Holdtbrandon3751

Previously, we uncovered a novel mechanism in which senescence is controlled by mitochondrial functional recovery upon Ataxia-telangiectasia mutated (ATM) inhibition. However, it remains elusive how ATM controls signaling pathways to achieve restorative effect. In this study, we performed microarray and found that p53 pathway was differentially expressed upon ATM inhibition. We found that ATM inhibition yields senescence amelioration through p53-dependent manner. The restorative effect was also afforded by direct p53 inhibition. Furthermore, mitochondrial metabolic reprogramming via p53 inhibition was a prerequisite for senescence amelioration. Taken together, our data indicated that p53 pathway functions as potential target for ATM-mediated senescence amelioration.Pathogenic mutations in NDUFAF4 have been reported in very few cases. Here we present new data to further delineate the phenotypic spectrum of NDUFAF4 deficiency. We describe two siblings presenting with facial dysmorphia and lactic acidosis in the neonatal period. Later on, they developed fatal early encephalopathy with apneic episodes, irritability, central hypoventilation, liver involvement and hyperammonemia. Abnormality of the cerebral white matter was demonstrated in one case, and cardiomyopathy in the other. Urine organic acid profile showed an increased excretion of lactate, Krebs cycle metabolites and 3-methylglutaconate. Whole-exome sequencing identified a novel homozygous nonsense mutation in NDUFAF4 (c.478G > T; p.Glu160Ter), encoding a mitochondrial complex I assembly factor. The disruptive effect of the mutation was corroborated by the absence of NDUFAF4 expression in patient fibroblasts. OXPHOS assembly studies demonstrated almost undetectable levels of fully assembled complex I and complex I-containing supercomplexes and an abnormal accumulation of SCIII2IV1 supercomplexes. Morphologically, fibroblasts showed rounder mitochondria and a diminished degree of branching of the mitochondrial network. Cellular respiratory capacity in fibroblasts was also markedly reduced. In sum, we provide insights into the physiopathological mechanisms underlying NDUFAF4 deficiency and expand the knowledge about the clinical and biochemical spectrum of this disorder.

We previously demonstrated that heme oxygenase-1 (HO-1) induction may contribute to a protective response against photodynamic therapy (PDT) using talaporfin sodium (TS) in rat malignant meningioma KMY-J cells. In the present study, we examined the mechanism of HO-1 induction by PDT with TS (TS-PDT) in KMY-J cells.

KMY-J cells were incubated with 25 μM TS for 2 h and then exposed to 664 nm diode laser irradiation at 1 J/cm

. The gene and protein expression levels of HO-1 and hypoxia-inducible factor-1α (HIF-1α) were determined by real-time RT-PCR and western blot analysis, respectively. Cell viability was measured using the cell counting kit-8 assay.

mRNA and protein levels of HO-1 in KMY-J cells were increased significantly at 3, 6, and 9 h after laser irradiation and the increased mRNA level of HO-1 was decreased by antioxidant N-acetyl cysteine treatment. The protein level of HIF-1α, which mediates transcriptional activation of the HO-1 gene, was increased significantly at 1 h after laser irradiation. Additionally, induction of mRNA expression of HO-1 by TS-PDT was diminished by HIF-1α inhibitor echinomycin. We also demonstrated that echinomycin significantly augmented the cytotoxic effect of TS-PDT.

Our findings indicate that TS-PDT may induce HO-1 expression via reactive oxygen species production and then HIF-1 pathway activation in KMY-J cells, and the HO-1 induction may cause attenuation of the therapeutic effect of TS-PDT.

Our findings indicate that TS-PDT may induce HO-1 expression via reactive oxygen species production and then HIF-1 pathway activation in KMY-J cells, and the HO-1 induction may cause attenuation of the therapeutic effect of TS-PDT.

The aims of this study were to evaluate the clinical applicability of a new fluorescent plaque index scoring (FPI) with the Turesky modified Quigley-Hein plaque index (mQH) and to evaluate its relationship with plaque maturity.

In total 69 subjects participated in this study. White-light and fluorescent images of anterior teeth were acquired using a Qraycam (AIOBIO, Seoul, Korea). FPI was obtained from fluorescent images using the proprietary software (Q-Ray v.1.39, Inspektor Research System BV, Amsterdam, The Netherlands). AMPK activator Teeth were stained with a two-tone disclosing agent. mQH was used to manually score the combined red and blue disclosed plaque (Combi-mQH) and blue disclosed plaque (Blue-mQH) with the white-light images. Linear relationships between FPI and Combi-mQH (or Blue-mQH) were evaluated by using simple linear regression analysis. Differences of Combi-mQH (or Blue-mQH) with respect to FPI scores were statistically evaluated by using ANOVA with Duncan post hoc correction.

FPI showed a moderate positive correlation with Combi-mQH (r = 0.66, P < 0.001) and a high positive correlation with Blue-mQH (r = 0.78, P < 0.001). The model explanatory power (R

) between FPI and Blue-mQH was 60.8 %, which is 16.8 % higher than the explanatory power observed with Combi-mQH (44.0 %). Both Combi-mQH and Blue-mQH increased significantly with increasing FPI score (P < 0.001).

In this study we found that the FPI scoring system can be used to detect plaque and quantitatively distinguish plaque levels. In addition, FPI was determined to be useful in clinic because of its ability to detect and distinguish old and mature plaque.

In this study we found that the FPI scoring system can be used to detect plaque and quantitatively distinguish plaque levels. In addition, FPI was determined to be useful in clinic because of its ability to detect and distinguish old and mature plaque.

To evaluate and compare the efficacy of antimicrobial Photodynamic therapy (aPDT), Local Drug Delivery (LDD) of 1.2 % Simvastatin gel as an adjunct to scaling and root planning (SRP) and SRP alone in the treatment of Periodontitis using clinical, microbiological and biochemical parameters.

A total of 33 test sites in 11 Grade A Stage II periodontitis patients were randomly divided into three groups GROUP I Treated by SRP alone (SRP group); GROUP II Treated by SRP followed by aPDT (aPDT group); GROUP III Treated by SRP followed by single subgingival application of 1.2 % simvastatin gel (SMV group). Clinical parameters including API, PBI, PPD and RAL were assessed. Quantification of Porphyromonas gingivalis was evaluated by RT -PCR technique and estimation of RANKL levels was checked by ELISA. All assessments were done at baseline and 3 months RESULTS All three groups showed significant reduction in the scores of clinical parameters, P. gingivalis DNA copy numbers and GCF RANKL levels at 3 months post therapy compared to baseline (p < 0.