Microarray based gene expression profiling of advanced gall bladder cancer.

BACKGROUND: Gall bladder cancer (GBC) is an aggressive cancer with specific predilection like female gender and specific geographical areas, however the molecular mechanisms and factors contributing to the clinical or biological behavior are not understood. AIM: The aim of this study was to perform a comprehensive analysis of differentially expressed genes in advanced GBC and chronic cholecystitis (CC) cases. MATERIALS AND METHODS: Microarray was planned on fresh specimens of advanced GBC and CC cases using single color cRNA based microarray technique (8X60K format; Agilent Technologies, USA). Twelve advanced GBC and four CC patients were included in the study. RESULTS: Of the total of 1307 differentially expressed genes, 535 genes were significantly upregulated, while 772 genes were significantly downregulated in advanced GBC vs CC samples. Differentially expressed genes were associated with biological processes (55.03%), cellular components (31.48%), and molecular functions (13.49%) respectively. The important pathways or key processes affected were cell cycle, DNA replication, oxidative stress, gastric cancer pathway. Using in silico analysis tools, three differentially expressed genes i.e. TPX2, Cdc45 and MCM4 were selected (for their significant role in DNA replication and microtubule function) and were further validated in 20 advanced GBC cohort by immunohistochemistry. Significant positive association of Cdc45 and MCM4 proteins was found in advanced GBC cases (p = 0.043), suggesting the probable oncogenic role of Cdc45 and MCM4 proteins in advanced GBC. CONCLUSION: Our data demonstrate the potential regulation of Cdc45-MCM4 axis in advanced GBC tumors. Additionally, our study also revealed a range of differentially expressed genes (e.g. TPX2, AKURA etc.) between GBC and CC, and further validation of these genes might provide a potential diagnostic or therapeutic target in future.

Evaluation of retrobulbar circulation in type 2 diabetic patients using color Doppler imaging.

Purpose: To investigate the retrobulbar circulatory parameters in type 2 diabetes mellitus patients with color Doppler imaging (CDI) and compare the results with nondiabetic controls. Methods: This prospective study included 50 type 2 diabetic patients and 50 age-matched controls. Seven field stereo fundus photography was used to diagnose and classify diabetic retinopathy (DR). Diabetic patients were further divided into two: Group 1, consisted of patients with no DR, mild and moderate non-proliferative DR (n = 36); Group 2, severe nonproliferative and proliferative DR (n = 14). CDI was performed using Philips iU22 xMATRIX ultrasound. The peak systolic velocity (PSV), end-diastolic velocity (EDV), resistivity index (RI) and pulsatile index (PI) of ophthalmic (OA), posterior ciliary artery (PCA), and central retinal artery (CRA) along with central retinal vein (CRV) were recorded. Results: RI in the ophthalmic artery was significantly higher in both DR groups than the control group (P = 0.000). Diabetic Group 1 had decreased blood flow velocity (PSV and EDV) in PCA compared to controls (P = 0.046 and P = 0.010, respectively). Group 2 DR had significantly reduced EDV and increased RI in CRA compared to Group 1 (P = 0.015). Binary logistic regression analysis revealed glycosylated hemoglobin and RI of OA to be independent risk factors of DR. Conclusion: Significant changes in resistivity index and flow velocities were observed in the retrobulbar vessels, especially in ophthalmic artery in diabetics compared to controls. CDI with results of increased resistance or decreased flow could be useful to predict individuals at higher risk for developing severe DR.

Adaptive hybrid intelligent MPPT controller to approximate effectual wind speed and optimal rotor speed of variable speed wind turbine.

Operating wind power generation system at optimal power point is essential which is achieved by employing a Maximum Power Point Tracking (MPPT) control strategy. This literature focuses on developing a novel particle swarm optimization algorithm enhanced radial basis function neural network supported TSR based MPPT control strategy for Doubly Fed Induction Generator (DFIG) based wind power generation system. The proposed hybrid MPPT control strategy estimates the effective wind speed and estimates the optimal rotor speed of the wind power generation system to track the maximum power. The proposed controller extremely reduces the speed dissimilarity range of wind power generation system, which leads to rationalizing the pulse width inflection of DFIG rotor side converter. This in turn, increases the system's reliability and delivers an effective power tracking with reduced converter losses. Furthermore, by utilizing the proposed MPPT controller, the converter size can be reduced to 40%. Therefore, the overall cost of the system can be gradually decreased. To validate the performance of the proposed MPPT controller, an extensive simulation study has been carried out under medium and high wind speed conditions in MATLAB/Simulink. The obtained results have been justified using experimental analysis.

Cytocompatible chitosan-graft-mPEG-based 5-fluorouracil-loaded polymeric nanoparticles for tumor-targeted drug delivery.

Biodegradable materials like chitosan (CH) and methoxy polyethylene glycol (mPEG) are widely being used as drug delivery carriers for various therapeutic applications. In this study, copolymer (CH-g-mPEG) of CH and carboxylic acid terminated mPEG was synthesized by carbodiimide-mediated acid amine reaction. The resultant hydrophilic copolymer was characterized by Fourier transform infrared spectroscopy and 1H NMR studies, revealing its relevant functional bands and proton peaks, respectively. Blank polymeric nanoparticles (B-PNPs) and 5-fluorouracil loaded polymeric nanoparticles (5-FU-PNPs) were formulated by ionic gelation method. Furthermore, folic acid functionalized FA-PNPs and FA-5-FU-PNPs were prepared for folate receptor-targeted drug delivery. FA-5-FU-PNPs were characterized by particle size, zeta potential, and in vitro drug release studies, resulting in 197.7 nm, +29.9 mv, and sustained drug release of 88% in 24 h, respectively. Cytotoxicity studies were performed for FA-PNPs and FA-5-FU-PNPs in MCF-7 cell line, which exhibited a cell viability of 80 and 41%, respectively. In vitro internalization studies were carried out for 5-FU-PNPs and FA-5-FU-PNPs which demonstrated increased cellular uptake of FA-5-FU-PNPs by receptor-mediated transport. Significant (p < .01) reduction (1.5-fold) of reactive oxygen species (ROS) accumulation was observed in lipopolysaccharides-stimulated RAW264.7 macrophages, revealing its potent antioxidant property. From the obtained results, it is concluded that folic acid functionalization of 5-FU-PNPs is an ideal approach for sustained and targeted drug delivery, thereby influencing better therapeutic effect.

Recent Trends of Biocompatible and Biodegradable Nanoparticles in Drug Delivery: A Review.

A vast amount of research on nanoparticles has been conducted in recent years with versatile applications in the field of drug delivery systems. Nanoparticles are designed as a carrier molecule to deliver drugs in a sustained and stimuli response manner. Recent advances in nanotechnology have led to the development of long circulating nanoparticles with high encapsulation efficiency. This article focuses on the properties such as biocompatibility and biodegradability, which are considered as essential criteria for nanoparticles to be successfully used as a carrier molecule in drug delivery systems. Physicochemical characterization of the nanoparticles such as size and size distribution, surface morphology, zeta potential and surface chemistry has a significant role in the successful formulation and applications in drug delivery systems. Mostly, the size and surface characteristics of nanoparticles enable enhanced intracellular accumulation in tumor cells through passive targeting mechanisms and rapid development of nanoengineering, and aid towards attaining active targeting delivery by co-functionalization of nanoparticles using appropriate targeting ligands. This article reviews the recent progress and development of employing different biocompatible and biodegradable nanoparticles in drug delivery systems. It also briefly recaps the important methods available to evaluate its biocompatibility, the mechanism of biodegradability and clearance properties of NPs.

Hyaluronic acid co-functionalized gold nanoparticle complex for the targeted delivery of metformin in the treatment of liver cancer (HepG2 cells).

In this study, green synthesis of gold nanoparticles (AuNPs) was achieved using the extract of eggplant as a reducing agent. Hyaluronic acid (HA) serves as a capping and targeting agent. Metformin (MET) was successfully loaded on HA capped AuNPs (H-AuNPs) and this formulation binds easily on the surface of the liver cancer cells. The synthesized nanoparticles were characterized by UV-Vis spectrophotometer, HR-TEM, particle size analyser and zeta potential measurement. Toxicity studies of H-AuNPs in zebra fish confirmed the in vivo safety of the AuNPs. The in vitro cytotoxicity results showed that the amount of MET-H-AuNPs enough to achieve 50% inhibition (IC50) was much lower than free MET. Flow cytometry analysis showed the significant reduction in G2/M phase after treatment with MET-H-AuNPs, and molecular level apoptosis were studied using western blotting. The novelty of this study is the successful synthesis of AuNPs with a higher MET loading and this formulation exhibited better targeted delivery as well as increased regression activity than free MET in HepG2 cells.

Congenital melanocytic nevi: catch them early!

We report a 2-week-old neonate with a large congenital melanocytic nevus over face treated with surgical curettage followed by a combination of carbon dioxide laser and Q-switched neodymium-doped yttrium aluminum garnet lasers. The results were satisfactory with near complete resolution after 1 year of age. This case is reported to emphasize the timely management and the importance of curettage prior to development of rete ridges.

An attempt for modeling the atmospheric transport of 3H around Kakrapar Atomic Power Station.

Prediction of downwind tritium air concentrations in the environment around Kakrapar Atomic Power Station (KAPS) was studied on the basis of Gaussian plume dispersion model. The tritium air concentration by field measurement [measured tritium air concentrations in the areas adjacent to KAPS] were compared with the theoretically calculated values (predicted) to validate the model. This approach will be useful in evaluating environmental radiological impacts due to pressurised heavy water reactors.

Anti-diabetic activity of flowers of Hibiscus rosasinensis.

The ethanol extract of flowers of Hibiscus rosasinensis at doses of 250 mg/kg and 500 mg/kg significantly reduced the blood glucose level in both acute (1, 3, 5 h) and sub acute (1, 3, 5, 7 days) treatments.

Comment on "The great Sumatra-Andaman earthquake of 26 December 2004".

Lay et al. (Research Articles, 20 May 2005, p. 1127) estimated a 600-km length for the tsunami source region. Adding tide-gauge data from Paradip, the northernmost of the Indian east-coast stations and therefore the most critical constraint on the northern extent of the source, we estimate that its length was greater by approximately 30%.