Marine-derived antimicrobial peptide piscidin-1 triggers extrinsic and intrinsic apoptosis in oral squamous cell carcinoma through reactive oxygen species production and inhibits angiogenesis.

Cancer of the head and neck encompasses a wide range of cancers, including oral and oropharyngeal cancers. Oral cancer is often diagnosed at advanced stages and has a dismal prognosis. Piscidin-1, a marine antimicrobial peptide (AMP) containing approximately 22 amino acids, also exhibits significant anticancer properties. We investigated the possible anti-oral cancer effects of piscidin-1 and clarified the mechanisms underlying these effects. We treated the oral squamous cell carcinoma cell lines OC2 and SCC4 with piscidin-1. Cell viability and the expression of different hallmark apoptotic molecules, including reactive oxygen species (ROS), were tested using the appropriate MTT assay, flow cytometry and western blotting assays, and human umbilical vein endothelial cell (HUVEC) wound healing, migration, and tube formation (angiogenesis) assays. Piscidin-1 increases cleaved caspase 3 levels to induce apoptosis. Piscidin-1 also increases ROS levels and intensifies oxidative stress in the endoplasmic reticulum and mitochondria, causing mitochondrial dysfunction. Additionally, it decreases the oxygen consumption rates and activity of mitochondrial complexes I-V. As expected, the antioxidants MitoTEMPOL and N-acetylcysteine reduce piscidin-1-induced ROS generation and intracellular calcium accumulation. Piscidin-1 also inhibits matrix metalloproteinase (MMP)-2/-9 expression in HUVECs, affecting migration and tube formation angiogenesis. We demonstrated that piscidin-1 can promote apoptosis via both intrinsic and extrinsic apoptotic pathways and findings indicate that piscidin-1 has anti-proliferative and anti-angiogenic properties in oral cancer treatment. Our study on piscidin-1 thus provides a basis for future translational anti-oral cancer drug research and a new theoretical approach for anti-oral cancer clinical research.

Direct aortic route versus transaxillary route for transcatheter aortic valve replacement: a systematic review and meta-analysis.

BACKGROUND: The transfemoral route is contraindicated in nearly 10% of transcatheter aortic valve replacement (TAVR) candidates because of unsuitable iliofemoral vessels. Transaxillary (TAx) and direct aortic (DAo) routes are the principal nonfemoral TAVR routes; however, few studies have compared their outcomes. METHODS: We performed a systematic review and meta-analysis to compare the rates of mortality, stroke, and other adverse events of TAx and DAo TAVR. The study was prospectively registered with PROSPERO (registration number: CRD42017069788). We searched Medline, PubMed, Embase, and Cochrane databases for studies reporting the outcomes of DAo or TAx TAVR in at least 10 patients. Studies that did not use the Valve Academic Research Consortium definitions were excluded. We included studies that did not directly compare the two approaches and then pooled rates of events from the included studies for comparison. RESULTS: In total, 31 studies were included in the quantitative meta-analysis, with 2,883 and 2,172 patients in the DAo and TAx TAVR groups, respectively. Compared with TAx TAVR, DAo TAVR had a lower Society of Thoracic Surgery (STS) score, shorter fluoroscopic time, and less contrast volume use. The 30-day mortality rates were significantly higher in the DAo TAVR group (9.6%, 95% confidence interval (CI) = [8.4-10.9]) than in the TAx TAVR group (5.7%, 95% CI = [4.8-6.8]; P for heterogeneity <0.001). DAo TAVR was associated with a significantly lower risk of stroke in the overall study population (2.6% vs. 5.8%, P for heterogeneity <0.001) and in the subgroup of studies with a mean STS score of ≥8 (1.6% vs. 6.2%, P for heterogeneity = 0.005). DAo TAVR was also associated with lower risks of permanent pacemaker implantation (12.3% vs. 20.1%, P for heterogeneity = 0.009) and valve malposition (2.0% vs. 10.2%, P for heterogeneity = 0.023) than was TAx TAVR. CONCLUSIONS: DAo TAVR increased 30-day mortality rate compared with TAx TAVR; by contrast, TAx TAVR increased postoperative stroke, permanent pacemaker implantation, and valve malposition risks compared with DAo TAVR.

Elderly versus non-elderly patients undergoing surgery for left-sided native valve infective endocarditis: A 10-year institutional experience.

This retrospective study aimed to clarify the short- and mid-term outcomes of elderly patients who underwent surgery to treat left-sided native valve infective endocarditis (LSNIE). Between July 2005 and September 2015, 179 patients underwent surgical treatment for active LSNIE at a single institution. Patients were classified into two groups: ≥65 years (elderly group) and <65 years (non-elderly group). Clinical features, surgical information, postoperative complications, and three-year survival rates were compared. The average ages were 74.2 ± 6.4 and 45.2 ± 12.6 years in the elderly and non-elderly groups, respectively. The elderly group had a higher predicted mortality rate and a lower incidence of preoperative septic emboli-related complications. Echocardiographic assessments of infected valves were generally homogenous between the groups. The elderly patients had a higher in-hospital mortality rate than the non-elderly patients (26.3% vs. 5.7%, P = 0.001). For patients who survived to discharge, the three-year cumulative survival rates were 75.0% ± 8.2% and 81.2% ± 3.4% in the elderly and non-elderly groups, respectively (P = 0.484). In conclusion, elderly patients are at a higher risk of in-hospital mortality after surgery for LSNIE. However, once elderly patients are stabilized by surgical treatment and survive to discharge, the mid-term outcomes are promising.

Risk factor analysis of postoperative acute respiratory distress syndrome after type A aortic dissection repair surgery.

To investigate the incidence, outcomes, and risk factors of postoperative acute respiratory distress syndrome (ARDS) in patients undergoing surgical repair for acute type A aortic dissection.This retrospective study involved 270 patients who underwent surgical repair for acute type A aortic dissection between January 2009 and December 2015. Data on clinical characteristics and outcomes were collected. Patients who immediately died after surgery and with preoperative myocardial dysfunction were excluded. The included patients were divided into the ARDS (ARDS patients who met the Berlin definition) and non-ARDS groups. Primary outcome was postoperative ARDS, according to the 2012 Berlin definition for ARDS and was reviewed by 2 qualified physicians with expertise in critical care and cardiac surgery. Outcomes of interest were the incidence and severity of risk factors for ARDS in this population, and perioperative outcomes and survival rates were compared with patients with or without ARDS.A total of 233 adult patients were enrolled into this study; of these, 37 patients (15.9%) had ARDS. Three, 20, and 14 patients had mild, moderate, and severe ARDS, respectively, according to the Berlin definition, with no significant difference in age, sex, and underlying disease. The ARDS group had lower mean oxygenation index (OI) than the non-ARDS group in the first 3 days post-surgery and demonstrated an improvement in lung function after the fourth day. Postoperative complication risks were higher in the ARDS group than in the non-ARDS group. However, no significant difference was observed in in-hospital mortality between the 2 groups (10.8% vs 5.6%, P = .268). Additionally, there was also no significant difference in the 3-year mortality rate between the 2 groups (P of log-rank test = .274). Postoperative hemoglobin level (odds ratio [OR]: 0.78; 95% confidence interval [CI]: 0.62-0.99) and perioperative blood transfusion volume (OR: 1.07; 95% CI: 1.03-1.12) were associated with ARDS risk.Postoperative ARDS after type A aortic dissection repair surgery was associated with risks of postoperative complications but not with risk of in-hospital mortality or 3-year mortality. A higher perioperative blood transfusion volume and a lower postoperative hemoglobin level may be risk factors for ARDS.

Impact of reduced left ventricular function on repairing acute type A aortic dissection: Outcome and risk factors analysis from a single institutional experience.

Preoperative left ventricular dysfunction is a risk factor for postoperative mortality and morbidity in cardiovascular surgeries with cardiopulmonary bypass, including thoracic aortic surgery. Using a retrospective study design, this study aimed to clarify the short- and mid-term outcomes of patients who underwent acute type A aortic dissection (ATAAD) repair with reduced left ventricular function.Between July 2007 and February 2018, a total of 510 adult patients underwent surgical repair of ATAAD in a single institution. The patients were classified as having left ventricular ejection fraction (LVEF) <50% (low EF group, n = 86, 16.9%) and LVEF ≥50% (normal group, n = 424, 83.1%) according to transesophageal echocardiographic assessment at the operating room. Preoperative demographics, surgical information, and postoperative complication were compared between the two groups. Three-year survival was analyzed using the Kaplan-Meier actuarial method. Serial echocardiographic evaluations were performed at 1, 2, and 3 years postoperation.Demographics, comorbidities, and surgical procedures were generally homogenous between the 2 groups, except for a lower rate of aortic arch replacement in the low EF group. The averaged LVEFs were 44.3 ±â€Š2.5% and 65.8 ±â€Š6.6% among the low EF and normal groups, respectively. The patients with low EF had higher in-hospital mortality (23.3% versus 13.9%, P = .025) compared with the normal group. Multivariate analysis revealed that intraoperative myocardial failure requiring extracorporeal membrane oxygenation support was an in-hospital mortality predictor (odds ratio, 16.99; 95% confidence interval, 1.23-234.32; P = .034), as was preoperative serum creatinine >1.5 mg/dL. For patients who survived to discharge, the 3-year cumulative survival rates were 77.8% and 82.1% in the low EF and normal groups, respectively (P = .522). The serial echocardiograms revealed no postoperative deterioration of LVEF during the 3-year follow-up.Even with a more conservative aortic repair procedure, the patients with preoperative left ventricular dysfunction are at higher surgical risk for in-hospital mortality. However, once such patients are able to survive to discharge, the midterm outcome can still be promising.

Skeletal muscle atrophy is attenuated in tumor-bearing mice under chemotherapy by treatment with fish oil and selenium.

Chemotherapy can cause cachexia, which is manifested by weight loss, inflammation and muscle atrophy. However, the mechanisms of tumor and chemotherapy on skeletal muscle proteolysis, remained unclear. In this report, we demonstrated that tumor-induced myostatin in turn induced TNF-α, thus activating calcium-dependent and proteasomal protein degradation. Chemotherapy activated myostatin-mediated proteolysis and muscle atrophy by elevating IL-6. In tumor-bearing mice under chemotherapy, supplementation with fish oil and selenium prevented a rise in IL-6, TNF-α and myostatin and muscle atrophy. The findings presented here allow us to better understand the molecular basis of cancer cachexia and potentiate nutrition supplementation in future cancer chemotherapy.