to XL)and 2024M76228(to XL).
文摘Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus.^(Sox2)is an important factor for NSCs to maintain proliferation.Therefore,^(Sox2)-overexpressing NSCs(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.
基金supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development(2015ZX09102010).
文摘The restoration of nerve dysfunction after traumatic brain injury(TBI)faces huge challenges due to the limited self-regenerative abilities of nerve tissues.In situ inductive recovery can be achieved utilizing biological scaffolds combined with endogenous human umbilical cord mesenchymal stem cells(HUCMSCs)-derived exosomes(MExos).In this study,brain-derived neurotrophic factor-stimulated HUCMSCs-derived exosomes(BMExos)were composited with collagen/chitosan by 3D printing technology.3D-printed collagen/chitosan/BMExos(3D-CC-BMExos)scaffolds have excellent mechanical properties and biocompatibility.Subsequently,in vivo experiments showed that 3D-CC-BMExos therapy could improve the recovery of neuromotor function and cognitive function in a TBI model in rats.Consistent with the behavioural recovery,the results of histomorphological tests showed that 3D-CC-BMExos therapy could facilitate the remodelling of neural networks,such as improving the regeneration of nerve fibres,synaptic connections and myelin sheaths,in lesions after TBI.
基金funded by National Key R&D Program of China(2018YFD0900400)Guangdong Basic and Applied Basic Research Foundation(2019A1515110115).
文摘A 12-wk trial was conducted to compare the tolerance of tilapia to high carbohydrate and high lipid diets.Three isonitrogenous and isoenergetic diets,whose carbohydrate and lipid levels were the following:35.0%and 8%(control),44.2%and 4%(D1,high carbohydrate),and 25.8%and 12%(D2,high lipid),respectively.Three hundred tilapias(27±0.11 g)were fed the diets for 10 wk(4 replicates per group);72 fish from the D1 group were continually fed the D1(D1D1)and 72 fish from the D2 were continually fed the D2(D2D2)diet for 2 wk(3 replicates each group)to evaluate the tilapia's capacity to tolerate high carbohydrate and high lipid diets,respectively.Another 36 fish from D1 group were continually fed D2(D1D2)for comparison with D1D1 and D2D2 groups.In phase 1,hepatosomatic index,liver triglycerides(TG),glucose tolerance(GT)and crude protein in the whole body in D1 group were higher than those in D2 group(P<0.05).During phase 2,D1D1 group had lower feed intake and weight gain,as well as lower serum total protein and albumin than that of D2D2 group(P<0.05),while its liver glycogen was significantly higher than that in D1D2 and D2D2 groups(P<0.05).Moreover,serum glucose and GT were higher in D1D1 and D1D2 groups than those in D2D2 group(P<0.05).By contrast,D2D2 group had significantly higher intraperitoneal fat,subcutaneous adipose tissue(SCAT)and liver TG than those in D1D1 group(P<0.05).The mRNA expression of brain npy,hepatic nrf2,gst1 and hepatic transcriptomic data showed that immune-related genes(gama,mrc2,mhc2 and cd163),were downregulated in D1D1 group compared to D2D2 and D1D2 groups.Taken together:1)tilapia have higher tolerance to a high lipid diet than high carbohydrate diet;2)despite retention of glucose tolerance,the continuous feeding of D1 diet impaired tilapia's appetite,weight gain rate and host immune response;3)specific distri-bution of fat in intraperitoneal regions,SCAT and liver may be a risk-avoidance strategy in tilapia in response to a continuous D2 diet.
