Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Trichilemmal cysts are common hair follicle-derived intradermal cysts. The trait shows an autosomal dominant mode of transmission with incomplete penetrance. Here, we describe the pathogenetic mechanism for the development of hereditary trichilemmal cysts. By whole-exome sequencing of DNA from the blood samples of 5 affected individuals and subsequent Sanger sequencing of a family cohort including 35 affected individuals, this study identified a combination of the Phospholipase C Delta 1 germline variants c.903A>G, p.(Pro301Pro) and c.1379C>T, p.(Ser460Leu) as a high-risk factor for trichilemmal cyst development. Allele-specific PCRs and cloning experiments showed that these two variants are present on the same allele. The analysis of tissue from several cysts revealed that an additional somatic Phospholipase C Delta 1 mutation on the same allele is required for cyst formation. In two different functional in vitro assays, this study showed that the protein function of the cyst-specific 1-phosphatidylinositol 4, 5-bisphosphate phosphodiesterase delta-1 protein variant is modified. This pathologic mechanism defines a monoallelic model of the two-hit mechanism proposed for tumor development and other hereditary cyst diseases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jid.2019.04.015 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
PTEN-mediated senescence of lung epithelial cells drives ventilator-induced pulmonary fibrosis.
Theranostics
August 2025
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Mechanical ventilation (MV), a life-saving intervention for acute respiratory distress syndrome (ARDS), may exacerbate pulmonary fibrosis (PF) through unclear mechanisms. Although Phosphatase and Tensin homolog (PTEN) suppresses chronic PF, its role in MV-induced PF remains unknown. This study will determine whether PTEN mediates MV-PF via lung epithelial cell senescence.
View Article and Find Full Text PDFPharmacological and genetic inhibition of ARG2 in CXCR2 myeloid-derived suppressor cells combats sepsis-induced lymphopenia.
Theranostics
August 2025
Department of Respiratory, Critical Care and Sleep Medicine, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361101, China.
Myeloid-derived suppressor cells (MDSCs) play a critical role in inducing T-cell lymphopenia in sepsis, and the highly heterogeneous MDSCs necessitate the identification of key molecules within these cells. By integrating bulk and single-cell transcriptomic sequences, we identified the critical molecular and MDSC subpopulation in pneumonia-induced sepsis (PIS) models. Through fluorescence-activated cell sorting (FACS) technology, we isolated the primary target subset to evaluate its immunosuppressive potential via T-cell proliferation assays, and investigate the underlying cellular and molecular mechanisms.
View Article and Find Full Text PDFCombination of hydroxycitric acid and capsaicin regulates IRS-1/AMPK-mTOR-SREBP-1c Axis/NLRP3-NF-κB/Nrf-2-ARE signaling pathways to ameliorate the two-hit process in high-fat diet-induced hepatic steatosis.
Biochim Biophys Acta Mol Cell Biol Lipids
August 2025
Chandigarh University, Gharuan, Mohali 140413, Punjab, India.
Metabolic (Dysfunction) Associated Steatotic Liver Disease (MASLD) is a complex metabolic condition, the progression of which toward steatohepatitis can be explained by the 'two-hit' hypothesis: the first hit involves lipid accumulation, and the second hit involves inflammation and oxidative stress. In this study, we aimed to evaluate the protective effects of a combination of hydroxycitric acid and capsaicin (CHC) against high-fat diet (HFD)-induced MASLD in rats, specifically by targeting the mechanisms associated with both hits. To establish the experimental model, rats were fed a HFD for 16 weeks, followed by treatment with CHC for 6 weeks starting on day one of the 16th week of HFD feeding.
View Article and Find Full Text PDFTransfusion-related acute lung injury (TRALI) is a leading cause of transfusion-related mortality. Though the precise mechanism is not fully understood, a two-hit model is widely accepted, involving both a predisposing patient condition and the transfusion itself. Mitochondrial damage-associated molecular patterns (mtDAMPs), such as mitochondrial DNA (mtDNA) and N-formylated peptides (NFPs), are elevated in trauma patients and stored blood products, and have been implicated in adverse transfusion outcomes, prompting us to investigated whether mtDAMPs could serve as a priming "first-hit" in TRALI.
View Article and Find Full Text PDFRole of Ferroptosis in the Redox Biology of Mycotoxins.
FASEB J
August 2025
College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
Ferroptosis, an iron-dependent regulated cell death process driven by lipid peroxidation, has emerged as a pivotal mechanism in mycotoxin-induced redox pathology. This review synthesizes the molecular interplay between fungal secondary metabolites (e.g.
View Article and Find Full Text PDF