Clonal hematopoiesis(CH)is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoi...Clonal hematopoiesis(CH)is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoietic cells carrying markers of the clonal mutation.Genes integral to critical cellular processes such as epigenetic regulation,DNA damage response,and inflammation frequently carry these mutations.Clonal hematopoiesis becomes increasingly prevalent with age and is associated with an increased risk of hematological tumors and some nonhematological conditions.Recent insights have revealed that the mutations driving CH are not only implicated in hematologic neoplasms but also possess the potential to influence cardiovascular pathogenesis.Here,we reviewed up-to-date findings about the roles of CH in cardiovascular diseases and tumors and explored the clinical significance of CH,as well as look forward to future related studies,so as to provide valuable references for future research and clinical practice.展开更多
目的观察参附汤联合同种异体NK细胞(alloreactive naturall killer cells,alloNK)对移植小鼠术后外周血象、骨髓有核细胞计数(nucleated cell counts,NCC)、骨髓造血组织容量(hematopoietic volume of bone marrow,HV)及骨髓病理的影响...目的观察参附汤联合同种异体NK细胞(alloreactive naturall killer cells,alloNK)对移植小鼠术后外周血象、骨髓有核细胞计数(nucleated cell counts,NCC)、骨髓造血组织容量(hematopoietic volume of bone marrow,HV)及骨髓病理的影响。方法BALB/c小鼠经过13.0 Gy剂量的全身照射(total body irradiation,TBI),4 h内经尾静脉注入供鼠骨髓单个核细胞(mononuclear cells,MNCs)8×10^(6)/kg,制作移植小鼠模型,然后随机分为模型组、alloNK组、参附汤组、参附+alloNK组4组,分别给予生理盐水、单用alloNK、单用参附汤和参附汤联合alloNK灌胃,观察治疗前及治疗后第7、14、30天,小鼠外周血象、骨髓NCC、HV及组织病理的变化。结果移植前及移植后第7天各组小鼠外周血象、骨髓NCC、HV无显著性差异。移植后第14天,模型组小鼠白细胞仍处于粒缺期,而单纯alloNK组和参附组小鼠的白细胞均有所上升,参附联合alloNK组小鼠上升幅度高于其他组。移植后第30天,模型组、alloNK组及参附组小鼠白细胞、骨髓NCC、HV均较前回升,但仍低于移植前水平,而参附联合alloNK组小鼠的白细胞、骨髓NCC、HV恢复至移植前水平,与其他组相比差异显著。结论参附汤可保护骨髓免受放射损伤、促进造血功能恢复、缩短粒细胞缺乏时间,而联合alloNK细胞促进造血功能恢复的作用更明显。展开更多
Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed ...Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.展开更多
Introduction: Sickle cell disease and thalassemia are the most frequent hemoglobinopathies. During their evolution, they present certain complications, among which are two neurosurgical emergencies, namely spontaneous...Introduction: Sickle cell disease and thalassemia are the most frequent hemoglobinopathies. During their evolution, they present certain complications, among which are two neurosurgical emergencies, namely spontaneous cranial epidural hematoma and non traumatic radiculo-medullary compression, with some particularities for each. Method: In order to highlight these particularities, we compared the characteristics of these two complications, from a number of publications reported between 2000 and 2021. Results: Sickle cell disease was complicated by spontaneous cranial epidural hematoma. Forty-two cases were reported, the mean age was 14.7 years (2 - 21 years) and the sex ratio was 6.4. The clinical presentation combined, in a non-traumatic context, signs of intracranial hypertension with those of neurological focalization. Neuroimaging showed epidural-type collection, often frontal and parietal in location. The incriminating mechanisms were ischemia, hemorrhage and extra medullary hematopoiesis. The treatment was surgical. Non traumatic radiculo-medullary was the complication of thalassemia. Of the 77 cases reported, the mean age was 27.5 years (9 - 66 years) and the sex ratio was 4.1. The lesions were epidural with a clear thoracic predominance and resulted from extra marrow hematopoiesis. Treatment included: hypertransfusion, radiotherapy, hydroxyurea and surgery. Vital and functional prognosis were globally satisfactory when the management was rapid. Conclusion: Cranial and spinal epidural lesions, respective complications of sickle cell disease and thalassemia, result from similar mechanisms. Their prognosis depends on the rapidity of management. .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
Intraperitoneal injection of recombinant mouse IL-3 in normal mice for 6 days did not induce any significant changes in leukocyte and neutrophil counts. In comparison with saline controls, IL-3-treated mice experience...Intraperitoneal injection of recombinant mouse IL-3 in normal mice for 6 days did not induce any significant changes in leukocyte and neutrophil counts. In comparison with saline controls, IL-3-treated mice experienced a 1.7-fold increase of bone marrow nucleated cells and 3.6-fold increase of CFU-GM colonies. Tritium thymidine incorporation of bone marrow cells significantly increased in IL-3-treated mice as compared with that in normal saline-treated mice. These results suggested that IL-3 expanded the number of granulocyte-macrophage progenitor cells but not the peripheral neutrophils. We examined the effect of IL-3 on hematopoietic reconstitution in a cyclophosphamide-treated mouse model. We found that the absolute neutrophil number of mice treated with IL-3 increased significantly on day 6 post injection when compared with the control mice (6.2± 4.1×109 / L versus 0.98± 1.4 × 109/ L, P【0.01) . The results demonstrated that IL-3 stimulated an early recovery of neutrophils after展开更多
基金Supported by a grant from the National Natural Science Founda-tion of China(no.82200319).
文摘Clonal hematopoiesis(CH)is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoietic cells carrying markers of the clonal mutation.Genes integral to critical cellular processes such as epigenetic regulation,DNA damage response,and inflammation frequently carry these mutations.Clonal hematopoiesis becomes increasingly prevalent with age and is associated with an increased risk of hematological tumors and some nonhematological conditions.Recent insights have revealed that the mutations driving CH are not only implicated in hematologic neoplasms but also possess the potential to influence cardiovascular pathogenesis.Here,we reviewed up-to-date findings about the roles of CH in cardiovascular diseases and tumors and explored the clinical significance of CH,as well as look forward to future related studies,so as to provide valuable references for future research and clinical practice.
文摘目的观察参附汤联合同种异体NK细胞(alloreactive naturall killer cells,alloNK)对移植小鼠术后外周血象、骨髓有核细胞计数(nucleated cell counts,NCC)、骨髓造血组织容量(hematopoietic volume of bone marrow,HV)及骨髓病理的影响。方法BALB/c小鼠经过13.0 Gy剂量的全身照射(total body irradiation,TBI),4 h内经尾静脉注入供鼠骨髓单个核细胞(mononuclear cells,MNCs)8×10^(6)/kg,制作移植小鼠模型,然后随机分为模型组、alloNK组、参附汤组、参附+alloNK组4组,分别给予生理盐水、单用alloNK、单用参附汤和参附汤联合alloNK灌胃,观察治疗前及治疗后第7、14、30天,小鼠外周血象、骨髓NCC、HV及组织病理的变化。结果移植前及移植后第7天各组小鼠外周血象、骨髓NCC、HV无显著性差异。移植后第14天,模型组小鼠白细胞仍处于粒缺期,而单纯alloNK组和参附组小鼠的白细胞均有所上升,参附联合alloNK组小鼠上升幅度高于其他组。移植后第30天,模型组、alloNK组及参附组小鼠白细胞、骨髓NCC、HV均较前回升,但仍低于移植前水平,而参附联合alloNK组小鼠的白细胞、骨髓NCC、HV恢复至移植前水平,与其他组相比差异显著。结论参附汤可保护骨髓免受放射损伤、促进造血功能恢复、缩短粒细胞缺乏时间,而联合alloNK细胞促进造血功能恢复的作用更明显。
基金supported by the Postdoctoral Research Funds of Hebei Medical University(30705010016-3759)Natural Science Foundation of China(32272328)+4 种基金Natural Science Foundation of Hebei Province(B2022321001)National Key Research Project of Hebei Province(20375502D)Postdoctoral Research Project of Hebei Province(B2022003031)Science and Technology Research Program of Hebei Provincial Colleges(QN2023229)Hebei Provincial Key Laboratory of Nutrition and Health(2023YDYY-KF05)。
文摘Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.
文摘Introduction: Sickle cell disease and thalassemia are the most frequent hemoglobinopathies. During their evolution, they present certain complications, among which are two neurosurgical emergencies, namely spontaneous cranial epidural hematoma and non traumatic radiculo-medullary compression, with some particularities for each. Method: In order to highlight these particularities, we compared the characteristics of these two complications, from a number of publications reported between 2000 and 2021. Results: Sickle cell disease was complicated by spontaneous cranial epidural hematoma. Forty-two cases were reported, the mean age was 14.7 years (2 - 21 years) and the sex ratio was 6.4. The clinical presentation combined, in a non-traumatic context, signs of intracranial hypertension with those of neurological focalization. Neuroimaging showed epidural-type collection, often frontal and parietal in location. The incriminating mechanisms were ischemia, hemorrhage and extra medullary hematopoiesis. The treatment was surgical. Non traumatic radiculo-medullary was the complication of thalassemia. Of the 77 cases reported, the mean age was 27.5 years (9 - 66 years) and the sex ratio was 4.1. The lesions were epidural with a clear thoracic predominance and resulted from extra marrow hematopoiesis. Treatment included: hypertransfusion, radiotherapy, hydroxyurea and surgery. Vital and functional prognosis were globally satisfactory when the management was rapid. Conclusion: Cranial and spinal epidural lesions, respective complications of sickle cell disease and thalassemia, result from similar mechanisms. Their prognosis depends on the rapidity of management. .
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Intraperitoneal injection of recombinant mouse IL-3 in normal mice for 6 days did not induce any significant changes in leukocyte and neutrophil counts. In comparison with saline controls, IL-3-treated mice experienced a 1.7-fold increase of bone marrow nucleated cells and 3.6-fold increase of CFU-GM colonies. Tritium thymidine incorporation of bone marrow cells significantly increased in IL-3-treated mice as compared with that in normal saline-treated mice. These results suggested that IL-3 expanded the number of granulocyte-macrophage progenitor cells but not the peripheral neutrophils. We examined the effect of IL-3 on hematopoietic reconstitution in a cyclophosphamide-treated mouse model. We found that the absolute neutrophil number of mice treated with IL-3 increased significantly on day 6 post injection when compared with the control mice (6.2± 4.1×109 / L versus 0.98± 1.4 × 109/ L, P【0.01) . The results demonstrated that IL-3 stimulated an early recovery of neutrophils after
