Lemon Peel Water Extract: A Novel Material for Retinal Health, Protecting Retinal Pigment Epithelial Cells against Dynamin-Related Protein 1-Mediated Mitochondrial Fission by Blocking ROS-Stimulated Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathway.

Previous studies showed that NaIO3 can induce oxidative stress-mediated retinal pigment epithelium (RPE) damage to simulate age-related macular degeneration (AMD). Lemon peel is rich in antioxidants and components that can penetrate the blood-retinal barrier, but their role in retinal oxidative damage remains unexplored. Here, we explore the protection of lemon peel ultrasonic-assisted water extract (LUWE), containing large amounts of flavonoids and polyphenols, against NaIO3-induced retinal degeneration. We initially demonstrated that LUWE, orally administered, prevented retinal distortion and thinning on the inner and outer nuclei layers, downregulating cleaved caspase-3 protein expression in RPE cells in NaIO3-induced mice. The effect of LUWE was achieved through the suppression of apoptosis and the associated proteins, such as cleaved PARP and cleaved caspase-3, as suggested by NaIO3-induced ARPE-19 cell models. This is because LUWE reduced reactive oxygen species-mediated mitochondrial fission via regulating p-Drp-1 and Fis1 expression. We further confirmed that LUWE suppresses the expression of p-MEK-1/2 and p-ERK-1/2 in NaIO3-induced ARPE-19 cells, thereby providing the protection described above, which was confirmed using PD98059 and U0126. These results indicated that LUWE prevents mitochondrial oxidative stress-mediated RPE damage via the MEK/ERK pathway. Elucidation of the molecular mechanism may provide a new protective strategy against retinal degeneration.

Luteolin Reduces Aqueous Extract PM2.5-induced Metastatic Activity in H460 Lung Cancer Cells.

Fine particulate matter (PM2.5) is the critical cause of lung cancer and can further promote tumor cell migration and invasion. This study investigated the effects of luteolin, an antiangiogenic flavonoid agent, on blocking aqueous extract PM2.5-prompted cancer progression. We observed that luteolin reduced cell migration and the expression of pro-metastatic factors pro-matrix metalloproteinase (MMP)-2 and intercellular adhesion molecule (ICAM)-1 in PM2.5-exposed H460 lung cancer cells. Luteolin treatment also reduced the transduction of PM2.5-induced epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) cascade signaling. Furthermore, the reduction of MMP-2 expression and ICAM-1 production by luteolin in PM2.5-stimulated H460 cells is EGFR-PI3K-AKT pathway dependent. These results suggest that luteolin exhibits antitumor progression by inhibiting EGFR-PI3K-AKT pathway.

Suppressive Effect of Tetrahydrocurcumin on Pseudomonas aeruginosa Lipopolysaccharide-Induced Inflammation by Suppressing JAK/STAT and Nrf2/HO-1 Pathways in Microglial Cells.

Brain inflammation, a pathological feature of neurodegenerative disorders, exhibits elevated microglial activity and increased levels of inflammatory factors. The present study was aimed at assessing the anti-inflammatory response of tetrahydrocurcumin (THC), the primary hydrogenated metabolite of curcumin, which was applied to treat Pseudomonas aeruginosa (P.a.) lipopolysaccharide- (LPS-) stimulated BV2 microglial cells. THC reduced P.a. LPS-induced mortality and the production of inflammatory mediators IL-6, TNF-α, MIP-2, IP-10, and nitrite. A further investigation revealed that THC decreased these inflammatory cytokines synergistically with JAK/STAT signaling inhibitors. THC also increased Nrf2/HO-1 signaling transduction which inhibits iNOS/COX-2/pNFκB cascades. Additionally, the presence of the HO-1 inhibitor Snpp increased the levels of IP-10, IL-6, and nitrite while THC treatment reduced those inflammatory factors in P.a. LPS-stimulated BV2 cells. In summary, we demonstrated that THC exhibits anti-inflammatory activities in P.a. LPS-induced inflammation in brain microglial cells by inhibiting STAT1/3-dependent NF-κB activation and inducing Nrf2-mediated HO-1 expression.

The Protective Effects of α-Mangostin Attenuate Sodium Iodate-Induced Cytotoxicity and Oxidative Injury via Mediating SIRT-3 Inactivation via the PI3K/AKT/PGC-1α Pathway.

It is well known that age-related macular degeneration (AMD) is an irreversible neurodegenerative disease that can cause blindness in the elderly. Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is a part of the pathogenesis of AMD. In this study, we evaluated the protective effect and mechanisms of alpha-mangostin (α-mangostin, α-MG) against NaIO3-induced reactive oxygen species (ROS)-dependent toxicity, which activates apoptosis in vivo and in vitro. MTT assay and flow cytometry demonstrated that the pretreatment of ARPE-19 cells with α-MG (0, 3.75, 7.5, and 15 µM) significantly increased cell viability and reduced apoptosis from NaIO3-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cleaved PARP-1, cleaved caspase-3 protein expression, and enhancement of Bcl-2 protein. Furthermore, pre-incubation of ARPE-19 cells with α-MG markedly inhibited the intracellular ROS and extracellular H2O2 generation via blocking of the abnormal enzyme activities of superoxide dismutase (SOD), the downregulated levels of catalase (CAT), and the endogenous antioxidant, glutathione (GSH), which were regulated by decreasing PI3K-AKT-PGC-1α-STRT-3 signaling in ARPE-19 cells. In addition, our in vivo results indicated that α-MG improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer by inhibiting the expression of cleaved caspase-3 protein. Taken together, our results suggest that α-MG effectively protects human ARPE-19 cells from NaIO3-induced oxidative damage via antiapoptotic and antioxidant effects.

Patients with Liver Cirrhosis as Frequent Attenders of Emergency Departments.

OBJECTIVES: Frequent attendance for nonemergency problems to emergency departments (EDs) contributes to ED overcrowding, resulting in medical care delays, increased medical errors, and social and economic burdens. Most studies regarding frequent attenders of EDs examine general patients without classifying certain subgroups. This study aimed to investigate patients with liver cirrhosis who present repeatedly to the ED. METHODS: This was a retrospective, observational cohort study of adult patients with a history of liver cirrhosis presenting to the ED from January 2011 to December 2015. We included patients with cirrhosis whose first ED visit occurred during the study period. We went far back for 20 years and excluded patients with any ED visits (including both cirrhosis and noncirrhosis-related ones) before the study period. We categorized frequent attenders as patients with more than 4 ED visits within 12 months after the first ED visit; infrequent attenders were those who did not meet this criterion. RESULTS: A total of 3513 patients with cirrhosis were included in this retrospective cohort study. Compared with the infrequent attenders, frequent attenders had a higher rate of presentations due to hepatic encephalopathy (15.2% vs 13.7%, P < 0.001) and ascites (10% vs 4%, P < 0.001) and ascites (10% vs 4%, P < 0.001) and ascites (10% vs 4%. CONCLUSIONS: Hepatic encephalopathy and ascites account for more ED visits in frequent than in infrequent attenders. Our findings provide information for those planning outpatient support for patients with cirrhosis. Further research is warranted.

Massive transfusion in upper gastrointestinal bleeding: a new scoring system.

Background: Massive transfusion in patients with upper gastrointestinal bleeding (UGIB) was not investigated. We developed a new scoring system to predict massive transfusion and to enhance care and early resource mobilization. Methods: Massive transfusion was defined as transfusion with ≥10 units of red blood cells within the first 24 h. Data were extracted from a 10-year, six-hospital database. Logistic regression was applied to derive a risk score for massive transfusion using data from 2006 to 2010, in 24,736 patients (developmental cohort). The score was then validated using data from 2011 to 2015 in 27,449 patients (validation cohort). Area under the receiver operating characteristic (AUROC) curve was performed to assess prediction accuracy. Results: Five characteristics were independently associated (p < .001) with massive transfusion: presence of band-form cells among white blood cells (band form >0), international normalized ratio (INR) >1.5, pulse >100 beats per minute or systolic blood pressure <100 mmHg (shock), haemoglobin <8.0 g/dL and endoscopic therapy. The new scoring system successfully discriminated well between UGIB patients requiring massive transfusion and those who did not in both cohorts (AUROC: 0.831, 95%CI: 0.827-0.836; AUROC: 0.822, 95% CI: 0.817-0.826, respectively). Conclusions: The new scoring system predicts massive transfusion requirement in patients with UGIB well. Key messages Massive transfusion is a life-saving management in massive upper gastrointestinal bleeding. How to identify patients requiring massive transfusion in upper gastrointestinal bleeding is poorly documented. Approximately 3.9% of upper gastrointestinal bleeding patients require massive transfusion. A new scoring system is developed to identify patients requiring massive transfusion with high accuracy.