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In this study, we confirmed the anti-inflammatory effect of Apo-9-fucoxanthinone (AF) in in vitro RAW 264.7 cells and in vivo zebrafish model. In lipopolysaccharide (LPS)-stimulated zebrafish, AF significantly decreased the production of reactive oxygen species (ROS), nitric oxide (NO) and cell death. In addition, the mRNA expression of inducible nitric oxide synthase (iNOS), suppressed cyclooxygenase-2 (COX-2) and an inflammatory cytokines; IL-1β, TNF-α were shown reduction. And AF significantly inhibited NO production and expression of iNOS in LPS-stimulated RAW 264.7 cells. Further, AF suppressed COX-2, prostaglandin E2 (PGE 2 ), and pro-inflammatory cytokines such as interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) at 25, 50 and 100 μg/mL, respectively. Further mechanistic studies showed that AF suppressed the nuclear factor-kB (NF-kB) pathway and phosphorylation of mitogen-activated protein kinase (MAPK) pathway molecules such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). According to the results, AF can be used and applied as a useful anti-inflammatory agent of nutraceutical or pharmaceutical., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Phlorotannins (PH) derived from brown algae have been shown to have biological effects. However, the application of PH in biomedical materials has not been investigated. Here, we investigated the effects of PH on normal human dermal fibroblast (NHDF) proliferation and fabricated a composite hydrogel consisting PH and poly (vinyl alcohol) (PVA) (PVA/PH) by a freezing-thawing method for wound healing applications. Cell proliferation was significantly higher in the PH-treated (0.01 and 0.02%) cells than in non-treated cells. Based on the mechanical properties, the PVA/PH hydrogel had a significantly increased swelling ratio and ultimate strain compared to the PVA hydrogel, but the ultimate tensile strength and tensile modulus were decreased. Additionally, cell attachment and proliferation on the composites were evaluated using NHDFs. The results showed that after 1 and 5 days, cell attachment and proliferation were significantly increased on the PVA/PH hydrogel compared with that on the PVA hydrogel. The findings from this study suggest that the PVA/PH hydrogel may be a candidate biomedical material for wound healing applications.

In this study, the monodisperse amorphous silica nanoparticles (SiO2 NPs) with uniform size distribution and high surface area were successfully synthesized from fly ash as a silica source by chemical sol-gel method. The influence of reaction conditions such as surfactant concentration, aging temperature (Ta), and aging time (Ta) on formation of SiO2 NPs was investigated. Through SEM characterization, it was founded that the uniform and small spherical SiO2 NPs with diameter of 20-30 nm could be synthesized at the appropriate CTAB content of 3 wt%, Ta of 60 °C, and Ta of 8 h. In addition, XRD and nitrogen adsorption-desorption measurements indicated that the SiO2 NPs were obtained under amorphous structure, which possesses a high specific surface area of 408 m2 g-1. The obtained results imply that the successful synthesis of SiO2 NPs from fly ash not only displays an effectively alternative approach to provide high quality SiO2 NPs for various necessary applications but also help solving environmental issues due to large amount of fly ash waste each year.

Fish bone, a by-product of fishery processing, is composed of protein, calcium, and other minerals. The objective of this study was to investigate the effects of a bioactive peptide isolated from the bone of the marine fish, Johnius belengerii, on the osteoblastic differentiation of MC3T3-E1 pre-osteoblasts. Post consecutive purification by liquid chromatography, a potent osteogenic peptide, composed of 3 amino acids, Lys-Ser-Ala (KSA, MW: 304.17 Da), was identified. The purified peptide promoted cell proliferation, alkaline phosphatase activity, mineral deposition, and expression levels of phenotypic markers of osteoblastic differentiation in MC3T3-E1 pre-osteoblast. The purified peptide induced phosphorylation of mitogen-activated protein kinases, including p38 mitogen-activated protein kinase, extracellular regulated kinase, and c-Jun N-terminal kinase as well as Smads. As attested by molecular modelling study, the purified peptide interacted with the core interface residues in bone morphogenetic protein receptors with high affinity. Thus, the purified peptide could serve as a potential pharmacological substance for controlling bone metabolism., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background/objectives: In this randomized, placebo-controlled, double-blind study, we evaluated the antihypertensive effects of enzymatic hydrolysate from Styela clava flesh tissue in patients with type 2 diabetes mellitus (T2DM) and hypertension., Subjects/methods: S. clava flesh tissue hydrolysate (SFTH) (n = 34) and placebo (n = 22) were randomly allocated to the study subjects. Each subject ingested two test capsules (500 mg) containing powdered SFTH (SFTH group) or placebo capsules (placebo group) during four weeks., Results: In the SFTH group, systolic and diastolic blood pressure decreased significantly 4 weeks after ingestion by 9.9 mmHg ( P < 0.01) and 7.8 mmHg ( P < 0.01), respectively. In addition, the SFTH group exhibited a significant decrease in hemoglobin A 1c with a tendency toward improvement in homeostasis model assessment of insulin resistance, triglyceride, apolipoprotein B and plasma insulin levels after 4 weeks. No adverse effects were observed in other indexes, including biochemical and hematological parameters in both groups., Conclusion: The results of our study suggested that SFTH exerts a regulatory, antihypertensive effect in patients with T2DM and hypertension., Competing Interests: CONFLICT OF INTEREST: The authors declare no potential conflicts of interests.

In this study, a marine microalga Spirulina sp.-derived protein was hydrolyzed using gastrointestinal enzymes to produce an angiotensin I (Ang I)-converting enzyme (ACE) inhibitory peptide. Following consecutive purification, the potent ACE inhibitory peptide was composed of 7 amino acids, Thr-Met‑Glu‑Pro‑Gly‑Lys-Pro (molecular weight, 759 Da). Analysis using the Lineweaver-Burk plot and molecular modeling suggested that the purified peptide acted as a mixed non-competitive inhibitor of ACE. The inhibitory effects of the peptide against the cellular production of vascular dysfunction-related factors induced by Ang II were also investigated. In human endothelial cells, the Ang II-induced production of nitric oxide and reactive oxygen species was inhibited, and the expression of inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) was downregulated when the cells were cultured with the purified peptide. Moreover, the peptide blocked the activation of p38 mitogen‑activated protein kinase. These results indicated that this Spirulina sp.-derived peptide warrants further investigation as a potential pharmacological inhibitor of ACE and vascular dysfunction.

Microglia are the immune cells of the central nervous system (CNS). Overexpression of inflammatory mediators by microglia can induce several neurological diseases. Thus, the underlying basic requirement for neural tissue engineering is to develop materials that exhibit little or no neuro-inflammatory effects. In this study, we have developed a method to create porous scaffolds by adding fucoidan (Fu) into porous sodium alginate (Sa)/gelatine (G) (SaGFu). For mechanical characterization, in vitro degradation, stress/strain, swelling, and pore size were measured. Furthermore, the biocompatibility was evaluated by assessing the adhesion and proliferation of BV2 microglial cells on the SaGFu porous scaffolds using scanning electron microscopy (SEM) and lactate dehydrogenase (LDH) assay, respectively. Moreover, we studied the neuro-inflammatory effects of SaGFu on BV2 microglial cells. The effect of gelatine and fucoidan content on the various properties of the scaffold was investigated and the results showed that mechanical properties increased porosity and swelling ratio with an increase in the gelatine and fucoidan, while the in vitro biodegradability decreased. The average SaGFu diameter attained by fabrication of SaGFu ranged from 60 to 120μm with high porosity (74.44%-88.30%). Cell culture using gelatine 2.0% (SaG2Fu) and 4.0% (SaG4Fu), showed good cell proliferation; more than 60-80% that with Sa alone. Following stimulation with 0.5μg/mL LPS, microglia cultured in porous SaGFu decreased their expression of nitric oxide (NO), prostaglandin E2 (PGE2), and reactive oxygen species (ROS). SaG2Fu and SaG4Fu also inhibited the activation and translocation of p65 NF-κB protein levels, resulting in reduction of NO, ROS, and PGE2 production. These results provide insights into the diverse biological effects and opens new avenues for the applications of SaGFu in neuroscience., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In the present study, we designed and fabricated composite fibrous mats consisting of poly(ε-caprolactone) (PCL), chitosan (CH), or chitosan-caffeic acid conjugate (CCA) by an electrospinning technique for wound dressing application. The average fiber diameters of PCL, PCL/CH, and PCL/CCA composite fibrous mats were 1.30±1.07, 1.20±1.22, and 0.94±0.68μm, respectively. Based on universal tensile machine (UTM) analysis, the PCL/CCA fibrous mat significantly increased tensile properties compared with the PCL and PCL/CH fibrous mat. Additionally, initial cell attachment and cell proliferation of the composites using normal human dermal fibrolast-neonatal (NHDF-neo) cells, as well as the antimicrobial effect against Staphylococcus aureus, was investigated. The PCL/CCA fibrous mat show significantly higher initial cell attachment and cell proliferation than the PCL and PCL/CH fibrous mat, and a high antimicrobial effect was observed compared to the PCL and PCL/CH fibrous mat. Based on these results, the PCL/CCA fibrous mat can be used as candidate biomaterial for wound dressing applications and skin tissue engineering., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The aim of the present study was to investigate the effects of 5-bromo-2-hydroxy-4-methyl-benzaldehyde (BHMB) on inflammatory responses to lipopolysaccharide (LPS) in RAW 264.7 cells and the associated mechanism of action. BHMB concentration-dependently suppressed protein and mRNA expressions of iNOS and COX-2, thereby inhibiting the production of NO and PGE2 in LPS-stimulated RAW 264.7 cells. BHMB also reduced the mRNA expression of TNF-α, IL-6, and IL-1β in LPS-stimulated RAW 264.7 cells. To elucidate the mechanism underlying the anti-inflammatory activity of BHMB, we investigated the effects of BHMB on the mitogen-activated protein kinase and nuclear factor-kappa B (NF-κB) pathways. BHMB suppressed the phosphorylation and degradation of IκB-α and markedly inhibited the nuclear translocation of p65 and p50 in LPS-stimulated RAW 264.7 cells. The compound also inhibited the LPS-stimulated phosphorylation of ERK and p38. Taken together, these results illustrated that BHMB suppresses pro-inflammatory mediator and cytokine expression in LPS-stimulated RAW 264.7 cells by inhibiting the phosphorylation of ERK and p38 and the activation of NF-κB., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to compare the short-term outcomes between 2 different treatments for unilateral chronic shoulder pain of myofascial origin, that is, local tender area related meridians (LTARMs) treatment and collateral meridian therapy (CMT), which were performed 6 times over a period of 4 weeks.Seventy patients with unilateral shoulder pain of chronic myofascial origin were enrolled. The patients were randomly assigned to 2 different treatment groups: 1 group received CMT (n = 35) and the other received LTARM (n = 35). Before and after the 2 treatment processes, all patients rated their overall pain intensity on a visual analogue scale (VAS) and a validated 13-question shoulder pain and disability index (SPADI) questionnaire was used to measure shoulder pain and functional impairment after therapy for 4 weeks.After CMT, the pain intensity was reduced after CMT. VAS score is reduced from 5.90 ± 2.07 (a mean of 5.90 and standard deviation of 2.07) to 3.39 ± 1.2. This was verified by the SPADI pain subscale scores (from 0.58 ± 0.193 to 0.33 ± 0.14). The pain-relief effect of CMT was significantly better than that of LTARM (VAS score from 5.78 ± 1.64 to 4.58 ± 1.40; P < 0.005; SPADI pain subscale score from 0.58 ± 0.16 to 0.45 ± 0.14, P < 0.001). In addition, the VAS scores of patients changed considerably in the CMT group after 4 weeks of treatment, where 63% of patients felt no or mild pain, whereas the VAS scores for moderate pain were even higher in the LTARM group in 75% of patients (P < 0.001). Moreover, the SPADI disability subscale scores improved significantly in the CMT group because of their greater mobility associated with shoulder impairment (disability score: from 0.58 ± 0.20 to 0.35 ± 0.14) than those in the LTARM group (disability score: from 0.55 ± 0.17 to 0.44 ± 0.14, P < 0.001).CMT may be more effective in reducing chronic shoulder pain of myofascial origin than the LTARM treatment, where treatment with the former resulted in better functional recovery after 4 weeks than the latter., Competing Interests: The authors declare that they have no conflict of interest.

Background and Purpose: A high incidence of cardiac-type Fabry disease with an α-galactosidase A mutation, IVS4 + 919 G>A, has been identified in the Taiwanese population. The neurologic manifestation has not been understood in this specific cardiac variant. This study aimed to investigate the typical imaging features of classic Fabry disease in patients with IVS4 Fabry disease., Materials and Methods: Twenty-six patients with IVS4-type Fabry disease (20 men and 6 women; age range, 43-71 years; median age, 61 years) and 26 age- and sex-matched healthy controls (age range, 44-68 years; median age, 60 years) were analyzed for white matter hyperintensities, the pulvinar sign, and basilar artery diameter. The volumes of white matter hyperintensities were calculated by comparison with an in-house data base of 276 controls., Results: Infarctions were found in 9 patients with IVS4 Fabry disease (35%) and in none of the healthy controls (P = .001). A pulvinar sign was found in 8 patients with IVS4 Fabry disease (30%) and in none of the healthy controls (P = .002). No significant difference was found in Fazekas scale scores for white matter hyperintensities; however, white matter hyperintensity volume in the deep white matter was higher in patients with IVS4 Fabry disease than in those from the healthy control data base (P = .004)., Conclusions: Along with its involvement of the cardiac system, IVS4-type Fabry disease has features similar to those of classic Fabry disease and a higher frequency of deep white matter hyperintensities and a higher incidence of infarctions and pulvinar signs than in healthy controls., (© 2016 by American Journal of Neuroradiology.)

Background: Ninety percent of perinatal hepatitis B virus (HBV) infections result in chronic HBV (CHBV), which carries 25% risk of premature death from progressive liver injury, cirrhosis, and liver cancer. In 1990, the Centers for Disease Control and Prevention (CDC) funded Perinatal Hepatitis B Prevention Programs (PHBPP) to ensure postexposure prophylaxis for exposed infants and accelerate elimination of perinatal CHBV in the United States. From 2000 to 2009, the annual rates of perinatal CHBV reported by PHBPP (0.8%-2.4%) were consistently lower than expected rates from CDC models (3.0%-4.1%), suggesting that rates of CHBV might be higher among infants whose outcomes were not identified by PHBPP. To better understand the factors impacting modeled expected number and rates of perinatal CHBV, we examined historic CDC models, applied updated inputs to the 2009 CDC model, and performed sensitivity analyses over a range of parameter values., Methods: Models employed estimates of the annual number of births to hepatitis B surface antigen (HBsAg)-positive pregnant women, and data from PHBPP and National Immunization Surveys. Published literature provided prenatal HBsAg screening rates, efficacy of postexposure prophylaxis (PEP), and perinatal HBV transmission rates., Results: The updated 2009 model predicted 952 perinatal CHBV infections, equivalent to a baseline rate of 3.84%, among infants of HBsAg-positive women. Sensitivity analyses yielded a possible range of perinatal CHBV rates between 0.60% and 15.41%. The proportion of infants receiving timely PEP, the efficacy of PEP, and perinatal HBV transmission rate were major "drivers" of CHBV rates. Three-way sensitivity analysis yielded possible perinatal CHBV rates between 0.79% and 13.64%., Conclusions: Modeling provided useful programmatic goals for achieving elimination of perinatal CHBV in the United States. Limitations of data inputs likely contributed to discrepancies between predicted and reported rates., (© The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Octaphlorethol A (OPA), a type of phlorotannin isolated from Ishige foliacea has been shown to have antidiabetic activities. However, the mechanism of action of OPA in type 2 diabetes has not been investigated extensively. Here, we investigated the antidiabetic effects and mechanism of OPA in C57BL/KsJ-db/db mice, a model of type 2 diabetes. Levels of postprandial blood glucose were significantly lower in OPAtreated db/db mice than in control db/db mice. In addition, the OPA supplements significantly improved fasting blood glucose level and impaired glucose tolerance compared to control db/db mice. OPA also significantly decreased the level of serum insulin, augmented the activation of AMP-activated protein kinase (AMPK), and increased the expression of glucose transporter 4 (GLUT4) protein in skeletal muscle. In addition, it significantly suppressed the increases in hepatic mRNA expression level of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), gluconeogenesis-related enzymes. Therefore, the mechanisms of OPA may involve suppression of gluconeogenesis by inhibiting PEPCK and G6Pase activity in the liver and affecting GLUT4-mediated glucose uptake in skeletal muscle through activation of AMPK. These findings provide a new insight into the antidiabetic clinical applications of OPA and demonstrate the potential of OPA as a new drug candidate for type 2 diabetes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The popular edible seaweed, Gelidium amansii is broadly used as food worldwide. To determine whether G. amansii extract (GAE) has protective effects on obesity, mice fed a high-fat diet (HFD) treated with GAE (1 and 3 %) were studied. After 12 weeks of GAE treatment, body weight was greatly decreased in mice fed a high-fat diet. This effect could be due to decreased adipogenesis, as evidenced by the fact that GAE suppressed adipogenic gene expression in adipocytes. In addition, blood glucose and serum insulin levels were reduced by GAE treatment in mice fed a high-fat diet, suggesting improvement in glucose metabolism. GAE supplementation also led to a significant decrease in total cholesterol and triglyceride levels. These data are further confirmed by H&E staining. Our findings indicate that Gelidium amansii prevents against the development of diet-induced obesity, and further implicate that GAE supplementation could be the therapeutical option for treatment of metabolic disorder such as obesity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The seaweeds were collected from the coast of Jeju Island, South Korea. We investigated ethanol extracts from seaweed as potential antiobesity agents by testing their effect on adipogenic differentiation in 3T3-L1 cells. Among the red algae extracts tested, the Plocamium telfairiae extract (PTE) showed the highest inhibitory effect on lipogenesis in adipocytes and, thus, was selected as a potential antiobesity agent. PTE treatment significantly decreased the expression of the adipogenic-specific proteins peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein-α, sterol regulatory element-binding protein 1, and fatty acid-binding protein 4 compared with that in the untreated 3T3-L1 cells. PTE also inhibited high-fat diet (HFD)-induced obesity in male C57BL/6 mice. Oral administration of PTE significantly reduced the body weight, fatty liver, amount of white adipose tissue, and levels of triglyceride and glucose in the tested animals. Taken together, these data demonstrate that PTE can be developed as a therapeutic agent for obesity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Over the past decades, little progress has been made to improve the extremely low survival rates in pancreatic cancer patients. Extreme hypoxia observed in pancreatic tumors contributes to the aggressive and metastatic characteristics of this tumor and can reduce the effectiveness of conventional radiation therapy and chemotherapy. In an attempt to reduce hypoxia-induced obstacles to effective radiation treatment, we used a novel device, the implantable micro-oxygen generator (IMOG), for in situ tumor oxygenation. After subcutaneous implantation of human pancreatic xenograft tumors in athymic rats, the IMOG was wirelessly powered by ultrasonic waves, producing 30 μA of direct current (at 2.5 V), which was then utilized to electrolyze water and produce oxygen within the tumor. Significant oxygen production by the IMOG was observed and corroborated using the NeoFox oxygen sensor dynamically. To test the radiosensitization effect of the newly generated oxygen, the human pancreatic xenograft tumors were subcutaneously implanted in nude mice with either a functional or inactivated IMOG device. The tumors in the mice were then exposed to ultrasonic power for 10 min, followed by a single fraction of 5 Gy radiation, and tumor growth was monitored thereafter. The 5 Gy irradiated tumors containing the functional IMOG exhibited tumor growth inhibition equivalent to that of 7 Gy irradiated tumors that did not contain an IMOG. Our study confirmed that an activated IMOG is able to produce sufficient oxygen to radiosensitize pancreatic tumors, enhancing response to single-dose radiation therapy.

Objective: Understanding the chemical composition of any calculus in different human organs is essential for choosing the best treatment strategy for patients. The purpose of this study was to assess the capability of determining the chemical composition of a human cardiac calculus using gemstone spectral imaging (GSI) mode on a single-source dual-energy computed tomography (DECT) in vitro., Methods: The cardiac calculus was directly scanned on the Discovery CT750 HD FREEdom Edition using GSI mode, in vitro. A portable fiber-optic Raman spectroscopy was also applied to verify the quantitative accuracy of the DECT measurements., Results: The results of spectral DECT measurements indicate that effective Z values in 3 designated positions located in this calculus were 15.02 to 15.47, which are close to values of 15.74 to 15.86, corresponding to the effective Z values of calcium apatite and hydroxyapatite. The Raman spectral data were also reflected by the predominant Raman peak at 960 cm for hydroxyapatite and the minor peak at 875 cm for calcium apatite., Conclusions: A potential single-source DECT with GSI mode was first used to examine the morphological characteristics and chemical compositions of a giant human cardiac calculus, in vitro. The CT results were consistent with the Raman spectral data, suggesting that spectral CT imaging techniques could be accurately used to diagnose and characterize the compositional materials in the cardiac calculus.

This study investigated the outcomes and the prognostic factors among the very elderly (patients ≥80 years old) requiring prolonged mechanical ventilation (PMV).Between 2006 and 2014, all of the very elderly patients of age 80 or more transferred to respiratory care center (RCC) of a tertiary medical center were retrospectively identified, and only patients who used mechanical ventilation (MV) for >3 weeks were included in this study.A total of 510 very elderly patients undergoing PMV were identified. The mean age of the patients was 84.3 ± 3.3 years, and it ranged from 80 to 96 years. Male comprised most of the patients (n = 269, 52.7%), and most of the patients were transferred to RCC from medical ICU (n = 357, 70.0%). The APACHE II scores on RCC admission was 17.6 ± 6.0. At least 1 comorbidity was found in 419 (82.2%) patients. No significant differences of gender, disease severity, diagnosis, dialysis, laboratory examinations, comorbidities, and outcome were found between octogenarians (aged 80-89) and nonagenarians (aged ≥ 90). The overall in-hospital mortality rate was 21.8%. In the multivariate analysis, patients who had APACHE II score ≥ 15(odds ratio [OR], 2.30, 95% confidence interval [CI], 1.36-3.90), or albumin ≤ 2 g/dL (OR, 3.92, 95% CI, 2.17-7.01) were more likely to have significant in-hospital mortality (P < 0.05).The in-hospital mortality rate of the very elderly PMV patients in our RCC is 21.8%, and poor outcomes in this specific population were found to be associated with a higher APACHE II score and lower albumin level.

Background: The human immunodeficiency virus (HIV) epidemic in Russia, driven by injection drug use, has seen a steady rise in the past two decades. Hepatitis C virus (HCV) infection is highly prevalent in people who inject drugs (PWID). The study aimed to describe the current frequency of HCV testing and treatment among HIV-infected PWID in St. Petersburg, Russia., Methods: This study examined baseline data from the "Linking Infectious and Narcology Care" (LINC) and "Russia Alcohol Research Collaboration on HIV/AIDS" (Russia ARCH) studies. Participants included in this analysis were HIV-infected with a history of injection drug use. Descriptive statistics were performed to assess frequency of HCV testing and treatment., Results: Participants (n=349 [LINC], 207 [Russia ARCH]) had a mean age of 33.8 years (IQR: 31-37) in LINC and 33.0 (IQR: 30-36) in Russia ARCH; 26.6% (LINC) and 29.0% (Russia ARCH) were female; 100% were Caucasian. Nearly all participants had been tested for HCV (98.9% in LINC, 97.1% in Russia ARCH). Almost all reported being diagnosed HCV positive (98.9% in LINC, 97.1% in Russia ARCH). Only 2.3% of LINC and 5.0% of Russia ARCH participants reported ever receiving HCV treatment., Conclusions: Among these cohorts of HIV-infected PWID in St. Petersburg, Russia, as of 2015 nearly all reported being tested for HCV and testing positive, while only 3.3% received any HCV treatment. In this new era of effective HCV pharmacotherapy, an enormous chasm in the HCV treatment cascade in Russia exists providing substantial opportunities for curing HCV in HIV-infected Russians with a history of injection drug use.

The aim of the present study was to examine whether the intestine gastrointestinal (GI) digests of abalone [Haliotis discus hannai (H. discus hannai)] modulate inflammatory responses and to elucidate the mechanisms involved. The GI digests of the abalone intestines were fractionated into fractions I (>10 kDa), II (5-10 kDa) and Ⅲ (<5 kDa). Of the abalone intestine GI digests (AIGIDs), fraction Ⅲ inhibited the passive cutaneous anaphylaxis (PCA) reaction in mice. Subsequently, a bioactive peptide [abalone intestine GI digest peptide (AIGIDP)] isolated from fraction Ⅲ was determined to be 1175.2 Da, and the amino acid sequence was found to be PFNQGTFAS. We noted that the purified nonameric peptide (AIGIDP) attenuated the phorbol‑12‑myristate 13-acetate plus calcium ionophore A23187 (PMACI)-induced histamine release and the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in human mast cells (HMC-1 cells). In addition, we also noted that AIGIDP inhibited the PMACI‑induced activation of nuclear factor‑κB (NF-κB) by suppressing IκBα phosphorylation and that it suppressed the production of cytokines by decreasing the phosphorylation of JNK. The findings of our study indicate that AIGIDP exerts a modulatory, anti-allergic effect on mast cell-mediated inflammatory diseases.

An emerging paradigm in wound healing techniques is that a tissue-engineered skin substitute offers an alternative approach to create functional skin tissue. Here we developed a fish collagen/alginate (FCA) sponge scaffold that was functionalized by different molecular weights of chitooligosaccharides (COSs) with the use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as a cross-linking agent. The effects of cross-linking were analyzed by Fourier transform infrared spectroscopy. The results indicate that the homogeneous materials blending and cross-linking intensity were dependent on the molecular weights of COSs. The highly interconnected porous architecture with 160-260μm pore size and over 90% porosity and COS's MW driven swelling and retention capacity, tensile property and in vitro biodegradation behavior guaranteed the FCA/COS scaffolds for skin tissue engineering application. Further improvement of these properties enhanced the cytocompatibility of all the scaffolds, especially the scaffolds containing COSs with MW in the range of 1-3kDa (FCA/COS1) showed the best cytocompatibility. These physicochemical, mechanical, and biological properties suggest that the FCA/COS1 scaffold is a superior candidate that can be used for skin tissue regeneration., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Snake venom toxin (SVT) from Vipera lebetina turanica contains a mixture of different enzymes and proteins. Peroxiredoxin 6 (PRDX6) is known to be a stimulator of lung cancer cell growth. PRDX6 is a member of peroxidases, and has calcium-independent phospholipase A2 (iPLA2) activities. PRDX6 has an AP-1 binding site in its promoter region of the gene. Since AP-1 is implicated in tumor growth and PRDX6 expression, in the present study, we investigated whether SVT inhibits PRDX6, thereby preventing human lung cancer cell growth (A549 and NCI-H460) through inactivation of AP-1. A docking model study and pull down assay showed that SVT completely fits on the basic leucine zipper (bZIP) region of c-Fos of AP-1. SVT (0-10 μg/ml) inhibited lung cancer cell growth in a concentration dependent manner through induction of apoptotic cell death accompanied by induction of cleaved caspase-3, -8, -9, Bax, p21 and p53, but decreased cIAP and Bcl2 expression via inactivation of AP-1. In an xenograft in vivo model, SVT (0.5 mg/kg and 1 mg/kg) also inhibited tumor growth accompanied with the reduction of PRDX6 expression, but increased expression of proapoptotic proteins. These data indicate that SVT inhibits tumor growth via inhibition of PRDX6 activity through interaction with its transcription factor AP-1.

Neurodegenerative disease in patients with chronic obstructive pulmonary disease (COPD) was observed. We aim to clarify the risk of dementia in patients with COPD. The study used claims data from Taiwan's National Health Insurance Research Database. Subjects were those who received a discharge diagnosis of COPD between January 1, 2002 and December 31, 2011. Only the first hospitalization was enrolled, and the index date was the first day of admission. Patients younger than 40 years or those with a history of Alzheimer disease (AD) or Parkinson disease (PD) before the index date were excluded. The patients with COPD were then followed until receiving a diagnosis of AD or PD, death, or the end of the study. Control subjects were selected from hospitalized patients without a history of COPD, AD, or PD and were matched according to age (±3 years), gender, and the year of admission at a 2:1 ratio. The comorbidities were measured from 1 year before the index date based on the ICD-9-CM codes. The study included 8640 patients with COPD and a mean age of 68.76 (±10.74) years. The adjusted hazard ratio of developing dementia (AD or PD) was 1.74 (95% confidence interval = 1.55-1.96) in patients with COPD compared with patients without COPD after adjusting for age, gender, and comorbidities. This nationwide cohort study demonstrates that the risk of dementia, including AD and PD, is significantly increased in patients with COPD compared with individuals in the general population.

Background/objectives: In this study, potential anti-inflammatory effect of enzymatic hydrolysates from Styela clava flesh tissue was assessed via nitric oxide (NO) production in lipopolysaccahride (LPS) induced RAW 264.7 macrophages and in vivo zebrafish model., Materials/methods: We investigated the ability of enzymatic hydrolysates from Styela clava flesh tissue to inhibit LPS-induced expression of pro-inflammatory mediators in RAW 264.7 macrophages, and the molecular mechanism through which this inhibition occurred. In addition, we evaluated anti-inflammatory effect of enzymatic hydrolysates against a LPS-exposed in in vivo zebrafish model., Results: Among the enzymatic hydrolysates, Protamex-proteolytic hydrolysate exhibited the highest NO inhibitory effect and was fractionated into three ranges of molecular weight by using ultrafiltration (UF) membranes (MWCO 5 kDa and 10 kDa). The above 10 kDa fraction down-regulated LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), thereby reducing production of NO and prostaglandin E2 (PGE2) in LPS-activated RAW 264.7 macrophages. The above 10 kDa fraction suppressed LPS-induced production of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. In addition, the above 10 kDa fraction inhibited LPS-induced phosphorylation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinase (JNK), and p38. Furthermore, NO production in live zebrafish induced by LPS was reduced by addition of the above 10 kDa fraction from S. clava enzymatic hydrolysate., Conclusion: The results of this study suggested that hydrolysates derived from S. clava flesh tissue would be new anti-inflammation materials in functional resources.

Wound healing is a complex biological process that depends on the wound condition, the patient's health, and the physicochemical support given through external materials. The development of bioactive molecules and engineered tissue substitutes to provide physiochemical support to enhance the wound healing process plays a key role in advancing wound-care management. Thus, identification of ideal molecules in wound treatment is still in progress. The discovery of natural products that contain ideal molecules for skin tissue regeneration has been greatly advanced by exploration of the marine bioenvironment. Consequently, tremendously diverse marine organisms have become a great source of numerous biological macromolecules that can be used to develop tissue-engineered substitutes with wound healing properties. This review summarizes the wound healing process, the properties of macromolecules from marine organisms, and the involvement of these molecules in skin tissue regeneration applications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: This study compared the therapeutic effects of collateral meridian therapy (CMT) with traditional acupoint pressure therapy (APT) in patients with unilateral upper back pain., Material and Methods: Forty-nine patients with active myofascial trigger points in upper trapezius muscle were randomly allocated to the control (CTL), APT, or CMT group. Each subject in the CMT and APT groups received 2 sessions of treatment per week over 1 month., Results: Patients in the APT and CMT groups showed significant improvements 1 month after treatment in visual analogue scale, range of motion, pain pressure threshold, regional superficial blood flow, and physical health, as compared to the CTL group. No significant differences in outcome measures were found between APT and CMT groups 1 month after treatment., Conclusion: Both APT and CMT have comparable therapeutic efficacy in the treatment of unilateral upper back pain with active myofascial trigger points in the upper trapezius muscle., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

α-Glucosidase inhibitors are important agents for decreasing postprandial hyperglycemia. The current study examined the inhibitory effects of octaphlorethol A (OPA) isolated from Ishige foliacea, a brown alga, on α-glucosidase, and analyzed the inhibitor's binding modes using the crystal structure of α-glucosidase. The effects of OPA on postprandial blood glucose levels after meals were also investigated. The IC50 value of OPA against α-glucosidase was 0.11 mM, which is higher than that of the commercial inhibitor acarbose. For further insights, we predicted the 3D structure of α-glucosidase and used a docking algorithm to simulate binding between α-glucosidase and OPA. These molecular modeling studies were successful, and indicated that OPA interacts with Phe575, His600, Arg526, Met444, Asp542, Tyr605, Ser448, Asp203, Lys480, and Phe450. Furthermore, increases in postprandial blood glucose levels were significantly suppressed in the OPA-treated group compared with those in the streptozotocin-induced diabetic or normal mice. Additionally, the area under the curve was significantly reduced following OPA administration (907 versus 1034 mg h dL(-1)) in the diabetic mice, along with a delay in the absorption of dietary carbohydrates. Collectively, these results indicated that OPA is a potent inhibitor of α-glucosidase, and shows potential to be used as an anti-diabetic agent.

In this study, we investigated the ability of 6,7-dimethoxy-4-methylcoumarin (DMC) to inhibit lipopolysaccharide (LPS)-induced expression of pro-inflammatory mediators in mouse macrophage (RAW 264.7) cells, and the molecular mechanism through which this inhibition occurred. Our results indicated that DMC downregulated LPS-induced nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, thereby reducing the production of NO and prostaglandin E2 (PGE2) in LPS-activated RAW 264.7 cells. Furthermore, DMC suppressed LPS-induced production of pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. To elucidate the mechanism underlying the anti-inflammatory activity of DMC, we assessed its effects on the mitogen-activated protein kinase (MAPK) pathway and the activity and expression of nuclear transcription factor kappa-B (NF-κB). The experiments demonstrated that DMC inhibited LPS-induced phosphorylation of extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinase (JNK), and p38. In addition, it attenuated LPS-induced NF-κB activation via the inhibition of IκB-α phosphorylation. Taken together, these data suggest that DMC exerts its anti-inflammatory effects in RAW 264.7 cells through the inhibition of LPS-stimulated NF-κB and MAPK signaling, thereby downregulating the expression of pro-inflammatory mediators.

Purpose: Annually, an estimated 25,000 infants are born to hepatitis B surface antigen (HBsAg)-positive women in the United States. Hepatitis B (HepB) vaccine and hepatitis B immune globulin (HBIG) are recommended at birth, followed by completion of vaccine series and post-vaccination serologic testing (PVST). In a large cohort of infants born to HBsAg-positive women, factors influencing vaccine response were evaluated., Methods: Data were from HBsAg-negative infants born to HBsAg-positive women in the Enhanced Perinatal Hepatitis B Prevention Program (EPHBPP) from 2008 to 2013. Vaccine non-responders were defined as infants with antibody to hepatitis B surface antigen (anti-HBs) <10mIU/mL at PVST after receiving ≥3 vaccine doses. Multivariable analyses modeled statistically significant predictor variables associated with non-response., Results: A total of 17,951 maternal-infant pairs were enrolled; 8654 HBsAg-negative infants born to HBsAg-positive mothers received ≥3 doses of vaccine with anti-HBs results. 8199 (94.7%) infants responded to a primary HepB series; 199 (94.8%) to a second series. Factors associated with anti-HBs <10mIU/mL included gestational age <37 weeks, vaccine birth dose >12h after birth, timing of final vaccine dose <6 months after birth, receipt of 3 vs. 4 vaccine doses, and PVST interval >6 months from final vaccine dose in bivariate analysis. PVST interval >6 months from final vaccine dose (OR=2.7, CI=2.0, 3.6) was significantly associated with anti-HBs <10mIU/mL; the proportion increased from 2% at 1-2 months to 21.6% at 15-16 months after the final dose. Receipt of a 4th dose improved the response rate (OR=0.5, CI=0.3, 0.8)., Conclusions: Ninety-five percent of a large cohort of uninfected infants born to HBsAg-positive mothers in the United States responded to primary HepB vaccine series. The proportion of infants with anti-HBs <10mIU/mL increased with longer interval between the final vaccine dose and PVST. Optimal timing of PVST is within 1-2 months of final vaccine dose to avoid unnecessary revaccination., (Published by Elsevier Ltd.)

Fucoidan, extracted from Ecklonia cava, has been extensively studied because of its wide biological activities. However, antioxidative activities have not been yet examined. Therefore we evaluated in vitro and in vivo studies on antioxidative activities of E. cava fucoidan (ECF). ECF exhibited more prominent effects in peroxyl radical scavenging activity, compared to the other scavenging activities. Thus, ECF was further evaluated for its protective ability against 2,2'-azobis dihydrochloride induced oxidative stress in Vero cells and ECF strongly reduced the AAPH-induced oxidative damage through scavenging intracellular reactive oxygen species. Furthermore, we evaluated protective effect of ECF against AAPH-induced oxidative stress in zebrafish model. ECF significantly reduced ROS generation, lipid peroxidation and cell death in zebrafish model. These findings indicate that ECF has antioxidant activities in vitro Vero cells and in vivo zebrafish model, even though ECF is not a polyphenol or flavonoid compound and does not contain benzene rings or conjugated structures., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: To image the intratumor vascular physiological status of pancreatic tumors xenografts and their response to anti-angiogenic therapy using dynamic contrast-enhanced computed tomography (DCE-CT), and to identify parameters of vascular physiology associated with tumor x-ray sensitivity after anti-angiogenic therapy., Methods and Materials: Nude mice bearing human BxPC-3 pancreatic tumor xenografts were treated with 5 Gy of radiation therapy (RT), either a low dose (40 mg/kg) or a high dose (150 mg/kg) of DC101, the anti-VEGF receptor-2 anti-angiogenesis antibody, or with combination of low or high dose DC101 and 5 Gy RT (DC101-plus-RT). DCE-CT scans were longitudinally acquired over a 3-week period post-DC101 treatment. Parametric maps of tumor perfusion and fractional plasma volume (Fp) were calculated and their averaged values and histogram distributions evaluated and compared to controls, from which a more homogeneous physiological window was observed 1-week post-DC101. Mice receiving a combination of DC101-plus-RT(5 Gy) were imaged baseline before receiving DC101 and 1 week after DC101 (before RT). Changes in perfusion and Fp were compared with alternation in tumor growth delay for RT and DC101-plus-RT (5 Gy)-treated tumors., Results: Pretreatment with low or high doses of DC101 before RT significantly delayed tumor growth by an average 7.9 days compared to RT alone (P ≤ .01). The increase in tumor growth delay for the DC101-plus-RT-treated tumors was strongly associated with changes in tumor perfusion (ΔP>-15%) compared to RT treated tumors alone (P=.01). In addition, further analysis revealed a trend linking the tumor's increased growth delay to its tumor volume-to-DC101 dose ratio., Conclusions: DCE-CT is capable of monitoring changes in intratumor physiological parameter of tumor perfusion in response to anti-angiogenic therapy of a pancreatic human tumor xenograft that was associated with enhanced radiation response., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The in vitro and in vivo antioxidant potentials of a polysaccharide isolated from aloe vera gel were investigated. Enzymatic extracts were prepared from aloe vera gel by using ten digestive enzymes including five carbohydrases and five proteases. Among them, the highest yield was obtained with the Viscozyme extract and the same extract showed the best radical scavenging activity. An active polysaccharide was purified from the Viscozyme extract using ethanol-added separation and anion exchange chromatography. Purified aloe vera polysaccharide (APS) strongly scavenged radicals including DPPH, hydroxyl and alkyl radicals. In addition, APS showed a protective effect against AAPH-induced oxidative stress and cell death in Vero cells as well as in the in vivo zebrafish model. In this study, it is proved that both the in vitro and in vivo antioxidant potentials of APS could be further utilized in relevant industrial applications., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In this study, we assessed the potential inhibitory effect of 5 species of brown seaweeds on adipogenesis the differentiation of 3T3-L1 preadipocytes into mature adipocytes by measuring Oil-Red O staining. The Ecklonia cava extract tested herein evidenced profound adipogenesis inhibitory effect, compared to that exhibited by the other four brown seaweed extracts. Thus, E. cava was selected for isolation of active compounds and finally the three polyphenol compounds of phlorotannins were obtained and their inhibitory effect on adipogenesis was observed. Among the phlorotannins, dieckol exhibited greatest potential adipogenesis inhibition and down-regulated the expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding proteins (C/EBPα), sterol regulatory element-binding protein 1 (SREBP1) and fatty acid binding protein 4 (FABP4) in a dose-dependent manner. The specific mechanism mediating the effects of dieckol was confirmed by AMP-activated protein kinase (AMPK) activation. These results demonstrate inhibitory effect of dieckol compound on adipogenesis through the activation of the AMPK signal pathway., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The superconducting flux flow transistor (SFFT) with three-channel was successfully fabricated by an electron beam lithography and Ar ion milling technique. In our paper the cross sectional analysis and topological views are investigated for the channel width and the channel height by the atomic force microscopy (AFM) image. Our result shows that the SFFT of multi-structure with a nano-channel is effectively fabricated by an electron-beam lithography method. We present a fabrication process of three-channel SFFT using the electron beam lithography. Mechanisms of nano-channel SFFT are studied.

Pancreatic β cells are extremely sensitive to oxidative stress, which probably has an important role in β cell damage in diabetes. The protective effect of octaphlorethol A (OPA), a novel phenolic compound isolated from Ishige foliacea, against streptozotocin (STZ)-induced pancreatic β cell damage was investigated using a rat insulinoma cell line (RINm5F pancreatic β cells). Pretreatment with OPA decreased the death of STZ-treated pancreatic β cells at concentrations of 12.5 μg/ml or 50 μg/ml, and reduced the generation of thiobarbituric acid reactive substances and intracellular reactive oxygen species in a dose-dependent manner in STZ-treated pancreatic β cells. In addition, the OPA pretreatment increased the activities of antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase in STZ-treated pancreatic β cells. Moreover, OPA treatment elevated the level of insulin, which was reduced by STZ treatment, and protected pancreatic β cells against damage under STZ-treated conditions. These effects were mediated by suppressing apoptosis and were associated with increased anti-apoptotic Bcl-xL expression and reduced pro-apoptotic Bax and cleaved caspase-3 expression. These findings indicate that OPA may be useful as a potential pharmaceutical agent to protect against pancreatic β cell damage caused by oxidative stress associated with diabetes., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Recently, there has been a growing in alternative prevents and therapies of marine organisms for metabolic syndrome. Marine-derived bioactive peptides attracted extensive interest due to their numerous health beneficial effects including antioxidant, antihypertensive, anti-diabetes, anti-obesity. The bioactive peptides may provide novel therapeutic applications for the prevention of metabolic syndrome. The facts summarized here may provide improvement of metabolic syndrome by peptides from marine organisms. However, further insightful researches on the prevention of metabolic syndrome by marine peptides in in vivo and clinical studies are needed to firmly establish their therapeutic potency.

In the present study, the attenuation of type ІІ diabetes by dieckol, a phlorotannin derivative isolated from brown seaweed, Ecklonia cava was investigated in C57BL/KsJ-db/db, a type ІІ diabetes mouse model. Dieckol was administered intraperitoneal injection at doses of 10 and 20 mg/kg body weight diabetes mice for 14 days. The blood glucose level, serum insulin level and body weight were significantly reduced in the dieckol administered group, compared to that of the saline administered group. Furthermore, reduced thiobarbituric acid reactive substraces (TBARS), as well as increased activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px) in liver tissues were observed in the dieckol administered group. In addition, increased levels of the phosphorylation of AMPK and Akt were observed in the muscle tissues of the dieckol administered group in a Western blotting analysis. According to the findings of this study, it could be suggested that, dieckol can be developed as a therapeutic agent for type ІІ diabetes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The expression of cytokines, such as IL-1β, and the activation of the epidermal growth factor receptor (EGFR) are crucial regulators in the process of carcinogenesis. The correlation between growth factor and activated cytokine signals in the control of tumor development is a critical issue to be clarified. In our study, we found that the IL-1β gene and protein expression were induced by EGF in squamous cell carcinoma. To clarify the mechanism involved in EGF-regulated IL-1β expression, we examined the transcriptional activity and mRNA stability of IL-1β in EGF-treated cells. We found that EGF induced the expression of IL-1β and was mediated through transcriptional activation, but not through mRNA stability. The involvement of Akt and NF-κB signaling pathways in the EGF-induced IL-1β gene expression was confirmed by knockdown of RelA and Akt in cells or treating cells with Akt and NF-κB inhibitors, LY294002 and parthenolide, respectively. The expression of dominant negative IκB also repressed the activation of NF-κB and inhibited EGF-induced IL-1β expression. Using immunofluorescence staining assay, the EGF-stimulated nuclear translocation of NF-κB (p65) was inhibited by pre-treating cells with LY294002 and parthenolide. Furthermore, EGF increased the binding of NF-κB to the NF-κB binding site of the IL-1β promoter through the activation of the Akt/NF-κB pathway, which resulted in activating IL-1β promoter activity. The expression and secretion of IL-1β induced by EGF considerably reduced chemotherapeutic drug cisplatin-induced cell death. These results showed that EGF enhanced the expression of IL-1β, which was mediated by the Akt/NF-κB pathway. The activation of EGF signaling and increase of IL-1β contributed to chemotherapeutic resistance of cancer cells, suggesting that the expression of IL-1β may be used as a biomarker to evaluate successful cancer treatment.

Objective: The purpose of this preliminary study was to examine whether collateral meridian (CM) therapy was feasible in treating knee osteoarthritis (OA) pain., Methods: Twenty-eight patients with knee OA and knee pain were randomly allocated to 2 groups. The CM group patients received CM therapy, whereas the control patients received placebo treatment for knee pain relief. Patients in the CM group received 2 CM treatments weekly for 3 weeks. The outcome measures were pain intensity on a visual analog scale, and knee function was determined using the Western Ontario and McMaster Universities Osteoarthritis Index., Results: In the CM group, the posttreatment visual analog scale and Western Ontario and McMaster Universities Osteoarthritis Index scores were lower than those of the control group; a significant reduction in pain intensity (P = .02, P = .01, respectively) and improvement in knee function (P = .04, P = .03, respectively) were shown in the CM group at the second and third week., Conclusion: Collateral meridian therapy may be feasible and effective for knee OA pain relief and knee function recovery. Therefore, additional randomized control trials are warranted., (Copyright © 2013 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.)

In our previous study, an anti-angiotensin I converting enzyme (ACE) peptide (Ala-His-Ile-Ile-Ile, MW: 565.3Da) was isolated from Styela clava flesh tissue. In this study the fractions obtained during the isolation process and the finally purified peptide were examined to see if they had vasorelaxation effects in isolated rat aortas, and then the peptide was investigated for anti-hypertensive effect in spontaneously hypertensive rats (SHRs). The induction of vasorelaxation in the rat aortas was observed with the isolated fractions and the peptide from the enzymatic hydrolysate of S. clava flesh tissue and could be markedly blocked by pretreatment with the nitric oxide synthase (NOS) inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME). In human endothelial cells, NO synthesis was found to be increased and eNOS phosphorylation was upregulated when the cells were cultured with the purified peptide. Furthermore, systolic blood pressure was reduced by administration of the potent vasorelaxation peptide in SHRs., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Protein derived the marine Chlorella ellipsoidea was hydrolyzed using different proteases (papain, trypsin, pepsin and α-chymotrypsin) for production of antioxidative peptide, and the antioxidant activities of their hydrolysates were investigated using free radical scavenging assay by electron spin resonance spin-trapping technique. Among the hydrolysates, the peptic hydrolysate exhibited the highest antioxidant activity compared to other hydrolysates. To identify antioxidant peptide, the peptic hydrolysate was purified using consecutive chromatographic methods, and the antioxidant peptide was identified to be Leu-Asn-Gly-Asp-Val-Trp (702.2 Da) by Q-TOF ESI mass spectroscopy. The antioxidant peptide scavenged peroxyl, DPPH and hydroxyl radicals at the IC(50) values of 0.02, 0.92 and 1.42 mM, respectively. The purified peptide enhanced cell viability against AAPH-induced cytotoxicity on normal cells. Furthermore, the purified peptide reduced the proportion of apoptotic and necrotic cells induced by AAPH, as demonstrated by decreased sub-G(1) hypodiploid cells and decreased apoptotic body formation by flow cytometry., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Alcoholic liver disease, which is one of the most serious liver disorders, has been known to cause by ethanol intake. In the present study, in vivo hepatoprotective effects of dieckol-rich phlorotannins (DRP) from Ecklonia cava, a brown seaweed, on ethanol induced hepatic damage in BALB/c mice liver were investigated. After administration of 5 and 25mg/kg mouse of DRP and 4 g/kg mice ethanol, the body weights and survival rates were increased as compared to the control, which is ethanol-treated group without DRP. The glutamic oxaloacetic transaminase and glutamic pyruvic transaminase levels in the serum were lower than those of the control. DRP exhibited a reduction of the total cholesterol. The lower levels of SOD enzyme and a reduction of the formation of malondialdehyde were occurred in mice fed with 5 and 25mg/kg mouse of DRP. Finally the effect on improvement of fatty liver induced by ethanol was observed by taking out the liver immediately after dissecting the mouse. However, no significant difference was observed on hepatic histopathological changes. In conclusion, this study indicated that DRP could protect liver injury induced by ethanol in vivo. It suggested that DRP possesses the beneficial effect to human against ethanol-induced liver injury., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Skeletal muscle is the major site of glucose disposal. Promoting glucose uptake into this tissue may attenuate the insulin resistance that precedes type 2 diabetes. However, the anti-diabetic effect of marine algae on glucose uptake and metabolism in skeletal muscle remains poorly understood. Here, we report the glucose uptake effects of octaphlorethol A (OPA), a novel phenolic compound isolated from Ishige foliacea, on skeletal muscle cells. OPA increased glucose uptake in differentiated L6 rat myoblast cells in a dose-dependent manner relative to the control. In addition, we found that OPA increased glucose transporter 4 (Glut4) translocation to the plasma membrane. Furthermore, we also demonstrated these OPA effects essentially depended on the protein kinase B (Akt) and AMP-activated protein kinase (AMPK) activation. In summary, PI3-K/Akt and AMPK activation were involved in mediating the effects of OPA on glucose transport activation and insulin sensitivity. OPA can be further developed as a potential anti-diabetic therapy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Pancreatic β cells are very sensitive to oxidative stress and this might play an important role in β cell death with diabetes. The protective effect of dieckol, one of the phlorotannin polyphenol compounds purified from Ecklonia cava (E. cava), against high glucose-induced oxidative stress was investigated by using rat insulinoma cells. A high-glucose (30 mM) treatment induced the death of rat insulinoma cells, but dieckol, at a concentration 17.5 or 70 µM, significantly inhibited the high-glucose induced glucotoxicity. Treatment with dieckol also dose-dependently reduced thiobarbituric acid reactive substances (TBARS), the generation of intracellular reactive oxygen species (ROS), and the nitric oxide level increased by a high glucose concentration. In addition, the dieckol treatment increased the activities of antioxidative enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in high glucose-pretreated rat insulinoma cells. Dieckol protected rat insulinoma cells damage under high glucose conditions. These effects were mediated by suppressing apoptosis and were associated with increased anti-apoptotic Bcl-2 expression, and reduced pro-apoptotic cleaved caspase-3 expression. These findings indicate that dieckol might be useful as a potential pharmaceutical agent to protect against the glucotoxicity caused by hyperglycemia-induced oxidative stress associated with diabetes.

In this paper, we present an ultrasonically powered implantable micro-oxygen generator (IMOG) that is capable of in situ tumor oxygenation through water electrolysis. Such active mode of oxygen generation is not affected by increased interstitial pressure or abnormal blood vessels that typically limit the systemic delivery of oxygen to hypoxic regions of solid tumors. Wireless ultrasonic powering (2.15 MHz) was employed to increase the penetration depth and eliminate the directional sensitivity associated with magnetic methods. In addition, ultrasonic powering allowed for further reduction in the total size of the implant by eliminating the need for a large area inductor. IMOG has an overall dimension of 1.2 mm × 1.3 mm × 8 mm, small enough to be implanted using a hypodermic needle or a trocar. In vitro and ex vivo experiments showed that IMOG is capable of generating more than 150 μA which, in turn, can create 0.525 μL/min of oxygen through electrolytic disassociation. In vivo experiments in a well-known hypoxic pancreatic tumor models (1 cm (3) in size) also verified adequate in situ tumor oxygenation in less than 10 min.

α-Tomatine, isolated from Lycopersicon esculentum Linn., is a naturally occurring steroidal glycoalkaloid in immature green tomatoes. Some reports demonstrated that α-tomatine had various anticarcinogenic properties. The purpose of this study is to investigate the anti-metastatic effect of α-tomatine in NCI-H460 human non-small cell lung cancer cells. First, the results showed that α-tomatine significantly suppressed the abilities of the adhesion, invasion, and migration of NCI-H460 cells under non-cytotoxic concentrations. Molecular data also showed α-tomatine could inhibit the activation of focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K)/Akt signal involve in the downregulation the enzyme activities, protein and messenger RNA levels of matrix metalloproteinase-7 (MMP-7). Next, α-tomatine also strongly inhibited the degradation of inhibitor of kappaBα (IκBα) and the nuclear levels of nuclear factor kappa B (NF-κB). Also, a dose-dependent inhibition on the binding ability of NF-κB by α-tomatine treatment was further observed. Furthermore, α-tomatine significantly decreased the levels of phospho-Akt and MMP-7 in Akt1-cDNA-transfected cells concomitantly with a marked reduction on cell invasion and migration. Presented results indicated α-tomatine might be further application for treating cancer metastasis.

Purpose: Suboptimal dosage evaluated from postimplant dosimetry of prostate brachytherapy creates conundrum that needs resolution. This pilot study was undertaken to explore the feasibility of summing and visualizing radiation dosage from multimodality treatment., Methods and Materials: Four weeks after (125)I permanent prostate seed implant, CT scans were performed on the whole pelvis of patients using our standard protocol for prostate planning. The acquired CT data sets were reconstructed using different sizes of field of view (FOV). The images with limited FOV focusing on prostate were imported into Variseed (Varian Medical Systems, Inc., Palo Alto, CA) for postimplant evaluation, whereas images with full FOV were imported to Eclipse (Varian Medical Systems, Inc., Palo Alto, CA) treatment planning system (TPS) for future managements, that is, for external beam salvage., Results: The dose matrix resulted from the postimplant dosimetry was exported from Variseed in standard DICOM format and imported into Eclipse TPS. The brachytherapy dose matrix was registered with the patient images with full FOV in Eclipse TPS. Targets for dose boost were defined based on the isodose curves generated from brachytherapy. An external photon beam plan was successfully generated to deliver dose for selected underdose regions., Conclusion: Accurate external beam radiation treatment planning can be accomplished using our planning protocols when inadequate brachytherapy dose delivery occurs. The proposed technique can be used to safely deliver additional external radiation dose using intensity-modulated radiation therapy technique after suboptimal brachytherapy procedure., (Copyright © 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Inhibition of angiotensin I-converting enzyme (ACE) activity is the most common mechanism underlying the lowering of blood pressure. In the present study, five organic extracts of a marine brown seaweed Ecklonia cava were prepared by using ethanol, ethyl acetate, chloroform, hexane, and diethyl ether as solvents, which were then tested for their potential ACE inhibitory activities. Ethanol extract showed the strongest ACE inhibitory activity with an IC(50) value of 0.96 mg/ml. Five kinds of phlorotannins, phloroglucinol, triphlorethol-A, eckol, dieckol, and eckstolonol, were isolated from ethanol extract of E. cava, which exhibited potential ACE inhibition. Dieckol was the most potent ACE inhibitor and was found to be a non-competitive inhibitor against ACE according to Lineweaver-Burk plots. Dieckol had an inducible effect on the production of NO in EAhy926 cells without having cytotoxic effect. The results of this study indicate that E. cava could be a potential source of phlorotannins with ACE inhibitory activity for utilization in production of functional foods.

In order to find new anti-browning and whitening agents in this study, we investigated 43 indigenous marine algae for tyrosinase inhibitory activity. The extracts from Endarachne binghamiae, Schizymenia dubyi, Ecklonia cava (EC) and Sargassum silquastrum (SS) evidenced potent tyrosinase inhibitory activity similar to that of positive control, kojic acid. Among those marine algae, EC and SS are distributed abundantly on Jeju Island. Therefore, we selected those two species for further studies. Our results evidenced that both species reduced cellular melanin synthesis and tyrosinase activity. On the other hand, we utilized zebrafish as an alternative in vivo model. All the tested samples evidenced excellent inhibitory effects on the pigmentation of zebrafish, most likely due to their potential tyrosinase inhibitory activity. In simultaneous in vivo toxicity tests, no toxicity was observed in either algal species, on the other hand, toxicity was observed in positive controls. These results provided that EC and SS extract could be used as an ingredient for whiting cosmetics and that zebrafish is an alternative in vivo model., (© 2010 Japanese Dermatological Association.)