Search results for: in vivo biomarkers
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1060

Search results for: in vivo biomarkers

880 The Response of Soil Biodiversity to Agriculture Practice in Rhizosphere

Authors: Yan Wang, Guowei Chen, Gang Wang

Abstract:

Soil microbial diversity is one of the important parameters to assess the soil fertility and soil health, even stability of the ecosystem. In this paper, we aim to reveal the soil microbial difference in rhizosphere and root zone, even to pick the special biomarkers influenced by the long term tillage practices, which included four treatments of no-tillage, ridge tillage, continuous cropping with corn and crop rotation with corn and soybean. Here, high-throughput sequencing was performed to investigate the difference of bacteria in rhizosphere and root zone. The results showed a very significant difference of species richness between rhizosphere and root zone soil at the same crop rotation system (p < 0.01), and also significant difference of species richness was found between continuous cropping with corn and corn-soybean rotation treatment in the rhizosphere statement, no-tillage and ridge tillage in root zone soils. Implied by further beta diversity analysis, both tillage methods and crop rotation systems influence the soil microbial diversity and community structure in varying degree. The composition and community structure of microbes in rhizosphere and root zone soils were clustered distinctly by the beta diversity (p < 0.05). Linear discriminant analysis coupled with effect size (LEfSe) analysis of total taxa in rhizosphere picked more than 100 bacterial taxa, which were significantly more abundant than that in root zone soils, whereas the number of biomarkers was lower between the continuous cropping with corn and crop rotation treatment, the same pattern was found at no-tillage and ridge tillage treatment. Bacterial communities were greatly influenced by main environmental factors in large scale, which is the result of biological adaptation and acclimation, hence it is beneficial for optimizing agricultural practices.

Keywords: tillage methods, biomarker, biodiversity, rhizosphere

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879 Relationship of Oxidative Stress to Elevated Homocysteine and DNA Damage in Coronary Artery Disease Patients

Authors: Shazia Anwer Bukhari, Madiha Javeed Ghani, Muhammad Ibrahim Rajoka

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Objective: Biochemical, environmental, physical and genetic factors have a strong effect on the development of coronary disease (CAD). Plasma homocysteine (Hcy) level and DNA damage play a pivotal role in its development and progression. The aim of this study was to investigate the predictive strength of an oxidative stress, clinical biomarkers and total antioxidant status (TAS) in CAD patients to find the correlation of homocysteine, TOS and oxidative DNA damage with other clinical parameters. Methods: Sixty confirmed patients with CAD and 60 healthy individuals as control were included in this study. Different clinical and laboratory parameters were studied in blood samples obtained from patients and control subjects using commercially available biochemical kits and statistical software Results: As compared to healthy individuals, CAD patients had significantly higher concentrations of indices of oxidative stress: homocysteine (P=0.0001), total oxidative stress (TOS) (P=0.0001), serum cholesterol (P=0.04), low density lipoprotein cholesterol (LDL) (P=0.01), high density lipoprotein-cholesterol (HDL) (P=0.0001), and malondialdehyde (MDA) (P=0.001) than those of healthy individuals. Plasma homocysteine level and oxidative DNA damage were positively correlated with cholesterol, triglycerides, systolic blood pressure, urea, total protein and albumin (P values= 0.05). Both Hcy and oxidative DNA damage were negatively correlated with TAS and proteins. Conclusion: Coronary artery disease patients had a significant increase in homocysteine level and DNA damage due to increased oxidative stress. In conclusion, our study shows a significantly increase in lipid peroxidation, TOS, homocysteine and DNA damage in the erythrocytes of patients with CAD. A significant decrease level of HDL-C and TAS was observed only in CAD patients. Therefore these biomarkers may be useful diagnosis of patients with CAD and play an important role in the pathogenesis of CAD.

Keywords: antioxidants, coronary artery disease, DNA damage, homocysteine, oxidative stress, malondialdehyde, 8-Hydroxy-2’deoxyguanosine

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878 Treatment of Premalignant Lesions: Curcumin a Promising Non-Surgical Option

Authors: Heba A. Hazzah, Ragwa M. Farid, Maha M. A. Nasra, Mennatallah Zakria, Magda A. El Massik, Ossama Y. Abdallah

Abstract:

Introduction: Curcumin (Cur) is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. The buccal delivery of curcumin can be useful for both systemic and local disease treatments such as gingivitis, periodontal diseases, oral carcinomas, and precancerous oral lesions. Despite of its high activity, it suffers a limited application due to its low oral bioavailability, poor aqueous solubility, and instability. Aim: Preparation and characterization of curcumin solid lipid nanoparticles with a high loading capacity into a mucoadhesive gel for buccal application. Methodology: Curcumin was formulated as nanoparticles using different lipids, namely Gelucire 39/01, Gelucire 50/13, Precirol, Compritol, and Polaxomer 407 as a surfactant. The SLN were dispersed in a mucoadhesive gel matrix to be applied to the buccal mucosa. All formulations were evaluated for their content, entrapment efficiency, particle size, in vitro drug dialysis, ex vivo mucoadhesion test, and ex vivo permeation study using chicken buccal mucosa. Clinical evaluation was conducted on 15 cases suffering oral erythroplakia and erosive lichen planus. Results: The results showed high entrapment efficiency reaching almost 90 % using Gelucire 50, the loaded gel with Cur-SLN showed good adhesion property and 25 minutes in vivo residence time. In addition to stability enhancement for the Cur powder. All formulae did not show any drug permeated however, a significant amount of Cur was retained within the mucosal tissue. Pain and lesion sizes were significantly reduced upon topical treatment. Complete healing was observed after 6 weeks of treatment. Conclusion: These results open a room for the pharmaceutical technology to optimize the use of this golden magical powder to get the best out of it. In addition, the lack of local anti-inflammatory compounds with reduced side effects intensifies the importance of studying natural products for this purpose.

Keywords: curcumin, erythroplakia, mucoadhesive, pain, solid lipid nanoparticles

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877 Synthesis of Double Dye-Doped Silica Nanoparticles and Its Application in Paper-Based Chromatography

Authors: Ka Ho Yau, Jan Frederick Engels, Kwok Kei Lai, Reinhard Renneberg

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Lateral flow test is a prevalent technology in various sectors such as food, pharmacology and biomedical sciences. Colloidal gold (CG) is widely used as the signalling molecule because of the ease of synthesis, bimolecular conjugation and its red colour due to intrinsic SPRE. However, the production of colloidal gold is costly and requires vigorous conditions. The stability of colloidal gold are easily affected by environmental factors such as pH, high salt content etc. Silica nanoparticles are well known for its ease of production and stability over a wide range of solvents. Using reverse micro-emulsion (w/o), silica nanoparticles with different sizes can be produced precisely by controlling the amount of water. By incorporating different water-soluble dyes, a rainbow colour of the silica nanoparticles could be produced. Conjugation with biomolecules such as antibodies can be achieved after surface modification of the silica nanoparticles with organosilane. The optimum amount of the antibodies to be labelled was determined by Bradford Assay. In this work, we have demonstrated the ability of the dye-doped silica nanoparticles as a signalling molecule in lateral flow test, which showed a semi-quantitative measurement of the analyte. The image was further analysed for the LOD=10 ng of the analyte. The working range and the linear range of the test were from 0 to 2.15μg/mL and from 0 to 1.07 μg/mL (R2=0.988) respectively. The performance of the tests was comparable to those using colloidal gold with the advantages of lower cost, enhanced stability and having a wide spectrum of colours. The positives lines can be imaged by naked eye or by using a mobile phone camera for a better quantification. Further research has been carried out in multicolour detection of different biomarkers simultaneously. The preliminary results were promising as there was little cross-reactivity being observed for an optimized system. This approach provides a platform for multicolour detection for a set of biomarkers that enhances the accuracy of diseases diagnostics.

Keywords: colorimetric detection, immunosensor, paper-based biosensor, silica

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876 Monitoring Air Pollution Effects on Children for Supporting Public Health Policy: Preliminary Results of MAPEC_LIFE Project

Authors: Elisabetta Ceretti, Silvia Bonizzoni, Alberto Bonetti, Milena Villarini, Marco Verani, Maria Antonella De Donno, Sara Bonetta, Umberto Gelatti

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Introduction: Air pollution is a global problem. In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and particulate matter as carcinogenic to human. The study of the health effects of air pollution in children is very important because they are a high-risk group in terms of the health effects of air pollution and early exposure during childhood can increase the risk of developing chronic diseases in adulthood. The MAPEC_LIFE (Monitoring Air Pollution Effects on Children for supporting public health policy) is a project founded by EU Life+ Programme which intends to evaluate the associations between air pollution and early biological effects in children and to propose a model for estimating the global risk of early biological effects due to air pollutants and other factors in children. Methods: The study was carried out on 6-8-year-old children living in five Italian towns in two different seasons. Two biomarkers of early biological effects, primary DNA damage detected with the comet assay and frequency of micronuclei, were investigated in buccal cells of children. Details of children diseases, socio-economic status, exposures to other pollutants and life-style were collected using a questionnaire administered to children’s parents. Child exposure to urban air pollution was assessed by analysing PM0.5 samples collected in the school areas for PAHs and nitro-PAHs concentration, lung toxicity and in vitro genotoxicity on bacterial and human cells. Data on the chemical features of the urban air during the study period were obtained from the Regional Agency for Environmental Protection. The project created also the opportunity to approach the issue of air pollution with the children, trying to raise their awareness on air quality, its health effects and some healthy behaviors by means of an educational intervention in the schools. Results: 1315 children were recruited for the study and participate in the first sampling campaign in the five towns. The second campaign, on the same children, is still ongoing. The preliminary results of the tests on buccal mucosa cells of children will be presented during the conference as well as the preliminary data about the chemical composition and the toxicity and genotoxicity features of PM0.5 samples. The educational package was tested on 250 children of the primary school and showed to be very useful, improving children knowledge about air pollution and its effects and stimulating their interest. Conclusions: The associations between levels of air pollutants, air mutagenicity and biomarkers of early effects will be investigated. A tentative model to calculate the global absolute risk of having early biological effects for air pollution and other variables together will be proposed and may be useful to support policy-making and community interventions to protect children from possible health effects of air pollutants.

Keywords: air pollution exposure, biomarkers of early effects, children, public health policy

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875 Identification of Blood Biomarkers Unveiling Early Alzheimer's Disease Diagnosis Through Single-Cell RNA Sequencing Data and Autoencoders

Authors: Hediyeh Talebi, Shokoofeh Ghiam, Changiz Eslahchi

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Traditionally, Alzheimer’s disease research has focused on genes with significant fold changes, potentially neglecting subtle but biologically important alterations. Our study introduces an integrative approach that highlights genes crucial to underlying biological processes, regardless of their fold change magnitude. Alzheimer's Single-cell RNA-seq data related to the peripheral blood mononuclear cells (PBMC) was extracted from the Gene Expression Omnibus (GEO). After quality control, normalization, scaling, batch effect correction, and clustering, differentially expressed genes (DEGs) were identified with adjusted p-values less than 0.05. These DEGs were categorized based on cell-type, resulting in four datasets, each corresponding to a distinct cell type. To distinguish between cells from healthy individuals and those with Alzheimer's, an adversarial autoencoder with a classifier was employed. This allowed for the separation of healthy and diseased samples. To identify the most influential genes in this classification, the weight matrices in the network, which includes the encoder and classifier components, were multiplied, and focused on the top 20 genes. The analysis revealed that while some of these genes exhibit a high fold change, others do not. These genes, which may be overlooked by previous methods due to their low fold change, were shown to be significant in our study. The findings highlight the critical role of genes with subtle alterations in diagnosing Alzheimer's disease, a facet frequently overlooked by conventional methods. These genes demonstrate remarkable discriminatory power, underscoring the need to integrate biological relevance with statistical measures in gene prioritization. This integrative approach enhances our understanding of the molecular mechanisms in Alzheimer’s disease and provides a promising direction for identifying potential therapeutic targets.

Keywords: alzheimer's disease, single-cell RNA-seq, neural networks, blood biomarkers

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874 Immunosupressive Effect of Chloroquine through the Inhibition of Myeloperoxidase

Authors: J. B. Minari, O. B. Oloyede

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Polymorphonuclear neutrophils (PMNs) play a crucial role in a variety of infections caused by bacteria, fungi, and parasites. Indeed, the involvement of PMNs in host defence against Plasmodium falciparum is well documented both in vitro and in vivo. Many of the antimalarial drugs such as chloroquine used in the treatment of human malaria significantly reduce the immune response of the host in vitro and in vivo. Myeloperoxidase is the most abundant enzyme found in the polymorphonuclear neutrophil which plays a crucial role in its function. This study was carried out to investigate the effect of chloroquine on the enzyme. In investigating the effects of the drug on myeloperoxidase, the influence of concentration, pH, partition ratio estimation and kinetics of inhibition were studied. This study showed that chloroquine is concentration-dependent inhibitor of myeloperoxidase with an IC50 of 0.03 mM. Partition ratio estimation showed that 40 enzymatic turnover cycles are required for complete inhibition of myeloperoxidase in the presence of chloroquine. The influence of pH on the effect of chloroquine on the enzyme showed significant inhibition of myeloperoxidase at physiological pH. The kinetic inhibition studies showed that chloroquine caused a non-competitive inhibition with an inhibition constant Ki of 0.27mM. The results obtained from this study shows that chloroquine is a potent inhibitor of myeloperoxidase and it is capable of inactivating the enzyme. It is therefore considered that the inhibition of myeloperoxidase in the presence of chloroquine as revealed in this study may partly explain the impairment of polymorphonuclear neutrophil and consequent immunosuppression of the host defence system against secondary infections.

Keywords: myeloperoxidase, chloroquine, inhibition, neutrophil, immune

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873 Dynamics of Antioxidant and Anti-Radical Activity of the Extracts of Certain Plants of Kazakhstan

Authors: A. Kazbekova, A. Kudaibergenov, G. Atazhanova, S. Adekenov

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In recent years, it achieved some progress such a direction as to study the possibility of correlation between different types of biological activity. In particular, in our work, we consider questions such as: the impact of the qualitative composition of total substances in the example of plant extracts on antioxidant and antiradical activity, the presents of correlation between these types of activity, etc. It is known that there is a relationship between the values of optical density of working solutions of extracts and corresponding bioactivity in vitro, in particular, the antioxidant and hepatoprotective effects. In this study, we have identified that among some studied species of wormwood (Artemisia viridis Wild, Artemisia jacutica Drob, Artemisia annua L, Artemisia siversiana Wild, Artemisia adamsii Bess, Artemisia tianschanica, Artemisia obtusiloba Ledeb., Artemisia heptopotamica), as well as extracts of Inula caspica, Аjania tenuifolia, Abies sibirica, Galatella songorica, Mentha asiatica and Thymus mugodzharicus it was identified that the highest content of polyphenol compounds is in Thymus mugodzharicus. At the same time, we determined the antioxidant and antiradical activity, which was the highest for the Thymus mugodzharicus. Butylhydroxyanisole and ascorbic acid were used as comparison substances. Also, it was established that antioxidant and anti-radical activities depend on the concentration of the of all investigated samples. Based on obtained data, we believe that the extract of Thymus mugodzharicus can be recommended for further study on the antioxidant and antiradical activity in vivo, as well as the opportunity of this sample to demonstrate hepatoprotective effect. The study was sponsored by SANTO academic program.

Keywords: in vitro, in vivo, antioxidant, hepatoprotective effect

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872 Anti-Angiogenic Effects of the Macrovipera lebetina obtusa Snake Crude Venom and Obtustatin

Authors: Narine Ghazaryan, Joana Catarina Macedo, Sara Vaz, Naira Ayvazyan, Elsa Logarinho

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Macrovipera lebetina obtusa (MLO) is a poisonous snake in Armenia. Obtustatin represents the shortest known monomeric disintegrin, isolated from the snake venom of MLO, and is known to specifically inhibit α1β1 integrin. Its oncostatic effect is due to the inhibition of angiogenesis, which likely arises from α1β1 integrin inhibition in the endothelial cells. To explore the therapeutic potential of the MLO snake venom and obtustatin, we studied activity of obtustatin and MLO venom in vitro, by testing their efficacy in human dermal microvascular endothelial cells (HMVEC-D) and in vivo, using chick embryo chorioallantoic membrane assay (CAM assay). Our in vitro results showed that obtustatin in comparison with MLO venom did not exhibit cytotoxic activity in HMVEC-D cells in comparison to MLO venom. But in vivo results have shown that 4µg /embryo (90 µM) of obtustatin inhibited angiogenesis induced by FGF2 by 17% while MLO snake venom induced 22% reduction of the angiogenic index. The concentration of obtustatin in the crude MLO venom was 0.3 nM, which is 300.000 times less than the concentration of the obtustatin itself. Given this enormous difference in concentration, it is likely that some components of the crude venom contribute to the observed anti-angiogenic effect. Hypotheses will be ascertained to justify this action: components in the MLO venom may increase obtustatin efficacy or have independent but synergic anti-angiogenic activities.

Keywords: angiogenesis, alpa1 beta 1 integrin, Macrovipera lebetina obtusa, obtustatin

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871 In vitro and in vivo Infectivity of Coxiella burnetii Strains from French Livestock

Authors: Joulié Aurélien, Jourdain Elsa, Bailly Xavier, Gasqui Patrick, Yang Elise, Leblond Agnès, Rousset Elodie, Sidi-Boumedine Karim

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Q fever is a worldwide zoonosis caused by the gram-negative obligate intracellular bacterium Coxiella burnetii. Following the recent outbreaks in the Netherlands, a hyper virulent clone was found to be the cause of severe human cases of Q fever. In livestock, Q fever clinical manifestations are mainly abortions. Although the abortion rates differ between ruminant species, C. burnetii’s virulence remains understudied, especially in enzootic areas. In this study, the infectious potential of three C. burnetii isolates collected from French farms of small ruminants were compared to the reference strain Nine Mile (in phase II and in an intermediate phase) using an in vivo (CD1 mice) model. Mice were challenged with 105 live bacteria discriminated by propidium monoazide-qPCR targeting the icd-gene. After footpad inoculation, spleen and popliteal lymph node were harvested at 10 days post-inoculation (p.i). The strain invasiveness in spleen and popliteal nodes was assessed by qPCR assays targeting the icd-gene. Preliminary results showed that the avirulent strains (in phase 2) failed to pass the popliteal barrier and then to colonize the spleen. This model allowed a significant differentiation between strain’s invasiveness on biological host and therefore identifying distinct virulence profiles. In view of these results, we plan to go further by testing fifteen additional C. burnetii isolates from French farms of sheep, goat and cattle by using the above-mentioned in vivo model. All 15 strains display distant MLVA (multiple-locus variable-number of tandem repeat analysis) genotypic profiles. Five of the fifteen isolates will bee also tested in vitro on ovine and bovine macrophage cells. Cells and supernatants will be harvested at day1, day2, day3 and day6 p.i to assess in vitro multiplication kinetics of strains. In conclusion, our findings might help the implementation of surveillance of virulent strains and ultimately allow adapting prophylaxis measures in livestock farms.

Keywords: Q fever, invasiveness, ruminant, virulence

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870 Effects of Cymbopogon citratus, Stapf (CS) or Lemon Grass Ethanol Extract on Antioxidant and Vascular Disorders Parameters in Rat

Authors: Suphaket Saenthaweesuk, Nutiya Somparn, Atcharaporn Thewmore

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The present study aims to investigate the effects of Cymbopogon citratus, Stapf (CS) or lemon grass ethanol extract on antioxidant and vascular disorders parameters in rat. The CS ethanol extract was screened for its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Rats were orally administered with CS at 1,000 mg/kg/day for 30 days. Phytochemical screening of CS extract indicated the presence of tannins, flavonoids and phenolic compounds. The extract contained phenolic compounds 1,400.10 ± 0.47 mg of gallic acid equivalents per gram CS extract. The free radical scavenging activity assessed by DPPH assay gave IC50 of 168.77 ± 3.32µg/mL, which is relatively lower than that of BHT with IC50 of 12.34 ± 1.14 µg/mL. In the animals, the protein expression of antioxidant enzymes, γ-glutamylcysteine ligase (γ-GCL) in liver was significantly increased. This was consistent with elevation of serum catalase (CAT) and superoxide dismutase (SOD) activities. However, Protein expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial nitric oxide synthase (eNOS) in heart and aorta were not differenced from normal control. Taken together, the present study provides evidence that CCS water extract exhibits direct antioxidant properties and can induce cytoprotective enzymes in vivo.

Keywords: antioxidant, Cymbopogon citratus Stapf, VCAM-1, γ-glutamylcysteine ligase

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869 Sphingosomes: Potential Anti-Cancer Vectors for the Delivery of Doxorubicin

Authors: Brajesh Tiwari, Yuvraj Dangi, Abhishek Jain, Ashok Jain

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The purpose of the investigation was to evaluate the potential of sphingosomes as nanoscale drug delivery units for site-specific delivery of anti-cancer agents. Doxorubicin Hydrochloride (DOX) was selected as a model anti-cancer agent. Sphingosomes were prepared and loaded with DOX and optimized for size and drug loading. The formulations were characterized by Malvern zeta-seizer and Transmission Electron Microscopy (TEM) studies. Sphingosomal formulations were further evaluated for in-vitro drug release study under various pH profiles. The in-vitro drug release study showed an initial rapid release of the drug followed by a slow controlled release. In vivo studies of optimized formulations and free drug were performed on albino rats for comparison of drug plasma concentration. The in- vivo study revealed that the prepared system enabled DOX to have had enhanced circulation time, longer half-life and lower elimination rate kinetics as compared to free drug. Further, it can be interpreted that the formulation would selectively enter highly porous mass of tumor cells and at the same time spare normal tissues. To summarize, the use of sphingosomes as carriers of anti-cancer drugs may prove to be a fascinating approach that would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Keywords: sphingosomes, anti-cancer, doxorubicin, formulation

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868 Coffee Consumption and Glucose Metabolism: a Systematic Review of Clinical Trials

Authors: Caio E. G. Reis, Jose G. Dórea, Teresa H. M. da Costa

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Objective: Epidemiological data shows an inverse association of coffee consumption with risk of type 2 diabetes mellitus. However, the clinical effects of coffee consumption on the glucose metabolism biomarkers remain controversial. Thus, this paper reviews clinical trials that evaluated the effects of coffee consumption on glucose metabolism. Research Design and Methods: We identified studies published until December 2014 by searching electronic databases and reference lists. We included randomized clinical trials which the intervention group received caffeinated and/or decaffeinated coffee and the control group received water or placebo treatments and measured biomarkers of glucose metabolism. The Jadad Score was applied to evaluate the quality of the studies whereas studies that scored ≥ 3 points were considered for the analyses. Results: Seven clinical trials (total of 237 subjects) were analyzed involving adult healthy, overweight and diabetic subjects. The studies were divided in short-term (1 to 3h) and long-term (2 to 16 weeks) duration. The results for short-term studies showed that caffeinated coffee consumption may increase the area under the curve for glucose response, while for long-term studies caffeinated coffee may improve the glycemic metabolism by reducing the glucose curve and increasing insulin response. These results seem to show that the benefits of coffee consumption occur in the long-term as has been shown in the reduction of type 2 diabetes mellitus risk in epidemiological studies. Nevertheless, until the relationship between long-term coffee consumption and type 2 diabetes mellitus is better understood and any mechanism involved identified, it is premature to make claims about coffee preventing type 2 diabetes mellitus. Conclusion: The findings suggest that caffeinated coffee may impairs glucose metabolism in short-term but in the long-term the studies indicate reduction of type 2 diabetes mellitus risk. More clinical trials with comparable methodology are needed to unravel this paradox.

Keywords: coffee, diabetes mellitus type 2, glucose, insulin

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867 Arisarum Vulgare: Bridging Tradition and Science through Phytochemical Characterization and Exploring Therapeutic Potential via in vitro and in vivo Biological Activities

Authors: Boudjelal Amel

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Arisarum vulgare, a member of the Araceae family, is an herbaceous perennial widely distributed in the Mediterranean region. A. vulgare is recognized for its medicinal properties and holds significant traditional importance in Algeria for the treatment of various human ailments, including pain, infections, inflammation, digestive disorders, skin problems, eczema, cancer, wounds, burns and gynecological diseases. Despite its extensive traditional use, scientific exploration of A. vulgare remains limited. The study aims to investigate for the first time the therapeutic potential of A. vulgare ethanolic extract obtained by ultrasound-assisted extraction. The chemical composition of the extract was determined by LC-MS/MS analysis. For in vitro phytopharmacological evaluation, several assays, including DPPH, ABTS, FRAP and reducing power, were employed to evaluate the antioxidant activity. The antibacterial activity was assessed againt Escherichia coli, Salmonella typhimurium, Staphylococus aureus, Enterococcus feacium by disk diffusion and microdilution methods. The possible inhibitory activity of ethanolic extract was analyzed against the cholinesterases enzymes (AChE and BChE). The DNA protection activity of A. vulgare ethanolic extract was estimated using the agarose gel electrophoresis method. The capacities of the extract to protect plasmid DNA (pBR322) from the oxidizing effects of H2O2 and UV treatment were evaluated by their DNA-breaking forms. The in vivo wound healing potential of a traditional ointment containing 5% of A. vulgare ethanolic extract was also investigated. The LC-MS/MS profiling of the extract revealed the presence of various bioactive compounds, including naringenin, chlorogenic, vanillic, cafeic, coumaric acids, trans-cinnamic and trans ferrulic acids. The plant extract presented considerable antioxidant potential, being the most active for Reducing power (0,07326±0.001 mg/ml) and DPPH (0.14±0.004 mg/ml). The extract showed the highest inhibition zone diameter against Enterococcus feacium (36±0.1 mm). The ethanolic extract of A. vulgare suppressed the growth of Staphylococus aureus, Escherichia coli and Salmonella typhimurium according to the MIC values. The extract of the plant significantly inhibited both AChE and BChE enzymes. DNA protection activity of the A. vulgare extract was determined as 90.41% for form I and 51.92% for form II. The in vivo experiments showed that 5% ethanolic extract ointment accelerated the wound healing process. The topical application of the traditional formulation enhanced wound closure (95,36±0,6 %) and improved histological parameters in the treated group compared to the control groups. The promising biological properties of Arisarum vulgare revealed that the plant could be appraised as a potential origin of bioactive molecules having multifunctional medicinal uses.

Keywords: arisarum vulgare, LC-MS/MS, antioxidant activity, antimicrobial activity, cholinesterases enzymes inhibition, dna-damage activity, in vivo wound healing

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866 The Efficacy of Andrographis paniculata and Chromolaena odorata Plant Extract against Malaria Parasite

Authors: Funmilola O. Omoya, Abdul O. Momoh

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Malaria constitutes one of the major health problems in Nigeria. One of the reasons attributed for the upsurge was the development of resistance of Plasmodium falciparum and the emergence of multi-resistant strains of the parasite to anti-malaria drugs. A continued search for other effective, safe and cheap plant-based anti-malaria agents thus becomes imperative in the face of these difficulties. The objective of this study is therefore to evaluate the in vivo anti-malarial efficacy of ethanolic extracts of Chromolaena odorata and Androgaphis paniculata leaves. The two plants were evaluated for their anti-malaria efficacy in vivo in a 4-day curative test assay against Plasmodium berghei strain in mice. The group treated with 500mg/ml dose of ethanolic extract of A. paniculata plant showed parasite suppression with increase in Packed Cell Volume (PCV) value except day 3 which showed a slight decrease in PCV value. During the 4-day curative test, an increase in the PCV values, weight measurement and zero count of Plasmodium berghei parasite values was recorded after day 3 of drug administration. These results obtained in group treated with A. paniculata extract showed anti-malarial efficacy with higher mortality rate in parasitaemia count when compared with Chromolaena odorata group. These results justify the use of ethanolic extracts of A. paniculata plant as medicinal herb used in folklore medicine in the treatment of malaria.

Keywords: anti-malaria, curative, plant-based anti-malaria agents, biology

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865 Ex Vivo Permeation Comparison Study of Flurbiprofen from Nanoparticles through Human Skin

Authors: Sheimah El Bejjaji, Lara Gorsek, Chandler Quilchez, Joaquim Suñer, Mireia Mallandrich

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Flurbiprofen is an anti-inflammatory drug used in several treatments. The purpose of this study was to compare the permeation of two different formulations of flurbiprofen through the human skin. The first formulation was a solution of flurbiprofen dissolved with polyethylene glycol 3350 (PEG 3350). The second formulation was flurbiprofen encapsulated in poly-ɛ-caprolactone (PɛCL) nanoparticles (NPs), stabilized with poloxamer 188, submitted individually for freeze-drying with PEG 3350 as a cryoprotectant and sterilized by gamma-irradiation. Human skin was obtained from the abdominal region of a healthy patient. The experimental protocol was approved by the Bioethics Committee of Barcelona SCIAS Hospital (Spain), and they obtained the written informed consent forms. After being frozen to -20ºC, the skin samples were cut with a dermatome at 400 µm. The ex vivo permeation study was performed in Franz diffusion cells with a diffusion area of 2.54 cm². Skin samples were placed between two compartment sites, the dermal side in contact with the receptor medium and the epidermis side in contact with the donor chamber to which the formulation was applied. The permeation study was conducted for 24 hours at 32 ± 0.5 °C in accordance with sink conditions. The results were analyzed with an unpaired t-test, and the p-values indicate the formulation with nanoparticles had a higher permeability coefficient, flux, partition parameter, diffusion parameter, and lag time. The applicability of this formulation topically can benefit articulations and ligament inflammation as an alternative to oral drugs.

Keywords: anti-inflammatory drug, flurbiprofen, human skin, nanoparticles, skin permeation

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864 Development and Characterization of a Film Based on Hydroxypropyl Methyl Cellulose Incorporated by a Phenolic Extract of Fennel and Reinforced by Magnesium Oxide: In Vivo - in Vitro

Authors: Mazouzi Nourdjihane, K. Boutemak, A. Haddad, Y. Chegreouche

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In the last decades, biodegradable polymers have been considered as one of the most popular options for the delivery of drugs and various conventional doses. The film forming system (FFS) can be used in topical, transdermal, ophthalmic, oral and gastric applications. Recently this system has focused on improving drug delivery, which can promote drug release. In this context, the aim of this study is to create polymeric film-forming systems for the stomach and to evaluate and test their gastroprotective effects, comparing the effects of changes in composition on film characteristics. It uses a plant-derived polyphenol extract extracted from fennel to demonstrate anti-inflammatory activity in the film. The films are made from hydroxypropyl methylcellulose polymer and different types of plastic, glycerol and polyethylene glycol. The ffs properties show that MgO-glycerol-reinforced hydroxypropylmethylcellulose (HPMC-MgO-Gly) is better than that based on MgO-PEG-reinforced hydroxypropylmethylcellulose (HPMC-MgO-PEG). It is durable, has a faster drying time and allows for maximum recovery. Water vapor strength and blowing speed and other additions show another advantage of HPMC-MgO-Gly compared to HPMC-MgO-PEG, indicating good adhesion between the support (top) and film production. In this study, the gastroprotective effect of fennel phenol extract was found, showing that this plant material has a gastroprotective effect on ulcers and that the film can absorb the active substance.

Keywords: film formin system, hydroxypropyl methylcellulose, magnesium oxide, in vivo

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863 In silico Designing and Insight into Antimalarial Potential of Chalcone-Quinolinylpyrazole Hybrids by Preclinical Study in Mice

Authors: Deepika Saini, Sandeep Jain, Ajay Kumar

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The quinoline scaffold is one of the most widely studied in the discovery of derivatives with various heterocyclic moieties due to its potential antimalarial activities. In the present study, a chalcone series of quinoline derivatives clubbed with pyrazole were synthesized to evaluate their antimalarial property by in vitro schizont maturation inhibition assay against both chloroquine sensitive, 3D7 and chloroquine resistant, RKL9 strain of Plasmodium falciparum. Further, top five compounds were studied for in vivo preclinical study for antimalarial potential against P. berghei in Swiss albino mice. To understand the mechanism of synthesized analogues, they were screened computationally by molecular docking techniques. Compounds were docked into the active site of a protein receptor, Plasmodium falciparum Cysteine Protease Falcipain-2. The compounds were successfully synthesized, and structural confirmation was performed by FTIR, 1H-NMR, mass spectrometry and elemental analysis. In vitro study suggested that the compounds 5b, 5g, 5l, 5s and 5u possessed best antimalarial activity and further tested for in vivo screening. Compound 5u (CH₃ on both rings) with EC₅₀ 0.313 & 0.801 µg/ml against CQ-S & CQ-R strains of P. falciparum respectively and 78.01% suppression of parasitemia. The molecular docking studies of the compounds helped in understanding the mechanism of action against falcipain-2. The present study reveals the binding signatures of the synthesized ligands within the active site of the protein, and it explains the results from in vitro study in their EC₅₀ values and percentage parasitemia.

Keywords: antimalarial activity, chalcone, docking, quinoline

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862 Transdermal Therapeutic System of Lercanıdipine Hydrochloride: Fabrication and in Vivo Evaluation

Authors: Jiji Jose, R. Narayanacharyulu, Molly Mathew, Jisha Prems

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Introduction: Lercanidipine hydrochloride (LD), an effective calcium channel blocker, widely used for the treatment of chronic stable angina and hypertension seems to be potential transdermal therapeutic system candidate, mainly due to its low oral bio availability, short half life and high first-pass metabolism. Objective: To develop transdermal therapeutic systems for LD and to evaluate its in vivo performance in rabbits. Methodology: Transdermal patches of LD were formulated using the polymer blend of eudragit RL100 (ERL) and polyvinyl pyrolidone (PVP) by casting method Propylene glycol (PG) and tween 80 were used as plasticizer and permeation enhancer respectively. The pharmaco kinetic parameters of LD after the administration of transdermal patches was compared with that of oral administration. The study was carried out in a two way crossover design in male New Zealand albino rabbits. Results: The formulation with ERL: PVP ratio 1:4 with 15% w/w PG as plasticizer and 4% w/w tween 80 as permeation enhancer showed the best drug release results. The pharmacokinetic parameters such as Cmax, tmax, mean residence time (MRT) and area under the curve (AUC 0-∞) were significantly different following transdermal administration compared to oral administration. The terminal half life of transdermally administered LD was found to similar that of oral administration. A sustained drug release over a period of 24 hrs was observed after transdermal administration. Conclusion: The fabricated transdermal delivery system have the potential to provide controlled and extended drug release, better bio availability and thus, this may improve the patient compliance.

Keywords: transdermal therapeutic system, lercanidipine hydrochloride, eudragit, skinpermeation

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861 Air Pollutants Exposure and Blood High Sensitivity C-Reactive Protein Concentrations in Healthy Pregnant Women

Authors: Gwo-Hwa Wan, Tai-Ho Hung, Fen-Fang Chung, Wan-Ying Lee, Hui-Ching Yang

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Air pollutant exposure results in elevated concentrations of oxidative stress and inflammatory biomarkers in general populations. Increased concentrations of inflammatory biomarkers in pregnant women would be associated with preterm labor and low birth weight. To our best knowledge, the associations between air pollutants exposure and inflammation in pregnant women and fetuses are unknown, as well as their effects on fetal growth. This study aimed to evaluate the influences of outdoor air pollutants in northern Taiwan areas on the inflammatory biomarker (high sensitivity C-reactive protein, hs-CRP) concentration in the blood of healthy pregnant women and how the biomarker impacts fetal growth. In this study, 38 healthy pregnant women who are in their first trimester and live in northern Taiwan area were recruited from the Taipei Chang Gung Memorial Hospital. Personal characteristics and prenatal examination data (e.g., blood pressure) were obtained from recruited subjects. The concentrations of inflammatory mediators, hs-CRP, in the blood of healthy pregnant women were analyzed. Additionally, hourly data of air pollutants (PM10, SO2, NO2, O3, CO) concentrations were obtained from air quality monitoring stations in Taipei area, established by the Taiwan Environmental Protection Administration. The definition of lag 0 and lag 01 are the exposure to air pollutants on the day of blood withdrawal, and the average exposure to air pollutants one day before and on the day of blood withdrawal, respectively. The statistical analyses were conducted using SPSS software version 22.0 (SPSS, Inc., Chicago, IL, USA). This analytical result indicates that the healthy pregnant women aged between 28 and 42 years old. The body mass index before pregnancy averaged 21.51 (sd = 2.51) kg/m2. Around 90% of the pregnant women had never smoking habit, and 28.95% of them had allergic diseases. Approximately around 84% and 5.26% of the pregnant women worked at indoor and outdoor environments, respectively. The mean hematocrit level of the pregnant women was 37.10%, and the hemoglobin levels were ranged between 10.1 and 14.7 g/dL with 12.47 g/dL of mean value. The blood hs-CRP concentrations of healthy pregnant women in the first trimester ranged between 0.32 and 32.5 mg/L with 2.83 (sd = 5.69) mg/L of mean value. The blood hs-CRP concentrations were positively associated with ozone concentrations at lag 0-14 (r = 0.481, p = 0.017) in healthy pregnant women. Significant lag effects were identified in ozone at lag 0-14 with a positive excess concentration of blood hs-CRP.

Keywords: air pollutant, hs-CRP, pregnant woman, ozone, first trimester

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860 Antimicrobial Evaluation of Polyphenon 60 and Ciprofloxacin Loaded Nano Emulsion against Uropathogenic Escherichia coli Bacteria and Its in vivo Analysis

Authors: Atinderpal Kaur, Shweta Dang

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Our aim is to develop a nanoemulsion-based delivery system containing polyphenon 60 (P60) and ciprofloxacin (Cipro) for intravaginal delivery to treat urinary tract infection. In the present study Polyphenon 60 (P60) and ciprofloxacin (Cipro) were loaded in a single nano emulsion (NE) system via ultra-sonication technique and characterized for particle size, in vitro release and antibacterial efficacy against Bcl-2 level Escherichia coli bacteria. To determine in vivo pharmacokinetic parameters and intravaginal transportation of NE, gamma scintigraphy and biodistribution study was conducted by radiolabelling NE with technetium pertechnetate (99mTc). The preliminary antibacterial investigation showed synergy between these compounds with FICindex of 0.42. The developed formulation showed zeta potential +55.3 and particle size of 151.7 nm, with PDI of 0.196. The in vitro release percentage of P60 at the end of 7th hours was 94.8 ± 0.9 % whereas the release for Cipro was 75.1± 0.15 % in simulated vaginal media. MBC was identified and the findings demonstrated that in both ESBL (Extended Spectrum β- lactamase) and MBL (Metallo β- lactamase) cultures the P60+Cipro NE showed inhibition of growth of all the isolates at 2 mg/ml dilutions. The percentage per gram of radiolabelled drug was found (3.50±0.26) and (3.81±0.30) in kidney and urinary bladder, respectively at 3 h. From the findings, it was concluded that the developed P60+Cipro NE was transported efficiently throughout the target organs, had long duration of action and high biocompatibility via intravaginal administration as compared to oral administration.

Keywords: ciprofloxacin, gamma scintigraphy, intravaginal drug delivery, Polyphenon 60

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859 The Biofumigation Activity of Volatile Compounds Produced from Trichoderma afroharzianum MFLUCC19-0090 and Trichoderma afroharzianum MFLUCC19-0091 against Fusarium Infections in Fresh Chilies

Authors: Sarunpron Khruengsai, Patcharee Pripdeevech

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This study aimed to investigate the fumigation activities of the volatile compounds produced by Trichoderma spp. against Fusarium oxysporum and F. proliferatum fungi that cause significant rot in fresh chilies. Two Trichoderma spp. were isolated from the leaves of Schefflera leucantha grown in Thailand and later identified as T. afroharzianum MFLUCC19-0090 and T. afroharzianum MFLUCC19-0091. Both in vitro and in vivo dual culture volatile assays were used to study the effects of the produced volatile compounds on mycelial growth. In vitro results showed that the volatile compounds produced by T. afroharzianum MFLUCC19-0090 significantly inhibited the growth of F. oxysporum, while the volatile compounds produced by T. afroharzianum MFLUCC19-0091 significantly inhibited the growth of F. proliferatum. The effectiveness of Trichoderma-derived volatile compounds in inhibiting the mycelial growth of the selected pathogens in the inoculated, fresh chili samples was further demonstrated in vivo. The volatile profiles of both Trichoderma spp. were characterized using gas chromatography-mass spectrometry. Seventy-three volatile compounds were detected from both strains. Among the major volatile compounds detected, phenyl ethyl alcohol was found to possess the strongest antifungal activity against both pathogens. The results support the possibility of using volatile compounds produced by T. afroharzianum MFLUCC19-0090 and T. afroharzianum MFLUCC19-0091 as alternative fumigants for preventing Fusarium rot of fresh chilies during the post-harvest period.

Keywords: antifungal activity, biocontrol, endophytic fungi, post-harvest

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858 Anti-diabetic Potential of Olive (Olea Europaea) Leaves Extract: In Vitro and in Vivo Evaluation

Authors: Sobhy El-Sohaimy, Abduvali Toshev, Hanem Mansour

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(1) Objective: The main objective of the current study was to evaluate in an In Vitro and In Vivo, the potential activity of olive leaves extract (OLE) in the treatment and/or preventing the diabetes mellitus type II and related implications; (2) Methodology: Five groups of male rats were used in the current study: group (1)- negative control (normal); group (2)- positive control, streptozotocin (STZ) induced rats; group (3)-diabetic rats treated with metformin (200 mg/kg) plus OLE (200 mg/kg); group 4- diabetic rats treated with metformin (200 mg/kg); group 5- diabetic rats treated with OLE (200 mg/kg). A four-week regime of oral treatment was administered once daily; (3) Results: Diabetic rats treated with metformin + OLE clearly showed normal blood glucose level (121.67 ± 5.49 mg/dl), and glycated hemoglobin (HbA1c) (3.70 ± 0.10%). The combination of metformin + OLE obviously showed a superior improvement in the lipid profile (TG, TC, HDL and LDL) compared to both metformin and OLE individually. The histological examination revealed that the combination of metformin + Olive leaves extract successfully repaired of the liver, kidneys, and pancreatic tissues in diabetic rats to be near to the normal status; (4) Conclusion: Finally, it can be concluded that, the combination of metformin and OLE exhibited a superior improvement than metformin and OLE individually which emphasized the promising adjuvant role of the OLE in the treatment protocol of diabetes mellitus type II.

Keywords: olive (olea europaea) leaves extracts, hypoglycemic agents, cytotoxicity, nitic oxide scavenging activity, α-glucose oxidase inhibitor

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857 Vascularized Adipose Tissue Engineering by Using Adipose ECM/Fibroin Hydrogel

Authors: Alisan Kayabolen, Dilek Keskin, Ferit Avcu, Andac Aykan, Fatih Zor, Aysen Tezcaner

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Adipose tissue engineering is a promising field for regeneration of soft tissue defects. However, only very thin implants can be used in vivo since vascularization is still a problem for thick implants. Another problem is finding a biocompatible scaffold with good mechanical properties. In this study, the aim is to develop a thick vascularized adipose tissue that will integrate with the host, and perform its in vitro and in vivo characterizations. For this purpose, a hydrogel of decellularized adipose tissue (DAT) and fibroin was produced, and both endothelial cells and adipocytes that were differentiated from adipose derived stem cells were encapsulated in this hydrogel. Mixing DAT with fibroin allowed rapid gel formation by vortexing. It also provided to adjust mechanical strength by changing fibroin to DAT ratio. Based on compression tests, gels of DAT/fibroin ratio with similar mechanical properties to adipose tissue was selected for cell culture experiments. In vitro characterizations showed that DAT is not cytotoxic; on the contrary, it has many natural ECM components which provide biocompatibility and bioactivity. Subcutaneous implantation of hydrogels resulted with no immunogenic reaction or infection. Moreover, localized empty hydrogels gelled successfully around host vessel with required shape. Implantations of cell encapsulated hydrogels and histological analyses are under study. It is expected that endothelial cells inside the hydrogel will form a capillary network and they will bind to the host vessel passing through hydrogel.

Keywords: adipose tissue engineering, decellularization, encapsulation, hydrogel, vascularization

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856 In vitro and in vivo Effects of 'Sonneratia alba' Extract against the Fish Pathogen 'Aphanomyces invadans'

Authors: S. F. Afzali, W. L. Wong

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The epizootic ulcerative syndrome (EUS) causes by the oomycete fungus, Aphanomyces invadans; known to be one of the infectious fish diseases for farmed and wild fishes in fresh and brackish-water from the Asia-pacific region, America and Africa. Although, EUS had been documented by the Office International des Epizooties (OIE) since 1995, hitherto, there is neither standard chemical agents that can be used for successful treatment of this destructive infection in the time of outbreak; nor available vaccine for prevention. Plant-based remedies in controlling fish diseases are gaining much attention recently as an alternative to chemical treatments, which possess negative effects to the environment and human. In present study, Sonneratia alba, a mangrove plant belongs to the Sonneratiaceae family, was screened in vitro and in vivo for its antifungal activity against A. invadans mycelium growth and its effects on fish innate immune system and disease resistant. The in vitro tests was performed using the disc diffusion methods with measurements of minimum inhibitory concentration (MIC) and inhibition zone. For in vivo study, the S. alba extract supplemented diets were administrated at 0.0, 1.0%, 3.0%, and 5.0% on healthy goldfish, Carassius auratus, which challenged with A. invadans zoospores (100 spores/ml). To compare the significant differences in the hematological and immunological parameters obtained from the experiments, the data were analysed using the SPSS. The methanol extract of S. alba effectively inhibited the mycelial growth of A. invadans at a minimum concentration of 1000 ppm for agar and filter paper diffusion experiments. In the agar diffusion test, 500 ppm of the extract inhibited the fungus mycelial growth up to 96 hours after exposure. The mycelial growth from the edge of the pre-inoculated A. invadans agar discs treated with S. alba extracts at concentrations of 100, 500 and 1000 ppm were 15, 8 and 0 mm respectively. The results of the filter paper disc test showed that the S. alba extract at its minimal inhibitory concentration (1000 ppm) has similar qualitative inhibitory effect as malachite green at 1 ppm and formalin at 250 ppm. According to the in vivo tests findings, in the infected fish fed with 3.0% and 5.0% supplementation diet, the numbers of white blood cell and myeloperoxidase activity significantly increased after the second week of treatment. Whilst the numbers of red blood cell significantly decreased in the infected fish fed with 0.0 and 1.0% supplementation diet. After the third week of feeding, significant increases in the total protein, albumin level, lysozyme activity were recorded in the infected fish fed with 3.0% and 5.0% supplementation diet. Also, the enriched diets increased the survival rate as compared to the untreated group that suffered from 90% mortality. The present study indicated that S. alba extract may inhibit the mycelial growth of A. invadans effectively, suggesting an alternative to other chemotherapeutic agents, which brought much environmental and health concerns to the public, for EUS treatment.

Keywords: fungal pathogen, goldfish, organic extract, treatment

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855 In vivo Inhibition and Restoration of Acetyl Cholinesterase Activities in Induced Clarias Gariepinus

Authors: T. O. Ikpesu, I. Tongo, A. Ariyo

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This study was conducted to assess the effects of an organophosphate pesticide glyphosate formulation on neurological enzymes in the brain, liver and serum of juvenile Clarias gariepinus, and also to examine the antidotal prospect of Garcinia kola seeds extract. The fish divided into five groups were exposed to different treatments of glyphosate formulation and Garcinia kola seeds extract. Acetyl cholinesterase activities in the brain, liver and serum of the fish were estimated in the experimental and control fishes on day -7, 14, 21 and of 28 by spectrophotometrical methods. The enzyme was significantly (p < 0.05) inhibited in glyphosate formulation test. The inhibition percentages of AChE ranged for the brain, liver and serum between 40.7–59.4%, 50-57% and 27.5–51.3%, respectively. The aberrated parameters were recovered in G. kola seeds extract treated aquaria, and was dose and time dependent. The present study demonstrated that in vivo glyphosate formulation exposure caused AChE inhibition in the brain, liver and the serum. The brain tissue, however, might be suggested as a good indicator tissue for aquatic pollutants exposure in the fish and G. kola seeds extract has shown to be a good remedy for neurology restoration in a noxious circumstance. The findings has shown that xenobiotics could be eliminated from aquatic organisms, especially fish, and could be put into practice in areas at risk of pollutants. This approach can reduce the risks of biomagnification of poison in sea food. Hence, formulation of this plant extracts into capsule should be encouraged and supported.

Keywords: glyphosate, Clarias gariepinus, brain, Garcinia kola, acetyl cholinesterase, enzymes

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854 Oral Administration of Azithromycin Ameliorates Trypanosomosis in Trypanosoma congolense and T. Brucei Brucei Infected Mice

Authors: Nthatisi I. Molefe-Nyembe, Keisuke Suganuma, Oriel M. M. Thekisoe, Xuan Xuenan, Noboru Inoue

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African trypanosomosis is a devastating disease of animals caused by parasites of the genus Trypanosoma negatively affecting the economic status of more than 36 African countries. Few available drugs for the treatment of trypanosomosis remain inaccessible in remote areas, are associated with severe toxicity and most importantly, resistance has widely developed against their usage. Therefore, safe, effective and easily administrable drugs are urgently in need. The objective of the current study was to determine efficacy of azithromycin (AZM), on T. congolense, T. brucei brucei in vitro and in vivo. A 96 well luciferase assay was conducted to determine the trypanocidal effect of AZM on T. congolense, T. b. brucei and T. evansi as well as the cytotoxicity effect on the MDBK and NIH 3T3 cells. Additionally, TEM analysis was conducted to determine the morphological alteration on the AZM treated samples. Mice were infected with T. congolense and T. b. brucei and orally treated with AZM for 7 and 28 days referred to as the short and the long-term treatment. The in vitro IC50 values of AZM on T. congolense, T. b. brucei and T. evansi was 0.19 ± 0.17; 3.69 ± 2.26 and 1.81 ± 1.82 μg/mL, respectively, while the cytotoxicity effects values were greater than 25 μg/mL. A vacuole-like structure was observed in the TEM imaging of AZM treated T. congolense, while the presence of glycosomes and acidocalcisome-like structured were detected in T. b. brucei samples. In vivo, AZM was more effective against T. congolense infected mice than T. b. brucei. In conclusion, AZM exhibited the trypanocidal effects on T. congolense and T. b. brucei infected mice. However, further studies are necessary to determine the metabolic pathway responsible for the observed efficacy.

Keywords: animal trypanosomosis, azithromycin, oral administration, trypanosoma congolense

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853 Differentially Expressed Genes in Atopic Dermatitis: Bioinformatics Analysis Of Pooled Microarray Gene Expression Datasets In Gene Expression Omnibus

Authors: Danna Jia, Bin Li

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Background: Atopic dermatitis (AD) is a chronic and refractory inflammatory skin disease characterized by relapsing eczematous and pruritic skin lesions. The global prevalence of AD ranges from 1~ 20%, and its incidence rates are increasing. It affects individuals from infancy to adulthood, significantly impacting their daily lives and social activities. Despite its major health burden, the precise mechanisms underlying AD remain unknown. Understanding the genetic differences associated with AD is crucial for advancing diagnosis and targeted treatment development. This study aims to identify candidate genes of AD by using bioinformatics analysis. Methods: We conducted a comprehensive analysis of four pooled transcriptomic datasets (GSE16161, GSE32924, GSE130588, and GSE120721) obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed using the R statistical language. The differentially expressed genes (DEGs) between AD patients and normal individuals were functionally analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, a protein-protein interaction (PPI) network was constructed to identify candidate genes. Results: Among the patient-level gene expression datasets, we identified 114 shared DEGs, consisting of 53 upregulated genes and 61 downregulated genes. Functional analysis using GO and KEGG revealed that the DEGs were mainly associated with the negative regulation of transcription from RNA polymerase II promoter, membrane-related functions, protein binding, and the Human papillomavirus infection pathway. Through the PPI network analysis, we identified eight core genes: CD44, STAT1, HMMR, AURKA, MKI67, and SMARCA4. Conclusion: This study elucidates key genes associated with AD, providing potential targets for diagnosis and treatment. The identified genes have the potential to contribute to the understanding and management of AD. The bioinformatics analysis conducted in this study offers new insights and directions for further research on AD. Future studies can focus on validating the functional roles of these genes and exploring their therapeutic potential in AD. While these findings will require further verification as achieved with experiments involving in vivo and in vitro models, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Keywords: atopic dermatitis, bioinformatics, biomarkers, genes

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852 Generation Mechanism of Opto-Acoustic Wave from in vivo Imaging Agent

Authors: Hiroyuki Aoki

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The optoacoustic effect is the energy conversion phenomenon from light to sound. In recent years, this optoacoustic effect has been utilized for an imaging agent to visualize a tumor site in a living body. The optoacoustic imaging agent absorbs the light and emits the sound signal. The sound wave can propagate in a living organism with a small energy loss; therefore, the optoacoustic imaging method enables the molecular imaging of the deep inside of the body. In order to improve the imaging quality of the optoacoustic method, the more signal intensity is desired; however, it has been difficult to enhance the signal intensity of the optoacoustic imaging agent because the fundamental mechanism of the signal generation is unclear. This study deals with the mechanism to generate the sound wave signal from the optoacoustic imaging agent following the light absorption by experimental and theoretical approaches. The optoacoustic signal efficiency for the nano-particles consisting of metal and polymer were compared, and it was found that the polymer particle was better. The heat generation and transfer process for optoacoustic agents of metal and polymer were theoretically examined. It was found that heat generated in the metal particle rapidly transferred to the water medium, whereas the heat in the polymer particle was confined in itself. The confined heat in the small particle induces the massive volume expansion, resulting in the large optoacoustic signal for the polymeric particle agent. Thus, we showed that heat confinement is a crucial factor in designing the highly efficient optoacoustic imaging agent.

Keywords: nano-particle, opto-acoustic effect, in vivo imaging, molecular imaging

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851 Prospects in Development of Ecofriendly Biopesticides in Management of Postharvest Fungal Deterioration of Cassava (Manihot esculenta Crantz)

Authors: Anderson Chidi Amadioha, Promise Chidi Kenkwo, A. A. Markson

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Cassava (Manihot esculenta Crantz) is an important food and cash crop that provide cheap source of carbohydrate for food, feed and raw material for industries hence a commodity for feature economic development of developing countries. Despite the importance, its production potentials is undermined by disease agents that greatly reduce yield and render it unfit for human consumption and industrial use. Pathogenicity tests on fungal isolates from infected cassava revealed Aspergillus flavus, Rhizopus stolonifer, Aspergillus niger, and Trichodderma viride as rot-causing organisms. Water and ethanol extracts of Piper guineense, Ocimum graticimum, Cassia alata, and Tagetes erecta at 50% concentration significantly inhibited the radial growth of the pathogens in vitro and their development and spread in vivo. Low cassava rot incidence and severity was recorded when the extracts were applied before than after spray inoculating with spore suspension (1x105 spores/ml of distilled water) of the pathogenic organisms. The plant materials are readily available, and their extracts are biodegradable and cost effective. The fungitoxic potentials of extracts of these plant materials could be exploited as potent biopesticides in the management of postharvest fungal deterioration of cassava especially in developing countries where synthetic fungicides are not only scarce but also expensive for resource poor farmers who produce over 95% of the food consumed.

Keywords: cassava, biopesticides, in vitro, in vivo, pathogens, plant extracts

Procedia PDF Downloads 149