A direct-write microfluidic fabrication process for CMOS-based Lab-on-Chip applications

In this paper, we propose an efficient microfluidic fabrication process for Lab-on-Chip (LoC) applications. This low temperature process is employed to implement different microfluidic components including microchannels, microvalves as well as microfluidic packaging of CMOS chips. Furthermore, we describe the applicability of this direct-write microfluidic fabrication process (DWFP) for LoCs by demonstrating the experimental results of a thermally-actuated microvalve incorporated with a capacitive sensor.     

Protective Effect of Low-Dose Alcohol Consumption against Post-Ischemic Neuronal Apoptosis: Role of L-PGDS

Ischemic stroke is one of the leading causes of permanent disability and death in adults worldwide. Apoptosis is a major element contributing to post-ischemic neuronal death. We previously found that low-dose alcohol consumption (LAC) protects against neuronal apoptosis in the peri-infarct cortex following transient focal cerebral ischemia. Lipocalin-type prostaglandin D2 synthase (L-PGDS), which is mainly localized in the central nervous system (CNS), was previously shown to inhibit neuronal apoptosis. Therefore, we determined whether L-PGDS is involved in the protective effect of LAC against post-ischemic neuronal apoptosis. Wild-type (WT), CaMKIIα^CreERT2/+/L-PGDS^+/+, and CaMKIIα^CreERT2/+/L-PGDS^flox/flox mice on a C57BL/6J background were gavage fed with ethanol or volume-matched water once a day for 8 weeks. Tamoxifen (2 mg/day) was given intraperitoneally to CaMKIIα^CreERT2/+/L-PGDS^+/+ and CaMKIIα^CreERT2/+/L-PGDS^flox/flox mice for 5 days during the fourth week. AT-56 (30 mg/kg/day), a selective inhibitor of L-PGDS, was given orally to AT-56-treated WT mice from the fifth week for four weeks. Cerebral ischemia/reperfusion (I/R) injury, TUNEL-positive neurons, and cleaved caspase-3-positive neurons were measured at 24 h of reperfusion after a 90 min unilateral middle cerebral artery occlusion (MCAO). We found that 0.7 g/kg/day but not 2.8 g/kg/day ethanol significantly upregulated L-PGDS in the cerebral cortex. In addition, 0.7 g/kg/day ethanol diminished cerebral ischemia/reperfusion (I/R) injury and TUNEL-positive and cleaved caspase-3-positive neurons in the peri-infarct cortex in WT and CaMKIIα^CreERT2/+/L-PGDS^+/+ mice. Furthermore, the neuroprotective effect of 0.7 g/kg/day ethanol was alleviated in AT-56-treated WT and CaMKIIα^CreERT2/+/L-PGDS^flox/flox mice. Our findings suggest that LAC may protect against cerebral I/R injury by suppressing post-ischemic neuronal apoptosis via an upregulated L-PGDS.     

Rotenone-Induced 4-HNE Aggresome Formation and Degradation in HL-1 Cardiomyocytes: Role of Autophagy Flux

Reactive oxygen species (ROS) cause oxidative stress by generating reactive aldehydes known as 4-hydroxynonenal (4-HNE). 4-HNE modifies protein via covalent adduction; however, little is known about the degradation mechanism of 4-HNE-adducted proteins. Autophagy is a dynamic process that maintains cellular homeostasis by removing damaged organelles and proteins. In this study, we determined the role of a superoxide dismutase (SOD) mimetic MnTnBuOE-2-PyP⁵⁺ (MnP, BMX-001) on rotenone-induced 4-HNE aggresome degradation in HL-1 cardiomyocytes. A rotenone treatment (500 nM) given for 24 h demonstrated both increased ROS and 4-HNE aggresome accumulation in HL-1 cardiomyocytes. In addition, cardiomyocytes treated with rotenone displayed an increase in the autophagy marker LC3-II, as shown by immunoblotting and immunofluorescence. A pre-treatment with MnP (20 µM) for 24 h attenuated rotenone-induced ROS formation. An MnP pre-treatment showed decreased 4-HNE aggresomes and LC3-II formation. A rotenone-induced increase in autophagosomes was attenuated by a pre-treatment with MnP, as shown by fluorescent-tagged LC3 (tfLC3). Rotenone increased tubulin hyperacetylation through the ROS-mediated pathway, which was attenuated by MnP. The disruption of autophagy caused HL-1 cell death because a 3-methyladenine inhibitor of autophagosomes caused reduced cell death. Yet, rapamycin, an inducer of autophagy, increased cell death. These results indicated that a pre-treatment with MnP decreased rotenone-induced 4-HNE aggresomes by enhancing the degradation process.     

Effect of Extraction Techniques and Solvents on Antioxidant Activity of Pomegranate (<Emphasis Type="Italic">Punica granatum</Emphasis> L.) Leaf and Stem

The effect of commonly used techniques and solvents in the antioxidant activities of Pomegranate leaves and stems were studied. The extraction techniques compared were successive, individual (cold percolation), and decoction methods in both parts using solvents viz. petroleum ether, toluene, ethyl acetate, acetone, and water. The antioxidant activity of all the different solvent extracts of leaves and stem was evaluated using antioxidant assays like 2,2-diphenyl-1-picryl hydrazyl free radical scavenging assay, superoxide anion radical scavenging assay and ferric-reducing antioxidant power. Total phenol and flavonoid content was also measured. Successive extraction was a better technique to extract the antioxidants from pomegranate than other techniques evaluated in the present study. For the aqueous extraction, decoction method was found to be the best method to extract the antioxidants and it is the most convenient, exhaustive, and time-saving extraction technique for both parts of pomegranate. The results showed that the extracting solvent significantly altered the antioxidant property estimations of pomegranate leaf and stem. High correlations between phenolic compositions and antioxidant activities of pomegranate extracts were observed. High levels of antioxidant activities were detected in pomegranate leaf as compared to stem indicating that the leaf may serve as an excellent source of natural antioxidants.     

The Effect of Sequential Fractionation Technique on the Various Efficacies of Pomegranate (Punica granatum L.)

The pomegranate (Punica granatum L.) is a fruit-bearing deciduous shrub. Various parts of this plant are used in the treatment of dyspepsia, bronchitis, hypotensive, throat inflammation, etc. and its nutritional value has well been accepted. In the present study, antioxidant and antimicrobial efficacy of different solvent fractions of P. granatum leaves was investigated. Fractionation was done sequentially in Soxhlet apparatus, using various solvents like petroleum ether, toluene, ethyl acetate, acetone, and water. Antioxidant activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, superoxide anion radical scavenging assay, and reducing capacity assessment. Total phenol and flavonoid content was also measured. The antimicrobial activity was assessed by agar well diffusion method against some of the tested food borne, pathogenic, and skin disease causing microorganisms. Antiulcer activity of the P. granatum acetone fraction (PGA) was evaluated using ethanol-induced gastric ulcer model. The PGA had maximum phenol content and had higher antioxidant activity. The PGA showed better DPPH free radical and superoxide anion radical scavenging activity than that of the standards. The results demonstrated that acetone fraction had potent gastroprotective and antisecretory effects. This study suggests that sequential fractionation technique is an excellent technique of extracting bioactive components of this plant at least. This study also demonstrated that PGA can serve as a potential natural source for use in food, nutraceutical, and pharmaceutical industry.     

Comparative characterisation of durian,mango and avocado

The aim of this investigation was to determine the nutritional and bioactive properties of relatively less investigated exotic fruit durian (Durio zibethinus Murr.) and to compare these indices with widely used mango (Mangifera indica L.) and avocado (Persea americana). For this purpose HPLC, three‐dimensional fluorescence (3D‐FL), several radical scavenging assays and multivariate factor analysis were used. It was found a similarity in acetone extracts between durian and mango in the contents of polyphenols (1.66 ± 0.08, 1.48 ± 0.05, mg GAE g^?1 DW, respectively), and in some antioxidant assays such as ABTS (11.98 ± 0.5, 12.24 ± 0.5, μm TE g^?1DW, respectively) and DPPH (5.61 ± 0.3, 5.22 ± 0.2, μm TE g^?1 DW, respectively). Durian and avocado were similar in the contents of polyphenols, and ABTS and DPPH values in water and in methanol extracts, respectively. Based on the obtained results the nutritional and bioactive properties of durian are comparable with those indices in mango and avocado. In conclusion, durian can be recommended as a part of disease prevented diets.     

Structural and Optical Properties of Barium Strontium Titanate (Ba0.5Sr0.5TiO3) Thin Films

Ferroelectric Barium Strontium Titanate (Ba_0.5Sr_0.5TiO₃) or BST thin films on quartz substrates have been prepared by using a modified sol gel processing technique. The starting materials are Barium 2-ethylhexanoate Ba[CH₃(CH₂)₃CH(C₂H₅)CO₂]_2, Strontium 2-ethylhexanoate Sr[CH₃(CH₂)₃CH(C₂H₅)CO₂]₂ and Titanium(IV) isopropoxide [TiOCH(CH₃)₂]₄. The precursors except [TiOCH(CH₃)₂]₄ were synthesized in the laboratory. Transparent and crack-free films were fabricated on quartz substrates by spin coating. The as-fired films were found to be amorphous, which crystallized to cubic phase after annealing at 550°C in air for 1 hr. In this paper we report the structural and optical properties of BST films prepared by the modified sol-gel process.

Communicated by Prof. E. C. Subbarao     

In-Silico Evaluation of Genetic Alterations in Ovarian Carcinoma and Therapeutic Efficacy of NSC777201, as a Novel Multi-Target Agent for TTK,NEK2, and CDK1

Ovarian cancer is often detected at the advanced stages at the time of initial diagnosis. Early-stage diagnosis is difficult due to its asymptomatic nature, where less than 30% of 5-year survival has been noticed. The underlying molecular events associated with the disease’s pathogenesis have yet to be fully elucidated. Thus, the identification of prognostic biomarkers as well as developing novel therapeutic agents for targeting these markers become relevant. Herein, we identified 264 differentially expressed genes (DEGs) common in four ovarian cancer datasets ({"type":"entrez-geo","attrs":{"text":"GSE14407","term_id":"14407"}}GSE14407, {"type":"entrez-geo","attrs":{"text":"GSE18520","term_id":"18520"}}GSE18520, {"type":"entrez-geo","attrs":{"text":"GSE26712","term_id":"26712"}}GSE26712, {"type":"entrez-geo","attrs":{"text":"GSE54388","term_id":"54388"}}GSE54388), respectively. We constructed a protein-protein interaction (PPI) interaction network with the overexpressed genes (72 genes) and performed gene enrichment analysis. In the PPI networks, three proteins; TTK Protein Kinase (TTK), NIMA Related Kinase 2 (NEK2), and cyclin-dependent kinase (CDK1) with higher node degrees were further evaluated as therapeutic targets for our novel multi-target small molecule NSC777201. We found that the upregulated DEGs were enriched in KEGG and gene ontologies associated with ovarian cancer progression, female gamete association, otic vesicle development, regulation of chromosome segregation, and therapeutic failure. In addition to the PPI network, ingenuity pathway analysis also implicate TTK, NEK2, and CDK1 in the elevated salvage pyrimidine and pyridoxal pathways in ovarian cancer. The TTK, NEK2, and CDK1 are over-expressed, demonstrating a high frequency of genetic alterations, and are associated with poor prognosis of ovarian cancer cohorts. Interestingly, NSC777201 demonstrated anti-proliferative and cytotoxic activities (GI₅₀ = 1.6 µM~1.82 µM and TGI₅₀ = 3.5 µM~3.63 µM) against the NCI panels of ovarian cancer cell lines and exhibited a robust interaction with stronger affinities for TTK, NEK2, and CDK1, than do the standard drug, paclitaxel. NSC777201 displayed desirable properties of a drug-like candidate and thus could be considered as a novel small molecule for treating ovarian carcinoma.     

Simple,Selective, and Rapid Quantification of 1-Deoxynojirimycin in Mulberry Leaf Products by High-Performance Anion-Exchange Chromatography with Pulsed Amperometric Detection

ABSTRACT: 1-Deoxynojirimycin (DNJ) occurs in mulberry and other plants and is a highly potent glycosidase inhibitor reported to suppress blood glucose levels, thus preventing diabetes. Derivatization is required for quantification of DNJ upon use of spectral detection methods. Because of this difficulty, the DNJ contents of mulberry-based food products are rarely stated, even if DNJ is their active component. A simple, selective, and rapid method of high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) to quantify DNJ in mulberry-based food products was developed. Stability testing of DNJ under heat treatment was also performed. A water extract of mulberry tea sample was subjected to HPAEC-PAD in a CarboPac MA1 column with a sodium hydroxide gradient. DNJ was clearly separated at a retention time of 7.26 min without interference and was selectively detected in the water extract. The detection limit was 5 ng. Heat stability studies suggested that DNJ was heat stable. HPAEC-PAD was not subject to interference, was highly selective for DNJ, and was superior to other high-performance liquid chromatography (HPLC) techniques in terms of sample preparation, resolution, and sensitivity. The method allowed simple, selective, and rapid analysis of DNJ in food matrices and might be useful for development of mulberry-based food products. Heat treatment could be an option for sterilizing mulberry-based products.