Search results for: in vitro toxicity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2256

Search results for: in vitro toxicity

486 Kinetics of Inhibition of Xanthine Oxidase by Lycium Arabicum and Its Protective Effect against Oxonate-Induced Hyperuricemia and Renal Dysfunction in Mice

Authors: Naouel Boussoualim, Hayat Trabsa, Imane Krache, Seddik Khennouf, Noureddine Charef, Lekhmici Arrar, Abderrahmane Baghiani

Abstract:

Purpose: To evaluate the in-vitro inhibition of xanthine oxidase (purified from bovine milk) by extracts of Lycium arabicum, as well as it is in vivo hypouricemic and renal protective effects. Methods: Four extracts of Lycium arabicum, methanol (CrE), chloroform (ChE), ethyl acetate (EaE) and aqueous (AqE) extracts, were screened for their total phenolics and potential inhibitory effects on purified bovine milk xanthine oxidase (XO) activity by measuring the formation of uric acid or superoxide radical. The mode of inhibition was investigated and compared with the standard drugs, allopurinol, quercitin, and catechin. To evaluate their hypouricemic effect, the extracts were administered to potassium oxonate-induced hyperuricemic mice at a dose of 50 mg/kg body weight. Results: The results showed that EaE had the highest content of phenolic compounds and was the most potent inhibitor of uric acid formation (IC50 = 0.017 ± 0.001 mg/mL) and formation of superoxide (IC50 = 0.035 ± 0.001 mg/ml). Lineweaver-Burk analysis showed that CrE and EaE inhibited XO competitively, whereas the inhibitory activities exerted by ChE and AqE were of a mixed type. Intraperetoneal injection of L. arabicum extracts (50 mg/kg) elicited hypouricemic actions in hyperuricemic mice. Hyperuricemic mice presented a serum uric acid concentration of 4.71 ± 0.29 mg/L but this was reduced to 1.78 ± 0.11 mg/L by EaE, which was the most potent hyporuricemic extract. Conclusion: L. arabicum fractions have a strong inhibitory effect on xanthine oxidase and and also have a significantly lowering effect on serum and liver creatinine and urea levels in hyperuricemic mice.

Keywords: lycium arabicum, uric acid, creatinine, superoxide, phenolic compounds, flavonoids, hyperuricemia

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

Authors: Rachmat Mauludin, Nurmazidah

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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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484 Comparative Evaluation of a Dynamic Navigation System Versus a Three-Dimensional Microscope in Retrieving Separated Endodontic Files: An in Vitro Study

Authors: Mohammed H. Karim, Bestoon M. Faraj

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Introduction: This study aimed to compare the effectiveness of a Dynamic Navigation System (DNS) and a three-dimensional microscope in retrieving broken rotary NiTi files when using trepan burs and the extractor system. Materials and Methods: Thirty maxillary first bicuspids with sixty separate roots were split into two comparable groups based on a comprehensive Cone-Beam Computed Tomography (CBCT) analysis of the root length and curvature. After standardized access opening, glide paths, and patency attainment with the K file (sizes 10 and 15), the teeth were arranged on 3D models (three per quadrant, six per model). Subsequently, controlled-memory heat-treated NiTi rotary files (#25/0.04) were notched 4 mm from the tips and fractured at the apical third of the roots. The C-FR1 Endo file removal system was employed under both guidance to retrieve the fragments, and the success rate, canal aberration, treatment time and volumetric changes were measured. The statistical analysis was performed using IBM SPSS software at a significance level of 0.05. Results: The microscope-guided group had a higher success rate than the DNS guidance, but the difference was insignificant (p > 0.05). In addition, the microscope-guided drills resulted in a substantially lower proportion of canal aberration, required less time to retrieve the fragments and caused minimal change in the root canal volume (p < 0.05). Conclusion: Although dynamically guided trephining with the extractor can retrieve separated instruments, it is inferior to three-dimensional microscope guidance regarding treatment time, procedural errors, and volume change.

Keywords: separated instruments retrieval, dynamic navigation system, 3D video microscope, trephine burs, extractor

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483 Human Health Risk Assessment of Mercury-Contaminated Soils in Alebediah Mining Community, Sudan

Authors: Ahmed Elwaleed, Huiho Jeong, Ali H. Abdelbagi, Nguyen Thi Quynh, Koji Arizono, Yasuhiro Ishibashi

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Artisanal and small-scale gold mining (ASGM) poses substantial risks to both human health and the environment, particularly through contamination of soil, water, and air. Prolonged exposure to ASGM-contaminated soils can lead to acute or chronic mercury toxicity. This study assesses the human health risks associated with mercury-contaminated soils and tailings in the Alebediah mining community in Sudan. Soil samples were collected from various locations within Alebediah, including ASGM areas, farmlands, and residential areas, along with tailings samples commonly found within ASGM sites. The evaluation of potential health risks to humans included the computation of the estimated daily intake (AvDI), the hazard quotient (HQ), and the hazard index (HI) for both adults and children. The primary exposure route identified as potentially posing a significant health risk was the volatilization of mercury from tailings samples, where mercury concentrations reached up to 25.5 mg/kg. In contrast, other samples within the ASGM area showed elevated mercury levels but did not present significant health risks, with HI values below 1. However, all areas indicated HI values above 1 for the remaining exposure routes. The study observed a decrease in mercury concentration with increasing distance from the ASGM community. Additionally, soil samples revealed elevated mercury levels exceeding background values, prompting an assessment of contamination levels using the enrichment factor (EF). The findings indicated that farmlands and residential areas exhibited depleted EF, while areas surrounding the ASGM community showed none to moderate pollution. In contrast, ASGM areas exhibited significant to extreme pollution. A GIS map was generated to visually depict the extent of mercury pollution, facilitating communication with stakeholders and decision-makers.

Keywords: mercury pollution, artisanal and small-scale gold mining, health risk assessment, hazard index, soil and tailings, enrichment factor

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482 Fabrication of Ligand Coated Lipid-Based Nanoparticles for Synergistic Treatment of Autoimmune Disease

Authors: Asiya Mahtab, Sushama Talegaonkar

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The research is aimed at developing targeted lipid-based nanocarrier systems of chondroitin sulfate (CS) to deliver an antirheumatic drug to the inflammatory site in arthritic paw. Lipid-based nanoparticle (TEF-lipo) was prepared by using a thin-film hydration method. The coating of prepared drug-loaded nanoparticles was done by the ionic interaction mechanism. TEF-lipo and CS-coated lipid nanoparticle (CS-lipo) were characterized for mean droplet size, zeta potential, and surface morphology. TEF-lipo and CS-lipo were further subjected to in vitro cell line studies on RAW 264.7 murine macrophage, U937, and MG 63 cell lines. The pharmacodynamic study was performed to establish the effectiveness of the prepared lipid-based conventional and targeted nanoparticles in comparison to pure drugs. Droplet size and zeta potential of TEF-lipo were found to be 128. 92 ± 5.42 nm and +12.6 ± 1.2 mV. It was observed that after the coating of TEF-lipo with CS, particle size increased to 155.6± 2.12 nm and zeta potential changed to -10.2± 1.4mV. Transmission electron microscopic analysis revealed that the nanovesicles were uniformly dispersed and detached from each other. Formulations followed sustained release pattern up to 24 h. Results of cell line studies ind icated that CS-lipo formulation showed the highest cytotoxic potential, thereby proving its enhanced ability to kill the RAW 264.7 murine macrophage and U937 cells when compared with other formulations. It is clear from our in vivo pharmacodynamic results that targeted nanocarriers had a higher inhibitory effect on arthritis progression than nontargeted nanocarriers or free drugs. Results demonstrate that this approach will provide effective treatment for rheumatoid arthritis, and CS served as a potential prophylactic against the advancement of cartilage degeneration.

Keywords: adjuvant induced arthritis, chondroitin sulfate, rheumatoid arthritis, teriflunomide

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481 A New Technology for Metformin Hydrochloride Mucoadhesive Microparticles Preparation Utilizing BÜCHI Nano-Spray Dryer B-90

Authors: Tamer M. Shehata

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Objective: Currently, mucoadhesive microparticles acquired a high interest in both research and pharmaceutical technology fields. Recently, BÜCHI lunched its latest fourth generation nano spray dryer B-90 used for nanoparticle production. B-90 offers an elegant technology combined particle engineering and drying in one step. In our laboratory, we successfully developed a new formulation for metformin hydrochloride, mucoadhesive microparticles utilizing B-90 technology for treatment of type 2-diabetis. Method: Gelatin or sodium alginate, natural occurring polymers with mucoadhesive properties, solely or in combination was used in our formulation trials. Preformulation studies (atomization head mesh size, flow rate, head temperature, polymer solution viscosity and surface tension) and postformulation characters (particle size, flowability, surface scan and dissolution profile) were evaluated. Finally, hypoglycemic effect of the selected formula was evaluated in streptozotocin-induced diabetic rats. Spray head with 7 µm hole, flow rate of 3.5 mL/min and head temperature 120 ºC were selected. Polymer viscosity was less than 11.5 cP with surface tension less than 70.1 dyne/cm. Result: 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. Conclusion: B-90 technology can open a new era of , mucoadhesive microparticles preparation offering convenient dosage form that can enhance compliance of type 2 diabetic patients.

Keywords: mucoadhesive, microparticles, technology, diabetis

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480 Investigation into the Phytochemistry and Biological Activities of Medicinal Plants Used in Algerian Folk Medicine: Potential Use in Human Medicine

Authors: Djebbar Atmani, Dina Kilani, Tristan Richard

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Medicinal plants are an important source for the discovery of potential new substances for use in medicine and food. Pistacia lentiscus, Fraxinus angustifolia and Clematis flammula, plants growing in the Mediterranean basin, are widely used in traditional medicine. Therefore, the present study was designed to investigate their antioxidant, anti-inflammatory, antidiabetic, anti-mutagenic/genotoxic and neuroprotective potential and identification of active compounds using appropriate methodology. Plant extracts and fractions exhibited high scavenging capacity against known radicals, enhanced superoxide dismutase and catalase activitiesand restored blood glucose levels, in vivo, to normal values, in agreement with the in vitro enzymatic inhibition data, through inhibition of amylase and glucosidase activities. Administration of Pistacia lentiscus extracts significantly decreased carrageenan-induced mice paw oedema and reduced effectively IL-1β levels in cell culture, whereas Fraxinus angustifolia extracts showed good healing capacity against wounds when applied topically on rabbits. Pistacia lentiscus and Fraxinus angustifolia extracts showed good neuro-protection and restored cognitive functions in mice, while Clematis flammula extracts showed potent anti-ulcerogenic activity associated to a promising anti-mutagenic/genotoxic activity. HPLC-MS and NMR analyses allowed the identification and structural elucidation of several known and new anthocyanins, flavonols and flavanols. Therefore, Pistacia lentiscus, Fraxinus angustifolia and Clematis flammulacould be used in palliative treatments against inflammatory conditions and diabetes complications, as well as against deterioration of cognitive functions.

Keywords: pistacia lentiscus, clematis flammula, fraxinus angustifolia, phenolic compounds, biological activity

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479 Association between Levels of Volatile Organic Compound Metabolites and Cigarette Smoking-Related Urothelial Carcinoma

Authors: Chi-Jung Chung, Chao-Hsiang Chang, Chiu-Shong Liu, Sheng-Wei Li, Mu-Chi Chung, Ting-Jie Wen, Hui-Ling Lee

Abstract:

Cigarette smoke contains volatile organic compounds (VOCs), such as acrylamide, 1,3-butadiene, and benzene. This study aimed to explore the associations between the urinary levels of cotinine and VOC metabolites and the risk of urothelial carcinoma (UC). A hospital-based case–control study involving two groups matched on the basis of age ( ± 3 years) and gender was designed. UC was clinically diagnosed through urological examinations and pathologically verified. Smoking-related information was collected through questionnaires and face-to-face interviews with all study participants. Urine samples were collected for the analysis of the urinary levels of VOC metabolites, cotinine, and 8-hydroxydeoxygua- nosine (8-OHdG), which was selected as a proxy of oxidative stress. Multiple logistic regressions were applied to estimate the risk of UC. The urinary cotinine and 8-OHdG levels of the UC group were higher than those of the control group. The urinary levels of VOC metabolites, including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N- acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, N-acetyl-S- (4- hydroxy-2-buten-1-yl)-Lcysteine-3, trans, trans-muconic acid (t,t- MA), and S-phenylmercapturic acid (SPMA) increased as the urinary levels of cotinine increased. Relevant dose-response relationships between the risk of UC risk and the urinary levels of AAMA , t,t-MA, SPMA, and 8-OHdG were found after adjusting for potential risk factors. The UC risk of participants with high urinary levels of cotinine, AAMA, t,t-MA, SPMA, and 8-OHdG were 3.5–6-fold higher than those of other participants. Increased urinary levels of VOC metabolites were associated with smoking-related UC risk. The development of UC should be explored in large-scale in vitro or in vivo studies with the repeated measurement of VOC metabolites.

Keywords: volatile organic compound, urothelial carcinoma, cotinine, 8-hydroxydeoxyguanosine

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478 Antioxidant Activity of Morinda citrifolia L. (Noni) Fruits at Three Different Stages of Maturity in Food Systems

Authors: Deena Ramful-Baboolall, Eshana B. N. Bhatoo

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Morinda citrifolia L., commonly known as noni fruit, is rich in phytochemicals. This study investigated the phytophenolics content and antioxidant activity of green, mature green and ripe noni fruits. The vitamin C content ranged from 41.12 ± 0.083 to 143.63 ± 0.146 mg / 100 ml in fresh noni fruits. Ripe fruits contained the highest level of ascorbic acid followed by mature green and green fruits (p < 0.05). The total phenol content ranged from 0.909 (green) to 2.305 (ripe) mg / g of FW whilst the total flavonoid content ranged from 1.054 (green) to 2.116 (ripe) mg/g of FW. The in vitro antioxidant activity of the Morinda citrifolia L. extracts was also analysed using FRAP and TEAC assays. The reducing power of the fruit extracts as assessed by the FRAP assay decreased in the following order: ripe > mature green > green (p < 0.05). The TEAC values ranged from 0.2631 to 0.8921 µmol / g FW, with extracts of fruits at the mature green stage having highest values followed by fruits at the ripe and green stage respectively (p < 0.05). High correlation values were obtained between total phenolics, total flavonoids, ascorbic acid contents and the TEAC and FRAP assays (r > 0.8). Noni fruit extracts (0.2 and 0.4 % m / m) were compared with BHT (0.02 % m / m) on their ability to protect canola oil and mayonnaise, prepared with canola oil, against lipid oxidation during storage at 40°C. Mature green and ripe extracts, at both concentrations, were more effective than BHT in retarding oxidation in both food systems as evidenced by peroxide value and conjugated diene value determinations. Noni extracts were also very effective in inhibiting lipid peroxidation in tuna fish homogenates, assessed using TBARS assay. Noni fruits at the mature green and ripe stages represent a potential source of natural antioxidants for use a food additive.

Keywords: antioxidant, canola oil, mayonnaise, Morinda citrifolia L. fruit extracts, total flavonoids, total phenol

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477 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

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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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476 DeepLig: A de-novo Computational Drug Design Approach to Generate Multi-Targeted Drugs

Authors: Anika Chebrolu

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Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

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475 Improved Visible Light Activities for Degrading Pollutants on ZnO-TiO2 Nanocomposites Decorated with C and Fe Nanoparticles

Authors: Yuvraj S. Malghe, Atul B. Lavand

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In recent years, semiconductor photocatalytic degradation processes have attracted a lot of attention and are used widely for the destruction of organic pollutants present in waste water. Among various semiconductors, titanium dioxide (TiO2) is the most popular photocatalyst due to its excellent chemical stability, non-toxicity, relatively low cost and high photo-oxidation power. It has been known that zinc oxide (ZnO) with band gap energy 3.2 eV is a suitable alternative to TiO2 due to its high quantum efficiency, however it corrodes in acidic medium. Unfortunately TiO2 and ZnO both are active only in UV light due to their wide band gaps. Sunlight consist about 5-7% UV light, 46% visible light and 47% infrared radiation. In order to utilize major portion of sunlight (visible spectrum), it is necessary to modify the band gap of TiO2 as well as ZnO. This can be done by several ways such as semiconductor coupling, doping the material with metals/non metals. Doping of TiO2 using transition metals like Fe, Co and non-metals such as N, C or S extends its absorption wavelengths from UV to visible region. In the present work, we have synthesized ZnO-TiO2 nanocomposite using reverse microemulsion method. Visible light photocatalytic activity of synthesized nanocomposite was investigated for degradation of aqueous solution of malachite green (MG). To increase the photocatalytic activity of ZnO-TiO2 nanocomposite, it is decorated with C and Fe. Pure, carbon (C) doped and carbon, iron(C, Fe) co-doped nanosized ZnO-TiO2 nanocomposites were synthesized using reverse microemulsion method. These composites were characterized using, X-ray diffraction (XRD), Energy dispersive X-ray spectroscopy (EDX), Scanning electron microscopy (SEM), UV visible spectrophotometery and X-ray photoelectron spectroscopy (XPS). Visible light photocatalytic activities of synthesized nanocomposites were investigated for degradation of aqueous malachite green (MG) solution. C, Fe co-doped ZnO-TiO2 nanocomposite exhibit better photocatalytic activity and showed threefold increase in photocatalytic activity. Effect of amount of catalyst, pH and concentration of MG solution on the photodegradation rate is studied. Stability and reusability of photocatalyst is also studied. C, Fe decorated ZnO-TiO2 nanocomposite shows threefold increase in photocatalytic activity.

Keywords: malachite green, nanocomposite, photocatalysis, titanium dioxide, zinc oxide

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474 Consumption of Fat Burners Leads to Acute Liver Failure: A Systematic Review protocol

Authors: Anjana Aggarwal, Sheilja Walia

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Prevalence of obesity and overweight is increasing due to sedentary lifestyles and busy schedules of people that spend less time on physical exercise. To reduce weight, people are finding easier and more convenient ways. The easiest solution is the use of dietary supplements and fat burners. These are products that decrease body weight by increasing the basal metabolic rate. Various reports have been published on the consumption of fat burners leading to heart palpitations, seizures, anxiety, depression, psychosis, bradycardia, insomnia, muscle contractions, hepatotoxicity, and even liver failure. Case reports and series are reporting that the ingredients present in the fat burners caused acute liver failure (ALF) and hepatic toxicity in many cases. Another contributing factor is the absence of regulations from the Food and Drug Administration on these products, leading to increased consumption and a higher risk of liver diseases among the population. This systematic review aims to attain a better understanding of the dietary supplements used globally to reduce weight and document the case reports/series of acute liver failure caused by the consumption of fat burners. Electronic databases like PubMed, Cochrane, Google Scholar, etc., will be systematically searched for relevant articles. Various websites of dietary products and brands that sell such supplements, Journals of Hepatology, National and international projects launched for ALF, and their reports, along with the review of grey literature, will also be done to get a better understanding of the topic. After discussing with the co-author, the selection and screening of the articles will be performed by the author. The studies will be selected based on the predefined inclusion and exclusion criteria. The case reports and case series that will be included in the final list of the studies will be assessed for methodological quality using the CARE guidelines. The results from this study will provide insights and a better understanding of fat burners. Since the supplements are easily available in the market without any restrictions on their sale, people are unaware of their adverse effects. The consumption of these supplements causes acute liver failure. Thus, this review will provide a platform for future larger studies to be conducted.

Keywords: acute liver failure, dietary supplements, fat burners, weight loss supplements

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473 Evaluation of Azo Dye Toxicity Using Some Haematological and Histopathological Alterations in Fish Catla Catla

Authors: Jagruti Barot

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The textile industry plays a major role in the economy of India and on the other side of the coin it is the major source for water pollution. As azo dyes is the largest dye class they are extensively used in many fields such as textile industry, leather tanning industry, paper production, food, colour photography, pharmaceuticals and medicine, cosmetic, hair colourings, wood staining, agricultural, biological and chemical research etc. In addition to these, they can have acute and/or chronic effects on organisms depending on their concentration and length of exposure when they discharged as effluent in the environment. The aim of this study was to assess the genotoxic and histotoxic potentials of environmentally relevant concentrations of RR 120 on Catla catla, important edible freshwater fingerlings. For this, healthy Catla catla fingerlings were procured from the Government Fish Farm and acclimatized in 100 L capacity and continuously aerated glass aquarium in laboratory for 15 days. According to APHA some physic-chemical parameters were measured and maintained such as temperature, pH, dissolve oxygen, alkalinity, total hardness. Water along with excreta had been changed every 24 hrs. All fingerlings were fed artificial food palates once a day @ body weight. After 15 days fingerlings were grouped in 5 (10 in each) and exposed to various concentrations of RR 120 (Control, 10, 20, 30 and 40 mg/L) and samples (peripheral blood and gills, kidney) were collected and analyzed at 96 hrs. of interval. All results were compared with the control. Micronuclei (MN), nuclear buds (NB), fragmented-apoptotic (FA) and bi-nucleated (BN) cells in blood cells and in tissues (gills and kidney cells) were observed. Prominent histopathological alterations were noticed in gills such as aneurism, hyperplasia, degenerated central axis, lifting of gill epithelium, curved secondary gill lamellae etc. Similarly kidney showed some detrimental changes like shrunken glomeruli with increased periglomerular space, degenerated renal tubules etc. Both haematological and histopathological changes clearly reveal the toxic potential of RR 120. This work concludes that water pollution assessment can be done by these two biomarkers which provide baseline to the further chromosomal or molecular work.

Keywords: micronuclei, genotoxicity, RR 120, Catla catla

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472 Expression of Micro RNAs in the Liver Tissue of Mice Generated through in vitro Embryo Culture and Embryo Transfer

Authors: Göksel Doğan, Murat Öztürk, Didar Tuğçe Karakulak, Mehmet Nurullah Orman, Nicolas Sylvius, Matthew Blades, Mustafa Sandıkçı, Cengiz Ünsal, Mehtap Kılıç Eren, Funda Kıral, Levent Karagenç

Abstract:

Assisted reproduction is associated with impaired glucose metabolism in adulthood. miRNAs are key regulators of glucose metabolism. Whether embryo culture and/or transfer alters the expression of miRNAs and to what extent this process affects glucose metabolism remain largely unknown. The purpose of the present study was to examine the expression of miRNAs in the liver in mice obtained by the transfer of blastocysts. The study was comprised of an experimental (EG) and a control group (CG). EG was generated by embryo transfer to pseudo-pregnant females. Mice born from naturally ovulating females were used as the CG. Differential expression of miRNAs, blood glucose, plasma insulin, liver glycogen, and activities of some of the rate-limiting enzymes involved in glucose metabolism were determined at ten weeks of age. Blood glucose, plasma insulin, and glycogen concentrations were similar between the groups in both sexes. Activities of enzymes were similar among females. EG males had significantly less glucokinase and phosphofructokinase activity compared to CG males. None of the miRNAs were differentially expressed in males. On the other hand, miR-143-3p expression was upregulated in EG females. Expression of none of the genes targeted by miR143-3p differed between the groups. These results demonstrate that miR143-3p, a novel regulator of type 2 diabetes, is upregulated in mice generated by assisted reproduction in a sexually-dimorphic manner with no apparent effect on glucose and insulin levels at ten weeks of age. It remains to be determined if this process is associated with impaired glucose homeostasis in the long term.

Keywords: assisted reproduction, blastocyst, embryo culture, glucose metabolism, miR143-3p, oxygen

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471 Biochar-induced Metals Immobilization in the Soil as Affected by Citric Acid

Authors: Md. Shoffikul Islam, Hongqing Hu

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Reducing trace elements' mobility and bioavailability through amendment addition, especially biochar (BC), is a cost-effective and efficient method to address their toxicity in the soil environment. However, the low molecular weight organic acids (LMWOAs) in the rhizosphere could affect BC's efficiency to stabilize trace metals as the LMWOAs could either mobilize or fix metals in the soils. Therefore, understanding the BC's and LMWOAs' interaction mechanisms on metals stabilization in the rhizosphere is crucial. The present study explored the impact of BC derived from rice husk and citric acid (CA) and the combination of BC and CA on the redistribution of cadmium (Cd), lead (Pb), and zinc (Zn) among their geochemical forms through incubation experiment. The changes of zeta potential and X-ray diffraction (XRD) pattern of BC and BC-amended soils to investigate the probable mechanisms of trace elements' immobilization by BC under the CA attack were also examined. The rice husk BC at 5% (w/w) was mixed with the air-dry soil (an Anthrosols) contaminated with Cd, Pb, and Zn in the plastic pot. The 2, 5, 10, and 20 mM kg-1 (w/v) of CA were added separately into the pot. All the ingredients were mixed thoroughly with the soil. A control (CK) treatment was also prepared without BC and CA addition. After 7, 15, and 60 days of incubation with 60% (w/v) moisture level at 25 °C, the incubated soils were determined for pH and EC and were sequentially extracted to assess the metals' transformation in soil. The electronegative charges and XRD peaks of BC and BC-amended soils were also measured. Compared to CK, the application of BC, low level of CA (2 mM kg-1 soil) (CA2), and BC plus the low concentration of CA (BC-CA2) considerably declined the acid-soluble Cd, Pb, and Zn in which BC-CA2 was found to be the most effective treatment. The reversed trends were observed concerning the high levels of CA (>5-20 mM kg-1 soil) and the BC plus high concentrations of CA treatments. BC-CA2 changed the highest amounts of acid-soluble and reducible metals to the oxidizable and residual forms with time. The most increased electronegative charges of BC-CA2 indicate its (BC-CA2) highest Cd, Pb, and Zn immobilizing efficiency, probably through metals adsorption and fixation with the negative charge sites. The XRD study revealed the presence of P, O, CO32-, and Cl1- in BC, which might be responsible for the precipitation of CdCO3, pyromorphite, and hopeite in the case of Cd, Pb, and Zn immobilization, respectively. The findings depicted that the low concentration of CA increased metals' stabilization, whereas the high levels of CA enhanced their mobilization. The BC-CA2 emerged as the best amendment among treatments for metals stabilization in contaminated soils.

Keywords: Biochar, citric acid, immobilization, trace elements contaminated soil

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470 Nanoprecipitation with Ultrasonication for Enhancement of Oral Bioavailability of Fursemide: Pharmacokinetics and Pharmacodynamics Study in Rat Model

Authors: Malay K. Das, Bhanu P. Sahu

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Furosemide is a weakly acidic diuretic indicated for treatment of edema and hypertension. It has very poor solubility but high permeability through stomach and upper gastrointestinal tract (GIT). Due to its limited solubility it has poor and variable oral bioavailability of 10-90%. The aim of this study was to enhance the oral bioavailability of furosemide by preparation of nanosuspensions. The nanosuspensions were prepared by nanoprecipitation with sonication using DMSO (dimethyl sulfoxide) as a solvent and water as an antisolvent (NA). The prepared nanosuspensions were sterically stabilized with polyvinyl acetate (PVA).These were characterized for particle size, ζ potential, polydispersity index, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behavior. The effect of nanoprecipitation on oral bioavailability of furosemide nanosuspension was studied by in vitro dissolution and in vivo absorption study in rats and compared to pure drug. The stable nanosuspension was obtained with average size range of the precipitated nanoparticles between 150-300 nm and was found to be homogenous showing a narrow polydispersity index of 0.3±0.1. DSC and XRD studies indicated that the crystalline furosemide drug was converted to amorphous form upon precipitation into nanoparticles. The release profiles of nanosuspension formulation showed up to 81.2% release in 4 h. The in vivo studies on rats revealed a significant increase in the oral absorption of furosemide in the nanosuspension compared to pure drug. The AUC0→24 and Cmax values of nanosuspension were approximately 1.38 and 1.68-fold greater than that of pure drug, respectively. Furosemide nanosuspension showed 20.06±0.02 % decrease in systolic blood pressure compared to 13.37±0.02 % in plain furosemide suspension, respectively. The improved oral bioavailability and pharmacodynamics effect of furosemide may be due to the improved dissolution of furosemide in simulated gastric fluid which results in enhanced oral systemic absorption of furosemide from stomach region where it has better permeability.

Keywords: furosemide, nanosuspension, bioavailability enhancement, nanoprecipitation, oral drug delivery

Procedia PDF Downloads 573
469 Study the Multifaceted Therapeutic Properties of the IQGAP1shRNA Plasmid on Rat Liver Cancer Model

Authors: Khairy M. A. Zoheir, Nehma A. Ali, Ahmed M. Darwish, Mohamed S. Kishta, Ahmed A. Abd-Rabou, Mohamed A. Abdelhafez, Karima F. Mahrous

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The study comprehensively investigated the multifaceted therapeutic properties of the IQGAP1shRNA plasmid, encompassing its hepatoprotective, immunomodulatory, and anticancer activities. The study employed a Prednisolone-induced immunosuppressed rat model to assess the hepatoprotective and immunomodulatory effects of IQGAP1shRNA plasmid. Using this model, IQGAP1shRNA plasmid was found to modulate haematopoiesis, improving RBC, platelet, and WBC counts, underscoring its potential in hematopoietic homeostasis. Organ atrophy, a hallmark of immunosuppression in spleen, heart, liver, ovaries, and kidneys, was reversed with IQGAP1shRNA plasmid treatment, reinforcing its hepatotrophic and organotropic capabilities. Elevated hepatic biomarkers (ALT, AST, ALP, LPO) indicative of hepatocellular injury and oxidative stress were reduced with GST, highlighting its hepatoprotective and antioxidative effects. IQGAP1shRNA plasmid also restored depleted antioxidants (GSH and SOD), emphasizing its potent antioxidative and free radical scavenging capabilities. Molecular insights into immune dysregulation revealed downregulation of IQGAP1, IQGAP3 interleukin-2 (IL-2), and interleukin-4 (IL-4) mRNA expression in the liver of immunosuppressed rats. IL-2 and IL-4 play pivotal roles in immune regulation, T-cell activation, and B-cell differentiation. Notably, treatment with IQGAP1shRNA plasmid exhibited a significant upregulation of IL-2 and IL-4 mRNA expression, thereby accentuating its immunomodulatory potential in orchestrating immune homeostasis. Additionally, immune dysregulation was associated with increased levels of TNF-α. However, treatment with IQGAP1shRNA plasmid effectively decreased the levels of TNF-α, further underscoring its role in modulating inflammatory responses and restoring immune balance in immunosuppressed rats. Additionally, pharmacokinetics, bioavailability, drug-likeness, and toxicity risk assessment prediction suggest its potential as a pharmacologically favourable agent with no serious adverse effects. In conclusion, this study confirms the therapeutic potential of the IQGAP1shRNA plasmid, showcasing its effectiveness against hepatotoxicity, oxidative stress, immunosuppression, and its notable anticancer activity.

Keywords: IQGAP1, shRNA, cancer, liver, rat

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468 The Subcellular Localisation of EhRRP6 and Its Involvement in Pre-Ribosomal RNA Processing in Growth-Stressed Entamoeba histolytica

Authors: S. S. Singh, A. Bhattacharya, S. Bhattacharya

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The eukaryotic exosome complex plays a pivotal role in RNA biogenesis, maturation, surveillance and differential expression of various RNAs in response to varying environmental signals. The exosome is composed of evolutionary conserved nine core subunits and the associated exonucleases Rrp6 and Rrp44. Rrp6p is crucial for the processing of rRNAs, other non-coding RNAs, regulation of polyA tail length and termination of transcription. Rrp6p, a 3’-5’ exonuclease is required for degradation of 5’-external transcribed spacer (ETS) released from the rRNA precursors during the early steps of pre-rRNA processing. In the parasitic protist Entamoeba histolytica in response to growth stress, there occurs the accumulation of unprocessed pre-rRNA and 5’ ETS sub fragment. To understand the processes leading to this accumulation, we looked for Rrp6 and the exosome subunits in E. histolytica, by in silico approaches. Of the nine core exosomal subunits, seven had high percentage of sequence similarity with the yeast and human. The EhRrp6 homolog contained exoribonuclease and HRDC domains like yeast but its N- terminus lacked the PMC2NT domain. EhRrp6 complemented the temperature sensitive phenotype of yeast rrp6Δ cells suggesting conservation of biological activity. We showed 3’-5’ exoribonuclease activity of EhRrp6p with in vitro-synthesized appropriate RNAs substrates. Like the yeast enzyme, EhRrp6p degraded unstructured RNA, but could degrade the stem-loops slowly. Furthermore, immunolocalization revealed that EhRrp6 was nuclear-localized in normal cells but was diminished from nucleus during serum starvation, which could explain the accumulation of 5’ETS during stress. Our study shows functional conservation of EhRrp6p in E.histolytica, an early-branching eukaryote, and will help to understand the evolution of exosomal components and their regulatory function.

Keywords: entamoeba histolytica, exosome complex, rRNA processing, Rrp6

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467 Synthesis and Analgesic activity of 2-(p-Substituted phenyl)-3-[4-(N-Substituted amino) methyl-2-oxo indoilin-3-ylidene]benzenesulfonyl Quinazolin-4(3H)-One Derivatives

Authors: N. Gopal, K. Jaasminerjiit, L. Z. Xiang

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Quinazoline-4(3H)-one ring system has been consistently regarded as promising privileged structural icon owing to its pharmacodynamic versatility in many of its synthetic derivatives as well as in several naturally occurring alkaloids. The literature reveals that 2nd & 3rd positions of the quinazolin-4(3H)-one pharmacophore are the target for substitution with other moieties. On the other hand, sulphanilamide derivatives and isatin moiety also displayed valuable biological activities. Hence, it was thought worthwhile to study the effects of three pharmacophoric moieties like quinazolinone, sulphanilamide and isatin in a single molecule for the better analgesic activity with lower toxicity. Series of novel 2,3-disubstituted quinazolin-4(3H)-one derivatives have been synthesised from the intermediate Schiff base of 2-(4’-substitutedphenyl)-3-[(N-2-oxoindolin-3-ylidene)-4”-sulphonamidophenyl]-quinazolin-4(3H)-one derivatives, which was prepared from reacting 2-(substituted phenyl)-4H-benzo[d][1,3]-oxazin-4-one with sulphanilamide. The required benzoxazinone derivatives were prepared by reacting anthranilic acid with benzoyl chloride. All the compounds structure was characterised by using H1 NMR, IR and Mass spectroscopy. The intermediate Schiff base and final Mannich base compounds were evaluated for their analgesic activity by acetic acid-induced writhing method at the dose of 25mg/kg, 50 mg/kg, and 100 mg/kg (bw) and Diclofenac (25mg/kg of body weight) will be used as the reference drugs. From the results of the study, it has been observed that final Mannich base showed a better analgesic activity when compared to the parent Schiff bases, it was found that compound substituted with N-methyl piperazine at 1st position of the indole nucleus of the final quinazolinone derivatives (GA4B1) i.e. 2-(4’-methoxy phenyl)-3-[4-(N-(1-N-methyl piperazine amine) methyl-2-oxo indoilin-3-ylidene] benzenesulfonyl quinazolin-4(3H)-one increases the analgesic activity and among the synthesised compounds, GA4B1 exhibited quite superior analgesic activity. The remaining Schiff bases and Mannich base derivatives exhibited moderate analgesic activity. All the compounds showed a dose dependent activity. None of the synthesised compound showed ulcer index whereas the standard drug, diclofenac [25 mg/kg (bw)] showed significantly higher gross ulcer index values.

Keywords: analgesic activity, isatin, mannich base, quinazolin-4(3H)-one

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

Authors: Tamer Shehata

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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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465 In-situ Phytoremediation Of Polluted Soils By Micropollutants From Artisanal Gold Mining Processes In Burkina Faso

Authors: Yamma Rose, Kone Martine, Yonli Arsène, Wanko Ngnien Adrien

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Artisanal gold mining has seen a resurgence in recent years in Burkina Faso with its corollary of soil and water pollution. Indeed, in addition to visible impacts, it generates discharges rich in trace metal elements and acids. This pollution has significant environmental consequences, making these lands unusable while the population depends on the natural environment for its survival. The goal of this study is to assess the decontamination potential of Chrysopogon zizanioides on two artisanal gold processing sites in Burkina Faso. The cyanidation sites of Nebia (1Ha) and Nimbrogo (2Ha) located respectively in the Central West and Central South regions were selected. The soils were characterized to determine the initial pollution levels before the implementation of phytoremediation. After development of the site, parallel trenches equidistant 6 m apart, 30 cm deep, 40 cm wide and opposite to the water flow direction were dug and filled with earth amended with manure. The Chrysopogon zizanioides plants were transplanted 5 cm equidistant into the trenches. The mere fact that Chrysopogon zizanioides grew in the polluted soil is an indication that this plant tolerates and resists the toxicity of trace elements present on the site. The characterization shows sites very polluted with free cyanide 900 times higher than the national standard, the level of Hg in the soil is 5 times more than the limit value, iron and Zn are respectively 1000 times and 200 more than the tolerated environmental value. At time T1 (6 months) and T2 (12 months) of culture, Chrysopogon zizanioides showed less development on the Nimbrogo site than that of the Nebia site. Plant shoots and associated soil samples were collected and analyzed for total As, Hg, Fe and Zn concentration. The trace element content of the soil, the bioaccumulation factor and the hyper accumulation thresholds were also determined to assess the remediation potential. The concentration of As and Hg in the soil was below international risk thresholds, while that of Fe and Zn was well above these thresholds. The CN removal efficiency at the Nebia site is respectively 29.90% and 68.62% compared to 6.6% and 60.8% at Nimbrogo at time T1 and T2.

Keywords: chrysopogon zizanioides, in-situ phytoremediation, polluted soils, micropollutants

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464 Advances in Health Risk Assessment of Mycotoxins in Africa

Authors: Wilfred A. Abiaa, Chibundu N. Ezekiel, Benedikt Warth, Michael Sulyok, Paul C. Turner, Rudolf Krska, Paul F. Moundipa

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Mycotoxins are a wide range of toxic secondary metabolites of fungi that contaminate various food commodities worldwide especially in sub-Saharan Africa (SSA). Such contamination seriously compromises food safety and quality posing a serious problem for human health as well as to trade and the economy. Their concentrations depend on various factors, such as the commodity itself, climatic conditions, storage conditions, seasonal variances, and processing methods. When humans consume foods contaminated by mycotoxins, they exert toxic effects to their health through various modes of actions. Rural populations in sub-Saharan Africa, are exposed to dietary mycotoxins, but it is supposed that exposure levels and health risks associated with mycotoxins between SSA countries may vary. Dietary exposures and health risk assessment studies have been limited by lack of equipment for the proper assessment of the associated health implications on consumer populations when they eat contaminated agricultural products. As such, mycotoxin research is premature in several SSA nations with product evaluation for mycotoxin loads below/above legislative limits being inadequate. Few nations have health risk assessment reports mainly based on direct quantification of the toxins in foods ('external exposure') and linking food levels with data from food frequency questionnaires. Nonetheless, the assessment of the exposure and health risk to mycotoxins requires more than the traditional approaches. Only a fraction of the mycotoxins in contaminated foods reaches the blood stream and exert toxicity ('internal exposure'). Also, internal exposure is usually smaller than external exposure thus dependence on external exposure alone may induce confounders in risk assessment. Some studies from SSA earlier focused on biomarker analysis mainly on aflatoxins while a few recent studies have concentrated on the multi-biomarker analysis of exposures in urine providing probable associations between observed disease occurrences and dietary mycotoxins levels. As a result, new techniques that could assess the levels of exposures directly in body tissue or fluid, and possibly link them to the disease state of individuals became urgent.

Keywords: mycotoxins, biomarkers, exposure assessment, health risk assessment, sub-Saharan Africa

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463 Probiotic Potential and Antimicrobial Activity of Enterococcus faecium Isolated from Chicken Caecal and Fecal Samples

Authors: Salma H. Abu Hafsa, A. Mendonca, B. Brehm-Stecher, A. A. Hassan, S. A. Ibrahim

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Enterococci are important inhabitants of the animal intestine and are widely used in probiotic products. A probiotic strain is expected to possess several desirable properties in order to exert beneficial effects. Therefore, the objective of this study was to isolate and characterize strains of Enterococcus sp. from chicken cecal and fecal samples to determine potential probiotic properties. Enterococci were isolated from thirty one chicken cecal and fecal samples collected from a local farm. In vitro studies were performed to assess antibacterial activity (using agar well diffusion and cell free supernatant broth technique against Salmonella enterica serotype Enteritidis), susceptibility to antibiotics (amoxycillin, cotrimoxazole, chloramphenicol, cefuroxime, ceftriaxone, ciprofloxacin, and nalidixic acid), survival in acidic conditions, resistance to bile salts, and their survival during simulated gastric juice conditions at pH 2.5. Isolates were identified using biochemical and molecular assays (API 50 CHL, and API ZYM kits followed by 16S rDNA gene sequence analysis). Two strains were identified, of which, Enteroccocus faecium was capable of inhibiting the growth of S. enteritidis and was susceptible to a wide range of antibiotics. In addition, the isolated strain exhibited significant resistance under highly acidic conditions (pH=2.5) for 8 hours and survived well in bile salt at 0.2% for 24 hours and showing ability to survive in the presence of simulated gastric juice at pH 2.5. Based on these results, the E. faecium isolate fulfills some of the criteria to be considered as a probiotic strain and therefore, could be used as a feed additive with good potential for controlling S. enteritidis in chickens. However, in vivo studies are needed to determine the safety of the strain.

Keywords: acid tolerance, antimicrobial activity, Enterococcus faecium, probiotic

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462 Angiogenic Potential of Collagen Based Biomaterials Implanted on Chick Embryo Chorioallantoic Membrane as Alternative Microenvironment for in Vitro and in Vivo Angiogenesis Assays

Authors: Anca Maria Cimpean, Serban Comsa

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Chick embryo chorioallantoic membrane (CAM) is a well vascularised in vivo experimental model used as a platform for testing the behavior of different implants inserted on it from tumor fragments to therapeutic agents or various biomaterials. Five types of collagen-based biomaterials with 2D and 3D structure (MotifMesh, Optimaix2D, Optimaix3D, Dual Layer Collagen and Xenoderm) were implanted on CAM and continuously evaluated by stereomicroscope for up to 5 days post-implant with an emphasis of their ability to requisite and develop new blood vessels (BVs) followed by microscopic analysis. MotifMEsh did not induce any angiogenic response lacking to be invaded by BVs from the CAM, but it induced intense inflammatory response necrosis and fibroblastic reaction around the implant. Optimaix2D has good adherence. CAM with minimal or no inflammatory reaction, a good integration of the CAM between the collagen mesh’s fibers, consistent adhesion of the cells to the collagen fibers,and a good ability to form pseudo-vascular channels filled with cells. Optimaix3D induced the highest angiogenic effects on CAM. The material shows good integration on CAM. The collagen fibers of the material show the ability to organize themselves into linear and tubular structures. It is possible to see blood elements, especially at the periphery of the implant. Dual-layer collagen behaves similar to Optimaix 3D, while Xenoderm induced a moderate angiogenic effect on CAM. Based on these data, we may conclude that collagen-based materials have variable ability to requisite and develop new blood vessels. A proper selection of collagen-based biomaterial scaffolds may crucially influence the acquisition and development of blood vessels during angiogenesis assays.

Keywords: chick embryo chorioallantoic membrane, collagen scaffolds, blood vessels, vascular microenvironment

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461 Evaluation of Anti-Typhoid Effects of Azadirachta indica L. Fractions

Authors: A. Adetutu, T. M. Awodugba, O. A. Owoade

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The development of resistance to currently known conventional anti-typhoid drugs has necessitated search into cheap, more potent and less toxic anti-typhoid drugs of plant origin. Therefore, this study investigated the anti-typhoid activity of fractions of A. indica in Salmonella typhi infected rats. Leaves of A. indica were extracted in methanol and fractionated into n-hexane, chloroform, ethyl-acetate, and aqueous fractions. The anti-salmonella potentials of fractions of A. indica were assessed via in-vitro inhibition of S. typhi using agar well diffusion, Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and biofilm assays. The biochemical and haematological parameters were determined by spectrophotometric methods. The histological analysis was performed using Haematoxylin and Eosin staining methods. Data analysis was performed by one-way ANOVA. Results of this study showed that S. typhi was sensitive to aqueous and chloroform fractions of A. indica, and the fractions showed biofilm inhibition at concentrations of 12.50, 1.562, and 0.39 mg/mL. In the in-vivo study, the extract and chloroform fraction had significant (p < 0.05) effects on the number of viable S. typhi recovered from the blood and stopped salmonellosis after 6 days of treatment of rats at 500 mg/kg b.w. Treatments of infected rats with chloroform and aqueous fractions of A. indica normalized the haematological parameters in the animals. Similarly, treatment with fractions of the plants sustained a normal antioxidant status when compared with the normal control group. Chloroform and ethyl-acetate fractions of A. indica reversed the liver and intestinal degeneration induced by S. typhi infection in rats. The present investigation indicated that the aqueous and chloroform fractions of A. indica showed the potential to provide an effective treatment for salmonellosis, including typhoid fever. The results of the study may justify the ethno-medicinal use of the extract in traditional medicine for the treatment of typhoid and salmonella infections.

Keywords: Azadirachta indica L, salmonella, typhoid, leave fractions

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460 Sider Bee Honey: Antitumor Effect in Some Experimental Tumor Cell Lines

Authors: Aliaa M. Issa, Mahmoud N. ElRouby, Sahar A. S. Ahmad, Mahmoud M. El-Merzabani

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Sider honey is a type of honey produced by bees feeding on the nectar of Sider tree, Ziziphus spina-christi (L) Desf . Honey is an effective agent for preventing, inhibiting and treating the growth of human and animal cancer cell lines in vitro and in vivo. The aim of the present study was to evaluate the impact of different dilutions from crude Sider honey and different duration times of exposure on the growth of six tumor cell lines (human cervical cancer cell line, HeLa; human hepatocellular carcinoma cell line, HepG-2; human larynx carcinoma cell line, Hep-2; brain tumor cell line, U251) as well as one animal cancerous cell line (Ehrlich ascites carcinoma cells line, EAC) and one normal cell line, Homo sapiens, human, (WISH) CCL-25. Different concentrations and treatment durations with Sider honey were tested on the growth of several cancer cell lines types. Histopathological changes in the tumor masses, animal survival, apoptosis and necrosis of the used cancer cell lines (using flow cytometry) were evaluated. Sider honey was administers either to the tumor mass itself by intratumoral injection or via drinking water. One-way ANOVA test was used for the analysis of (the means + standard error) of the optical density obtained from the Elisa reader and flow cytometry. The study revealed that different concentrations of Sider honey affected the growth patterns of all the studied cancer cell lines as well as their histopathological changes, and it depended on the cell line nature and the concentration of honey used. It is obvious that the relative animal survival percentage (bearing Ehrlich ascites carcinoma, EAC cells) was proportionally increased with the increase in the used honey concentrations. The study of apoptosis and necrosis using the flow cytometry technique emphasized the viability results. In conclusion, Sider honey was effective as antitumor agent, in the used concentrations.

Keywords: antitumor, honey, sider, tumor cell lines

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459 Harnessing the Power of Mixed Ligand Complexes: Enhancing Antimicrobial Activities with Thiosemicarbazones

Authors: Sakshi Gupta, Seema Joshi

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Thiosemicarbazones (TSCs) have garnered significant attention in coordination chemistry due to their versatile coordination modes and pharmacological properties. Mixed ligand complexes of TSCs represent a promising area of research, offering enhanced antimicrobial activities compared to their parent compounds. This review provides an overview of the synthesis, characterization, and antimicrobial properties of mixed ligand complexes incorporating thiosemicarbazones. The synthesis of mixed ligand complexes typically involves the reaction of a metal salt with TSC ligands and additional ligands, such as nitrogen- or oxygen-based ligands. Various transition metals, including copper, nickel, and cobalt, have been employed to form mixed ligand complexes with TSCs. Characterization techniques such as spectroscopy, X-ray crystallography, and elemental analysis are commonly utilized to confirm the structures of these complexes. One of the key advantages of mixed ligand complexes is their enhanced antimicrobial activity compared to pure TSC compounds. The synergistic effect between the TSC ligands and additional ligands contributes to increased efficacy, possibly through improved metal-ligand interactions or enhanced membrane permeability. Furthermore, mixed ligand complexes offer the potential for selective targeting of microbial species while minimizing toxicity to mammalian cells. This selectivity arises from the specific interactions between the metal center, TSC ligands, and biological targets within microbial cells. Such targeted antimicrobial activity is crucial for developing effective treatments with minimal side effects. Moreover, the versatility of mixed ligand complexes allows for the design of tailored antimicrobial agents with optimized properties. By varying the metal ion, TSC ligands, and additional ligands, researchers can fine-tune the physicochemical properties and biological activities of these complexes. This tunability opens avenues for the development of novel antimicrobial agents with improved efficacy and reduced resistance. In conclusion, mixed ligand complexes of thiosemicarbazones represent a promising class of compounds with potent antimicrobial activities. Further research in this field holds great potential for the development of novel therapeutic agents to combat microbial infections effectively.

Keywords: metal complex, thiosemicarbazones, mixed ligand, selective targeting, antimicrobial activity

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458 Induction of Callus and Expression of Compounds in Capsicum Frutescens Supplemented with of 2, 4-D

Authors: Jamilah Syafawati Yaacob, Muhammad Aiman Ramli

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Cili padi or Capsicum frutescens is one of capsicum species from nightshade family, Solanaceae. It is famous in Malaysia and is widely used as a food ingredient. Capsicum frutescens also possess vast medicinal properties. The objectives of this study are to determine the most optimum 2,4-D hormone concentration for callus induction from stem explants C. frutescens and the effects of different 2,4-D concentrations on expression of compounds from C. frutescens. Seeds were cultured on MS media without hormones (MS basal media) to yield aseptic seedlings of this species, which were then used to supply explant source for subsequent tissue culture experiments. Stem explants were excised from aseptic seedlings and cultured on MS media supplemented with various concentrations (0.1, 0.3 and 0.5 mg/L) of 2,4-D to induce formation of callus. Fresh weight, dry weight and callus growth percentage in all samples were recorded. The highest mean of dry weight was observed in MS media supplemented with 0.5 mg/L 2,4-D, where 0.4499 ± 0.106 g of callus was produced. The highest percentage of callus growth (16.4%) was also observed in cultures supplemented with 0.5 mg/L 2,4-D. The callus samples were also subjected to HPLC-MS to evaluate the effect of hormone concentration on expression of bio active compounds in different samples. Results showed that caffeoylferuloylquinic acids were present in all samples, but was most abundant in callus cells supplemented with 0.3 & 0.5 mg/L 2,4-D. Interestingly, there was an unknown compound observed to be highly expressed in callus cells supplemented with 0.1 mg/L 2,4-D, but its presence was less significant in callus cells supplemented with 0.3 and 0.5 mg/L 2,4-D. Furthermore, there was also a compound identified as octadecadienoic acid, which was uniquely expressed in callus supplemented with 0.5 mg/L 2,4-D, but absent in callus cells supplemented with 0.1 and 0.3 mg/L 2,4-D. The results obtained in this study indicated that plant growth regulators played a role in expression of secondary metabolites in plants. The increase or decrease of these growth regulators may have triggered a change in the secondary metabolite biosynthesis pathways, thus causing differential expression of compounds in this plant.

Keywords: callus, in vitro, secondary metabolite, 2, 4-Dichlorophenoxyacetic acid

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457 Adsorption and Photocatalytic Degradation of Textile Wastewater Using Green Synthesized Sequesters

Authors: Omotayo Sarafadeen Amuda, Kazeem Kolapo Salam, Oyediran Olarike Favour

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This study carried out the physicochemical analysis of the Textile WasteWater (TWW) before and after the adsorption and photocatalytic processes. The adsorbents and catalysts that were used for this study were prepared from C. albidum seed shell activated with steam and then loaded with Titanium Dioxide Nanoparticles (TiO2NPs) and Copper Nanoparticles (Cu NPs), which were synthesized from green tea leaf extract and Citrus limon fruits extract, respectively. The photocatalytic activity was carried out under sunlight irradiation, and the effect of various parameters, such as catalyst dose, pH, contact time, and initial dye concentration, on the removal efficiency, were studied. The reusability of the catalyst was also observed to determine its stability and long-term efficacy. Ultra-violet visible spectroscopy (UV-Vis spectroscopy) was used to determine the dye concentration after each experiment. The adsorbents, nanoparticles, and photocatalysts were appropriately characterized for morphological, functional group, structural, and surface area using Scanning Electron Microscopy (SEM), Fourier-Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD) analysis, and Brunauer–Emmett–Teller (BET) analysis respectively. Batch adsorption studies were carried out on the wastewater, using the composite adsorbents, to determine the effects of pH, adsorbent dose, initial dye concentration, and contact time. The batch adsorption studies were conducted based on the runs generated from the Definitive Screen Design (DSD) of the Response Surface Methodology (RSM). The obtained data were subjected to the pseudo-first-order, pseudo-second-order, and intra-particle diffusion kinetic models, the Langmuir and Freundlich isotherm models, and thermodynamic parameters. The findings of this study contribute to the existing knowledge by providing more insights into the identification of efficient, low-cost, and environmentally-friendly approach to textile wastewater treatment. This approach enhances the reduction of potential toxicity from the discharged textile wastewater into the environment and, thus, conforms to Sustainable Development Goal 6 (SDG 6), which ensures the sustainability of the water resources, wastewater, and ecosystems.

Keywords: adsorption, photocatalytic, textile wastewater, green synthesized sequesters, degradation

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