Pheophorbide A isolated from Gelidium amansii inhibits adipogenesis by regulating adipogenic transcription factors and AMPK in 3T3-L1 adipocytes.

Adipocyte lipid accumulation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. As part of our efforts to isolate antiobesity agents from natural products, we first isolated the active compound from the extract of Gelidium amansii through bioassay-guided fractionation. We then hypothesized that pheophorbide A isolated from G amansii inhibits adipogenesis by downregulating adipogenic transcription factors; therefore, the antiadipogenic effects of pheophorbide A were investigated in 3T3-L1 adipocytes. On differentiation of 3T3-L1 preadipocytes into adipocytes, they were treated with pheophorbide A (0-83 µM). Pheophorbide A inhibited triglyceride accumulation (half maximal inhibitory concentration = 114.2 µM) and stimulated glycerol release in a dose-dependent manner in 3T3-L1 adipocytes. In addition, pheophorbide A significantly decreased leptin concentrations in 3T3-L1 adipocytes. Pheophorbide A inhibited adipogenesis by suppressing the expression of adipogenic transcriptional factors including peroxisome proliferator-activated receptor γ, CCATT/enhancer binding protein α, sterol regulatory element binding protein 1c, and fatty acid synthase. It also induced the expression of phosphorylation of AMP-activated protein kinase. Therefore, these results suggest that pheophorbide A may be useful for preventing or treating obesity because of its inhibitory effect on adipogenesis.

Robot-Assisted Repair of Atrial Septal Defect: A Comparison of Beating and Non-Beating Heart Surgery.

BACKGROUND: Robot-assisted repair of atrial septal defect (ASD) can be performed under either beating-heart or non-beating-heart conditions. However, the risk of cerebral air embolism (i.e., stroke) is a concern in the beating-heart approach. This study aimed to compare the outcomes of beating- and non-beating-heart approaches in robot-assisted ASD repair. METHODS: From 2010 to 2019, a total of 45 patients (mean age, 43.4±14.6 years; range, 19-79 years) underwent ASD repair using the da Vinci robotic surgical system. Twenty-seven of these cases were performed on a beating heart (beating-heart group, n=27) and the other cases were performed on an arrested or fibrillating heart (non-beating-heart group, n=18). Cardiopulmonary bypass (CPB) was achieved via cannulation of the femoral vessels and the right internal jugular vein in all patients. RESULTS: Complete ASD closure was verified using intraoperative transesophageal echocardiography in all patients. Conversion to open surgery was not performed in any cases, and there were no major complications. All patients recovered from anesthesia without any immediate postoperative neurologic symptoms. In a subgroup analysis of isolated ASD patch repair (beating-heart group: n=22 vs. non-beating-heart group: n=5), the operation time and CPB time were shorter in the beating-heart group (234±38 vs. 253±29 minutes, p=0.133 and 113±28 vs. 143±29 minutes, p=0.034, respectively). CONCLUSION: Robot-assisted ASD repair can be safely performed with the beating-heart approach. No additional risk in terms of cerebral embolism was found in the beating-heart group.

Impact of chronic kidney disease on clinical outcomes in patients with Stage B progressive aortic regurgitation (mild to moderate and moderate grades).

BACKGROUND: Chronic kidney disease (CKD) is a significant comorbidity in patients with heart failure and valvular heart disease. Renal impairment is not well evaluated in the patients with Stage B progressive aortic regurgitation (AR) (mild to moderate and moderate grades in this study), for estimating outcome. HYPOTHESIS: We sought to investigate the prognostic factor, especially CKD, in the patients with progressive AR. METHODS: We enrolled 262 patients with Stage B progressive AR and preserved left ventricular systolic function (ejection fraction ≥ 50%). Based on the presence of CKD, the patients were divided into CKD (n = 70) and non-CKD (n = 192) groups, which CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2 . The primary outcome was major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, hospitalization for heart failure, and aortic valve replacement. RESULTS: The median follow-up duration was 41.5 (interquartile range: 16.2-71.7) months. Between groups, the CKD patients were older; they had a higher pulse pressure and higher incidence of hypertension, diabetes mellitus, dyslipidemia, cerebrovascular accident, and atrial fibrillation. Compared to the non-CKD group, the CKD group had lower e' velocity (4.36 ± 2.21 vs. 5.20 ± 2.30 cm/s, p = .009), higher right ventricular systolic pressure (38.02 ± 15.79 vs. 33.86 ± 11.77 mmHg, p = .047). The CKD group was associated with increased risk of MACEs (41.4% vs. 22.4%; unadjusted hazard ratio [HR]: 1.78, 95% confidence interval [CI]: 1.11-2.85, p = .017). In multivariate Cox regression analyses, the risk of MACEs was significantly different between groups (adjusted HR: 1.71, 95% CI: 1.11-2.62, p = .015); furthermore, the risk of hospitalization for heart failure (10.0% vs. 2.6%; adjusted HR: 2.30, 95% CI: 1.16-4.55, p = .017) was significantly higher in the CKD group than in the non-CKD group. CONCLUSIONS: In patients with Stage B progressive AR, CKD is an independent prognostic factor for clinical outcomes (composite clinical outcome, hospitalization for heart failure).

Incidence of spinal cord ischemia according to the patency of reimplanted segmental arteries during thoracoabdominal aortic replacement.

BACKGROUND: This study aimed to investigate the impact of segmental artery reimplantation and its patency on spinal cord ischemia (SCI) in thoracoabdominal aorta replacement. METHODS: For 193 patients who underwent early postoperative computed tomographic (CT) angiography after thoracoabdominal aorta replacement, the technique of segmental artery reimplantation, their patency, and postoperative SCI were retrospectively investigated. RESULTS: The early patency rate of reimplanted segmental artery was 83.3% (210 of 252), as 13 were taken down intraoperatively and 42 were not visualized in the postoperative CT angiography. The patency rate differed according to the reimplantation technique: 93.6% (131/140) for en bloc patch, 95.6% (43/45) for small individual patch, and 53.7% (36/67) for graft interposition. SCI occurred in 13 (6.3%) patients, 4 of whom (2.0%) remained paraplegic permanently. SCI was significantly more frequent (P=0.044) in the patients in whom segmental artery reimplantation was not successful (take-down or occlusion, 6/37=16.2%) than in those who had all segmental arteries sacrificed intentionally (2/64=3.1%) and those who showed patency of all reimplanted segmental arteries (5/92=5.4%). Especially, there was no permanent paraplegia in the last group. Failure of intended segmental artery reimplantation was a significant risk factor of postoperative SCI in logistic regression analysis (P=0.012; odds ratio 4.65, 95% confidence interval 1.41-15.36). CONCLUSIONS: During thoracoabdominal aorta replacement, attention should be paid to the segmental artery reimplantation technique, which affects the risk of occlusion or intraoperative take-down and thereby may have impact on postoperative SCI.

Prevalence and urodynamic characteristics of detrusor overactivity with impaired contractility in the community-dwelling elderly with non-neurogenic lower urinary tract symptoms: Is it from a single or two independent bladder dysfunctions?

PURPOSE: To identify the prevalence of detrusor overactivity with impaired contractility (DOIC) in the community-dwelling elderly and explore whether it is from a single or two independent bladder dysfunctions. MATERIALS AND METHODS: Based on a 10-year urodynamic database of the SEOUL Study Group, elderly patients who met inclusion criteria were selected. Bladder sensation, capacity, and compliance were designated as evaluation elements for storage function, and free maximal flow rate (Qmax) and post void residual volume, detrusor pressure at maximal flow (PdetQmax), and bladder voiding efficiency for voiding function. RESULTS: The prevalence rate of DOIC was 18.8% and 5.5% among 2,571 men and 688 women, respectively, and increased significantly with age. In men, patients with DOIC showed no differences in storage parameters and significantly lower free Qmax and PdetQmax among voiding parameters, compared to those with detrusor overactivity (DO) only. Compared to men with detrusor underactivity (DU) only, those with DOIC had worse parameters in the majority of storage and voiding functions. In women, most of the storage and voiding functions were worse in patients with DOIC than in those with DO only. On the other hand, women with DU showed lower PdetQmax and worse voiding functions than those with DOIC, although some parameters did not reach statistical significance. CONCLUSIONS: It seems that DOIC is developed from a coincidental combination of two independent DO and DU in men. In contrast, DOIC is likely to be an intermediate step during the process of progression from DO to DU in women.

Idiopathic hypereosinophilic syndrome with intracardiac atypical linear-shaped and floating thrombus presenting as embolic cerebral infarction.

Knowledge of the multi-organ involvement in hypereosinophilic syndrome (HES) is important for the diagnosis and care of patients with this condition, even in cases with atypical presentation. This report aims to describe cerebral embolic infarction and intracardiac atypical linear-shaped thrombus in a patient with idiopathic HES and to discuss the approach of appropriate diagnosis and timely interventional management. A 55-year-old man presented with general weakness, including left-sided weakness, mild cognitive dysfunction, and mild exertional dyspnea for about 2 weeks. Initial magnetic resonance imaging for evaluating the brain showed multifocal acute to subacute infarction of both cerebral hemispheres and both cerebellums. Laboratory findings revealed leukocytosis (25,620 cells/mm3) and eosinophilia (54.9%). To evaluate the intracardiac embolic source, the patient underwent echocardiography, and a 1.5 cm linear thread-like and mobile mass was detected. Consequently, the patient was diagnosed with idiopathic HES. After bone marrow biopsy, corticosteroid and hydroxyurea were administered to control the eosinophilia. This case indicates that HES can present as a floating intracardiac atypical linear-shaped thrombus attached to the left ventricle. After appropriate diagnostic approaches, proper treatment could be given for the patient. .

Temporary use of unusually high dose of catecholamine improved severe ventricular dysfunction associated with stunned myocardium without significant myocardial injury in a post cardiac surgical patient: A case report.

INTRODUCTION: Some cardiac surgical patients present low cardiac output syndrome due to ventricular dysfunction resulting from postischemic myocardial stunning. We present a case of using unusually high dose of inotropes so that we could avoid mechanical circulatory support after cardiac surgery. PRESENTATION OF CASE: A 65-year-old man underwent elective cardiac surgery. His immediate cardiac output was poor and vital signs were unstable. We aggressively increased the dose of catecholamine above usual dose and the cardiac output was elevated. The patient recovered without significant myocardial injury. After a few years, TTE showed more improved left ventricular function compared with preoperative state. DISCUSSION: In a stunned myocardium, response to catecholamine is thought to be dull. Thus, if adequate response to usual dose of catecholamine is not achieved in a post cardiac surgical patient, we think that there may be a room for more increment of inotropes. CONCLUSION: Unusually high dose of catecholamine may be helpful in a patient with severe ventricular dysfunction associated with stunned myocardium.

Outcomes and Patency of Complex Configurations of Composite Grafts Using Bilateral Internal Thoracic Arteries.

BACKGROUND: It is generally agreed that using a bilateral internal thoracic artery (BITA) composite graft improves long-term survival after coronary artery bypass grafting (CABG). Although the left internal thoracic artery (LITA)-based Y-composite graft is widely adopted, technical or anatomical difficulties necessitate complex configurations. We aimed to investigate whether BITA configuration impacts survival or patency in patients undergoing coronary revascularization. METHODS: Between January 2006 and June 2017, 1,161 patients underwent CABG at Seoul National University Bundang Hospital, where the standard technique is a LITA-based Y-composite graft with the right internal thoracic artery (RITA) sequentially anastomosed to non-left anterior descending (LAD) targets. Total of 160 patients underwent CABG using BITA with modifications. Their medical records and imaging data were reviewed retrospectively to investigate technical details, clinical outcomes, and graft patency. RESULTS: Modifications of the typical Y-graft (group 1, n=90), LITA-based I-graft (group 2, n=39), and RITA-based composite graft (group 3, n=31) were used due to insufficient RITA length (47%), problems using LITA (28%), and target vessel anatomy (25%). The overall 30-day mortality rate was 1.9%. Among 116 patients who underwent computed tomography or conventional angiography at a mean interval of 29.9±33.1 months postoperatively, the graft patency rates were 98.7%, 95.3%, and 83.6% for the LAD, left circumflex artery, and right coronary artery territories, respectively. Patency rates for the inflow, secondary, and tertiary grafts were 98.2%, 90.5%, and 80.4%, respectively. The RITA-based graft (group 3) had the lowest patency rate of the various configurations (p<0.011). CONCLUSION: LITA-based Y composite graft, showed satisfactory clinical outcomes and patency whereas modifications of RITA-based composite graft had the lowest patency and 5-year survival rates. Therefore, when using RITA-based composite graft, other options should be considered before proceeding atypical configurations.

Impact of diagnostic ureteroscopy before radical nephroureterectomy on intravesical recurrence in patients with upper tract urothelial cancer.

Purpose: To evaluate the impact of diagnostic ureteroscopy performed before radical nephroureterectomy (RNU) on intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC). Materials and Methods: From May 2003 to December 2018, patients who underwent RNU for UTUC were enrolled and divided into two groups according to whether they underwent preoperative ureteroscopy (Pre-U vs. Non-U). We excluded patients who had a history of bladder cancer and did not receive bladder cuff resection during surgery. Perioperative parameters were compared between the two groups by use of t-tests or chi-square tests. Kaplan-Meier and Cox proportional hazards analyses were used to assess the association between Pre-U and IVR. Results: Of the 453 total patients, 226 patients (49.9%, Pre-U group) had received diagnostic ureteroscopy before RNU, and 227 patients (50.1%, Non-U group) had not. IVR occurred in 99 patients (43.8%) in the Pre-U group and 61 patients (26.9%) in the Non-U group (p=0.001). The median time to recurrence was 107 months. The 5-year IVR-free survival rates were 56.2% and 73.1% in the Pre-U and Non-U groups, respectively (log rank test, p<0.001). Multivariate Cox proportional hazards analysis showed that Pre-U was a significant factor (hazard ratio, 1.413; 95% confidence interval, 1.015-1.965; p=0.040) after adjustment for other factors including tumor stage, location, etc. Conclusions: Preoperative diagnostic ureteroscopy before RNU was a significant factor for IVR. Therefore, we should carefully consider Pre-U before RNU for nonobvious ureteral lesions. These results should be validated in a prospective study.

The Impact of an Attending Intensivist on the Clinical Outcomes of Patients Admitted to the Cardiac Surgical Intensive Care Unit after Coronary Artery Bypass Grafting.

BACKGROUND: We aimed to investigate the associations of critical care provided in a cardiac surgical intensive care unit (CSICU) staffed by an attending intensivist with improvements in intensive care unit (ICU) quality and reductions in postoperative complications. METHODS: Patients who underwent elective isolated coronary artery bypass grafting (CABG) between January 2007 and December 2012 (the control group) were propensity-matched (1:1) to CABG patients between January 2013 and June 2018 (the intensivist group). RESULTS: Using propensity score matching, 302 patients were extracted from each group. The proportion of patients with at least 1 postoperative complication was significantly lower in the intensivist group than in the control group (17.2% vs. 28.5%, p=0.001). In the intensivist group, the duration of mechanical ventilation (6.4±13.7 hours vs. 13.7±49.3 hours, p=0.013) and length of ICU stay (28.7±33.9 hours vs. 41.7±90.4 hours, p=0.018) were significantly shorter than in the control group. The proportions of patients with prolonged mechanical ventilation (2.3% vs. 7.6%, p=0.006), delirium (1.3% vs. 6.3%, p=0.003) and acute kidney injury (1.3% vs. 5.3%, p=0.012) were significantly lower in the intensivist group than in the control group. CONCLUSION: A transition from an open ICU model with trainee coverage to a closed ICU model with attending intensivist coverage can be expected to yield improvements in CSICU quality and reductions in postoperative complications.

Aliishimia ponticola gen. nov., sp. nov., isolated from seawater.

A Gram-stain-negative, aerobic, non-motile and coccoid, ovoid or rod-shaped bacterial strain, designated MYP11T, was isolated from seawater around Jeju island, Republic of Korea and identified by polyphasic taxonomic study. A neighbour-joining phylogenetic tree of 16S rRNA gene sequences showed that strain MYP11T joined the cluster comprising the type strains of Shimiaabyssi, Shimiaaestuarii and Shimiaaquaeponti, showing 16S rRNA gene sequence similarities of 96.3-96.8 %. Strain MYP11T exhibited 16S rRNA gene sequence similarity values of 94.2-94.9 % to the type strains of other Shimia species. In the upgma dendrogram based on the average nucleotide identity values of genomic sequences, strain MYP11T formed an evolutionary lineage independent of those of Shimia species and other taxa. Strain MYP11T contained Q-10 as the predominant ubiquinone and C18 : 1 ω7c and cyclo C19 : 0 ω8c as the major fatty acids. The major polar lipids of strain MYP11T were phosphatidylcholine, phosphatidylglycerol, two unidentified lipids and one unidentified aminolipid. The DNA G+C content of strain MYP11T was 63.1 or 61.5 mol%. The differences in the fatty acid and polar lipid profiles and DNA G+C contents made it reasonable to distinguish strain MYP11T from the type strains of S. abyssi, S. aestuarii and S. aquaeponti and those of other Shimia species. On the basis of the polyphasic data presented here, strain MYP11T is considered to constitute a new genus and species within the class Alphaproteobacteria, for which the name Aliishimia ponticola gen. nov., sp. nov. is proposed. The type strain is MYP11T (=KCTC 62899T=NBRC 113544T).

Fermented Asterina pectinifera with Cordyceps militaris Mycelia Induced Apoptosis in B16F10 Melanoma Cells.

This prime objective of this study was to explore the anti-cancer activity of fermented Asterina pectinifera with Cordyceps militaris mycelia (FACM) in B16F10 murine melanoma cells. The effect of FACM on cell viability was assessed using MTT assay. Furthermore, the effect of FACM was compared with unfermented A. pectinifera on cell viability. The results demonstrated that the fermented FACM extract has a higher inhibitory activity on the proliferation of B16F10 murine melanoma cells than unfermented A. pectinifera. In addition, FACM also promoted the expression of pro-apoptotic protein Bax leading to stimulate apoptosis in B16F10 cells. Therefore the present study demonstrates that the FACM might be a potential effective anti-cancer agent, as a result of its stronger anti-proliferative effect and apoptosis inducing effect than A. pectinifera or C. militaris on melanoma cells.

Gelidium amansii extract ameliorates obesity by down-regulating adipogenic transcription factors in diet-induced obese mice.

BACKGROUND/OBJECTIVES: In this study, we investigated whether Gelidium amansii extract (GAE) ameliorates obesity in diet-induced obese (DIO) mice. MATERIALS/METHODS: The mice were maintained on a high-fat diet (HD) for 5 weeks to generate the DIO mouse model. And then mice fed HD plus 0.5% (GAE1), 1% (GAE2) or 2% (GAE3) for 8 weeks. RESULTS: After the experimental period, GAE-supplemented groups were significantly lower than the HD group in body weight gain and liver weight. GAE supplemented groups were significantly lower than the HD group in both epididymal and mesenteric adipose tissue mass. The plasma leptin level was significantly higher in the HD group than in GAE-supplemented groups. The leptin level of HD+GAE3 group was significantly lower than that of the HD+conjugated linoleic acid (CLA) group. In contrast, plasma adiponectin level of the HD group was significantly lower than those of HD+GAE2 and HD+GAE3 groups. The expression levels of adipogenic proteins such as fatty acid synthase, sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer binding protein α in the GAE supplemented groups were significantly decreased than those in HD group, respectively. In addition, the expression levels of HD+GAE2 and HD+GAE3 groups are significantly decreased compared to those of HD+CLA group. On the contrary, the expression levels of hormone-sensitive lipase and phospho-AMP-activated protein kinase, proteins associated with lipolysis, were significantly increased in the GAE supplemented groups compared to those in the HD group. HD+GAE3 group showed the highest level among the GAE supplemented groups. CONCLUSIONS: These results suggested that GAE supplementation stimulated the expressions of lipid metabolic factors and reduced weight gain in HD-fed C57BL/6J obese mice.

Gelidium amansii ethanol extract suppresses fat accumulation by down-regulating adipogenic transcription factors in ob/ob mice model.

The purpose of this study was to determine the anti-obesity effects of Gelidium amansii extract (GAE) in the C57BL/6J-ob/ob mice. The ob/ob mice were fed GAE at 0.5% for 4 weeks, after which body weight, epididymal adipose tissue weight, plasma triglycerides, and hepatic lipid accumulation were significantly reduced in GAE-fed mice compared with ob/ob control mice. Plasma adiponectin levels were significantly higher in GAE-fed mice than in ob/ob control mice. These findings were supported by the expression levels of enzymes and proteins related to lipid metabolism assessed by western blotting: protein expression levels of the peroxisome proliferator-activated receptor γ and CCATT/enhancer binding protein α decreased significantly, while hormone-sensitive lipase and phospho-AMP-activated protein kinase levels increased in the GAE-fed mice compared with ob/ob control mice. These findings demonstrate that GAE regulates plasma lipid profiles and increasing highdensity lipoprotein cholesterol levels as well as by regulating the expression levels of lipid metabolic factors, resulting in reduced weight gain in ob/ob mice.

Anti-inflammatory effect of the extract from fermented Asterina pectinifera with Cordyceps militaris mycelia in LPS-induced RAW264.7 macrophages.

In our previous work, Asterina pectinifera was fermented with Cordyceps militaris mycelia to improve its bioactivities and was reported to have strong antioxidant activities. The aim of the current study was to investigate its anti-inflammatory effect and mechanisms of action. In this study, we observed the inhibitory effect of the extract from fermented A. pectinifera with C. militaris mycelia (FACM) on nitric oxide (NO) production and its molecular mechanism in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. FACM could decrease LPS-induced NO production. Western blot analysis showed that FACM could down-regulate LPS-induced expression of inducible NO synthase without affecting cyclooxygenase-2. Moreover, FACM exhibited anti-inflammatory activity in LPS-induced RAW264.7 mouse macrophage cells through proinflammatory mediators including TNF-α and IL-6 via nuclear factor kappa B pathway. FACM inhibited LPS-induced phosphorylation of extracellular-signal-regulated kinase expression. Our results suggest that FACM may be a potential candidate for inflammation therapy by attenuating the generation of cytokines, production of NO, and generation of ROS in RAW264.7 cells.

Radical scavenging activities of Asterina pectinifera fermented with Cordyceps militaris mycelia.

Asterina pectinifera was fermented with Cordyceps militaris mycelia for improvement of anti-oxidant activities. DPPH, alkyl, hydroxyl, and superoxide radical scavenging activities were evaluated using electron spin resonance. Anti-oxidant activities were also determined based on the ferric reducing anti-oxidant power assays and the ABTS radical scavenging activity. The lipid peroxidation inhibition activity was confirmed using ferric thiocyanate and thiobarbituric acid assays. The free radical scavenging activity and anti-oxidative effects of A. pectinifera fermented with C. militaris mycelia (FACM) extracts were higher than for A. pectinifera and C. militaris mycelia extracts alone. FACM extracts contained different biochemical ingredients due to fermentation of A. pectinifera and provide a beneficial anti-oxidant activity. FACM extracts are a promising source of beneficial antioxidants for use in food industries.

Anti-inflammatory effects of calcium citrate in RAW 264.7cells via suppression of NF-κB activation.

Here we aimed to investigate the anti-inflammatory effects of calcium citrate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The anti-inflammatory effects of calcium citrate were investigated by assessing pro-inflammatory factors (NO, ROS, NF-κB, iNOS, and COX-2) and pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Treatment of cells with calcium citrate (10-100µM) significantly reduced the generation of intracellular reactive oxygen species and increased the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in LPS-stimulated macrophages. Calcium citrate was further shown to inhibit NO production in LPS-stimulated RAW 264.7cells. The expression levels of iNOS, COX-2, and NF-κB were also suppressed by treatment with calcium citrate. Calcium citrate was furthermore found to significantly inhibit the production of IL-1ß, IL-6, and TNF-α in response to LPS-stimulation. These findings demonstrate that calcium citrate may be an effective anti-inflammatory agent.

Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-κB signaling in activated HMC-1 human mast cells.

CONTEXT: Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown. OBJECTIVE: The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells in vitro. MATERIALS AND METHODS: To investigate the bioactive potential of CAPE (10 or 20 µM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used. RESULTS: CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 µM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1ß (4.775 versus 0.713 pg/ml, IC50 = 6.67 µM), IL-6 (4771.5 versus 449.1 pg/ml, IC50 = 5.25 µM), and IL-8 (5991.7 versus 2213.1 pg/ml, IC50 = 9.95 µM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-κB activation by suppressing IκBα phosphorylation and its degradation. DISCUSSION AND CONCLUSION: Our results indicated that CAPE can modulate mast cell-mediated allergic disease.

Inhibitory effect of Gastrodia elata extract on melanogenesis in HM3KO melanoma cells.

Effective and safe antimelanogenic agents derived from natural products get interest continuously for both medical and cosmetic purposes. Melanin synthesis is regulated by melanogenic enzymes such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2) in mammals. Gastrodia elata (GE) has been shown to have multiple therapeutic actions related to antioxidation in many diseases. In this study, we investigate whether water extraction of GE has inhibitory effects on melanogenesis in vitro and on the expression of mRNA and protein of tyrosinase, TRP-1, and TRP-2 in HM3KO melanoma cells. To examine the inhibitory effect of GE on melanogenesis, mushroom tyrosinase inhibition assay; reverse transcription polymerase chain reaction; and western blotting of tyrosinase, TRP-1, and TRP-2 were performed using HM3KO melanoma cells. In this study, the GE extract was found to significantly inhibit mushroom tyrosinase activity (69.3 ± 7.2% of the control, p < 0.05), and the expression of mRNA and protein of tyrosinase, TRP-1, and TRP-2 was reduced significantly. These results suggest that the antimelanogenic effect of GE extract is mainly due to the decreased expression of mRNA and protein of tyrosinase, TRP-1, and TRP-2 in the process of melanin synthesis.

Anti-inflammatory Effect of Oyster Shell Extract in LPS-stimulated Raw 264.7 Cells.

This study was designed to investigate the anti-inflammatory effect of oyster shell extract on the production of pro-inflammatory factors [NO, reactive oxygen species (ROS), nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2)] and pro-inflammatory cytokines [Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) and TNF-α] in the lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. Cell viability, as measured by the MTT assay, showed that oyster shell extract had no significant cytotoxicity in Raw 264.7 cells. The treatment with oyster shell extract decreased the generation of intracellular reactive oxygen species dose dependently and increased antioxidant enzyme activities, such as SOD, catalase, GSH-px in LPS-stimulated macrophage cells. Oyster shell extract significantly suppressed the production of NO and also decreased the expressions of iNOS, COX-2 and NF-κB. Additionally, oyster shell extract significantly inhibited the production of IL-1ß, IL-6, and TNF-α in LPS-stimulated Raw 264.7 cells. Thus, these results showed that the oyster shell extract had an anti-inflammatory effect on LPS-stimulated Raw 264.7 cells.