ABSTRACT
Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.
ABSTRACT
Objective:To explore and analyze the effect of massive transfusion protocol (MTP) in early massive transfusion and prevention of coagulation disease for patients with multiple injuries.Methods:A retrospective analysis was made in 117 patients with multiple injuries admitted to Yiwu Central Hospital from March 2015 to May 2019.According to different blood transfusion schemes, they were divided into control group(53 cases) and observation group(64 cases). The patients in the control group received routine blood transfusion scheme, and the patients in the observation group received MTP blood transfusion scheme.The changes of blood routine and coagulation function, the amount of blood loss within 24h, the amount of allogeneic blood component input, the length of hospital stay and mortality were compared between the two groups.Results:The levels of Hb, HCT and PLT in the two groups after 24h of blood transfusion were significantly higher than admission[(112.73±12.73)g/L vs.(96.74±10.28)g/L, (115.28±19.27)g/L vs.(95.37±11.47)g/L, (39.72±5.21)% vs.(31.47±4.22)%, (39.10±4.97)% vs.(30.56±4.13)%, (220.93±54.28)×10 9/L vs.(142.83±36.47)×10 9/L, (216.87±64.03)×10 9/L vs.(148.96±40.22)×10 9/L, t=7.818, 6.464, 9.844, 9.621, 9.554, 6.538, all P<0.05], but there were no statistically significant differences between the two groups( t=0.681, 1.172, 0.864, 0.746, 0.740, 1.363, all P>0.05). After 24h of blood transfusion, the time of Pt and APTT in the observation group were significantly lower than admission[(13.21±2.93)s vs.(16.28±4.26)s, (46.28±3.97)s vs.(54.37±6.42)s, t=4.705, 8.574, all P<0.05], but there were no statistically significant changes in the control group[(15.84±3.62)s vs.(16.93±5.17)s, (54.02±6.39)s vs.(55.29±7.02)s, t=0.212, 0.332, all P>0.05]. The time of Pt and APTT in the observation group after 24h of blood transfusion were significantly lower than those in the control group ( t=4.344, 8.006, all P<0.05). There were no statistically significant differences in FIB levels between the two groups[(4.30±0.48)g/L vs.(4.36±0.56)g/L, (4.41±0.58)g/L vs.(4.51±0.63)g/L, t=0.651, 0.934, all P>0.05]. There were no statistically significant differences in 24h bleeding volume and fresh frozen plasma(RBC) input between the two groups[(2 684.92±703.47)mL vs.(2 725.86±810.32)mL, (17.28±3.74)U vs.(17.02±2.95)U, t=0.293, 0.411, all P>0.05]. The input amount of red blood cell suspension(PF) and the ratio of PF: RBC in the observation group were significantly higher than those in the control group[(9.28±3.27)U vs.(6.29±3.18)U, (0.55±0.12) vs.(0.39±0.10), t=4.985, 7.733, all P<0.05]. The observation group had significantly lower SOFA scores and ICU stays compared with the control group[(5.93±1.64)points vs.(7.28±2.10)points, (7.21±1.85)d vs.(9.10±2.37)d, t=3.814, 4.732, all P<0.05], and the mortality rate in the observation group was significantly lower than that in the control group[6.25%(4/64) vs.20.75%(11/53), χ 2=5.457, P<0.05]. Conclusion:The standardized rescue strategy of a large number of blood transfusion treatment schemes and the early proportion of components of blood products (erythrocyte suspension, fresh frozen plasma, platelets) can significantly improve the coagulation function of patients with multiple injuries, reduce the incidence of coagulopathy and help reduce the fatality rate of major bleeding, which is worthy of clinical promotion.
ABSTRACT
Elicitation by chemical means including heavy metals is one of a new technique for drug discoveries. In this research, the effect of heavy metals on marine actinobacteria Streptomyces sp. H-1003 for the production of enterocin, with a strong broad spectrum activity, along optimized fermented medium was firstly investigated. The optimum metal stress conditions consisted of culturing marine actinobacteria strain H-1003 with addition of cobalt ions at 2mM in optimized Gause's medium having starch at 20mg/L for 10 days at 180 revolution/min. Under these conditions, enterocin production was enhanced with a value of 5.33mg/L, which was totally absent at the normal culture of strain H-1003 and much higher than other tested metal-stress conditions. This work triumphantly announced a prodigious effect of heavy metals on marine actinobacteria with fringe benefits as a key tool of enterocin production