Health, Medicine

Nrf2- and Bach1 May Play a Role in the Modulation of Ultraviolet A-Induced Oxidative Stress by Acetyl-11-Keto-β-Boswellic Acid in Skin Keratinocytes

Background: Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress with damage to various cellular components and concomitant inflammation and carcinogenesis. Objective: The aim of this study is to investigate the protective effect of acetyl-11-keto-β-boswellic acid (AKBA) against UVA radiation on human skin keratinocytes. Methods: HaCaT cells were pretreated with AKBA followed by UVA irradiation. Radiation effects on cell morphology, cell viability, intracellular reactive oxygen species (ROS) levels, and antioxidant enzymes were examined. Results: AKBA reduces UVA irradiation-induced cell viability loss, accompanied by a decreased production of UVA-induced ROS, decreased malondialdehyde, and increased superoxide dismutase expression. In addition, AKBA increased basal and UVA-induced levels of Nrf2 (NF-E2-related factor 2), the redox-sensitive factor, and its target genes NQO1 and heme oxygenase-1 (HO-1), whereas expression of the transcriptional repressor Bach1 (BTB and CNC homology 1) was reduced. Furthermore, the cytoprotective effects of AKBA against UVA-derived oxidative damage were accompanied by modulating expression of inflammatory mediators (i.e., cyclooxygenase-2 and nuclear factor-#x03BA;B) and NOX1. Conclusions: AKBA protects skin cells from UVA-induced damage by modulating inflammatory mediators and/or ROS production. Therefore, AKBA has potential in the development of skin care products.
Skin Pharmacol Physiol 2017;30:13-23

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Health, Medicine

Intact wound repair activity of human mesenchymal stem cells after YM155 mediated selective ablation of undifferentiated human embryonic stem cells

Publication date: Available online 31 January 2017
Source:Journal of Dermatological Science
Author(s): Keun-Tae Kim, Ho-Chang Jeong, C-Yoon Kim, Eun-Young Kim, Si-Hyun Heo, Seung-Ju Cho, Ki-Sung Hong, Hyuk-Jin Cha
BackgroundRisk of teratoma formation during human pluripotent stem cell (hPSC)-based cell therapy is one of the technical hurdles that must be resolved before their wider clinical application. To this end, selective ablation of undifferentiated hPSCs has been achieved using small molecules whose application should be safe for differentiated cells derived from the hPSCs.ObjectiveHowever, the functional safety of such small molecules in the cells differentiated from hPSCs has not yet been extensively validated.MethodWe used the survivin inhibitor YM155, which induced highly selective cell death of hPSCs for ablating undifferentiated hESCs after differentiation to human mesenchymal stem cells (hMSCs) and examined whether hMSCs remained fully functional after being exposed by YM155.ResultsWe demonstrated that human mesenchymal stem cells (hMSCs) derived from human embryonic stem cells (hESCs) remained fully functional in vitro and in vivo, while hESCs were selectively ablated.ConclusionThese results suggest that a single treatment with YM155 after differentiation of hMSCs would be a valid approach for teratoma-free cell therapy.

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Health, Medicine

Perirhinal cortex tracks degree of recent as well as cumulative lifetime experience with object concepts

Publication date: Available online 31 January 2017
Source:Cortex
Author(s): Devin Duke, Chris B. Martin, Ben Bowles, Ken McRae, Stefan Köhler
Evidence from numerous sources indicates that recognition of the prior occurrence of objects requires computations of perirhinal cortex (PrC) in the medial temporal lobe. Extant research has primarily probed recognition memory based on item exposure in a recent experimental study episode. Outside the laboratory, however, familiarity for objects typically accrues gradually with learning across many different episodic contexts, which can be distributed over a lifetime of experience. It is currently unknown whether PrC also tracks this cumulative lifetime experience with object concepts accrued outside the laboratory. To address this issue, we conducted an fMRI experiment in healthy individuals in which we compared judgments of the perceived lifetime familiarity with object concepts, a task that has previously been employed in many normative studies on concept knowledge, with frequency judgments for recent laboratory exposure in a study phase. Guided by neurophysiological data showing that neurons in primate PrC signal prior object exposure at multiple time scales, we predicted that PrC responses would track perceived prior experience in both types of judgments. Left perirhinal cortex and a number of cortical regions that are often co-activated as part of the default-mode network showed an increase in BOLD response in relation to increases in the perceived cumulative lifetime familiarity of object concepts. These regions included the left hippocampus, left mid-lateral temporal cortex, as well as anterior and posterior cortical midline structures. Critically, left PrC was found to be the only region that showed this response in combination with the typically observed decrease in signal for perceived recent exposure in the experimental study phase. These findings provide, to our knowledge, the first evidence tying signals in human PrC to variations in cumulative lifetime experience with object concepts. These results offer a new link between its role in recognition memory and a broader role in conceptual processing.

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Health, Medicine

Action perception as hypothesis testing

Publication date: Available online 31 January 2017
Source:Cortex
Author(s): Francesco Donnarumma, Marcello Costantini, Ettore Ambrosini, Karl Friston, Giovanni Pezzulo
We present a novel computational model that describes action perception as an active inferential process that combines motor prediction (the reuse of our own motor system to predict perceived movements) and hypothesis testing (the use of eye movements to disambiguate amongst hypotheses). The system uses a generative model of how (arm and hand) actions are performed to generate hypothesis-specific visual predictions, and directs saccades to the most informative places of the visual scene to test these predictions – and underlying hypotheses. We test the model using eye movement data from a human action observation study. In both the human study and our model, saccades are proactive whenever context affords accurate action prediction; but uncertainty induces a more reactive gaze strategy, via tracking the observed movements. Our model offers a novel perspective on action observation that highlights its active nature based on prediction dynamics and hypothesis testing.

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Health, Medicine

Current update on the diagnosis and management of head and neck soft-tissue sarcomas

Abstract

Head and neck soft tissue sarcomas are a group of rare heterogeneous tumours arising from embryonic mesoderm. They comprise less than 1% of all head and neck malignancies and 5-15% of all sarcomas with most head and neck sarcomas arising from soft tissues. Although rare, they are associated with both high recurrence and mortality rates. We review the current management of head and neck soft tissue sarcomas.

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Health, Medicine

Antioxidative and anticancer properties of Licochalcone A from licorice

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Xiangrong Chen, Zuojia Liu, Rizeng Meng, Ce Shi, Na Guo
Ethnopharmacological relevanceLicochalcone A (LCA) is a characteristic chalcone that is found in licorice, which is a traditional medicinal plant. In traditional medicine, LCA possesses many potential biological activities, including anti-parasitic, anti-inflammatory and antitumor activities.Aim of the studyTo determine the antioxidant activity of LCA and, on this basis, to investigate the role of its anticancer activity.Materials and methodsTo validate the antioxidant activity of LCA, the proteins SOD, CAT and GPx1 were analyzed using western blotting and cellular antioxidant activity (CAA) assays. Oxidative free radicals are associated with cancer cells. Therefore, the anticancer activity of LCA was also evaluated. To assess the anticancer activity, cell viability assays were performed and apoptosis was evaluated. In addition, MAPK-related proteins were analyzed using western blotting.ResultsThe experimental data showed that the EC50 of LCA is 58.79±0.05μg/mL and 46.29±0.05μg/mL under the two conditions tested, with or without PBS. In addition, LCA at a concentration of approximately 2–8μg/mL can induce the expression of SOD, CAT and GPx1 proteins. Further, LCA inhibits the growth of HepG2 cells through cell proliferation arrest and the subsequent induction of apoptosis, and LCA attenuated the p38/JNK/ERK signaling pathway in a dose-dependent manner.ConclusionThe results showed that LCA suppresses the oxidation of cells and markedly inhibits the proliferation of cancer cells. These findings confirm the traditional use of LCA in folk medicine.

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Health, Medicine

Anti-malarial synergy of secondary metabolites from Morinda lucida Benth

Publication date: Available online 30 January 2017
Source:Journal of Ethnopharmacology
Author(s): Bertha Chithambo, Xavier Siwe Noundou, Rui W.M. Krause
Ethnopharmacological relevanceThe roots, stem and leaves of Morinda lucida are used in some African countries as treatment against different types of fevers including yellow fever, malaria, trypanosomiasis and feverish conditions during child birth.Aim of the studyTo determine the in vitro cell toxicity and anti-malarial activity of the extracts of stem bark of M. lucida and to identify the secondary metabolites in the extract that may be responsible for this activity.Materials and methodsThe cell toxicity studies of crude extract [dichloromethane (DCM):Methanol (MeOH) in a ratio of1:1 (v/v)] as well as compounds isolated from the same extract were carried out using human cervix adenocarcinoma cells (HeLa cells); while the anti-malarial activities of the same samples were performed against Plasmodium falciparum strain 3D7 using the parasite lactate dehydrogenase (pLDH) assay. The isolation of the active compounds was carried out using chromatographic techniques (column and thin layer chromatography) where as mass spectrometry (MS), Fourier transform infrared spectroscopy (FTIR) as well as 1D- and 2D- nuclear magnetic resonance (NMR) analyses were employed in the characterisation and identification of the isolated secondary metabolites.ResultsThe pLDH and cell toxicity assays for the crude extract and the fractions of M. lucida indicated that some fractions reduced the malaria parasite viability by approximately 50% at 100μg/mL and they were not significantly cytotoxic. An IC50 done on the crude extract gave a value of 25μg/mL. The % cell viability for the crude extract in cell toxicity assay remained at 100%. Seven chemical constituents i.e. asperuloside (1), asperulosidic acid (2), stigmasterol (3a), β-sitosterol (3b), cycloartenol (3c), campesterol (3d) and 5,15-O-dimethylmorindol (4) were isolated from the DCM-MeOH extract of stem bark. The isolated compounds tested were not that active by themselves individually at 20μM but their activities were increased when the isolated compounds were combined. As seen when compounds 2, 3 and 4 (% viability: 93, 123 and 101 respectively) were combined yielding an IC50 value of 17μM. Furthermore, this is the first report of compounds 1, 2, 3c, 3d and 4 isolated from M. lucida.ConclusionThe crude extract completely suppressed the growth of P. falciparum. This indicates that the crude extract contains many compounds that might be acting in synergy. The observed activity of the crude extract and the samples containing a mixture of different compounds support the traditional use of M. lucida for the treatment of malaria.

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