In vitro characterization of mitochondrial function and structure in rat and human cells with a deficiency of the NADH:ubiquinone oxidoreductase Ndufc2 subunit

Ndufc2, a subunit of the NADH:ubiquinone oxidoreductase, plays a key role in the assembly and activity of complex I within the mitochondrial OXPHOS chain. Its deficiency has been shown to be involved in diabetes, cancer and stroke. To improve our knowledge on the mechanisms underlying the increased disease risk due to Ndufc2 reduction, we performed the present in vitro study aimed at the fine characterization of the derangements in mitochondrial structure and function consequent to Ndufc2 deficiency. We found that both fibroblasts obtained from skin of heterozygous Ndufc2 knock-out rat model showed marked mitochondrial dysfunction and PBMC obtained from subjects homozygous for the TT genotype of the rs11237379/NDUFC2 variant, previously shown to associate with reduced gene expression, demonstrated increased generation of reactive oxygen species and mitochondrial damage. The latter was associated with increased oxidative stress and significant ultrastructural impairment of mitochondrial morphology with a loss of internal cristae. In both models the exposure to stress stimuli, such as high-NaCl concentration or LPS, exacerbated the mitochondrial damage and dysfunction. Resveratrol significantly counteracted the ROS generation. These findings provide additional insights on the role of an altered pattern of mitochondrial structure-function as a cause of human diseases. In particular, they contribute to underscore a potential genetic risk factor for cardiovascular diseases, including stroke

SEPT7 (septin 7)

Review on SEPT7, with data on DNA/RNA, on the protein encoded and where the gene is implicated

MCM3 (minichromosome maintenance complex component 3)

Review on MCM3, with data on DNA/RNA, on the protein encoded and where the gene is implicated

Endothelial nitric oxide synthase gene polymorphisms associated with periodontal diseases in Turkish adults

Endothelial nitric oxide synthase (NOS3) is involved in key steps of immune response. Genetic factors predispose individuals to periodontal disease. This study's aim was to explore the association between NOS3 gene polymorphisms and clinical parameters in patients with periodontal disease. Genomic DNA was obtained from the peripheral blood of 23 subjects with aggressive periodontitis (AgP), 26 with chronic periodontitis (CP), 31 with gingivitis (G) and 50 healthy controls. Probing depth (PD), clinical attachment loss (CAL), plaque index (PI) and gingival index (GI) were recorded as clinical parameters. We genotyped NOS3 polymorphisms using the PCR and/or PCR-RFLP method. Genotype frequencies differed significantly among periodontal diseases and controls for these polymorphisms. A significant association was detected between NOS3 +894 polymorphism and PD and CAL in the CP and AgP patient groups; whereas NOS VNTR analysis detected no associations with clinical parameters in theCP and AgP groups. However, a significant association was detected between the AA genotype and both PI and GI in patients with gingivitis; and a significant association was shown between the BB genotype and PI. The present study shows that two common polymorphisms of the NOS3 gene cluster are significantly associated with the occurrence of periodontal diseases

ATP5B (ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide)

Review on ATP5B, with data on DNA/RNA, on the protein encoded and where the gene is implicated

ATP2B4 (ATPase, Ca++ transporting, plasma membrane 4)

Review on ATP2B4, with data on DNA/RNA, on the protein encoded and where the gene is implicated

Factors Predicting Microinvasion in Ductal Carcinoma in situ

Background: Whether sentinel lymph node biopsy (SLNB) should be performed in patients with pure ductal carcinoma in situ (DCIS) of the breast has been a question of debate over the last decade. The aim of this study was to identify factors associated with microinvasive disease and determine the criteria for performing SLNB in patients with DCIS. Materials and Methods: 125 patients with DCIS who underwent surgery between January 2000 and December 2008 were reviewed to identify factors associated with DCIS and DCIS with microinvasion (DCISM). Results: 88 patients (70.4%) had pure DCIS and 37 (29.6%) had DCISM. Among 33 DCIS patients who underwent SLNB, one patient (3.3%) was found to have isolated tumor cells in her biopsy, whereas 1 of 14 (37.8%) patients with DCISM had micrometastasis (7.1%). Similarly, of 16 patients (18.2%) with pure DCIS and axillary lymph node dissection (ALND) without SLNB, none had lymph node metastasis. Furthermore, of 20 patients with DCISM and ALND, only one (5%) had metastasis. In multivariate analysis, the presence of comedo necrosis [relative risk (RR)=4.1, 95% confidence interval (CI)=1.6-10.6, P=0.004], and hormone receptor (ER or PR) negativity (RR=4.0, 95% CI=1.5-11, P=0.007), were found to be significantly associated with microinvasion. Conclusions: Our findings suggest patients presenting with a preoperative diagnosis of DCIS associated with comedo necrosis or hormone receptor negativity are more likely to have a microinvasive component in definitive pathology following surgery, and should be considered for SLNB procedure along with patients who will undergo mastectomy due to DCIS