A potential role of macrophage phenotypes in the early evaluation of the effects of combined Yersinia Pestis and Brucella bovis vaccine immunization / 国际药学研究杂志

Objective In emergency situations where simultaneous immunization by multiple vaccines are required,how to rapidly evaluate the effect of combined immunization is an urgent issue that needs to be solved.This study aimed to investigate the po-tential role and application value of the phenotypic changes of macrophages in rapid evaluation of the effect of combined Yersinia pestis and Brucella bovis vaccine immunization at early stage.Methods Y.pestis and B.bovis vaccines were injected into mice alone or in combination to establish animal models.The changes of the macrophage phenotypes(M1 or M2 polarization)and the CD8+T cell pheno-types and functions were detected in the early(4 d)and the late(14 d)stage of the immunization,respectively.The effect of the immuno-phenotype of macrophages at early stage on the function of CD8+T cells at late stage was analyzed.Results The co-immunization by Y.pestis and B.bovis vaccines led to the attenuation of the M1-polarization of macrophages at early stage,which were marked by de-creased expression of CD16/32 and increased expression of Detectin-1 on cell surface as well as decreased expression of IL-12 and in-creased expression of IL-4 inside the macrophage,in comparison with single vaccine groups,suggesting an interference between the two vaccines.Meanwhile,the activity of CD8+T cells(including the ratio of CD8+CD69+T,CD8+IFN-γ+T and CD8+GranzymeB+T cells) in combined immunization group showed similar tendency to the attenuated phenotypic M1-polarization of macrophages. Conclusion The phenotype of macrophages at the early stage of the co-immunization by Y.pestis and B.bovis vaccines showed consistency with the phenotype and function of CD8+T cells at late stage.It might give us some hint about the possibility of utilizing the phenotypic changes of macrophages to rapidly evaluate the effect of the co-immunization at early stage.

Increased Expression of the NOD-like Receptor Family, Pyrin Domain Containing 3 Inflammasome in Dermatomyositis and Polymyositis is a Potential Contributor to Their Pathogenesis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dermatomyositis (DM) and polymyositis (PM) are common inflammatory myopathies whose immunopathogenic mechanisms remain poorly understood. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome is a type of cytoplasmic multiprotein inflammasome and is responsible for the activation of inflammatory reactivations. Responding to a wide range of exogenous and endogenous microbial or sterile stimuli, NLRP3 inflammasomes can cleave pro-caspase-1 into active caspase-1, which processes the pro-inflammatory cytokines pro-interleukin (IL)-1β and pro-IL-18 into active and secreted IL-1β and IL-18. The NLRP3 inflammasome is implicated in infectious and sterile inflammatory diseases. However, it remains unclear whether it is involved in the pathogenesis of DM/PM, which we aim to address in our research.</p><p><b>METHODS</b>In this study, 22 DM/PM patients and 24 controls were recruited. The protein and RNA expression of IL-1β, IL-18, NLRP3, and caspase-1 in serum and muscle samples were tested and compared between the two groups.</p><p><b>RESULTS</b>The serum IL-1β and IL-18 levels were significantly higher in DM/PM patients than those in the controls by enzyme linked immunosorbent assay (ELISA, DM vs. control, 25.02 ± 8.29 ng/ml vs. 16.49 ± 3.30 ng/ml,P < 0.001; PM vs. control, 26.49 ± 7.79 ng/ml vs. 16.49 ± 3.30 ng/ml,P < 0.001). Moreover, the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed that DM/PM patients exhibited higher RNA expression of IL-1β, IL-18, and NLRP3 in the muscle (for IL-1β, DM vs. control, P= 0.0012, PM vs. control, P= 0.0021; for IL-18, DM vs. control, P= 0.0045, PM vs. control, P= 0.0031; for NLRP3, DM vs. control, P= 0.0017, PM vs. control, P= 0.0006). Moreover, the protein expression of NLRP3 and caspase-1 in muscle samples of DM/PM patients were also significantly elevated compared to that in the muscles of the controls.</p><p><b>CONCLUSIONS</b>Our findings demonstrate that the NLRP3 inflammasome is implicated in the pathogenesis of DM/PM. High NLRP3 expression led to elevated levels of IL-1β and IL-18 and could be one of the factors promoting disease progress.</p>

Study on efficacy of liujunzi decoction combined with zuojin pills in treating acute radioactive duodenitis and their mechanism / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of Liujunzi decoction combined with Zuojin pills in treating the radioactive duodenitis and their mechanism, and compare with clinical routine acid suppressants combined with mucous membrane protective preparations to study the mechanism of their efficacy.</p><p><b>METHOD</b>According to the study of Williams J P and characteristics of duodenitis, and by reference to the radiation enteritis modeling standard, we took the lead in establishing the mouse radioactive duodenal injury model. The model mice were randomly divided into the control group (n = 26), traditional Chinese medicine (TCM) group (n = 16) and the western medicine (oral administration with famotidine 0.5 mL + almagate suspension 0.3 mL per mouse, once a day) group (n = 16). After the standard administrating, such objective indexes as general condition, weight, changes in health score, pathology and expression of inflammatory factors were observed to evaluate the efficacy.</p><p><b>RESULT</b>The radioactive duodenitis model of mice was successfully established with 12 Gy. Mice in the control group suffered from weight loss, anorexia, low fluid intake, loose stools, and occasionally mucous bloody stool, poor spirit, dim fur, lack of exercise and arch back. Mice in drug intervention groups were generally better than those in the pure irradiation group. The IL-6, IL-1beta, TNF-alpha mRNA expressions in spleen and mesenteric lymph node tissues in TCM and western medicine groups showed a declining trend compared with the control group. Their concentrations in peripheral blood serum also slightly changed. The TCM group revealed notable advantage in reducing inflammatory factors. The microscopic observation showed that a better mucosa repair in intervention groups than the pure irradiation group. The improved Chiu's scoring method showed a statistical significance in the difference between TCM and western medicine groups (P < 0.05).</p><p><b>CONCLUSION</b>Liujunzi decoction combined with Zuojin pills could treat acute radiation enteritis, regulate organic immunity, and inhibit acute injury, promote local tissue repair, with the potential to resist such adverse effects as radiation intestinal fibrosis. The regulation of inflammatory factor release is one of efficacy generation mechanisms.</p>

Establishment and evaluation of experimental sepsis mouse model / 中国实验血液学杂志

After treating with chemotherapy or immunosuppressant, malignant diseases of hematopoietic system such as leukemia, malignant lymphoma and aplastic anemia usually induced severe infection such as sepsis. Sepsis which is hard to be diagnosed causes high death rate. This study was purposed to establish an experimental sepsis mouse model so as to provide a basis for pathogenesis and intervention study. A classic caecal ligation and puncture (CLP) was used to establish experimental sepsis model. ELISA was used to detect levels of C5a, IL-6, TNFalpha, and IFN-gamma. Flow Cytometry was applied to measure apoptosis of lymphocytes in thymus and mesentery. The pathologic changes of thymus and spleen were confirmed by HE staining. The results showed that almost 70%-80% mice died at 72 hours after CLP. Only approximate 20% animal survived during finite time, mice in CLP group had significant weight lose. Meanwhile large release of different inflammatory mediators which are related with sepsis (C5a, IL-6, TNF-alpha, and IFN-gamma) was observed after CLP. Apoptosis of lymphocytes in thymus and mesentery lymphonodus was enhanced markedly after CLP. Significantly pathologic injury was also observed in thymus and spleen. It is concluded that a mouse model of experimental sepsis was successfully established by caecal ligation and puncture which can well mimic the clinical symptom of sepsis. The experimental sepsis mouse model provides an excellent tool for exploring the pathogenesis and intervention ways for sepsis accompanied with complicated malignant hematological diseases in vivo.