Active photonic wireless power transfer into live tissues.

Recent advances in soft materials and mechanics activate development of many new types of electrical medical implants. Electronic implants that provide exceptional functions, however, usually require more electrical power, resulting in shorter period of usages although many approaches have been suggested to harvest electrical power in human bodies by resolving the issues related to power density, biocompatibility, tissue damage, and others. Here, we report an active photonic power transfer approach at the level of a full system to secure sustainable electrical power in human bodies. The active photonic power transfer system consists of a pair of the skin-attachable photon source patch and the photovoltaic device array integrated in a flexible medical implant. The skin-attachable patch actively emits photons that can penetrate through live tissues to be captured by the photovoltaic devices in a medical implant. The wireless power transfer system is very simple, e.g., active power transfer in direct current (DC) to DC without extra circuits, and can be used for implantable medical electronics regardless of weather, covering by clothes, in indoor or outdoor at day and night. We demonstrate feasibility of the approach by presenting thermal and mechanical compatibility with soft live tissues while generating enough electrical power in live bodies through in vivo animal experiments. We expect that the results enable long-term use of currently available implants in addition to accelerating emerging types of electrical implants that require higher power to provide diverse convenient diagnostic and therapeutic functions in human bodies.

Olive leaf components apigenin 7-glucoside and luteolin 7-glucoside direct human hematopoietic stem cell differentiation towards erythroid lineage.

The generation of blood cellular components from hematopoietic stem cells is important for the therapy of a broad spectrum of hematological disorders. In recent years, several lines of evidence suggested that certain nutrients, vitamins and flavonoids may have important roles in controlling the stem cell fate decision by maintaining their self-renewal or stimulating the lineage-specific differentiation. In this study, main olive leaf phytochemicals oleuropein (Olp), apigenin 7-glucoside (Api7G) and luteolin 7-glucoside (Lut7G) were investigated for their potential effects on hematopoietic stem cell differentiation using both phenotypic and molecular analysis. Oleuropein and the combination of the three compounds enhanced the differentiation of CD34+ cells into myelomonocytic cells and lymphocytes progenitors and inhibited the commitment to megakaryocytic and erythroid lineages. Treatment with Lut7G stimulated both the erythroid and the myeloid differentiation, while treatment with Api7G specifically induced the differentiation of CD34+ cells towards the erythroid lineage and inhibited the myeloid differentiation. Erythroid differentiation induced by Api7G and Lut7G treatments was confirmed by the increase in hemoglobin genes expressions (α-hemoglobin, ß-hemoglobin and γ-hemoglobin) and erythroid transcription factor GATA1 expression. As revealed by microarray analysis, the mechanisms underlying the erythroid differentiation-inducing effect of Api7G on hematopoietic stem cells involves the activation of JAK/STAT signaling pathway. These findings prove the differentiation-inducing effects of olive leaf compounds on hematopoietic stem cells and highlight their potential use in the ex vivo generation of blood cells.

Assessment of organic micropollutants occurrence in treated wastewater using heat shock protein 47 stress responses in Chinese hamster ovary cells and GC/MS-based non-target screening.

Combining bioassays and analytical chemistry screening is a powerful approach to assess organic micropollutants which are the main contributors to toxic potential in complex mixtures of treated wastewater (TWW). The aim of this study was to perform a comprehensive toxicity assessment of treated effluents using stress response bioassays and then to assess the occurrence of the organic micropollutants which were responsible for this biological response using gas chromatography coupled with a mass spectrometry detector (GC/MS). Results showed that TWW samples induced significant stress response on Chinese hamster ovary cells, stably transfected with heat shock protein 47 promoter, at 0.1%, 1%, 5% and 10% concentrations. The organic chemical compounds responsible for stress response potential were identified at different percentage values using non-target chemical screening. Of the compounds detected in TWW1 and TWW4, 55.09% and 74.5% respectively, fell within the class of aliphatic hydrocarbons. Aliphatic hydrocarbons were also present in TWW3 at 26.46% whereas 11.96% corresponded to 6-acetyl-1,1,2,4,4,7-hexamethyltetralin and 16.08% to triethoxysilane. Moreover, 76.73% of TWW2 was recorded as decamethylcyclopentasiloxane (D5) and 17.44% as n-hexadecanoic acid.

Protective effects of Nitraria retusa extract and its constituent isorhamnetin against amyloid ß-induced cytotoxicity and amyloid ß aggregation.

Nitraria retusa is a halophyte species that is distributed in North Africa and used as a traditional medicinal plant. In this study, N. retusa ethanol extract and its constituent isorhamnetin (IRA) protected against amyloid ß (Aß)-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. An in vitro Aß aggregation assay suggested that IRA destabilizes Aß fibrils.

Identification of 6-octadecynoic acid from a methanol extract of Marrubium vulgare L. as a peroxisome proliferator-activated receptor γ agonist.

6-Octadecynoic acid (6-ODA), a fatty acid with a triple bond, was identified in the methanol extract of Marrubium vulgare L. as an agonist of peroxisome proliferator-activated receptor γ (PPARγ). Fibrogenesis caused by hepatic stellate cells is inhibited by PPARγ whose ligands are clinically used for the treatment of diabetes. Plant extracts of Marrubium vulgare L., were screened for activity to inhibit fibrosis in the hepatic stellate cell line HSC-T6 using Oil Red-O staining, which detects lipids that typically accumulate in quiescent hepatic stellate cells. A methanol extract with activity to stimulate accumulation of lipids was obtained. This extract was found to have PPARγ agonist activity using a luciferase reporter assay. After purification using several chromatographic methods, 6-ODA, a fatty acid with a triple bond, was identified as a candidate of PPARγ agonist. Synthesized 6-ODA and its derivative 9-octadecynoic acid (9-ODA), which both have a triple bond but in different positions, activated PPARγ in a luciferase reporter assay and increased lipid accumulation in 3T3-L1 adipocytes in a PPARγ-dependent manner. There is little information about the biological activity of fatty acids with a triple bond, and to our knowledge, this is the first report that 6-ODA and 9-ODA function as PPARγ agonists.

Arthrophytum scoparium inhibits melanogenesis through the down-regulation of tyrosinase and melanogenic gene expressions in B16 melanoma cells.

Melanin performs a crucial role in protecting the skin against harmful ultraviolet light. However, hyperpigmentation may lead to aesthetic problems and disorders such as solar lentigines (SL), melasma, postinflammatory hyperpigmentation and even melanoma. Arthrophytum scoparium grows in the desert in the North African region, and given this type of environment, A. scoparium exhibits adaptations for storing water and produces useful bioactive factors. In this study, the effect of A. scoparium ethanol extract (ASEE) on melanogenesis regulation in B16 murine melanoma cells was investigated. Cells treated with 0.017% (w/v) ASEE showed a significant inhibition of melanin biosynthesis in a time-dependent manner without cytotoxicity. To clarify the mechanism behind the ASEE-treated melanogenesis regulation, the expressions of tyrosinase enzyme and melanogenesis-related genes were determined. Results showed that the expression of tyrosinase enzyme was significantly decreased and Tyr, Trp-1, Mitf and Mc1R mRNA expressions were significantly down-regulated. LC-ESI-TOF-MS analysis of the extract identified the presence of six phenolic compounds: coumaric acid, cinnamic acid, chrysoeriol, cyanidin, catechol and caffeoylquinic acid. The melanogenesis inhibitory effect of ASEE may therefore be attributed to its catechol and tetrahydroisoquinoline derivative content. We report here that ASEE can inhibit melanogenesis in a time-dependent manner by decreasing the tyrosinase protein and Tyr, Trp-1, Mitf and Mc1R mRNA expressions. This is the first report on the antimelanogenesis effect of A. scoparium and on its potential as a whitening agent.

Proteomic study of granulocytic differentiation induced by apigenin 7-glucoside in human promyelocytic leukemia HL-60 cells.

BACKGROUND: Nutritional factors is one of the most important regulators in the progression of cancer. Some dietary elements promote the growth of cancer but others, such as plant-derived compounds, may reverse this process. PURPOSE: We tried to investigate yet another approach of cancer prevention through cancer cell differentiation, using a common non-mutagenic flavonoid apigenin 7-glucoside. METHODS: HL-60 cells were treated with or without apigenin 7-glucoside. Cell proliferation was measured by MTT assay, and the cell cycle distribution was estimated by propidium iodide staining of DNA. To determine cellular differentiation, cell surface differentiation markers CD11b and CD14 were used. Two-dimensional gel electrophoresis was then performed to identify proteins that may be important in HL-60 cell differentiation following apigenin 7-glucoside treatment. RESULTS: Apigenin 7-glucoside inhibited HL-60 cell growth, dose- and time-dependently, but did not cause apoptosis. The distribution of cells at different stages in the cell cycle indicated an accumulation of treated cells in G(2)/M phase. Moreover, apigenin 7-glucoside induced granulocytic differentiation of HL-60 cells. Ten proteins that might play essential role in granulocytic differentiation were identified by proteomics. CONCLUSIONS: A complete understanding of the preventive effects of plant-based diet on cancer depends on the mechanisms of action of different plant components on processes. We hope these findings may contribute to the understandings of the different approaches for chemoprevention of cancer.

Inhibition of amyloid ß aggregation by acteoside, a phenylethanoid glycoside.

We examined the effects of acteoside (1a), which was isolated from Orobanche minor, and its derivatives on the aggregation of a 42-mer amyloid ß protein (Aß42) in our search for anti-amyloidogenic compounds for Alzheimer's disease (AD) therapy. Acteoside (1a) strongly inhibited the aggregation of Aß42 in a dose-dependent manner. The structure-activity relationship for acteoside (1a) and related compounds suggests the catechol moiety of phenylethanoid glycosides to be essential for this inhibitory activity.

Lupenone from Erica multiflora leaf extract stimulates melanogenesis in B16 murine melanoma cells through the inhibition of ERK1/2 activation.

Hypopigmentation diseases are usually managed using UVB light which increases the patients' risk for skin cancer. Here, we evaluated the melanogenesis stimulatory effects of leaf extracts of Erica multiflora, a medicinal plant from the Mediterranean region, and its active component, lup-20(29)-en-3-one, as possible therapeutic agents to address hypopigmentation disorders. B16 murine melanoma cells were treated with E. multiflora extracts or its active component lupenone to evaluate their effects on melanin biosynthesis. The mechanism underlying the observed effects was also determined. Bioactivity-guided fractionation of fifteen ethyl acetate fractions identified fraction 2 to have melanogenesis stimulatory effects due to its ability to decrease mitogen-activated protein kinase phosphorylated extracellular signal-regulated kinases 1 and 2 activation. Preparative TLC of ethyl acetate fraction 2 revealed the presence of lup-20(29)-en-3-one as the major bioactive component. B16 cells treated with lup-20(29)-en-3-one increased melanin content without cytotoxicity. To determine the mechanism for the observed effects of lup-20(29)-en-3-one, the tyrosinase enzyme activity, the tyrosinase protein expression, and the activation of phosphorylated extracellular signal-regulated kinases 1 and 2 were determined. In addition, the expression of the tyrosinase mRNA was quantified using real-time PCR. Results showed that lup-20(29)-en-3-one has no effect on the tyrosinase enzyme activity but can increase tyrosinase expression at both the transcriptional and translational levels. The increase in the tyrosinase mRNA expression was most likely due to the inhibited mitogen-activated protein kinase phosphorylated extracellular signal-regulated kinases 1 and 2 activation. We report for the first time that E. multiflora ethyl acetate extract and its active compound lup-20(29)-en-3-one stimulate melanogenesis by increasing the tyrosinase enzyme expression via mitogen-activated protein kinase phosphorylated extracellular signal-regulated kinases 1 and 2 phosphorylation inhibition, making it a possible treatment for hypopigmentation diseases.

Metabolomics analysis of Cistus monspeliensis leaf extract on energy metabolism activation in human intestinal cells.

Energy metabolism is a very important process to improve and maintain health from the point of view of physiology. It is well known that the intracellular ATP production is contributed to energy metabolism in cells. Cistus monspeliensis is widely used as tea, spices, and medical herb; however, it has not been focusing on the activation of energy metabolism. In this study, C. monspeliensis was investigated as the food resources by activation of energy metabolism in human intestinal epithelial cells. C. monspeliensis extract showed high antioxidant ability. In addition, the promotion of metabolites of glycolysis and TCA cycle was induced by C. monspeliensis treatment. These results suggest that C. monspeliensis extract has an ability to enhance the energy metabolism in human intestinal cells.

Protective effects of caffeoylquinic acids on the aggregation and neurotoxicity of the 42-residue amyloid ß-protein.

Alzheimer's disease (AD), a neurodegenerative disorder, is characterized by aggregation of 42-mer amyloid ß-protein (Aß42). Aß42 aggregates through ß-sheet formation and induces cytotoxicity against neuronal cells. Aß42 oligomer, an intermediate of the aggregates, causes memory loss and synaptotoxicity in AD. Inhibition of Aß42 aggregation by small molecules is thus a promising strategy for the treatment of AD. Caffeoylquinic acid (CQA), a phenylpropanoid found widely in natural sources including foods, shows various biological activities such as anti-oxidative ability. Previously, our group reported that 3,5-di-O-caffeoylquinic acid (3,5-di-CQA) rescued the cognitive impairment in senescence-accelerated-prone mice 8. However, structure-activity relationship of CQA derivatives on the aggregation and neurotoxicity of Aß42 remains elusive. To evaluate the anti-amyloidogenic property of CQA-related compounds for AD therapy, we examined the effect of CQA and its derivatives on the aggregation and neurotoxicity of Aß42. In particular, 4,5-di-O-caffeoylquinic acid (4,5-di-CQA) and 3,4,5-tri-O-caffeoylquinic acid (3,4,5-tri-CQA) strongly inhibited the aggregation of Aß42 in a dose-dependent manner. Structure-activity relationship studies suggested that the caffeoyl group in CQA is essential for the inhibitory activity. These CQAs also suppressed the transformation into ß-sheet and cytotoxicity against human neuroblastoma cells of Aß42. Furthermore, 3,4,5-tri-CQA blocked the formation of Aß42 oligomer. These results indicate that 3,4,5-tri-CQA could be a potential agent for the prevention of AD.

Inflammatory and degranulation effect of yellow sand on RBL-2H3 cells in relation to chemical and biological constituents.

Recent studie pointed out that allergic diseases have increased during the Asian dust storm event (ADSE) in Japan. Daily observations and the atmospheric concentrations of yellow sand (YS) aerosol have been increasing. In this study, YS samples collected from three sites of Japan during ADSE in 2009-2010 were used. The particles were analyzed by X-ray photoelectron spectroscopy (XPS) and X-ray fluorescence-energy dispersive spectrometer (XRF-EDS). We investigate ability of YS extract on enhancing the chemical mediator release and cytokine production from rat basophilic leukemia (RBL-2H3) cells. The dust particles at Fukuoka and Tsukuba were abundant in aluminum (Al), iron (Fe), potassium (K) and titan (Ti) than those at Naha. Concentration of the trace endotoxin and Cryptomeria japonica pollen allergen (Cry j 1) were measured in YS extract. After exposure of RBL-2H3 cells to YS extract, the ß-hexosaminidase (ß-hex) release, tumor necrosis factor-alpha (TNF-α) production were enhanced in RBL-2H3 cells. This process depends on endotoxin, Cry j 1 and other allergen present in the YS extract. YS water extract also show a strong cytotoxic effect on the cells. This data suggest that low levels of endotoxin and Cry j 1 in YS may cause allergy during the ADSE.

Heat shock protein 47 stress responses in Chinese hamster ovary cells exposed to raw and reclaimed wastewater.

As wastewater reclamation and reuse becomes more widespread, risks of exposure to treated wastewater increase. Moreover, an unlimited number of pollutants can be identified in wastewater. Therefore, comprehensive toxicity assessment of treated wastewater is imperative. The objective of this study was to perform a comprehensive toxicity assessment of wastewater treatment systems using stress response bioassays. This powerful tool can comprehensively assess the toxicity of contaminants. In this study, samples from conventional activated sludge treatment, membrane bioreactors (MBRs) with different pore sizes and sludge retention times (SRTs), rapid sand filtration, coagulation, nano-filtration (NF) and reverse osmosis (RO) were investigated. The results of stress response bioassays confirmed that the secondary effluent showed higher stress response than influent indicating that biological treatment generates toxic compounds. The results obtained from molecular weight fractionation of water samples demonstrated that organic matter with a higher molecular weight fraction (>0.1 µm) causes toxicity in secondary effluent. Furthermore, supernatant from MBR reactors showed toxicity regardless of SRT. On the other hand, stress response was not detected in MBR permeates except for an MBR equipped with a larger pore size membrane (0.4 µm) and with a short SRT (12 days). While rapid sand filtration could not remove the toxic compounds found in secondary effluent, coagulation tests, operated at an appropriate pH, were effective for reducing stress response in the secondary effluent. Experimental findings also showed that stress response was not detected in cases of NF and RO permeate subsequent to MBR treatment.

Structure-activity relationship of caffeoylquinic acids on the accelerating activity on ATP production.

Caffeoylquinic acid (CQA) is one of the phenylpropanoids which have various bioactivities such as antioxidant, antibacterial, anticancer, antihistamic, and other biological effects. We previously reported that 3,5-di-O-caffeoylquinic acid inhibited amyloid ß(1-42)-induced cellular toxicity on human neuroblastoma SH-SY5Y cells and increased the mRNA expression level of glycolytic enzymes and the intracellular ATP level. To investigate structure-activity relationship on the accelerating activity on ATP production, we synthesized 1,4,5-tri-O-caffeoylquinic acid, 4,5-di-O-caffeoylquinic acid, 3,4,5-tri-O-caffeoylquinic acid, and other derivatives. Additionally, we evaluated intracellular ATP level in SH-SY5Y treated with each CQA derivative. As a result, 3,4,5-tri-O-caffeoylquinic acid showed the highest accelerating activity on ATP production among tested compounds. It was suggested that caffeoyl groups bound to quinic acid are important for activity and the more caffeoyl groups are bound to quinic acid, the higher accelerating activity on ATP production exhibits.

Hirseins inhibit melanogenesis by regulating the gene expressions of Mitf and melanogenesis enzymes.

Previously, we reported that Thymelaea hirsuta extract has antimelanogenesis effect on B16 murine melanoma cells. The extract was subjected to fractionation, and hirsein A (HA) and hirsein B (HB) were discovered and tested for their ability to regulate melanogenesis in B16 cells. Western blot (WB) analysis was carried out to determine the expression of tyrosinase. Moreover, to elucidate the possible mechanism behind melanogenesis regulation, real-time PCR using primers for Mitf, Tyr, Trp1 and Dct genes, and protein kinase C (PKC) activity assay were carried out. Results clearly show that 0.1 mum HA and HB significantly reduced the melanin content. This reduction in melanin content was accompanied by reduced tyrosinase expression as detected by WB analysis. There was also a significant decrease in the expression level of Mitf gene in HA- and HB-treated cells. HA down-regulated the expressions of Tyr, Trp1 and Dct, whereas HB down-regulated only those of Trp1 and Dct. Interestingly, HB-treated cells had lower kinase activity than HA-treated cells indicating a possible difference in the activities of the compounds but with the same mechanism of melanogenesis regulation. We report for the first time that HA and HB can down-regulate melanogenesis by down-regulating Mitf gene expression, leading to reduced expressions of Tyr, Trp1 and Dct. The hirseins were also able to reduce the kinase activity, suggesting the possible involvement of PKC in the overall ability of the hirseins to down-regulate melanogenesis.

Inhibitory effect of acteoside isolated from Cistanche tubulosa on chemical mediator release and inflammatory cytokine production by RBL-2H3 and KU812 cells.

The immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis, and sinusitis. In this study, we investigated the effect of acteoside extracted from CISTANCHE TUBULOSA (Schrenk) R. Wight on the basophilic cell-mediated allergic reaction. The effect of acteoside on ß-hexosaminidase release and intracellular [Ca (2+)] I level from rat basophilic leukemia (RBL-2H3) cells was determined. Also, ELISA was used to determine the level of histamine, tumor necrosis factor (TNF)- α, and interleukin (IL)-4 on human basophilic (KU812) cells. The effect of acteoside on basophilic cell viability was determined using the 3-[4,5-dimethylthiazolyl]-2,5-diphenyltetrazolium bromide (MTT) assay. These results indicated that 0.1-10.0 µg/mL acteoside inhibits the release of ß-hexosaminidase and [Ca (2+)] I influx from IgE-mediated RBL-2H3 cells. Moreover, acteoside inhibited histamine release, TNF- α, and IL-4 production in a dose-dependent manner from calcium ionophore A23187 plus phorbol 12-myristate 13-acetate (PMA) or compound 48/80-stimulated KU812 cells. Our findings provide evidence that acteoside inhibits basophilic cell-derived immediate-type and delayed-type allergic reactions. This is the first report describing antiallergic activity of acteoside extracted from CISTANCHE TUBULOSA on basophilic cells.

Properties of fulvic acid extracted from excess sludge and its inhibiting effect on beta-hexosaminidase release.

The physicochemical and biological properties of fulvic acid extracted and purified from excess sludge and solubilized excess sludge were studied. Solubilization was introduced to improve the recovery rate of fulvic acid from the sludge. The structural features of fulvic acid from excess sludge and solubilized excess sludge were characterized by using an elemental analysis, Fourier transform infrared spectroscopy and (1)H-nuclear magnetic resonance spectroscopy, and were compared with fulvic acid extracted from peat which had an inhibitory effect on the type I allergy in our previous study. The results show that they had a higher aliphatic characteristic with lower oxygen group content than fulvic acid from peat, and that the aliphatic characteristic was further strengthened by the use of solubilization. The biological properties of fulvic acid from excess sludge and solubilized excess sludge showed an inhibitory effect on beta-hexosaminidase release at the antigen-antibody binding stage and antigen-receptor binding stage by using rat basophilic leukemia cells.

Cofilin mediates tight-junction opening by redistributing actin and tight-junction proteins.

We previously found that capsaicin induces tight-junction (TJ) opening accompanied with cofilin dephosphorylation/activation in intestinal Caco-2 cells. Here, we examined the role of cofilin in TJ regulation, and analyzed the structural events that lead to TJ opening. We transfected Caco-2 cells with wild-type cofilin [cofilin(wt)] or its constitutively active mutant cofilin(S3A). We found that the decreases in transepithelial electrical resistance (TER) was slower in cofilin(wt) transfectants and faster in cofilin(S3A) mutants than in vector controls. Moreover, cofilin dephosphorylation corresponded to the rate of TER decrease. Capsaicin treatment changed the localization of TJ proteins and altered the F-actin structure, but in a manner different from those depend on myosin light chain kinase (MLCK). These results strongly support the importance of cofilin in TJ opening, suggesting cofilin as a target for TJ permeability regulation in epithelial cells.

Application of heat shock protein assay and proteome assay to water from wastewater treatment plant.

In this study we applied bioassay using Chinese hamster ovary (CHO) cells with a heat shock protein (HSP) 47 promoter to the effluent of the wastewater treatment plants in Sapporo and we observed the statistically significant HSP production. This implied the effluent contained some organic matter which can stress the CHO cells. To investigate the possible causes of the toxicity of the effluent, we applied the assay to the rejected water from the sludge treatment plant, the mixtures of sewage and rejected water. The evolution of HSP production during the aerobic decay process and thickening process of sludge was also examined. These assay results showed that dissolved microbial products generated and/or released from activated sludge during its decay process in the aeration tank and during thickening and dewatering process in the sludge treatment train contributed to develop HSP production. The proteomics analysis was also applied to the effluent and detected the production of elongation factor 1beta. This result implies that the effluent from wastewater treatment plants may cause changes in cell proteins involved in allergic reaction.

Human intestinal cells incubated with activated sludge and lipopolysaccharide express Hsp90b.

Intestinal cells are the first line of defense against toxic substances that may enter the body orally. Some of these substances may emanate from wastewater treatment plants and thus may eventually enter the food chain. In this study, human intestinal Caco-2 cells were incubated with biologically treated activated sludge and lipopolysaccharide (LPS) to determine changes in protein expression and cell monolayer integrity. Caco-2 cells incubated for 3 h with 24-h-aerated activated sludge or 220 microg/ml LPS showed enhanced expression of the heat shock protein 90b (Hsp90b). The results further show that 220 microg/ml LPS is sufficient to irreversibly disrupt tight-junction permeability in 30 min. The Hsp90b expression by the Caco-2 cells incubated with biologically treated activated sludge may be a cellular protective mechanism against LPS-induced stress.