Sodium tanshinone IIA silate increases melanin synthesis by activating the MAPK and PKA pathways and protects melanocytes from H2O2-induced oxidative stress

Vitiligo is an intriguing depigmentation disorder that affects about 0.5–2% of the world population. In the past decade, first-line treatments of vitiligo have involved the use of calcineurin inhibitors and corticosteroids. Sodium tanshinone IIA sulfonate (STS) has been widely applied in the treatment of cardiovascular and cerebrovascular diseases in China. In the present study, the effect of STS on melanogenesis was confirmed in the B16F10 cells and zebrafish by direct observation. The prevention of hydrogen peroxide (H₂O₂)-induced oxidative stress has been proven to be beneficial to vitiligo patients, and STS that can protect the B16F10 cells against oxidative stress has been investigated in the present reversed study. Moreover, we found that pre-treatment with STS led to a concentration-dependent mitochondrial impairment and decreased cell apoptosis of the B16F10 cells in response to H₂O₂. In addition, we demonstrated that STS increased melanin synthesis in the B16F10 cells by activating the mitogen-activated protein kinase (MAPK) and protein kinase A (PKA) pathways. STS also increased the Cdc42 and KIF5b expression to stimulate the translocation of melanin. These results suggest that STS protects the B16F10 cells against H₂O₂-induced oxidative stress and exerts melanin synthesis activity in the B16F10 cells by activating the MAPK and PKA pathways; thus, it shows therapeutic potential for vitiligo.

Vitiligo is an intriguing depigmentation disorder that affects about 0.5–2% of the world population.     

Solvent-dependent regio- and stereo-selective reactions of 3-formylchromones with 2-aminobenzothiazoles and transacetalization efficiency of the product 3-((benzo[d]thiazol-2-ylimino)butyl)-4H-chromen-4-one

Using 2-propanol as the solvent, 3-formylchromones and 2-aminobenzothiaoles formed corresponding imines, while 1° and 2°-alcohols formed the corresponding 2-alkoxy-3-enamines with selectivity for the Z-isomer. Changing the substrates with similar molecules such as 3-formylchromone with quinoline-, quinolone- and indole-3-carbaldehydes sometimes resulted in the formation of the corresponding imines, whereas replacing 2-aminobenzothiazole with amides resulted in the formation of acetals. Considering the effect of the solvent, replacing alcohols with the aprotic solvents THF and CH₂Cl₂ resulted in the formation of imines and enamines, which are the characteristic reactions of 2-propanol and other 1° and 2°-alcohols, respectively. 2-Alkoxy-3-enamines were found to undergo transacetalization with both short and long chain alcohols. The novelty of these reactions is that they did not require an external catalyst, all the reactions were performed at the same temperature, and purification was achieved by filtration. The transacetalization we performed herein is a new concept, which has not been reported to date. In contrast, other similar reactions, such as transalkoxylation, transalkylation, and transetherification, are performed on a commercial scale using expensive catalysts such as Otera''s catalyst. The highly sensitive nature of 3-formylchromones towards variations in the substrates and solvents to form different products and the reason behind the selective formation of the Z-isomer of 2-alkoxy-3-enamines and its transacetalization efficiency need further studies to understand the reaction mechanism and possibly other factors such as solvent effects.

2-Propanol forms lmine (4), other alcohols forms enamine (3) which can undergo transacetalization and replacing 2 with amides forms acetals (5).     

Excision of a left atrial myxoma via a minimally-invasive technique: a possible routine access

We would like to present our experience of surgical excision of intracardiac tumors using a video-assisted minimally-invasive cardiac surgery (MIC) technique. An 83-year-old female patient received video-assisted cardiac surgery for excision of a left atrial tumor. The surgery was performed through a right anterior submammary minithoracotomy and guided by video-assisted endoscopic techniques by projected images on a video monitor while under femoro-femoral bypass. The myocardium was protected by single-dose antegrade crystalloid cardioplegia. The tumor was excised completely recording a 61-minute bypass time and a 103-minute total operative time. Histopathological examination revealed left atrial myxoma. Transthoracic echocardiography examination showed good ventricular function and the absence of residual tumors. The patient was satisfied by the cosmetic healing of the wound and was discharged eight days after the surgery. Video-assisted MIC surgery is technically feasible and could be applied as a routine access in all left atrial tumors without the fear of inadequate intraoperative exposure and its drawbacks.     

Immunomodulator tuftsin increases the susceptibility of Cryptococcus neoformans to liposomal amphotericin B in immunocompetent BALB/c mice

The co-administration of immunomodulators and antibiotics has been proved very successful for treatment of opportunistic infectious diseases. In the present study, we evaluated the combination of liposomal amphotericin B (lip-Amp B) and immunomodulator tuftsin to cure Cryptococcus neoformans infection in BALB/c mice. Mice infected with C. neoformans were treated with Amp B deoxycholate and tuftsin free or tuftsin-loaded Amp B liposomes. The results of the present study demonstrated higher efficacy of tuftsin-loaded Amp B liposomes against experimental murine cryptococcosis, in terms of enhanced survival rate and reduced fungal burden in organs (lungs and brain) of the treated mice. Interestingly, pre-treatment of mice with liposomal tuftsin before challenging them with the C. neoformans infection resulted in 100% survival of the treated animals followed by treatment with lip-Amp B. Immunomodulator-based therapy seems likely to be more beneficial for treatment of fungal infectious diseases.     

Immunomodulator Effect of Picroliv and its Potential in Treatment Against Resistant Plasmodium yoelii (MDR) Infection in Mice

PURPOSE: The present study was envisaged to evaluate potential of combination therapy comprising of immunomodulator picroliv and antimalarial chloroquine against drug resistant Plasmodium yoelii (P. yoelii) infection in BALB/c mice. METHODS: The immunomodulatory potential of picroliv was established by immunizing animals with model antigen along with picroliv. Immune response was assessed using T-cell proliferation assay and also by determining the antibody isotype-profile induced in the immunized mice. In the next set of experiment, prophylactic potential of picroliv to strengthen antimalarial properties of chloroquine against P. yoelii (MDR) infection in BALB/c mice was assessed. RESULTS: T-cell proliferation as well as antibody production study reveals that picroliv helps in evoking strong immuno-potentiating response against model antigen in the immunized mice. Co-administration of picroliv enhances efficacy of CHQ against experimental murine malaria. CONCLUSION: The activation of host immune system can increase the efficacy of chloroquine for suppression of drug resistant malaria infection in BALB/c mice.     

Spatiotemporal calibration and resolution refinement of output from deterministic models

Spatiotemporal calibration of output from deterministic models is an increasingly popular tool to more accurately and efficiently estimate the true distribution of spatial and temporal processes. Current calibration techniques have focused on a single source of data on observed measurements of the process of interest that are both temporally and spatially dense. Additionally, these methods often calibrate deterministic models available in grid‐cell format with pixel sizes small enough that the centroid of the pixel closely approximates the measurement for other points within the pixel. We develop a modeling strategy that allows us to simultaneously incorporate information from two sources of data on observed measurements of the process (that differ in their spatial and temporal resolutions) to calibrate estimates from a deterministic model available on a regular grid. This method not only improves estimates of the pollutant at the grid centroids but also refines the spatial resolution of the grid data. The modeling strategy is illustrated by calibrating and spatially refining daily estimates of ambient nitrogen dioxide concentration over Connecticut for 1994 from the Community Multiscale Air Quality model (temporally dense grid‐cell estimates on a large pixel size) using observations from an epidemiologic study (spatially dense and temporally sparse) and Environmental Protection Agency monitoring stations (temporally dense and spatially sparse). Copyright © 2016 John Wiley & Sons, Ltd.     

CuO Bionanocomposite with Enhanced Stability and Antibacterial Activity against Extended-Spectrum Beta-Lactamase Strains

Worldwide, bacterial resistance to beta-lactam antibiotics is the greatest challenge in public health care. To overcome the issue, metal-based nanoparticles were extensively used as an alternative to traditional antibiotics. However, their unstable nature limits their use. In the present study a very simple, environmentally friendly, one-pot synthesis method that avoids the use of organic solvents has been proposed to design stable, novel nanocomposites. Formulation was done by mixing biogenic copper oxide (CuO) nanomaterial with glycerol and phospholipids isolated from egg yolk in an appropriate ratio at optimum conditions. Characterization was done using dynamic light scattering DLS, Zeta potential, high performance liquid chromatography (HPLC), and transmission electron microscopy (TEM). Further, its antibacterial activity was evaluated against the extended-spectrum beta-lactamase strains based on zone of inhibition and minimal inhibitory concentration (MIC) indices. Results from this study have demonstrated the formulation of stable nanocomposites with a zeta potential of 34.9 mV. TEM results indicated clear dispersed particles with an average of 59.3 ± 5 nm size. Furthermore, HPLC analysis of the egg yolk extract exhibits the presence of phospholipids in the sample and has significance in terms of stability. The newly formed nanocomposite has momentous antibacterial activity with MIC 62.5 μg/mL. The results suggest that it could be a good candidate for drug delivery in terms of bactericidal therapeutic applications.