Last update 01 Nov 2024

Trichothiodystrophy Syndromes

Last update 01 Nov 2024

Basic Info

Synonyms

ABHS, AMISH BRITTLE HAIR BRAIN SYNDROME, Amish Brittle Hair Brain Syndrome

+ [76]

Introduction

Autosomal recessive neuroectodermal disorders characterized by brittle sulfur-deficient hair associated with impaired intellect, decreased fertility, and short stature. It may include nail dystrophy, ICHTHYOSIS, and photosensitivity correlated with a NUCLEOTIDE EXCISION REPAIR defect. All individuals with this disorder have a deficiency of cysteine-rich KERATIN-ASSOCIATED PROTEINS found in the interfilamentous matrix. Photosensitive trichothiodystrophy can be caused by mutation in at least 2 separate genes: ERCC2 PROTEIN gene and the related ERCC3. Nonphotosensitive trichothiodystrophy can be caused by mutation in the TTDN1 gene.

Drugs associated with Trichothiodystrophy Syndromes

Oxiracetam

Target

GRIA2

Mechanism

GRIA2 positive allosteric modulator

Active Org.

Hunan Jianlang Pharmaceutical Co. Ltd. [+2]

Originator Org.-

Active Indication

Brain Injuries [+2]

Inactive Indication

Perioperative ischaemia [+1]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date01 Jan 1987

Clinical Trials associated with Trichothiodystrophy Syndromes

NCT05972512 / RecruitingNot ApplicableIIT

A Randomized, Double-Blind, Placebo-Controlled, Safety, and Efficacy Study of Plant Based Biotin and Plant Based Biotin With Silica in Healthy Adult Human Subjects With Complaints of Hair Fall Thin, Dry, & Brittle Hair, and Dry Skin

A randomized, double-blind, three-arm, placebo-controlled, safety, and efficacy study of plant-based Biotin and plant-based Biotin with Silica in healthy adult human subjects with complaints of hair fall, thin, dry, and brittle hair, and dry skin.
A sufficient number (maximum of 105 (35 subject/test treatment)) of female/male adult subjects will be recruited/enrolled to ensure a total of 96 subjects (32 subjects/test treatment) complete the study.

Start Date24 Oct 2023

Sponsor / Collaborator-

NCT05800496 / CompletedNot ApplicableIIT

A Proof-of-Concept, Placebo-Controlled, Safety, and Efficacy Study of Plant Based Biotin in Healthy Adult Human Subjects With Thin, Dry, and Brittle Hair

This is a randomized, placebo-controlled, double-blind, two-arm, single-centre, proof-of-concept, clinical study to evaluate the safety and efficacy of Plant based Biotin in Healthy Human Subjects with thin, dry, and brittle hair.
a sufficient number (maximum of 54 (27/arm)) of female/male adult subjects were recruited/enrolled to ensure a total of 50 subjects (25 subjects/arm) completed the study.

Start Date31 Oct 2022

Sponsor / Collaborator-

NCT05484570 / RecruitingNot ApplicableIIT

Natural History Study for DNA Repair Disorders

This will be a single-center, single-arm, non-interventional natural history study to evaluate the longitudinal clinical course, functional outcome measures, and candidate biomarkers for individuals with DNA repair disorders, including Cockayne syndrome (CS), xeroderma pigmentosum (XP), and trichothiodystrophy (TTD).

Start Date01 Oct 2022

Sponsor / Collaborator

University of Minnesota

100 Clinical Results associated with Trichothiodystrophy Syndromes

100 Translational Medicine associated with Trichothiodystrophy Syndromes

0 Patents (Medical) associated with Trichothiodystrophy Syndromes

692

Literatures (Medical) associated with Trichothiodystrophy Syndromes

31 Dec 2024·Animal Cells and Systems

Effect of RNF113A deficiency on oxidative stress-induced NRF2 pathway

Article

Author: Kim, Yong-Eun ; Park, Chungoo ; Cho, Namjoon ; Lee, Yunkyeong ; Kim, Jung-Hwan ; Kim, Kee K ; Choi, Dong Wook ; Kim, Keun Il

The ring finger protein 113A (RNF113A) serves as an E3 ubiquitin ligase and a subunit of the spliceosome. Mutations in the RNF113A gene are associated with X-linked trichothiodystrophy (TTD). However, the cellular roles of RNF113A remain largely unknown. In this study, we performed transcriptome profiling of RNF113A knockout (KO) HeLa cells using RNA sequencing and revealed the upregulation of NRF2 pathway-associated genes. Further analysis confirmed that the KO of RNF113A promotes nuclear localization of the NRF2 protein and elevates the mRNA levels of NRF2 target genes. RNF113A KO cells showed high levels of intracellular reactive oxygen species (ROS) and decreased resistance to cell death following H₂O₂ treatment. Additionally, RNF113A KO cells more sensitively formed stress granules (SGs) under arsenite-induced oxidative stress. Moreover, RNF113A KO cells exhibited a decrease in glutathione levels, which could be attributed to a reduction in GLUT1 expression levels, leading to decreased glucose uptake reactions and lower intracellular glucose levels. These alterations potentially caused a reduction in ROS scavenging activity. Taken together, our findings suggest that the loss of RNF113A promotes oxidative stress-mediated activation of the NRF2 pathway, providing novel insights into RNF113A-associated human diseases.

01 Nov 2024·Archives of Biochemistry and Biophysics

RNF113A as a poor prognostic factor promotes metastasis and invasion of cervical cancer through miR197/PRP19/P38MAPK signaling pathway

Article

Author: Yin, Rutie ; Zhang, Qingwei ; Xu, Tenghan ; Fu, Xiuhong ; Sun, Mingzhen ; Li, Suhong ; Song, Jiayu

It has been discovered that aberrant expression of RNF113A plays a significant role in various diseases, including esophageal cancer, hepatocellular carcinoma, and X-linked trichothiodystrophy syndrome. Nevertheless, its functional implications in cervical cancer (CC) remain unclear. The objective of this study was to investigate the role of RNF113A in both the development and prognosis of CC. To achieve this objective, a total of sixty cases were included in the follow-up investigation. The findings revealed a significant up-regulation of RNF113A protein in CC tissues compared to paired paracancerous tissues, and a high expression level of RNF113A was strongly associated with malignant phenotypes such as lymph node metastasis, differentiation degree, depth of invasion, and FIGO stage. Meanwhile, RNF113A was found to be an independent prognostic risk factor, with its high expression significantly correlating with a reduced overall survival period in patients. To elucidate the underlying cause and mechanism of the unfavorable prognosis associated with RNF113A, comprehensive functional investigations were conducted both in vitro and in vivo.Interestingly, it was revealed that RNF113A promoted migration and invasion while inhibiting apoptosis of CC cells, thereby contributing to a poor prognosis. Mechanistically, RNF113A regulated the progression and prognosis of CC through the miR197/Prp19/p38Mark signaling pathway. Overall, our findings underscore the potential clinical significance of RNF113A as an unfavorable prognostic factor in CC.

01 Nov 2024·Journal of Ethnopharmacology

Apigenin inhibits proliferation and differentiation of cardiac fibroblasts through AKT/GSK3β signaling pathway

Article

Author: Wang, Pengyu ; Wang, Miao ; Kan, Hongshuang ; Liu, Aimei ; Yang, Yayuan ; Jia, Hongyu ; Yang, Xiaosong ; Ouyang, Changhan

ETHNOPHARMACOLOGICAL RELEVANCESalvia miltiorrhiza Bunge (S. miltiorrhiza) is an important Traditional Chinese herbal Medicine (TCM) used to treat cardio-cerebrovascular diseases. Based on the pharmacodynamic substance of S. miltiorrhiza, the aim of present study was to investigate the underlying mechanism of S. miltiorrhiza against cardiac fibrosis (CF) through a systematic network pharmacology approach, molecular docking and dynamics simulation as well as experimental investigation in vitro.MATERIALS AND METHODSA systematic pharmacological analysis was conducted using the Traditional Chinese Medicine Pharmacology (TCMSP) database to screen the effective chemical components of S. miltiorrhiza, then the corresponding potential target genes of the compounds were obtained by the Swiss Target Prediction and TCMSP databases. Meanwhile, GeneCards, DisGeNET, OMIM, and TTD disease databases were used to screen CF targets, and a protein-protein interaction (PPI) network of drug-disease targets was constructed on S. miltiorrhiza/CF targets by Search Tool for the Retrieval of Interacting Genes/Proteins (STING) database. After that, the component-disease-target network was constructed by software Cytoscape 3.7. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for the intersection targets between drug and disease. The relationship between active ingredient of S. miltiorrhiza and disease targets of CF was assessed via molecular docking and molecular dynamics simulation. Subsequently, the underlying mechanism of the hub compound on CF was experimentally investigated in vitro.RESULTS206 corresponding targets to effective chemical components from S. miltiorrhiza were determined, and among them, there were 82 targets that overlapped with targets of CF. Further, through PPI analysis, AKT1 and GSK3β were the hub targets, and which were both enriched in the PI3K/AKT signaling pathway, it was the sub-pathways of the lipid and atherosclerosis pathway. Subsequently, compound-disease-genes-pathways diagram is constructed, apigenin (APi) was a top ingredients and AKT1 (51) and GSK3β (22) were the hub genes according to the degree value. The results of molecular docking and dynamics simulation showed that APi has strong affinities with AKT and GSK3β. The results of cell experiments showed that APi inhibited cells viability, proliferation, proteins expression of α-SMA and collagen I/III, phosphorylation of AKT1 and GSK3β in MCFs induced by TGFβ1.CONCLUSIONThrough a systematic network pharmacology approach, molecular docking and dynamics simulation, and confirmed by in vitro cell experiments, these results indicated that APi interacts with AKT and GSK3β to disrupt the phosphorylation of AKT and GSK3β, thereby inhibiting the proliferation and differentiation of MCFs induced by TGFβ1, which providing new insights into the pharmacological mechanism of S. miltiorrhiza in the treatment of CF.

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Trichothiodystrophy Syndromes

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