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High-expression of recombinant human concensus interferon-α by Pichia pastoris

HAO Yuyou, SHI Qiqi, HE Yun, ZHUANG Yingping, WANG Yonghong, ZHANG Siliang, CHU Ju, LIU Zhimin

《化学科学与工程前沿（英文）》 2007年 第1卷 第4期   页码 399-403 doi: 10.1007/s11705-007-0073-x

摘要： The present work focused on the high expression of recombinant human consensus interferon- (cIFN) by Pichia pastoris. The cycle of glycerol feeding, the strategy of methanol feeding and the optimum pH for protein induction were studied. The optimized strategies were a 4-h glycerol-feeding period, induction pH being kept at 5.0 and methanol concentration being kept under 5 g/L. The maximum dry cell weight, cIFN production and bioactivity obtained were 168, 1.24 g/L and 5.4×10 U/mL, respectively.

关键词： bioactivity     pastoris     maximum     induction     optimized    

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Interferon-α salvage treatment is effective for patients with acute leukemia/myelodysplastic syndrome

Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang

《医学前沿（英文）》 2019年 第13卷 第2期   页码 238-249 doi: 10.1007/s11684-017-0599-3

摘要： The efficacy of salvage interferon-α (IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI) ( =24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2–3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and>2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.

关键词： interferon-α     hematopoietic stem cell transplantation     minimal residual disease     donor lymphocyte infusion    

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Testing of tuberculosis infection among Chinese adolescents born after terminating the Bacillus Calmette--Guérin booster vaccination: subgroup analysis of a population-based cross-sectional study

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《医学前沿（英文）》 2017年 第11卷 第4期   页码 528-535 doi: 10.1007/s11684-017-0573-0

摘要：

The prevalence of tuberculosis infection among adolescents born after terminating the Bacillus Calmette–Guérin (BCG) booster vaccination in China was estimated using tuberculin skin testing (TST) and QuantiFERON-TB Gold assay (QFT) to investigate the influence of neonatal BCG vaccination on the performance of TST. Data analysis was conducted for 2831 eligible participants aged 5–15 years from the baseline survey of a population-based multi-center prospective study. The prevalence rates of TST (induration≥10 mm) and QFT positivity were 9.3% (264/2827) and 2.5% (71/2831), respectively. The rate of QFT indeterminate result was 2.2% (62/2831). The overall agreement between TST and QFT was low (concordance= 88.0%; κ coefficient= 0.125). Only TST was positively associated with BCG vaccination with an adjusted odds ratio of 1.71 [95% confidence interval, 1.26–2.31]. A history of close contact with patients of active TB was significantly associated with positivity for TST and QFT. Our results suggested that BCG neonatal vaccination still affects TST performance, and a two-step approach might be considered for TB infection testing among adolescents in China.

关键词： tuberculin skin test     interferon-γ release assays     adolescent     agreement    

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Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation

Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang

《医学前沿（英文）》 2019年 第13卷 第3期   页码 354-364 doi: 10.1007/s11684-018-0665-5

摘要： The efficacy of minimal residual disease (MRD)-directed immunotherapy, including interferon- (IFN- ) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI), was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT). High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after allo-HSCT were studied ( =47). The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms’ tumor gene 1 expression is present in a single bone marrow sample. The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% ( =0.377) and 9.1% and 0.0% ( =0.985) for patients in the IFN- and chemo-DLI groups, respectively. The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% ( =0.891) and 84.3% and 84.6% ( =0.972) for patients in the IFN- and chemo-DLI groups, respectively. Persistent MRD after immunotherapy was associated with poor survival. Thus, the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after allo-HSCT, and the efficacy was comparable between chemo-DLI and IFN- treatment.

关键词： donor leukocyte infusion     hematopoietic stem cell transplantation     interferon-   

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Phase separation in cGAS-STING signaling

《医学前沿（英文）》   页码 855-866 doi: 10.1007/s11684-023-1026-6

摘要： Biomolecular condensates formed by phase separation are widespread and play critical roles in many physiological and pathological processes. cGAS-STING signaling functions to detect aberrant DNA signals to initiate anti-infection defense and antitumor immunity. At the same time, cGAS-STING signaling must be carefully regulated to maintain immune homeostasis. Interestingly, exciting recent studies have reported that biomolecular phase separation exists and plays important roles in different steps of cGAS-STING signaling, including cGAS condensates, STING condensates, and IRF3 condensates. In addition, several intracellular and extracellular factors have been proposed to modulate the condensates in cGAS-STING signaling. These studies reveal novel activation and regulation mechanisms of cGAS-STING signaling and provide new opportunities for drug discovery. Here, we summarize recent advances in the phase separation of cGAS-STING signaling and the development of potential drugs targeting these innate immune condensates.

关键词： biomolecular condensates     phase separation     cGAS-STING pathway     cGAS     STING     cGAMP     interferon    

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Control of lupus activity during pregnancy via the engagement of IgG sialylation: novel crosstalk between IgG sialylation and pDC functions

《医学前沿（英文）》 2023年 第17卷 第3期   页码 549-561 doi: 10.1007/s11684-022-0965-7

摘要： Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.

关键词： pregnancy     IgG glycome     type I interferon     systemic lupus erythematosus    

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标题 作者 时间 类型 操作

High-expression of recombinant human concensus interferon-α by Pichia pastoris

HAO Yuyou, SHI Qiqi, HE Yun, ZHUANG Yingping, WANG Yonghong, ZHANG Siliang, CHU Ju, LIU Zhimin

期刊论文

Interferon-α salvage treatment is effective for patients with acute leukemia/myelodysplastic syndrome

Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang

期刊论文

Testing of tuberculosis infection among Chinese adolescents born after terminating the Bacillus Calmette--Guérin booster vaccination: subgroup analysis of a population-based cross-sectional study

null

期刊论文

Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation

Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang

期刊论文

Phase separation in cGAS-STING signaling

期刊论文

Control of lupus activity during pregnancy via the engagement of IgG sialylation: novel crosstalk between IgG sialylation and pDC functions

期刊论文