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更新于：2025-05-07

GCA

更新于：2025-05-07

基本信息

别名

GCA、GCL、grancalcin

简介

Calcium-binding protein that may play a role in the adhesion of neutrophils to fibronectin. May play a role in the formation of focal adhesions.

关联

项与 GCA 相关的药物

CN116672447

专利挖掘

靶点

GCA

作用机制-

在研机构

中南大学湘雅医院

原研机构

中南大学湘雅医院

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

CN118634324

专利挖掘

靶点

GCA

作用机制-

在研机构

中南大学湘雅医院

原研机构

中南大学湘雅医院

在研适应症

纤维化 [+2]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

CN117281901

专利挖掘

靶点

GCA

作用机制-

在研机构

中南大学湘雅医院

原研机构

中南大学湘雅医院

在研适应症

营养和代谢疾病 [+1]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 GCA 相关的临床结果

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100 项与 GCA 相关的转化医学

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0 项与 GCA 相关的专利（医药）

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290

项与 GCA 相关的文献（医药）

2025-07-01·Food and Chemical Toxicology

Bavachinin causes cholestasis by down-regulating BAAT expression and disrupting glycocholic acid synthesis in human liver organoids

Article

作者: Wang, Xue ; Jia, Jidong ; Liu, Lin ; Chen, Xiaomeng ; Su, Yu ; Zhao, Xinyan

Psoraleae Fructus (Bu Gu Zhi, BGZ) is extensively utilized for dermatological and osseous disorders in China. BGZ-induced liver injury has become one of the major concerns, which predominantly cause cholestasis, with the pathogenesis not being fully elucidated. Currently, studies on hepatotoxic mechanisms of BGZ have mainly been conducted on 2D cell culture systems or rodent models, which may not fully encapsulate human pathophysiology. Therefore, we generated human liver organoids (HLOs) from healthy donor(s) for living-related liver transplantation to explore the hepatotoxic mechanism. We identified bavachinin (BVC) as the most hepatotoxic component for cholestasis. After validating by CLF tests, we identified BVC caused cholestasis by down-regulating BAAT, which catalyzes the amidation of bile acids. We also found that up-regulating BAAT with harmaline could mitigate cholestasis and enhance cell viabilities in HLOs. We further demonstrated that glycocholic acid (GCA) levels decreased in BVC-treated HLOs. Supplementation of GCA to BVC-treated HLOs significantly improved cell viabilities. Collectively, our data suggested that BVC impaired the GCA synthesis by down-regulating the expression of BAAT, thereby inducing cholestasis.

2025-06-01·Journal of Structural Biology

Determinants of site-selectivity in human ileal bile acid-binding protein by NMR dynamic analysis of a functionally-impaired mutant

Article

作者: Horváth, Gergő ; Teski, Tamara ; Toke, Orsolya

Human ileal bile acid-binding protein (hI-BABP), a member of the family of intracellular lipid-binding proteins, has a key role in the enterohepatic circulation of bile salts. The two internal binding sites of hI-BABP exhibit positive cooperativity accompanied by a site preference of glycocholate (GCA) and glycochenodeoxycholate (GCDA), the two most abundant bile salts in the human body. Previous study of Q51A hI-BABP in its apo state, a mutant with lost site-selectivity, suggests that disruption of the hydrogen-bonding network in the vicinity of the C/D-turn has long-range dynamic effects. To improve our understanding of the determinants of site-selectivity in hI-BABP, a comparative NMR chemical shift and spin relaxation analysis of homo- and heterotypic bile salt complexes of wild-type and Q51A hI-BABP was carried out. The wild-type GCDA-complex shows a striking similarity with the thermodynamically most stable hI-BABP:GCDA:GCA complex in terms of both structure and dynamic behaviour, suggesting that the bound GCDA at site 1 has a decisive role in conveying key stabilizing interactions in the physiologically most abundant heterotypic complex. Destabilization of hI-BABP-GCDA by the functionally impairing mutation Q51A is indicated by both the increase of ms-timescale motions in key segments of the protein as well as by increased ps-ns local fluctuations superimposed on slow motions. Our study suggests that binding interactions in hI-BABP might be modulated by altering the dynamic behaviour of specific segments in the protein with implications for targeting the intracellular trafficking of bile salts and bile salt-induced stimulation of nuclear receptors.

2025-04-01·Theoretical and Applied Genetics

Integrative mapping in large inbred and hybrid association panels along with an F2 population advanced a novel understanding of general combining ability for plant height in maize

Article

作者: Bai, Guangxiao ; Peng, Zhonghua ; Yi, Qiang ; Luo, Jie ; Jiang, Yulin ; Li, Yangjing ; Zhang, Xiaoxiang ; Hou, Xianbin

KEY MESSAGEWe identified 44 QTL for PH-related traits evaluated for inbreds per se and GCA effects in large inbred and hybrid association panels and seven QTL for EH/PH in an F₂ population coupled with BSA-seq. Among four co-localized QTL, seven novel potential candidate genes were significantly associated with PH-related traits, shedding new light on understanding the genetics of GCA for PH. Breeding optimal plant height (PH) is essential for improving maize (Zea mays L.) plant architecture, yield, lodging resistance, and density tolerance, yet there is limited genetic loci available regarding the general combining ability (GCA) for PH-related traits. In the current study, an inbred association panel of 312 inbred lines (IAP) along with a hybrid association panel (HAP) of 764 hybrid combinations were utilized to dissect the genetics of PH-related traits and their GCA effects across three environments. We found 44 quantitative trait loci (QTL) with 76 significant single-nucleotide polymorphisms (SNPs) for PH-related traits evaluated for inbreds per se and GCA effects; however, no overlapping loci were identified across inbreds per se and GCA effects, indicating conspicuous discrepancies in their genetics. In addition, GCA effects with complex genetic basis differed for diverse testers, which highlighted the specificity and complexity among heterotic groups. Correspondingly, we evaluated an F₂ population derived from two parental lines LY-02 and LH513 with the contrasting EH/PH coupled with bulked segregant analysis by sequencing (BSA-seq) and found seven QTL for EH/PH. Among four co-localized loci across the association and QTL mapping, seven novel candidate genes were found to differently express among LY-02, LH513, and their F₁ and were potentially associated with PH-related traits. The current study with combined mapping in diverse mapping populations provided a novel understanding of GCA for PH-related traits in maize.

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