Neferine induces reactive oxygen species mediated intrinsic pathway of apoptosis in HepG2 cells

Evidence has accumulated concerning the medicinal application of Nelumbo nucifera in the treatment of various diseases. Neferine, an alkaloid from N. nucifera was found to exert cytotoxicity on liver cancer cells HepG2 in a dose-dependent manner. We evaluated its anticancer potential by studying its effect on mitochondrial membrane potential, intracellular calcium levels [Ca²⁺]_i, cell membrane integrity, apoptotic body formation and DNA fragmentation in cultured HepG2 cells. The reactive oxygen species level has been increased upon neferine treatment with concomitant decrease in reduced glutathione. Our data further indicate reduction of ΔψM and increased [Ca²⁺]_i during apoptosis induction by neferine with increased expression of apoptotic proteins such as Bax, Bad, cleaved forms of caspase 3, caspase 9 and PARP, with the downregulation of anti-apoptotic protein Bcl2 in HepG2 cells. Moreover, the expressions of tumour suppressor proteins p53 and PTEN were upregulated along with the downregulation of P-Akt. In addition, expression levels of TNF-α, p38 and ERK1/2 MAP kinases were increased upon neferine treatment. These results imply that mitochondrial-mediated ROS generation induced by neferine leads to caspase-dependent apoptosis in HepG2 cells.     

Epikeratoplasty for keratoconus using manually dissected fresh lenticules: 4-year follow-up

BACKGROUND: Epikeratoplasty for keratoconus, in the absence of apical scarring, aims at reducing high irregular myopic astigmatism and provides an ectatic cornea with mechanical support. METHODS: We performed epikeratoplasty on 11 keratoconic corneas using fresh or McCarey-Kaufman preserved, manually dissected donor lenticules. A disparity of 0.5 mm was maintained between the host and the donor. Patients with keratoconus having a preoperative spectacle-corrected visual acuity of less than 6/60 and intolerance to contact lens wear were included in this prospective study. Spectacle-corrected visual acuity, keratometry, and refraction were analyzed over a 4-year follow-up period. RESULTS: Four year follow-up was completed on 10 eyes. Of these, 80% achieved a postoperative spectacle-corrected visual acuity of 6/12 or better. Average postoperative keratometry was 45.79 +/- 2.07 D and a decrease of 4.60 +/- 0.09 D was observed in refractive cylinder. Spherical equivalent showed a significant decrease in myopia of -4.35 +/- 0.26 D. Mean time to stabilization was 8 +/- 2.3 weeks. Epithelial defects occurred in three eyes; two were successfully treated by patching. One lenticule was removed due to graft infection following a persistent epithelial defect. CONCLUSION: Epikeratoplasty for keratoconus is a useful procedure with good long-term visual acuity results and an early stabilizing period.     

HDR and image abstraction framework for dirt free line drawing to convey the shapes from blatant range images

Multidimensional Systems and Signal Processing - Due to the evolution of computer vision and non-photorealistic rendering (NPR) techniques, enhancements of image features from blatant range images...     

Identification of environmental reservoirs of nontyphoidal salmonellosis: aptamer-assisted bioconcentration and subsequent detection of salmonella typhimurium by quantitative polymerase chain reaction

In this study, identification of environmental reservoirs of Salmonella enterica subsp. enterica serovar Typhimurium (abbreviated as Salmonella Typhimurium) in sediments, water, and aquatic flora collected from the Ganges River (Ganges riverine material) was carried out by adopting a two-step strategy. Step 1 comprised a selective serovar-specific capture of Salmonella Typhimurium from potential reservoirs. Step 2 involved culture-free detection of selectively captured Salmonella Typhimurium by ttr gene-specific molecular beacon (MB) based quantitative polymerase chain reaction (q-PCR). The ttr gene-specific MB designed in this study could detect 1 colony-forming unit (cfu)/PCR captured by serovar-specific DNA aptamer. Sediments, water, and aquatic flora collected from the Ganges River were highly contaminated with Salmonella Typhimurium. The preanalytical step in the form of serovar-specific DNA aptamer-based biocapture of bacterial cells was found to enhance the sensitivity of the fluorescent probe in the presence of nonspecific DNA . Information about the presence of environmental reservoirs of Salmonella Typhimurium in the Ganges River region may pave the way for forecasting and management of nontyphoidal salmonellosis in south Asia.     

Self-assembly of Cationic, Hetero- or Homo-nuclear Ru(II) Macrocyclic Rectangles and their Photophysical, Electrochemical and Biological Studies

A series of supramolecular rectangles, including two mixed-metal Ru/Pt complexes, have been formed by the coordination-driven self-assembly of a range of arene-Ru "molecular clip" acceptors (1a-1d) with rigid dipyridyl-based ligands (2a-2d) over the course of 10 hours in solution. The isolated products were characterized by multinuclear NMR ((1)H and (13)C or (31)P), HR-ESI-MS and an X-ray diffraction study to support the ascribed two-component rectangular structures. The rectangles were further characterized by UV-Vis and fluorescence studies. The redox behaviors of rectangles 3ca and 3da were also determined using cyclic voltammetry. Additionally, the antitumor activities of the suite of rectangles were determined against various human cancer cell lines and significant activity was shown by complexes 3ca, 3da, 3cb, 3cc and 3cd, with IC(50) values as low as 2.65 μM.     

Studies on black electroless nickel coatings on titanium alloys for spacecraft thermal control applications

A process of blackening of electroless nickel coating is investigated to produce ultra black coating on titanium alloys with higher optical properties. Process optimization was carried out by investigating the influence of various operating conditions, namely, processing time of etching solutions, thickness of electroless nickel deposit, temperature of blackening solutions, and pH of electroless nickel solution on the physico-optical properties of the black coating. It was observed that an optimum thickness of 35 + 5 μm of electroless nickel is required to achieve the ultra high optical properties after blackening. Energy dispersive X-ray spectroscopy studies suggested that films containing ~7% phosphorous are good for further blackening. Scanning electron and optical microscopic studies confirmed that the surface morphology played the major role to get the ultra high optical properties. The environmental tests, namely, humidity, corrosion resistance, thermal cycling, thermo vacuum performance, and thermal stability tests were used to evaluate the space worthiness of the coating. Optical properties of the coating were measured before and after each environmental test to ascertain its stability. The blackened electroless nickel provides higher optical properties in the order of ~0.85; this coating has good adhesion, uniformity, and stability in adverse space conditions. Hence, these coatings were extremely suitable for spacecraft thermal control applications.     

The effect of distractor modality and processing code on human-automation interaction

We examined the effect of distractor characteristics (modality and processing code) on visual search performance and interaction with an automated decision aid. Multiple Resource Theory suggests that concurrent tasks that are processed similarly (e.g. two visual tasks) will cause greater interference than tasks that are not (e.g., a visual and auditory task). The impact of tasks that share processing and perceptual demands and their interaction with human-automation interaction is not established. In order to examine this, participants completed two blocks of a luggage screening simulation with or without the assistance of an automated aid. For one block, participants performed a concurrent distractor task drawn from one of four combinations of modality and processing code: auditory-verbal; auditory-spatial; visual-verbal; visual-spatial. We measured sensitivity, criterion setting, perceived workload, system trust, perceived system reliability, compliance, reliance, and confidence. Participants demonstrated highest sensitivity when performing with an auditory-spatial secondary task. Automation compliance was higher when the auditory-spatial distraction was present versus absent; however, system trust was highest in the auditory-verbal condition. Confidence (when disagreeing with the aid) was also highest when the distractor was auditory. This study indicates that some forms of auditory ‘distractors’ may actually help performance; these results further contribute to understanding how distractions influence performance when operators interact with automation and have implications for improved work environment and system design.     

Polymer nanoneedle-mediated intracellular drug delivery

Delivery of drugs into the cellular cytoplasm of target cells represents a major hurdle in treating various diseases. This challenge can be addressed by encapsulation of drugs onto or within nanoparticles, which can then be targeted to diseased cells. Here, needle-shaped particles are shown to exhibit substantially higher cytoplasmic delivery of drugs such as siRNA compared to their spherical counterparts. Furthermore, these needles are designed to lose their sharp tips over time and can render themselves ineffective over time, thereby offering control over their duration of activity and toxicity. Such polymer nanoneedles open new avenues for delivering drug molecules directly into the cytoplasm with low toxicity.     

Neferine from Nelumbo nucifera induces autophagy through the inhibition of PI3K/Akt/mTOR pathway and ROS hyper generation in A549 cells

Previously we have reported that neferine from the medicinal plant Nelumbo nucifera, inhibited cancer cell proliferation by inducing apoptosis. The present study was focused on the action mechanism of neferine in inducing autophagy in lung cancer cells. Neferine markedly inhibited A549 cell proliferation in a dose dependent manner. Acidic vesicular accumulation was observed in neferine treated cells as an indication of autophagy. Neferine could induce the conversion of LC3B-I to LC3B-II without affecting the expression levels of PI3KCIII and Beclin1. It has been observed that neferine mediated autophagy is dependent on inhibition of PI3K/Akt/mTOR signaling by neferine. Neferine treatment could also lead to the ROS hypergeneration and depletion of cellular antioxidant, GSH. The results demonstrate that neferine-induced autophagy is mediated through ROS hypergeneration and mTOR inhibition. Taken together, the present study unveils a novel mechanism of action of neferine on lung cancer cells in the induction of autophagy.     

Models for measuring and predicting shareholder value: A study of third party software service providers

In this study, we use the strategic profit model (SPM) and the economic value-added (EVA to measure shareholder value). SPM measures the return on net worth (RONW) which is defined as the return on assets (ROA) multiplied by the financial leverage. EVA is defined as the firm's net operating profit after taxes (NOPAT) minus the capital charge. Both, RONW and EVA provide an indication of how much shareholder value a firm creates for its shareholders, year on year. With the increasing focus on creation of shareholder value and core competencies, many companies are outsourcing their information technology (IT) related activities to third party software companies. Indian software companies have become leaders in providing these services. Companies from several other countries are also competing for the top slot. We use the SPM and EVA models to analyse the four listed players of the software industry using the publicly available published data. We compare the financial data obtained from the models, and use peer average data to provide customized recommendations for each company to improve their shareholder value. Assuming that the companies follow these rules, we also predict future RONW and EVA for the companies for the financial year 2005. Finally, we make several recommendations to software providers for effectively competing in the global arena.