Nitroglycerine-induced nitrate tolerance compromises propofol protection of the endothelial cells against TNF-α: the role of PKC-β2 and NADPH oxidase

published_or_final_versio

Inhibition of Caveolae Contributes to Propofol Preconditioning-Suppressed Microvesicles Release and Cell Injury by Hypoxia-Reoxygenation

Endothelial microvesicles (EMVs), released after endothelial cell (EC) apoptosis or activation, may carry many adverse signals and propagate injury by intercellular transmission. Caveolae are 50–100 nm cell surface plasma membrane invaginations involved in many pathophysiological processes. Recent evidence has indicated EMVs and caveolae may have functional effects in cells undergoing H/R injury. Propofol, a widely used anaesthetic, confers antioxidative stress capability in the same process. But the connection between EMVs, H/R, and caveolae remains largely unclear. Here, we found that H/R significantly increased the release of EMVs, the expression of CAV-1 (the structural protein responsible for maintaining the shape of caveolae), oxidative stress, and the mitochondrial damage, and all these changes were inhibited by propofol preconditioning. Interestingly, the caveolae inhibitor Mβ-CD strengthened the protective effect of propofol preconditioning. We further found that the release of EMVs is more significantly reduced under propofol preconditioning in the presence of the caveolae inhibitor Mβ-CD. EMVs released from H/R-treated cells caused a substantially increased mitochondrial and cellular damage to normal HUVECs after 4 hours of coculture. Thus, we conclude that inhibition of caveolae contributes to propofol preconditioning-suppressed microvesicles release and cell injury by H/R

The Pro12Ala Polymorphism of PPAR- γ

Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-binding nuclear receptor, and its activation plays a prominent role in regulating the inflammatory response. Therefore, PPAR-γ has been suggested as a candidate gene for sepsis. In the present study, we investigated the association between the Pro12Ala polymorphism of PPAR-γ and sepsis in a Han Chinese population. A total of 308 patients with sepsis and 345 healthy controls were enrolled in this study. Genotyping was performed using the polymerase chain reaction-ligation detection reaction (PCR-LDR) method. No significant differences were detected in the allele and genotype distributions of the PPAR-γ Pro12Ala SNP between septic patients and controls (P=0.622 for genotype; P=0.629 for allele). However, stratification by subtypes (sepsis, septic shock, and severe sepsis) revealed a statistically significant difference in the frequency of the Ala allele and Ala-carrier genotype between the patients with the sepsis subtype and the healthy controls (P=0.014 for allele and P=0.012, for genotype). Moreover, significant differences were found in the frequency of the Ala allele and genotype between the sepsis survivors and nonsurvivors (all P=0.002). In the survivors, the PPAR-γ Pro12Ala genotype was significantly associated with decreased disease severity and recovery time (all P<0.001). Thus, genetic polymorphism is thought to play a role in the development and outcome of sepsis

MicroRNA-93 Regulates Hypoxia-Induced Autophagy by Targeting ULK1

The expression of the core autophagy kinase, Unc51-like kinase 1 (ULK1), is regulated transcriptionally and translationally by starvation-induced autophagy. However, how ULK1 is regulated during hypoxia is not well understood. Previously, we showed that ULK1 expression is induced by hypoxia stress. Here, we report a new ULK1-modulating microRNA, miR-93; its transcription is negatively correlated with the translation of ULK1 under hypoxic condition. miR-93 targets ULK1 and reduces its protein levels under hypoxia condition. miR-93 also inhibits hypoxia-induced autophagy by preventing LC3-I to LC3-II transition and P62 degradation; these processes are reversed by the overexpression of an endogenous miR-93 inhibitor. Re-expression of ULK1 without miR-93 response elements restores the hypoxia-induced autophagy which is inhibited by miR-93. Finally, we detected the effects of miR-93 on cell viability and apoptosis in noncancer cell lines and cancer cells. We found that miR-93 sustains the viability of MEFs (mouse embryonic fibroblasts) and inhibits its apoptosis under hypoxia. Thus, we conclude that miR-93 is involved in hypoxia-induced autophagy by regulating ULK1. Our results provide a new angle to understand the complicated regulation of the key autophagy kinase ULK1 during different stress conditions

Household, community, sub-national and country-level predictors of primary cooking fuel switching in nine countries from the PURE study

Introduction. Switchingfrom polluting (e.g. wood, crop waste, coal)to clean (e.g. gas, electricity) cooking fuels can reduce household air pollution exposures and climate-forcing emissions.While studies have evaluated specific interventions and assessed fuel-switching in repeated cross-sectional surveys, the role of different multilevel factors in household fuel switching, outside of interventions and across diverse community settings, is not well understood. Methods.We examined longitudinal survey data from 24 172 households in 177 rural communities across nine countries within the Prospective Urban and Rural Epidemiology study.We assessed household-level primary cooking fuel switching during a median of 10 years offollow up (∼2005–2015).We used hierarchical logistic regression models to examine the relative importance of household, community, sub-national and national-level factors contributing to primary fuel switching. Results. One-half of study households(12 369)reported changing their primary cookingfuels between baseline andfollow up surveys. Of these, 61% (7582) switchedfrom polluting (wood, dung, agricultural waste, charcoal, coal, kerosene)to clean (gas, electricity)fuels, 26% (3109)switched between different polluting fuels, 10% (1164)switched from clean to polluting fuels and 3% (522)switched between different clean fuels

Аванпроект середньомагістрального пасажирського літака місткістю 150 пасажирів

Робота публікується згідно наказу Ректора НАУ від 27.05.2021 р. №311/од "Про розміщення кваліфікаційних робіт здобувачів вищої освіти в репозиторії університету". Керівник роботи: професор, д.т.н. Карускевич Михайло ВіталійовичThis diploma work is about preliminary design of the mid-range aircraft with 150 passengers capacity and its design characteristics estimation. In the work was performed analyzis of prototypes and selection of the most advanced technical decisions to calculate the geometry for main parts of the fuselage, such as wing geometry calculation, tail unit geometry, fuselage layout and landing gear design. Besides center of gravity calculation is another significant portion in the design. The diploma work contains the flexible conveyor concept for loading of passengers' luggage.У даній дипломній роботі йдеться про ескізний проект літака середньої магістральності на 150 пасажирів і оцінку його конструктивних характеристик. У роботі проведено аналіз прототипів та вибір найбільш передових технічних рішень для розрахунку геометрії основних частин фюзеляжу, таких як розрахунок геометрії крила, геометрії хвостового оперення, компонування фюзеляжу та конструкції шасі. Крім того, розрахунок центру ваги є ще однією важливою частиною конструкції. У дипломній роботі представлена концепція гнучкого конвеєра для завантаження багажу пасажира

Endothelial Microparticles Act as Novel Diagnostic and Therapeutic Biomarkers of Diabetes and Its Complications: A Literature Review

Diabetes mellitus- (DM-) related vascular diseases attract increased attention due to their high morbidity and mortality. The incidence of obesity, atherosclerosis, coronary heart disease, hypertension, and dyslipidemia is significantly higher in DM patients, with an earlier onset and faster progression compared with non-DM patients. DM-related vascular diseases including macrovascular and microvascular complications are characterized by endothelial dysfunction. Therefore, a better understanding of the etiology and mechanisms of endothelial dysfunction is important for the diagnosis and treatment of DM. Endothelial microparticles (EMPs) are new diagnostic and therapeutic targets and biomarkers in DM-related vascular disease. Circulating EMPs containing biologically active substances act as intercellular signals under physiological and pathological conditions. They serve as biological markers of altered vascular endothelium and reflect the pathological progression and diminished endothelial function of blood vessels. Recent evidence suggests that the plasma level of EMPs is significantly higher in DM patients than in healthy population and is significantly correlated with DM-related complications. These observations have prompted speculation that EMPs play a crucial role in the pathophysiology of DM. This review summarizes the known and potential roles of EMPs in the diagnosis, staging, treatment, and clinical prognosis of DM and related vascular diseases