The protective effect of a kind of purified polysaccharides extracted from Radix of Phytolacca acinosa Roxb,with a molecular weight of 10 KDa,on hematopoiesis was investigated.Average survival time of mice treated wit...The protective effect of a kind of purified polysaccharides extracted from Radix of Phytolacca acinosa Roxb,with a molecular weight of 10 KDa,on hematopoiesis was investigated.Average survival time of mice treated with cyclophosphamide (CY) 300 mg/kg once alone was 13.3 ± 7.2d(n=7) however,average survival time of mice treated with CY 300 mg/kg in com-bination with PAP-1 10 mg/kg,3 times/wk was 36.7± 16.4d(n=7,P<0.01).PAP-1,ip had benefi-cial effect on the recovery of the CY induced decrease of peripheral leukocyte number,and the nu-cleated bone marrow cell(BMC)number and[3￣H]TdR uptaken by BMC induced by rmGM-CSF in S180 bearing mice treated with CY,In mice,after the first ip treatment with CY 100 mg/kg on d7,the peripheral leukocyte number decreased on d9 and recovered to normal level about d13 to d15. Such recovery was accelerated by administrating PAP-1,10mg/kg, 3 times/wk.A significant in-crease of the activity to form colony in spleen(colony-forming unit in spleen, CFU-S_8, CUF-S12) in mice irradiated with 550 rad 6O￣Co γ-rays and an enhancement of proliferative response of BMC to rmGM-CSF treated with PAP-1,10mg/kg,3 times/wk, ip were observed.After PAP-1,10 mg/kg,ip once,a significant increase in the number of peripheral blood leukocytes and a rise in the serum of colony stimulating factor(CSF) were also confirmed.The types of CSF in serum were M-CSF and other hematopoietic growth factors,which were confirmed by using McAb of IL-3, GM-CSF and PcAb of M-CSF. These beneficial effects of PAP-1 on hematopoiesis may be related to its activityinducing CSFs and other hematopoietic growth factors and warrant further evaluation of its use-fulness.展开更多
miR-142 and miR-223 have been identified as hematopoietic specific microRNAs, miR-223 has crucial functions in myeloid lineage development. However, the function of miR-142 remains unclear. In this study, we found tha...miR-142 and miR-223 have been identified as hematopoietic specific microRNAs, miR-223 has crucial functions in myeloid lineage development. However, the function of miR-142 remains unclear. In this study, we found that both miR-142 and miR-223 attenuated the proliferation of hematopoietic cells, and that miR-223 up-regulated miR-142 expression through the LMO2-L/-S isoforms and CEBP-p. miR-223 negatively regulated both LMO2-L/-S isoforms and CEBP-β post-transcriptionally, while CEBP-βpositively regulated the LMO2-L/-S isoforms and both of the LMO2-L/-S isoforms negatively regulated miR-142. These results reveal a novel miR-223--CEBP-β-LMO2-- miR-142 regulatory pathway, which has pivotal functions in hematopoiesis.展开更多
Hematopoietic stem cells （HSCs） are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between ...Hematopoietic stem cells （HSCs） are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal （in which the ability to function as HSCs is retained） and initiation of hematopoietic differentiation. Multiple signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. Wnt signaling pathways play a crucial role during embryogenesis and deregulation of these pathways has been implicated in the formation of solid tumors. Wnt signaling also plays a role in the regulation of stem cells from multiple tissues, such as embryonic, epidermal, and intestinal stem cells. However, the function of Wnt signaling in HSC biology is still controversial. In this review, we will discuss the basic characteristics of the adult HSC and its regulatory microenvironment, the ＂niche＂, focusing on the regulation of the HSC and its niche by the Wnt signaling pathways.展开更多
Extramedullary hematopoiesis consists in the appearance and proliferation of hematopoietic cells outside the bone marrow. In this article, the authors describe a case of hepatosplenic hematopoiesis in a 9-year-old, ma...Extramedullary hematopoiesis consists in the appearance and proliferation of hematopoietic cells outside the bone marrow. In this article, the authors describe a case of hepatosplenic hematopoiesis in a 9-year-old, male Goeldi＇s monkey concurrent with a Calodium hepaticum infestation, belonging to the Lisbon＇s Zoo primate collection （Portugal）. Lesions were identified upon necropsy after euthanasia due to the presence of an apparently non-excisable, metastatic aortic mass. Histopathological analysis of samples taken was carried out and immunohistochemical staining was used to characterize the cellular population involved, confirming the diagnosis of extramedullary hematopoiesis. To the best of the authors＇ knowledge, this is the first report of hepatosplenic extramedullary hematopoiesis in a Goeldi＇s monkey.展开更多
RUNXI is absolutely required for definitive hematopoiesis, but the function of RUNXlb/c, two isoforms of human RUNX1, is unclear. We established inducible RUNXlb/c-overexpressing human embryonic stem cell （hESC） lin...RUNXI is absolutely required for definitive hematopoiesis, but the function of RUNXlb/c, two isoforms of human RUNX1, is unclear. We established inducible RUNXlb/c-overexpressing human embryonic stem cell （hESC） lines, in which RUNXlb/c overexpression prevented the emergence of CD34＋ cells from early stage, thereby drastically reducing the production of hematopoi- etic stem/prognnitor cells. Simultaneously, the expression of hematopoiesis-related factors was downregulated. However, such blockage effect disappeared from day 6 in hESC/AGM-S3 ceU co-cultures, proving that the blockage occurred before the generation of hemogenic endothelial cells. This blockage was partially rescued by RepSox, an inhibitor of the transforming growth factor （TGF）-β signaling pathway, indicating a close relationship between RUNX1b/c and TGF-β pathway. Our results suggest a unique inhibitory function of RUNX1b/c in the development of early hematopoiesis and may aid further understanding of its biological function in normal and diseased models.展开更多
Long non-coding RNAs(lncRNAs)are defined as a class of nonprotein-coding transcripts greater than 200 nucleotides in length,which have diverse functions in development and diseases including hematopoiesis.Recent advan...Long non-coding RNAs(lncRNAs)are defined as a class of nonprotein-coding transcripts greater than 200 nucleotides in length,which have diverse functions in development and diseases including hematopoiesis.Recent advances have revealed that lncRNAs regulate hematopoietic development at almost every stage,including differentiation of the myelocyte,lymphocyte,and erythrocyte.Abnormal regulation of the lncRNAs may block aspects of blood development,which can lead to different types of hematopoietic disorders.These findings highlight the role of lncRNAs as potential therapeutic tools in malignant hematopoiesis.In this review,we summarize recent progress in the study of functional lncRNAs associated with blood development,as well as dysregulated lncRNAs involved in diverse blood diseases by interacting with crucial susceptibility genes in different pathways.In addition,we discuss genome-wide studies on lncRNAs,which are helpful for genome screening and in-depth functional study of lncRNAs associated with blood development and disease.展开更多
Objective： To retrospectively analyze 95 cases of traumatic carotid cavernous fistula treated by endovascular embolization. Methods： From January 1994 to December 2008, 95 patients with traumatic carotid cavernous ...Objective： To retrospectively analyze 95 cases of traumatic carotid cavernous fistula treated by endovascular embolization. Methods： From January 1994 to December 2008, 95 patients with traumatic carotid cavernous fistula were treated in our hospital. All patients received selective cerebral angiography through femoral artery catheterization. Accordingly, 89 cases were treated by detachable balloon embolization, 5 by platinum microcoils and 1 by coveredstem, respectively. Results： In the study, 61 cases achieved successful balloon embolization at the first time. Fifty-six cases had multiple balloons due to the big fistula. Nine cases received balloon embolization twice. But among the 5 patients treated with platinum microcoils, one developed slight brainstem ischemia. After operation the patient had herniparesis and swallow difficulty, but gradually recovered 3 months later. No neurological deficits were observed in other cases. All the cases recovered. Eighty-five cases were followed up for 1-15 years and no recurrence was found. Conclusions： The endovascular embolization for traumatic carotid cavernous fistula is minimally invasive, safe, effective and reliable. The detachable balloon embolization is the first choice in the treatment of TCCF.展开更多
A decade ago mainstream molecular biologists regarded it impossible or biologically ill-motivated to understand the dynamics of complex biological phenomena, such as cancer genesis and progression, from a network pers...A decade ago mainstream molecular biologists regarded it impossible or biologically ill-motivated to understand the dynamics of complex biological phenomena, such as cancer genesis and progression, from a network perspective. Indeed, there are numerical difficulties even for those who were determined to explore along this direction. Undeterred, seven years ago a group of Chinese scientists started a program aiming to obtain quantitative connections between tumors and network dynamics. Many interesting results have been obtained. In this paper we wish to test such idea from a different angle: the connection between a normal biological process and the network dynamics. We have taken early myelopoiesis as our biological model. A standard roadmap for the cell-fate diversification during hematopoiesis has already been well established experimentally, yet little was known for its underpinning dynamical mechanisms. Compounding this difficulty there were additional experimental challenges, such as the seemingly conflicting hematopoietic roadmaps and the cell-fate inter-conversion events. With early myeloid cell-fate determination in mind, we constructed a core molecular endogenous network from well-documented gene regulation and signal transduction knowledge. Turning the network into a set of dynamical equations, we found computationally several structurally robust states. Those states nicely correspond to known cell phenotypes. We also found the states connecting those stable states.They reveal the developmental routes—how one stable state would most likely turn into another stable state. Such interconnected network among stable states enabled a natural organization of cell-fates into a multi-stable state landscape. Accordingly, both the myeloid cell phenotypes and the standard roadmap were explained mechanistically in a straightforward manner. Furthermore,recent challenging observations were also explained naturally. Moreover, the landscape visually enables a prediction of a pool of additional cell states and developmental routes, including the non-sequential and cross-branch transitions, which are testable by future experiments. In summary, the endogenous network dynamics provide an integrated quantitative framework to understand the heterogeneity and lineage commitment in myeloid progenitors.展开更多
文摘The protective effect of a kind of purified polysaccharides extracted from Radix of Phytolacca acinosa Roxb,with a molecular weight of 10 KDa,on hematopoiesis was investigated.Average survival time of mice treated with cyclophosphamide (CY) 300 mg/kg once alone was 13.3 ± 7.2d(n=7) however,average survival time of mice treated with CY 300 mg/kg in com-bination with PAP-1 10 mg/kg,3 times/wk was 36.7± 16.4d(n=7,P<0.01).PAP-1,ip had benefi-cial effect on the recovery of the CY induced decrease of peripheral leukocyte number,and the nu-cleated bone marrow cell(BMC)number and[3￣H]TdR uptaken by BMC induced by rmGM-CSF in S180 bearing mice treated with CY,In mice,after the first ip treatment with CY 100 mg/kg on d7,the peripheral leukocyte number decreased on d9 and recovered to normal level about d13 to d15. Such recovery was accelerated by administrating PAP-1,10mg/kg, 3 times/wk.A significant in-crease of the activity to form colony in spleen(colony-forming unit in spleen, CFU-S_8, CUF-S12) in mice irradiated with 550 rad 6O￣Co γ-rays and an enhancement of proliferative response of BMC to rmGM-CSF treated with PAP-1,10mg/kg,3 times/wk, ip were observed.After PAP-1,10 mg/kg,ip once,a significant increase in the number of peripheral blood leukocytes and a rise in the serum of colony stimulating factor(CSF) were also confirmed.The types of CSF in serum were M-CSF and other hematopoietic growth factors,which were confirmed by using McAb of IL-3, GM-CSF and PcAb of M-CSF. These beneficial effects of PAP-1 on hematopoiesis may be related to its activityinducing CSFs and other hematopoietic growth factors and warrant further evaluation of its use-fulness.
基金This work was supported by the National Natural Science Foundation of China （Grant No. 30771054）.
文摘miR-142 and miR-223 have been identified as hematopoietic specific microRNAs, miR-223 has crucial functions in myeloid lineage development. However, the function of miR-142 remains unclear. In this study, we found that both miR-142 and miR-223 attenuated the proliferation of hematopoietic cells, and that miR-223 up-regulated miR-142 expression through the LMO2-L/-S isoforms and CEBP-p. miR-223 negatively regulated both LMO2-L/-S isoforms and CEBP-β post-transcriptionally, while CEBP-βpositively regulated the LMO2-L/-S isoforms and both of the LMO2-L/-S isoforms negatively regulated miR-142. These results reveal a novel miR-223--CEBP-β-LMO2-- miR-142 regulatory pathway, which has pivotal functions in hematopoiesis.
文摘Hematopoietic stem cells （HSCs） are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal （in which the ability to function as HSCs is retained） and initiation of hematopoietic differentiation. Multiple signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. Wnt signaling pathways play a crucial role during embryogenesis and deregulation of these pathways has been implicated in the formation of solid tumors. Wnt signaling also plays a role in the regulation of stem cells from multiple tissues, such as embryonic, epidermal, and intestinal stem cells. However, the function of Wnt signaling in HSC biology is still controversial. In this review, we will discuss the basic characteristics of the adult HSC and its regulatory microenvironment, the ＂niche＂, focusing on the regulation of the HSC and its niche by the Wnt signaling pathways.
文摘Extramedullary hematopoiesis consists in the appearance and proliferation of hematopoietic cells outside the bone marrow. In this article, the authors describe a case of hepatosplenic hematopoiesis in a 9-year-old, male Goeldi＇s monkey concurrent with a Calodium hepaticum infestation, belonging to the Lisbon＇s Zoo primate collection （Portugal）. Lesions were identified upon necropsy after euthanasia due to the presence of an apparently non-excisable, metastatic aortic mass. Histopathological analysis of samples taken was carried out and immunohistochemical staining was used to characterize the cellular population involved, confirming the diagnosis of extramedullary hematopoiesis. To the best of the authors＇ knowledge, this is the first report of hepatosplenic extramedullary hematopoiesis in a Goeldi＇s monkey.
基金This work was supported by the National Program on Key Basic Research Project of China （973 Program 2015CB964902）, the National Natural Science Foundation of China （NSFC H81170466 and H81370597）, and the CAMS Initiatives for Innovative Medicine （2016-12M-1-018） awarded to F.M.
文摘RUNXI is absolutely required for definitive hematopoiesis, but the function of RUNXlb/c, two isoforms of human RUNX1, is unclear. We established inducible RUNXlb/c-overexpressing human embryonic stem cell （hESC） lines, in which RUNXlb/c overexpression prevented the emergence of CD34＋ cells from early stage, thereby drastically reducing the production of hematopoi- etic stem/prognnitor cells. Simultaneously, the expression of hematopoiesis-related factors was downregulated. However, such blockage effect disappeared from day 6 in hESC/AGM-S3 ceU co-cultures, proving that the blockage occurred before the generation of hemogenic endothelial cells. This blockage was partially rescued by RepSox, an inhibitor of the transforming growth factor （TGF）-β signaling pathway, indicating a close relationship between RUNX1b/c and TGF-β pathway. Our results suggest a unique inhibitory function of RUNX1b/c in the development of early hematopoiesis and may aid further understanding of its biological function in normal and diseased models.
基金supported by the National Basic Research Program of China(2011CB8113015,2011CBA0110)National Natural Science Foundation of China(81270629)
文摘Long non-coding RNAs(lncRNAs)are defined as a class of nonprotein-coding transcripts greater than 200 nucleotides in length,which have diverse functions in development and diseases including hematopoiesis.Recent advances have revealed that lncRNAs regulate hematopoietic development at almost every stage,including differentiation of the myelocyte,lymphocyte,and erythrocyte.Abnormal regulation of the lncRNAs may block aspects of blood development,which can lead to different types of hematopoietic disorders.These findings highlight the role of lncRNAs as potential therapeutic tools in malignant hematopoiesis.In this review,we summarize recent progress in the study of functional lncRNAs associated with blood development,as well as dysregulated lncRNAs involved in diverse blood diseases by interacting with crucial susceptibility genes in different pathways.In addition,we discuss genome-wide studies on lncRNAs,which are helpful for genome screening and in-depth functional study of lncRNAs associated with blood development and disease.
文摘Objective： To retrospectively analyze 95 cases of traumatic carotid cavernous fistula treated by endovascular embolization. Methods： From January 1994 to December 2008, 95 patients with traumatic carotid cavernous fistula were treated in our hospital. All patients received selective cerebral angiography through femoral artery catheterization. Accordingly, 89 cases were treated by detachable balloon embolization, 5 by platinum microcoils and 1 by coveredstem, respectively. Results： In the study, 61 cases achieved successful balloon embolization at the first time. Fifty-six cases had multiple balloons due to the big fistula. Nine cases received balloon embolization twice. But among the 5 patients treated with platinum microcoils, one developed slight brainstem ischemia. After operation the patient had herniparesis and swallow difficulty, but gradually recovered 3 months later. No neurological deficits were observed in other cases. All the cases recovered. Eighty-five cases were followed up for 1-15 years and no recurrence was found. Conclusions： The endovascular embolization for traumatic carotid cavernous fistula is minimally invasive, safe, effective and reliable. The detachable balloon embolization is the first choice in the treatment of TCCF.
基金supported by the National Basic Research Program of China(2010CB529200)National Natural Science Foundation of China(91029738)
文摘A decade ago mainstream molecular biologists regarded it impossible or biologically ill-motivated to understand the dynamics of complex biological phenomena, such as cancer genesis and progression, from a network perspective. Indeed, there are numerical difficulties even for those who were determined to explore along this direction. Undeterred, seven years ago a group of Chinese scientists started a program aiming to obtain quantitative connections between tumors and network dynamics. Many interesting results have been obtained. In this paper we wish to test such idea from a different angle: the connection between a normal biological process and the network dynamics. We have taken early myelopoiesis as our biological model. A standard roadmap for the cell-fate diversification during hematopoiesis has already been well established experimentally, yet little was known for its underpinning dynamical mechanisms. Compounding this difficulty there were additional experimental challenges, such as the seemingly conflicting hematopoietic roadmaps and the cell-fate inter-conversion events. With early myeloid cell-fate determination in mind, we constructed a core molecular endogenous network from well-documented gene regulation and signal transduction knowledge. Turning the network into a set of dynamical equations, we found computationally several structurally robust states. Those states nicely correspond to known cell phenotypes. We also found the states connecting those stable states.They reveal the developmental routes—how one stable state would most likely turn into another stable state. Such interconnected network among stable states enabled a natural organization of cell-fates into a multi-stable state landscape. Accordingly, both the myeloid cell phenotypes and the standard roadmap were explained mechanistically in a straightforward manner. Furthermore,recent challenging observations were also explained naturally. Moreover, the landscape visually enables a prediction of a pool of additional cell states and developmental routes, including the non-sequential and cross-branch transitions, which are testable by future experiments. In summary, the endogenous network dynamics provide an integrated quantitative framework to understand the heterogeneity and lineage commitment in myeloid progenitors.
