When adipose-derived stem cells （ASCs） arc retrieved from the stromal vascular portion of adipose tissue, a large amount of mature adipocytes are often discarded. However, by modified ceiling culture technique based...When adipose-derived stem cells （ASCs） arc retrieved from the stromal vascular portion of adipose tissue, a large amount of mature adipocytes are often discarded. However, by modified ceiling culture technique based on their buoyancy, mature adipocytes can be easily isolated from the adipose cell suspension and dediffercn- tiated into lipid-frce fibroblast-like cells, named dediffercntiated fat （DFAT） cells. DFAT cells rc-establish active proliferation ability and undertake multipotent capacities. Compared with ASCs and other adult stem cells, DFAT cells showed unique advantages in their abundance, isolation and homogeneity. In this concise review, the establishment and culture methods of DFAT cells arc introduced and the current profiles of their cellular nature are summarized. Under proper inducti~,n culture in vitro or environment in vivo, DFAT cells could demonstrate adipogenic, osteogenic, chondrogenie and myogenic potentials. In angiogenie conditions, DFAT cells could exhibit perivascular characteristics antt elicit neovascularization. Our preliminary findings also suggested the pericyte phenotype underlying such cell lineage, which supported a novel interpretation about the common origin of mesenchymal stem cells and tissue-specific stem cells within blood vessel walls. Current research on DFAT cells indicated that this alternative source of adult multipotent cells has great potential in tissue engineering and regenerative medicine.展开更多
Objective To provide basis of reference values for relevant parameters of Chinese Reference Man. Methods Eighteen kinds of major organ or tissue samples, including muscle, rib, liver, and so on, were obtained from 4 a...Objective To provide basis of reference values for relevant parameters of Chinese Reference Man. Methods Eighteen kinds of major organ or tissue samples, including muscle, rib, liver, and so on, were obtained from 4 areas (Hebei, Shanxi, Jiangsu, and Sichuan provinces) with different dietary patterns in China in autopsy of 16 healthy adult men, who had just encountered sudden deaths. At the same time, whole blood samples were collected from 10 volunteers living in each of these areas. The concentrations of 56 elements in these samples were detected by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES), and Graphite Furnace Atomic Absorption Spectrometry (GF-AAS) techniques. Based on obtained concentrations and reference values of these organ or tissue weights for Chinese Reference Man, the relative elemental burdens in these organs or tissues as well whole body were also estimated. Results The concentrations of 56 elements in 18 main organs or tissues were determined all together and their elemental organ or tissue and whole body burdens were estimated. Furthermore, the distributions of important elements for radiation protection in these organs or tissues were emphatically discussed. Conclusion By summing with past related results, the total results obtained from the series of research may provide more reliable and better representative basis of these reference values for Chinese Reference Man than before.展开更多
Aberrant adrenocortical tissue in spermatic cord is rare in adult population. We report an unusual case of a 52-year-old male patient with an aberrant adrenocortical tissue which is incidentally resected within lipoma...Aberrant adrenocortical tissue in spermatic cord is rare in adult population. We report an unusual case of a 52-year-old male patient with an aberrant adrenocortical tissue which is incidentally resected within lipoma of spermatic cord and identified on microscopic examination. Although he was diagnosed with right inguinal hernia, there was no significant hernia orifice intraoperatively. When the 2nd operation by anterior open approach was undergone, there was a fat-like tissue adhered to the spermatic cord. It was removed and the histopathological finding first revealed aberrant adrenocortical tissue in the resected lipoma of spermatic cord (Figure 1). This abnormal tissue is usually found incidentally during inguinal operation. In general, most of the aberrant adrenal tissue becomes atrophic by adult life. Moreover, it is not clinically significant and also not associated with endocrine abnormalities.展开更多
AIM: To help clarifying the possibility of connective-tissue diseases in men with penile or testicular prostheses. METHODS: Eight patients underwent inflatable penile prostheses and 15, testicular prostheses consented...AIM: To help clarifying the possibility of connective-tissue diseases in men with penile or testicular prostheses. METHODS: Eight patients underwent inflatable penile prostheses and 15, testicular prostheses consented to the study. Their medical records were reviewed and a follow-up interview and physical and serological examinations were performed. RESULTS: In patients with penile prostheses, there was no abnormal antinuclear antibody (ANA) or IgM elevation. The serum levels of the rheumatoid factor (RF), C4, IgA and IgG were abnormal in one patient, and the levels of erythrocyte sedimentation rate (ESR) and C3, abnormal in two. Four had elevated IgE. In patients with testicular prostheses, there was no abnormal RF, ANA or IgM. The serum levels of ESR and IgA were abnormal in two, and three had abnormal C4, ten abnormal C3, and eleven decreased IgG. All had increased IgE. Men with penile prostheses had higher serum levels of IgG and IgM than those with testicular prostheses (P=0.001, P=0.016, respectively). The rates of abnormal values of IgE and IgG were higher in men with testicular prostheses than in men with penile prostheses (P=0.008, P=0.009, respectively). Physical examination was normal in all patients and nobody had documented symptoms pertinent to connective-tissue diseases. CONCLUSION: Our findings suggest that the risk of connective-tissue diseases is not higher in patients wearing prostheses as the ANA is negative and there is no apparent manifestation suggestive of connective-tissue diseases.展开更多
Aim of Study: Gonadal hormones exert a profound influence on the development, structure and function of the sexual organs. The testosterone is one of the androgens that plays an essential role in the development of se...Aim of Study: Gonadal hormones exert a profound influence on the development, structure and function of the sexual organs. The testosterone is one of the androgens that plays an essential role in the development of sexual organs in male mammals. Therefore, the present study was undertaken to evaluate the testosterone levels and developmental pattern of the penile spines and seminiferous tubules during early postnatal life of Wistar rats. Methods and Materials: At 7, 14, 21, 28, 35, 42, 49, 56, 63 and 70 days after birth, penile and testicular tissues of male rats were dissected out and fixed for histological study and plasma testosterone levels were determined using high resolution chromatography. Results: An increase in the number of penile follicles, primarily in the distal region of the penis, was observed from postnatal days 14 to 42, followed by a gradual decrease. Penile spines were absent from birth until the first growth peak, which was observed at 42 postnatal days. Both testicular weight and the area of seminiferous tubules showed gradual increases before achieving their highest values at 42 postnatal days. Similarly, a gradual increase in testosterone levels was detected from day 28, with a peak at 42 postnatal days. Conclusions: These data show a temporal association between the development of the penile spines and testicular tissue with gradual increases in testosterone levels. These results may contribute to a better understanding of the behavioral, hormonal and morphological changes underlying sexual maturation in male rats.展开更多
The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge stillpending in tissue engineering. The loss of hair follic...The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge stillpending in tissue engineering. The loss of hair follicles caused by injuries or pathologies such as alopecia not only affects the patients' psychological well-being, but also endangers certain inherent functions of the skin. It is then of great interest to find different strategies aiming to regenerate or neogenerate the hair follicle under conditions proper of an adult individual. Based upon current knowledge on the epithelial and dermal cells and their interactions during the embryonic hair generation and adult hair cycling, many researchers have tried to obtain mature hair follicles using different strategies and approaches depending on the causes of hair loss. This review summarizes current advances in the different experimental strategies to regenerate or neogenerate hair follicles, with emphasis on those involving neogenesis of hair follicles in adult individuals using isolated cells and tissue engineering. Most of these experiments were performed using rodent cells, particularly from embryonic or newborn origin. However, no successful strategy to generate human hair follicles from adult cells has yet been reported. This review identifies several issues that should be considered to achieve this objective. Perhaps the most important challenge is to provide threedimensional culture conditions mimicking the structure of living tissue. Improving culture conditions that allow the expansion of specific cells while protecting their inductive properties, as well as methods for selecting populations of epithelial stem cells, should give us the necessary tools to overcome the difficulties that constrain human hair follicle neogenesis. An analysis of patent trends shows that the number of patent applications aimed at hair follicle regeneration and neogenesis has been increasing during the last decade. This field is attractive not only to academic researchers but also to the companies that own almost half of the patents in this field.展开更多
AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of t...AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of this study was to evaluate the effect of ulcerative colitis(UC)on MMP- 1 and TIMP-1 plasma concentrations,as two possible biomarkers of the disease activity. METHODS:MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16 patients with endoscopically confirmed active UC. RESULTS:Plasma concentrations of both MMP-1(13.7±0.2 ng/ml)and TIMP-1(799±140 ng/ml)were significantly elevated in UC patients in comparison to healthy controls (11.9±0.9 ng/ml and 220±7 ng/ml respectively).There was no correlation between TIMP-1 and MMP-1 concentrations (r=0.02).TIMP-1 levels revealed significant positive correlations with scored endoscopic degree of mucosal injury, disease activity index and clinical activity index values as well as C-reactive protein concentration.There was no correlation between MMP-1 and laboratory,clinical or endoscopic indices of the disease activity.CONCLUSION: These results confirm the role of both MMP- 1 and TIMP-1 in the pathogenesis of ulcerative colitis. However only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating association with clinical and endoscopic pictures.展开更多
AIM:To deduce strategic guidelines of gastric mucosa associated lymphoid tissue lymphoma (MALTOMA) by evaluating the long-term outcome of patients in respect to various treatment modalities. METHODS:A total of 55 pati...AIM:To deduce strategic guidelines of gastric mucosa associated lymphoid tissue lymphoma (MALTOMA) by evaluating the long-term outcome of patients in respect to various treatment modalities. METHODS:A total of 55 patients with MALTOMA from May 1992 to August 2002 were retrospectively reviewed. RESULTS:Complete remission was obtained in 24 (82.8%) of 29 patients treated with anti Helicobacter pylori (Hpylori) regimen only.The duration to reach complete remission was 12 months (85 percentile,2-33 months).Five patients showed complete remission with radiation therapy (26-86 months).Two of them were Hpyloritreatment failure cases. CONCLUSION:Hpylorieradication is an effective primary treatment option for low grade MALTOMA and radiation therapy could be considered in patients with no evidence of Hpyloriinfection or who do not respond to Hpylorieradication therapy 12 months after successful eradication.展开更多
Transplantation of adult spinal cord tissue(aSCT)is a promising treatment for spinal cord injury(SCI)basing on various types of neural cells and matrix components inside aSCT.However,long-term systemic administration ...Transplantation of adult spinal cord tissue(aSCT)is a promising treatment for spinal cord injury(SCI)basing on various types of neural cells and matrix components inside aSCT.However,long-term systemic administration of immunosuppressors(e.g.tacrolimus,TAC)is required for the survival of allogeneic tissue,which often associated with severe side effects such as infection,liver damageand renal failure.In this study,a triglycerol monostearate(TGM)-based TAC delivery system(e.g.TAC@TGM)with high drug loading concentration was developed,which possessed injectable properties as well as sustainable and immune-responsive drug release behaviors.In complete transected SCI model,locally injected TAC@TGM could reduce the infiltration of inflammation cells,enhance the survival of transplanted aSCT(e.g.Tuj-1^(+)and NF^(+)neurons)and promote the recovery of locomotor function.Moreover,controlled release of TAC by TAC@TGM attenuated side effects of TAC on liver and kidneys compared with traditional systemic administration.More importantly,the developed TAC@TGM system provided a facile single dose of long-term immunosuppressive effect not just for aSCT transplantation,but also for other tissue/organ and cell transplantations.展开更多
Whether endogenous neurogenesis occurs in the adult cortex remains controversial.An increasing number of reports suggest that doublecortin(DCX)-positive neurogenesis persists in the adult primate cortex,attracting eno...Whether endogenous neurogenesis occurs in the adult cortex remains controversial.An increasing number of reports suggest that doublecortin(DCX)-positive neurogenesis persists in the adult primate cortex,attracting enormous attention worldwide.In this study,different DCX antibodies were used together with NeuN antibodies in immunohistochemistry and western blot assays using adjacent cortical sections from adult monkeys.Antibody adsorption,antigen binding,primary antibody omission and antibody-free experiments were used to assess specificity of the signals.We found either strong fluorescent signals,medium-weak intensity signals in some cells,weak signals in a few perikarya or near complete lack of labeling in adjacent cortical sections incubated with the various DCX antibodies.The putative DCX-positive cells in the cortex were also positive for NeuN,a specific marker of mature neurons.However,further experiments showed that most of these signals were either the result of antibody cross reactivity,the non-specificity of secondary antibodies or tissue autofluorescence.No confirmed DCX-positive cells were detected in the adult macaque cortex by immunofluorescence.Our findings show that DCX-positive neurogenesis does not occur in the cerebral cortex of adult primates,and that false-positive signals(artefacts)are caused by antibody cross reactivity and autofluorescence.The experimental protocols were approved by the Institutional Animal Care and Use Committee of the Institute of Neuroscience,Beijing,China(approval No.IACUC-AMMS-2014-501).展开更多
Several lines of evidence have established that proliferation and differentiation of neural stem cells into neurons within the sub-granular zone of the dentate gyrus,a process named adult hippocampal neurogenesis,cont...Several lines of evidence have established that proliferation and differentiation of neural stem cells into neurons within the sub-granular zone of the dentate gyrus,a process named adult hippocampal neurogenesis,contribute to maintaining healthy cognitive functions throughout life.The rate of adult hippocampal neurogenesis decreases with aging and a premature impairment of adult hippocampal neurogenesis has been observed both in animal models of Alzheimer’s disease and human post-mortem tissues.The causal relationship between adult hippocampal neurogenesis and the development of Alzheimer’s disease pathology has,however,not been established.This is partly due to the limitation of recapitulating the development of Alzheimer’s disease pathology in rodent models and the lack of translatable biomarkers to identify tractable targets in humans.While it is tempting to postulate that adult hippocampal neurogenesis could be leveraged to improve cognitive deficits in Alzheimer’s disease,consensual results have yet to be reached to fully explore this hypothesis.In this review,we discuss how the recent progress in identifying molecular pathways in adult hippocampal neurogenesis provides a good framework to initiate strategies for drug-based intervention in neurodegenerative diseases,especially in Alzheimer’s disease.We outline how discrepancies in pre-clinical disease models and experimental methodology have resulted in contradictory findings and propose a shift towards using more translatable approaches to model neurogenesis in Alzheimer’s disease.In particular,we review how exploring novel experimental paradigms including the use of human induced pluripotent stem cells and more complex cell culture systems,as well as standardizing protocols used to investigate evidence of neurogenesis in human tissues,could deliver deeper mechanistic insights that would kick-start innovative drug discovery efforts to promote healthy aging and cellular rejuvenation.展开更多
文摘When adipose-derived stem cells （ASCs） arc retrieved from the stromal vascular portion of adipose tissue, a large amount of mature adipocytes are often discarded. However, by modified ceiling culture technique based on their buoyancy, mature adipocytes can be easily isolated from the adipose cell suspension and dediffercn- tiated into lipid-frce fibroblast-like cells, named dediffercntiated fat （DFAT） cells. DFAT cells rc-establish active proliferation ability and undertake multipotent capacities. Compared with ASCs and other adult stem cells, DFAT cells showed unique advantages in their abundance, isolation and homogeneity. In this concise review, the establishment and culture methods of DFAT cells arc introduced and the current profiles of their cellular nature are summarized. Under proper inducti~,n culture in vitro or environment in vivo, DFAT cells could demonstrate adipogenic, osteogenic, chondrogenie and myogenic potentials. In angiogenie conditions, DFAT cells could exhibit perivascular characteristics antt elicit neovascularization. Our preliminary findings also suggested the pericyte phenotype underlying such cell lineage, which supported a novel interpretation about the common origin of mesenchymal stem cells and tissue-specific stem cells within blood vessel walls. Current research on DFAT cells indicated that this alternative source of adult multipotent cells has great potential in tissue engineering and regenerative medicine.
基金Supported by the National Natural Sciences Foundation of China(30370443)
文摘Objective To provide basis of reference values for relevant parameters of Chinese Reference Man. Methods Eighteen kinds of major organ or tissue samples, including muscle, rib, liver, and so on, were obtained from 4 areas (Hebei, Shanxi, Jiangsu, and Sichuan provinces) with different dietary patterns in China in autopsy of 16 healthy adult men, who had just encountered sudden deaths. At the same time, whole blood samples were collected from 10 volunteers living in each of these areas. The concentrations of 56 elements in these samples were detected by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES), and Graphite Furnace Atomic Absorption Spectrometry (GF-AAS) techniques. Based on obtained concentrations and reference values of these organ or tissue weights for Chinese Reference Man, the relative elemental burdens in these organs or tissues as well whole body were also estimated. Results The concentrations of 56 elements in 18 main organs or tissues were determined all together and their elemental organ or tissue and whole body burdens were estimated. Furthermore, the distributions of important elements for radiation protection in these organs or tissues were emphatically discussed. Conclusion By summing with past related results, the total results obtained from the series of research may provide more reliable and better representative basis of these reference values for Chinese Reference Man than before.
文摘Aberrant adrenocortical tissue in spermatic cord is rare in adult population. We report an unusual case of a 52-year-old male patient with an aberrant adrenocortical tissue which is incidentally resected within lipoma of spermatic cord and identified on microscopic examination. Although he was diagnosed with right inguinal hernia, there was no significant hernia orifice intraoperatively. When the 2nd operation by anterior open approach was undergone, there was a fat-like tissue adhered to the spermatic cord. It was removed and the histopathological finding first revealed aberrant adrenocortical tissue in the resected lipoma of spermatic cord (Figure 1). This abnormal tissue is usually found incidentally during inguinal operation. In general, most of the aberrant adrenal tissue becomes atrophic by adult life. Moreover, it is not clinically significant and also not associated with endocrine abnormalities.
文摘AIM: To help clarifying the possibility of connective-tissue diseases in men with penile or testicular prostheses. METHODS: Eight patients underwent inflatable penile prostheses and 15, testicular prostheses consented to the study. Their medical records were reviewed and a follow-up interview and physical and serological examinations were performed. RESULTS: In patients with penile prostheses, there was no abnormal antinuclear antibody (ANA) or IgM elevation. The serum levels of the rheumatoid factor (RF), C4, IgA and IgG were abnormal in one patient, and the levels of erythrocyte sedimentation rate (ESR) and C3, abnormal in two. Four had elevated IgE. In patients with testicular prostheses, there was no abnormal RF, ANA or IgM. The serum levels of ESR and IgA were abnormal in two, and three had abnormal C4, ten abnormal C3, and eleven decreased IgG. All had increased IgE. Men with penile prostheses had higher serum levels of IgG and IgM than those with testicular prostheses (P=0.001, P=0.016, respectively). The rates of abnormal values of IgE and IgG were higher in men with testicular prostheses than in men with penile prostheses (P=0.008, P=0.009, respectively). Physical examination was normal in all patients and nobody had documented symptoms pertinent to connective-tissue diseases. CONCLUSION: Our findings suggest that the risk of connective-tissue diseases is not higher in patients wearing prostheses as the ANA is negative and there is no apparent manifestation suggestive of connective-tissue diseases.
文摘Aim of Study: Gonadal hormones exert a profound influence on the development, structure and function of the sexual organs. The testosterone is one of the androgens that plays an essential role in the development of sexual organs in male mammals. Therefore, the present study was undertaken to evaluate the testosterone levels and developmental pattern of the penile spines and seminiferous tubules during early postnatal life of Wistar rats. Methods and Materials: At 7, 14, 21, 28, 35, 42, 49, 56, 63 and 70 days after birth, penile and testicular tissues of male rats were dissected out and fixed for histological study and plasma testosterone levels were determined using high resolution chromatography. Results: An increase in the number of penile follicles, primarily in the distal region of the penis, was observed from postnatal days 14 to 42, followed by a gradual decrease. Penile spines were absent from birth until the first growth peak, which was observed at 42 postnatal days. Both testicular weight and the area of seminiferous tubules showed gradual increases before achieving their highest values at 42 postnatal days. Similarly, a gradual increase in testosterone levels was detected from day 28, with a peak at 42 postnatal days. Conclusions: These data show a temporal association between the development of the penile spines and testicular tissue with gradual increases in testosterone levels. These results may contribute to a better understanding of the behavioral, hormonal and morphological changes underlying sexual maturation in male rats.
基金Supported by the Agencia Nacional de Producción Científica y Tecnológica(ANPCyT),No.ANR BIO 0032/10
文摘The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge stillpending in tissue engineering. The loss of hair follicles caused by injuries or pathologies such as alopecia not only affects the patients' psychological well-being, but also endangers certain inherent functions of the skin. It is then of great interest to find different strategies aiming to regenerate or neogenerate the hair follicle under conditions proper of an adult individual. Based upon current knowledge on the epithelial and dermal cells and their interactions during the embryonic hair generation and adult hair cycling, many researchers have tried to obtain mature hair follicles using different strategies and approaches depending on the causes of hair loss. This review summarizes current advances in the different experimental strategies to regenerate or neogenerate hair follicles, with emphasis on those involving neogenesis of hair follicles in adult individuals using isolated cells and tissue engineering. Most of these experiments were performed using rodent cells, particularly from embryonic or newborn origin. However, no successful strategy to generate human hair follicles from adult cells has yet been reported. This review identifies several issues that should be considered to achieve this objective. Perhaps the most important challenge is to provide threedimensional culture conditions mimicking the structure of living tissue. Improving culture conditions that allow the expansion of specific cells while protecting their inductive properties, as well as methods for selecting populations of epithelial stem cells, should give us the necessary tools to overcome the difficulties that constrain human hair follicle neogenesis. An analysis of patent trends shows that the number of patent applications aimed at hair follicle regeneration and neogenesis has been increasing during the last decade. This field is attractive not only to academic researchers but also to the companies that own almost half of the patents in this field.
文摘AIM:Overexpression of mucosal metalloproteinases(MMP) has been demonstrated recently in inflammatory bowel disease.Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases(TIMP).The aim of this study was to evaluate the effect of ulcerative colitis(UC)on MMP- 1 and TIMP-1 plasma concentrations,as two possible biomarkers of the disease activity. METHODS:MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16 patients with endoscopically confirmed active UC. RESULTS:Plasma concentrations of both MMP-1(13.7±0.2 ng/ml)and TIMP-1(799±140 ng/ml)were significantly elevated in UC patients in comparison to healthy controls (11.9±0.9 ng/ml and 220±7 ng/ml respectively).There was no correlation between TIMP-1 and MMP-1 concentrations (r=0.02).TIMP-1 levels revealed significant positive correlations with scored endoscopic degree of mucosal injury, disease activity index and clinical activity index values as well as C-reactive protein concentration.There was no correlation between MMP-1 and laboratory,clinical or endoscopic indices of the disease activity.CONCLUSION: These results confirm the role of both MMP- 1 and TIMP-1 in the pathogenesis of ulcerative colitis. However only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating association with clinical and endoscopic pictures.
文摘AIM:To deduce strategic guidelines of gastric mucosa associated lymphoid tissue lymphoma (MALTOMA) by evaluating the long-term outcome of patients in respect to various treatment modalities. METHODS:A total of 55 patients with MALTOMA from May 1992 to August 2002 were retrospectively reviewed. RESULTS:Complete remission was obtained in 24 (82.8%) of 29 patients treated with anti Helicobacter pylori (Hpylori) regimen only.The duration to reach complete remission was 12 months (85 percentile,2-33 months).Five patients showed complete remission with radiation therapy (26-86 months).Two of them were Hpyloritreatment failure cases. CONCLUSION:Hpylorieradication is an effective primary treatment option for low grade MALTOMA and radiation therapy could be considered in patients with no evidence of Hpyloriinfection or who do not respond to Hpylorieradication therapy 12 months after successful eradication.
基金supported by the Key Research and Development Program of Hunan Province(Grant Number 2021DK2003)the National Natural Science Foundation of China(Grant Number 81891000)+1 种基金Fundamental Research Funds of the Central Universities(Grant Number 521119200010)Strategic Priority Research Program of the Chinese Academy of Sciences(Grant Numbers XDA16040601,XDA16040704).
文摘Transplantation of adult spinal cord tissue(aSCT)is a promising treatment for spinal cord injury(SCI)basing on various types of neural cells and matrix components inside aSCT.However,long-term systemic administration of immunosuppressors(e.g.tacrolimus,TAC)is required for the survival of allogeneic tissue,which often associated with severe side effects such as infection,liver damageand renal failure.In this study,a triglycerol monostearate(TGM)-based TAC delivery system(e.g.TAC@TGM)with high drug loading concentration was developed,which possessed injectable properties as well as sustainable and immune-responsive drug release behaviors.In complete transected SCI model,locally injected TAC@TGM could reduce the infiltration of inflammation cells,enhance the survival of transplanted aSCT(e.g.Tuj-1^(+)and NF^(+)neurons)and promote the recovery of locomotor function.Moreover,controlled release of TAC by TAC@TGM attenuated side effects of TAC on liver and kidneys compared with traditional systemic administration.More importantly,the developed TAC@TGM system provided a facile single dose of long-term immunosuppressive effect not just for aSCT transplantation,but also for other tissue/organ and cell transplantations.
基金supported by the National Natural Science Foundation of China(Key Program),No.30430310(to SJL)the State Key Laboratories Development Program of China,No.SKLP-K201401(to SJL)
文摘Whether endogenous neurogenesis occurs in the adult cortex remains controversial.An increasing number of reports suggest that doublecortin(DCX)-positive neurogenesis persists in the adult primate cortex,attracting enormous attention worldwide.In this study,different DCX antibodies were used together with NeuN antibodies in immunohistochemistry and western blot assays using adjacent cortical sections from adult monkeys.Antibody adsorption,antigen binding,primary antibody omission and antibody-free experiments were used to assess specificity of the signals.We found either strong fluorescent signals,medium-weak intensity signals in some cells,weak signals in a few perikarya or near complete lack of labeling in adjacent cortical sections incubated with the various DCX antibodies.The putative DCX-positive cells in the cortex were also positive for NeuN,a specific marker of mature neurons.However,further experiments showed that most of these signals were either the result of antibody cross reactivity,the non-specificity of secondary antibodies or tissue autofluorescence.No confirmed DCX-positive cells were detected in the adult macaque cortex by immunofluorescence.Our findings show that DCX-positive neurogenesis does not occur in the cerebral cortex of adult primates,and that false-positive signals(artefacts)are caused by antibody cross reactivity and autofluorescence.The experimental protocols were approved by the Institutional Animal Care and Use Committee of the Institute of Neuroscience,Beijing,China(approval No.IACUC-AMMS-2014-501).
文摘Several lines of evidence have established that proliferation and differentiation of neural stem cells into neurons within the sub-granular zone of the dentate gyrus,a process named adult hippocampal neurogenesis,contribute to maintaining healthy cognitive functions throughout life.The rate of adult hippocampal neurogenesis decreases with aging and a premature impairment of adult hippocampal neurogenesis has been observed both in animal models of Alzheimer’s disease and human post-mortem tissues.The causal relationship between adult hippocampal neurogenesis and the development of Alzheimer’s disease pathology has,however,not been established.This is partly due to the limitation of recapitulating the development of Alzheimer’s disease pathology in rodent models and the lack of translatable biomarkers to identify tractable targets in humans.While it is tempting to postulate that adult hippocampal neurogenesis could be leveraged to improve cognitive deficits in Alzheimer’s disease,consensual results have yet to be reached to fully explore this hypothesis.In this review,we discuss how the recent progress in identifying molecular pathways in adult hippocampal neurogenesis provides a good framework to initiate strategies for drug-based intervention in neurodegenerative diseases,especially in Alzheimer’s disease.We outline how discrepancies in pre-clinical disease models and experimental methodology have resulted in contradictory findings and propose a shift towards using more translatable approaches to model neurogenesis in Alzheimer’s disease.In particular,we review how exploring novel experimental paradigms including the use of human induced pluripotent stem cells and more complex cell culture systems,as well as standardizing protocols used to investigate evidence of neurogenesis in human tissues,could deliver deeper mechanistic insights that would kick-start innovative drug discovery efforts to promote healthy aging and cellular rejuvenation.
