A combination study on WP-1303 or placebo and latanoprost ophthalmic solution in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).

开始日期2019-09-06

申办/合作机构

Wakamoto Pharmaceutical Co., Ltd.

JPRN-JapicCTI-194923 / Recruiting临床3期

A combination study on WP-1303 or placebo and timolol ophthalmic solution in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH)

开始日期2019-09-06

申办/合作机构

Wakamoto Pharmaceutical Co., Ltd.

JPRN-JapicCTI-194920 / Recruiting临床3期

A comparison study on WP-1303 and ripasudil ophthalmic solution in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).

开始日期2019-09-06

申办/合作机构

Wakamoto Pharmaceutical Co., Ltd.

100 项与 ROCK2 x HSP90 相关的临床结果

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100 项与 ROCK2 x HSP90 相关的转化医学

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0 项与 ROCK2 x HSP90 相关的专利（医药）

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项与 ROCK2 x HSP90 相关的文献（医药）

2023-12-01·Journal of Cellular and Molecular Medicine

Identification of immune‐associated signatures and potential therapeutic targets for pulmonary arterial hypertension

Article

作者: Zhang, Juqi ; Zhao, Dai ; Gu, Yanlun ; He, Xu ; Xie, Ran ; Gong, Mingli ; Cui, Yimin ; Ma, Lingyue ; Pang, Xiaocong ; Fang, Jiansong

AbstractPulmonary arterial hypertension (PAH) comprises a heterogeneous group of diseases with diverse aetiologies. It is characterized by increased pulmonary arterial pressure and right ventricular (RV) failure without specific drugs for treatment. Emerging evidence suggests that inflammation and autoimmune disorders are common features across all PAH phenotypes. This provides a novel idea to explore the characteristics of immunological disorders in PAH and identify immune‐related genes or biomarkers for specific anti‐remodelling regimens. In this study, we integrated three gene expression profiles and performed Gene Ontology (GO) and KEGG pathway analysis. CIBERSORT was utilized to estimate the abundance of tissue‐infiltrating immune cells in PAH. The PPI network and machine learning were constructed to identify immune‐related hub genes and then evaluate the relationship between hub genes and differential immune cells using ImmucellAI. Additionally, we implemented molecular docking to screen potential small‐molecule compounds based on the obtained genes. Our findings demonstrated the density and distribution of infiltrating CD4 T cells in PAH and identified four immune‐related genes (ROCK2, ATHL1, HSP90AA1 and ACTR2) as potential targets. We also listed 20 promising molecules, including TDI01953, pemetrexed acid and radotinib, for PAH treatment. These results provide a promising avenue for further research into immunological disorders in PAH and potential novel therapeutic targets.

2022-07-06·Open Medicine

Identification of autophagy-related biomarkers in patients with pulmonary arterial hypertension based on bioinformatics analysis

Article

作者: Ge, Haiyan ; Yang, Zhisong ; Shan, Lin ; Zhou, Li ; Shen, Weimin

AbstractAutophagy participates in the regulation of pulmonary arterial hypertension (PAH). However, the role of autophagy-related genes (ARGs) in the pathogenesis of the PAH is still unclear. This study aimed to identify the ARGs in PAH via bioinformatics analysis. A microarray dataset (GSE113439) was downloaded from the Gene Expression Omnibus database to identify differentially expressed ARGs (DEARGs). Protein–protein interactions network, gene ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to screen hub genes and the underlying molecular mechanisms of PAH. Finally, the mRNA expression of the hub genes was validated using the GSE53408 dataset. Twenty-six DEARGs were identified, all of which were upregulated. Enrichment analyses revealed that these DEARGs were mainly enriched in the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, PI3K-Akt signaling pathway, response to hypoxia, response to nutrient levels, and autophagy. Among these hub genes, the mRNA expression levels of HSP90AA1, HIF1A, MET, IGF1, LRRK2, CLTC, DNM1L, MDM2, RICTOR, and ROCK2 were significantly upregulated in PAH patients than in healthy individuals. Ten hub DEARGs were identified and may participate in the pathogenesis of the PAH via the regulation of autophagy. The present study may provide novel therapeutic targets for PAH prevention and treatment and expand our understanding of PAH.

2020-12-01·Genome Medicine1区 · 生物学

De novo variants in exomes of congenital heart disease patients identify risk genes and pathways

1区 · 生物学

ArticleOA

作者: Gelb, Bruce D ; Tristani-Firouzi, Martin ; Sevim Bayrak, Cigdem ; Zhang, Peng ; Itan, Yuval

AbstractBackgroundCongenital heart disease (CHD) affects ~ 1% of live births and is the most common birth defect. Although the genetic contribution to the CHD has been long suspected, it has only been well established recently. De novo variants are estimated to contribute to approximately 8% of sporadic CHD.MethodsCHD is genetically heterogeneous, making pathway enrichment analysis an effective approach to explore and statistically validate CHD-associated genes. In this study, we performed novel gene and pathway enrichment analyses of high-impact de novo variants in the recently published whole-exome sequencing (WES) data generated from a cohort of CHD 2645 parent-offspring trios to identify new CHD-causing candidate genes and mutations. We performed rigorous variant- and gene-level filtrations to identify potentially damaging variants, followed by enrichment analyses and gene prioritization.ResultsOur analyses revealed 23 novel genes that are likely to cause CHD, including HSP90AA1, ROCK2, IQGAP1, and CHD4, and sharing biological functions, pathways, molecular interactions, and properties with known CHD-causing genes.ConclusionsUltimately, these findings suggest novel genes that are likely to be contributing to CHD pathogenesis.