1.NF-κB signaling pathway is involved in retinoic acid inhibiting dendritic cell differentiation and antigen presentation
Guoping LIU ; Jie GUO ; Zhiyun WANG ; Dongchun LIANG
Chinese Journal of Microbiology and Immunology 2012;32(7):622-628
Objective To clarify whether the regulatory effect of all-trans-retinoic acid (atRA) on the antigen presentation function of dendritic cell(DC) is tightly associated with NF-κB signaling pathway.Also to clarify atRA mainly affected differentiated DC or influence the differentiation procedure from bone marrow cell to DC.Methods MOG35-55 immunized C57BL/6J mice received administration of atRA or not,splenic DC and CD4 cells isolated from immunized mice were subjected to in vitro cross-culture,treated with IL-12 and IL-23 respectively.Th1 and Th17 polarization of stimulated CD4 cells were determined by intracellular staining and FACS analysis,while the production of their corresponding cytokines,IFN-γ and IL-17,were measured by ELISA.Bone marrow cells were isolated from the femurs of the na(i)ve mice,treated with IL-4 and GM-CSF with or without synergistic RA treatment.MHC Ⅱ and CD11c molecules on the DC were assayed by immune staining and FACS analysis,their antigen presentation functions were decided by the proliferation and cytokine production of the Th1 effecter cells stimulated by antigen pulsed DC.To investigate the status of the NF-κB signaling pathway,the amount of phospho-Ser536 NF-κB p65 in the whole DC lysate and total NF-κB p65 in the nucleus were detected by Western blot.Finally,selective RA receptor antagonists were studied to figure out which receptor was majorly involved in the regulatory effect of RA on DC.Results Splenic DC from RA treated mice showed significantly decreased function of presenting antigen to stimulate CD4 cell polarization and cytokine production.Compared with untreated control,RA in vitro treated DC showed decreased expression of MHC Ⅱ and CD11c on its cell surface,which was accompanied with depressed function of stimulating Th1 cell proliferation and IFN-γ production.Further study revealed that RA mainly affect the differentiation procedure from BMC to DC,however,has no significant effect on differentiated DC as the aspects of MHC Ⅱ,CD11c expression,responder cell proliferation and cytokine production were evaluated.Decreased amount of phosphor-Ser536 NF-κB p65 in the whole cell lysate and total NF-κB p65 in the nucleus was investigated in RA treated DC,and decreased antigen presentation function of RA treated DC always came together with diminished activation of NF-κB signaling pathway.Finally it was demonstrated that RARβγ antagonist,but not RARα antagonist,could entirely block the RA effect on DC.Conclusion Retinoic acid inhibit the differentiation of DC as well as decrease its antigen presentation function,which might be resulted from the inactivation of NF-κB p65 signaling pathway and mediated by RARβγ.
2.Comparison of Immune Responses Elicited by Recombinant Fusion Hapten and Coupled Hapten
Ying LIU ; Bei SUN ; Yan MA ; Xueqin ZHAO ; Dongchun LIANG ; Gang GUO ; Jingyu ZHANG
Tianjin Medical Journal 2009;37(10):862-864
Objective:To identify the immune characteristics elicited by immunogen prepared in two different ways against a 36AA-peptide. Methods:Rabbits were immunized by a 36-AA-hapten coupled with carrier proteins or recombinant fusion protein separately. The kinetics and specificities of antibody responses were compared. Results:After about 3 months of primary immunity, the antisera elicited by two kinds of immunogen reached the peak titer. The highest titer elicited by the immunogen prepared with coupled-hapten method reached 1∶12 000, while the highest titer elicited by the immunogen prepared with gene engineering method was 1∶6 000. But the immune response produced by the recombinant fusion protein was more long-lasting. Conclusion:Both kinds of immunogen can successfully elicit 36-AA specific antibody response in rabbits, which have different immune characteristics. To couple the hapten with vector proteins is a quicker and more effective way to prepare the immunogen.
3.The prognostic value of the number of negative lymph nodes in esophageal carcinoma without lymphatic metastasis after esophagectomy
Mingran XIE ; Xinyu MEI ; Tian LI ; Changqing LIU ; Xiaohui SUN ; Zhenghua ZHANG ; Dongchun MA
Chinese Journal of Thoracic and Cardiovascular Surgery 2014;30(4):221-224
Objective To investigate the correlation between the number of resected lymph nodes(LNs) and the prognosis of patients with node-negative esophageal carcinoma.Methods A retrospective review of 429 patients receiving esophagectomy with morden two-field lymphadenectomy for cancer between January 1998 and December 2008 was performed.All patients were proved without lymph node involvement histopathologically.The prognostic impact of the number of negative LNs and the clinicopathologic factors were analyzed.Results The overall median survival time was 63.0 months,and the 1-,3-,and 5-year overall survival rates were 78.5%,64.0% and 51.2%,respectively.Survival analysis confirmed that the number of negative LNs and the depth of tumor invasion were showed to be independent prognostic factors.Patients with a high number of negative LNs had better overall survival than patients with a low number of negative LNs(P < 0.05).The patients had better long-term survival outcomes with dissected LNs counts of more than 15 for cases with pT1 tumor(P < 0.05),and more than 20 for cases with pT2-3 tumor(P < 0.05).Conclusion The number of negative lymph nodes is an independent prognostic predicting factor for node-negative esophageal carcinoma.Sufficient dissection of LNs is recommended to improve the survival of patients with node-negative esophageal carcinoma.
4.Toll like receptors signaling pathways directly increase the expression of functional IL-17RA in neu-roglial cells
Shumin ZHOU ; Song CHEN ; Guoping LIU ; Jie GUO ; Zhiyun WANG ; Dongchun LIANG
Chinese Journal of Microbiology and Immunology 2014;(3):179-185
Objective To investigate whether toll like receptor ( TLR) signaling pathways can in-crease the expression of IL-17 R in neuralglial cells , and if they can whether the increased IL-17 R is func-tional.Methods Experimental autoimmune encephalomyelitis (EAE) was induced in B6 mice by immuni-zation with an emulsion of myelin oligodendrocyte glycoprotein 35-55 ( MOG35-55 ) in complete Freund's adju-vant (CFA).The expression of Il17ra and Il17rc in the brains and spinal cords of mice with EAE were de-tected by real-time PCR.Luxol fast blue ( LFB) staining was performed to the spinal cord sections to detect tissue demyelination.Immunohistological staining against IL-17RA and CD3 were undertook to visualize IL-17RA+and CD3 + cells.Same approaches were also applied to immunized Rag1 -/- mice to figure out whether T cells infiltration is necessary for increasing IL-17RA expression in the central nervous system ( CNS) .Then B6 mice were immunized with incomplete Freund′s adjuvant ( IFA) plus different TLRs ago-nists to measure the expression of Il17ra in the brains and spinal cords by qPCR .The purified astrocytes , microglia and oligodendrocytes isolated from neonatal mice brains were cultured in vitro for two weeks , and then treated with different TLRs agonists .The expression of Il17ra at mRNA and protein levels in the cells were determined by qPCR and Western blot respectively .The astrocytes were treated with IL-17A and LPS individually or in the combination to detect the level of CCL 2, CXCL8 and IP-10 in the supernatant by ELISA.Results B6 mice with induced EAE showed significantly increased Il17ra expressions in the brain and spinal cord , which was also detected in immunized Rag1 -/-mice.Although no spinal cord demyeliza-tion and CD3 cells infiltration were detected in Rag1 -/-mice, significantly increased number of IL-17RA positive cells could still be visualized .In vivo TLRs agonist participated immunization and in vitro treatment of purified neuroglial cells demonstrated that TLRs agonists could directly evoke IL -17RA expression in the CNS or cultured astrocytes , microglia and oligodendrocytes with high efficiency .Both IL-17 A and LPS could stimulate astrocytes to secrete CCL2, CXCL8 and IP-10, however, a combined use of IL-17A and LPS fur-ther augmented the production of these chemokines to a large extend .Conclusion Taken together , we con-cluded that TLRs agonists could directly stimulate neuroglial cells to express IL -17RA which functionally re-spond to IL-17A by secreting chemokines .
5.Pharmaceutical Care for One Case of Allergic Reactions Caused by Oxaliplatin
Dongchun ZHU ; Ling FANG ; Jiatao LIU ; Xuqun SUN ; Dujuan XU ; Yong QIAN ; Congjun ZHANG
China Pharmacy 2016;27(5):694-696
OBJECTIVE:To explore the role of clinical pharmacists on pharmaceutical care for allergic reaction caused by ox-aliplatin. METHODS:Clinical pharmacists conducted pharmaceutical care for a patient with oxaliplatin-induced allergic reaction, and suggested stopping taking oxaliplatin,giving Dexamethasone injection 5 mg and then slowing down injection speed. RE-SULTS:Physicians adopted the suggestions of clinical pharmacists. Allergic reaction relieved 5 min after giving Dexamethasone in-jection. The patient didn't suffered from this allergic reaction again under tight supervision. CONCLUSIONS:Oxaliplatin is often used for tumor therapy. Medical staff should be familiar with the prevention,diagnosis and treatment of ADR,evaluate oxaliplatin chemotherapy plan in advance and screen high risk allergy factor. The participation of clinical pharmacists in pharmaceutical care contribute to ADR monitoring and promote safe and rational drug use in the clinic.
6.Prevalence of toxoplasma, rubella virus, cytomegalovirus and herpes simplex virus infections among 3084 individuals with childbearing-age in Henan province
Wanhai WANG ; Qingfang WANG ; Jianli LI ; Meifen WANG ; Jiatian LIU ; Yuanding MEI ; Dongchun QIN ; Liang MING
Chinese Journal of Clinical Infectious Diseases 2012;5(5):270-273
Objective To investigate the prevalence of toxoplasma gondii (Tox),rubella virus (RV),cytomegalovirus (CMV) and herpes simplex virus (HSV) infections (TORCH infections) among childbearing-age population in Henan province.Methods Enzyme-linked immunosorbent assay (ELISA) was applied to detect plasma TORCH IgM and IgG among 3084 childbearing-age men and women from theFirst Affiliated Hospital of Zhengzhou University during July and September,2011.The positive rates of anti-TORCH antibodies were compared among the various age and gender groups by x2 test.Results The total positive rate of anti-TORCH IgM was 5.5% (170/3084),in which the positive rate of anti-RV IgM was the highest (2.9%),followed by anti-HSV IgM (1.0%).Within positive rate of anti-TORCH IgG,anti-HSV IgG was the highest (90.4%),followed by anti-CMV IgG (89.7%),RV IgG (48.1%) and Tox IgG (0.7%).The positive rate of anti-TORCH IgM was the lowest in individuals aged > 30-40 year old.With the age increasing,the positive rates of anti-Tox IgG,anti-CMV IgG and anti-HSV IgG increased,but the positive rate of anti-RV IgG decreased.Women had higher positive rates of anti-CMV IgG and antiHSV IgG than men (x2 =83.470 and 7.026,P < 0.O1).Conclusions Current infection of TORCH exists in childbearing-age population of Henan province,and the positive rate of anti-RV IgG is low.It is recommended to screen for TORCH infection in childbearing-age men and women.
7.Breeding and application of SPF Bama miniature pig
Qian JIANG ; Lingxia HAN ; Changde SI ; Huan LIN ; Caixia GAO ; Dongchun GUO ; Wei ZHANG ; Jiasen LIU ; Liandong QU
Chinese Journal of Comparative Medicine 2017;27(5):1-3
In this study, a Specific Pathogen-Free (SPF) Bama miniature pig herd was established.The standards for breeding experimental pigs, genetic test and microbiological quality control had been drafted.The local standards of Heilongjiang province SPF technical specifications for microbiological monitoring of pigs had been formulated.The genetic and microbiological quality criterion had been used to control of the SPF pig herd.Classical swine fever virus (CSFV) and highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) infection models of Bama miniature pigs were established, especially the infection miniature pig model of PRRSV was used to evaluated commercially vaccine.The comparison of the cytokine homology between Bama miniature pigs and domestic pigs showed that the Bama miniature pigs can be used to instead of domestic pigs as an ideal experiental animal.At present the SPF Bama miniature pig colonies have been widely used to study the mechanism of prevention and pathogenic in the classical swine fever virus, porcine reproductive and respiratory syndrome virus and porcine transmissible gastroenteritis virus and porcine circovirus and so on.The completion of the project solved the bottleneck problem of the experimental pig usage which provided a new ideal experimental animal for animal disease and life science research.
8.Adalimumab in the treatment of severe plaque psoriasis: a clinical observation
Hongwei LIU ; Xueying HU ; Dongchun LEI ; Shoumin ZHANG
Chinese Journal of Dermatology 2020;53(9):744-746
Objective:To evaluate the efficacy and safety of adalimumab in the treatment of severe plaque psoriasis.Methods:From June 2018 to April 2019, 20 patients with severe plaque psoriasis were collected from Department of Dermatology, Henan Provincial People′s Hospital. After initial subcutaneous injection of adalimumab at a dose of 80 mg, these patients were subcutaneously injected with adalimumab at a dose of 40 mg at weeks 1, 3, 5, 7, 9 and 11. At weeks 4, 8 and 12, psoriasis area and severity index (PASI) was recorded, and changes in skin lesions were observed by reflectance confocal microscopy (RCM) . Adverse reactions were monitored during treatment.Results:At week 4, 12 patients achieved a 50% reduction in PASI (PASI50) ; at week 8, 14 achieved PASI75; at week 12, 20 patients achieved PASI75, of which 5 achieved PASI90 and 2 achieved PASI100. As RCM showed, the melanin content in the basal layer of skin lesions was lower compared with that of perilesional normal skin before treatment, gradually increased within 4 weeks, and nearly returned to normal at week 12. No infections, tumors or other related adverse reactions occurred in the 20 patients.Conclusion:Subcutaneous injection of adalimumab every other week is markedly effective in the treatment of severe psoriasis, with few related adverse reactions.
9.Comparison of short-term outcomes between fluorescence method versus modified inflation-deflation method on thoracoscopic anatomical segmentectomy: a study based on propensity score matching
Baoming WANG ; Feng WU ; Dongchun MA ; Mingming WANG ; Tangbin LIU ; Congshu HUA ; Chaodong ZHANG ; Wensheng WANG ; Xiang DING ; Jian ZHAO ; Chen DAI
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(3):134-141
Objective:To investigate the application value of fluorescence imaging in single-port thoracoscopic anatomic segmentectomy.Methods:The clinical data of 280 patients (145 patients with fluorescence method and 135 patients with modified inflation-deflation method) who underwent thoracoscopic anatomic segmentectomy were retrospectively studied in the Anhui Chest Hospital from June 2020 to June 2021. There were 113 patients in the simple segmentectomy group and 167 patients in the complex segmentectomy group. The baseline data of the fluorescence method and the modified inflation-deflation method in the complex segmentectomy group were corrected by propensity score matching, and the perioperative results were compared between the groups.Results:There were no significant differences in segmental resection time, intraoperative blood loss, postoperative drainage, postoperative pain, postoperative extubation time, length of hospital stay, incidence of complications and cost of hand-holding between the fluorescence method and the modified method of the simple segmentectomy group.In the complex segmentectomy group, the time of segmental resection with the fluorescence method was significantly shorter than that with the modified inflation-deflation method( P<0.05), and other indexes had no significant difference. Conclusion:Fluorescence method single-port thoracoscopic anatomic segmentectomy has the same perioperative safety and short-term efficacy as modified inflation-deflation method, which can significantly shorten the operative time and improve the operative efficiency in complex anatomic segmentectomy.
10.Pure redox-sensitive paclitaxel-maleimide prodrug nanoparticles: Endogenous albumin-induced size switching and improved antitumor efficiency.
Xinyu LOU ; Dong ZHANG ; Hao LING ; Zhonggui HE ; Jin SUN ; Mengchi SUN ; Dongchun LIU
Acta Pharmaceutica Sinica B 2021;11(7):2048-2058
A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer. However, its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier. Herein, we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy. Using diverse linkages (thioether bond and disulfide bond), paclitaxel (PTX) was conjugated with an albumin-binding maleimide (MAL) functional group. These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles (NPs) in aqueous solution without any excipients. By immediately binding to blood circulating albumin after intravenous administration, NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates