Optimal Treatment of Tumor in Upper Human Respiratory Tract Using Microaerosols.

Lung cancer is a frequently diagnosed respiratory disease caused by particulate matter in the environment, especially among older individuals. For its effective treatment, a promising approach involves administering drug particles through the inhalation route. Multiple studies have investigated the flow behavior of inhaled particles in the respiratory airways of healthy patients. However, the existing literature lacks studies on the precise understanding of the transportation and deposition (TD) of inhaled particles through age-specific, unhealthy respiratory tracts containing a tumor, which can potentially optimize lung cancer treatment. This study aims to investigate the TD of inhaled drug particles within a tumorous, age-specific human respiratory tract. The computational model reports that drug particles within the size range of 5-10 µm are inclined to deposit more on the tumor located in the upper airways of a 70-year-old lung. Conversely, for individuals aged 50 and 60 years, an optimal particle size range for achieving the highest degree of particle deposition onto upper airway tumor falls within the 11-20 µm range. Flow disturbances are found to be at a maximum in the airway downstream of the tumor. Additionally, the impact of varying inhalation flow rates on particle TD is examined. The obtained patterns of airflow distribution and deposition efficiency on the tumor wall for different ages and tumor locations in the upper tracheobronchial airways would be beneficial for developing an efficient and targeted drug delivery system.

The Mechanistic Role of Thymoquinone in Parkinson's Disease: Focus on Neuroprotection in Pre-Clinical Studies.

Thymoquinone (TQ) is one of the leading phytochemicals, which is abundantly found in Nigella sativa L. seeds. TQ exhibited various biological effects such as antioxidant, anti-inflammatory, antimicrobial, and anti-tumoral in several pre-clinical studies. Parkinson's disease (PD) is a long-term neurodegenerative disease with movement difficulties, and the common feature of neurodegeneration in PD patients is caused by dopaminergic neural damage in the substantia nigra pars compacta. The neuroprotective activity of TQ has been studied in various neurological disorders. TQ-mediated neuroprotection against PD is yet to be reported in a single frame; therefore, this review is intended to narrate the potentiality of TQ in the therapy of PD. TQ has been shown to protect against neurotoxins via amelioration of neuroinflammation, oxidative stress, and apoptosis, thereby protecting neurodegeneration in PD models. TQ could be an emerging therapeutic intervention in PD management, but mechanistic studies remain to be investigated to clarify its neuroprotective role.

Radiation response of mesenchymal stem cells derived from bone marrow and human pluripotent stem cells.

Mesenchymal stem cells (MSCs) isolated from human pluripotent stem cells are comparable with bone marrow-derived MSCs in their function and immunophenotype. The purpose of this exploratory study was comparative evaluation of the radiation responses of mesenchymal stem cells derived from bone marrow- (BMMSCs) and from human embryonic stem cells (hESMSCs). BMMSCs and hESMSCs were irradiated at 0 Gy (control) to 16 Gy using a linear accelerator commonly used for cancer treatment. Cells were harvested immediately after irradiation, and at 1 and 5 days after irradiation. Cell cycle analysis, colony forming ability (CFU-F), differentiation ability, and expression of osteogenic-specific runt-related transcription factor 2 (RUNX2), adipogenic peroxisome proliferator-activated receptor gamma (PPARγ), oxidative stress-specific dismutase-1 (SOD1) and Glutathione peroxidase (GPX1) were analyzed. Irradiation arrested cell cycle progression in BMMSCs and hESMSCs. Colony formation ability of irradiated MSCs decreased in a dose-dependent manner. Irradiated hESMSCs showed higher adipogenic differentiation compared with BMMSCs, together with an increase in the adipogenic PPARγ expression. PPARγ expression was upregulated as early as 4 h after irradiation, along with the expression of SOD1. More than 70% downregulation was found in Wnt3A, Wnt4, Wnt 7A, Wnt10A and Wnt11 in BMMSCs, but not in hESMSCs. hESMSCs are highly proliferative but radiosensitive compared with BMMSCs. Increased PPARγ expression relative to RUNX2 and downregulation of Wnt ligands in irradiated MSCs suggest Wnt mediated the fate determination of irradiated MSCs.

Characterization of timed changes in hepatic copper concentrations, methionine metabolism, gene expression, and global DNA methylation in the Jackson toxic milk mouse model of Wilson disease.

BACKGROUND: Wilson disease (WD) is characterized by hepatic copper accumulation with progressive liver damage to cirrhosis. This study aimed to characterize the toxic milk mouse from The Jackson Laboratory (Bar Harbor, ME, USA) (tx-j) mouse model of WD according to changes over time in hepatic copper concentrations, methionine metabolism, global DNA methylation, and gene expression from gestational day 17 (fetal) to adulthood (28 weeks). METHODS: Included liver histology and relevant biochemical analyses including hepatic copper quantification, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) liver levels, qPCR for transcript levels of genes relevant to methionine metabolism and liver damage, and DNA dot blot for global DNA methylation. RESULTS: Hepatic copper was lower in tx-j fetuses but higher in weanling (three weeks) and adult tx-j mice compared to controls. S-adenosylhomocysteinase transcript levels were significantly lower at all time points, except at three weeks, correlating negatively with copper levels and with consequent changes in the SAM:SAH methylation ratio and global DNA methylation. CONCLUSION: Compared to controls, methionine metabolism including S-adenosylhomocysteinase gene expression is persistently different in the tx-j mice with consequent alterations in global DNA methylation in more advanced stages of liver disease. The inhibitory effect of copper accumulation on S-adenosylhomocysteinase expression is associated with progressively abnormal methionine metabolism and decreased methylation capacity and DNA global methylation.

Maternal choline modifies fetal liver copper, gene expression, DNA methylation, and neonatal growth in the tx-j mouse model of Wilson disease.

Maternal diet can affect fetal gene expression through epigenetic mechanisms. Wilson disease (WD), which is caused by autosomal recessive mutations in ATP7B encoding a biliary copper transporter, is characterized by excessive hepatic copper accumulation, but variability in disease severity. We tested the hypothesis that gestational supply of dietary methyl groups modifies fetal DNA methylation and expression of genes involved in methionine and lipid metabolism that are impaired prior to hepatic steatosis in the toxic milk (tx-j) mouse model of WD. Female C3H control and tx-j mice were fed control (choline 8 mmol/Kg of diet) or choline-supplemented (choline 36 mmol/Kg of diet) diets for 2 weeks throughout mating and pregnancy to gestation day 17. A second group of C3H females, half of which were used to cross foster tx-j pups, received the same diet treatments that extended during lactation to 21 d postpartum. Compared with C3H, fetal tx-j livers had significantly lower copper concentrations and significantly lower transcript levels of Cyclin D1 and genes related to methionine and lipid metabolism. Maternal choline supplementation prevented the transcriptional deficits in fetal tx-j liver for multiple genes related to cell growth and metabolism. Global DNA methylation was increased by 17% in tx-j fetal livers after maternal choline treatment (P<0.05). Maternal dietary choline rescued the lower body weight of 21 d tx-j mice. Our results suggest that WD pathogenesis is modified by maternal in utero factors, including dietary choline.

Estimating sub-surface dispersed oil concentration using acoustic backscatter response.

The recent Deepwater Horizon disaster resulted in a dispersed oil plume at an approximate depth of 1000 m. Several methods were used to characterize this plume with respect to concentration and spatial extent including surface supported sampling and autonomous underwater vehicles with in situ instrument payloads. Additionally, echo sounders were used to track the plume location, demonstrating the potential for remote detection using acoustic backscatter (ABS). This study evaluated use of an Acoustic Doppler Current Profiler (ADCP) to quantitatively detect oil-droplet suspensions from the ABS response in a controlled laboratory setting. Results from this study showed log-linear ABS responses to oil-droplet volume concentration. However, the inability to reproduce ABS response factors suggests the difficultly in developing meaningful calibration factors for quantitative field analysis. Evaluation of theoretical ABS intensity derived from the particle size distribution provided insight regarding method sensitivity in the presence of interfering ambient particles.

Human embryonic stem cell-derived CD34+ cells function as MSC progenitor cells.

Mesenchymal stem/stromal cells (MSCs) have been isolated from various tissues and utilized for an expanding number of therapies. The developmental pathways involved in producing MSCs and the phenotypic precursor/progenitor cells that give rise to human MSCs remain poorly defined. Human embryonic stem cells (hESCs) have the capability to generate functional hemato-endothelial cells and other mesoderm lineage cells. hESC-derived CD73(+) cells have been isolated and found to have similar phenotypic and functional characteristics as adult MSCs. Here we demonstrate hESC-derived CD34(+)CD73(-) cells can serve as MSC progenitor cells with the ability to differentiate into adipocytes, osteoblasts and chondrocytes. Additionally, gene array analysis of hESC-derived MSCs show substantially different gene expression compared to bone marrow (BM)-derived MSCs, especially with increased expression of pluripotent and multipotent stem cell and endothelial cell-associated genes. The isolation of functional MSCs from hESC-derived CD34(+)CD73(-) cells provides improved understanding of MSC development and utilization of pluripotent stem cells to produce MSCs suited for novel regenerative therapies.

Determination of benzene, toluene, ethylbenzene and xylene in river water by solid-phase extraction and gas chromatography.

A rapid and reproducible method is described that employs solid-phase extraction (SPE) using dichloromethane, followed by gas chromatography (GC) with flame ionization detection for the determination of benzene, toluene, ethylbenzene, xylene and cumene (BTEXC) from Buriganga River water of Bangladesh. The method was applied to detect BTEXC in a sample collected from the surface, or 5 cm depth of water. Two-hundred milliliters of n-hexane-pretreated and filtered water samples were applied directly to a C18 SPE column. BTEXC were extracted with dichloromethane and the BTEX concentrations were obtained to be 0.1 to 0.37 microg ml(-1). The highest concentration of benzene was found as 0.37 microg ml(-1) with a relative standard deviation (RSD) of 6.2%; cumene was not detected. The factors influencing SPE e.g., adsorbent types, sample load volume, eluting solvent, headspace and temperatures, were investigated. A cartridge containing a C18 adsorbent and using dichloromethane gave a better performance for the extraction of BTEXC from water. Average recoveries exceeding 90% could be achieved for cumene at 4 degrees C with a 2.7% RSD.