Biologics for targeting inflammatory cytokines and their clinical application / 生物工程学报

Inflammatory cytokines can mediate many biological processes and are tightly regulated by the body. Loss of control can trigger a range of diseases such as autoimmune inflammation and cancer. Therefore, a number of biological agents that can effectively regulate the biological effects of inflammatory cytokines such as recombinant anti-inflammatory cytokines, cytokine receptors and neutralizing antibodies have been extensively used in the treatment of related diseases caused by the imbalance of inflammatory cytokines. In recent years, in particular, a number of new innovative biological agents for blocking and regulating cytokine activities are emerging. In this article, we review the recent development and clinical use of the biologics targeting TNF-α, IL-1, IL-6 and IL-17, and point out their inherent limitations and clinical risks. Finally, based on the research findings of our own and other scholars, we suggest some approaches and methods for reducing their side-effects and clinical risk. We consider that using modern biotechnology to improve the tissue specificity to inflammatory site and tumor will be an important development direction of such biologics.

Expression and characterization of a bispecific antibody targeting TNF-α and ED-B containing fibronectin / 生物工程学报

To enhance the specificity of anti-TNF-α single chain Fv antibody (TNF-scFv) to inflamed site, we constructed a bispecific antibody BsDb that targets TNF-α and ED-B-containing fibronectin (B-FN) by covalently linking TNF-scFv and the anti-ED-B scFv L19 at the gene level via a flexible peptide linker deriving from human serum albumin. BsDb was successfully secreted from Pichia pastoris as functional protein, identified by immunoblotting, and purified to homogeneity with affinity chromatography. BsDb retained the immunoreactivity of its original antibodies TNF-scFv and L19, and showed a marked gain in antigen-binding affinity and in TNF-α-neutralizing ability, when compared to TNF-scFv and L19 that were produced in Escherichia coli. In the adjuvant-induced arthritis (AIA) mice model, BsDb showed selective accumulation and retention in the inflamed paws but rapid clearance from blood, resulting in high arthritic paw to blood ratios. These data indicate that BsDb is endowed with high specificity to inflamed site and low toxicity to normal tissues and holds great potential for in vivo application for the targeted therapy of RA and other chronic inflammatory diseases.

Study on acinetobacter baumannii infection distribution and drug resistance analysis in a hospital during 2012 / 国际检验医学杂志

Objective To analyze the distribution and drug resistance of 130 clinical strains of acinetobacter (A ) .baumannii in 2012 .Methods The bacterial identification and the susceptibility test were performed by using the micro-organisms identification and susceptibility plate produced by the Zhuhai Deere Company .The data were collected and statistically analyzed by the SPSS 17 .0 software .Results 130 strains of A .baumannii were isolated from 1 391 clinical samples during 2012 ,the detection rate was 9.35% .Thesamplesweremainlyderivedfromsputum(89.23% )andthedepartmentwasmainlydistributedinICU(46.15% ).A. baumannii isolates showed the lowest resistant rates to cefoperazone-sulbactam and polymyxin B ,which were 6 .9% and 7 .7% re-spectively .The drug resistance rate against the third-generation of cephalosporin commonly used in clinic was more than 70% .The resistant rates to imipenem and meropenem were 44 .6% and 58 .5% respectively .The drug resistance rates of A .baumannii isolates to 13 usual antibacterial drugs in ICU were significantly higher than those in non-ICU departments(P<0 .05) .Conclusion The re-sistance of A .baumannii to antibacterial drugs is gradually serious ,which should be paid high attention to in clinic ,and at the same time the comprehensive measures of prevention and control of hospital infection should be adopted to reduce the spread of drug-re-sistant bacteria .

Construction and functional analysis of a bispecific antibody that targets TNF-α and ED-B / 药学学报

In order to enhance the specificity of TNF-α monoclonal antibody to inflamed site, a bispecific antibody BsDb that targets TNF-α and the extra-domain B (ED-B) of fibronectin (FN) was constructed by covalently linking the anti-TNF-α single chain Fv antibody (TNF-scFv) and the anti-ED-B scFv L19 via a flexible peptide linker deriving from human serum albumin (HSA). ED-B is an antigen specifically expressed at the inflamed site. BsDb is expressed in E. coli, identified by immunoblot, and purified with affinity chromatography. This was followed by further examination of its bioactivities and pharmacokinetics. We demonstrated that BsDb retained the immunoreactivity of its original antibodies as it could simultaneously bind to TNF-α and ED-B and neutralize the biological action of TNF-α. In the collagen-induced arthritis mice model, BsDb selectively accumulate in the inflamed joint with a maximal uptake of (12.2 ± 1.50)% ID/g in a single inflamed paw and retain in the inflamed paw for at least 72 h. In contrast, BsDb showed a short serum half-life of (0.50 ± 0.05) h and a rapid clearance from normal tissues. The findings reported herein indicate that BsDb has good specificity to the inflamed site and low toxicity to normal tissues. BsDb is therefore likely to have greater clinical applications in the treatment of rheumatoid arthritis and other autoimmune diseases. This laid a stable basis for its preclinical study.

Trace detection of arsenic and mercury in Fructus Mume by atom fluorescene spectrum / 中成药

AIM:To determine the content of the trace arsenic and mercury in Fructus Mume and Fructus Mume charcoal. METHODS:Atomic fluorescence spectrometry was used. RESULTS:The content of arsenic in Fructus Mume is 0.0597～1.0001 mg?g -1, that of mercury is 0.0198～0.0300 mg?g -1. CONCLUSION:This method is simple to handle, the quantitative analysis is accurate.