Mechanistic studies of anti-hyperpigmentary compounds: elucidating their inhibitory and regulatory actions.

Searching for depigmenting agents from natural sources has become a new direction in the cosmetic industry as natural products are generally perceived as relatively safer. In our previous study, selected Chinese medicines traditionally used to treat hyperpigmentation were tested for anti-hyperpigmentary effects using a melan-a cell culture model. Among the tested chemical compounds, 4-ethylresorcinol, 4-ethylphenol and 1-tetradecanol were found to possess hypopigmentary effects. Western blot analysis, reverse transcriptase polymerase chain reaction (RT-PCR), cyclic adenosine monophosphate (cAMP) assay, protein kinase A (PKA) activity assay, tyrosinase inhibition assay and lipid peroxidation inhibition assay were performed to reveal the underlying cellular and molecular mechanisms of the hypopigmentary effects. 4-Ethylresorcinol and 4-ethylphenol attenuated mRNA and protein expression of tyrosinase-related protein (TRP)-2, and possessed antioxidative effect by inhibiting lipid peroxidation. 1-Tetradecanol was able to attenuate protein expression of tyrosinase. The hypopigmentary actions of 4-ethylresorcinol, 4-ethylphenol and 1-tetradecanol were associated with regulating downstream proteins along the PKA pathway. 4-Ethylresorcinol was more effective in inhibiting melanin synthesis when compared to 4-ethylphenol and 1-tetradecanol

Stochastic separated flow models with applications in numerical computations of supersonic particle-laden turbulent flows

In this article, three stochastic separated flow models were applied to predict the dispersion of inertial fuel particles in the supersonic turbulent flows. The flow field of continuous phase was simulated by means of Reynolds-averaged Navier–Stokes method with a two-equation turbulence model. Clift’s expression was used to modify the drag force on the particle considering the compressibility effects. The particle-phase statistics were obtained by a secondary-order time-weighed Eulerian method. The ability of those stochastic separated flow models was then compared for predicting the mean particle velocity and the particle dispersion. For obtaining a statistically stationary solution, the stochastic separated flow model required the largest number of computational particles, whereas the improved stochastic separated flow model was found to need the least. The time-series stochastic separation flow model lay in-between. Compared with the other two models, the particle dispersion was over-predicted by the stochastic separated flow model in the supersonic particle-laden boundary layer flow, while the improved stochastic separated flow model was less predictable for the particle spatial distribution in the particle-laden strut-injection flow. Three models could well predict the mean velocities of the particle phase. This study is valuable for selecting a validated model used for predicting the particle dispersion in supersonic turbulent flows

Genetic diversity among Toxoplasma gondii isolates from different hosts and geographical locations revealed by analysis of ROP13 gene sequences

Toxoplasma gondii can infect almost all the warm-blooded animals and human beings, causing serious public health problems and economic losses worldwide. Rhoptry protein 13 (ROP13) plays some roles in the invasion process of T. gondii. In this study, sequence variation in ROP13 gene among 14 T. gondii isolates from different geographical locations and hosts was examined. The ROP13 gene was amplified from individual isolates and sequenced. Results show that the length of the ROP13 sequences was 1203 bp. In total, there were 44 variable nucleotide positions in the ROP13 sequences, and sequence variations were 0.1 to 2.0% among the 14 examined T. gondii isolates, representing higher rate in transversion than in transition. Intra-specific nucleotide variations were mainly at the second codon positions. Phylogenetic analysis of the 14 examined T. gondii isolates indicate that the ROP13 sequence was not a suitable genetic marker to differentiate T. gondii isolates of different genotypes from different hosts and geographical regions. Low variation in ROP13 gene sequence may suggest that ROP13 gene could represent a good vaccine candidate against toxoplasmosis.Key words: Toxoplasma gondii, toxoplasmosis, rhpotry protein 13 (ROP13), sequence variation, phylogenetic analysis

A Vibrant Community of Readers, Authors and Reviewers: A Medical Editors' Necessity and a Challenge for Medical Education

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Potential of herbal medicine in protecting neurons in neurodegenerative diseases

This journal suppl. entitled: Alzheimer's and Parkinson's Diseases: Advances, Concepts and New Challenges - 9th International Conference AD/PD ... 2009: abstractsAlzheimer's disease (AD) is a multi-factorial disease in which β-amyloid peptide, oxidative stress, and inflammatory factors contribute to certain level of toxic effects to neurons. Similar to multi-hit theory in cancer cell development, neurons receive different endogenous toxins at different pathological states. It is important to find neuroprotective agent that can fight against different toxins. Therefore, we focus on finding certain chemicals from herbal medicine that can provide neuroprotection …postprin

The Nrf2 inhibitor brusatol is a potent antitumour agent in an orthotopic mouse model of colorectal cancer

© Evans et al. Nrf2 is a transcription factor that regulates cellular stress response and irinotecan-metabolising pathways. Its aberrant activity has been reported in a number of cancers, although relatively few studies have explored a role for Nrf2 in colorectal cancer (CRC). This study assessed the expression of Nrf2 in patient CRC tissues and explored the effect of Nrf2 modulation alone, or in combination with irinotecan, in human (HCT116) and murine (CT26) cell lines in vitro and in an orthotopic syngeneic mouse model utilising bioluminescent imaging. Using a tissue microarray, Nrf2 was found to be overexpressed (p < 0.01) in primary CRC and metastatic tissue relative to normal colon, with a positive correlation between Nrf2 expression in matched primary and metastatic samples. In vitro experiments in CRC cell lines revealed that Nrf2 siRNA and brusatol, which is known to inhibit Nrf2, decreased viability and sensitised cells to irinotecan toxicity. Furthermore, brusatol effectively abrogated CRC tumour growth in subcutaneously and orthotopicallyallografted mice, resulting in an average 8-fold reduction in luminescence at the study end-point (p=0.02). Our results highlight Nrf2 as a promising drug target in the treatment of CRC

Evidence for Anthropogenic Surface Loading as Trigger Mechanism of the 2008 Wenchuan Earthquake

Two and a half years prior to China's M7.9 Wenchuan earthquake of May 2008, at least 300 million metric tons of water accumulated with additional seasonal water level changes in the Minjiang River Valley at the eastern margin of the Longmen Shan. This article shows that static surface loading in the Zipingpu water reservoir induced Coulomb failure stresses on the nearby Beichuan thrust fault system at <17km depth. Triggering stresses exceeded levels of daily lunar and solar tides and perturbed a fault area measuring 416+/-96km^2. These stress perturbations, in turn, likely advanced the clock of the mainshock and directed the initial rupture propagation upward towards the reservoir on the "Coulomb-like" Beichuan fault with rate-and-state dependent frictional behavior. Static triggering perturbations produced up to 60 years (0.6%) of equivalent tectonic loading, and show strong correlations to the coseismic slip. Moreover, correlations between clock advancement and coseismic slip, observed during the mainshock beneath the reservoir, are strongest for a longer seismic cycle (10kyr) of M>7 earthquakes. Finally, the daily event rate of the micro-seismicity (M>0.5) correlates well with the static stress perturbations, indicating destabilization.Comment: 22 pages, 4 figures, 3 table

Facile Synthesis of High Quality Graphene Nanoribbons

Graphene nanoribbons have attracted attention for their novel electronic and spin transport properties1-6, and because nanoribbons less than 10 nm wide have a band gap that can be used to make field effect transistors. However, producing nanoribbons of very high quality, or in high volumes, remains a challenge. Here, we show that pristine few-layer nanoribbons can be produced by unzipping mildly gas-phase oxidized multiwalled carbon nanotube using mechanical sonication in an organic solvent. The nanoribbons exhibit very high quality, with smooth edges (as seen by high-resolution transmission electron microscopy), low ratios of disorder to graphitic Raman bands, and the highest electrical conductance and mobility reported to date (up to 5e2/h and 1500 cm2/Vs for ribbons 10-20 nm in width). Further, at low temperature, the nanoribbons exhibit phase coherent transport and Fabry-Perot interference, suggesting minimal defects and edge roughness. The yield of nanoribbons was ~2% of the starting raw nanotube soot material, which was significantly higher than previous methods capable of producing high quality narrow nanoribbons1. The relatively high yield synthesis of pristine graphene nanoribbons will make these materials easily accessible for a wide range of fundamental and practical applications.Comment: Nature Nanotechnology in pres