ABSTRACT
With the rapid development of antibody genetic engineering, bispecific antibody technology has been advanced. They are capable of binding two or more different epitopes simultaneously, thus offering specific advantages over natural monoclonal antibodies in immunotherapy. Bispecific antibodies have been successfully used in cancer therapy (e.g. melanoma, Hodgkin's lymphoma, liver cancer, and stomach cancer) and inflammation therapy (e.g. rheumatoid arthritis, psoriasis and Crohn's disease), but are still in their early stage for viral immunotherapy. In this study, we reviewed the research progress of bispecific antibodies for immunotherapy of virus infections, especially those with good effects in vivo and in vitro, to provide references for the research and development of bispecific antibodies for antivirus treatment.
Subject(s)
Humans , Antibodies, Bispecific , Therapeutic Uses , Antibodies, Monoclonal , Epitopes , Immunotherapy , Virus DiseasesABSTRACT
The clinical utility of macrolide antibiotics has declined due to the appearance of resistant isolates.A spiramycin Ⅰ-resistant Staphylococcus aureus ATCC29213-R was induced and isolated with increasing the concentration of spiramycin Ⅰ,which exhibits an A→C transversion at position 2089 in the 23S rRNA gene,which is first reported in the S.aureus.A RNA-seq based transcriptomic analysis was performed to understand the overall response of resistant bacteria to spiramycin Ⅰ treatment with subinhibitory dosage.Inn this study,There are a total of 322 up-regulated and 82 down-regulated genes in spiramycin Ⅰ-treated S.aureus ATCC29213-R and 426 up regulated,838 down-regulated in spiramycin Ⅰ-treated S.aureus ATCC29213,which were identified differentially expressed compared to their control with a minimum 2-fold change (Q ＜ 0.05).Interestingly,The data showed that argH and argG transcripts,in the arginine biosynthetic pathway,were decreased by 13.51-fold and 21.45-fold,respectively,compared to the control,while the expression level of three genes involved in arginine catabolism,arcA,arcC,and argF,increased by 35-fold,18.05-fold and 30.84-fold,respectively.The results revealed that spiramycin Ⅰ could trigger the up-regulation of the genes of ACME-Arc system which allows S.aureus to survive in acidic environments of human skin.This suggesed the arginine-deiminase pathway may be a potential target for treatment of the resistant S.aureus.
ABSTRACT
A novel sesquiterpenoid (1) and three known compounds identified as isoaltenuene (2), altenuene (3), and alternariol 4, 10-O-dimethyl ether (4), were isolated in our investigation of the cytotoxic constituents from solid cultures of the endophytic fungus Colletotrichum sp. The structures of these compounds were elucidated through spectroscopic data analysis. All compounds exhibited cytotoxic activity against lung cancer cell line A549, breast cancer cell line MDA-MB-231 and pancreatic cancer cell line PANC-1. Compound 4 could induce the PANC-1 cells inflation or death, but couldn't induce apoptosis at the IC50 of 60.2 microg x mL(-1).
ABSTRACT
Aim: To clone and over-express the gene encoding aminoglycoside(AG)phosphotransferase(APH)from clinical MRSA isolates in E.coli and to develop an assay method for the recombinant APH.Methods: The susceptibility of clinical MRSA isolates to AGs was tested by disk diffusion.A nucleic acid sequence encoding APH was amplified from the genomic DNA of an isolate and ligated to expression vector pET-28a,and then trans-formed into E.coli BL21(DE3).After purification of the recombinant protein by affinity chromatography,the phosphorylation activity of the enzyme was determined by ESI-MS and disk diffusion.Flesults: All 6 clinical MRSA isolates were unsusceptible to AGs.After cloning and expression,the recombinant APH was purified to90%.The in vitro activity assay indicated that the recombinant protein could inactivate kanamycin B in the assay mixture within 2 h.Conclusion: The recombinant APH showed excellent enzymatic activity.The assay method was simple and convenient,which may provide the basis of developing a screening model for APH inhibitors.