Association between SGK1 and α-synuclein in skeletal muscle in an MPTP-induced Parkinson's disease model.

Parkinson's disease (PD) is a neurodegenerative disease caused by loss of dopaminergic neurons in the substantia nigra and it is known to involve the accumulation of α-synuclein (α-syn), which is a neuroprotein that promotes degeneration of dopaminergic neurons. Serum/glucocorticoid-related kinase 1 (SGK1) is involved in the physiological and pathological processes in neurons. The aim of this study was to examine the relationship between SGK1 and α-syn expression in muscle tissue of a PD model and in C2C12 cells. Western blotting, immunohistochemistry, and immunofluorescence microscopy confirmed reduced SGK1 and increased α-syn expression in skeletal muscle of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice compared to the control group. To determine the relationship between SGK1 and α-syn, SGK1 small interfering RNA (siRNA) knockdown was performed in C2C12 cells, which showed that suppression of SGK1 levels resulted in increased α-syn expression. The main finding of our study is that reduction of SGK1 expression contributes to the pathogenesis of PD by increasing the expression of α-syn in skeletal muscle of MPTP-treated mice and C2C12 cells. This study confirms that decreased SGK1 induces increased α-syn expression in skeletal muscle, which suggests that maintaining SGK1 expression may improve PD symptoms.

Anti-Tumor Potential of a 5-HT3 Receptor Antagonist as a Novel Autophagy Inducer in Lung Cancer: A Retrospective Clinical Study with In Vitro Confirmation.

Unlike 5-hydroxytryptamine (5-HT, serotonin) 1 and 5-HT2, the effect of 5-HT3 receptors on tumor cells is poorly understood. We conducted this study to determine whether the perioperative use of 5-HT3 receptor antagonists, which are widely used antiemetics, impacts the recurrence and mortality after lung cancer surgery and related anti-tumor mechanisms. From data on 411 patients, propensity score matching was used to produce 60 1:2 matched pairs of patients, and variables associated with the prognosis after open lung cancer surgery were analyzed. Additionally, the effects of 5-HT3 receptor antagonists were confirmed in vitro on A549 human lung adenocarcinoma cells. Cancer recurrence occurred in 10 (8.2%) and 14 (22.95%) patients (p = 0.005), treated or untreated, with palonosetron or ramosetron. Perioperative usage of palonosetron or ramosetron was also associated with lower recurrence rate after lung cancer surgery (hazard ratio (HR), 0.293; 95% confidence interval (CI) 0.110-0.780, p = 0.0141). Our in vitro experiments also showed that palonosetron and ramosetron inhibited cell proliferation and colony formation and reduced migration, which was associated with autophagic cell death via the extracellular signal-regulated kinase (ERK) pathway. Palonosetron and ramosetron may have anti-tumor potential against lung cancer cells, suggesting the need to consider these drugs as first-choice antiemetics in patients undergoing lung cancer surgery.

Propofol intravenous anaesthesia with desflurane compared with desflurane alone on postoperative liver function after living-donor liver transplantation: A randomised controlled trial.

BACKGROUND: Propofol is an anaesthetic that resembles α-tocopherol and it has been suggested that it protects against ischaemia-reperfusion injury in liver transplantation. Living-donor liver transplantation (LDLT) presents an opportunity to test this hypothesis in both donors and recipients. OBJECTIVES: We compared clinical outcomes after LDLT following anaesthesia with propofol and desflurane against desflurane alone. DESIGN: A randomised, parallel study. SETTING: Single-centre trial, study period June 2014 and May 2017. PATIENTS: Sixty-two pairs of adult donors and recipients who underwent LDLT. INTERVENTION: Patients were randomised to receive either desflurane balanced anaesthesia or propofol total intravenous anaesthesia combined with desflurane anaesthesia. MAIN OUTCOME MEASURES: The primary outcome was peak liver transaminase levels during the first 7 days after surgery. Liver function was assessed at 10 different time-points (before surgery, 1 h after reperfusion, upon arrival in the ICU, and daily until postoperative day 7). Creatinine was measured to evaluate the incidence of acute kidney injury. TNF-α, IL-1ß, IL-6 and TGF-ß1 were assessed in 31 donors after induction, at hepatectomy and at the end of surgery and in 52 recipients after induction, and 1, 3 and 24 h after reperfusion. RESULTS: Peak liver transaminase levels were not significantly different between the two groups. Liver function tests and creatinine were also similar between groups at all time-points. There was no difference in the incidence of postoperative complications, including acute kidney injury. With the exception of higher TNF-α in donors of the Propofol group at hepatectomy (0.60 ±â€Š0.29 vs. 1.03 ±â€Š0.53, P = 0.01) cytokine results were comparable between the two groups. CONCLUSION: Despite the simultaneous administration of propofol infusion in both donors and recipients, no improvement in laboratory or surgical outcome was observed after LDLT compared with patients who received desflurane anaesthesia alone. TRIAL REGISTRATION: NCT02504138 at clinicaltrials.gov.

Impact of interval from primary cytoreductive surgery to initiation of adjuvant chemotherapy in advanced epithelial ovarian cancer.

OBJECTIVE: To determine the optimal timing of adjuvant chemotherapy after primary cytoreductive surgery for advanced epithelial ovarian cancer. METHODS: In a retrospective cohort analysis, data were assessed from women with advanced epithelial ovarian carcinoma treated at Princess Margaret Cancer Centre, Toronto, Canada between 2002 and 2012, and at Samsung Medical Centre, Seoul, Korea, between 2002 and 2015. The treatment interval was defined as the time period between primary cytoreductive surgery and the first cycle of adjuvant chemotherapy. RESULTS: Overall, 711 women met the inclusion criteria. Among them, 247 (34.7%) had optimal cytoreduction (residual 1-9 mm), 229 (32.2%) had microscopic residual disease (0 mm), and 235 (33.1%) had suboptimal cytoreduction (≥10 mm). The median time of treatment interval was 10 days (range 3-86 days). In the optimal (1-9 mm) group, a longer treatment interval was significantly associated with poor overall survival (hazard ratio 1.02, 95% confidence interval 1.01-1.03; P=0.001) in multivariate analysis. Treatment interval was not associated with a significant difference in overall survival in the microscopic or suboptimal residual disease groups. CONCLUSION: Overall survival might be negatively affected by longer treatment intervals among women with advanced epithelial ovarian carcinoma.