Cheonggukjang is a soybean paste made by fermenting whole cooked soybeans with Bacillus subtilis. Cheonggukjang contains a fibrinolytic enzyme that could provide clinical applications for removing blood clots. In the ...Cheonggukjang is a soybean paste made by fermenting whole cooked soybeans with Bacillus subtilis. Cheonggukjang contains a fibrinolytic enzyme that could provide clinical applications for removing blood clots. In the present study, the term ＂cheonggukjang kinase＂ （CGK） was used to refer to this fibrinolytic enzyme. The thrombolytic effects of CGK were analyzed in a rat model of cerebral embolic stroke produced by middle cerebral artery occlusion （MCAO）. Results from fibrin and platelet-rich clot lysis assays demonstrated that thrombolytic activity was greatest in CGKs, which were cultured for 40 hours. In addition, T50, the time needed to decompose 50% of the clot, did not change with plasminogen treatment, indicating that CGK was not a plasminogen activator, but was rather presumed to act as a plasmin-like protein. An intravenous infusion of CGK （1 U plasmin-like activity/100 μg CGK/kg） at 1 hour after MCAO resulted in removal of clots in a rat model of cerebral embolic stroke. CGK-treated groups exhibited a significant dose-dependent reduction in infarct volume. CGK treatment also improved functional recovery, as assessed by neurological deficit scores. Decreased infarct volume and improved functional recovery following CGK treatment was greater compared with recombinant tissue plasminogen activator （10 mg/kg）. These results suggested that CGK effectively reduced infarct volume and improved functional recovery following ischemic brain injury. CGK exhibits a number of potential clinical applications ir the treatment of cerebral embolic stroke.展开更多
Poly-gamma-glutamic acid(γ-PGA)is a natural,edible and non-toxic polymer synthesized by Bacillus subtilis and is suggested as a safe biomaterial for the use in hydrogels and vaccine adjuvants.However,the effect ofγ-...Poly-gamma-glutamic acid(γ-PGA)is a natural,edible and non-toxic polymer synthesized by Bacillus subtilis and is suggested as a safe biomaterial for the use in hydrogels and vaccine adjuvants.However,the effect ofγ-PGA on inflammasome activation has not yet been studied in macrophages.Inflammasomes,which are intracellular multi-protein complexes,promote acute and chronic inflammation via interleukin-1βor interleukin-18 maturation,and they are known targets for metabolic syndromes and cancer.In this study,we observed thatγ-PGA attenuated NLRP3,NLRC4 and AIM2 inflammasome activation,whereas it upregulated pro-inflammatory cytokine expression in human and murine macrophages.Althoughγ-PGA had conflicting effects on cytokine production and maturation,it clearly alleviated the severity of lipopolysaccharide-induced endotoxin shock in an animal model.Thus,we suggestγ-PGA as a candidate to control inflammasome-mediated disorders.展开更多
基金the National Research Foundation of Korea,funded by the Korean Ministry of Education,Sci-ence and Technology,No.2007-0055330Inje Univer-sity Research Grant (2008)
文摘Cheonggukjang is a soybean paste made by fermenting whole cooked soybeans with Bacillus subtilis. Cheonggukjang contains a fibrinolytic enzyme that could provide clinical applications for removing blood clots. In the present study, the term ＂cheonggukjang kinase＂ （CGK） was used to refer to this fibrinolytic enzyme. The thrombolytic effects of CGK were analyzed in a rat model of cerebral embolic stroke produced by middle cerebral artery occlusion （MCAO）. Results from fibrin and platelet-rich clot lysis assays demonstrated that thrombolytic activity was greatest in CGKs, which were cultured for 40 hours. In addition, T50, the time needed to decompose 50% of the clot, did not change with plasminogen treatment, indicating that CGK was not a plasminogen activator, but was rather presumed to act as a plasmin-like protein. An intravenous infusion of CGK （1 U plasmin-like activity/100 μg CGK/kg） at 1 hour after MCAO resulted in removal of clots in a rat model of cerebral embolic stroke. CGK-treated groups exhibited a significant dose-dependent reduction in infarct volume. CGK treatment also improved functional recovery, as assessed by neurological deficit scores. Decreased infarct volume and improved functional recovery following CGK treatment was greater compared with recombinant tissue plasminogen activator （10 mg/kg）. These results suggested that CGK effectively reduced infarct volume and improved functional recovery following ischemic brain injury. CGK exhibits a number of potential clinical applications ir the treatment of cerebral embolic stroke.
基金We thank Young Jin Kim(Korea Food Research Institute)for providing the cheonggukjang extractsThis research was supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology(NRF-2015R1A2A2A01004183).
文摘Poly-gamma-glutamic acid(γ-PGA)is a natural,edible and non-toxic polymer synthesized by Bacillus subtilis and is suggested as a safe biomaterial for the use in hydrogels and vaccine adjuvants.However,the effect ofγ-PGA on inflammasome activation has not yet been studied in macrophages.Inflammasomes,which are intracellular multi-protein complexes,promote acute and chronic inflammation via interleukin-1βor interleukin-18 maturation,and they are known targets for metabolic syndromes and cancer.In this study,we observed thatγ-PGA attenuated NLRP3,NLRC4 and AIM2 inflammasome activation,whereas it upregulated pro-inflammatory cytokine expression in human and murine macrophages.Althoughγ-PGA had conflicting effects on cytokine production and maturation,it clearly alleviated the severity of lipopolysaccharide-induced endotoxin shock in an animal model.Thus,we suggestγ-PGA as a candidate to control inflammasome-mediated disorders.
