Objective:To explore the effect and mechanism of Xuebijing injection (XBJ) on the hematopoietic homeostasis of bone marrow (BM) in septic mice. Methods:BM cells stimulated with XBJ were analyzed by inverted optical mi...Objective:To explore the effect and mechanism of Xuebijing injection (XBJ) on the hematopoietic homeostasis of bone marrow (BM) in septic mice. Methods:BM cells stimulated with XBJ were analyzed by inverted optical microscope and qPCR, to evaluate the effect of XBJ on differentiation function of BM cells in vitro. Lipopolysaccharide (LPS) 055:B5 at the dose of 20mg/kg was used to establish the sepsis model. To determine the hematopoietic stem cells homeostasis affected by LPS in mice, BM cells were isolated and analyzed by flow cytometry based on the immunophenotypic surface markers. 20ml/kg of XBJ was administered by tail vein once/day after peritoneal injection of LPS. All animals were sacrificed on the fifth day. The frequency of hematopoietic stem cells (HSC) and immune cells in mice were quantified by flow cytometry. The gene expression of transcription factors were detected by qPCR. Results:XBJ promoted myeloid differentiation of BM cells in vitro, which may be related to the mRNA expression of the transcription factors. The results in vivo showed the percentage of BM Lin-SCA-1+c-KIT+(LSK) cells, and Long-term HSCs (LT-HSC) were significantly increased in LPS group. But the percentage of multipotential progenitors (MPPs), granulocyte-monocyte progenitor (GMP) and megakaryocytic-erythroid precursor (MEP) were significantly decreased in LPS group. Whereas, XBJ improved the immune function in sepsis mice by suppression the LSK expansion in vivo. The result of qPCR showed that LSD1 and PU.1 mRNA expression in XBJ group were significantly higher than LPS group and control group respectively. Conclusion:Xuebijing injection can improve immune function in sepsis mice by regulating hematopoietic homeostasis. Its mechanism may be related to the up-regulation of LSD1 and PU.1 gene expressions.展开更多
Though imaging-guided multimodal therapy has been demonstrated as an effective strategy to improve cancer diagnosis and therapy,challenge remains as to simplify the sophisticated synthesis procedure for the correspond...Though imaging-guided multimodal therapy has been demonstrated as an effective strategy to improve cancer diagnosis and therapy,challenge remains as to simplify the sophisticated synthesis procedure for the corresponding nanoagents.Herein,an insitu one-step reduction-encapsulated method has been reported,for the first time,to synthesize multicore-shell polydopaminecoated Ag nanoparticles(AgNPs@PDA)as a cancer theranostic agent,integrating amplified photoacoustic imaging,enhanced photothermal therapy,and photothermal promoted dual tumor microenvironment-coactivated chemodynamic therapy.The photoacoustic signal and the photothermal conversion efficiency of AgNPs@PDA nanosystem present a 6.6-and 4.2-fold enhancement compared to those of M-AgNPs-PDA(simply mixing PDA and AgNPs)derived from the increased interface heat transfer coefficient and the stronger near-infrared absorption.Importantly,AgNPs@PDA coactivated by dual tumor microenvironment(TME)enables controllable long-term release of hydroxyl radicals(·OH)and toxic Ag+,which can be further promoted by near-infrared light irradiation.Moreover,the high efficiency of AgNPs@PDA nanosystem with prominent photoacoustic imaging-guided synergistic photothermal-chemodynamic cancer treatment is also found in in vitro and in vivo studies.As a special mention,the formation mechanism of the one-step synthesized multicore-shell nanomaterials is systematically investigated.This work provides a much simplified one-step synthesis method for the construction of a versatile nanoplatform for cancer theranostics with high efficacy.展开更多
文摘Objective:To explore the effect and mechanism of Xuebijing injection (XBJ) on the hematopoietic homeostasis of bone marrow (BM) in septic mice. Methods:BM cells stimulated with XBJ were analyzed by inverted optical microscope and qPCR, to evaluate the effect of XBJ on differentiation function of BM cells in vitro. Lipopolysaccharide (LPS) 055:B5 at the dose of 20mg/kg was used to establish the sepsis model. To determine the hematopoietic stem cells homeostasis affected by LPS in mice, BM cells were isolated and analyzed by flow cytometry based on the immunophenotypic surface markers. 20ml/kg of XBJ was administered by tail vein once/day after peritoneal injection of LPS. All animals were sacrificed on the fifth day. The frequency of hematopoietic stem cells (HSC) and immune cells in mice were quantified by flow cytometry. The gene expression of transcription factors were detected by qPCR. Results:XBJ promoted myeloid differentiation of BM cells in vitro, which may be related to the mRNA expression of the transcription factors. The results in vivo showed the percentage of BM Lin-SCA-1+c-KIT+(LSK) cells, and Long-term HSCs (LT-HSC) were significantly increased in LPS group. But the percentage of multipotential progenitors (MPPs), granulocyte-monocyte progenitor (GMP) and megakaryocytic-erythroid precursor (MEP) were significantly decreased in LPS group. Whereas, XBJ improved the immune function in sepsis mice by suppression the LSK expansion in vivo. The result of qPCR showed that LSD1 and PU.1 mRNA expression in XBJ group were significantly higher than LPS group and control group respectively. Conclusion:Xuebijing injection can improve immune function in sepsis mice by regulating hematopoietic homeostasis. Its mechanism may be related to the up-regulation of LSD1 and PU.1 gene expressions.
基金the National Natural Science Foundation of China(Nos.21804036 and 21972039)the Science and Technology Project of Hunan Province(Nos.2020SK2014,2020RC3021,and 2020JJ3005).
文摘Though imaging-guided multimodal therapy has been demonstrated as an effective strategy to improve cancer diagnosis and therapy,challenge remains as to simplify the sophisticated synthesis procedure for the corresponding nanoagents.Herein,an insitu one-step reduction-encapsulated method has been reported,for the first time,to synthesize multicore-shell polydopaminecoated Ag nanoparticles(AgNPs@PDA)as a cancer theranostic agent,integrating amplified photoacoustic imaging,enhanced photothermal therapy,and photothermal promoted dual tumor microenvironment-coactivated chemodynamic therapy.The photoacoustic signal and the photothermal conversion efficiency of AgNPs@PDA nanosystem present a 6.6-and 4.2-fold enhancement compared to those of M-AgNPs-PDA(simply mixing PDA and AgNPs)derived from the increased interface heat transfer coefficient and the stronger near-infrared absorption.Importantly,AgNPs@PDA coactivated by dual tumor microenvironment(TME)enables controllable long-term release of hydroxyl radicals(·OH)and toxic Ag+,which can be further promoted by near-infrared light irradiation.Moreover,the high efficiency of AgNPs@PDA nanosystem with prominent photoacoustic imaging-guided synergistic photothermal-chemodynamic cancer treatment is also found in in vitro and in vivo studies.As a special mention,the formation mechanism of the one-step synthesized multicore-shell nanomaterials is systematically investigated.This work provides a much simplified one-step synthesis method for the construction of a versatile nanoplatform for cancer theranostics with high efficacy.
