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Biomedical subjects

Shuqing Chen

Publications and source records attributed to Shuqing Chen.

7 recordsLinked to original sources

TRAIT: A Comprehensive Database for T-cell Receptor-antigen Interactions.

Comprehensive and integrated resources on interactions between T-cell receptors (TCRs) and antigens are still lacking for adoptive T-cell-based immunotherapies, highlighting a significant gap that must be addressed to fully understand the mechanisms of antigen recognition by T cells. In this study, we present the T-cell receptor-antigen interaction database (TRAIT), a comprehensive database that profiles the interactions between TCRs and antigens. TRAIT stands out due to its comprehensive description of TCR-antigen interactions by integrating sequences, structures, and affinities. It provides millions of experimentally validated TCR-antigen pairs, resulting in an exhaustive landscape of antigen-specific TCRs. Notably, TRAIT emphasizes single-cell omics as a major reliable data source for TCR-antigen interactions and includes millions of reliable non-interactive TCRs. Additionally, it thoroughly demonstrates the interactions between mutations of TCRs and antigens, thereby benefiting affinity optimization of engineered TCRs as well as vaccine design. TCRs on clinical trials are innovatively provided. With the significant efforts made toward elucidating the complex interactions between TCRs and antigens, TRAIT is expected to ultimately contribute superior algorithms and substantial advancements in the field of T-cell-based immunotherapies. TRAIT is freely accessible at https://pgx.zju.edu.cn/traitdb.

Receptors, Antigen, T-Cell↗

Ethnic differences in frequencies of gene polymorphisms in the MYCL1 region and modulation of lung cancer patients' survival.

Linkage disequilibrium (LD) analysis to refine a region associated with lung cancer progression on chromosome 1p34 identified a 106 kb LD block that includes MYCL1, TRIT1 (tRNA isopentenyltransferase 1) and MFSD2 (major facilitator superfamily domain-containing 2). Case-only association study on SNPs mapping in TRIT1 and MFSD2 indicated that the rare Leu allele (frequency: 0.04) of the TRIT1 Phe202Leu variation predicts short survival as compared to the common Phe/Phe genotype (hazard ratio (HR)=1.7; 95% CI, 1.03-2.86; P=0.039) in 335 Italian lung adenocarcinoma samples. A replication study in an independent population of 246 Norwegian lung cancer patients confirmed the significant association of the Phe202Leu polymorphism with patients' survival, but the rare allele was associated with better survival rate (HR=0.5; 95% CI, 0.26-0.91; P=0.023). The rare allele of TRIT1 Phe202Leu SNP was approximately seven-fold more frequent in Asian than in Caucasian subjects and three additional SNPs in the TRIT1 and MFSD2 genes showed ethnic differences in allelic frequencies. These results suggest that polymorphisms in the MYCL1 LD region affect lung cancer survival but that the functional element(s) may show population-specific patterns.

Adenocarcinoma↗

Genetic variants of human UGT1A3: functional characterization and frequency distribution in a Chinese Han population.

UDP-glucuronosyltransferase 1A3 (UGT1A3) contributes to glucuronidation of many important endogenous compounds and xenobiotics, including some flavonoids. Recently, a total of six single nucleotide polymorphisms (SNPs) have been identified in the human UGT1A3 gene. Among them, four SNPs (A17G, Q6R; T31C, W11R; C133T, R45W; and T140C, V47A) cause amino acid substitutions. Variants caused by these SNPs showed an activity change in estrone metabolism, whereas their activities toward other substrates were not examined. In the present study, three common flavonoids, quercetin, luteolin, and kaempferol, were used as substrates for glucuronidation by wild-type and variant UGT1A3s. Our results demonstrated that the activities of three variants, UGT1A3.2, UGT1A3.3, and UGT1A3.5, were remarkably lower than that of UGT1A3.1. In contrast, UGT1A3.4 exhibited an increase in glucuronidation efficiency of approximately 4 times and a clear preference to quercetin 7- and 3-hydroxyl groups. The frequency distributions of UGT1A3 alleles and SNPs in UGT1A3 in a Chinese Han population were statistically different from the reported value in German-Caucasians (p < 0.05). UGT1A3 variants have an altered glucuronidation activity toward quercetin, luteolin, and kaempferol and may alter human susceptibility to flavonoid exposure.

China↗

Differences in cytochrome P450 2C19 (CYP2C19) expression in adjacent normal and tumor tissues in Chinese cancer patients.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) exhibits polymorphic expression in humans and deficiencies in its expression have been associated with a number of different cancers. Our aim was to determine if CYP2C19 mRNA and CYP2C19 enzyme protein expression differed between various tumors and normal tissue adjacent to the tumor tissue in Han Chinese cancer patients. MATERIALS AND METHODS: The level of CYP2C19 mRNA expression was examined in tumor and adjacent normal tissue from liver, colon, stomach, breast, esophagus, lung, uterus, brain, pancreas, ovary, kidney, and several cell lines by semi-quantitative RT-PCR Western immunoblots were also used to qualitatively assess CYP2C19 protein in the above tissues and cell lines. RESULTS: CYP2C19 mRNA was found only in normal livers, hepatic carcinomas, and hepatocarcinoma cell lines. The CYP2C19 mRNA was expressed at significantly higher levels in hepatocellular carcinomas (x +/- s: 3.72 +/- 1.21, n = 14) than in adjacent normal liver tissue (x +/- s: 1.79 +/- 0.33, n = 14, p = 0.000). CYP2C19 protein was also detected in hepatocarcinoma tissues, adjacent normal tissues, and the hepatocarcinoma cell lines HepG2, HepGA, and 7721 based on Western blotting methods. These results are in accordance with observations employing RT-PCR. CONCLUSIONS: CYP2C19 mRNA expression is highest in hepatocarcinoma tissue, moderate in adjacent normal liver tissue, and absent in other cancer tissues and their adjacent normal tissues. The significantly elevated expression of CYP2C19 mRNA in hepatocarcinoma indicates an association between the occurrence of hepatocarcinoma and the expression and/or turnover of CYP2C19 mRNA.

Aryl Hydrocarbon Hydroxylases↗

Cloning and expression of human UDP-glucuronosyltransferase 1A4 in Bac-to-Bac system.

UDP-glucuronosyltransferases (UGTs) catalyze the transfer of glucuronic acid from uridine diphosphate-glucuronic acid (UDP-GA) to compounds with amine, hydroxyl, and carboxylic acid moieties. N-glucuronidation is an important pathway for elimination of many tertiary amine therapeutic agents used in humans. UGT1A4 has been reported to be specific for glucuronidating primary, secondary, and tertiary amines, forming N-glucuronides. To further investigate the drugs metabolized by UGT1A4, the Bac-to-Bac expression system was used to express the recombinant UGT1A4 with His-tag on the C-terminal. The His-tagged recombinant UGT1A4 expressed in Spodoptera frugiperda (Sf9) cells were detected using anti-His antibody and the molecular weight of the recombinant protein was approximately 55kDa. The enzyme activity towards imipramine in cell homogenate protein was found to be 83.14+/-15pmol/min/mg protein (n=3) with 0.5mM imipramine by HPLC, but was not detectable in blank Sf9 cells. It paved the way for the further studies for drug glucuronidation by UGT1A4. The purification of the UGT1A4 can be done by Ni-resin. This is helpful to do research on the structure of the UFT1A4.

Animals↗

Mapping of chorismate mutase and prephenate dehydrogenase domains in the Escherichia coli T-protein.

The Escherichia coli bifunctional T-protein transforms chorismic acid to p-hydroxyphenylpyruvic acid in the l-tyrosine biosynthetic pathway. The 373 amino acid T-protein is a homodimer that exhibits chorismate mutase (CM) and prephenate dehydrogenase (PDH) activities, both of which are feedback-inhibited by tyrosine. Fifteen genes coding for the T-protein and various fragments thereof were constructed and successfully expressed in order to characterize the CM, PDH and regulatory domains. Residues 1-88 constituted a functional CM domain, which was also dimeric. Both the PDH and the feedback-inhibition activities were localized in residues 94-373, but could not be separated into discrete domains. The activities of cloned CM and PDH domains were comparatively low, suggesting some cooperative interactions in the native state. Activity data further indicate that the PDH domain, in which NAD, prephenate and tyrosine binding sites were present, was more unstable than the CM domain.

Binding Sites↗