Allele-specific sirna corrects aberrant cellular phenotype in keratitis-ichthyosis-deafness syndrome keratinocytes

Keratitis-ichthyosis-deafness (KID) syndrome is a severe, untreatable condition characterized by ocular, auditory and cutaneous abnormalities, with major complications of infection and skin cancer. 86% of cases are caused by a heterozygous missense mutation (c.148G>A, p.D50N) in the GJB2 gene, encoding gap junction protein connexin 26 (Cx26), which alters gating properties of Cx26 channels in a dominant manner. We hypothesized that a mutant-allele-specific siRNA (AS-siRNA) could rescue the cellular phenotype in patient keratinocytes.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Original Article Source Type: research

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New England Journal of Medicine, Ahead of Print.
Source: New England Journal of Medicine - Category: Internal Medicine Authors: Source Type: research
New England Journal of Medicine, Ahead of Print.
Source: New England Journal of Medicine - Category: Internal Medicine Authors: Source Type: research
New England Journal of Medicine, Ahead of Print.
Source: New England Journal of Medicine - Category: Internal Medicine Authors: Source Type: research
Publication date: Available online 11 December 2019Source: The Lancet Global HealthAuthor(s): Adam Wagstaff, Sven NeelsenSummaryBackgroundThe goal of universal health coverage (UHC) requires that everyone receive needed health services, and that families who get needed services do not suffer undue financial hardship. Tracking progress towards UHC requires measurement of both these dimensions, and a way of trading them off against one another.MethodsWe measured service coverage by a weighted geometric average of four prevention indicators (antenatal care, full immunisation, and screening for breast and cervical cancers) and...
Source: The Lancet Global Health - Category: International Medicine & Public Health Source Type: research
os AC Abstract PURPOSE: To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats. METHODS: We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500μg/kg injected i.p; DMBA+ACE+Vincristine 250μg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, ...
Source: Acta Cirurgica Brasileira - Category: Surgery Authors: Tags: Acta Cir Bras Source Type: research
Triple-negative breast cancer is difficult to treat. A new study indicates that a common chemotherapy drug improves overall survival in this tumor type -- big news in cancer treatment.Medscape Medical News
Source: Medscape General Surgery Headlines - Category: Surgery Tags: Hematology-Oncology News Source Type: news
al-Filho DC Abstract Carbohydrate antigen 125 (CA125) has long been used as an ovarian cancer biomarker. However, because it is not specific for ovarian cells, CA125 could also be used to monitor congestion and inflammation in heart disease. Acute heart failure (HF) is used to identify patients with a worse prognosis in ST-segment elevation myocardial infarction (STEMI). We aimed to determine the association of CA125 with acute HF in STEMI and to compare CA125 with N-terminal pro brain natriuretic peptide (NTproBNP) with a cross-sectional study. At admission, patients were examined to define Killip class and then ...
Source: Braz J Med Biol Res - Category: Research Authors: Tags: Braz J Med Biol Res Source Type: research
Abstract Polydatin (PD), a monocrystalline polyphenolic drug mainly found in the roots of Polygonum cuspidatum, has various pharmacological activities. Long non-coding RNAs (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) was found to participate in the suppression of multiple cancers. Here, we proposed to study the effect of PD on myocardial infarction (MI) by inducing DGCR5. CCK-8 assay was performed to detect the viability of H9c2 cells. Flow cytometry was utilized to test apoptosis of H9c2 cells. These results determined the optimal concentration and effect time of hypoxia as well as PD. Si-DGCR5 was ...
Source: Braz J Med Biol Res - Category: Research Authors: Tags: Braz J Med Biol Res Source Type: research
ConclusionTo that end, a KID syndrome cell line (KID-KC) was established from primary keratinocytes of a KID syndrome patient with heterozygous p.D50N mutation, which displayed impaired gap junction intercellular communication and hyperactive hemichannels, confirmed by dye transfer, patch clamp and neurobiotin uptake assays. In KID-KCs, treatment with AS-siRNA led to robust inhibition of the mutant GJB2 allele without altering expression of the wildtype allele. This resulted in correction of both gap junction intercellular communication and hemichannel activity. Furthermore, AS-siRNA treatment caused only low-level off-tar...
Source: Cytotherapy - Category: Cytology Source Type: research
Abstract Skin cancer has become the most common type of cancer worldwide as a result of environmental exposure and medical treatments. A small group of patients are genetically predisposed to skin cancer and this article is intended as a diagnostic tool when encountering patients with multiple skin cancer lesions. The disorders are described with clinical characteristics, genetics and management. The most common syndromes associated with basal cell carcinoma are: Gorlin-Goltz syndrome, Rombo syndrome, and Bazex-Dupré-Christol syndrome. Multiple squamous cell carcinomas can be related to: xeroderma pigmentos...
Source: Acta Dermato-Venereologica - Category: Dermatology Authors: Tags: Acta Derm Venereol Source Type: research
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