Miro1 improves the exogenous engraftment efficiency and therapeutic potential of mitochondria transfer using Wharton's jelly mesenchymal stem cells.

Mitochondria are important for maintaining cellular energy metabolism and regulating cellular senescence. Mitochondrial DNA (mtDNA) encodes subunits of the OXPHOS complexes which are essential for cellular respiration and energy production. Meanwhile, mtDNA variants have been associated with the pathogenesis of neurodegenerative diseases, including MELAS, for which no effective treatment has been developed. To alleviate the pathological conditions involved in mitochondrial disorders, mitochondria transfer therapy has shown promise. Wharton's jelly mesenchymal stem cells (WJMSCs) have been identified as suitable mitochondria donors for mitochondria-defective cells, wherein mitochondrial functions can be rescued. Miro1 participates in mitochondria trafficking by anchoring mitochondria to microtubules. In this study, we identified Miro1 over-expression as a factor that could help to enhance the efficiency of mitochondrial delivery. More specifically, we reveal that Miro1 over-expressed WJMSCs significantly improved intercellular communications, cell proliferation rates, and mitochondrial membrane potential, while restoring mitochondrial bioenergetics in mitochondria-defective fibroblasts. Furthermore, Miro1 over-expressed WJMSCs decreased rates of induced apoptosis and ROS production in MELAS fibroblasts; although, Miro1 over-expression did not rescue mtDNA mutation ratios nor mitochondrial biogenesis. This study presents a potentially novel therapeutic strategy for treating mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), and other diseases associated with dysfunctional mitochondria, while the pathophysiological relevance of our results should be further verified by animal models and clinical studies.

A new formula to predict the size and insertion depth of cuffed nasotracheal tube in children receiving dental surgery: a retrospective study.

This retrospective study aimed to develop a new formula for selecting the appropriate size and determining the depth of the cuffed nasotracheal intubation (NTI) for a cuffed endotracheal tube (cETT) in pediatric patients undergoing dental surgery. In addition, the clinical data on cETT (i.e., the size and depth of insertion) was compared with those calculated with age-based formulas to evaluate their correlation. A total number of 684 patients who received NTI were enrolled (healthy group, n = 607; special-need group, n = 77). The ETT size used in real-world scenarios was smaller (i.e., about 0.5 and 0.94 mm) than the age-based formula, while the ETT depth was greater (i.e., about 1.5 cm) than the age-based formula in both groups. In the healthy group, age, gender, and body weight were identified as predictors of ETT size and depth through multiple linear regression analysis, while only age and body weight were predictors in the special-needs group. New formulas were developed based on these findings, with ETT size = 3.98 + 0.052 × age + 0.048 × gender (male = 1, female = 0) + 0.023 × body weight (kg) and ETT depth = 15.1 + 0.43 × age + 0.300 × gender (male = 1, female = 0) + 0.007 × body weight (kg). The new formula could be useful for both healthy and special-need pediatric populations undergoing dental procedures.

Iron Brain Menace: The Involvement of Ferroptosis in Parkinson Disease.

Parkinson disease (PD) is the second-most common neurodegenerative disease. The characteristic pathology of progressive dopaminergic neuronal loss in people with PD is associated with iron accumulation and is suggested to be driven in part by the novel cell death pathway, ferroptosis. A unique modality of cell death, ferroptosis is mediated by iron-dependent phospholipid peroxidation. The mechanisms of ferroptosis inhibitors enhance antioxidative capacity to counter the oxidative stress from lipid peroxidation, such as through the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis and the coenzyme Q10 (CoQ10)/FSP1 pathway. Another means to reduce ferroptosis is with iron chelators. To date, there is no disease-modifying therapy to cure or slow PD progression, and a recent topic of research seeks to intervene with the development of PD via regulation of ferroptosis. In this review, we provide a discussion of different cell death pathways, the molecular mechanisms of ferroptosis, the role of ferroptosis in blood-brain barrier damage, updates on PD studies in ferroptosis, and the latest progress of pharmacological agents targeting ferroptosis for the intervention of PD in clinical trials.

Adverse respiratory events with sevoflurane compared with desflurane in ambulatory surgery: A systematic review and meta-analysis.

BACKGROUND: An increasing number of studies have concluded that the number of adverse events in the upper airway caused by desflurane does not differ significantly from the number of adverse events caused by sevoflurane. The advantages of desflurane in ambulatory surgery should be reassessed. OBJECTIVES: The aim of this study was to compare adverse respiratory events and recovery outcomes in patients undergoing desflurane or sevoflurane-based anaesthesia in ambulatory surgery. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: A systematic search for eligible RCTs in PubMed, Medline, Cochrane Central Register of Controlled Trials, ScienceDirect and Embase published up to June 2019. ELIGIBILITY CRITERIA: RCTs investigating the occurrence of adverse respiratory events, including airway irritation, stridor, coughing, respiratory distress and laryngospasm, emergence agitation, postoperative nausea and vomiting (PONV), time to eye opening and time to discharge from the operation room after desflurane or sevoflurane-based anaesthesia. RESULTS: Thirteen trials were included and analysed. A total of 634 patients were included in the desflurane group, and 633 patients in the sevoflurane group. The occurrence of respiratory complications was significantly higher with desflurane-based anaesthesia than with sevoflurane-based anaesthesia (Total n = 673, 20.0 vs. 12.8%, relative risk (RR) 1.59 (95% CI 1.15 to 2.20)) with low heterogeneity (I = 20%). There was no difference in the occurrence of emergence agitation (Total n = 626, 29.1 vs. 27.2%, RR 1.05 (95% CI 0.84 to 1.30)) or the incidence of PONV between the desflurane and sevoflurane groups (Total n = 989, 19.0 vs. 21.0%, RR 0.95 (95% CI 0.71 to 1.26)). Time to eye opening was significantly faster with desflurane than that with sevoflurane (Total n = 1072, mean difference = -3.32 min (95% CI -4.02 to -2.61)) with a substantial heterogeneity (I = 72.6%). There was no significant difference in the time to discharge from the operation room between the two groups (Total n = 1056, mean difference = -0.45 min (95% CI -5.89 to 4.99)). CONCLUSION: Despite recent reports that there is no significant difference in adverse respiratory events between desflurane and sevoflurane, a pooled analysis revealed that desflurane resulted in a higher rate than sevoflurane. Therefore, the consequences of desflurane should not be neglected and its airway irritant properties should be taken into account. TRIAL REGISTRATION: PROSPERO (CRD42019147939).

Resveratrol provides neuroprotective effects through modulation of mitochondrial dynamics and ERK1/2 regulated autophagy.

Mitochondrial dysfunction and oxidative stress are underlying contributors to Parkinson's disease (PD). The reduction of aberrant proteins and dysfunctional mitochondria through constitutive autophagy is essential for neuronal survival. We investigated the neuroprotective effects of the natural red wine extract, resveratrol, on the Complex I inhibitor, rotenone-induced oxidative stress SH-SY5Y cellular model. With rotenone exposure, cellular reactive oxygen species (ROS), apoptosis and cell death increased at both 6 and 18 h; at the same time, mitochondrial membrane potential (ΔΨm) and the balance of mitochondrial dynamic proteins were disrupted, resulting with fragmented mitochondria. Rotenone was also noted to elevate autophagy initiation but downregulate the autophagy flux. Pretreatment with resveratrol to rotenone exposed cells lowered cellular ROS, apoptosis, and increased survival rates. Resveratrol administration also recovered rotenone induced ΔΨm, mitochondria dynamics alteration, and elongated fragmented mitochondria. Both autophagic induction and autophagic flux were enhanced with resveratrol pre-treatment which is compatible with cellular survival. The mitogen-activated protein kinase (MEK) inhibitor, U0126, abolished the rescuing effect of resveratrol on rotenone treated neurons through the inhibition of autophagy flux. Thus, our work implies that the neuroprotective effect of resveratrol works in part through modulation of mitochondria dynamics and upregulating autophagic flux via the MEK/extracellular signal-regulated kinase (ERK) signalling pathway.