Evaluation of Retinol Palmitate Ophthalmic Suspension in Severe Dry Eye and Ocular Surface Keratinisation associated with Chronic Stevens Johnson Syndrome

开始日期2021-11-22

申办/合作机构-

ChiCTR2100052140 / Suspended临床4期

The Effect of Vitamin A Paimitate Eye Gel on Corneal Abrasions During General Anesthesia

开始日期2021-11-01

申办/合作机构

北京同仁医院管理有限公司

JPRN-jRCTs031200260 / CompletedN/AIIT

Evaluation of a cosmetic gel containing retinol palmitate for its improvement effect on wrinkles

开始日期2021-01-07

申办/合作机构-

100 项与 RXRs x RARs 相关的临床结果

登录后查看更多信息

100 项与 RXRs x RARs 相关的转化医学

登录后查看更多信息

0 项与 RXRs x RARs 相关的专利（医药）

登录后查看更多信息

1,474

项与 RXRs x RARs 相关的文献（医药）

2024-10-17·FEBS letters

Feedback regulation of retinaldehyde reductase DHRS3, a critical determinant of retinoic acid homeostasis.

Article

作者: Varshosaz, Parisa ; Moise, Alexander R ; O'Connor, Catherine

Retinoic acid is crucial for vertebrate embryogenesis, influencing anterior-posterior patterning and organogenesis through its interaction with nuclear hormone receptors comprising heterodimers of retinoic acid receptors (RARα, β, or γ) and retinoid X receptors (RXRα, β, or γ). Tissue retinoic acid levels are tightly regulated since both its excess and deficiency are deleterious. Dehydrogenase/reductase 3 (DHRS3) plays a critical role in this regulation by converting retinaldehyde to retinol, preventing excessive retinoic acid formation. Mutations in DHRS3 can result in embryonic lethality and congenital defects. This study shows that mouse Dhrs3 expression is responsive to vitamin A status and is directly regulated by the RAR/RXR complex through cis-regulatory elements. This highlights a negative feedback mechanism that ensures retinoic acid homeostasis.

2024-08-01·Gene

Elucidating the mechanism of action of Isobavachalcone induced autophagy and apoptosis in non-small cell lung cancer by network pharmacology and experimental validation methods

Article

作者: Wang, Xue ; Wang, Ziqiang ; Ni, Yuhan ; Zhang, Jing ; Wang, Luyao ; Wang, Xiaojing ; Hu, Mengling ; Zhang, Tingting ; Lian, Chaoqun

BACKGROUNDLung cancer is the leading cause of cancer deaths, and non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer-related mortality. In recent years, there have been numerous treatments for non-small cell lung cancer, but the cure and survival rates are still extremely low. Isobavachalcone (IBC) belongs to the chalcone component of the traditional Chinese medicine Psoralea corylifolia L., and is a unique Protein kinase B (AKT) pathway inhibitor with significant anticancer effects. Previous studies have shown that IBC possess a variety of biological properties, including anti-cancer, anti-inflammatory, and antioxidant properties. This study focused on the use of network pharmacology analysis, molecular docking technology and experimental validation to elucidate the potential mechanisms of IBC for the treatment of NSCLC.METHODSScreening key genes and pathways of IBC action in NSCLC using network pharmacology. The IBC target genes were from The Encyclopedia of Traditional Chinese Medicine (ETCM) and BATMAN-TCM databases, the NSCLC target genes were from GeneCards, Online Mendelian Inheritance in Man (OMIM) and The Therapeutic Target database (TTD) databases, both of which were taken as intersecting genes for protein-protein interaction network analysis and enrichment analysis, and the binding energies of the compounds to the core targets were further verified by molecular docking. Cell lines in vitro experiments were then performed to further unravel the mechanism of IBC for NSCLC.RESULTSA total of 279 potential targets were retrieved by searching the intersection of IBC and NSCLC targets. Protein-protein interaction (PPI) network analysis indicated that 6 targets, including AKT1, RXRA, NCOA1, RXRB, RARA, PPARG were hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that IBC treatment of NSCLC mainly involves steroid binding, transcription factor activity, Pathways in cancer, cAMP signaling pathway, Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. Among them, the AMPK signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of NSCLC. Then, the results of in vitro experiment indicated that IBC could inhibit proliferation of NSCLC cells and induce cell autophagy and apoptosis. The results also showed that IBC could increase the protein expression of AMPK and decrease the protein expression of AKT and mammalian target of rapamycin (mTOR), suggesting that IBC can treat NSCLC by inducing cellular autophagy and apoptosis as well as modulating AMPK and AKT signaling pathways.CONCLUSIONSIn summary, this study provided a new insight into the protective mechanism of IBC against NSCLC through network pharmacology and experimental validation.

2024-06-01·Biotechnology Journal

Development and validation of CYP26A1 inhibition assay for high‐throughput screening

Article

作者: Ma, Dongping ; Xia, Menghang ; Knudsen, Thomas B ; Cali, James J ; Kleinstreuer, Nicole ; Sakamuru, Srilatha ; Baker, Nancy C ; Pierro, Jocylin D

AbstractAll‐trans retinoic acid (atRA) is an endogenous ligand of the retinoic acid receptors, which heterodimerize with retinoid X receptors. AtRA is generated in tissues from vitamin A (retinol) metabolism to form a paracrine signal and is locally degraded by cytochrome P450 family 26 (CYP26) enzymes. The CYP26 family consists of three subtypes: A1, B1, and C1, which are differentially expressed during development. This study aims to develop and validate a high throughput screening assay to identify CYP26A1 inhibitors in a cell‐free system using a luminescent P450‐Glo assay technology. The assay performed well with a signal to background ratio of 25.7, a coefficient of variation of 8.9%, and a Z‐factor of 0.7. To validate the assay, we tested a subset of 39 compounds that included known CYP26 inhibitors and retinoids, as well as positive and negative control compounds selected from the literature and/or the ToxCast/Tox21 portfolio. Known CYP26A1 inhibitors were confirmed, and predicted CYP26A1 inhibitors, such as chlorothalonil, prochloraz, and SSR126768, were identified, demonstrating the reliability and robustness of the assay. Given the general importance of atRA as a morphogenetic signal and the localized expression of Cyp26a1 in embryonic tissues, a validated CYP26A1 assay has important implications for evaluating the potential developmental toxicity of chemicals.

项与 RXRs x RARs 相关的新闻（医药）

2024-08-13

·Pharmaceutical Technology

Syros’ stock craters after Phase II AML trial termination due to inefficacy

Syros still plans to continue the development of tamibarotene in higher-risk myelodysplastic syndromes (HR-MDS) indication, with pivotal complete response data from a Phase III trial expected in Q4 this year. Image Credit: eamesBot / Shutterstock. Syros Pharmaceuticals has discontinued enrolment in the Phase II SELECT-AML-1 trial evaluating its cancer therapy, tamibarotene, after a futility analysis found that the study had a “low” likelihood of success. Following the news, the US-based company’s stock took a nosedive and was down by more than 62% in premarket trading on 13 August, compared to the market close on the previous day. This is a sharp contrast to December when its stock assumed an upward trajectory after Syros shared initial positive data from the Phase II SELECT-AML-1 trial. At its peak, the company’s stock was worth over $7.79 and is currently worth $1.83 in premarket today. Syros’s current market cap is $134.3m. The futility analysis was conducted on the data from the first 40 randomised patients enrolled in the Phase II trial (NCT04905407). The study evaluated the triplet therapy of tamibarotene in combination with AbbVie ’s Venclyxto (venetoclax) and azacitidine versus the double treatment of Venclyxto and azacitidine. The data showed that the complete response (CR)/complete response with incomplete haematologic recovery (CRi) rates observed across both arms were similar, 65% and 70% in the triplet and doublet arms, respectively. The analysis then concluded that the final analysis of 80 randomised patients had a “low probability of success”. See Also: Bavarian Nordic wins positive CHMP opinion to amend Imvanex approval EAN 2024: anti-CGRPs more effective than onabotulinumtoxinA in chronic migraine prevention in real world Tamibarotene is a specific agonist for retinoic acid receptor alpha/beta with possible binding to retinoid X receptors (RXR). The RXR receptors regulate the transcription of signalling pathways that impact numerous hallmarks of cancer by controlling both inflammation and immune responses that modulate the tumour microenvironment. Syros was adamant that the company was not ditching the cancer therapy completely. The company stated that it will continue to evaluate tamibarotene in patients with higher-risk myelodysplastic syndromes (HR-MDS). The Phase III SELECT-MDS-1 trial (NCT04797780) is evaluating tamibarotene in combination with azacitidine. The study passed a prespecified futility analysis in Q1, with pivotal complete response data expected in Q4 this year.