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Acta Pharmaceutica Sinica B ; (6): 4511-4522, 2023.
Article in English | WPRIM | ID: wpr-1011181


Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8+ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8+ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Acta Pharmaceutica Sinica B ; (6): 2835-2849, 2021.
Article in English | WPRIM | ID: wpr-888890


Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3

Chinese Journal of General Practitioners ; (6): 904-907, 2020.
Article in Chinese | WPRIM | ID: wpr-870721


Epidemiologic, clinical and imaging data were collected from 14 children with confirmed coronavirus disease 2019 (COVID-19) admitted in Beijing Ditan Hospital from January 27, 2020 to February 12, 2020. There were 6 boys and 8 girls with a median age of 3.5 years (6 months-9.4 years). Four patients had a history of travel to Wuhan City or Hubei Province and 2 patients had contacted with people from Wuhan; 13 patients were familial cluster of infection. The incubation period was 4 to 16 days. The clinical manifestations were fever in 8 cases, cough in 5 cases, diarrhea in 1 case; and 2 cases were asymptomatic. Four patients had abnormal peripheral blood routine, including 1 had lymphocytosis, 3 had lymphocytopenia; 3 patients had a slightly elevated CRP, and 3 patients had hepatic dysfunction. Thirteen patients underwent chest CT; and 1 case showed bilateral lung glass exudation, 1 case showed multiple patchy high density shadows of bilateral lung. One patient underwent chest X-ray examination, which was showed no abnormal findings. The pediatric patients with COVID-19 in this series generally have a traceable epidemiological history. The clinical manifestations are fever, cough and diarrhea. Peripheral white blood cell counts were most normal. Chest CT reveals less severe changes than those in adults, most child patients show no manifestation of pneumonia.

Journal of Clinical Hepatology ; (12): 724-727, 2019.
Article in Chinese | WPRIM | ID: wpr-778787


Nowadays, many clinical studies have demonstrated that some patients can achieve the reversal of liver cirrhosis. Therefore, the methods for accurate assessment of whether the reversal of liver cirrhosis can be achieved and when it is achieved have become the hotspots in clinical research. This helps with the specific evaluation of therapeutic outcome, the adjustment of treatment regimen, and the prediction of prognosis. This article introduces the application of various indices after the reversal of liver cirrhosis due to different etiologies from the aspects of noninvasive models and liver biopsy, in order to search for the methods that can accurately reflect the features of reversal.

Journal of Clinical Hepatology ; (12): 2001-2003, 2017.
Article in Chinese | WPRIM | ID: wpr-664155


Muscle cramp is one of the common symptoms of patients with liver cirrhosis and significantly affects patients' quality of life.In general,the research on liver cirrhosis mainly focuses on the management and prevention of causes or common complications,and there are relatively few studies on the treatment of muscle cramp.Therefore,it is very important to find safe and effective therapeutic regimens.This article describes the pathogenesis and manifestations of muscle cramp in patients with liver cirrhosis,summarizes the therapeutic regimens with clinical value,including new drugs such as baclofen,L-carnitine,and taurine,and further elaborates on the protective effect of taurine against liver fibrosis via its activation of extracellular matrix and hepatic stellate cells,in order to provide new evidence for the treatment of muscle cramp in liver cirrhosis.