[Objectives]To study the immediate-release mechanism of dehydrotrametenolic acid and dehydroeburicoic acid in Poriae Cutis total triterpenoids tablets by liquid-solid compacts technique.[Methods] Taking dehydrotramete...[Objectives]To study the immediate-release mechanism of dehydrotrametenolic acid and dehydroeburicoic acid in Poriae Cutis total triterpenoids tablets by liquid-solid compacts technique.[Methods] Taking dehydrotrametenolic acid and dehydroeburicoic acid as indicators,differences in dissolution were compared between liquid-solid compressed tablets and crude drug of total triterpenoids in Poriae Cutis;crude drug,powder of liquid-solid compressed tablets and excipients of liquid-solid compressed tablets were characterized by differential scanning calorimetry( DSC).[Results]Liquid-solid compact technique could significantly improve dissolution rate of dehydrotrametenolic acid and dehydroeburicoic acid. The total dissolution rate of dehydrotrametenolic acid and dehydroeburicoic acid in Poriae Cutis total triterpenoids tablets was 92%,t50( time for 50% total dissolution rate) and t_D( time for 63. 2% total dissolution rate) were 11. 18 min and 22. 71 min; the total dissolution rate of dehydrotrametenolic acid and dehydroeburicoic acid in crude drug of total triterpenoids was 29%,and t50 and t_D were231. 06 min and 359. 23 min. DSC showed that there was no mutual interaction between excipients and total triterpenoids in Poriae Cutis; on the DSC curve for powder of liquid-solid compressed tablets,the absorption peak vanished completely,indicating that the drug exists in the amorphous form in the liquid-solid powder.[Conclusions] Liquid-solid compact technique can increase the dissolution rate of total triterpenoids in Poriae Cutis and allow rapid release of poorly water soluble drugs.展开更多
Chronic hypoxia affects stem cell function during tissue repair.Thus far,the hypoxia-associated impact on periosteal stem cells(PSCs),the main contributor to bone repair,remains unknown,and a tailored oxygen modulatio...Chronic hypoxia affects stem cell function during tissue repair.Thus far,the hypoxia-associated impact on periosteal stem cells(PSCs),the main contributor to bone repair,remains unknown,and a tailored oxygen modulation strategy for optimizing PSC function is lacking.Here,PSCs exhibit time-dependent proliferation and survival upon hypoxic exposure and a critical 48-h time-point is identified at which hypoxia transitions from beneficial to detrimental.Then,a photothermal-sensitive coaxial fiber-reinforced membrane containing oxygen and pravastatin is constructed to function as an intelligent oxygen supply system.Leveraging near-infrared light as an ON/OFF switch,the system noninvasively scales up oxygen release beginning 48 h post-implantation,counteracting prolonged hypoxia and mitigating its adverse effects on PSCs.The sustained release of pravastatin from the membrane accelerates early neovascularization both directly through its pro-angiogenic effect and indirectly by stimulating vascular endothelial growth factor secretion from PSCs,ensuring a continuous oxygen supply after exogenous oxygen exhaustion.Notably,pravastatin steers PSCs toward robust osteogenic differentiation and provides multifunctional bioactive cues for advanced bone regeneration in vivo.This time-scheduled approach to modulate oxygen supply noninvasively could be applicable beyond bone regeneration for hypoxia-related diseases and multi-tissue repair.展开更多
In previous study, we found that the chemokine receptor 9 （CCR9） was highly expressed on CD4^＋T cells from patients with T-cell lineage acute lymphocytic leukemia （T-ALL） and mediated leukemia cell infiltration a...In previous study, we found that the chemokine receptor 9 （CCR9） was highly expressed on CD4^＋T cells from patients with T-cell lineage acute lymphocytic leukemia （T-ALL） and mediated leukemia cell infiltration and metastasis. Combined use of interleukin 2 （IL-2） and IL-4 promoted the internalization of CCR9 and therefore attenuated leukemia cell infiltration and metastasis. In this study, we preliminarily investigated the mechanism of internalization of CCR9 on MOLT4 cell model （a human leukemia T-cell line, naturally expresses CCR9） and found that IL-2 upregulated the cell surface expression of IL-4Rα （CD124） greatly, whereas IL-4 had no significant influence on α （CD25） and β subunits （CD122） of IL-2R. Moreover, specific inhibitors, such as staurosporine, H89 and heparin, inhibited internalization of CCR9, which indicated a role of protein kinase C （PKC） and G protein-coupled kinase 2 （GRK2）, respectively. Furthermore, GRK2 was upregulated and translocated to cell membrane in IL-2 and IL-4 treated cells which indicated that PKC could be a prerequisite for GRK2 activity.展开更多
基金Supported by Project of National Natural Science Foundation of Shandong Province(ZR2015PH015)
文摘[Objectives]To study the immediate-release mechanism of dehydrotrametenolic acid and dehydroeburicoic acid in Poriae Cutis total triterpenoids tablets by liquid-solid compacts technique.[Methods] Taking dehydrotrametenolic acid and dehydroeburicoic acid as indicators,differences in dissolution were compared between liquid-solid compressed tablets and crude drug of total triterpenoids in Poriae Cutis;crude drug,powder of liquid-solid compressed tablets and excipients of liquid-solid compressed tablets were characterized by differential scanning calorimetry( DSC).[Results]Liquid-solid compact technique could significantly improve dissolution rate of dehydrotrametenolic acid and dehydroeburicoic acid. The total dissolution rate of dehydrotrametenolic acid and dehydroeburicoic acid in Poriae Cutis total triterpenoids tablets was 92%,t50( time for 50% total dissolution rate) and t_D( time for 63. 2% total dissolution rate) were 11. 18 min and 22. 71 min; the total dissolution rate of dehydrotrametenolic acid and dehydroeburicoic acid in crude drug of total triterpenoids was 29%,and t50 and t_D were231. 06 min and 359. 23 min. DSC showed that there was no mutual interaction between excipients and total triterpenoids in Poriae Cutis; on the DSC curve for powder of liquid-solid compressed tablets,the absorption peak vanished completely,indicating that the drug exists in the amorphous form in the liquid-solid powder.[Conclusions] Liquid-solid compact technique can increase the dissolution rate of total triterpenoids in Poriae Cutis and allow rapid release of poorly water soluble drugs.
基金supported by the National Natural Science Foundation of China(Grant Nos.82122043 and 82372404)the Quick Response project of AFMU(2023KXKT030).
文摘Chronic hypoxia affects stem cell function during tissue repair.Thus far,the hypoxia-associated impact on periosteal stem cells(PSCs),the main contributor to bone repair,remains unknown,and a tailored oxygen modulation strategy for optimizing PSC function is lacking.Here,PSCs exhibit time-dependent proliferation and survival upon hypoxic exposure and a critical 48-h time-point is identified at which hypoxia transitions from beneficial to detrimental.Then,a photothermal-sensitive coaxial fiber-reinforced membrane containing oxygen and pravastatin is constructed to function as an intelligent oxygen supply system.Leveraging near-infrared light as an ON/OFF switch,the system noninvasively scales up oxygen release beginning 48 h post-implantation,counteracting prolonged hypoxia and mitigating its adverse effects on PSCs.The sustained release of pravastatin from the membrane accelerates early neovascularization both directly through its pro-angiogenic effect and indirectly by stimulating vascular endothelial growth factor secretion from PSCs,ensuring a continuous oxygen supply after exogenous oxygen exhaustion.Notably,pravastatin steers PSCs toward robust osteogenic differentiation and provides multifunctional bioactive cues for advanced bone regeneration in vivo.This time-scheduled approach to modulate oxygen supply noninvasively could be applicable beyond bone regeneration for hypoxia-related diseases and multi-tissue repair.
基金This study was supported by the National Natural Science Foundation of China （No. 30570780）, National Ministry of Education Doctoral Fund （No. 200804860039） and Department of Science and Technology of Hubei Province, China （No. 2006AA301B64）.
文摘In previous study, we found that the chemokine receptor 9 （CCR9） was highly expressed on CD4^＋T cells from patients with T-cell lineage acute lymphocytic leukemia （T-ALL） and mediated leukemia cell infiltration and metastasis. Combined use of interleukin 2 （IL-2） and IL-4 promoted the internalization of CCR9 and therefore attenuated leukemia cell infiltration and metastasis. In this study, we preliminarily investigated the mechanism of internalization of CCR9 on MOLT4 cell model （a human leukemia T-cell line, naturally expresses CCR9） and found that IL-2 upregulated the cell surface expression of IL-4Rα （CD124） greatly, whereas IL-4 had no significant influence on α （CD25） and β subunits （CD122） of IL-2R. Moreover, specific inhibitors, such as staurosporine, H89 and heparin, inhibited internalization of CCR9, which indicated a role of protein kinase C （PKC） and G protein-coupled kinase 2 （GRK2）, respectively. Furthermore, GRK2 was upregulated and translocated to cell membrane in IL-2 and IL-4 treated cells which indicated that PKC could be a prerequisite for GRK2 activity.
