Severe pneumonia is one of the most serious infectious diseases.Delayed intervention may lead to pulmonary fibrosis,which greatly threatens people’s life and health.Blood stasis syndrome is an important underlying sy...Severe pneumonia is one of the most serious infectious diseases.Delayed intervention may lead to pulmonary fibrosis,which greatly threatens people’s life and health.Blood stasis syndrome is an important underlying syndrome throughout the evolution of severe pneumonia-pulmonary fibrosis.Xuebijing injection(XBJ)was developed under the theoretical system of“Three syndromes and three methods”,demonstrating a good efficacy in treating severe pneumonia and pulmonary fibrosis due to its effect of removing blood stasis and dispersing toxins.Previous studies have shown that XBJ can protect vascular endothelial function,improve coagulation function and regulate immunity by inhibiting inflammatory.Hence,the research hypothesis is put forward that XBJ treats blood stasis syndrome by removing blood stasis and dredging blood vessels,to inhibit the disease progress of severe pneumonia to pulmonary fibrosis.Further researches are need to confirm the function and explore the mechanism of XBJ.展开更多
Objective: To investigate the effects of Xuebijing Injection(血必净注射液, XBJ) on survival rate and pulmonary vasopermeability in a rat model of severe scald injury. Methods: Rats were divided into two experiments: e...Objective: To investigate the effects of Xuebijing Injection(血必净注射液, XBJ) on survival rate and pulmonary vasopermeability in a rat model of severe scald injury. Methods: Rats were divided into two experiments: experiment 1 was monitored for 12 h post-injury for survival analysis after severe burns; in experiment 2, rats were killed for determination of pulmonary vascular permeability and pro-inflammatory mediators. In both experiments, rats were subject to third-degree 50% total body surface area(TBSA) burns or sham injury followed by XBJ or normal saline(NS) treatment. In addition, rat pulmonary microvascular endothelium cells(PMECs) were pretreated with either XBJ or phosphate buffer saline(PBS), and then subjected to sham serum or scald serum stimulation for 2 or 6 h, followed by transwell examination for the permeability of PMECs. Meanwhile, pro-inflammatory mediators in PMECs culture supernatant were also investigated. Results: The average survival time in the scald+XBJ group was 582.1±21.2 min, which was significantly longer than that in the scald + NS group(345.8±25.4 min, P<0.01). Plasma levels of tumor necrosis factor-alpha(TNF-α), E-selectin, interleukin-6(IL-6), vascular permeability and water content of lung tissues were significantly increased in animals after severe burns(P<0.01). However, administration of XBJ significantly decreased these levels in plasma and lung tissue. In in vitro cell experiments, XBJ markedly attenuated permeability in PMECs monolayer and reduced the levels of TNF-α, IL-6 and soluble E-selectin after stimulation with scald serum(P<0.01). Conclusions: XBJ increases early survival rate by alleviating pulmonary vasopermeability and inhibiting pro-inflammatory mediators in rats subjected to lethal scald injury. XBJ may be a potent drug in treatment of severe burns.展开更多
Objective:To observe the in vivo effects of oxysophoridine on hepatocellular carcinoma in mice and to study the related mechanisms.Methods:C57BL mice were inoculated with mouse hepatoma H22 cells subcutaneously,then d...Objective:To observe the in vivo effects of oxysophoridine on hepatocellular carcinoma in mice and to study the related mechanisms.Methods:C57BL mice were inoculated with mouse hepatoma H22 cells subcutaneously,then divided into 5 groups(14 per group),and treated with oxysophoridine(50,100,or 150 mg/kg) or cisplatin(4 mg/kg) for 10 days.Inhibitory rate of tumor,body weight gain,and influence indices on internal organs(liver,spleen and thymus) were evaluated.The differentially expressed genes between the oxysophoridine-treated group,and the control group were analyzed using cDNA microarray and quantitative real-time PCR(qRT-PCR) experiments.Results:Compared with the tumor weight of the control group(2.75±0.66 g),oxysophoridine significantly suppressed hepatocellular carcinoma growth in mice(P<0.01),with 0.82±0.36 g,0.57±0.22 g,and 1.22±0.67 g for the tumor weight in the low,moderate,and high dose treatment group, respectively.The moderate dose led to the highest inhibitory rate,79.3%.Observation of body weight gain and influence on three organs showed that compared with cisplatin,oxysophoridine produced fewer side effects in vivo.cDNA microarray and qRT-PCR showed that the most significant differentially expressed genes in the tumor samples of oxysophoridine-treated mice were mostly involved in regulating apoptosis,with the Tnfrsf11b (osteoprotegerin) gene being the most significantly affected.Conclusion:Oxysophoridine was a promising compound for developing drugs against hepatocellular carcinoma,and its anti-hepatoma effect was probably related to osteoprotegerin activation.展开更多
PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients,and their indications are expanding incessantly.Currently,most PD-1/PD-L1 agents are administered intravenously,which ma...PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients,and their indications are expanding incessantly.Currently,most PD-1/PD-L1 agents are administered intravenously,which may be uncomfortable for some cancer patients.Herein,we develop a novel oral-delivered small molecular,YPD-29B,which specifically targets human PD-L1.Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1,but did not inhibit any other immune checkpoints.Mechanistically,YPD-29B induced human PD-L1 dimerization and internalization,which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro.YDP-29B was modified as the YPD-30 prodrug to improve druggability.Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells,we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo.Taken together,our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.展开更多
基金the second batch of“Ten thousand plan”-National high level talents special support plan(W02020052).
文摘Severe pneumonia is one of the most serious infectious diseases.Delayed intervention may lead to pulmonary fibrosis,which greatly threatens people’s life and health.Blood stasis syndrome is an important underlying syndrome throughout the evolution of severe pneumonia-pulmonary fibrosis.Xuebijing injection(XBJ)was developed under the theoretical system of“Three syndromes and three methods”,demonstrating a good efficacy in treating severe pneumonia and pulmonary fibrosis due to its effect of removing blood stasis and dispersing toxins.Previous studies have shown that XBJ can protect vascular endothelial function,improve coagulation function and regulate immunity by inhibiting inflammatory.Hence,the research hypothesis is put forward that XBJ treats blood stasis syndrome by removing blood stasis and dredging blood vessels,to inhibit the disease progress of severe pneumonia to pulmonary fibrosis.Further researches are need to confirm the function and explore the mechanism of XBJ.
基金Supported by the National Natural Science Foundation of China(No.81471872)
文摘Objective: To investigate the effects of Xuebijing Injection(血必净注射液, XBJ) on survival rate and pulmonary vasopermeability in a rat model of severe scald injury. Methods: Rats were divided into two experiments: experiment 1 was monitored for 12 h post-injury for survival analysis after severe burns; in experiment 2, rats were killed for determination of pulmonary vascular permeability and pro-inflammatory mediators. In both experiments, rats were subject to third-degree 50% total body surface area(TBSA) burns or sham injury followed by XBJ or normal saline(NS) treatment. In addition, rat pulmonary microvascular endothelium cells(PMECs) were pretreated with either XBJ or phosphate buffer saline(PBS), and then subjected to sham serum or scald serum stimulation for 2 or 6 h, followed by transwell examination for the permeability of PMECs. Meanwhile, pro-inflammatory mediators in PMECs culture supernatant were also investigated. Results: The average survival time in the scald+XBJ group was 582.1±21.2 min, which was significantly longer than that in the scald + NS group(345.8±25.4 min, P<0.01). Plasma levels of tumor necrosis factor-alpha(TNF-α), E-selectin, interleukin-6(IL-6), vascular permeability and water content of lung tissues were significantly increased in animals after severe burns(P<0.01). However, administration of XBJ significantly decreased these levels in plasma and lung tissue. In in vitro cell experiments, XBJ markedly attenuated permeability in PMECs monolayer and reduced the levels of TNF-α, IL-6 and soluble E-selectin after stimulation with scald serum(P<0.01). Conclusions: XBJ increases early survival rate by alleviating pulmonary vasopermeability and inhibiting pro-inflammatory mediators in rats subjected to lethal scald injury. XBJ may be a potent drug in treatment of severe burns.
基金Supported by Tianjin Key Technology Research & Development Program(No.07ZCKFSH00200)
文摘Objective:To observe the in vivo effects of oxysophoridine on hepatocellular carcinoma in mice and to study the related mechanisms.Methods:C57BL mice were inoculated with mouse hepatoma H22 cells subcutaneously,then divided into 5 groups(14 per group),and treated with oxysophoridine(50,100,or 150 mg/kg) or cisplatin(4 mg/kg) for 10 days.Inhibitory rate of tumor,body weight gain,and influence indices on internal organs(liver,spleen and thymus) were evaluated.The differentially expressed genes between the oxysophoridine-treated group,and the control group were analyzed using cDNA microarray and quantitative real-time PCR(qRT-PCR) experiments.Results:Compared with the tumor weight of the control group(2.75±0.66 g),oxysophoridine significantly suppressed hepatocellular carcinoma growth in mice(P<0.01),with 0.82±0.36 g,0.57±0.22 g,and 1.22±0.67 g for the tumor weight in the low,moderate,and high dose treatment group, respectively.The moderate dose led to the highest inhibitory rate,79.3%.Observation of body weight gain and influence on three organs showed that compared with cisplatin,oxysophoridine produced fewer side effects in vivo.cDNA microarray and qRT-PCR showed that the most significant differentially expressed genes in the tumor samples of oxysophoridine-treated mice were mostly involved in regulating apoptosis,with the Tnfrsf11b (osteoprotegerin) gene being the most significantly affected.Conclusion:Oxysophoridine was a promising compound for developing drugs against hepatocellular carcinoma,and its anti-hepatoma effect was probably related to osteoprotegerin activation.
基金supported by the National Natural Science Foundation of China(No.81872923)the CAMS Innovation Fund for Medical Sciences(2016-I2M-3-008,China)The Drug Innovation Major Project(No.2018ZX09711001-003,China)。
文摘PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients,and their indications are expanding incessantly.Currently,most PD-1/PD-L1 agents are administered intravenously,which may be uncomfortable for some cancer patients.Herein,we develop a novel oral-delivered small molecular,YPD-29B,which specifically targets human PD-L1.Our data suggested that YPD-29B could potently and selectively block the interaction between PD-L1 and PD-1,but did not inhibit any other immune checkpoints.Mechanistically,YPD-29B induced human PD-L1 dimerization and internalization,which subsequently activated T lymphocytes and therefore overcomes immunity tolerance in vitro.YDP-29B was modified as the YPD-30 prodrug to improve druggability.Using humanized mice with human PD-1 xenografts of human PD-L1 knock-in mouse MC38 cancer cells,we demonstrated that YPD-30 exhibited significant antitumor activity and was well tolerated in vivo.Taken together,our results indicate that YPD-30 serves as a promising therapeutic candidate for anti-human PD-L1 cancer immunotherapy.