预约演示

更新于：2025-05-07

CTSZ

更新于：2025-05-07

基本信息

别名

carboxypeptidase LB、cathepsin B2、cathepsin IV

+ [9]

简介

Exhibits carboxy-monopeptidase as well as carboxy-dipeptidase activity (PubMed:10504234). Capable of producing kinin potentiating peptides (By similarity).

关联

项与 CTSZ 相关的药物

WO2024136397

专利挖掘

靶点

CTSZ

作用机制-

在研机构

Kookmin University Industry-Academic Cooperation [+1]

原研机构

Kookmin University Industry-Academic Cooperation [+1]

在研适应症

肿瘤 [+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 CTSZ 相关的临床结果

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100 项与 CTSZ 相关的转化医学

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0 项与 CTSZ 相关的专利（医药）

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213

项与 CTSZ 相关的文献（医药）

2025-12-31·The Journal of Maternal-Fetal & Neonatal Medicine

Mendelian randomization analysis of blood uric acid and risk of preeclampsia: based on GWAS and eQTL data

Article

作者: Zhu, Baosheng ; Zhang, Jinman ; Wang, Jiao ; Liu, Xiaohu ; Fu, Youmou

BACKGROUNDThe causal association between blood uric acid and preeclampsia (Preeclampsia, PE) has not been conclusively established based on the literature reviewed to date. This bi-directional Mendelian randomization study aimed to investigate the bi-directional causal association between blood uric acid concentration and PE at different genetic levels.METHODSPooled data on preeclampsia (sample size = 82,085) and blood uric acid (sample size = 129,405) were conducted based on publicly available genome-wide association analysis (Genome-Wide Association Study, GWAS) on the East Asian populations regarding preeclampsia and blood uric acid, respectively. We assessed blood uric acid and PE associations using two-sample Mendelian randomization (TSMR) analyses based on GWAS pooled statistics using inverse variance weighted (Inverse variance weighted), MR-Egger, and Weighted median (Weighted median) to examine the association between blood uric acid and pre-eclampsia. Causal relationship between blood uric acid and pre-eclampsia.Cochran's Q statistic was used to quantify the heterogeneity of instrumental variables among other methods. Subsequently, we extracted the expression quantitative trait loci (eQCTL, Expression quantitative trait loci) data corresponding to each gene as the instrumental variables using the genes corresponding to the intersecting instrumental variables of the exposure and the outcome in the respective analyses of the forward and backward TSMR respectively, so as to analyze the genetic causality of the genes with the different forward and backward TSMR methods further. Inverse variance weighted (IVW) was used to analyze the genetic causality of genes with different positive and negative outcomes.RESULTSGenetically determined blood uric acid level IVW method, ratio (OR) 1.30, 95% confidence interval (CI): [0.6, 2.83], p = 0.51 was not risk associated with PE. In addition according to the inverse MR analysis, we found an OR of 0.99, 95% CI [0.99, 1.0], p = 0.999) for PE on blood uric acid level IVW method and no significant heterogeneity in instrumental variables or level polytropy was found. (ii) Although GWAS data suggested no risk association between PE and uric acid, gene association analysis of eQTL data at blood uric acid levels with PE suggested a risk effect of the TP53INP1 gene for PE (IVW, OR = 11.476, 95% CI 2.511-52.452, p = 1.648 × 10^-3) and a protective effect of CTSZ (IVW, OR = 0.011, 95% CI 0.001-0.189, p = 1.804 × 10^-3), while a risk effect of ETV7 on hyperuricemia was suggested in a genetic association analysis of PE eQTL data with blood uric acid levels (OR = 1.018, 95% CI 1.007-1.029, p = 1.289 × 10^-3).CONCLUSIONOur MR (Mendelian Randomization) study based on the GWAS database did not support a bidirectional causal effect between blood uric acid levels and PE, whereas MR based on quantitative trait loci suggested that TP53INP1, which affects uric acid levels, has a risk association for PE, whereas CTSZ is protective against preeclampsia. Among the genes affecting PE the ETV7 gene may play a positive role in elevating uric acid levels.

2025-03-07·Medicine

Cathepsins and their role in gynecological cancers: Evidence from two-sample Mendelian randomization analysis

Article

作者: Li, Xiaoying ; Ma, Xiuli ; Wu, Xiaoting ; Qiu, Meng ; Sun, Lingyi

Prior studies have reported connections between cathepsins (CTS) and gynecological cancers; however, the exact causal links are yet to be fully understood. Leveraging publicly accessible genome-wide association study summary datasets, we performed a two-sample bidirectional Mendelian randomization (MR) and multivariate MR (MVMR) analysis, with the inverse variance weighted (IVW) method as the primary approach. MR analysis demonstrated inverse associations between CTSB and cervical cancer (IVW: odds ratio [OR] = 0.9995, 95% confidence interval [CI] = 0.9991–0.9999, P = .0418), CTSE and ovarian cancer (IVW: OR = 0.9197, 95% CI = 0.8505–0.9944, P = .0358), CTSZ and ovarian cancer (IVW: OR = 0.9449, 95% CI = 0.8938–0.9990, P = .0459), CTSE and high grade serous ovarian cancer (IVW: OR = 0.8939, 95% CI = 0.8248–0.9689, P = .0063), and CTSZ and high grade serous ovarian cancer (IVW: OR = 0.9269, 95% CI = 0.8667–0.9913, P = .0268). A positive correlation was identified between CTSH and clear cell ovarian cancer (IVW: OR = 1.1496, 95% CI = 1.0368–1.2745, P = .0081). Nevertheless, subsequent adjustment for the false discovery rate revealed that none of the P-values retained statistical significance (P FDR > 0.05). MVMR analysis results elucidated that CTSZ was inversely associated with cervical cancer (IVW: OR = 0.9988, 95% CI = 0.9981–0.9996, P = .0022). Moreover, a positive association was noted between CTSF and cervical cancer (IVW: OR = 1.0007, 95% CI = 1.0000–1.0014, P = .0364), and similarly, between CTSS and cervical cancer (IVW: OR = 1.0005, 95% CI = 1.0000–1.0011, P = .0490). CTSO exhibited a positive association with non-endometrioid endometrial cancer (IVW: OR = 1.4405, 95% CI = 1.1864–1.7490, P < .001), and CTSH was positively associated with clear cell ovarian cancer (IVW: OR = 1.1167, 95% CI = 1.0131–1.2310, P = .0263). The MVMR analysis findings reveal that CTSZ emerges as a protective element against cervical cancer, whereas CTSF and CTSS represent risk factors for this disease. CTSO stands out as a risk factor for non-endometrioid endometrial cancer, and CTSH acts as a risk factor for clear cell ovarian cancer. This study elucidates causative connections between CTS and gynecological cancers, providing innovative insights for diagnostic and therapeutic optimization.

2025-02-01·Archivos de Bronconeumología

Quantitative Proteomics Analysis of Serum and Urine With DIA Mass Spectrometry Reveals Biomarkers for Pediatric Obstructive Sleep Apnea

Article

作者: Wu, Yunxiao ; Xu, Zhifei ; Zhang, Kai ; Li, Mansheng ; Ma, Jie ; Gozal, David ; Zhu, Yunping

OBJECTIVESIdentification of suitable biomarkers that facilitate the screening and evaluation of pediatric obstructive sleep apnea (OSA) and its severity was explored.METHODSData-independent acquisition quantitative proteomic analysis was employed to identify serum and urine proteins with differential expression patterns between children with OSA and controls. Differentially expressed proteins that gradually increased or decreased with the severity of OSA were retained as potential biomarkers and underwent ELISA validation.RESULTSWe found that with increasing severity of OSA, there was a gradual upregulation of 34 proteins in the serum and 124 proteins in the urine, along with a respective downregulation of 10 serum proteins and 64 urinary proteins in the initial cohort of 40 children. These proteins primarily participate in immune activation, the complement pathway, oxygen transport, and reactive oxygen metabolism. Notably, cathepsin Z exhibited a positive correlation with the obstructive apnea hypopnea index, whereas sex hormone-binding globulin (SHBG) was negatively correlated. These proteins were then validated by ELISA in an independent cohort (n=21). Circulating cathepsin Z and SHBG levels displayed acceptable diagnostic performance of OSA with AUC values of 0.863 and 0.738, respectively.CONCLUSIONSWe identified two promising circulating proteins as novel biomarkers for clinical diagnosis and assessment of pediatric OSA severity. Furthermore, the comprehensive proteomic profile in pediatric OSA should aid in exploring the underlying pathophysiological mechanisms associated with this prevalent condition.

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