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Since the skin covers most surfaces of the body, it is susceptible to damage, which can be fatal depending on the degree of injury to the skin because it defends against external attack and protects internal structures. Various types of artificial skin are being studied for transplantation to repair damaged skin, and recently, the production of replaceable skin using three-dimensional (3D) bioprinting technology has also been investigated. In this study, skin tissue was produced using a 3D bioprinter with human skin cell lines and cells extracted from mouse skin, and the printing conditions were optimized. Gelatin was used as a bioink, and fibrinogen and alginate were used for tissue hardening after printing. Printed skin tissue maintained a survival rate of 90% or more when cultured for 14 days. Culture conditions were established using 8 mM calcium chloride treatment and the skin tissue was exposed to air to optimize epidermal cell differentiation. The skin tissue was cultured for 14 days after differentiation induction by this optimized culture method, and immunofluorescent staining was performed using epidermal cell differentiation markers to investigate whether the epidermal cells had differentiated. After differentiation, loricrin, which is normally found in terminally differentiated epidermal cells, was observed in the cells at the tip of the epidermal layer, and cytokeratin 14 was expressed in the lower cells of the epidermis layer. Collectively, this study may provide optimized conditions for bioprinting and keratinization for three-dimensional skin production.

Background Although extracorporeal membrane oxygenation (ECMO) has been used for the treatment of acute high-risk pulmonary embolism (PE), there are limited reports which focus on this approach. Herein, we described our experience with ECMO in patients with acute high-risk PE. Methods We retrospectively reviewed medical records of patients diagnosed with acute high-risk PE and treated with ECMO between January 2014 and December 2018. Results Among 16 patients included, median age was 51 years (interquartile range [IQR], 38 to 71 years) and six (37.5%) were male. Cardiac arrest was occurred in 12 (75.0%) including two cases of out-of-hospital arrest. All patients underwent veno-arterial ECMO and median ECMO duration was 1.5 days (IQR, 0.0 to 4.5 days). Systemic thrombolysis and surgical embolectomy were performed in seven (43.8%) and nine (56.3%) patients, respectively including three patients (18.8%) received both treatments. Overall 30-day mortality rate was 43.8% (95% confidence interval, 23.1% to 66.8%) and 30-day mortality rates according to the treatment groups were ECMO alone (33.3%, n=3), ECMO with thrombolysis (50.0%, n=4) and ECMO with embolectomy (44.4%, n=9). Conclusions Despite the vigorous treatment efforts, patients with acute high-risk PE were related to substantial morbidity and mortality. We report our experience of ECMO as rescue therapy for refractory shock or cardiac arrest in patients with PE.

Background/aim: We performed this prospective randomized double-blind study to compare the effects of nefopam versus ketorolac in intravenous fentanyl-based patient-controlled analgesia (PCA) after shoulder arthroscopic orthopedic surgery. Materials and methods: Ninety-two patients were randomly divided into two groups to receive intravenous PCA. Patients were assigned to either the nefopam group (nefopam 120 mg and fentanyl 20 µg/kg) or the ketorolac group (ketorolac 2 mg/kg and fentanyl 20 µg/kg). Pain was assessed on a visual analogue scale (VAS) and a numeric rating scale (NRS). Additionally, patient satisfaction, adverse events, and vital signs were monitored. Results: There were no significant differences in VAS score (P = 0.48) or NRS score (P = 0.15) between the two groups. Similarly, patient satisfaction did not differ between the two groups [8.5(0.8) vs. 8.2(1.0), P = 0.14]. There were no statistically significant differences in the incidence of nausea (P = 0.72), vomiting (P = 0.46), urinary retention (P = 0.82), sweating (P = 0.49), or dizziness (P = 0.45) between the two groups. Likewise, there were no differences in heart rate [78.2(7.7) vs. 75.2(6.5), P = 0.18] or SpO2 [98.4(1.8) vs. 98.5(1.9), P = 0.83]. Conclusion: Nefopam is an appropriate alternative for co-administration with fentanyl-based PCA in patients who have difficulty using nonsteroidal antiinflammatory drugs.

Objective To determine whether intubation education using the Pentax Airway Scope (AWS) in normal airways is more useful than direct laryngoscopy (Macintosh laryngoscope) in novice personnel. Methods Eleven intern doctors without intubation experience performed 60 sequential intubations with each device on a manikin and 10 sequential intubations in adult patients. The time required for successful intubation, percentage of glottic opening (POGO) score, number of intubation attempts, and number of dental injuries were analyzed for each intubation technique. Results The mean (standard deviation) time required for successful intubation decreased as the number of intubations increased and was significantly shorter with the Pentax AWS than direct laryngoscope [22.6 (7.3) vs. 29.6 (10.0) and 33.0 (8.0) vs. 44.7 (5.6) s, respectively] in both the manikin and clinical studies. The Pentax AWS was also associated with higher POGO scores than the direct laryngoscope [81.7 (8.9) vs. 55.1 (13.2) and 80.9 (9.7) vs. 49.6 (16.5), respectively] and fewer intubation attempts. Fewer dental injuries occurred with the Pentax AWS in the manikin study. Conclusions Novices performed intubation more rapidly and easily with an improved laryngeal view using the Pentax AWS. We suggest that intubation education with video laryngoscopy should be mandatory along with direct laryngoscope training.

Background Sorbus rufopilosa, a tsema rowan, is a species of the small ornamental trees in the genus Sorbus and the family Rosaceae found in East Asia. The bioactivities of S. rufopilosa have not yet been fully determined. The objective of this study is to evaluate the antioxidant and anticancer effects of ethanol extract of S. rufopilosa (EESR) and to determine the molecular mechanism of its anticancer activity in human colon carcinoma HT29 cells. Methods To examine the antioxidant activity of EESR, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity assay was performed. Inhibitory effect of EESR on cancer cell growth and proliferation was determined by water-soluble tetrazolium salt assay. To investigate the mechanism of EESR-mediated cytotoxicity, HT29 cells were treated with various concentrations of EESR and the induction of cell cycle arrest and apoptosis was analyzed by flow cytometry, 4,6-diamidino-2-phenylindole staining, and Western blot analysis. Results EESR showed significant antioxidant activity and inhibitory effect on HT29 cell growth in a dose-dependent manner. EESR induced cell cycle arrest at G2/M phase in a dose-dependent manner by modulating cyclin B, cyclin-dependent kinase 1 (CDK1), and CDK inhibitor p21 expression. EESR-induced apoptosis was associated with the upregulation of p53, a death receptor Fas, and a pro-apoptotic protein Bax and the activation of caspase 3, 8, and 9, resulting in the degradation of PARP. Conclusions EESR possessing antioxidant activity efficiently inhibits proliferation of HT29 cells by inducing both cell cycle arrest and apoptosis. EESR may be a possible candidate for the anticancer drug development.

Background The current early warning scores may be insufficient for medical emergency teams (METs) to use in assessing the severity and the prognosis of activated patients. We evaluated the predictive powers of the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS) for 28-day mortality and to analyze predictors of 28-day mortality in general ward patients who activate the MET. Methods Adult general ward inpatients who activated the MET in a tertiary referral teaching hospital between March 2009 and December 2016 were included. The demographic and clinical characteristics and physiologic parameters at the time of MET activation were collected, and MEWS and NEWS were calculated. Results A total of 6,729 MET activation events were analyzed. Patients who died within 28 days were younger (mean age 60 vs 62 years), were more likely to have malignancy (72% vs 53%), were more likely to be admitted to the medical department rather than the surgical department (93% vs 80%), had longer intervals from admission to MET activation (median, 7 vs 5 days), and were less likely to activate the MET during nighttime hours (5 PM to 8 AM) (61% vs 66%) compared with those who did not die within 28 days (P < 0.001 for all comparisons). The areas under the receiver operating characteristic curves of MEWS and NEWS for 28-day mortality were 0.58 (95% CI, 0.56–0.59) and 0.60 (95% CI, 0.59–0.62), which were inferior to that of the logistics regression model (0.73; 95% CI, 0.72–0.74; P < 0.001 for both comparisons). Conclusions Both the MEWS and NEWS had poor predictive powers for 28-day mortality in patients who activated the MET. A new scoring system is needed to stratify the severity and prognosis of patients who activated the MET.

Background: Osmanthus matsumuranus, a species of Oleaceae, is found in East Asia and Southeast Asia. The bioactivities of O. matsumuranus have not yet been fully understood. Here, we studied on the molecular mechanisms underlying anti-cancer effect of ethanol extract of O. matsumuranus (EEOM). Methods: Inhibitory effect of EEOM on cell growth and proliferation was determined by WST assay in various cancer cells. To investigate the mechanisms of EEOM-mediated cytotoxicity, HepG2 cells were treated with various concentration of EEOM and analyzed the cell cycle arrest and apoptosis induction by flow cytometry, Western blot analysis, 4,6-diamidino-2-phenylindole (DAPI) staining and DNA fragmentation. Results: EEOM showed the cytotoxic activities in a dose-dependent manner in various cancer cell lines but not in normal cells, and HepG2 cells were most susceptible to EEOM-induced cytotoxicity. EEOM induced G2/M arrest in HepG2 cells associated with decreased expression of cyclin-dependent kinase 1 (CDK1), cyclin A and cylcin B, and increased expression of phospho-checkpoint kinase 2, p53 and CDK inhibitor p21. Immunofluorescence staining showed that EEOM-treated HepG2 increased doublet nuclei and condensed actin, resulting in cell rounding. Furthermore, EEOM-mediated apoptosis was determined by Annexin V staining, chromatin condensation and DNA fragmentation. EEOM caused upregulation of FAS and Bax, activation of caspase-3, -8, -9, and fragmentation of poly ADP ribose polymerase. Conclusions: These results suggest that EEOM efficiently inhibits proliferation of HepG2 cells by inducing both G2/M arrest and apoptosis via intrinsic and extrinsic pathways, and EEOM may be used as a cancer chemopreventive agent in the food or nutraceutical industry.

Background: We reviewed our experience with on-pump beating (OPB) heart coronary artery bypass grafting (CABG) to evaluate the impacts of obviating aortic cross-clamping and cardioplegic arrest on clinical outcomes compared with conventional CABG (C-CABG). Methods: Between 2006 and 2012, elective isolated cardiopulmonary bypass (CPB)-assisted CABG was consecutively performed in 645 patients (mean patient age 63.3±9.1 years, 471 women) with 254 (39.4%) undergoing OPB-CABG and 391 (60.6%) undergoing C-CABG. The early and long-term clinical outcomes were compared between the two groups after adjusting for risk profiles through propensity score (PS) analyses. Results: The OPB-CABG group presented significant morbidities more frequently than the C-CABG group, including severe chronic kidney disease (CKD) (P=0.026), severe chest pain (P vs . 3.0±1.0, P=0.816). After PS matching, the incidence of major complications such as stroke (P>0.99) and new-onset dialysis (P=0.109) was comparable. During a median follow-up of 81.0 months (quartiles 1–3, 66.6–95.0 months), 118 patients died and the PS-matched models showed no significant between-group differences in the risk of overall death [hazard ratio (HR), 1.19; 95% confidence interval (CI), 0.72–1.95; P=0.507] and major adverse cardiac events (MACE) (HR, 1.49; 95% CI, 0.67–3.31; P=0.328). Conclusions: The OPB strategy may be as safe and effective as the conventional strategy during CABG among patients with similar risk profiles. A prospective randomized trial is warranted to better ascertain the beneficial impact of OPB-CABG as both a viable and a durable alternative strategy to C-CABG.

Background: Stainless steel wiring remains the most popular technique for primary sternal closure. Recently, a multifilament cable wiring system (Pioneer Surgical Technology Inc., Marquette, MI, USA) was introduced for sternal closure and has gained wide acceptance due to its superior resistance to tension. We aimed to compare conventional steel wiring to multifilament cable fixation for sternal closure in patients undergoing major cardiac surgery. Methods: Data were collected retrospectively on 1,354 patients who underwent sternal closure after major cardiac surgery, using either the multifilament cable wiring system or conventional steel wires between January 2009 and October 2010. The surgical outcomes of these two groups of patients were compared using propensity score matching based on 18 baseline patient characteristics. Results: Propensity score matching yielded 392 pairs of patients in the two groups whose baseline profiles showed no significant differences. No significant differences between the two groups were observed in the rates of early mortality (2.0% vs. 1.3%, p=0.578), major wound complications requiring reconstruction (1.3% vs. 1.3%, p＞0.99), minor wound complications (3.6% vs. 2.0%, p=0.279), or mediastinitis (0.8% vs. 1.0%, p=1.00). Patients in the multifilament cable group had fewer sternal bleeding events than those in the conventional wire group, but this tendency was not statistically significant (4.3% vs. 7.4%, p=0.068). Conclusion: The surgical outcomes of sternal closure using multifilament cable wires were comparable to those observed when conventional steel wires were used. Therefore, the multifilament cable wiring system may be considered a viable option for sternal closure in patients undergoing major cardiac surgery.

We report the case of a 37-year-old man who suffered from biventricular failure due to left isomerism, inferior vena cava interruption with azygos vein continuation, bilateral superior vena cava, double outlet of right ventricle, complete atrioventricular septal defect, pulmonary stenosis, and isolated dextrocardia. Heart transplantation in patients with systemic venous anomalies often requires the correction and reconstruction of the upper & lower venous drainage. We present a case of heart transplantation in a patient with left isomerism, highlighting technical modifications to the procedure, including the unifocalization of the caval veins and reconstruction with patch augmentation.

Widdrol is an odorous compound derived from Juniperus chinensis that is widely used in traditional medicine to treat fever, inflammation and cancer. It was previously reported that widdrol has antitumor activity by apoptosis induction in cancer cells in vitro. However, its anti-angiogenic activity remains elusive. In the present study, we investigated the anti‑angiogenic activity of widdrol and the molecular mechanisms involved. Widdrol inhibited cell proliferation via G1 phase arrest induction in human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Additionally, it was associated with a decreased expression of cyclin-dependent kinase 2 (CDK2) and an increased expression of p21, a CDK inhibitor. Widdrol significantly inhibited the cell migration and tube formation of HUVECs using an in vitro angiogenesis assay. The results showed that widdrol suppressed phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream proteins, such as AKT, focal adhesion kinase (FAK) and endothelial nitric oxide synthase (eNOS). Moreover, widdrol effectively reduced tumor growth and blood vessel formation in colon tumor xenograft mice. Collectively, these results suggested that widdrol may act as a potential anti-angiogenic agent by inhibiting vessel sprouting and growth, which may have implications for angioprevention.

Although heart transplantation is a final therapeutic option in pediatric patients with dilated cardiomyopathy (DCMP), the shortage of pediatric heart donors is a major obstacle. In adults with DCMP characterized by cardiac dyssynchrony, cardiac resynchronization therapy (CRT) is known to be an effective treatment option. However, there is a lack of evidence on the effectiveness of CRT in infants with DCMP. Several studies have reported improvement in hemodynamics and cardiac performance following CRT in infants with DCMP. Here, we report CRT in an infant with DCMP during extracorporeal membrane oxygenation with 5 months of follow-up.

Previously, betulinic acid was identified as one of the main compounds responsible for the anti-melanogenic effect in Vitis amurensis root. In this study, we investigated the precise mechanism underlying the anti-melanogenic activity of betulinic acid in B16F10 cells. Betulinic acid significantly attenuated 3-isobutyl-1-methylxanthine (IBMX)-induced melanin production by inhibiting tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 expression through the modulation of their corresponding transcription factors, microphthalamia associated transcription factor (MITF) and cAMP response element binding protein (CREB), in B16F10 cells. In addition, phosphorylation of mitogen-activated protein kinase kinase (MEK)/extracellular regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/Akt, involved in the melanogenic processes, were ameliorated by betulinic acid treatment. Role of MEK/ERK and PI3K/Akt signaling pathway in the melanogenesis was confirmed by using specific inhibitors, PD98059 (for MEK/ERK) and LY294002 (for PI3K/Akt), respectively. As a result, betulinic acid inhibited melanin production by tyrosinase, TRP-1, and TRP-2 inhibition through the regulation of CREB and MITF, which was accompanied with MEK/ERK and PI3K/Akt inactivation in IBMX-stimulated B16F10 cells. Consequently, these results demonstrate a novel molecular function of betulinic acid derived from V. amurensis root in melanogenesis, which in turn enhances our understanding on the application of cosmetic therapy for reducing skin hyperpigmentation.

Salsola collina, also known as Russian thistle, is widely distributed in and around waste facilities, roadsides, and drought and semi-drought areas, and is used as a traditional folk remedy in Chinese medicine for the treatment of hypertension. In this study, we have evaluated the anti-oxidative and anti-cancer activities of the ethanol extract of S. collina Pall. (EESC), and the molecular mechanisms of its anti-cancer effects on human colon carcinoma HT29 cells. EESC exhibited anti-oxidative activity through DPPH radical scavenging capacity and showed cytotoxic activity in a dose-dependent manner in HT29 cells. After EESC treatment, HT29 cells altered their morphology, becoming smaller and irregular in shape. EESC also induced cell accumulation in the G2/M phase in a dose-dependent manner, accompanied by a decrease of cell population in the G1 phase. The G2/M arrest by EESC was associated with the increased expression of cyclin-dependent kinase (CDK) inhibitor p21 and Wee1 kinase, which phosphorylates, or inactivates, Cdc2. EESC treatment induced the phosphorylation of Cdc2 and Cdc25C, and inhibited cyclin A and Cdc25C protein expression. In addition, S arrest was induced by the highest concentration of EESC treatment, associated with a decrease of cyclin A and Cdk2 expression. These findings suggest that EESC may possess remarkable anti-oxidative activity and exert an anti-cancer effect in HT29 cells by cell cycle regulation.

Typha orientalis, also known as bulrush or cattail, is a perennial herbaceous plant found in freshwater wetlands and has been widely used in constructed wetlands for wastewater treatment. Recent data has revealed that SH21B, a mixture composed of seven herbs including T. orientalis, exhibited an anti-adipogenic activity by the inhibition of the expression of adipogenic regulators. However, the anti-cancer effect of T. orientalis and its molecular mechanisms remain unclear. In this study, we evaluated the anti-cancer effect and its mechanism in the methanol extract of T. orientalis (METO) on human colon carcinoma HT29 cells. It was found that METO treatment showed cytotoxic activity in a dose-dependent manner, and induced G2/M cell cycle arrest and apoptosis in HT29 cells. The induction of G2/M arrest by METO was associated with the up-regulation of phospho-Cdc2 (Tyr15), an inactive form of Cdc2 and the down-regulation of Cdc25c phosphatase. METO also induced tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) expression. In addition, METO-induced apoptosis was characterized by the proteolytic activation of caspase-3, degradation of poly ADP ribose polymerase (PARP), and up-regulation of death receptor FAS and pro-apoptotic Bax expression. Collectively, these results indicate that the cell cycle inhibition and apoptosis induction of METO in HT29 cells allows for the possibility of its use in anti-cancer therapies.

Angiotensin converting enzyme (ACE) plays a major role in the regulation of blood pressure. The potential antihypertensive activity of Angelica gigas was evaluated in vitro by its ability to inhibit ACE. A methanol extract of A. gigas roots exerted an inhibitory effect against ACE and was fractionated using several organic solvents, including dichloromethane, ethyl acetate, and n-butanol. The n-butanol soluble fraction, which manifested potent ACE inhibitory properties, was further purified via repeated silica gel and RP-18 column chromatography. Three benzopyriansides, such as nodakenin (1), umbelliferone (2), and umbelliferone 6-carboxylic acid (3) were isolated from A. gigas roots. Compounds 1–3 inhibited ACE activity in a dose-dependent manner, with IC50 values of 63.95±0.16, 190.49±0.54, and 158.35±1.53 μM, respectively. The inhibition kinetics analyzed by Lineweaver-Burk plots revealed that the three compounds showed a mixed-type inhibition. The equilibrium constants for the inhibitor binding (Ki) of 1, 2, and 3 were estimated to be 1.56×10−4, 4.70×10−4, and 2.17×10−4 M, respectively. We used A. gigas roots to isolate nodakinin, umbelliferone, and umbelliferone 6-carboxylic acid and tested their inhibition efficacy against ACE for the first time.

In this study, we analyzed the anti-oxidative and anti-inflammatory activities of seven medicinal herbs. All extracts of the tested herbs, Euryale ferox Salisbury, Echinops setifer Iljin, Amomum cardamomum Linne, Tetrapanax papyriferus, Illicium verum Hook. f., Typha orientalis Presl, and Piper longum Linne, exhibited potent anti-oxidative activity as confirmed by DPPH radical scavenging capacity. Lipopolysaccharide (LPS) induced nitric oxide (NO) production, in the RAW 264.7 cell line, was also ameliorated by all extracts' treatments in a dose dependent manner. NO suppressive activity originated from the inhibition of inducible nitric oxide synthase (iNOS) protein expression by the extracts. Three extracts, E. ferox S., I. verum Hook. f., and P. longum L., possessed suppressive activity against, not only iNOS, but also cycloxygenase 2 (COX-2) protein expression. These three extracts may then serve as potential candidates for non steroidal analgesic inflammation drugs (NSAIDs). Furthermore, all extracts induced anti-oxidative enzyme, heme oxygenase 1, protein expression. Taken together, these results provide an important new insight into the fact that various medicinal herbs possess potent anti-oxidative and anti-inflammatory activities and might be utilized as promising agents in the field of health products. Further studies for the identification of the active compounds from medicinal herbs are clearly needed.

In the DBC (direct bonding of copper) process the oxygen partial pressure surrounding the AlN/Cu bonding pairs has been controlled by Ar gas mixed with oxygen. However, the direct bonding of Cu with sound interface and good adhesion strength is complicated process due to the difficulty in the exact control of oxygen partial pressure by using Ar gas. In this study, we have utilized the in-situ equilibrium established during the reaction of + 1/2 by placing powder bed of CuO or around the Cu/AlN bonding pair at . The adhesion strength was relatively better in case of using CuO powder than when powder was used. Microstructural analysis by optical microscopy and XRD revealed that the interface of bonding pair was composed of , Cu and small amount of CuO phase. Thus, it is explained that the good adhesion between Cu and AlN is attributed to the wetting of eutectic liquid formed by reaction of Cu and .

Vitis amurensis Rupreche , a sort of grape, grows naturally in Asian countries. It is known for important biological effects such as antioxidation, anti-inflammation, neuroprotection, and angiogenesis inhibition. Although its root is used as a traditional folk medicine in Korea, the root’s biological activities are poorly studied. In the present study, the effects of V. amurensisroot methanol extract (VARM) and its solvent fractions on adipocyte differentiation and adipogenesis in 3T3-L1 preadipocytes were investigated. The VARM significantly suppressed adipocyte differentiation, lipid accumulation, and the triglyceride (TG) content of 3T3-L1 preadipocytes in a dose-dependent manner, without cytotoxicity. To identify active molecules, the VARM was fractionated with a series of organic solvents including dichloromethane (CH₂Cl₂), ethyl acetate (EtOAc), and n-butanol ( n-BuOH). All the fractions also showed inhibition of lipid accumulation in the 3T3-L1 preadipocytes. The CH₂Cl₂ fraction showed the most powerful anti-obesity effect through the modulation of cytidine-cytidine-adenosine-adenosinethymidine (CCAAT)/enhancer binding protein α (C/EBPα), C/EBPβ, peroxisome proliferator-activated receptor γ (PPARγ) gene and protein expression. Oleanolic acid was one of the main active compounds involved in the anti-obesity activity of the V. amurensisroot. These results provide important new insight into the potential potent anti-adipogenic effect of the V. amurensisroot and illustrate that one of the main compounds involved in this effect is oleanolic acid.

This study was designed to explore new nutraceutical and cosmetic resources possessing biological activities from the plant kingdom. To fulfill this purpose, we analyzed the anti-oxidative, anti-melanogenic, and anti-inflammatory activities of Zanthoxylum schinifolium extract (ZSE) and its solvent fractions using in vitro assays and cell culture model systems. Three kinds of ZSE treated with methanol, ethanol, and water exhibited potent anti-oxidative activities through DPPH radical scavenging capacity, and inhibited in vitro DOPA oxidation. Furthermore, Z. schinifolium methanol extract (ZSME) inhibited the -melanocyte stimulating hormone, which induces melanin contents in B16F10 cells. Its anti-melanogenic activity originates from the inhibition of tyrosinase enzyme activity and melanogenesis related protein expression. Moreover, lipopolysaccharide induced nitric oxide production in the RAW 264.7 cell line was also ameliorated by ZSME treatment in a dose dependent manner. Among the four solvent fractions of ZSME treated with dichloromethane, ethyl acetate, n-butanol, and water, three fractions, except water, showed significant anti-melanogenic and anti-inflammatory activities. Taken together, these results provide important new insights into Z. schinifolium, indicating that it possesses numerous biological activities such as anti-oxidative, anti-melanogenic, and anti-inflammatory activities. Therefore, it may well serve as a promising material in the field of nutraceuticals and cosmetics.

Background A growing body of evidence suggests that neuroinflammation, which is characterized by infiltration of immune cells, activation of mast cells and glial cells, and production of inflammatory mediators in the peripheral and central nervous systems, plays an important role in the induction and maintenance of chronic pain. Palmitoylethanolamide (PEA), which is a type of N-acylethanolamide and a lipid, has an anti-inflammatory effect. Relative to the anti-inflammatory effect, little is known about its analgesic effect in chronic pain. This study aimed to determine whether PEA relieves chronic inflammatory and neuropathic pain. Methods Male Sprague-Dawley rats were injured by transection of the left L5 and L6 spinal nerves to induce neuropathic pain or were injected with monoiodoacetic acid into the synovial cavity of knee joints to induce inflammatory pain. To assess the degree of pain, two kinds of stimuli - pressing von Frey filaments and wetting with acetone - were applied to the plantar surface of the rat to measure mechanical and cold sensitivity, respectively. Pain was measured by assessing behavioral responses, including paw withdrawal response threshold and paw withdrawal frequency upon stimulation. Results Neuropathic pain caused by spinal nerve transection (SNT) decreased the mechanical threshold and increased the frequency of response to acetone application. But, cold allodynia caused by SNT did not decrease the withdrawal frequency. Mechanical hyperalgesia caused by chronic inflammation was significantly reduced by both intraperitoneal and intra-articular injections of PEA. Conclusions These outcomes revealed that PEA might be effective in relieving inflammatory and neuropathic pain, especially pain induced by mechanical hyperalgesia, but not cold allodynia.

Radix platycodi is the root of Platycodon grandiflorus A. DC, which has been widely used as a food material and for the treatment of a number of chronic inflammatory diseases in traditional oriental medicine. In this study, the anti‑inflammatory effects of the saponins isolated from radix platycodi (PGS) on the production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated BV2 murine microglial cells were examined. We also investigated the effects of PGS on LPS‑induced nuclear factor‑κB (NF-κB) activation and phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways. Following stimulation with LPS, elevated nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokine production was detected in the BV2 microglial cells. However, PGS significantly inhibited the excessive production of NO, PGE2 and pro‑inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner without causing any cytotoxic effects. In addition, PGS suppressed NF-κB translocation and inhibited the LPS-induced phosphorylation of AKT and MAPKs. Our results indicate that the inhibitory effect of PGS on LPS-stimulated inflammatory response in BV2 microglial cells is associated with the suppression of NF-κB activation and the PI3K/AKT and MAPK signaling pathways. Therefore, these findings suggest that PGS may be useful in the treatment of neurodegenerative diseases by inhibiting inflammatory responses in activated microglial cells.

BACKGROUND/OBJECTIVES The root of Vitis amurensis Ruprecht, a sort of wild-growing grape, has been used in oriental medicine for treatment of skin ailments; however, its dermatological activity is not sufficiently understood. The aim of this study was to investigate tyrosinase inhibitory and anti-melanogenic activities of V. amurensis Ruprecht root methanol extract (VARM) in B16F10 mouse melanoma cells and to attempt to isolate and identify the active compound issued from VARM. MATERIALS/METHODS Anti-melanogenic activity of VARM was analyzed in α-melanocyte stimulating hormone (MSH)-stimulated B16F10 cells through evaluation of antioxidative activity as well as inhibited tyrosinase activity and melanin contents compared with those of kojic acid and arbutin. After anti-melanogenic analysis of VARM, serial fractionation, nuclear magnetic resonance (NMR), and thin layer chromatorgraphy (TLC) were applied for identification of active compounds contained in VARM. RESULTS VARM significantly inhibited oxidative stress and tyrosinase activity and attenuated α-MSH-induced melanin production in B16F10 cells. For isolation of active compounds, VARM was fractionated using a series of organic solvents, including dichloromethane (CH2Cl2), ethyl acetate (EtOAc), and n-butanol (n-BuOH). Among fractions showing anti-melanogenic activity, the CH2Cl2 fraction induced the most potent attenuation of melanogenesis without cytotoxicity and the major compound in the CH2Cl2 fraction was identified as betulinic acid. Betulinic acid isolated from the CH2Cl2 fraction of VARM significantly attenuated α-MSH-induced melanogenesis in a dose dependent manner, which was stronger than that of arbutin used as a positive control. CONCLUSIONS These results indicate that VARM inhibits oxidative stress, tyrosinase activity, and α-MSH-induced melanogenesis in B16F10 cells, due primarily to the active compound, betulinic acid, in the CH2Cl2 fraction.