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https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/27
2024-03-28T08:01:47ZTranscriptomic data of human adrenocortical NCI-H295R cells treated with cortisol biosynthesis inhibitors
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/65474
Title: Transcriptomic data of human adrenocortical NCI-H295R cells treated with cortisol biosynthesis inhibitors
Authors: Kim, Soo Hyun; Kim, Hyun Jung; Jung, Jong-Wha; Chung, Sooyoung; Son, Gi Hoon
Abstract: Adrenal corticosteroid biosynthesis dysregulation can give rise to various pathological conditions, such as Cushing's syndrome, a disorder characterized by the sustained and excessive production of cortisol. Despite the development of several classes of steroidogenesis inhibitors to treat human diseases associated with cortisol overproduction, their use is limited by insufficient efficacy, adverse effects, and/or tolerability. Recently, we identified a series of benzimidazolylurea derivatives, including the representative compound CJ28, as novel cortisol biosynthesis inhibitors [1l . They significantly inhibited both basal and stimulated production of cortisol in NCI-H295R cells, a human adrenocarcinoma cell line. The inhibitory effects were attributed to both attenuated steroidogenesis and de novo cholesterol biosynthesis. Here, we provide transcriptomic (RNA-seq) data from adrenal cell cultures in response to treatment with either CJ28 or metyrapone (MET), an inhibitor of 11 beta-hydroxylase). Total RNA was extracted from the cells treated with vehicle (0.1% DMSO), CJ28 (30 mu M), or MET (30 mu M) for 24 h. Primary sequence data were acquired using paired-end sequencing on an Illumina NovaSeq 60 0 0 platform. The raw RNA-seq data have been deposited in the Gene Expression Omnibus (GEO) database (GSE236435). This dataset is a useful resource for providing valuable information on the gene expression networks underlying adrenocortical steroidogenesis.(c) 2023 Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )2024-02-01T00:00:00ZFunctional Characterization of Circadian Nuclear Receptors REV-ERBα and REV-ERBβ in Human Osteosarcoma Cell Cultures
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/65431
Title: Functional Characterization of Circadian Nuclear Receptors REV-ERBα and REV-ERBβ in Human Osteosarcoma Cell Cultures
Authors: Cho, Hana; Yun, Ahee; Kim, Joohee; Park, Eunjeong; Jung, Jong-Wha; Chung, Sooyoung; Son, Gi Hoon
Abstract: REV-ERB alpha and its paralog, REV-ERB beta, encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock and can be pharmacologically targeted to treat various circadian rhythm-related diseases, such as cardiometabolic, inflammatory, and neuropsychiatric diseases, as well as cancer. REV-ERBs are believed to be functionally redundant and compensatory, although they often affect the expression of gene subsets in an isoform-specific manner. Therefore, this study aimed to identify the redundant and distinct roles of each isoform in controlling its target genes by comparing the transcriptome profiles of a panel of mutant U2OS human osteosarcoma cells in which either NR1D1 or NR1D2 was ablated. Indeed, our transcriptomic analyses revealed that most REV-ERB-regulated genes are controlled by redundant or even additive actions. However, the RNA expression profiles of each single mutant cell line also provide strong evidence for isoform-dependent actions. For example, REV-ERB alpha is more responsible for regulating the NF-kappa Beta signaling pathway, whereas a group of extracellular matrix components requires REV-ERB beta to maintain their expression. We found that REV-ERBs have isoform-selective functions in the regulation of certain circadian output pathways despite their overlapping roles in the circadian molecular clock. Thus, the development of isoform-selective REV-ERB modulators can help treat metabolic disturbances and certain types of cancer.2024-01-01T00:00:00ZIdentification of a novel class of cortisol biosynthesis inhibitors and its implications in a therapeutic strategy for hypercortisolism
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/63507
Title: Identification of a novel class of cortisol biosynthesis inhibitors and its implications in a therapeutic strategy for hypercortisolism
Authors: Kim, Soo Hyun; Son, Gi Hoon; Seok, Joo Young; Chun, Sung Kook; Yun, Hwayoung; Jang, Jaebong; Suh, Young-Ger; Kim, Kyungjin; Jung, Jong-Wha; Chung, Sooyoung
Abstract: Aims
Dysregulation of adrenocortical steroid (corticosteroids) biosynthesis leads to pathological conditions such as Cushing's syndrome. Although several classes of steroid biosynthesis inhibitors have been developed to treat cortisol overproduction, limitations such as insufficient efficacy, adverse effects, and/or tolerability still remain. The present study aimed to develop a new class of small molecules that inhibit cortisol production, and investigated their putative modes of action.
Main methods
We screened an in-house chemical library with drug-like chemical scaffolds using human adrenocortical NCI-H295R cells. We then evaluated and validated the effects of the selected compounds at multiple regulatory steps of the adrenal steroidogenic pathway. Finally, genome-wide RNA expression analysis coupled with gene enrichment analysis was conducted to infer possible action mechanisms.
Key findings
A subset of benzimidazolylurea derivatives, including a representative compound (designated as CJ28), inhibited both basal and stimulated production of cortisol and related intermediate steroids. CJ28 attenuated the mRNA expression of multiple genes involved in steroidogenesis and cholesterol biosynthesis. Furthermore, CJ28 significantly attenuated de novo cholesterol biosynthesis, which contributed to its suppression of cortisol production.
Significance
We identified a novel chemical scaffold that exerts inhibitory effects on cortisol and cholesterol biosynthesis via coordinated transcriptional silencing of gene expression networks. Our findings also reveal an additional adrenal-directed pharmacological strategy for hypercortisolism involving a combination of inhibitors targeting steroidogenesis and de novo cholesterol biosynthesis.2023-07-01T00:00:00ZEstimating the Post-mortem Interval Using Black Larder Beetles (Coleoptera: Dermestidae): A Case Study of Cats Abandoned Indoors in Daegu, Korea
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/64319
Title: Estimating the Post-mortem Interval Using Black Larder Beetles (Coleoptera: Dermestidae): A Case Study of Cats Abandoned Indoors in Daegu, Korea
Authors: 백인성; 김나연; 문태영; 강태모; 최진혁; 박성환; 이경현; 김아영; 박상현
Abstract: Black larder beetles prefer to feed on decomposing animal bodies, particularly those that are dried. When conditions are dry and warm, these beetles often appear in large numbers on dried animal carcasses. In our case, the dried carcasses of several cats were found nearly skeletonized at a villa in Daegu Metropolitan City on July 13, 2022. There were very few empty pupae of Lucilia sericata (Meigen) in the villa, but many adult black larder beetles, larvae, and larval cast skin (exuviae) (Dermestes haemorrhoidalis Küster) belonging to the family of larder beetles (Dermestidae) were found. We estimated the minimum post-mortem interval to be 44.5 days using temperature data from the nearest meteorological observatory and reported animal carcass decomposition and Dermestidae developmental rates. Police investigation confirmed that the cats were alive at least 3 months ago. Consequently, the neglected cats could not have been deceased in the villa for more than 3 months. As a result, the estimate closely matched the statement from the suspect.2023-05-01T00:00:00Z