Search results for: protein cage nanoparticles
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3721

Search results for: protein cage nanoparticles

841 Digestibility in Yankasa Rams Fed Brachiaria ruziziensis – Centrosema pascuorum Hay Mixtures with Concentrate

Authors: Ibrahim Sani, J. T. Amodu, M. R. Hassan, R. J. Tanko, N. Adamu

Abstract:

This study investigated the digestibility of Brachiaria ruziziensis and Centrosema pascuorum hay mixtures at varying proportions in Yankasa rams. Twelve Yankasa rams with average initial weight 10.25 ± 0.1 kg were assigned to three dietary treatments of B. ruziziensis and C. pascuorum hay at different mixtures (75BR:25CP, 50BR:50CP and 25BR:75CP, respectively) in a Completely Randomized Design (CRD) for a period of 14 days. Concentrate diet was given to the experimental animals as supplement at fixed proportion, while the forage mixture (basal diet) was fed at 3% body weight. Animals on 50BR:50CP had better nutrient digestibility (crude protein, acid and neutral detergent fibre, ether extract and nitrogen free extract) than other treatment diets, except in dry matter digestibility (87.35%) which compared with 87.54% obtained in 25BR:75CP treatment diet and also organic matter digestibility. All parameters taken on nitrogen balance with the exception of nitrogen retained were significantly higher (P < 0.05) in animals fed 25BR:75CP diet, but were statistically similar with values obtained for animals on 50BR:50CP diet. From results obtained in this study, it is concluded that mixture of 25%BR75%CP gave the best nutrient digestibility and nitrogen balance in Yankasa rams. It is therefore recommended that B. ruziziensis and C. pascuorum should be fed at 50:50 mixture ratio for enhanced animal growth and performance in Nigeria.

Keywords: B. ruziziensis, C. pascuorum, digestibilty, rams, Yankasa

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840 Lipid Profile of Civil Servants in Abeokuta Ogun State Nigeria

Authors: Sunday Sedodo Nupo, Clara Berstien Oguntona, Babatunde Oguntona, Oluseyi Akinloye, P. A. Olunusi Adeboye

Abstract:

Cardiovascular diseases are now becoming dominant sources of morbidity and mortality worldwide. This study investigated the lipid profile of civil servants. A cross-sectional study was carried out among randomly selected 202 male and 298 female civil servants in Abeokuta Ogun state. A pretested structured questionnaire was used to elicit information on history of non-communicable diseases and physical activity pattern of the respondents. The blood pressures of the subjects were measured and classified using World Health Organization criteria. The total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL). Ethical approval was obtained from Ogun State Ministry of Health. Data collected were analysed using Statistical package for social science version 17.1. Results showed that majority (76%) of the subjects were within the age range of 20 - 40 years, 75% earned between N58,500 - N98,000 monthly and 68% were sedentary. The mean energy intake of men and women were 3942±38 kcal and 2791±3 kcal respectively, while the protein intake for men was 65±49 g/day and 54.28±40 g/day for women. Desirable TC level (<200 mg/dl) was found in 80% of the selected subjects while the normal TG (<150 mg/dl) and LDL (<129 mg/dl) was found in 95% and 90% subjects respectively. The mean TC was 78.91±11 mg/dl and 62.69±9 mg/dl in men and women respectively. The study showed that most of the subjects had normal lipid in terms of serum triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol.

Keywords: high density lipoprotein, morbidity, mortality, triglycerides

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839 The Role of Glutamine-Rich Region of Candida Albicans Tec1p in Mediating Morphological Transition and Invasive Growth

Authors: W. Abu Rayyan, A. Singh, A. M. Al-Jaafreh, W. Abu Dayyih, M. Bustami, S. Salem, N. Seder, K. Schröppel

Abstract:

Hyphal growth and the transcriptional regulation to the host environment are key issues during the pathogenesis of C. albicans. Tec1p is the C. albicans homolog of a TEA transcription factor family, which share a conserved DNA-binding TEA domain in their N-terminal. In order to define a structure-function relationship of the C. albicans Tec1p protein, we constructed several mutations on the N terminal, C terminal or in the TEA binding domain itself by homologous recombination technology. The modifications in the open reading frame of TEC1 were tested for reconstitution of the morphogenetic development of the tec1/tec1 mutant strain CaAS12. Mutation in the TEA consensus sequence did not confer transition to hyphae whereas the reconstitution of the full-length Tec1p has reconstituted hyphal development. A deletion in one of glutamine-rich regions either in the Tec1p N-terminal or the C-terminal in regions of 53-212 or 637–744 aa, respectively, did not restore morphological development in mutant CaAS12 strain. Whereas, the reconstitution with Tec1p mutants other than the glutamate-rich region has restored the morphogenetic switch. Additionally, the deletion of the glutamine-rich region has attenuated the invasive growth and the heat shock resistance of C. albicans. In conclusion, we show that a glutamine-rich region of Tec1p is essential for the hyphal development and mediating adaptation to the host environment of C. albicans.

Keywords: Candida albicans, morphogenetic development, TEA domain, hyphal formation, TEC1

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838 Distribution of Spotted Fever Group in Ixodid Ticks, Domestic Cattle and Buffalos of Faisalabad District, Punjab, Pakistan

Authors: Muhammad Sohail Sajid, Qurat-ul-Ain, Zafar Iqbal, Muhammad Nisar Khan, Asma Kausar, Adil Ejaz

Abstract:

Rickettsiosis, caused by a Spotted Fever Group Rickettsiae (SFGR), is considered as an emerging infectious disease from public and veterinary perspective. The present study reports distribution of SFGR in the host (buffalo and cattle) and vector (ticks) population determined through gene specific amplification through PCR targeting outer membrane protein (ompA). Tick and blood samples were collected using standard protocols through convenient sampling from district Faisalabad. Ticks were dissected to extract salivary glands (SG). Blood and tick SG pools were subjected to DNA extraction and amplification of ompA using PCR. Overall prevalence of SFGR was reported as 21.5% and 33.6 % from blood and ticks, respectively. Hyalomma anatolicum was more prevalent tick associated with SFGR as compared to Rhipicephalus sp. Higher prevalence of SFGR was reported in cattle (25%) population as compared to that of buffalo (17.07%). On seasonal basis, high SFGR prevalence was recorded during spring season (48.1%, 26.32%, 17.76%) as compared to winter (27.9%, 21.43%, 15.38%) in vector and host (cattle and buffalo respectively) population. Sequencing analysis indicated that rickettsial endo-symbionts were associated with ticks of the study area. These results provided baseline information about the prevalence of SFGR in vector and host population.

Keywords: Rickettsia, livestock, polymerase chain reaction, sequencing, ticks, vectors

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837 Development and Characterization of Biscuits Incorporated with Jackfruit (Artocarpus heterophyllus) Seeds and Cassava (Manihot esculenta)

Authors: Elina Brahma Hazarika, Jeuti Basumatary, Deepanka Saikia, Jaydeep Das, Micky Moni D'mary, Fungkha Basumatary

Abstract:

This study includes development of two varieties of biscuits incorporated with: the seeds of Jack fruit (Artocarpus heterophyllus), which post-consumption of it’s pulp, is discarded as a waste, and Cassava (Manihot esculenta) tubers.The jack fruit seeds and cassava were first ground into flour and its proximate and physiochemical properties were studied. The biscuits that were developed incorporating them had 50% wheat flour and 50% jackfruit seed flour and 50% cassava flours as the major composition, apart from the other general ingredients use in making biscuits. Various trials of compositions were made for baking to get the overall desirable acceptability in biscuits through sensory evaluation. Finally, the best composition of ingredients was selected to make the biscuits, and hence studies were done accordingly to compare it with the properties of their respective raw flours. The results showed that the proximate composition of the biscuits fared better than that of their respective flours: There was a decrease in the Moisture content of both Jackfruit Seed Biscuits and Cassava Biscuits to 4.5% and 6.7% than that of their respective raw flours (8 and 12%). Post-baking, there is increase in the percentages of ash, protein, and fibre contents in both Jackfruit Seed Biscuits and Cassava Biscuits; the values being 3% and 3.8%, 13.2% and 3.3%, and 3.2 and 4.1% respectively. Also the total carbohydrate content in Jackfruit Seed Biscuits and Cassava Biscuits were 66.7% and 71.7% respectively. Their sensory evaluation and texture study also yielded a clear review that they have an overall good acceptability.

Keywords: baking, proximate, sensory, texture

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836 NprRX Regulation on Surface Spreading Motility in Bacillus cereus

Authors: Yan-Shiang Chiou, Yi-Huang Hsueh

Abstract:

Bacillus cereus is a foodborne pathogen that causes two types of foodborne illness, the emetic and diarrheal syndromes. B. cereus consistently ranks among the top three among bacterial foodborne outbreaks in the ten years of 2001 to 2010 in Taiwan. Foodborne outbreak caused by B. cereus has been increased, and recently it ranks second foodborne pathogen after Vibrio parahaemolyticus. This pathogen is difficult to control due to its ubiquitousness in the environment, the psychrotrophic nature of many strains, and the heat resistance of their spores. Because complete elimination of biofilms is difficult, a better understanding of the molecular mechanisms of biofilm formation by B. cereus will help to develop better strategies to control this pathogen. Surface translocation can be an important factor in biofilm formation. In B. cereus, NprR is a quorum sensor, and its apo NprR is a dimer and changes to a tetramer in the presence of NprX. The small peptide NprX may induce conformational change allowing the apo dimer to switch to an active tetramer specifically recognizing target DNA sequences. Our result showed that mutation of nprRX causes surface spreading deficiency. Mutation of flagella, pili and surfactant genes (flgAB, bcpAB, krsABC), did not abolish spreading motility. Under nprRX mutant, mutation of spo0A restored the spreading deficiency. This suggests that spreading motility is not related surfactant, pili and flagella but other unknown mechanism and Spo0A, a sporulation initiation protein, inhibits spreading motility.

Keywords: Bacillus cereus, nprRX, spo0A, spreading motility

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835 Efficient Production of Cell-Adhesive Motif From Human Fibronectin Domains to Design a Bio-Functionalized Scaffold for Tissue Engineering

Authors: Amina Ben Abla, Sylvie Changotade, Geraldine Rohman, Guilhem Boeuf, Cyrine Dridi, Ahmed Elmarjou, Florence Dufour, Didier Lutomski, Abdellatif Elm’semi

Abstract:

Understanding cell adhesion and interaction with the extracellular matrix is essential for biomedical and biotechnological applications, including the development of biomaterials. In recent years, numerous biomaterials have emerged and were used in the field of tissue engineering. Nevertheless, the lack of interaction of biomaterials with cells still limits their bio-integration. Thus, the design of bioactive biomaterials to improve cell attachment and proliferation is of growing interest. In this study, bio-functionalized material was developed combining a synthetic polymer scaffold surface with selected domains of type III human fibronectin (FNIII-DOM) to promote cell adhesion and proliferation. Bioadhesive ligand includes cell-binding domains of human fibronectin, a major ECM protein that interacts with a variety of integrins cell-surface receptors, and ECM proteins through specific binding domains were engineered. FNIII-DOM was produced in bacterial system E. coli in 5L fermentor with a high yield level reaching 20mg/L. Bioactivity of the produced fragment was validated by studying cellular adhesion of human cells. The adsorption and immobilization of FNIII-DOM onto the polymer scaffold were evaluated in order to develop an innovative biomaterial.

Keywords: biomaterials, cellular adhesion, fibronectin, tissue engineering

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834 Assessment of Alteration in High Density Lipo Protein, Apolipoprotein A1, Serum Glutamic Pyruvic Transaminase and Serum Glutamic Oxaloacetic Transaminase in Oral Submucous Fibrosis Patients

Authors: Marina Lazar Chandy, N. Kannan, Rajendra Patil, Vinod Mathew, Ajmal Mohamed, P. K. Sreeja, Renju Jose

Abstract:

Introduction- Arecoline, a major constituent of arecanut has shown to have some effect on liver. The use of arecanut is found to be the most common etiological factor for the development of Oral Submucous fibrosis (O.S.M.F). The effect of arecanut usage on liver in patients with O.S.M.F needs to be assessed. Lipids play a role in structural maintenance of cell. Alterations of lipid profile were noted in cancer patients. O.S.M.F being a precancerous lesion can have some effect on the level of lipids in the body. Objectives: This study was done to assess the alterations in liver enzymes (Serum Glutamic Pyruvic Transaminase(S.G.P.T ,Serum Glutamic Oxaloacetic Transaminase(S.G.O.T)) and lipid metabolism (High Density Lipoprotien(H.D.L) and Apo Lipoprotien A1 (Apo A1)) in patients with O.S.M.F. Methods-130 patients were taken for the study,100 patients with O.S.M.F and 30 as control group without O.S.M.F. Fasting blood sugar levels were taken, centrifuged and analyzed for S.G.P.T,S.G.O.T, H.D.L and Apo A1 using semi automated spectrophotometer. Results: After statistical analysis, it was concluded that there is an elevation of levels of S.G.P.T, S.G.O.T, and decreased levels of H.D.L, Apo A1 for O.S.M.F group when compared with control group. With increased grade of O.S.M.F. and duration of habit, S.G.P.T. & S.G.O.T. increased whereas, H.D.L. & Apo A1 decreased. All the values were statistically significant at p<0.01.

Keywords: apolipoprotien A1, high density lipoprotien, oral submucous fibrosis, serum glutamic oxaloacetic transaminase

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833 Formulation of Famotidine Solid Lipid Nanoparticles (SLN): Preparation, Evaluation and Release Study

Authors: Rachmat Mauludin, Nurmazidah

Abstract:

Background and purpose: Famotidine is an H2 receptor blocker. Absorption orally is rapid enough, but famotidine can be degraded by stomach acid causing dose reduction until 35.8% after 50 minutes. This drug also undergoes first-pass metabolism which reduced its bio availability only until 40-50%. To overcome these problems, Solid Lipid Nano particles (SLNs) as alternative delivery systems can be formulated. SLNs is a lipid-based drug delivery technology with 50-1000 nm particle size, where the drug incorporated into the bio compatible lipids and the lipid particles are stabilized using appropriate stabilizers. When the particle size is 200 nm or below, lipid containing famotidine can be absorbed through the lymphatic vessels to the subclavian vein, so first-pass metabolism can be avoided. Method: Famotidine SLNs with various compositions of stabilizer was prepared using a high-speed homogenization and sonication method. Then, the particle size distribution, zeta potential, entrapment efficiency, particle morphology and in vitro release profiles were evaluated. Optimization of sonication time also carried out. Result: Particle size of SLN by Particle Size Analyzer was in range 114.6 up to 455.267 nm. Ultrasonicated SLNs within 5 minutes generated smaller particle size than SLNs which was ultrasonicated for 10 and 15 minutes. Entrapment efficiency of SLNs were 74.17 up to 79.45%. Particle morphology of the SLNs was spherical and distributed individually. Release study of Famotidine revealed that in acid medium, 28.89 up to 80.55% of famotidine could be released after 2 hours. Nevertheless in basic medium, famotidine was released 40.5 up to 86.88% in the same period. Conclusion: The best formula was SLNs which stabilized by 4% Poloxamer 188 and 1 % Span 20, that had particle size 114.6 nm in diameter, 77.14% famotidine entrapped, and the particle morphology was spherical and distributed individually. SLNs with the best drug release profile was SLNs which stabilized by 4% Eudragit L 100-55 and 1% Tween 80 which had released 36.34 % in pH 1.2 solution, and 74.13% in pH 7.4 solution after 2 hours. The optimum sonication time was 5 minutes.

Keywords: famotodine, SLN, high speed homogenization, particle size, release study

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832 Response of Barley Quality Traits, Yield and Antioxidant Enzymes to Water-Stress and Chemical Inducers

Authors: Emad Hafez, Mahmoud Seleiman

Abstract:

Two field experiments were carried out in order to investigate the effect of chemical inducers [benzothiadiazole 0.9 mM L-1, oxalic acid 1.0 mM L-1, salicylic acid 0.2 mM L-1] on physiological and technological traits as well as on yields and antioxidant enzyme activities of barley grown under abiotic stress (i.e. water surplus and deficit conditions). Results showed that relative water content, leaf area, chlorophyll and yield as well as technological properties of barley were improved with chemical inducers application under water surplus and water-stress conditions. Antioxidant enzymes activity (i.e. catalase and peroxidase) were significantly increased in barley grown under water-stress and treated with chemical inducers. Yield and related parameters of barley presented also significant decrease under water-stress treatment, while chemical inducers application enhanced the yield-related traits. Starch and protein contents were higher in plants treated with salicylic acid than in untreated plants when water-stress was applied. In conclusion, results show that chemical inducers application have a positive interaction and synergetic influence and should be suggested to improve plant growth, yield and technological properties of water stressed barley. Salicylic acid application was better than oxalic acid and benzothiadiazole in terms of plant growth and yield improvement.

Keywords: antioxidant enzymes, drought stress, Hordeum vulgare L., quality, yield

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831 Nutritional Properties and Lipid Oxidation Assessments of Sucuks Prepared with Camel (Camelus Dromedarius) Meat and Hump

Authors: Mina Kargozari, Isabel Revilla Martin, Ángel A. Carbonell-Barrachina

Abstract:

Different formulations of Turkish fermented sausages (sucuks) prepared with camel meat-hump (CH), camel meat-beef fat (CB), beef-hump (BH) and beef-beef fat (BB), were characterized. The sausages were analytically compared to determine differences in proximate composition and total cholesterol content (TCC), quality parameters such as fatty acids profile and fat quality characteristics, and lipid oxidation parameters including peroxide value, thiobarbituric acid-reactive substances (TBARS) and resulted carbonyl compounds. The PUFAs/SFAs ratio was higher in CB and BB samples than CH and BH (p<0.05). The higher calculated atherogenic and thrombogenic indexes (AI and TI) were obtained from the samples made with hump (p< 0.05) as a result of high amounts of their SFAs. The CH sausages contained high amount of total fat (p<0.05) among all samples. The CB sucuks exhibited the highest protein content and the lowest TCC and rancidity at the end of ripening (p<0.05). The TBARS results showed that beef fat samples were more susceptible to lipid oxidation. Moreover, no significant difference (p<0.05) was observed for the values of short aldehydes among the sucuk samples excepting nonanal. This study demonstrated that supplementing camel meat for the production of dry-fermented sausage resulted in high quality products with good functional and nutritional characteristics.

Keywords: fermented sausages, quality properties, SPME, total cholesterol content

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830 Anti-Fibrillation Propensity of a Flavonoid Baicalein against the Fibrils of Hen Egg White Lysozyme: Potential Therapeutics for Lysozyme Amyloidosis

Authors: Naveed Ahmad Fazili

Abstract:

More than 20 human diseases involve the fibrillation of a specific protein/peptide which forms pathological deposits at various sites. Hereditary lysozyme amyloidosis is a systemic disorder which mostly affects liver, spleen and kidney. This conformational disorder is featured by lysozyme fibril formation. In vivo lysozyme fibrillation was simulated under in vitro conditions using a strong denaturant GdHCl at 3M concentration. Sharp decline in the ANS fluorescence intensity compared to the partially unfolded states, almost 20 fold increase in ThT fluorescence intensity, increase in absorbance at 450 nm suggesting turbidity, negative ellipticity peak in the far-UVCD at 217 nm, red shift of 50 nm compared to the native state in congo red assay and appearance of a network of long rope like fibrils in TEM analysis suggested HEWL fibrillation. Anti-fibrillation potency of baicalein against the preformed fibrils of HEWL was investigated following ThT assay in which there was a dose dependent decrease in ThT fluorescence intensity compared to the fibrillar state of HEWL with the maximum effect observed at 150 μM baicalein concentration, loss of negative ellipticity peak in the far-UVCD region, dip in the Rayleigh scattering intensity and absorbance at 350 nm and 450 nm respectively together with a reduction in the density of fibrillar structure in TEM imaging. Thus, it could be suggested that baicalein could prove to be a positive therapeutics for hereditary human lysozyme amyloidosis.

Keywords: amyloid fibrils, baicalein, congo red, negative ellipticity, therapeutics

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829 Formation of ZnS/ZnO Heterojunction for Photocatalytic Hydrogen Evolution Using Partial Oxidation and Chemical Precipitation Synthesis Methods

Authors: Saba Didarataee, Abbas Ali Khodadadi, Yadollah Mortazavi, Fatemeh Mousavi

Abstract:

Photocatalytic water splitting is one of the most attractive alternative methods for hydrogen evolution. A variety of nanoparticle engineering techniques were introduced to improve the activity of semiconductor photocatalysts. Among these methods, heterojunction formation is an appealing method due to its ability to effectively preventing electron-hole recombination and improving photocatalytic activity. Reaching an optimal ratio of the two target semiconductors for the formation of heterojunctions is still an open question. Considering environmental issues as well as the cost and availability, ZnS and ZnO are frequently studied as potential choices. In this study, first, the ZnS nanoparticle was synthesized in a hydrothermal process; the formation of ZnS nanorods with a diameter of 14-30 nm was confirmed by field emission scanning electron microscope (FESEM). Then two different methods, partial oxidation and chemical precipitation were employed to construct ZnS/ZnO core-shell heterojunction. X-ray diffraction (XRD), BET, and diffuse reflectance spectroscopy (DRS) analysis were carried out to determine crystallite phase, surface area, and bandgap of photocatalysts. Furthermore, the temperature of oxidation was specified by a temperature programmed oxidation (TPO) and was fixed at 510℃, at which mild oxidation occurred. The bandgap was calculated by the Kubelka-Munk method and decreased by increasing oxide content from 3.53 (pure ZnS) to 3.18 (pure ZnO). The optimal samples were determined by testing the photocatalytic activity of hydrogen evolution in a quartz photoreactor with side irradiation of UVC lamps with a wavelength of 254 nm. In both procedures, it was observed that the photocatalytic activity of the ZnS/ZnO composite was sensibly higher than the pure ZnS and ZnO, which is attributed to forming a type-II heterostructure. The best ratio of oxide to sulfide was 0.24 and 0.37 in partial oxidation and chemical precipitation, respectively. The highest hydrogen evolution was 1081 µmol/gr.h, gained from partial oxidizing of ZnS nanoparticles at 510℃ for 30 minutes.

Keywords: heterostructure, hydrogen, partial oxidation, photocatalyst, water splitting, ZnS

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828 Kinetics and Toxicological Effects of Kickxia elatine Extract-Based Silver Nanoparticles on Rat Brain Acetylcholinesterase

Authors: Noor Ul Huda, Mushtaq Ahmed, Nadia Mushtaq, Naila Sher, Rahmat Ali Khan

Abstract:

Purpose: The green synthesis of AgNPs has been favored over chemical synthesis due to their distinctive properties such as high dispersion, surface-to-volume ratio, low toxicity, and easy preparation. In the present work, the biosynthesis of AgNPs (KE-AgNPs) was carried out in one step by using the traditionally used plant Kickxia elatine (KE) extract and then investigated its enzyme inhibiting activity against rat’s brain acetylcholinesterase (AChE) in vitro. Methods: KE-AgNPs were synthesized from 1mM AgNO₃ using KE extract and characterized by UV–spectroscopy, SEM, EDX, XRD, and FTIR analysis. Rat’s brain acetylcholinesterase (AChE) inhibition activity was evaluated by the standard protocol. Results: UV–spectrum at 416 nm confirmed the formation of KE-AgNPs. X-ray diffraction (XRD) pattern presented 2θ values corresponding to the crystalline nature of KE-AgNPs with an average size of 42.47nm. The scanning electron microscope (SEM) analysis confirmed the presence of spherical-shaped and huge density KE-AgNPs with a size of 50nm. Fourier transform infrared spectroscopy (FT-IR) suggested that the functional groups present in KE extract and on the surface of KE-AgNPs are responsible for the stability of biosynthesized NPs. Energy dispersive X-ray (EDX) displayed an intense sharp peak at 3.2 keV, presenting that Ag was the chief element with 61.67%. Both KE extract and KE-AgNPs showed good and potent anti-AChE activity, with higher inhibition potential at a concentration of 175 µg/ml. Statistical analysis showed that both KEE and AgNPs exhibited non-competitive type inhibition against AChE, i.e., Vmax decreased (34.17-68.64% and 22.29- 62.10%) in the concentration-dependent mode for KEE and KE-AgNPs respectively and while Km values remained constant. Conclusions: KEE and KE-AgNPs can be considered an inhibitor of rats’ brain AChE, and the synthesis of KE-AgNPs-based drugs can be used as a cheaper and alternative option against diseases such as Alzheimer’s disease.

Keywords: Kickxia elatine, AgNPs, brain homogenate, acetylcholinesterase, kinetics

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827 Hydrophobically Modified Glycol Chitosan Nanoparticles as a Carrier for Etoposide

Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Javaid Irfan, Andreas G. Schätzlein, Ijeoma F Uchegbeu

Abstract:

Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study was to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxy succinimide and quaternisation to glycol chitosan backbone. To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymer had the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9,p<0.001). Using the hydrophobic fluorescent dye Nile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenograft tumor in-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reduced side effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

Keywords: glycol chitosan, Nile red, micelles, etoposide, A431 xenografts

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826 Integrated Lateral Flow Electrochemical Strip for Leptospirosis Diagnosis

Authors: Wanwisa Deenin, Abdulhadee Yakoh, Chahya Kreangkaiwal, Orawon Chailapakul, Kanitha Patarakul, Sudkate Chaiyo

Abstract:

LipL32 is an outer membrane protein present only on pathogenic Leptospira species, which are the causative agent of leptospirosis. Leptospirosis symptoms are often misdiagnosed with other febrile illnesses as the clinical manifestations are non-specific. Therefore, an accurate diagnostic tool for leptospirosis is indeed critical for proper and prompt treatment. Typical diagnosis via serological assays is generally performed to assess the antibodies produced against Leptospira. However, their delayed antibody response and complicated procedure are undoubtedly limited the practical utilization especially in primary care setting. Here, we demonstrate for the first time an early-stage detection of LipL32 by an integrated lateral-flow immunoassay with electrochemical readout (eLFIA). A ferrocene trace tag was monitored via differential pulse voltammetry operated on a smartphone-based device, thus allowing for on-field testing. Superior performance in terms of the lowest detectable limit of detection (LOD) of 8.53 pg/mL and broad linear dynamic range (5 orders of magnitude) among other sensors available thus far was established. Additionally, the developed test strip provided a straightforward yet sensitive approach for diagnosis of leptospirosis using the collected human sera from patients, in which the results were comparable to the real-time polymerase chain reaction technique.

Keywords: leptospirosis, electrochemical detection, lateral flow immunosensor, point-of-care testing, early-stage detection

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825 The Effects of Different Sowing Times on Seed Yield and Quality of Fenugreek (Trigonella foenum graecum L.) in East Mediterranean Region of Turkey

Authors: Lale Efe, Zeynep Gokce

Abstract:

In this study carried out in 2013-14 growing season in East Mediterranean Region of Turkey, it was aimed to investigate the effects of different sowing times on the seed yield and quality of fenugreek (Trigonella foenum graceum L.). Three fenugreek genotypes (Gürarslan, Candidate Line-1 and Genotype-1) were sown on 13.11.2013 and 07.03.2014 according to factorial randomized block design with 3 replications. Plant height (cm), branch number per plant, first pod height (cm), pod length (mm), seed number per pod (g), seed yield per plant (g), seed yield per decar (kg), thousand seed weight (g), mucilage rate (%), seed protein ratio (%), seed oil ratio (%), oleic acid (%), linoleic acid (%), palmitic acid (%) and stearic acid (%) were investigated. Among genotypes, while the highest seed yield per plant was obtained from Genotype-1 (5 g/plant), the lowest seed yield per plant was obtained from cv. Gürarslan (3.4 g/plant). According to genotype x sowing date interactions, it can be said that the highest seed yield per plant was taken in autumn sowing from Genotype-1 (6.6 g/plant) and the lowest seed yield per plant was taken in spring sowing from cv. Gürarslan (2.9 g/plant). Genotype-1 had the highest linoleic acid ratio (41.6 %). Cv. Gürarslan and Candidate Line-1 had the highest oleic acid ratio (respectively 17.8 % and 17.6%).

Keywords: fenugreek, seed yield and quality, sowing times, Trigonella foenum graecum L.

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824 New Active Dioxin Response Element Sites in Regulatory Region of Human and Viral Genes

Authors: Ilya B. Tsyrlov, Dmitry Y. Oshchepkov

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A computational search for dioxin response elements (DREs) in genes of proteins comprising the Ah receptor (AhR) cytosolic core complex was performed by highly efficient tool SITECON. Eventually, the following number of new DREs in 5’flanking region was detected by SITECON: one in AHR gene, five in XAP2, eight in HSP90AA1, and three in HSP90AB1 genes. Numerous DREs found in genes of AhR and AhR cytosolic complex members would shed a light on potential mechanisms of expression, the stoichiometry of unliganded AhR core complex, and its degradation vs biosynthesis dynamics resulted from treatment of target cells with the AhR most potent ligand, 2,3,7,8-TCDD. With human viruses, reduced susceptibility to TCDD of geneencoding HIV-1 P247 was justified by the only potential DRE determined in gag gene encoding HIV-1 P24 protein, whereas the regulatory region of CMV genes encoding IE gp/UL37 has five potent DRE, 1.65 kb/UL36 – six DRE, pp65 and pp71 – each has seven DRE, and pp150 – ten DRE. Also, from six to eight DRE were determined with SITECON in the regulatory region of HSV-1 IE genes encoding tegument proteins, UL36 and UL37, and of UL19 gene encoding bindingglycoprotein C (gC). So, TCDD in the low picomolar range may activate in human cells AhR: Arnt transcription pathway that triggers CMV and HSV-1 reactivation by binding to numerous promoter DRE within immediate-early (IE) genes UL37 and UL36, thus committing virus to the lytic cycle.

Keywords: dioxin response elements, Ah receptor, AhR: Arnt transcription pathway, human and viral genes

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823 Colour Formation and Maillard Reactions in Spray-Dried Milk Powders

Authors: Zelin Zhou, Timothy Langrish

Abstract:

Spray drying is the final stage of milk powder production. Traditionally, the quality of spray-dried milk powders has mainly been assessed using their physical properties, such as their moisture contents, while chemical changes occurring during the spray drying process have often been ignored. With growing concerns about food quality, it is necessary to establish a better understanding of heat-induced degradation due to the spray-drying process of skim milk. In this study, the extent of thermal degradation for skim milk in a pilot-scale spray dryer has been investigated using different inlet gas temperatures. The extent of heat-induced damage has been measured by the formation of advanced Maillard reaction products and the loss of soluble proteins at pH 4.6 as assessed by a fluorometric method. A significant increase in the extent of thermal degradation has been found when the inlet gas temperature increased from 170°C to 190°C, suggesting protein unfolding may play an important role in the kinetics of heat-induced degradation for milk in spray dryers. Colour changes of the spray-dried skim milk powders have also been analysed using a standard lighting box. Colourimetric analysis results were expressed in CIELAB colour space with the use of the E index (E) and the Chroma (C) for measuring the difference between colours and the intensity of the colours. A strong linear correlation between the colour intensity of the spray-dried skim milk powders and the formation of advanced Maillard reaction products has been observed.

Keywords: colour formation, Maillard reactions, spray drying, skim milk powder

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822 Magnesium Ameliorates Lipopolysaccharide-Induced Liver Injury in Mice

Authors: D. M. El-Tanbouly, R. M. Abdelsalam, A. S. Attia, M. T. Abdel-Aziz

Abstract:

Lipopolysaccharide (LPS) endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis. LPS administration induces systemic inflammation that mimics many of the initial clinical features of sepsis and has deleterious effects on several organs including the liver and eventually leading to septic shock and death. The present study aimed to investigate the protective effect of magnesium, a well-known cofactor in many enzymatic reactions and a critical component of the antioxidant system, on hepatic damage associated with LPS induced- endotoxima in mice. Mg (20 and 40 mg/kg, po) was administered for 7 consecutive days. Systemic inflammation was induced one hour after the last dose of Mg by a single dose of LPS (2 mg/kg, ip) and three hours thereafter plasma was separated, animals were sacrificed and their livers were isolated. LPS-treated mice suffered from hepatic dysfunction revealed by histological observation, elevation in plasma transaminases activities, C-reactive protein content and caspase-3, a critical marker of apoptosis. Liver inflammation was evident by elevation in liver cytokines contents (TNF-α and IL-10) and myeloperoxidase (MPO) activity. Additionally, oxidative stress was manifested by increased liver lipoperoxidation, glutathione depletion, elevated total nitrate/nitrite (NOx) content and glutathione peroxidase (GPx) activity. Pretreatment with Mg largely mitigated these alternations through its anti-inflammatory and antioxidant potentials. Mg, therefore, could be regarded as an effective strategy for prevention of liver damage associated with septicemia.

Keywords: LPS, liver damage, magnesium, septicemia

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821 Formulation of the N-Acylethanolamine, Linoleoylethanolamide into Cubosomes for Delivery across the Blood-Brain Barrier

Authors: Younus Mohammad, Anita B. Fallah, Ben J. Boyd, Shakila B. Rizwan

Abstract:

N-acylethanolamines (NAEs) are endogenous lipids, which have neuromodulatory properties. NAEs have shown neuroprotective properties in various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and ischemic stroke. However, NAEs are eliminated rapidly in vivo by enzymatic hydrolysis. We propose to encapsulate NAEs in liquid crystalline nanoparticles (cubosomes) to increase their biological half-life and explore their therapeutic potential. Recently, we have reported the co-formulation and nanostructural characterization of cubosomes containing the NAE, oleoylethanolamide and a synthetic cubosome forming lipid phytantriol. Here, we report on the formulation of cubosomes with the NAE, linoleoylethanolamide (LEA) as the core cubosome forming lipid. LEA-cubosomes were formulated in the presence of three different steric stabilisers: two brain targeting ligands, Tween 80 and Pluronic P188 and a control, Pluronic F127. Size, morphology and internal structure of formulations were characterized by dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo–TEM) and small angle X–ray scattering (SAXS), respectively. Chemical stability of LEA in formulations was investigated using high-performance liquid chromatography (HPLC). Cytotoxicity of formulations towards human cerebral microvascular endothelial cell line (hCMEC/D3) was also investigated using an MTT (3-[4, 5- dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay. All cubosome formulations had mean particle size of less than 250 nm and were uniformly distributed with polydispersity indices less than 0.2. Cubosomes produced had a bicontinuous cubic internal structure with an Im3m space group but different lattice parameters, indicating the different modes of interaction between the stabilisers and LEA. LEA in formulations was found to be chemically stable. At concentrations of up to 20 µg/mL LEA in the presence of all the stabilisers, greater than 80% cell viability was observed.

Keywords: blood-brain barrier, cubosomes, linoleoyl ethanolamide, N-acylethanolamines (NAEs)

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820 Immunoinformatic Design and Evaluation of an Epitope-Based Tetravalent Vaccine against Human Hand, Foot, and Mouth Disease

Authors: Aliyu Maje Bello, Yaowaluck Maprang Roshorm

Abstract:

Hand, foot, and mouth disease (HFMD) is a highly contagious viral infection affecting mostly infants and children. Although the Enterovirus A71 (EV71) is usually the major causative agent of HFMD, other enteroviruses such as coxsackievirus A16, A10, and A6 are also found in some of the recent outbreaks. The commercially available vaccines have demonstrated their effectiveness against only EV71 infection but no protection against other enteroviruses. To address the limitation of the monovalent EV71 vaccine, the present study thus designed a tetravalent vaccine against the four major enteroviruses causing HFMD and primarily evaluated the designed vaccine using an immunoinformatics approach. The immunogen was designed to contain the EV71 VP1 protein and multiple reported epitopes from all four distinct enteroviruses and thus designated a tetravalent vaccine. The 3D structure of the designed tetravalent vaccine was modeled, refined, and validated. Epitope screening showed the presence of B-cell, CTL, CD4 T cell, and IFN epitopes with vast application among the Asian population. Docking analysis confirmed the stable and strong binding interactions between the immunogen and immune receptor B-cell receptor (BCR). In silico cloning and immune simulation analyses guaranteed high efficiency and sufficient expression of the vaccine candidate in humans. Overall, the promising results obtained from the in-silico studies of the proposed tetravalent vaccine make it a potential candidate worth further experimental validation.

Keywords: enteroviruses, coxsackieviruses, hand foot and mouth disease, immunoinformatics, tetravalent vaccine

Procedia PDF Downloads 49
819 Ellagic Acid Enhanced Apoptotic Radiosensitivity via G1 Cell Cycle Arrest and γ-H2AX Foci Formation in HeLa Cells in vitro

Authors: V. R. Ahire, A. Kumar, B. N. Pandey, K. P. Mishra, G. R. Kulkarni

Abstract:

Radiation therapy is an effective vital strategy used globally in the treatment of cervical cancer. However, radiation efficacy principally depends on the radiosensitivity of the tumor, and not all patient exhibit significant response to irradiation. A radiosensitive tumor is easier to cure than a radioresistant tumor which later advances to local recurrence and metastasis. Herbal polyphenols are gaining attention for exhibiting radiosensitization through various signaling. Current work focuses to study the radiosensitization effect of ellagic acid (EA), on HeLa cells. EA intermediated radiosensitization of HeLa cells was due to the induction γ-H2AX foci formation, G1 phase cell cycle arrest, and loss of reproductive potential, growth inhibition, drop in the mitochondrial membrane potential and protein expression studies that eventually induced apoptosis. Irradiation of HeLa in presence of EA (10 μM) to doses of 2 and 4 Gy γ-radiation produced marked tumor cytotoxicity. EA also demonstrated radio-protective effect on normal cell, NIH3T3 and aided recovery from the radiation damage. Our results advocate EA to be an effective adjuvant for improving cancer radiotherapy as it displays striking tumor cytotoxicity and reduced normal cell damage instigated by irradiation.

Keywords: apoptotic radiosensitivity, ellagic acid, mitochondrial potential, cell-cycle arrest

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818 The Rational Design of Original Anticancer Agents Using Computational Approach

Authors: Majid Farsadrooh, Mehran Feizi-Dehnayebi

Abstract:

Serum albumin is the most abundant protein that is present in the circulatory system of a wide variety of organisms. Although it is a significant macromolecule, it can contribute to osmotic blood pressure and also, plays a superior role in drug disposition and efficiency. Molecular docking simulation can improve in silico drug design and discovery procedures to propound a lead compound and develop it from the discovery step to the clinic. In this study, the molecular docking simulation was applied to select a lead molecule through an investigation of the interaction of the two anticancer drugs (Alitretinoin and Abemaciclib) with Human Serum Albumin (HSA). Then, a series of new compounds (a-e) were suggested using lead molecule modification. Density functional theory (DFT) including MEP map and HOMO-LUMO analysis were used for the newly proposed compounds to predict the reactivity zones on the molecules, stability, and chemical reactivity. DFT calculation illustrated that these new compounds were stable. The estimated binding free energy (ΔG) values for a-e compounds were obtained as -5.78, -5.81, -5.95, -5,98, and -6.11 kcal/mol, respectively. Finally, the pharmaceutical properties and toxicity of these new compounds were estimated through OSIRIS DataWarrior software. The results indicated no risk of tumorigenic, irritant, or reproductive effects and mutagenicity for compounds d and e. As a result, compounds d and e, could be selected for further study as potential therapeutic candidates. Moreover, employing molecular docking simulation with the prediction of pharmaceutical properties helps to discover new potential drug compounds.

Keywords: drug design, anticancer, computational studies, DFT analysis

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817 Hepatoprotective Effects of Parsley, Basil, and Chicory Aqueous Extracts against Dexamethasone-Induced in Experimental Rats

Authors: Hanan A. Soliman, Mohamed A. El-Desouky, Walaa G. Hozayen, Rasha R. Ahmed, Amal K . Khaliefa

Abstract:

Aim: The objective of this study is to investigate the hypoglycemic, hypolipidemic, and hepatoprotective effects of the aqueous extract of parsley, basil, and chicory whole plant in normal and dexamethasone (Dex) rats. Materials and Methods: 50 female albino rats were used in this study and divided into 5 groups (for each 10). Group (1) fed basal diet and maintained as negative control group. Group (2) received Dex in a dose of (0.1 mg/kg b. wt.). Groups 3, 4, and 5 were treated with Dex along with three different plant extracts of parsley, basil, and chicory (2 g/kg b. wt.), (400 mg/kg b. wt.), and (100 mg/kg b. wt.), respectively. Results: All these groups were treated given three times per week for 8 consecutive weeks. Dex-induced alterations in the levels of serum glucose, triglyceride, cholesterol, low-density lipoprotein-cholesterol levels and cardiovascular indices and serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, liver thiobarbituric acid (TBARS) levels increased, while high-density lipoprotein-cholesterol, total protein, albumin, and liver glutathione (GSH) levels decreased. On the other hand, plant extracts succeeded to modulate these observed abnormalities resulting from Dex as indicated by the reduction of glucose, cholesterol, TBARS, and the pronounced improvement of the investigated biochemical and antioxidant parameters. Conclusions: It was concluded that probably, due to its antioxidant property, parsley, basil, and chicory extracts have hepatoprotective effects in Dex-induced in rats.

Keywords: antioxidants, dexamethasone, hyperglycemia, hyperlipidemia

Procedia PDF Downloads 226
816 Intestine Characteristics and Blood Profile of Broiler Chickens Treated with Garlic

Authors: Mary Anthony Oguike, Ilouno, Amaduruonye

Abstract:

A completely randomized design experiment with 3 treatments was conducted to study the effects of garlic on intestine characteristics, haematology and serum biochemistry of Marshal broilers. Thirty three (33) broiler chicks were randomly allotted to each treatment designated T1, T2 and T3. The birds in each treatment were replicated 3 times with 11 broilers per replicate. They were fed diets supplemented with garlic at 0, 1.5 and 2.5 % /kg feed for t1, T2 and T3, respectively with T1 as control. Data were collected on intestine parameters, serum biochemical parameters and haematological indices. The results showed significant (P>0.05) dose-dependent decrease in intestine weight and caeca microbial load of the broilers. The intestine of broilers in the treatments showed normal histological architecture in all the treatments. The red blood cell (RBC), white blood cell (WBC), haemoglobin (Hb) and other haematological indices showed no significant differences (P<0.05) among the treatments. Cholesterol, globulin, glucose and alanin aminotransferase (ALT) were significantly different (P<0.05) among the treatment groups. Serum biochemical parameters such as, total protein albumin, bilirubin and others were not significant among the treatments. All the blood parameters studied fall within the normal range for broilers. Garlic supplementation in the diets of broilers did not have any detrimental effects on the treated birds since their serum biochemistry and haematology fall within the normal range for broilers birds. The microbial examination of intestine and caeca, as well as the histopathological studies of the intestine confirmed antimicrobial properties of garlic.

Keywords: broiler, biochemistry and haematology, garlic, intestine

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815 NiSe-Ni₃Se₂/Multiwalled Carbon Nanotubes as Efficient Electrocatalysts for the Oxygen Evolution Reaction in Alkaline Media

Authors: Oluwaseun A. Oyetade, Roelof J. Kriek

Abstract:

The development of effective catalysts for the oxygen evolution reaction (OER) is of great importance to combat energy-related concerns in the environment. Herein, we report a one-step solvothermal method employed for the fabrication of nickel selenide hybrids (NiSe-Ni₃Se₂) and a series of nickel selenide hybrid/multiwalled carbon nanotube composites (NiSe-Ni₃Se₂/MWCNT) as electrocatalysts for OER in alkaline media. The catalytic activities of these catalysts were investigated via several electrochemical characterization techniques, such as linear sweep voltammetry, chronoamperometric studies at constant potential, electrochemical surface area determination, and Tafel slope calculation, under alkaline conditions. Morphological observations demonstrated the agglomeration of non-uniform NiSe-Ni₃Se₂ microspheres around carbon nanotubes (CNTs), demonstrating the successful synthesis of NiSe-Ni₃Se₂/MWCNT nanocomposites. Among the tested electrocatalysts, the 20% NiSe-Ni₃Se₂/MWCNT nanocomposite demonstrated the highest activity, exhibiting an overpotential of 325 mV to achieve a current density of 10 mA.cm⁻² in 0.1 mol.dm⁻³ KOH solution. The NiSe-Ni₃Se₂/MWCNT nanocomposites showed improved activity toward OER compared to bare NiSe-Ni₃Se₂ hybrids and MWCNTs, exhibiting an overpotential of 528, 392 and 434 mV for 10%, 30% and 50% NiSe-Ni₃Se₂/MWCNT nanocomposites, respectively. These results compare favourably to the overpotential of noble catalysts, such as RuO₂ and IrO₂. Our results imply that the addition of MWCNTs increased the activity of NiSe-Ni₃Se₂ hybrids due to an increased number of catalytic sites, dispersion of NiSe-Ni₃Se₂ hybrid nanoparticles, and electronic conductivity of the nanocomposites. These nanocomposites also demonstrated better long-term stability compared to NiSe-Ni₃Se₂ hybrids and MWCNTs. Hence, NiSe-Ni₃Se₂/MWCNT nanocomposites possess the potential as effective electrocatalysts for OER in alkaline media.

Keywords: carbon nanotubes, electrocatalysts, nanocomposites, nickel selenide hybrids, oxygen evolution reaction

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814 Paraoxonase 1 (PON 1) Arylesterase Activity and Apolipoprotein B: Predictors of Myocardial Infarction

Authors: Mukund Ramchandra Mogarekar, Pankaj Kumar, Shraddha Vilas More

Abstract:

Background: Myocardial infarction (MI) is defined as myocardial cell death due to prolonged ischemia as a consequence of atherosclerosis. TC, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), Apo B, and lipoprotein(a) was found as atherogenic factors while high-density lipoprotein cholesterol (HDL-C) was anti-atherogenic. Methods and Results: The study group consists of 40, MI subjects and 40 healthy individuals in control group. PON 1 Arylesterase activity (ARE) was measured by using phenylacetate. Phenotyping was done by double substrate method, serum AOPP by using chloramine T and Apo B by Turbidimetric immunoassay. PON 1 ARE activities were significantly lower (p< 0.05) and AOPPs & Apo B were higher in MI subjects (p> 0.05). Trimodal distribution of QQ, QR, and RR phenotypes of study population showed no significant difference among cases and controls (p> 0.05). Univariate binary logistic regression analysis showed independent association of TC, HDL, LDL, AOPP, Apo B, and PON 1 ARE activity with MI and multiple forward binary logistic regression showed PON 1 ARE activity and serum Apo B as an independent predictor of MI. Conclusions: Decrease in PON 1 ARE activity in MI subjects than in controls suggests increased oxidative stress in MI which is reflected by significantly increased AOPP and Apo B. PON1 polymorphism of QQ, QR and RR showed no significant difference in protection against MI. Univariate and multiple binary logistic regression showed PON1 ARE activity and serum Apo B as an independent predictor of MI.

Keywords: advanced oxidation protein product, apolipoprotein B, PON 1 arylesterase activity, myocardial infarction

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813 Formulation and Evaluation of Metformin Hydrochloride Microparticles via BÜCHI Nano-Spray Dryer B-90

Authors: Tamer Shehata

Abstract:

Recently, nanotechnology acquired a great interest in the field of pharmaceutical production. Several pharmaceutical equipment were introduced into the research field for production of nanoparticles, among them, BÜCHI’ fourth generation nano-spray dryer B-90. B-90 is specialized with single step of production and drying of nano and microparticles. Currently, our research group is investigating several pharmaceutical formulations utilizing BÜCHI Nano-Spray Dryer B-90 technology. One of our projects is the formulation and evaluation of metformin hydrochloride mucoadhesive microparticles for treatment of type 2-diabetis. Several polymers were investigated, among them, gelatin and sodium alginate. The previous polymers are natural polymers with mucoadhesive properties. Preformulation studies such as atomization head mesh size, flow rate, head temperature, polymer solution viscosity and surface tension were performed. Postformulation characters such as particle size, flowability, surface scan and dissolution profile were evaluated. Finally, the pharmacological activity of certain selected formula was evaluated in streptozotocin-induced diabetic rats. B-90’spray head was 7 µm hole heated to 120 with air flow rate 3.5 mL/min. The viscosity of the solution was less than 11.5 cP with surface tension less than 70.1 dyne/cm. Successfully, discrete, non-aggregated particles and free flowing powders with particle size was less than 2000 nm were obtained. Gelatin and Sodium alginate combination in ratio 1:3 were successfully sustained the in vitro release profile of the drug. Hypoglycemic evaluation of the previous formula showed a significant reduction of blood glucose level over 24 h. In conclusion, mucoadhesive metformin hydrochloride microparticles obtained from B-90 could offer a convenient dosage form with enhanced hypoglycemic activity.

Keywords: mucoadhesive, microparticles, metformin hydrochloride, nano-spray dryer

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812 Revealing Potential Drug Targets against Proto-Oncogene Wnt10B by Comparative Molecular Docking

Authors: Shazia Mannan, Zunera Khalid, Hammad-Ul-Mubeen

Abstract:

Wingless type Mouse mammary tumor virus (MMTV) Integration site-10B (Wnt10B) is an important member of the Wnt protein family that functions as cellular messenger in paracrine manner. Aberrant Wnt10B activity is the cause of several abnormalities including cancers of breast, cervix, liver, gastric tract, esophagus, pancreas as well as physiological problems like obesity, and osteoporosis. The objective of this study was to determine the possible inhibitors against aberrant expression of Wnt10B in order to prevent and treat the physiological disorders associated with it. Wnt10B3D structure was predicted by using comparative modeling and then analyzed by PROCHECK, Verify3D, and Errat. The model having 84.54% quality value was selected and acylated to satisfy the hydrophobic nature of Wnt10B. For search of inhibitors, virtual screening was performed on Natural Products (NP) database. The compounds were filtered and ligand-based screening was performed using the antagonist for mouse Wnt-3A. This resulted in a library of 272 unique compounds having most potent drug like activities for Wnt-4. Out of the 271 molecules analyzed three small molecules ZINC35442871, ZINC85876388, and ZINC00754234 having activity against Wnt4 abbarent expression were found common through docking experiment of Wnt10B. It is concluded that the three molecules ZINC35442871, ZINC85876388, and ZINC00754234 can be considered as lead compounds for performing further drug designing experiments against aberrant Wnt expressions.

Keywords: Wnt10B inhibitors, comparative computational studies, proto-oncogene, molecular docking

Procedia PDF Downloads 137