Prevalence of hepatitis B in the blood donors of NW. F.P and FATA regions and the current scenario of HBV infection in Pakistan

Hepatitis B is a fatal liver disease caused by the hepatitis B virus. In this study, blood donors from various districts of the North-western frontier province and the federally administered tribal area (FATA) of Pakistan were tested for HBsAg and HBV DNA by ICT (Immuno-chromatographic test), ELISA and RTPCR. Out of the 7148 blood donors, 244 (3.41%) were positive for HBsAg by ICT, 147 (2.05%) by ELISA while 132 (1.85%) were positive by PCR. Our data indicates that the incidence of hepatitis B has decreased in these regions in recent times.Key words: HBV, HBsAg, Pakistan

Caracterización de aceites de semillas de diferentes variedades de sandía [Citrullus lanatus (Thunb.)] procedentes del Pakistán

This paper reports the physicochemical characteristics of the seed oils from different varieties of watermelon (Citrullus lanatus) cultivated in Pakistan, namely Sugar Baby, Q-F-12, D-W-H-21 and Red Circle-1885. The oil and crude protein contents from watermelon seeds, within the range of 28.25 to 35.65% and 20.50 to 35.00%, respectively, varied significantly (p < 0.05) among the varieties tested. The levels of moisture, ash, and crude fiber in the seeds tested were found to be 2.16-3.24%, 1.95-3.42% and 4.29-6.60%, respectively. The physicohemical characteristics of the extracted oils were: free fatty acid contents (1.17-2.10% as oleic acid), iodine value (97.10-116.32 g of I2 100g-1 of oil), saponification index (190.20-205.57 mg KOH g-1 of oil), unsaponifiable matter (0.54-0.82%) and color (1.12-4.30 R + 12.20-33.40 Y). The oils revealed a reasonable oxidative parameter range as depicted by the determinations of specific extinction at 232 and 270 nm (2.90-4.40 and 2.05- 3.09, respectively), p-anisidine value (5.60-7.70) and peroxide value (2.90-5.06 meqO2 kg-1 of oil). Linoleic acid was the major fatty acid found in all the seed oils with contributions of 45.30-51.80% of the total fatty acids (FA). Other fatty acids detected were known to be oleic acid (20.2- 23.5%), palmitic acid (15.1-16.9%) and stearic acid (11.5- 14.4%). The contents of α- and δ-tocopherol in the oils accounted for 120.6-195.6 and 9.1-58.3 mg kg-1, respectively. The physicochemical attributes of the watermelon seed oils showed a wider variation among the varieties tested. The results of the present study indicate that the seeds of the tested watermelon varieties from Pakistan are a potential source of high-linoleic oil and thus can be explored for commercial use and value addition.Se presentan las características físico-químicas de aceites de diferentes variedades de semillas de sandías (Citrullus lanatus) cultivadas en Pakistán: Sugar Baby, QF-12, DWH-21 y Círculo rojo-1885. El aceite y el contenido de proteína cruda de las semillas de sandía están dentro de los rangos: 28,25-35,65% y 20,50-35,00%, respectivamente y varian significativamente (p < 0,05) entre las variedades ensayadas. Los niveles de humedad, fibra cruda y cenizas en las semillas se encontró entre 2.16-3.24%, 1.95-3.42% y 4.29-6.60%, respectivamente. Las características fisico-químicas estudiadas de los aceites extraídos fueron: contenido de ácidos grasos libres (1.17-2.10% de ácido oleico), índice de yodo (97,10-116,32 g de I2 100 g-1 de aceite), índice de saponificación (190,20-205,57 mg de KOH g-1 de aceite), insaponificable (0,54-0.82%) y color (1.12-4.30 de I + 12.20- 33.40 y). Los aceites presentaron unos rangos de los parámetros de oxidación razonables, como se muestra en las determinaciones de la extinción específica a 232 y 270 nm (2.90-4.40 y 2.05-3.09 respectivamente), valores de p-anisidina (5.60-7.70) e índice de peróxidos (2,90-5,06 meqO2 kg-1 de aceite). El ácido linoleico es el principal ácido graso que se encuentra en todos los aceites de las semillas, con una contribución del 45.30-51.80% del total de ácidos grasos. Otros ácidos grasos determinados fueron oleico, 20,2-23,5%, palmítico, 15,1-16,9%) y esteárico, 11,5-14,4%. El contenido de α- y δ-tocoferol en los aceites fué de 120,6-195,6 y 9,1- 58,3 mg kg-1, respectivamente. Los atributos físico-químicos de los aceites de semillas de sandía variaron significativamente entre las variedades ensayadas. Los resultados del presente estudio indican que las semillas de las variedades de sandía ensayadas procedentes de Pakistán son una fuente potencial aceites con alto contenido en ácido linoleico y, por lo tanto, se puede explorar para usos comerciales y productos con valor añadido

Robotic Barrier Construction through Weaved, Inflatable Tubes

In this article, we present a mechanism and related path planning algorithm to construct light-duty barriers out of extruded, inflated tubes weaved around existing environmental features. Our extruded tubes are based on everted vine-robots and in this context, we present a new method to steer their growth. We characterize the mechanism in terms of accuracy resilience, and, towards their use as barriers, the ability of the tubes to withstand distributed loads. We further explore an algorithm which, given a feature map and the size and direction of the external load, can determine where and how to extrude the barrier. Finally, we showcase the potential of this method in an autonomously extruded two-layer wall weaved around three pipes. While preliminary, our work indicates that this method has the potential for barrier construction in cluttered environments, e.g. shelters against wind or snow. Future work may show how to achieve tighter weaves, how to leverage weave friction for improved strength, how to assess barrier performance for feedback control, and how to operate the extrusion mechanism off of a mobile robot

Development of a Real-Time Microchip PCR System for Portable Plant Disease Diagnosis

Rapid and accurate detection of plant pathogens in the field is crucial to prevent the proliferation of infected crops. Polymerase chain reaction (PCR) process is the most reliable and accepted method for plant pathogen diagnosis, however current conventional PCR machines are not portable and require additional post-processing steps to detect the amplified DNA (amplicon) of pathogens. Real-time PCR can directly quantify the amplicon during the DNA amplification without the need for post processing, thus more suitable for field operations, however still takes time and require large instruments that are costly and not portable. Microchip PCR systems have emerged in the past decade to miniaturize conventional PCR systems and to reduce operation time and cost. Real-time microchip PCR systems have also emerged, but unfortunately all reported portable real-time microchip PCR systems require various auxiliary instruments. Here we present a stand-alone real-time microchip PCR system composed of a PCR reaction chamber microchip with integrated thin-film heater, a compact fluorescence detector to detect amplified DNA, a microcontroller to control the entire thermocycling operation with data acquisition capability, and a battery. The entire system is 25 × 16 × 8 cm(3) in size and 843 g in weight. The disposable microchip requires only 8-µl sample volume and a single PCR run consumes 110 mAh of power. A DNA extraction protocol, notably without the use of liquid nitrogen, chemicals, and other large lab equipment, was developed for field operations. The developed real-time microchip PCR system and the DNA extraction protocol were used to successfully detect six different fungal and bacterial plant pathogens with 100% success rate to a detection limit of 5 ng/8 µl sample

Structure-based design and synthesis of fluorene derivatives as novel RORγt inverse agonists

A new series of fluorene derivatives was designed and synthesized as novel retinoic acid receptor-related orphan receptor gamma t (RORγt) inverse agonists utilizing a molecular hybridization approach. The new compounds 10-15 were evaluated for their RORγt activity using biochemical FRET and cellular reporter gene assays. Moreover, the inhibitory activity of the fluorene derivatives 10-15 in mouse Th17 cell differentiation assay was assessed. The hybrid compound 15 that combines both fluorene and arylsulfone moieties displayed promising RORγt activity with IC values of 68.6 and 99.5 nM in FRET and cellular assays, respectively. In addition, molecular modeling studies were employed to investigate potential binding mode of 15 to RORγt. These results render 15 a potential lead compound for development of therapeutics for Th17-driven autoimmune diseases

Pharmacophore-based tailoring of biphenyl amide derivatives as selective 5-hydroxytryptamine 2B receptor antagonists

We designed and synthesized a new biphenyl amide-tryptamine hybrid molecule 7 utilizing a pharmacophore-based approach as a 5-HT antagonist. The hybrid compound 7 was evaluated for its affinity to a panel of seven 5-HT receptors, demonstrating high selectivity for the 5-HT receptor. Functional assays revealed potent antagonism of 5-HT by 7 with an IC value of 14.1 nM. Moreover, compound 7 possessed a desirable in vitro pharmacokinetic profile and maintained its antagonistic potency in the presence of physiological concentrations of serum proteins. The design approach implemented in this investigation would facilitate the development of a second generation of highly selective and potent 5-HT antagonists

Synthesis, antiproliferative activity and autophagic flux inhibition of new arylsparteine derivatives

New series of arylsparteine derivatives were synthesized and evaluated for their cytotoxic activity against four human cancer cell lines (cervical epithelial carcinoma cells Hela, breast cancer cells MCF-7, lung cancer cells A549, and glioma cells U87 MG) and one normal fibroblast cell line. Structure-activity relationship revealed that introduction of 4-quinolinyl moiety to sparteine afforded a hybrid compound 10 with considerable antiproliferative activity against all tested cancer cell lines. Compound 10, the most active agent in this study possessed IC50 values of 5.97 +/- 1.1 and 9.52 +/- 0.3 mu M against A549 and Hela cancer cell lines, respectively. Inhibition of autophagic flux proved to be the underlying mechanism for the antiproliferative activity of 10 which was further validated by decreased levels of ATP in cancer cells treated with 10. In addition, co-treatment of 10 and rapamycin restored cell viability which comes in good agreement with the proposed autophagic flux inhibition for 10

Design and synthesis of donepezil analogues as dual AChE and BACE-1 inhibitors

Multi-target-directed ligands (MTDLs) centered on β-secretase 1 (BACE-1) inhibition are emerging as innovative therapeutics in addressing the complexity of neurodegenerative diseases. A new series of donepezil analogues was designed, synthesized and evaluated as MTDLs against neurodegenerative diseases. Profiling of donepezil, a potent acetylcholinesterase (hAChE) inhibitor, into BACE-1 inhibition was achieved through introduction of backbone amide linkers to the designed compounds which are capable of hydrogen-bonding with BACE-1 catalytic site. In vitro assays and molecular modeling studies revealed the dual mode of action of compounds 4-6 against hAChE and BACE-1. Notably, compound 4 displayed potent hAChE inhibition (IC value of 4.11 nM) and BACE-1 inhibition (IC value of 18.3 nM) in comparison to donepezil (IC values of 6.21 and 194 nM against hAChE and BACE-1, respectively). Moreover, 4 revealed potential metal chelating property, low toxicity on SH-SY5Y neuroblastoma cells and ability to cross the blood-brain barrier (BBB) in PAMPA-BBB assay which renders 4 a potential lead for further optimization of novel small ligands for the treatment of Alzheimer's disease

Structure-based design, synthesis, and evaluation of structurally rigid donepezil analogues as dual AChE and BACE-1 inhibitors

A new series of structurally rigid donepezil analogues was designed, synthesized and evaluated as potential multi-target-directed ligands (MTDLs) against neurodegenerative diseases. The investigated compounds 10-13 displayed dual AChE and BACE-1 inhibitory activities in comparison to donepezil, the FDA-approved drug. The hybrid compound 13 bearing 2-aminoquinoline scaffold exhibited potent AChE inhibition (IC value of 14.7 nM) and BACE-1 inhibition (IC value of 13.1 nM). Molecular modeling studies were employed to reveal potential dual binding mode of 13 to AChE and BACE-1. The effect of the investigated compounds on the viability of SH-SY5Y neuroblastoma cells and their ability to cross the blood-brain barrier (BBB) in PAMPA-BBB assay were further studied