Increased O-GlcNAcylation of Drp1 by amyloid-beta promotes mitochondrial fission and dysfunction in neuronal cells.

As a dynamic organelle, mitochondria continuously fuse and divide with adjacent mitochondria. Imbalance in mitochondria dynamics leads to their dysfunction, which implicated in neurodegenerative diseases. However, how mitochondria alteration and glucose defect contribute to pathogenesis of Alzheimer's disease (AD) is still largely unknown. Dynamin-related protein 1 (Drp1) is an essential regulator for mitochondria fission. Among various posttranslational modifications, O-GlcNAcylation plays a role as a sensor for nutrient and oxidative stress. In this study, we identified that Drp1 is regulated by O-GlcNAcylation in AD models. Treatment of Aβ as well as PugNAc resulted in mitochondrial fragmentation in neuronal cells. Moreover, we found that AD mice brain exhibits an upregulated Drp1 O-GlcNAcylation. However, depletion of OGT inhibited Drp1 O-GlcNAcylation in Aβ-treated cells. In addition, overexpression of O-GlcNAc defective Drp1 mutant (T585A and T586A) decreased Drp1 O-GlcNAcylation and Aβ-induced mitochondria fragmentation. Taken together, these finding suggest that Aβ regulates mitochondrial fission by increasing O-GlcNAcylation of Drp1

Sentinel Lymph Node Radiolocalization with 99mTc Filtered Tin Colloid in Clinically Node-Negative Squamous Cell Carcinomas of the Oral Cavity

The objective of this study was to evaluate the feasibility of sentinel lymph node biopsy by using a radiotracer lymphatic mapping technique in patients with squamous cell carcinoma of the oral cavity, and the diagnostic value of this technique. We studied twenty patients with previously untreated squamous cell carcinomas of the oral cavity and N0 necks. After the peritumoral injection of 99mTc filtered tin colloid preop-eratively, lymphoscintigraphy and intraoperative mapping using a gamma detector were performed to localize sentinel nodes. An open biopsy of the sentinel node was followed by complete neck dissection. We identified the sentinel nodes in 19 of 20 patients (95.0%) by lymphoscintigraphy and in all (100%) by intraoperative gamma detector. In all cases, the status of the sentinel node accurately predicted the pathologic status of the neck with the false negative rate being 0%. The negative predictive value for the absence of cervical metastases was 100%. In conclusion, our radio-localization technique of sentinel nodes using 99mTc filtered tin colloid in N0 squamous cell carcinomas of the oral cavity is technically feasible and appears to accurately predict the presence of the occult metastatic disease

Protective effects of protocatechuic acid against cisplatin-induced renal damage in rats

The protective effects of an extract from bitter melon (. Momordica charantia, Cucurbitaceae) against oxidative stress was previously reported and found that protocatechuic acid (PCA) was one of the major phenolic constituents in the extract. The renoprotective effect of PCA from bitter melon was investigated in the present study. In the LLC-PK1 cellular model, the decline in cells viabilities induced by oxidative stress, such as that induced by sodium nitroprusside, pyrogallol, and SIN-1, was significantly and dose-dependently inhibited by PCA. In the in vivo model, the cisplatin-treated rats showed increased plasma levels of creatinine, decreased creatinine clearance, and increased urine protein levels. However, these parameters related to renal dysfunction were markedly attenuated by PCA treatment. Administration of PCA resulted in remarkable improvement in the histological appearance and reduction in tubular cell damage in the cisplatin-treated rat kidneys. Moreover, the elevated levels of pro-caspase-3 induced by cisplatin in rat kidneys were down-regulated by PCA co-treatment. These results suggest that PCA has protective activity against anticancer drug-induced oxidative nephrotoxicity

Does apical root resection in endodontic microsurgery jeopardize the prosthodontic prognosis?

Apical surgery cuts off the apical root and the crown-to-root ratio becomes unfavorable. Crown-to-root ratio has been applied to periodontally compromised teeth. Apical root resection is a different matter from periodontal bone loss. The purpose of this paper is to review the validity of crown-to-root ratio in the apically resected teeth. Most roots have conical shape and the root surface area of coronal part is wider than apical part of the same length. Therefore loss of alveolar bone support from apical resection is much less than its linear length.The maximum stress from mastication concentrates on the cervical area and the minimum stress was found on the apical 1/3 area. Therefore apical root resection is not so harmful as periodontal bone loss. Osteotomy for apical resection reduces longitudinal width of the buccal bone and increases the risk of endo-perio communication which leads to failure. Endodontic microsurgery is able to realize 0 degree or shallow bevel and precise length of root resection, and minimize the longitudinal width of osteotomy. The crown-to-root ratio is not valid in evaluating the prosthodontic prognosis of the apically resected teeth. Accurate execution of endodontic microsurgery to preserve the buccal bone is essential to avoid endo-perio communication

Peroxisome quality control and dysregulated lipid metabolism in neurodegenerative diseases

Neurodegenerative diseases: The role of peroxisome organelles Systematic studies of cellular organelles called peroxisomes are needed to determine their influence on the progression of neurodegenerative diseases. Peroxisomes play vital roles in biological processes including the metabolism of lipids and reactive oxygen species, and the synthesis of key molecules, including bile acid and cholesterol. Disruption to peroxisome activity has been linked to metabolic disorders, cancers and neurodegenerative conditions. Dong-Hyung Cho at Kyungpook National University in Daegu, South Korea, and coworkers reviewed current understanding of peroxisome regulation, with a particular focus on brain disorders. The quantity and activity of peroxisomes alter according to environmental and stress cues. The brain is lipid-rich, and even small changes in fatty acid composition may influence neuronal function. Changes in fatty acid metabolism are found in early stage Alzheimer’s and Parkinson’s diseases, but whether peroxisome disruption is responsible requires clarification

Post-Translational Modifications of ATG4B in the Regulation of Autophagy

Autophagy plays a key role in eliminating and recycling cellular components in response to stress, including starvation. Dysregulation of autophagy is observed in various diseases, including neurodegenerative diseases, cancer, and diabetes. Autophagy is tightly regulated by autophagy-related (ATG) proteins. Autophagy-related 4 (ATG4) is the sole cysteine protease, and four homologs (ATG4A–D) have been identified in mammals. These proteins have two domains: catalytic and short fingers. ATG4 facilitates autophagy by promoting autophagosome maturation through reversible lipidation and delipidation of seven autophagy-related 8 (ATG8) homologs, including microtubule-associated protein 1-light chain 3 (LC3) and GABA type A receptor-associated protein (GABARAP). Each ATG4 homolog shows a preference for a specific ATG8 homolog. Post-translational modifications of ATG4, including phosphorylation/dephosphorylation, O-GlcNAcylation, oxidation, S-nitrosylation, ubiquitination, and proteolytic cleavage, regulate its activity and ATG8 processing, thus modulating its autophagic activity. We reviewed recent advances in our understanding of the effect of post-translational modification on the regulation, activity, and function of ATG4, the main protease that controls autophagy

Randomized clinical trial of pulpotomy using a premixed injectable calcium silicate cement on mature permanent teeth with reversible pulpitis

Abstract The aim of this two-center randomized controlled trial was to assess the outcomes and relative factors associated with pulpotomies performed using a premixed injectable calcium silicate cement, as compared to mineral trioxide aggregate in mature permanent premolar and molar teeth with reversible pulpitis. Included teeth were randomly divided into two groups according to pulpotomy material (ProRoot MTA [PMTA] group, Endocem MTA Premixed [EPM] group). After pulp exposure, the superficial pulp was either removed to a depth of 2 mm (partial pulpotomy) or completely amputated to the level of the root canal orifice (full pulpotomy). A 3-mm layer of either material was randomly placed over the pulp wound, followed by the application of a thin layer of a light-cured glass ionomer composite liner. The restoration procedure was then carried out during the same visit. After one year of treatment, the pulpotomy success rate was 94.4% (67/71), with no significant difference between the PMTA and EPM groups. The success rate was 93.9% in the PMTA group and 97.1% in the EPM group. There were no significant factors related to the procedures. EPM is a viable alternative to PMTA for single-visit pulpotomies of permanent premolars and molars