Association Between Impairment of DNA Double Strand Break Repair and Decreased Ovarian Reserve in Patients With Endometriosis

Background: Repair of DNA double strand break (DSB) is an important mechanism for maintaining genetic stability during a DNA damage event. Although, a growing body of recent evidence suggests that DNA DSBs and related repair mechanisms may be important in ovarian aging and in various cancers, there are few reports in endometriosis. We, therefore, examined expression levels of genes pertaining to DNA DSB repair in patients with endometriosis to assess the potential effects on ovarian reserves.Materials and methods: A total of 69 women undergoing laparoscopic surgery for endometriosis and other benign conditions was included; endometriosis group (n = 38) vs. controls (n = 31). DNA DSBs in endometrial and ovarian tissues of both groups were compared via immunohistochemistry, aimed at γ-H2AX expression. To gauge genotoxin-induced DNA DSBs in endometrial stromal cells, γ-H2AX expression was determined by western blot after H2O2 treatment of cultured endometrial stromal cells (endometriosis group and controls) and Ishikawa cell-line cultures. Endometrial and ovarian tissue levels of BRCA1, BRCA2, Rad51, and ATM (ataxia-telangiectasia mutated) mRNA expression were also compared. Correlations between expression levels of genes of interest and serum anti-müllerian hormone (AMH) levels were assessed as well.Results: Expression of γ-H2AX in immunostained endometrial and ovarian tissue preparations was greater in the endometriosis group, compared with controls. After H2O2 treatment, γ-H2AX expression levels were also significantly greater in cultured stromal cells of the endometriosis group and in the Ishikawa cell line than in controls. Endometrial expression of BRCA1 and Rad51 mRNA proved significantly lower in the endometriosis group (vs. controls), as did ovarian expression of BRCA1 and BRCA2 mRNA. Serum AMH concentration showed a significant correlation with ovarian BRCA1 mRNA expression in women with endometriosis (p = 0.03).Conclusions: In women with endometriosis, expression levels of various genes implicated in DSB repair are decreased and ovarian BRCA1 expression correlates wit

Pathogenic PSEN1 Thr119Ile Mutation in Two Korean Patients with Early-Onset Alzheimer’s Disease

We report a probable pathogenic Thr119Ile mutation in presenilin-1 (PSEN1) in two unrelated Korean patients, diagnosed with early onset Alzheimer’s disease (EOAD). The first patient presented with memory decline when she was 64 years old. Magnetic resonance imaging (MRI) scans showed diffuse atrophy in the fronto-parietal regions. In addition, 18F-fludeoxyglucose positron emission tomography (FDG-PET) showed reduced tracer uptake in the parietal and temporal cortices, bilaterally. The second patient developed memory dysfunction at the age of 49, and his mother was also affected. Amyloid positron emission tomography (PET) was positive, but MRI scans did not reveal any atrophy. Targeted NGS and Sanger sequencing identified a heterozygous C to T exchange in PSEN1 exon 5 (c.356C>T), resulting in a p.Thr119Ile mutation. The mutation is located in the conserved HL-I loop, where several Alzheimer’s disease (AD) related mutations have been described. Structure analyses suggested that Thr119Ile mutation may result in a significant change inside conservative loop. Additional in vitro studies are needed to estimate the role of the PSEN1 Thr119Ile in AD disease progression

Biosilicated collagen/β-tricalcium phosphate composites as a BMP-2-delivering bone‐graft substitute for accelerated craniofacial bone regeneration

Abstract Background Bioceramic β-tricalcium phosphate (β-TCP) is used as a bone-grafting material and a therapeutic drug carrier for treatment of bone defects in the oral and maxillofacial regions due to the osteoconductivity and biocompatibility. However, the low mechanical strength and limited osteoinductivity of β-TCP agglomerate restrict bone regenerating performance in clinical settings. Methods Herein, a biomimetic composite is proposed as a bone morphogenetic protein-2 (BMP-2)-delivering bone graft substitute to achieve a robust bone grafting and augmented bone regeneration. Results The sequential processes of brown algae-inspired biosilicification and collagen coating on the surface of β-TCP enable the effective incorporation of BMP-2 into the coating layer without losing its bioactivity. The sustained delivery of BMP-2 from the biosilicated collagen and β-TCP composites promoted in vitro osteogenic behaviors of pre-osteoblasts and remarkedly accelerated in vivo bone regeneration within a rat calvarial bone defect. Conclusions Our multicomposite bone substitutes can be practically applied to improve bone tissue growth in bone grafting applications with further expansion to general bone tissue engineering

High-resolution three-photon biomedical imaging using doped ZnS nanocrystals

Three-photon excitation is a process that occurs when three photons are simultaneously absorbed within a luminophore for photo-excitation through virtual states. Although the imaging application of this process was proposed decades ago, three-photon biomedical imaging has not been realized yet owing to its intrinsic low quantum efficiency. We herein report on high-resolution in vitro and in vivo imaging by combining three-photon excitation of ZnS nanocrystals and visible emission from Mn 2+ dopants. The large three-photon cross-section of the nanocrystals enabled targeted cellular imaging under high spatial resolution, approaching the theoretical limit of three-photon excitation. Owing to the enhanced Stokes shift achieved through nanocrystal doping, the three-photon process was successfully applied to high-resolution in vivo tumour-targeted imaging. Furthermore, the biocompatibility of ZnS nanocrystals offers great potential for clinical applications of three-photon imaging. © 2013 Macmillan Publishers Limited. All rights reserved.11331461sciescopu