Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells(USCs),which were noninvasively harvested from unlimited and easily available urine, as a "fac...Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells(USCs),which were noninvasively harvested from unlimited and easily available urine, as a "factory" to obtain extracellular vesicles(USCEVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition(with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1(CTHRC1) and osteoprotegerin(OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.展开更多
Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone form...Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout(omentin-1^-/-) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α(TNF-α), we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.展开更多
BACKGROUND Granulomatosis with polyangiitis is a necrotizing inflammation of small andmedium-sized vessels accompanied by formation of granuloma, involvement ofprimary granulomatous upper and lower respiratory tracts,...BACKGROUND Granulomatosis with polyangiitis is a necrotizing inflammation of small andmedium-sized vessels accompanied by formation of granuloma, involvement ofprimary granulomatous upper and lower respiratory tracts, glomerulonephritis,and vasculitis of small vessels.CASE SUMMARY Herein, we described a case of a 52-year-old man admitted with pulmonarynodules and high fever. Autoantibody workup revealed that the patient waspositive for c-anti-neutrophil cytoplasmic antibodies and proteinase-3 antineutrophilcytoplasmic antibodies. Pulmonary biopsies revealed a localgranulomatous structure. The patient received therapy with methylprednisoloneand intravenous immunoglobulin, and his clinical symptoms improved.CONCLUSION Intravenous immunoglobulin may act on granulomatosis with polyangiitis similarto immunosuppressants.展开更多
Obesity plays a crucial role in the development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanism for the pathogenesis of obesity-associated NAFLD remains largely obscure. Although the “...Obesity plays a crucial role in the development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanism for the pathogenesis of obesity-associated NAFLD remains largely obscure. Although the “multiple hit” theory provides a more accurate explanation of NAFLD pathogenesis, it still cannot fully explain precisely how obesity causes NAFLD. The liver is the key integrator of the body's energy needs, receiving input from multiple metabolically active organs. Thus, recent studies have advocated the “multiple crosstalk” hypothesis, highlighting that obesity-related hepatic steatosis may be the result of dysregulated “crosstalk” among multiple extra-hepatic organs and the liver in obesity. A wide variety of circulating endocrine hormones work together to orchestrate this “crosstalk”. Of note, with deepening understanding of the endocrine system, the perception of hormones has gradually risen from the narrow sense (i.e. traditional hormones) to the broad sense of hormones as organokines and exosomes. In this review, we focus on the perspective of organic endocrine hormones (organokines) and molecular endocrine hormones (exosomes), summarizing systematically how the two types of new hormones mediate the dialogue between extra-hepatic organs and liver in the pathogenesis of obesity-related NAFLD.展开更多
A novel supramolecular graft copolymer (SGP) composed of viologen-containing copolymer (P(DMA-co- diEV)) as the main chain and Np ended PNIPAM (Np-PNIPAm) as the grafts is prepared (DMA: N,N- dimethylacryami...A novel supramolecular graft copolymer (SGP) composed of viologen-containing copolymer (P(DMA-co- diEV)) as the main chain and Np ended PNIPAM (Np-PNIPAm) as the grafts is prepared (DMA: N,N- dimethylacryamide, diEV: ethylviologen dimer, Np: naphthalene, PNIPAM: poly(N-isopropylacrylamide)). The grafting is based on the triple complexation among a host of cucurbit[8]uril (CB[8]) and two guests of diEV and Np, which is characterized by UV-vis spectra and ITC. Temperature sensitive property of PNIPAm moiety allows SGP to self-assemble into non-covalently connected micelle (NCCM) at high temperature. The micelles are sensitive to reducing agents, for example Na2S203, which breaks the current inclusion complex pair and induces aggregation.展开更多
To the Editor:Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide.It is associated with visceral obesity and is considered to be the hepatic component of metabolic syndrome,as in...To the Editor:Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide.It is associated with visceral obesity and is considered to be the hepatic component of metabolic syndrome,as insulin resistance plays a major role in this process.展开更多
基金supported by the National Natural Science Foundation of China (Grant nos. 81522012, 81702237, 81670807, 81871822, 81801395, 81600699, 81701383, and 81802138)the Thousand Youth Talents Plan of China (Grant no. D1119003)+8 种基金the Medicine and Health Science and Technology Innovation Project of Chinese Academy of Medical Sciences (Grant no. 2018-I2M-HL-024)the High Level Talent Gathering Project of Hunan Province (Grant nos. 2017XK2039, and 2018RS3029)the Innovation Driven Project of Central South University (Grant nos. 2016CX028,2019CX014, and 2018CX029)the Youth Foundation of Xiangya Hospital in Central South University (Grant no. 2016Q10)the Hunan Provincial Innovation Foundation for Postgraduate (Grant no. CX2018B045)the Fundamental Research Funds for the Central Universities of Central South University (Grant nos. 2017zzts211 and 2018zzts895)the Hunan Province Natural Science Foundation of China (Grant no. 2017JJ3501)the China Postdoctoral Science Foundation (Grant nos. 2017M612596, 2017M622614, and 2018M632998)the Natural Science Foundation for Distinguished Yong Scholars of Guangdong Province (Grant no. 2016A030306051)
文摘Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells(USCs),which were noninvasively harvested from unlimited and easily available urine, as a "factory" to obtain extracellular vesicles(USCEVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition(with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1(CTHRC1) and osteoprotegerin(OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.
基金supported by the Excellent Young Scientist Foundation of the National Natural Science Foundation of China(Grant No.81522012)the National Natural Science Foundation of China(Grant No.81670807,81600699,81702237,81701383,81400858)+8 种基金the Thousand Youth Talents Plan of China(Grant No.D1119003)the Hunan Youth Talent Project(Grant No.2016RS3021)the Innovation Driven Project of Central South University(2016CX028)the Youth Foundation of Xiangya Hospital in Central South University(Grant No.2016Q10)the Fundamental Research Funds for the Central Universities of Central South University(Grant No.2017zzts032,2017zzts014)the Hunan Province Natural Science Foundation of China(Grant No.2017JJ3501)the China Postdoctoral Science Foundation(Grant No.2017M612596)the Natural Science Foundation for Distinguished Yong Scholars of Guangdong Province(2016A030306051)the National Basic Research Program of China(973 Program,Grant no.2014CB942903)
文摘Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout(omentin-1^-/-) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α(TNF-α), we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.
文摘BACKGROUND Granulomatosis with polyangiitis is a necrotizing inflammation of small andmedium-sized vessels accompanied by formation of granuloma, involvement ofprimary granulomatous upper and lower respiratory tracts, glomerulonephritis,and vasculitis of small vessels.CASE SUMMARY Herein, we described a case of a 52-year-old man admitted with pulmonarynodules and high fever. Autoantibody workup revealed that the patient waspositive for c-anti-neutrophil cytoplasmic antibodies and proteinase-3 antineutrophilcytoplasmic antibodies. Pulmonary biopsies revealed a localgranulomatous structure. The patient received therapy with methylprednisoloneand intravenous immunoglobulin, and his clinical symptoms improved.CONCLUSION Intravenous immunoglobulin may act on granulomatosis with polyangiitis similarto immunosuppressants.
基金supported by The National Natural Science Foundation of China(No.82070873,82000813)Major Special Projects of Hunan Provincial Health and Family Planning Commission(No.A2017011).
文摘Obesity plays a crucial role in the development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanism for the pathogenesis of obesity-associated NAFLD remains largely obscure. Although the “multiple hit” theory provides a more accurate explanation of NAFLD pathogenesis, it still cannot fully explain precisely how obesity causes NAFLD. The liver is the key integrator of the body's energy needs, receiving input from multiple metabolically active organs. Thus, recent studies have advocated the “multiple crosstalk” hypothesis, highlighting that obesity-related hepatic steatosis may be the result of dysregulated “crosstalk” among multiple extra-hepatic organs and the liver in obesity. A wide variety of circulating endocrine hormones work together to orchestrate this “crosstalk”. Of note, with deepening understanding of the endocrine system, the perception of hormones has gradually risen from the narrow sense (i.e. traditional hormones) to the broad sense of hormones as organokines and exosomes. In this review, we focus on the perspective of organic endocrine hormones (organokines) and molecular endocrine hormones (exosomes), summarizing systematically how the two types of new hormones mediate the dialogue between extra-hepatic organs and liver in the pathogenesis of obesity-related NAFLD.
基金Ministry of Science and Technology of China(Nos. 2011CB932503 and 2009CB930402)National Natural Science Foundation of China(No.91227203) are acknowledged for their financial support
文摘A novel supramolecular graft copolymer (SGP) composed of viologen-containing copolymer (P(DMA-co- diEV)) as the main chain and Np ended PNIPAM (Np-PNIPAm) as the grafts is prepared (DMA: N,N- dimethylacryamide, diEV: ethylviologen dimer, Np: naphthalene, PNIPAM: poly(N-isopropylacrylamide)). The grafting is based on the triple complexation among a host of cucurbit[8]uril (CB[8]) and two guests of diEV and Np, which is characterized by UV-vis spectra and ITC. Temperature sensitive property of PNIPAm moiety allows SGP to self-assemble into non-covalently connected micelle (NCCM) at high temperature. The micelles are sensitive to reducing agents, for example Na2S203, which breaks the current inclusion complex pair and induces aggregation.
基金grants from the National Natural Science Foundation of China(No.81870595)Major Special Projects of Hunan Provincial Health and Family Planning Commission(No.A2017011).
文摘To the Editor:Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide.It is associated with visceral obesity and is considered to be the hepatic component of metabolic syndrome,as insulin resistance plays a major role in this process.