Yih-Giun Cherng

Lipopolysaccharide stimulates syntheses of toll-like receptor 2 and surfactant protein-A in human alveolar epithelial A549 cells through upregulating phosphorylation of MEK1 and ERK1/2 and sequential activation of NF-κB.

Surfactant proteins (SPs) and toll-like receptors (TLRs) contribute to regulation of sepsis-induced acute lung injury. Lipopolysaccharide (LPS) is one of the major causes of septic shock. This study was designed to evaluate the effects of LPS on the regulation of tlr-2 and sp-a gene expression in human alveolar epithelial A549 cells and the possible mechanisms. Exposure of A549 cells to LPS increased the expressions of TLR2 and SP-A mRNA and protein in time-dependent manners. A search using a bioinformatic approach found that there are several nuclear factor kappa-B (NF-κB)-DNA-binding motifs in the promoter region of the tlr2 and sp-a genes. Immunoblotting analyses revealed that exposure to LPS time-dependently enhanced the translocation of NF-κB from the cytoplasm to nuclei. Analyses of an electrophoretic mobility shift assay further showed that LPS augmented the transactivation activity of NF-κB to its consensus oligonucleotides in A549cells. Sequentially, treatment of A549 cells with LPS increased phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38-mitogen-activated protein kinase (p38MAPK), and MAPK kinase-1 (MEK1). Pretreatment with PD98059, an inhibitor of ERK1/2, significantly decreased LPS-induced TLR2 and SP-A mRNA expression.

Resveratrol attenuates high-fat diet-induced disruption of the blood-brain barrier and protects brain neurons from apoptotic insults.

The blood-brain barrier (BBB) maintains brain microenvironment. Our previous study showed that oxidized low-density lipoprotein (oxLDL) can damage the BBB by inducing apoptosis of cerebrovascular endothelial cells. This study was aimed at evaluating the effects of resveratrol on high-fat diet-induced insults to the BBB and brain neurons. Exposure of mice to a high-fat diet for 8 weeks increased levels of serum total cholesterol (146 ± 13) and LDL (68 ± 8), but resveratrol decreased such augmentations (119 ± 6; 45 ± 8). Permeability assays showed that a high-fat diet induced breakage of the BBB (88 ± 21). Meanwhile, resveratrol alleviated this interruption (16 ± 6). Neither resveratrol nor a high-fat diet caused the death of cerebrovascular endothelial cells. Instead, exposure to a high-fat diet disrupted the polymerization of occludin and zonula occludens (ZO)-1, but resveratrol significantly attenuated those injuries. Neither a high-fat diet nor resveratrol changed the levels of occludin or ZO-1 in brain tissues. Resveratrol protected brain neurons against high-fat diet-induced caspase-3 activation and genomic DNA fragmentation. This study shows that resveratrol can attenuate the high-fat diet-induced disruption of the BBB via interfering with occludin and ZO-1 tight junctions, and protects against apoptotic insults to brain neurons.

Antihyperglycemic action of sinapic acid in diabetic rats

Sinapic acid is a hydroxycinnamic acid contained in plants. In an attempt to know the hyperglycemic effect of sinapic acid, this study applied streptozotocin (STZ) to induce type 1-like diabetic rats and fed fructose-rich chow to induce type 2-like diabetic rats. Sinapic acid dose-dependently reduced the hyperglycemia of STZ-diabetic rats (9.8 ± 1.8%, 11.6 ± 0.7%, and 19.4 ± 3.2% at 5 mg/kg, 10 mg/kg, and 25 mg/kg, respectively). Also, sinapic acid attenuated the postprandial plasma glucose without changing plasma insulin in rats. Repeated treatment of sinapic acid increased the gene expression of GLUT4 in soleus muscle of STZ-diabetic rats. Moreover, sinapic acid enhanced glucose uptake into isolated soleus muscle and L6 cells (337.0 ± 29.6%). Inhibition of phospholipase C (PLC) using U73122 (1.00 ± 0.02 μg/mg protein) or protein kinase C (PKC) using chelerythrine (0.97 ± 0.02 μg/mg protein) attenuated the sinapic acid-stimulated glucose uptake (1.63 ± 0.02 μg/mg protein) in L6 cells. Otherwise, the reduced glucose infusion rate (GIR) in fructose-rich chow-fed rats was also raised by sinapic acid. Our results suggest that sinapic acid ameliorates hyperglycemia through PLC-PKC signals to enhance the glucose utilization in diabetic rats.

GATA-2 Transduces LPS-Induced il-1β Gene Expression in Macrophages via a Toll-Like Receptor 4/MD88/MAPK-Dependent Mechanism

Lipopolysaccharide (LPS) is a critical factor for inducing acute lung injury. GATA-2, a transcription factor, contributes to the control of cell activity and function. Exposure of RAW 264.7 cells to LPS induced interleukin (IL)-1β mRNA and protein expression and GATA-2 translocation from the cytoplasm to nuclei in concentration- and time-dependent manners. A bioinformatic search revealed that GATA-2-specific binding elements exist in the 5’-promoter region of the il-1β gene. LPS could enhance the transactivation activity of GATA-2 in macrophages. Knocking-down translation of GATA-2 mRNA using RNA interference significantly alleviated LPS-induced IL-1β mRNA and protein expression. As to the mechanism, transfection of toll-like receptor (TLR) 4 small interfering (si)RNA into macrophages concurrently decreased LPS-caused increases in nuclear GATA-2 levels. Sequentially, treatment with myeloid differentiation factor 88 (MyD88) siRNA decreased LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) kinase 1/2 and subsequent translocation of GATA-2. Reducing MAPK activities using specific inhibitors simultaneously decreased GATA-2 activation. Furthermore, exposure of primary macrophages to LPS significantly increased the transactivation activities of GATA-2 and IL-1β mRNA and protein expression. Transfection of GATA-2 siRNA inhibited LPS-induced IL-1β mRNA expression. Results of this study show that LPS induction of il-1β gene expression in macrophages is mediated by GATA-2 via activation of TLR4, MyD88, and MAPKs.

Dexamethasone, ondansetron, and their combination and postoperative nausea and vomiting in children undergoing strabismus surgery: a meta-analysis of randomized controlled trials

Postoperative nausea and vomiting (PONV) is a common complication after pediatric strabismus surgery. Steroids and ondansetron (a 5‐HT3 antagonist) can effectively reduce nausea, vomiting, and pain and thus might be useful agents for the prevention of PONV in pediatric patients. The aim of this study was to conduct a systematic review and meta‐analysis of randomized controlled trials (RCTs) to evaluate the prophylactic effects of dexamethasone and ondansetron on PONV after strabismus surgery in pediatric patients.

Outcomes after non-neurological surgery in patients with Parkinson's disease a nationwide matched cohort study

AbstractPatients with Parkinson disease (PD) were known to have increased risk of complications during hospitalization. The purpose of this study is to validate the global features of postoperative adverse outcomes for patients with PD.Using reimbursement claims from Taiwans National Health Insurance Research Database, we conducted a nationwide retrospective cohort study of 6455 patients with preoperative PD receiving major surgery during 2008 to 2012. With a propensity score matching procedure, 12,910 surgical patients without PD were selected for comparison. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for 9 major postoperative complications and 30-day postoperative mortality associated with preoperative PD were calculated in the multivariate logistic regressions.Patients with PD had increased risk of postoperative pulmonary embolism (OR 2.72, 95% CI 1.45–5.10), stroke (OR 1.77, 95% CI 1.53–2.05), pneumonia (OR 1.98, 95% CI 1.70–2.31), urinary tract infection (OR 1.52, 95% CI 1.35–1.70), septicemia (OR 1.54, 95% CI 1.37–1.73), acute renal failure (OR 1.36, 95% CI 1.07–1.73), and mortality (OR 1.45, 95% CI 1.06–1.98). The association between preoperative PD and postoperative adverse events was significant in both sexes and every age group. Low income, ≥65 years of age, surgery not in medical center, highest quartile of PD medication users, and more medical conditions worsen the risk of postoperative adverse events in patients with PD.This study showed increased postoperative complications and mortality in patients with PD. Our findings suggest that revision of postoperative care protocols for this population is urgently needed.

Are non-cardiac surgeries safe for dialysis patients? - A population-based retrospective cohort study.

Background End-stage renal disease represents a risk complex that complicates surgical results. The surgical outcomes of dialysis patients have been studied in specific fields, but the global features of postoperative adverse outcomes in dialysis patients receiving non-cardiac surgeries have not been examined. Methods Taiwan’s National Health Insurance Research Database was used to study 8,937 patients under regular dialysis with 8,937 propensity-score matched-pair controls receiving non-cardiac surgery between 2004 and 2007. We investigated the influence of hemodialysis and peritoneal dialysis, effects of hypertension and diabetes, and impact of additional comorbidities on postoperative adverse outcomes. Results Postoperative mortality in dialysis patients was higher than in controls (odds ratio [OR] 3.33, 95% confidence interval [CI] 2.56 to 4.33) when receiving non-cardiac surgeries. Complications such as acute myocardial infarction, pneumonia, bleeding, and septicemia were significantly increased. Postoperative mortality was significantly increased among peritoneal dialysis patients (OR 2.71, 95% CI 1.70 to 4.31) and hemodialysis patients (OR 3.42, 95% CI 2.62 to 4.47) than in controls. Dialysis patients with both hypertension and diabetes had the highest risk of postoperative complications; these risks increased with number of preoperative medical conditions. Patients under dialysis also showed significantly increased length of hospitalization, more ICU stays and higher medical expenditures. Conclusion Surgical patients under dialysis encountered significantly higher postoperative complications and mortality than controls when receiving non-cardiac surgeries. Different dialysis techniques, pre-existing hypertension/diabetes, and various comorbidities had complication-specific impacts on surgical adverse outcomes. These findings can help surgical teams provide better risk assessment and postoperative care for dialysis patients.

Paraplegia Following Spinal Anesthesia in a Patient with an Undiagnosed Metastatic Spinal Tumor

Although extremely rare, paraplegia can be a complication following spinal anesthesia if the patient has a previously unrecognized spinal tumor. We describe a 75-year-old male patient who underwent retrograde ureteroscopic examination under spinal anesthesia. He developed complete paraplegia 24 hours later. Magnetic resonance imaging (MRI) revealed bone metastasis to T10, a vertebral body mass lesion at L3, and an epidural mass at T9-11 with cord compression. The aim of this case report is to highlight the importance of neurological examination of patients undergoing neuraxial block both in the pre-anesthetic interview and postoperative examination in the recovery period. Careful observation of the postoperative course is essential to exclude any possible neurological complications. If motor and sensory functions do not satisfactorily recover, an MRI examination should be undertaken without delay to determine whether the underlying pathology is treatable or reversible.

Rosiglitazone is effective to improve renal damage in type-1-like diabetic rats.

A marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats) showing diabetic nephropathy. It has been documented that klotho is the target gene of PPARγ. However, the effect of PPARγ agonist on klotho expression in kidney of STZ rats remains obscure. Thus, we used rosiglitazone (TZD) as PPARγ agonist to investigate the effect on renal dysfunction in STZ rats. Treatment of TZD reversed the lower levels of PPARγ, klotho, and FGFR1 expressions in kidneys of STZ rats without the correction of hyperglycemia. Also, renal functions and structural defeats were improved by TZD treatment. Taken together, oral administration of TZD may improve STZ-induced diabetic nephropathy due to restoration of the expression of klotho axis through an increase in PPARγ expression without changing blood glucose in rats.

Ginseng is useful to enhance cardiac contractility in animals

Ginseng has been shown to be effective on cardiac dysfunction. Recent evidence has highlighted the mediation of peroxisome proliferator-activated receptors (PPARs) in cardiac function. Thus, we are interested to investigate the role of PPARδ in ginseng-induced modification of cardiac contractility. The isolated hearts in Langendorff apparatus and hemodynamic analysis in catheterized rats were applied to measure the actions of ginseng ex vivo and in vivo. In normal rats, ginseng enhanced cardiac contractility and hemodynamic dP/dt max significantly. Both actions were diminished by GSK0660 at a dose enough to block PPARδ. However, ginseng failed to modify heart rate at the same dose, although it did produce a mild increase in blood pressure. Data of intracellular calcium level and Western blotting analysis showed that both the PPARδ expression and troponin I phosphorylation were raised by ginseng in neonatal rat cardiomyocyte. Thus, we suggest that ginseng could enhance cardiac contractility through increased PPARδ expression in cardiac cells.