AIM: To study the immunological effects of physiological doses of purple sweet potato leaves(PSPL). METHODS: The randomized crossover study(two periods, each lasting for 2 wk) involved 16 healthy non-smoking adults of...AIM: To study the immunological effects of physiological doses of purple sweet potato leaves(PSPL). METHODS: The randomized crossover study(two periods, each lasting for 2 wk) involved 16 healthy non-smoking adults of normal weight. The 6-wk study consisted of a run-in(wk 1) PSPL diet(daily consumption of 200 g PSPL) or a control diet(low polyphenols, with the amount of carotenoids adjusted to the same level as that of PSPL)(wk 2-3), washout diet(wk 4), and switched diet(wk 5-6). Fasting blood was collected weekly in the morning. T-lymphocyte function was assessed via the proliferation and secretion of immunoreactive cytokines. Salivary IgA secretion and the specific cytotoxic activities of cytotoxic T lymphocytes and natural killer(NK) cells were determined. RESULTS: The plasma β-carotene level increased with time in both groups, while the plasma polyphenol level decreased in the control group, and no significant difference was detected between the two groups. Although plasma polyphenol levels did not significantly increase in the PSPL group at the end of the study, they were significantly elevated in urine. PSPL consumption produced a significant increase in proliferation responsiveness of peripheral blood mononuclear cells(PBMC) and their secretion of immunoreactive IL-2 and IL-4. As well, lytic activity in NK cells was elevated in a time-dependent fashion. Salivary IgA secretion significantly decreased in control group after 2 wk, and returned to baseline following dietary switch to PSPL. CONCLUSION: Consumption of PSPL modulates various immune functions including increased proliferation responsiveness of PBMC, secretion of cytokines IL-2 and IL-4, and the lytic activity of NK cells. The responsible determinants of PSPL remain to be elucidated, as does the biological significance of the present observations.展开更多
Heterotopic ossification(HO)is a debilitating condition characterized by the pathologic formation of ectopic bone.HO occurs commonly following orthopedic surgeries,burns,and neurologic injuries.While surgical excision...Heterotopic ossification(HO)is a debilitating condition characterized by the pathologic formation of ectopic bone.HO occurs commonly following orthopedic surgeries,burns,and neurologic injuries.While surgical excision may provide palliation,the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone.Based on these clinical observations,we set out to examine the role of vascular signaling in HO.Vascular endothelial growth factor A(VEGFA)has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis.Our findings,using a validated mouse model of HO,demonstrate that HO lesions are highly vascular,and that VEGFA is critical to ectopic bone formation,despite lacking a contribution of endothelial cells within the developing anlagen.展开更多
The outer coverings of the skeleton,which is also known as the periosteum,are arranged in concentric layers and act as a reservoir for tissue-specific bone progenitors.The cellular heterogeneity within this tissue dep...The outer coverings of the skeleton,which is also known as the periosteum,are arranged in concentric layers and act as a reservoir for tissue-specific bone progenitors.The cellular heterogeneity within this tissue depot is being increasingly recognized.Here,inducible PDGFRαreporter animals were found to mark a population of cells within the periosteum that act as a stem cell reservoir for periosteal appositional bone formation and fracture repair.During these processes,PDGFRαreporter^(+)progenitors give rise to Nestin+periosteal cells before becoming osteoblasts and osteocytes.The diphtheria toxin-mediated ablation of PDGFRαreporter^(+)cells led to deficits in cortical bone formation during homeostasis and a diminutive hard callus during fracture repair.After ossicle transplantation,both mouse PDGFRαreporter^(+)periosteal cells and human Pdgfrα+periosteal progenitors expand,ossify,and recruit marrow to a greater extent than their counterpart periosteal cells,whereas PDGFRαreporter^(−)periosteal cells exhibit a predisposition to chondrogenesis in vitro.Total RNA sequencing identified enrichment of the secreted factors Fermt3 and Ptpn6 within PDGFRαreporter^(+)periosteal cells,which partly underlie the osteoblastogenic features of this cell population.展开更多
Human osteogenic progenitors are not precisely defined,being primarily studied as heterogeneous multipotent cell populations and termed mesenchymal stem cells(MSCs).Notably,select human pericytes can develop into bone...Human osteogenic progenitors are not precisely defined,being primarily studied as heterogeneous multipotent cell populations and termed mesenchymal stem cells(MSCs).Notably,select human pericytes can develop into bone-forming osteoblasts.Here,we sought to define the differentiation potential of CD146 f human pericytes from skeletal and soft tissue sources,with the underlying goal of defining cell surface markers that typify an osteoblastogenic pericyte.CD146+CD31~CD45_pericytes were derived by fluorescence-activated cell sorting from human periosteum,adipose,or dermal tissue.Periosteal CD146+CD31—CD45 cells retained canonical features of pericytes/MSC.Periosteal pericytes demonstrated a striking tendency to undergo osteoblastogenesis in vitro and skeletogenesis in vivo,while soft tissue pericytes did not readily.Transcriptome analysis revealed higher CXCR4 signaling among periosteal pericytes in comparison to their soft tissue counterparts,and CXCR4 chemical inhibition abrogated ectopic ossification by periosteal pericytes.Conversely,enrichment of CXCR4+pericytes or stromal cells identified an osteoblastic/non-adipocytic precursor cell.In sum,human skeletal and soft tissue pericytes differ in their basal abilities to form bone.Diversity exists in soft tissue pericytes,however,and CXCR4+pericytes represent an osteoblastogenic,non-adipocytic cell precursor.Indeed,enrichment for CXCR4-expressing stromal cells is a potential new tactic for skeletal tissue engineering.展开更多
Chlorophylls are important antioxidants found in foods. We explored the mechanisms through which the a and b forms of chlorophyll and of pheophytin (the Mg-chelated form of chlorophyll) reduce oxidation: we used comet...Chlorophylls are important antioxidants found in foods. We explored the mechanisms through which the a and b forms of chlorophyll and of pheophytin (the Mg-chelated form of chlorophyll) reduce oxidation: we used comet assay to measure prevention of H2O2 DNA damage;we tested for quenching of 1,1-diphenyl-2-picrylhydrazyl (DPPH);we measured the ability to chelate Fe(II);and, we tested their ability to prevent formation of thiobarbituric acid reactive substances (TBARS) during Cu-mediated peroxidation of low density lipoprotein (LDL) in a chemical assay. All chlorophylls and pheophytins showed significant dose-dependent activity in the assays, with the pheophytins being the strongest antioxidants. Thus, these chemicals can prevent oxidative DNA damage and lipid peroxidation both by reducing reactive oxygen species, such as DPPH, and by chelation of metal ions, such as Fe(II), which can form reactive oxygen species.展开更多
基金Supported by the Grant From the Taipei Medical University, No. TMU91-Y05-A110, TMU92-AE1-B33
文摘AIM: To study the immunological effects of physiological doses of purple sweet potato leaves(PSPL). METHODS: The randomized crossover study(two periods, each lasting for 2 wk) involved 16 healthy non-smoking adults of normal weight. The 6-wk study consisted of a run-in(wk 1) PSPL diet(daily consumption of 200 g PSPL) or a control diet(low polyphenols, with the amount of carotenoids adjusted to the same level as that of PSPL)(wk 2-3), washout diet(wk 4), and switched diet(wk 5-6). Fasting blood was collected weekly in the morning. T-lymphocyte function was assessed via the proliferation and secretion of immunoreactive cytokines. Salivary IgA secretion and the specific cytotoxic activities of cytotoxic T lymphocytes and natural killer(NK) cells were determined. RESULTS: The plasma β-carotene level increased with time in both groups, while the plasma polyphenol level decreased in the control group, and no significant difference was detected between the two groups. Although plasma polyphenol levels did not significantly increase in the PSPL group at the end of the study, they were significantly elevated in urine. PSPL consumption produced a significant increase in proliferation responsiveness of peripheral blood mononuclear cells(PBMC) and their secretion of immunoreactive IL-2 and IL-4. As well, lytic activity in NK cells was elevated in a time-dependent fashion. Salivary IgA secretion significantly decreased in control group after 2 wk, and returned to baseline following dietary switch to PSPL. CONCLUSION: Consumption of PSPL modulates various immune functions including increased proliferation responsiveness of PBMC, secretion of cytokines IL-2 and IL-4, and the lytic activity of NK cells. The responsible determinants of PSPL remain to be elucidated, as does the biological significance of the present observations.
基金B.L.:Supported by funding from NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH1R01AR071379American College of Surgeons Clowes Award.D.M.S.:Supported by Plastic Surgery Foundation Resident Research Award+6 种基金M.S.:Supported by Plastic Surgery Foundation National Endowment AwardC.H.:Supported by Howard Hughes Medical Institute Medical Research FellowshipJ.L.:Supported by Vascular Surgery T32 5-T32-HL-076123–14A.W.J.:Supported by the NIH/NIAMS(R01 AR070773,K08 AR068316,S10OD016374)the Orthopedic Research and Education Foundation with funding provided by the Maryland Stem Cell Research Foundation,and the Musculoskeletal Transplant FoundationP.B.Y.:Supported by funding from NIH/NIAMS R01 AR057374 and NHLBI R01 HL131910Y.M.:Supported by funding from NIH/NIDCR R01 DE020843 and DE027662
文摘Heterotopic ossification(HO)is a debilitating condition characterized by the pathologic formation of ectopic bone.HO occurs commonly following orthopedic surgeries,burns,and neurologic injuries.While surgical excision may provide palliation,the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone.Based on these clinical observations,we set out to examine the role of vascular signaling in HO.Vascular endothelial growth factor A(VEGFA)has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis.Our findings,using a validated mouse model of HO,demonstrate that HO lesions are highly vascular,and that VEGFA is critical to ectopic bone formation,despite lacking a contribution of endothelial cells within the developing anlagen.
基金supported by the NIH/NIAMS (R01 AR070773)NIH/NIDCR (R21 DE027922)+3 种基金the Department of Defense (W81XWH-18-1-0121, W81XWH-18-1-0336, W81XWH-1810613, W81XWH-20-1-0302)the American Cancer Society (Research Scholar Grant, RSG-18-027-01-CSM)the Maryland Stem Cell Research FoundationMTF Biologics
文摘The outer coverings of the skeleton,which is also known as the periosteum,are arranged in concentric layers and act as a reservoir for tissue-specific bone progenitors.The cellular heterogeneity within this tissue depot is being increasingly recognized.Here,inducible PDGFRαreporter animals were found to mark a population of cells within the periosteum that act as a stem cell reservoir for periosteal appositional bone formation and fracture repair.During these processes,PDGFRαreporter^(+)progenitors give rise to Nestin+periosteal cells before becoming osteoblasts and osteocytes.The diphtheria toxin-mediated ablation of PDGFRαreporter^(+)cells led to deficits in cortical bone formation during homeostasis and a diminutive hard callus during fracture repair.After ossicle transplantation,both mouse PDGFRαreporter^(+)periosteal cells and human Pdgfrα+periosteal progenitors expand,ossify,and recruit marrow to a greater extent than their counterpart periosteal cells,whereas PDGFRαreporter^(−)periosteal cells exhibit a predisposition to chondrogenesis in vitro.Total RNA sequencing identified enrichment of the secreted factors Fermt3 and Ptpn6 within PDGFRαreporter^(+)periosteal cells,which partly underlie the osteoblastogenic features of this cell population.
基金A.WJ.was supported by the NIH/NIAMS(R01 AR070773,K08 AR068316),NIH/NIDCR(R21 DE027922)Department of Defense(W81XWH-18-1-0121,W81XWH-18-1-0336,W81XWH-18-10613)+1 种基金American Cancer Society(Research Scholar Grant,RSG-18-027-01-CSM)the Maryland Stem Cell Research Foundation,and the Musculoskeletal Transplant Foundation.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health,Department of Defense,or US Army.We thank the JHU microscopy facility,JHMI deep sequencing and microarray core facility,and Hao Zhang within the JHU Bloomberg Flow Cytometry and Immunology Core for their technical assistance.
文摘Human osteogenic progenitors are not precisely defined,being primarily studied as heterogeneous multipotent cell populations and termed mesenchymal stem cells(MSCs).Notably,select human pericytes can develop into bone-forming osteoblasts.Here,we sought to define the differentiation potential of CD146 f human pericytes from skeletal and soft tissue sources,with the underlying goal of defining cell surface markers that typify an osteoblastogenic pericyte.CD146+CD31~CD45_pericytes were derived by fluorescence-activated cell sorting from human periosteum,adipose,or dermal tissue.Periosteal CD146+CD31—CD45 cells retained canonical features of pericytes/MSC.Periosteal pericytes demonstrated a striking tendency to undergo osteoblastogenesis in vitro and skeletogenesis in vivo,while soft tissue pericytes did not readily.Transcriptome analysis revealed higher CXCR4 signaling among periosteal pericytes in comparison to their soft tissue counterparts,and CXCR4 chemical inhibition abrogated ectopic ossification by periosteal pericytes.Conversely,enrichment of CXCR4+pericytes or stromal cells identified an osteoblastic/non-adipocytic precursor cell.In sum,human skeletal and soft tissue pericytes differ in their basal abilities to form bone.Diversity exists in soft tissue pericytes,however,and CXCR4+pericytes represent an osteoblastogenic,non-adipocytic cell precursor.Indeed,enrichment for CXCR4-expressing stromal cells is a potential new tactic for skeletal tissue engineering.
文摘Chlorophylls are important antioxidants found in foods. We explored the mechanisms through which the a and b forms of chlorophyll and of pheophytin (the Mg-chelated form of chlorophyll) reduce oxidation: we used comet assay to measure prevention of H2O2 DNA damage;we tested for quenching of 1,1-diphenyl-2-picrylhydrazyl (DPPH);we measured the ability to chelate Fe(II);and, we tested their ability to prevent formation of thiobarbituric acid reactive substances (TBARS) during Cu-mediated peroxidation of low density lipoprotein (LDL) in a chemical assay. All chlorophylls and pheophytins showed significant dose-dependent activity in the assays, with the pheophytins being the strongest antioxidants. Thus, these chemicals can prevent oxidative DNA damage and lipid peroxidation both by reducing reactive oxygen species, such as DPPH, and by chelation of metal ions, such as Fe(II), which can form reactive oxygen species.