miR-142 induces accumulation of reactive oxygen species (ROS) by inhibiting pexophagy in aged bone marrow mesenchymal stem cells.

Elevation of the levels of reactive oxygen species (ROS) is a major tissue-degenerative phenomenon involved in aging and aging-related diseases. The detailed mechanisms underlying aging-related ROS generation remain unclear. Presently, the expression of microRNA (miR)-142-5p was significantly upregulated in bone marrow mesenchymal stem cells (BMMSCs) of aged mice. Overexpression of miR-142 and subsequent observation revealed that miR-142 involved ROS accumulation through the disruption of selective autophagy for peroxisomes (pexophagy). Mechanistically, attenuation of acetyltransferase Ep300 triggered the upregulation of miR-142 in aged BMMSCs, and miR-142 targeted endothelial PAS domain protein 1 (Epas1) was identified as a regulatory protein of pexophagy. These findings support a novel molecular mechanism relating aging-associated ROS generation and organelle degradation in BMMSCs, and suggest a potential therapeutic target for aging-associated disorders that are accompanied by stem cell degeneration.

miR-155 inhibits mitophagy through suppression of BAG5, a partner protein of PINK1.

Removal of dysfunctional mitochondria is essential step to maintain normal cell physiology, and selective autophagy in mitochondria, called mitophagy, plays a critical role in quality control of mitochondria. While in several diseases and aging, disturbed mitophagy has been observed. In stem cells, accumulation of damaged mitochondria can lead to deterioration of stem cell properties. Here, we focused on miR-155-5p (miR-155), one of the most prominent miRNAs in inflammatory and aged tissues, and found that miR-155 disturbed mitophagy in mesenchymal stem cells (MSCs). As a molecular mechanism of miR-155-mediated mitophagy suppression, we found that BCL2 associated athanogene 5 (BAG5) is a direct target of miR-155. Reduction of BAG5 resulted in destabilization of PTEN-induced kinase (PINK1) and consequently disrupted mitophagy. Our study suggests a novel mechanism connecting aging and aging-associated inflammation with mitochondrial dysfunction in stem cells through a miRNA-mediated mechanism.

A spinal cord infarction that occurred after laparoscopic gastrectomy performed under general anesthesia and epidural analgesia.

BACKGROUND: Spinal cord infarction (SCI) after epidural anesthesia is quite rare. Although most cases of perioperative SCI are associated with aortic, cardiac, or spinal surgery, and/or abnormal preoperative conditions, such as spinal stenosis or hypercoagulopathy, intraoperative events, such as severe hypotension or epidural puncture and catheterization, can be contributory factors. CASE PRESENTATION: A 52-year-old male was underwent laparoscopic gastrectomy. Before induction of general anesthesia, an epidural catheter was placed without any problems. The patient had no pain and no complaint just after the operation, but suddenly complained of back pain and anuria, and could not move either of his lower limbs 30 h after the operation. As we thought that the incident would be caused by the migration of the epidural catheter into the subarachnoid space, we removed the catheter, but there was no recovery of the symptoms even 20 h later. The magnetic resonance imaging (MRI) scan showed no hematoma in the epidural space but an abnormal signal within the spinal cord, extending from the Th3 to Th8 levels, which was consistent with the SCI. Unfortunately, the patient's recovery from the paraplegia and abnormal sensation was poor. CONCLUSIONS: When a patient complains of lower limb muscle weakness and/or abnormal sensations, it is important to perform an MRI examination and treatment as early as possible to avoid permanent paraplegia, especially after epidural puncture and catheterization.

Sevoflurane prolonged the QTc interval and increased transmural dispersion of repolarization in a patient with long QT syndrome 3: a case report.

We report that sevoflurane not only caused marked QTc interval prolongation but also increased transmural dispersion of repolarization in a patient with long QT syndrome 3 (LQT3). A 16-year-old male with LQT3 underwent a shoulder operation. He experienced no episode of syncope or cardiac arrest, but his preoperative electrocardiography (ECG) showed marked QTc interval prolongation (631 ms) and Tp-e interval prolongation (126 ms). Anesthesia was induced with propofol and maintained with 2% sevoflurane and remifentanil. Although no lethal arrhythmias occurred in the perioperative period, not only the QTc interval but also Tp-e interval was further prolonged by sevoflurane. While sevoflurane has been recognized as a safe anesthetic in terms of QT interval prolongation, even in patients with long QT syndromes, we believe that sevoflurane might be avoided for poorly controlled LQT3 patients.

McGRATH MAC video laryngoscope for insertion of a transoesophageal echocardiography probe: A randomised controlled trial.

BACKGROUND: Transoesophageal echocardiography (TOE) probe insertion in anaesthetised patients can cause pharyngeal and oesophageal injuries. Kim et al. have shown that insertion assisted by a Macintosh laryngoscope can reduce such complications but it may sometimes be difficult to observe the passage of a TOE probe. The McGRATH MAC (McGRATH) has been shown to provide a better view of the glottis, piriform fossa and oesophageal inlet during tracheal intubation than the Macintosh. OBJECTIVE: We hypothesised that the McGRATH provided better visualisation of the oesophageal inlet and was useful as an aid to TOE probe placement, possibly reducing the incidence of pharyngeal injury related to insertion, compared with the Macintosh. DESIGN: A randomised controlled trial. SETTING: The study was conducted in a university hospital from February to December 2014. PATIENTS: One hundred patients undergoing elective surgery under intraoperative TOE monitoring were randomised to either a Macintosh group or a McGRATH group. INTERVENTIONS: Macintosh and McGRATH were used to visualise the passage of the TOE probe and guide its insertion. MAIN OUTCOME MEASURES: Visibility of the oesophageal inlet, the number of TOE insertion attempts and incidence of pharyngeal mucosal injury after the TOE probe had been removed were assessed. RESULTS: The percentage of patients in whom the oesophageal inlet was visible was higher in the McGRATH group (88%) than in the Macintosh group (41%) (P < 0.01). The number of TOE probe insertion attempts was significantly smaller in the McGRATH group than in the Macintosh group (P = 0.039). The incidence of pharyngeal mucosal injury was significantly smaller in the McGRATH group (4%) than in the Macintosh group (16%; P = 0.042). CONCLUSION: The McGRATH provided a better view of the oesophageal inlet and was useful as an aid to TOE probe placement, possibly reducing the incidence of pharyngeal injury related to its insertion. TRIAL REGISTRATION: University Hospital Medical Information Network in Japan (UMIN) 000012970.