1.Cellular immunotoxicity of rAAV gene medicine and possible solutions.
Yong DIAO ; Qi-zhao WANG ; Wei-dong XIAO ; Rui-an XU
Acta Pharmaceutica Sinica 2010;45(9):1071-1077
Gene medicine based on recombinant adeno-associated virus (rAAV) vector has rapidly become the prior-choose reagent for gene therapy, since it had been shown that the rAAV was able to stably express many genes in vivo without detectable side-effect. However, recent findings of CTL immune responses to AAV capsid in a clinical trial highlighted a new issue regarding safety that previously was not identified in animal studies. Obviously it is so important to understand the interaction of rAAV with the immune system in details for the safety and success of rAAV gene medicine. In this review we evaluate several current hypotheses aiming to explain the cellular immunotoxicity, also analysis the current findings including the presentation kinetics of the capsid antigen and the activation of CTL. Focusing on the key steps of the immune response several solutions are proposed, including immunosuppression, optimization of vector and improvement of purity, in order to insure clinical safety and efficacy of rAAV.
Animals
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Capsid
;
immunology
;
Dependovirus
;
genetics
;
Genetic Therapy
;
Genetic Vectors
;
adverse effects
;
immunology
;
Humans
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Immune Tolerance
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Immunity, Cellular
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Immunosuppressive Agents
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pharmacology
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Proteasome Endopeptidase Complex
;
metabolism
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Proteasome Inhibitors
;
Recombinant Proteins
;
adverse effects
;
immunology
;
T-Lymphocytes, Cytotoxic
;
immunology
2.Observation on clinical therapeutic effect of Yang's cotton moxibustion on neurodermatitis.
Can-yang DIAO ; Yun-kuan YANG ; Yong-hong LU ; Zhan WANG ; Xiao-rui YAN ; Yan WANG
Chinese Acupuncture & Moxibustion 2007;27(3):176-178
OBJECTIVETo compare the difference of the therapeutic effects between Yang's cotton moxibustion and hormonotherapy on neurodermatitis.
METHODSSixty cases of neurodermatitis were divided into a treatment group and a control group according to random number table. The treatment group were treated with Yang's cotton moxibustion and the control group with triamcinolone and urea cream. After treatment for one week, the therapeutic effect was start to be observed. After the treatment was given for 4 weeks, the therapeutic effect was evaluated.
RESULTSThe total effective rate was 93.3% in the treatment group and 80.0% in the control group, with a significant difference between the two groups (P < 0.05).
CONCLUSIONYang's cotton moxibustion has an obvious therapeutic effect on neurodermatitis with a good safety.
Adolescent ; Adult ; Aged ; Female ; Gossypium ; Humans ; Male ; Middle Aged ; Moxibustion ; methods ; Neurodermatitis ; therapy
3.IL-27: a novel cytokine mediating immune related diseases.
Na ZHANG ; Yang YANG ; Qiu-Yan LIANG ; Xiao-Rui DIAO ; Xue-Jie YI ; Bo CHANG
Acta Physiologica Sinica 2023;75(2):303-315
Interleukin 27 (IL-27) is a pleiotropic cytokine that is involved in the regulation of the body's innate and adaptive immunity. Previous studies have shown that IL-27 mediates a variety of inflammatory responses in vivo. With the development of animal models and technical tools, several studies have shown that it is also closely associated with autoimmune diseases and other immune related diseases, and is considered as an important candidate for the treatment of viral disease, autoimmune diseases, tumors and obesity. Therefore, this paper reviews recent progress on the role of IL-27 in acquired immunodeficiency syndrome (AIDS), rheumatoid arthritis, tumors and obesity, with the aim of providing new ideas for the treatment of immune related diseases.
Animals
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Cytokines
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Interleukin-27
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Autoimmune Diseases
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Arthritis, Rheumatoid
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Neoplasms
4.Clinical Application of Screening Cell Combination Method in the Prediction of Red Blood Cell Alloantibody.
Xiao-Fei LI ; Rong LANG ; Xue-Qin DIAO ; Rui-Rui SU ; Yuan ZHANG ; Bin HU
Journal of Experimental Hematology 2021;29(4):1325-1329
OBJECTIVE:
To explore the clinical application of screening cell combination method in the prediction of red blood cell alloantibody, so as to provide basis for clinical diagnosis.
METHODS:
From October 2018 to April 2020, 9 680 samples were screened with automatic blood group instrument, 79 patients with positive alloantibodies were identified by 4 sets of screening cells from different manufacturers (referred to as combined method). At the same time, cell panel Panocell-16 was used for comparative analysis. Meanwhile, the combined method was also used to identify the antibodies of 20 samples from National Center for Clinical Laboratories external quality assessment (EQA) in China and 12 samples from WHO EQA.
RESULTS:
The 79 alloantibodies included anti-Mia antibody (7 cases), anti-M antibody (13 cases), anti-Le
CONCLUSION
The combined method can identify the alloantibodies of red blood cells in Chinese population. The screening cells can be used for screening of irregular antibodies without wasting reagents at the same time.
Autoantibodies
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Blood Group Antigens
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China
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Erythrocytes
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Humans
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Isoantibodies
5.Emodin alleviates cardiac fibrosis by suppressing activation of cardiac fibroblasts upregulating metastasis associated protein 3.
Dan XIAO ; Yue ZHANG ; Rui WANG ; Yujie FU ; Tong ZHOU ; Hongtao DIAO ; Zhixia WANG ; Yuan LIN ; Zhange LI ; Lin WEN ; Xujuan KANG ; Philipp KOPYLOV ; Dmitri SHCHEKOCHIKHIN ; Yong ZHANG ; Baofeng YANG
Acta Pharmaceutica Sinica B 2019;9(4):724-733
Excess activation of cardiac fibroblasts inevitably induces cardiac fibrosis. Emodin has been used as a natural medicine against several chronic diseases. The objective of this study is to determine the effects of emodin on cardiac fibrosis and the underlying molecular mechanisms. Intragastric administration of emodin markedly decreased left ventricular wall thickness in a mouse model of pathological cardiac hypertrophy with excess fibrosis induced by transaortic constriction (TAC) and suppressed activation of cardiac fibroblasts induced by angiotensin II (AngII). Emodin upregulated expression of metastasis associated protein 3 (MTA3) and restored the MTA3 expression in the setting of cardiac fibrosis. Moreover, overexpression of MTA3 promoted cardiac fibrosis; in contrast, silence of MTA3 abrogated the inhibitory effect of emodin on fibroblast activation. Our findings unraveled the potential of emodin to alleviate cardiac fibrosis upregulating MTA3 and highlight the regulatory role of MTA3 in the development of cardiac fibrosis.
6.Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents.
Hao WANG ; Yu YUAN ; Bihao WU ; Mingzhong XIAO ; Zhen WANG ; Tingyue DIAO ; Rui ZENG ; Li CHEN ; Yanshou LEI ; Pinpin LONG ; Yi GUO ; Xuefeng LAI ; Yuying WEN ; Wenhui LI ; Hao CAI ; Lulu SONG ; Wei NI ; Youyun ZHAO ; Kani OUYANG ; Jingzhi WANG ; Qi WANG ; Li LIU ; Chaolong WANG ; An PAN ; Xiaodong LI ; Rui GONG ; Tangchun WU
Frontiers of Medicine 2023;17(4):747-757
Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.