Abstract: Batroxobin, a thrombin-like enzyme from Bothrops atrox moojeni venom, is associated with the reduction of fibrinogen levels in plasma and the enhancement of anticoagulation and fibrinolysis. In this study, 15 patients with deep vein thrombosis (DVT) achieved successful limb salvage after the administration of batroxobin. We found that the levels of CD34+, CD31+, CD34+/CD31+, and vascular endothelial cadherin (VE-cadherin+) cells had increased in the peripheral blood of patients at 7 days and 14 days after treatment. At 0 day, 7 days, and 14 days, the percentages of CD34+ cells, which are assumed to be hematopoietic stem cells, are 0.39% ± 0.43%, 0.71% ± 0.50%, and 1.11% ± 0.66%, respectively. The levels of CD34+ cells at 14 days are significantly higher than the levels on the first day (P = .004). The levels of CD31+ cells and VE-cadherin+ cells, which represent mature endothelial cells, at 7 days (34.15% ± 11.32%, P = .013; 1.25% ± 1.39%, P = .014) and 14 days (35.21% ± 7.66%, P = .071; 1.85% ± 2.60%, P = .117) were slightly elevated compared with those at 0 day (27.55% ± 8.65%; 0.25 ± 0.39%). The double positive of CD34 and CD31 cells are assumed to be endothelial progenitor cells (EPCs). The levels of CD34+/CD31+ cells at 7 days (0.69% ± 0.50%, P = .001) and 14 days (1.07% ± 0.66%, P = .006) are significantly higher than that on the initial day (0.28% ± 0.30%). The number of CD34+/CD31+ cells significantly increased, indicating that in addition to its role in anticoagulation and fibrinolysis, treatment with batroxobin might simultaneously activate circulating EPCs that might promote the recanalization of the damaged vessel wall.

Abstract: Objective The aim of the study was to explore the therapeutic efficacy and safety of batroxobin in patients with primary hepatic carcinoma (PHC) and the advantages of transcatheter arterial perfusion of batroxobin combined with transcatheter arterial chemoembolization (TACE).

Abstract: The invention aims to provide a method for preparing batroxobin through fermentation of recombinant methanol yeast. The method comprises batch fermentation and fed-batch fermentation of yeast, and methanol induced expression of the batroxobin, wherein the yeast is recombinant site-directed mutated batroxobin that the 45-position arginine of natural batroxobin is mutated into lysine. The method is characterized in that: a carbon source for the batch fermentation and fed-batch fermentation of the yeast is glycerol, and the pH is 5.0-5.5; and the pH in the methanol induced expression of the batroxobin is 6.8-7.0, the temperature is 25DEG C and the methanol concentration is 0.5 percent. Research results indicate that: by the method, the fermentation efficiency can be greatly improved, and the expression level of a target product is obviously improved.

Abstract: Multiple sclerosis (MS) was characterized with widespread demyelination and axonal loss of central ner- vous system (CNS). Fibrinogen (fibrin) deposition was considered as one of the pathogenesis of MS. Therefore, we explored the effects of fibrinogen depleting agent bat- roxobin in experimental autoimmune encephalomyelitis (EAE) mice model. Our study showed that prevention and suppression with batroxobin significantly ameliorated clinical severity of EAE, reduced inflammatory cells infiltration, and demyelination, and suppressed the activa- tion of astrocytes and macrophages comprising the CD11b ? population. Batroxobin treatment leads to reduced expression of p-Akt and increased expression of MBP as compared to control. In addition, batroxobin treatment partly reversed the dendric-like formation of macrophages irritated by fibrinogen in vitro. The reduced severity of EAE mice treated with batroxobin suggests that strategy targeting fibrin as a potential therapy for EAE may be beneficial for the treatment of MS patients.