Olea europaea Linn (Oleaceae) Fruit Pulp Exhibits Hypocholesterolemic and Hepatoprotective Effects via Regulation of Peroxisome Proliferation-Activated Receptor Alpha in High-Fat Diet-Fed Rats

Purpose: To investigate the hypocholesterolemic and hepatoprotective effects of Olea europaea Linn. (Oleaceae) fruit pulp (OFP-EA) extract in experimental rats. Methods: Sprague–Dawley rats were fed with a normal diet, a high-cholesterol diet or high-cholesterol diets supplemented with OFP-EA extract (100 or 300 mg/kg/day p.o.) for 28 days. Plasma lipid profile such as total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were measured using their respective commercial kits. Gross appearance and lipid content of liver samples were also analyzed. The changes in protein expressions of key enzymes such as hydroxymethylglutaryl-CoA reductase (HMGR), acyl-CoA:cholesterol acyltransferase (ACAT), cytochrome P450 7A1 (CYP7A1) and peroxisome proliferation-activated receptor alpha (PPAR-α) in rat livers were evaluated using Western blotting. Results: OFP-EA-extract markedly altered the increased plasma TC, TG, LDL and decreased the HDL induced by a hypercholesterolemic diet with a dose-dependent improvement on both atherogenic index and cardiac risk factor (p < 0.01 and p < 0.001 at 100 and 300 mg/kg dose, respectively). Lipid deposition in liver was attenuated significantly in hypercholesterolemic animals supplemented with OFP-EA-extract (p < 0.01 at 100 and p < 0.001 at 300 mg/kg dose, respectively). Further mechanistic studies revealed that OFP-EA extract regulated the altered expressional levels of CYP7A1 and PPAR-α in the livers of hypercholesterolemic diet-induced rats. Conclusion: The hypocholesterolemic and hepatoprotective functions of OFP-EA-extract are probably due to the increase in fatty acids unitization in liver via the up-regulation of PPAR-α level

Late Failure of High-Flow Nasal Cannula May Be Associated with High Mortality in COVID-19 Patients: A Multicenter Retrospective Study in the Republic of Korea

The aim of this study was to determine whether the late failure of high-flow nasal cannula (HFNC) is associated with mortality in patients with coronavirus disease 2019 (COVID-19). This multicenter study included seven university-affiliated hospitals in the Republic of Korea. We collected the data of patients hospitalized with COVID-19 between 10 February 2020 and 28 February 2021. Failure of HFNC was defined as the need for mechanical ventilation despite HFNC application. According to the time of intubation, HFNC failure was divided into early failure (within 48 h) and late failure (after 48 h). During the study period, 157 patients received HFNC and 133 were eligible. Among them, 70 received mechanical ventilation. The median time from HFNC initiation to intubation of the early failure group was 4.1 h (interquartile range [IQR]: 1.1–13.5 h), and that of the late failure group was 70.9 h (IQR: 54.4–145.4 h). Although the ratio of pulse oximetry/fraction of inspired oxygen (ROX index) within 24 h of HFNC initiation tended to be lower in the early failure group than in the late failure group, the ROX index before two hours of intubation was significantly lower in the late failure group (odds ratio [OR], 5.74 [IQR: 4.58–6.98] vs. 4.80 [IQR: 3.67–5.97], p = 0.040). The late failure of HFNC may be associated with high mortality in COVID-19 patients with acute respiratory failure

Comparison of Clinical Characteristics and Outcomes of Younger and Elderly Patients with Severe COVID-19 in Korea: A Retrospective Multicenter Study

Old age is associated with disease severity and poor prognosis among coronavirus disease 2019 (COVID-19) cases; however, characteristics of elderly patients with severe COVID-19 are limited. We aimed to assess the clinical characteristics and outcomes of patients hospitalized with severe COVID-19 at tertiary care centers in South Korea. This retrospective multicenter study included patients with severe COVID-19 who were admitted at seven hospitals in South Korea from 2 February 2020 to 28 February 2021. The Cox regression analyses were performed to assess factors associated with the in-hospital mortality. Of 488 patients with severe COVID-19, 318 (65.2%) were elderly (&ge;65 years). The older patient group had more underlying diseases and a higher severity score than the younger patient group. The older patient group had a higher in-hospital mortality rate than the younger patient group (25.5% versus 4.7%, p-value &lt; 0.001). The in-hospital mortality risk factors among patients with severe COVID-19 included age, acute physiology and chronic health evaluation II score, presence of diabetes and chronic obstructive lung disease, high white blood cell count, low neutrophil-lymphocyte ratio and platelet count, do-not-resuscitate order, and treatment with invasive mechanical ventilation. In addition to old age, disease severity and examination results must be considered in treatment decision-making

Olea europaea Linn (Oleaceae) Fruit Pulp Extract Exhibits Potent Antioxidant Activity and Attenuates Neuroinflammatory Responses in Lipopolysaccharide-Stimulated Microglial Cells

Purpose: To investigate the antioxidant and anti-neuroinflammatory potentials of Olea europaea Linn. fruit pulp (OFP-EA) extract in LPS-stimulated BV-2 microglial cells. Methods: Cell viabilities were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) assay. Antioxidant properties were evaluated using 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity. Lipopolysaccharide (LPS) was used to stimulate BV-2 microglia. Nitric oxide (NO) production was measured using Griess assay. Inducible NO synthase (iNOS) expression and tumor necrosis factor-alpha (TNF-α) production were measured using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Results: OFP-EA extract significantly (p<0.001 at 20-200 µg/ml, respectively) scavenged the free radicals in a dose-dependent fashion. The increased levels of No stimulated by LPS (34±2.41) were also inhibited by OFP-EA extract significantly and concentration dependently (27±2.32, 21±2.54, 17±1.92 and 11±1.94 at 10, 20, 40 and 80 µg/ml, respectively). Further, OFP-EA suppressed the elevated levels iNOS expression and TNF-α production (p<0.001 at 20, 40 and 80 µg/ml) in LPS-stimulated BV-2 cells. Conclusion: Results indicate that OFP-EA extract exhibited strong antioxidant properties and inhibited the excessive production of pro-inflammatory mediators such as NO, iNOS and TNF-α in LPS-stimulated BV-2 cells. The antioxidant activity exhibited by OFP-EA extract might play a critical role in ameliorating the inflammatory processes in LPS-stimulated BV-2 microglial cells

Overexpression of fatty acid synthase attenuates bleomycin induced lung fibrosis by restoring mitochondrial dysfunction in mice

Abstract Proper lipid metabolism is crucial to maintain alveolar epithelial cell (AEC) function, and excessive AEC death plays a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The mRNA expression of fatty acid synthase (FASN), a key enzyme in the production of palmitate and other fatty acids, is downregulated in the lungs of IPF patients. However, the precise role of FASN in IPF and its mechanism of action remain unclear. In this study, we showed that FASN expression is significantly reduced in the lungs of IPF patients and bleomycin (BLM)-treated mice. Overexpression of FASN significantly inhibited BLM-induced AEC death, which was significantly potentiated by FASN knockdown. Moreover, FASN overexpression reduced BLM-induced loss of mitochondrial membrane potential and the production of mitochondrial reactive oxygen species (ROS). Oleic acid, a fatty acid component increased by FASN overexpression, inhibited BLM-induced cell death in primary murine AECs and rescue BLM induced mouse lung injury/fibrosis. FASN transgenic mice exposed to BLM exhibited attenuated lung inflammation and collagen deposition compared to controls. Our findings suggest that defects in FASN production may be associated with the pathogenesis of IPF, especially mitochondrial dysfunction, and augmentation of FASN in the lung may have therapeutic potential in preventing lung fibrosis

Annexin A1 in plasma from patients with bronchial asthma: its association with lung function

Abstract Background Annexin-A1 (ANXA1) is a glucocorticoid-induced protein with multiple actions in the regulation of inflammatory cell activation. The anti-inflammatory protein ANXA1 and its N-formyl peptide receptor 2 (FPR2) have protective effects on organ fibrosis. However, the exact role of ANXA1 in asthma remains to be determined. The aim of this study was to identify the role of ANXA1 in bronchial asthma. Methods In mice sensitized and challenged with ovalbumin (OVA-OVA mice) and mice sensitized with saline and challenged with air (control mice), we investigated the potential links between ANXA1 levels and bronchial asthma using ELISA, immunoblotting, and immunohistochemical staining. Moreover, we also determined ANXA1 levels in blood from 50 asthmatic patients (stable and exacerbated states). Results ANXA1 protein levels in lung tissue and bronchoalveolar lavage fluid were significantly higher in OVA-OVA mice compared with control mice. FPR2 protein levels in lung tissue were significantly higher in OVA-OVA mice compared with control mice. Plasma ANXA1 levels were increased in asthmatic patients compared with healthy controls. Plasma ANXA1 levels were significantly lower in exacerbated patients compared with stable patients with bronchial asthma (p < 0.05). The plasma ANXA1 levels in controlled asthmatic patients were correlated with forced expiratory volume in 1 s (FEV1) (r = − 0.191, p = 0.033) and FEV1/forced vital capacity (FVC) (r = −0.202, p = 0.024). Conclusion These results suggest that ANXA1 may be a potential marker and therapeutic target for asthma

Corticosteroid outcome may be dependent of duration of use in severe COVID-19

Background/Aims For patients hospitalized with coronavirus disease 2019 (COVID-19) who require supplemental oxygen, the evidence of the optimal duration of corticosteroid is limited. This study aims to identify whether long-term use of corticosteroids is associated with decreased mortality. Methods Between February 10, 2020 and October 31, 2021, we analyzed consecutive hospitalized patients with COVID-19 with severe hypoxemia. The patients were divided into short-term (≤ 14 days) and long-term (> 14 days) corticosteroid users. The primary outcome was 60-day mortality. We performed propensity score (PS) analysis to mitigate the effect of confounders and conducted Kaplan-Meier curve analysis. Results There were 141 (52%) short-term users and 130 (48%) long-term corticosteroid users. The median age was 68 years and the median PaO2/FiO2 at admission was 158. Of the patients, 40.6% required high-flow nasal cannula, 48.3% required mechanical ventilation, and 11.1% required extracorporeal membrane oxygenation. The overall 60-day mortality rate was 23.2%, and that of patients with hospital-acquired pneumonia (HAP) was 22.9%. The Kaplan-Meier curve for 60-day survival in the PS-matched cohort showed that corticosteroid for > 14 days was associated with decreased mortality (p = 0.0033). There were no significant differences in bacteremia and HAP between the groups. An adjusted odds ratio for the risk of 60-day mortality in short-term users was 5.53 (95% confidence interval, 1.90–18.26; p = 0.003). Conclusions For patients with severe COVID-19, long-term use of corticosteroids was associated with decreased mortality, with no increase in nosocomial complications. Corticosteroid use for > 14 days can benefit patients with severe COVID-19

The Epidemiology and Economic Burden of Clostridium difficile Infection in Korea

The prevalence of Clostridium difficile infection and the associated burden have recently increased in many countries. While the main risk factors for C. difficile infection include old age and antibiotic use, the prevalence of this infection is increasing in low-risk groups. These trends highlight the need for research on C. difficile infection. This study pointed out the prevalence and economic burden of C. difficile infection and uses the representative national data which is primarily from the database of the Korean Health Insurance Review and Assessment Service, for 2008–2011. The annual economic cost was measured using a prevalence approach, which sums the costs incurred to treat C. difficile infection. C. difficile infection prevalence was estimated to have increased from 1.43 per 100,000 in 2008 to 5.06 per 100,000 in 2011. Moreover, mortality increased from 69 cases in 2008 to 172 in 2011. The economic cost increased concurrently, from $2.4 million in 2008 to$7.6 million, $10.5 million, and$15.8 million in 2009, 2010, and 2011, respectively. The increasing economic burden of C. difficile infection over the course of the study period emphasizes the need for intervention to minimize the burden of a preventable illness like C. difficile infection