Search results for: in vitro fertilization
425 Infused Mesenchymal Stem Cells Ameliorate Organs Morphology in Cerebral Malaria Infection
Authors: Reva Sharan Thakur, Mrinalini Tiwari, Jyoti das
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Cerebral malaria-associated over expression of pro-inflammatory cytokines and chemokines ultimately results in the up-regulation of adhesion molecules in the brain endothelium leading to sequestration of mature parasitized RBCs in the brain. The high-parasitic load subsequently results in increased mortality or development of neurological symptoms within a week of infection. Studies in the human and experimental cerebral malaria have implicated the breakdown of the integrity of blood-brain barrier during the lethal course of infection, cerebral dysfunction, and fatal organ pathologies that result in multi-organ failure. In the present study, using Plasmodium berghei Anka as a mouse model and in vitro conditions, we have investigated the effect of MSCs to attenuate cerebral malaria pathogenesis by diminishing the effect of inflammation altered organ morphology, reduced parasitemia, and increased survival of the mice. MSCs are also validated for their role in preventing BBB dysfunction and reducing malarial toxins. It was observed that administration of MSCs significantly reduced parasitemia and increased survival in Pb A infected mice. It was further demonstrated that MSCs play a significant role in reversing neurological complexities associated with cerebral malaria. Infusion of MSCs in infected mice decreased hemozoin deposition; oedema, and haemorrhagic lesions in vascular organs. MSCs administration also preserved the integrity of the blood-brain barrier and reduced neural inflammation. Taken together, our results demonstrate the potential of MSCs as an emerging anti-malarial candidate.Keywords: cerebral malaria, mesenchymal stem cells, erythropoesis, cell death
Procedia PDF Downloads 98424 Rapid and Easy Fabrication of Collagen-Based Biocomposite Scaffolds for 3D Cell Culture
Authors: Esra Turker, Umit Hakan Yildiz, Ahu Arslan Yildiz
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The key of regenerative medicine is mimicking natural three dimensional (3D) microenvironment of tissues by utilizing appropriate biomaterials. In this study, a synthetic biodegradable polymer; poly (L-lactide-co-ε-caprolactone) (PLLCL) and a natural polymer; collagen was used to mimic the biochemical structure of the natural extracellular matrix (ECM), and by means of electrospinning technique the real physical structure of ECM has mimicked. PLLCL/Collagen biocomposite scaffolds enables cell attachment, proliferation and nutrient transport through fabrication of micro to nanometer scale nanofibers. Biocomposite materials are commonly preferred due to limitations of physical and biocompatible properties of natural and synthetic materials. Combination of both materials improves the strength, degradation and biocompatibility of scaffold. Literature studies have shown that collagen is mostly solved with heavy chemicals, which is not suitable for cell culturing. To overcome this problem, a new approach has been developed in this study where polyvinylpyrrolidone (PVP) is used as co-electrospinning agent. PVP is preferred due to its water solubility, so PLLCL/collagen biocomposite scaffold can be easily and rapidly produced. Hydrolytic and enzymatic biodegradation as well as mechanical strength of scaffolds were examined in vitro. Cell adhesion, proliferation and cell morphology characterization studies have been performed as well. Further, on-chip drug screening analysis has been performed over 3D tumor models. Overall, the developed biocomposite scaffold was used for 3D tumor model formation and obtained results confirmed that developed model could be used for drug screening studies to predict clinical efficacy of a drug.Keywords: biomaterials, 3D cell culture, drug screening, electrospinning, lab-on-a-chip, tissue engineering
Procedia PDF Downloads 304423 Antiplasmodial Activity of Drimane Sesquiterpene Isolated from Warburgia salutaris
Authors: Mthokozisi Simelane
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Background: Malaria remains a life-threatening disease in tropical regions despite the advances in the treatment of this disease, it still remains a significant burden as some parasites have become resistant to the currently available drugs. This has created a necessity for the development of alternative, more efficient antimalarial drugs. Warburgia salutaris is a traditional medicinal plant used in malaria treatment by Zulu traditional healers. Materials and methods: The W. salutaris stem-bark was extracted with dichloromethane and the compound was isolated through column chromatography. The compound was identified and characterized by spectroscopic analysis (1H NMR, 13C NMR, IR and MS) and the structure was also confirmed by x-ray crystallography. The anti-plasmodial activity (in vitro) was studied on NF54 Plasmodium falciparum strain (CQS). Cytotoxicity was measured using the MTT assay on HEK239 and HEPG2 cell lines. Docking of Mukaadial acetate was conducted in AutoDock Vina. Structural modifications were conducted in UCSF Chimera and molecular interactions examined in LigPlot. Results: The compound, Mukaadial Acetate showed appreciable inhibition (IC50 0.44±0.10 µg/ml) of the parasite growth and cytotoxicity activity of 0.124±0.109 and 0.199±0.083 (µg/ml) on HEK293 and HEPG2 cells respectively. Molecular docking revealed that Mukaadial Acetate binds to the purine, pyrophosphate and ribose binding sites of the PfHGXPRT with an optimum binding conformation and forms hydrogen bond, steric and hydrophobic interactions with the residues inhabiting the respective binding sites. Conclusion: It is apparent that W. salutaris contains components (including Mukaadial Acetate) that exhibit antimalarial activity. This study scientifically validates the use of this plant in folk medicine.Keywords: plasmodium falciparum, molecular docking, antimalarial activity, PfHGXPRT, Warburgia salutaris, mukaadial acetate
Procedia PDF Downloads 192422 Protective Effect of Celosia Argentea Leaf Extract on Cadmium Induced Toxicity and Oxidative Stress in Rats
Authors: Sulyman Abdulhakeem Olarewaju, S. O. Malomo, M. T. Yakubu, J. O. Akolade
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The ameliorative effect of Celosia argentea var. cristata leaf extract against cadmium (Cd) induced oxidative stress and toxicity in selected tissues of rats was investigated. Toxicity coupled with oxidative stress was induced in rats by oral administration of Cd (8 mg/kg b. wt). Preliminary quantitative phytochemical and in vitro antioxidant analyses showed that the methanolic extract of C. argentea leaves was constituted by polyphenols (5.72%), saponins (3.20%), tannins (0.65%) and cadenolides (0.006%). IC50 of 9800, 7406, and 45.04 μg/ml were recorded for inhibition of linoleic acid oxidation, 2, 2-diphenyl-1-picrylhydrazyl and hydrogen peroxide radicals respectively. Simultaneous administration of C. argentea leaf extract with Cd significantly attenuated Cd-induced elevation of serum enzyme markers such as aspartate and alanine transaminase, alkaline and acid phosphatase as well as γ-glutaryltransferase in a dose-dependent fashion, while their reduced level in the liver were significantly increased. Higher levels of enzymatic antioxidants; superoxide dismutase and catalase activities were observed in the liver, brain, kidney and testes of the Cd-induced rats treated with C. argentea extract, while lipid peroxidation expressed in malondialdehyde concentrations were lower when compared to values in rats administered Cd only. Other Cd-induced toxicity and stress markers in the serum viz. reduced uric acid and albumin levels as well as elevated total and unconjugated bilirubin were attenuated by the extract and their values compared favorably with those animals co-administered cadmium with ascorbic acid. Data from the study showed that oral administration of extract from the leaf C. argentea may ameliorate Cd-induced oxidative stress and toxicity in rats.Keywords: toxicity, cadmium, celosia, antioxidants, oxidative stress
Procedia PDF Downloads 335421 Detection and Expression of Peroxidase Genes in Trichoderma harzianum KY488466 and Its Response to Crude Oil Degradation
Authors: Michael Dare Asemoloye, Segun Gbolagade Jonathan, Rafiq Ahmad, Odunayo Joseph Olawuyi, D. O. Adejoye
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Fungi have potentials for degrading hydrocarbons through the secretion of different enzymes. Crude oil tolerance and degradation by Trichoderma harzianum was investigated in this study with its ability to produce peroxidase enzymes (LiP and MnP). Many fungal strains were isolated from rhizosphere of grasses growing on a crude oil spilled site, and the most frequent strain based on percentage incidence was further characterized using morphological and molecular characteristics. Molecular characterization was done through the amplification of Ribosomal-RNA regions of 18s (1609-1627) and 28s (287-266) using ITS1 and ITS4 combinations and it was identified using NCBI BLAST tool. The selected fungus was also subjected to an in-vitro tolerance test at crude oil concentrations of 5, 10, 15, 20 and 25% while 0% served as control. In addition, lignin peroxidase genes (lig1-6) and manganese peroxidase gene (mnp) were detected and expressed in this strain using RT-PCR technique, its peroxidase producing activities was also studied in aliquots (U/ml). This strain had highest incidence of 80%, it was registered in NCBI as Trichoderma harzianum asemoJ KY488466. The strain KY488466 responded to crude oil concentrations as it increase, the dose inhibition response percentage (DIRP) increased from 41.67 to 95.41 at 5 to 25 % crude oil concentrations. All the peroxidase genes are present in KY488466, and expressed with amplified 900-1000 bp through RT-PCR technique. In this strain, lig2, lig4 and mnp genes were over-expressed, lig 6 was moderately expressed, while none of the genes was under-expressed. The strain also produced 90±0.87 U/ml lignin peroxidase and 120±1.23 U/mil manganese peroxidase enzymes in aliquots. These results imply that KY488466 can tolerate and survive high crude oil concentration and could be exploited for bioremediation of oil-spilled soils, the produced peroxidase enzymes could also be exploited for other biotechnological experiments.Keywords: crude oil, enzymes, expression, peroxidase genes, tolerance, Trichoderma harzianum
Procedia PDF Downloads 217420 Site-Specific Delivery of Hybrid Upconversion Nanoparticles for Photo-Activated Multimodal Therapies of Glioblastoma
Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu
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In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles
Procedia PDF Downloads 185419 Antiproliferative Effect of Polyphenols from Crocus sativus L. Leaves on Human Colon Adenocarcinoma Cells (Caco-2)
Authors: Gonzalo Ortiz de Elguea-Culebras, Raúl Sánchez-Vioquea, Adela Mena-Morales, Manuel Alaiz, Enrique Melero-Bravo, Esteban García-Romero, Javier Vioque, Lourdes Marchante-Cuevas, Julio Girón-Calle
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Saffron (Crocus sativus L.) is a highly valued crop for the manufacture of spice that consists of the dried stigma of the flowers. This is in contrast to other underutilized parts of the saffron plant as leaves, which represent abundant biomass whose use might help to enhance the sustainability of the saffron crop. Saffron leaves contain significant amounts of phenolic compounds, 7.8 equivalent grams of gallic acid per 100g of extract, and are very promising compounds in terms of exploring novel uses of saffron leaves. Given that phenolic compounds have numerous effects on cancer-related biological pathways, we have investigated the in vitro antiproliferative effect of saffron leaf polyphenols against human colon adenocarcinoma cells (Caco-2). Polyphenols were extracted from leaves with 70% ethanol, defatted with hexane, and purified by solid phase extraction using C18 silica gel and then silica gel 60. Analysis of polyphenols was performed by HPLC-ESI-MS. Di-, tri-, and tetrahexosides of quercetin, kaempferol, and isorhamnetin, as well as C-hexosides like isoorientin and vitexin, were tentatively identified. Polyphenols strongly inhibited the proliferation of Caco-2 cells, which is consistent with model studies in which several of the polyphenols identified in saffron leaves have demonstrated their potential as chemopreventive agents in cancer. Due to the low profitability that saffron leaf currently represents, we consider these results very encouraging and that this by-product deserves further investigation as a potential source of active molecules against colorectal cancer.Keywords: saffron leaves, agricultural by-products, polyphenols, antiproliferative effect, human colon adenocarcinoma cells
Procedia PDF Downloads 83418 Probiotic Antibacterial Test of Pediococcus pentosaceus Isolated from Dadih in Inhibiting Periodontitis Bacteria: In Vitro Study on Bacteria Aggregatibacter actinomycetemcomitans
Authors: Nurlaili Syafar Wulan, Almurdi, Suprianto Kosno
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Introduction: Periodontitis defined as an inflammatory disease of teeth supporting tissue with irritation of specific pathogens as the main aetiology. Periodontitis can be cured by giving medical action accompanied by administration of an antibiotic, but the use of antibiotic has a side effect that can cause bacterial resistance. This side effect can be corrected by probiotic, which has antibiotic-like substance but do not have bacterial resistance effect; it makes probiotic became a promising future periodontitis medication. West Sumatran people has their own typical traditional food product made from fermented buffalo’s milk called dadih, and it contained probiotics. Objectives: The aim of this study was to determine the ability of probiotic Pediococcus pentosaceus isolated from dadih in inhibiting the growth of bacteria Aggregatibacter actinomycetemcomitans. Material and Method: This was a true experimental study with post-test and control group design. This study was conducted on 36 samples of 2 treatment groups, the test group with probiotic Pediococcus pentosacesus isolated from dadih and the negative control group with sterile aquadest. The antibacterial effect was tested using the Kirby-Bauer disk diffusion method and calculated by measuring the zone of inhibition on MHA around paper disk using a sliding caliper with 0.5 mm accuracy. Result: The result of bivariate analysis using Independent t-test was p=0.00 where p < 0.05 means that there is a significant difference between the tested group and negative control group. Conclusion: Probiotic Pediococcus pentosaceus isolated from dadih are able to inhibit the growth of Aggregatibacter actinomycetemcomitans.Keywords: aggregatibacter actinomycetemcomitans, antibacterial activities, periodontitis, probiotic Pediococcus pentosaceus
Procedia PDF Downloads 125417 Formulation and Evaluation of Silibilin Loaded PLGA Nanoparticles for Cancer Therapy
Authors: Priya Patel, Paresh Patel, Mihir Raval
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Silibinin, a flavanone as an antimicrotubular agent used in the treatment of cancer, was encapsulated in nanoparticles (NPs) of poly (lactide-co-glycolide) (PLGA) polymer using the spray-drying technique. The effects of various experimental parameters were optimized by box-behnken experimental design. Production yield, encapsulation efficiency and dissolution study along with characterization by scanning electron microscopy, DSC, FTIR followed by bioavailability study. Particle size and zeta potential were evaluated by using zetatrac particle size analyzer. Experimental design it was evaluated that inlet temperature and polymer concentration influence on the drug release. Feed flow rate impact on particle size. Results showed that spray drying technique yield 149 nm indicate nanosize range. The small size of the nanoparticle resulted in an enhanced cellular entry and greater bioavailability. Entrapment efficiency was found between 89.35% and 98.36%. Zeta potential shows good stability index of nanoparticle formulation. The in vitro release studies indicated the silibinin loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Pharmacokinetic studies demonstrated that after oral administration of silibinin-loaded PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 8.85-fold, compared to silibinin suspension as control hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of silibinin loaded PLGA nanoparticles. These results describe an effective strategy of silibinin loaded PLGA nanoparticles and might provide a promising approach against the cancer.Keywords: silibinin, cancer, nanoparticles, PLGA, bioavailability
Procedia PDF Downloads 412416 Entry Inhibitors Are Less Effective at Preventing Cell-Associated HIV-2 Infection than HIV-1
Authors: A. R. Diniz, P. Borrego, I. Bártolo, N. Taveira
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Cell-to-cell transmission plays a critical role in the spread of HIV-1 infection in vitro and in vivo. Inhibition of HIV-1 cell-associated infection by antiretroviral drugs and neutralizing antibodies (NAbs) is more difficult compared to cell-free infection. Limited data exists on cell-associated infection by HIV-2 and its inhibition. In this work, we determined the ability of entry inhibitors to inhibit HIV-1 and HIV-2 cell-to cell fusion as a proxy to cell-associated infection. We developed a method in which Hela-CD4-cells are first transfected with a Tat expressing plasmid (pcDNA3.1+/Tat101) and infected with recombinant vaccinia viruses expressing either the HIV-1 (vPE16: from isolate HTLV-IIIB, clone BH8, X4 tropism) or HIV-2 (vSC50: from HIV-2SBL/ISY, R5 and X4 tropism) envelope glycoproteins (M.O.I.=1 PFU/cell).These cells are added to TZM-bl cells. When cell-to-cell fusion (syncytia) occurs the Tat protein diffuses to the TZM-bl cells activating the expression of a reporter gene (luciferase). We tested several entry inhibitors including the fusion inhibitors T1249, T20 and P3, the CCR5 antagonists MVC and TAK-779, the CXCR4 antagonist AMD3100 and several HIV-2 neutralizing antibodies (Nabs). All compounds inhibited HIV-1 and HIV-2 cell fusion albeit to different levels. Maximum percentage of HIV-2 inhibition (MPI) was higher for fusion inhibitors (T1249- 99.8%; P3- 95%, T20-90%) followed by co-receptor antagonists (MVC- 63%; TAK-779- 55%; AMD3100- 45%). NAbs from HIV-2 infected patients did not prevent cell fusion up to the tested concentration of 4μg/ml. As for HIV-1, MPI reached 100% with TAK-779 and T1249. For the other antivirals, MPIs were: P3-79%; T20-75%; AMD3100-61%; MVC-65%.These results are consistent with published data. Maraviroc had the lowest IC50 both for HIV-2 and HIV-1 (IC50 HIV-2= 0.06 μM; HIV-1=0.0076μM). Highest IC50 were observed with T20 for HIV-2 (3.86μM) and with TAK-779 for HIV-1 (12.64μM). Overall, our results show that entry inhibitors in clinical use are less effective at preventing Env mediated cell-to-cell-fusion in HIV-2 than in HIV-1 which suggests that cell-associated HIV-2 infection will be more difficult to inhibit compared to HIV-1. The method described here will be useful to screen for new HIV entry inhibitors.Keywords: cell-to-cell fusion, entry inhibitors, HIV, NAbs, vaccinia virus
Procedia PDF Downloads 300415 Influence of Cyperus Rotundus Active Principles Inhibit Viral Multiplication and Stimulate Immune System in Indian White Shrimp Fenneropenaeus Indicus against White Spot Syndrome Virus Infection
Authors: Thavasimuthu Citarasu, Mariavincent Michaelbabu, Vikram Vakharia
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The rhizome of Java grass, Cyperus rotundus was extracted different organic polar and non-polar solvents and performed the in vitro antiviral and immunostimulant activities against White Spot Syndrome Virus (WSSV) and Vibrio harveyi respectively. Based on the initial screening the ethyl acetate extract of C. rotundus was strong activities and further it was purified through silica column chromatography and the fractions were screened again for antiviral and immunostimulant activity. Among the different fractions screened against the WSSV and V. harveyi, the fractions, F-III to FV had strong activities. In order to study the in vivo influence of C. rotundus, the fractions (F-III to FV) were pooled and delivered to the F. indicus through artificial feed for 30 days. After the feeding trail the experimental and control diet fed F. indicus were challenged with virulent WSSV and studied the survival, molecular diagnosis, biochemical, haematological and immunological parameters. Surprisingly, the pooled fractions (F-III to FV) incorporated diets helped to significantly (P < 0.01) suppressed viral multiplication, showed significant (P < 0.01) differences in protein and glucose levels, improved total haemocyte count (THC), coagulase activity, significantly increased (P < =0.001) prophenol oxidase and intracellular superoxide anion production compared to the control shrimps. Based on the results, C. rotundus extracts effectively suppressed WSSV multiplication and improve the immune system in F. indicus against WSSV infection and this knowledge will helps to develop novel drugs from C. rotundus against WSSV.Keywords: antiviral drugs, cyperus rotundus, fenneropenaeus indicus, WSSV
Procedia PDF Downloads 444414 The Immunosuppressive Effects of Silymarin with Rapamaycin on the Proliferation and Apoptosis of T Cell
Authors: Nahid Eskandari, Marjan Ghagozolo, Ehsan Almasi
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Introduction: Silymarin, as a polyphenolic flavonoid derived from milk thistle (Silybum marianum), is known to have antioxidant, immunomodulatory, antiproliferative, antifibrotic, and antiviral effects. The goal of this study was to determine immunosuppressive effect of Silymarin on proliferation and apoptosis of human T cells in comparison with Rapamycin and FK506. Methods: Peripheral Blood Mononuclear Cells (PBMCs) from healthy individuals were activated with Con A (5µg/ml) and then treated with Silymarin, Rapamycin and FK506 in various concentrations (0.001, 0.01, 0.1, 1, 10,100 and 200M) for 5 days. PBMCs were examined for proliferation using CFSE assay and the concentration that inhibited 50% of the cell proliferation (IC50) was determined for each treatment. For apoptosis assay using flow cytometry, PBMCs were activated with Con A and treated with IC50 dose of Silymarin, Rapamycin and FK506 for 5 days, then cell apoptosis was analysed by FITC-annexin V/PI staining and flow cytometry. The effects of Silymarin, Rapamycin and FK506 on the activation of PARP (poly ADP ribose polymerase) pathway in PBMCs stimulated with Con A and treated with IC50 dose of drugs for 5 days evaluated using the PathScan cleaved PARP sandwich ELISA kit. Results: This study showed that Silymarin had the ability to inhibit T cell proliferation in vitro. Moreover, our results indicated that 100 μM (P < 0.001) and 200 μM (P < 0.001) of Silymarin has more inhibitory effect on T cells proliferation than FK506 and Rapamycin. Our data showed that the effective doses (IC50) of Silymarin, FK506 and Rapamycin were 3×10-5 µM, 10-8 µM and 10-6 µM respectively. Data showed that the inhibitory effect of Silymarin, FK506 and Rapamycin on T cell proliferation was not due to cytotoxicity and none of these drugs at IC50 concentration had not affected the level of cleaved PARP. Conclusion: Silymarin could be a good candidate for immunosuppressive therapy for certain medical conditions with superior efficacy and lesser toxicity in comparison with other immunosuppressive drugs.Keywords: silymarin, immunosuppressive effect, rapamycin, immunology
Procedia PDF Downloads 256413 Pyrroloquinoline Quinone Enhances the Mitochondrial Function by Increasing Beta-Oxidation and a Balanced Mitochondrial Recycling in Mice Granulosa Cells
Authors: Moustafa Elhamouly, Masayuki Shimada
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The production of competent oocytes is essential for reproductivity in mammals. Maintenance of mitochondrial efficiency is required to supply the ATP necessary for granulosa cell proliferation during the follicular development process. Treatment with Pyrroloquinoline quinone (PQQ) has been reported to increase the number of ovulated oocytes and pups per delivery in mice by maintaining healthy mitochondrial function. This study aimed to elucidate how PQQ maintains mitochondrial function during ovarian follicle growth. To do this, both in vitro and in vivo experiments were performed with granulosa cells from superovulated immature (3-week-old) mice that were pretreated with or without PQQ. The effects of PQQ on beta-oxidation, mitochondrial function, mitophagy, and mitochondrial biogenesis were examined. PQQ increased beta-oxidation-related genes and CPT1 protein content in granulosa cells and this was associated with a decreased phosphorylation of P38 signaling protein. Using the fatty acid oxidation assay on the flux analyzer, PQQ increased the reliance of beta-oxidation on the endogenous fatty acids and was associated with a mild UCP-dependant mitochondrial uncoupling, ATP production, mitophagy, and mitochondrial biogenesis. PQQ also increased the expression of endogenous antioxidant enzymes. Thus, PQQ induced beta-oxidation in growing granulosa cells relying on endogenous fatty acids. And reduced the Reactive oxygen species (ROS) production by inducing a mild mitochondrial uncoupling with keeping high mitochondrial function. Damaged mitochondria were recycled by the induced mitophagy and replaced by the increased mitochondrial biogenesis. Collectively, PQQ may enhance reproductivity by maintaining the efficiency of mitochondria to produce enough ATP required for normal folliculogenesis.Keywords: granulosa cells, mitochondrial uncoupling, mitophagy, pyrroloquinoline quinone (PQQ), reactive oxygen species (ROS).
Procedia PDF Downloads 73412 A 3D Cell-Based Biosensor for Real-Time and Non-Invasive Monitoring of 3D Cell Viability and Drug Screening
Authors: Yuxiang Pan, Yong Qiu, Chenlei Gu, Ping Wang
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In the past decade, three-dimensional (3D) tumor cell models have attracted increasing interest in the field of drug screening due to their great advantages in simulating more accurately the heterogeneous tumor behavior in vivo. Drug sensitivity testing based on 3D tumor cell models can provide more reliable in vivo efficacy prediction. The gold standard fluorescence staining is hard to achieve the real-time and label-free monitoring of the viability of 3D tumor cell models. In this study, micro-groove impedance sensor (MGIS) was specially developed for dynamic and non-invasive monitoring of 3D cell viability. 3D tumor cells were trapped in the micro-grooves with opposite gold electrodes for the in-situ impedance measurement. The change of live cell number would cause inversely proportional change to the impedance magnitude of the entire cell/matrigel to construct and reflect the proliferation and apoptosis of 3D cells. It was confirmed that 3D cell viability detected by the MGIS platform is highly consistent with the standard live/dead staining. Furthermore, the accuracy of MGIS platform was demonstrated quantitatively using 3D lung cancer model and sophisticated drug sensitivity testing. In addition, the parameters of micro-groove impedance chip processing and measurement experiments were optimized in details. The results demonstrated that the MGIS and 3D cell-based biosensor and would be a promising platform to improve the efficiency and accuracy of cell-based anti-cancer drug screening in vitro.Keywords: micro-groove impedance sensor, 3D cell-based biosensors, 3D cell viability, micro-electromechanical systems
Procedia PDF Downloads 123411 An Assessment of Finite Element Computations in the Structural Analysis of Diverse Coronary Stent Types: Identifying Prerequisites for Advancement
Authors: Amir Reza Heydari, Yaser Jenab
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Coronary artery disease, a common cardiovascular disease, is attributed to the accumulation of cholesterol-based plaques in the coronary arteries, leading to atherosclerosis. This disease is associated with risk factors such as smoking, hypertension, diabetes, and elevated cholesterol levels, contributing to severe clinical consequences, including acute coronary syndromes and myocardial infarction. Treatment approaches such as from lifestyle interventions to surgical procedures like percutaneous coronary intervention and coronary artery bypass surgery. These interventions often employ stents, including bare-metal stents (BMS), drug-eluting stents (DES), and bioresorbable vascular scaffolds (BVS), each with its advantages and limitations. Computational tools have emerged as critical in optimizing stent designs and assessing their performance. The aim of this study is to provide an overview of the computational methods of studies based on the finite element (FE) method in the field of coronary stenting and discuss the potential for development and clinical application of stent devices. Additionally, the importance of assessing the ability of computational models is emphasized to represent real-world phenomena, supported by recent guidelines from the American Society of Mechanical Engineers (ASME). Validation processes proposed include comparing model performance with in vivo, ex-vivo, or in vitro data, alongside uncertainty quantification and sensitivity analysis. These methods can enhance the credibility and reliability of in silico simulations, ultimately aiding in the assessment of coronary stent designs in various clinical contexts.Keywords: atherosclerosis, materials, restenosis, review, validation
Procedia PDF Downloads 78410 Solubility and Dissolution Enhancement of Poorly Soluble Drugs Using Biosericin
Authors: Namdeo Jadhav, Nitin Salunkhe
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Currently, sericin is being treated as waste of sericulture industry, especially at reeling process. Looking at prospective physicochemical properties, an attempt has been made to explore pharmaceutical applications of sericin waste in fabrication of medicated solid dispersions. Solid dispersions (SDs) of poorly soluble drugs (Lornoxicam, Meloxicam & Felodipine) were prepared by spray drying, solvent evaporation, ball milling and physical kneading in mass ratio of drug: sericin (1:0.5, 1:1, 1:1.5, 1:2, 1:2.5 and 1:3 w/w) and were investigated by solubility, ATR-FTIR, XRD and DSC, micromeritics and tablettability, surface morphology and in-vitro dissolution. It has been observed that sericin improves solubility of drugs by 8 to 10 times compared to pure drugs. The presence of hydrogen bonding between drugs and sericin was confirmed from the ATR-FTIR spectra. Amongst these methods, spray dried (1:2 w/w) SDs showed fully amorphous state representing molecularly distributed drug as confirmed from XRD and DSC study. Spray dried meloxicam SDs showed better compressibility and compactibility. The microphotograph of spray dried batches of lornoxicam (SDLX) and meloxicam SDs (SDMX) showed bowl shaped, and bowl plus spherical particles respectively, while spray dried felodipine SDs (SDFL) showed spherical shape. The SDLX, SDMX and SDFL (1:2 w/w) displayed better dissolution performance than other methods. Conclusively, hydrophilic matrix of sericin can be used to deliver poor water soluble drugs and its aerodynamic shape may show a great potential for various drug deliveries. If established as pharmaceutical excipient, sericin holds a potential to revolutionise economics of pharmaceutical industry, and sericulture farming, especially of Asian countries.Keywords: biosericin, poorly soluble drugs, solid dispersion, solubility and dissolution improvement
Procedia PDF Downloads 247409 Postprandial Glycemic and Appetite Responses of Muffins Supplemented with Different Vegetables in Young Males
Authors: Muhammad Umair Arshad
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Background and Objectives: Different vegetables have been reported to possess diabetic potential in in-vitro studies; however, the same role of these vegetables has not been much explored through human intervention. Therefore, the present study was conducted to examine the comparative effects of muffins supplemented with bitter gourd (BGM), and other vegetables like spinach (SPM) and eggplant (EPM) on subjective appetite, blood glucose (BG), gut hormones and food intake in healthy young males through a randomized, cross over experiment. Methods and Study Design: After 12 hours fasting, twenty-four healthy young males (18-30 Y) were fed 250ml of plain muffins (control) or supplemented with bitter gourd powder, BGM (10g/100g flour), or spinach powder, SPM (10g/100g flour), or eggplant powder, EPM (10g/100g flour). An ad libitum pizza meal was served at 120min to measure the food intake. Subjective appetite, blood glucose, and gut hormones (insulin, GLP-1, active ghrelin) were measured at intervals from baseline to 120min. Results: Post-treatment (0-120min) glucose, but not insulin, decreased following all the vegetables supplemented muffins compared to the control (p < 0.0001) with a more pronounced effect of BGM. However, post-treatment avg. subjective appetite (p=0.0017) and food intake (p=0.0021) were reduced following BGM but not SPM and EPM. BGM further improved GLP-1 concentration (p < 0.0001), and reduced active ghrelin (p=0.0022), compared with control. Conclusions: The bitter gourd supplemented baked foods possess potential more than other vegetables to regulate postprandial appetite and glycemic responses, without a disproportionate increase in insulin concentration.Keywords: vegetables, muffins, glucose homeostasis, subjective appetite, food intake
Procedia PDF Downloads 100408 Quantum Dot – DNA Conjugates for Biological Applications
Authors: A. Banerjee, C. Grazon, B. Nadal, T. Pons, Y. Krishnan, B. Dubertret
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Quantum Dots (QDs) have emerged as novel fluorescent probes for biomedical applications. The photophysical properties of QDs such as broad absorption, narrow emission spectrum, reduced blinking, and enhanced photostability make them advantageous over organic fluorophores. However, for some biological applications, QDs need to be first targeted to specific intracellular locations. It parallel, base pairing properties and biocompatibility of DNA has been extensively used for biosensing, targetting and intracellular delivery of numerous bioactive agents. The combination of the photophysical properties of QDs and targettability of DNA has yielded fluorescent, stable and targetable nanosensors. QD-DNA conjugates have used in drug delivery, siRNA, intracellular pH sensing and several other applications; and continue to be an active area of research. In this project, a novel method to synthesise QD-DNA conjugates and their applications in bioimaging are investigated. QDs are first solubilized in water using a thiol based amphiphilic co-polymer and, then conjugated to amine functionalized DNA using a heterobifunctional linker. The conjugates are purified by size exclusion chromatography and characterized by UV-Vis absorption and fluorescence spectroscopy, electrophoresis and microscopy. Parameters that influence the conjugation yield such as reducing agents, the excess of salt and pH have been investigated in detail. In optimized reaction conditions, up to 12 single-stranded DNA (15 mer length) can be conjugated per QD. After conjugation, the QDs retain their colloidal stability and high quantum yield; and the DNA is available for hybridization. The reaction has also been successfully tested on QDs emitting different colors and on Gold nanoparticles and therefore highly generalizable. After extensive characterization and robust synthesis of QD-DNA conjugates in vitro, the physical properties of these conjugates in cellular milieu are being invistigated. Modification of QD surface with DNA appears to remarkably alter the fate of QD inside cells and can have potential implications in therapeutic applications.Keywords: bioimaging, cellular targeting, drug delivery, photostability
Procedia PDF Downloads 414407 Sirt1 Activators Promote Skin Cell Regeneration and Cutaneous Wound Healing
Authors: Hussain Mustatab Wahedi, Sun You Kim
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Skin acts as a barrier against the harmful environmental factors. Integrity and timely recovery of the skin from injuries and harmful effects of radiations is thus very important. This study aimed to investigate the importance of Sirt1 in the recovery of skin from UVB-induced damage and cutaneous wounds by using natural and synthetic novel Sirt1 activators. Juglone, known as a natural Pin1 inhibitor, and NED416 a novel synthetic Sirt1 activator were checked for their ability to regulate the expression and activity of Sirt1 and hence photo-damage and wound healing in cultured skin cells (NHDF and HaCaT cells) and mouse model by using Sirt1 siRNA knockdown, cell migration assay, GST-Pulldown assay, western blot analysis, tube formation assay, and immunohistochemistry. Interestingly, Sirt1 knockdown inhibited skin cell migration in vitro. Juglone up regulated the expression of Sirt1 in both the cell lines under normal and UVB irradiated conditions, enhanced Sirt1 activity and increased the cell viability by reducing reactive oxygen species synthesis and apoptosis. Juglone promoted wound healing by increasing cell migration and angiogenesis through Cdc42/Rac1/PAK, MAPKs and Smad pathways in skin cells. NED416 upregulated Sirt1 expression in HaCaT and NHDF cells as well as increased Sirt1 activity. NED416 promoted the process of wound healing in early as well as later stages by increasing macrophage recruitment, skin cell migration, and angiogenesis through Cdc42/Rac1 and MAPKs pathways. So, both these compounds activated Sirt1 and promoted the process of wound healing thus pointing towards the possible role of Sirt1 in skin regeneration and wound healing.Keywords: skin regeneration, wound healing, Sirt1, UVB light
Procedia PDF Downloads 181406 In vitro Control of Aedes aegypti Larvae Using Beauveria bassiana
Authors: R. O. B. Bitencourt, F. S. Farias, M. C. Freitas, C. J. R. Balduino, E.S. Mesquita, A. R. C. Corval, P. S. Gôlo, E. G. Pontes, V. R. E. P. Bittencourt, I. C. Angelo
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Aedes aegypti larval survival rate was assessed after exposure to blastopores or conidia (mineral oil-in-water formulation or aqueous suspension) of Beauveria bassiana CG 479 propagules (blastospores or conidia). Here, mineral oil was used in the fungal formulation to control Aedes aegypti larvae. 1%, 0.5% or 0.1% mineral oil-in-water solutions were used to evaluate mineral oil toxicity for mosquito larvae. In the oil toxicity test, 0.1% mineral oil solution reduced only 4.5% larval survival; accordingly, this concentration was chosen for fungal oil-in-water formulations. Aqueous suspensions were prepared using 0.01% Tween 80® in sterile dechlorinated water. A. aegypti larvae (L2) were exposed in aqueous suspensions or mineral oil-in-water fungal formulations at 1×107 propagules mL-1; the survival rate (assessed daily, for 7 days) and the median survival time (S50) were calculated. Seven days after the treatment, mosquito larvae survival rates were 8.56%, 16.22%, 58%, and 42.56% after exposure to oil-in-water blastospores, oil-in-water conidia, blastospores aqueous suspension and conidia aqueous suspension (respectively). Larvae exposed to 0.01% Tween 80® had 100% survival rate and the ones treated with 0.1% mineral oil-in-water had 95.11% survival rate. Larvae treated with conidia (regardless the presence of oil) or treated with blastospores formulation had survival median time (S50) ranging from one to two days. S50 was not determined (ND) when larvae were exposed to blastospores aqueous suspension, 0.01% Tween 80® (aqueous control) or 0.1% mineral oil-in-water formulation (oil control). B. bassiana conidia and blastospores (mineral oil-in-water formulated or suspended in water) had potential to control A. aegypti mosquito larvae, despite mineral oil-in-water formulation yielded better results in comparison to aqueous suspensions. Here, B. bassiana CG 479 isolate is suggested as a potential biocontrol agent of A. aegypti mosquito larvae.Keywords: blastospores, formulation, mosquitoes, conidia
Procedia PDF Downloads 178405 Comparison of Growth Medium Efficiency into Stevia (Stevia rebaudiana Bertoni) Shoot Biomass and Stevioside Content in Thin-Layer System, TIS RITA® Bioreactor, and Bubble Column Bioreactor
Authors: Nurhayati Br Tarigan, Rizkita Rachmi Esyanti
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Stevia (Stevia rebaudiana Bertoni) has a great potential to be used as a natural sweetener because it contains steviol glycoside, which is approximately 100 - 300 times sweeter than sucrose, yet low calories. Vegetative and generative propagation of S. rebaudiana is inefficient to produce stevia biomass and stevioside. One of alternative for stevia propagation is in vitro shoot culture. This research was conducted to optimize the best medium for shoot growth and to compare the bioconversion efficiency and stevioside production of S. rebaudiana shoot culture cultivated in thin layer culture (TLC), recipient for automated temporary immersion system (TIS RITA®) bioreactor, and bubble column bioreactor. The result showed that 1 ppm of Kinetin produced a healthy shoot and the highest number of leaves compared to BAP. Shoots were then cultivated in TLC, TIS RITA® bioreactor, and bubble column bioreactor. Growth medium efficiency was determined by yield and productivity. TLC produced the highest growth medium efficiency of S. rebaudiana, the yield was 0.471 ± 0.117 gbiomass.gsubstrate-1, and the productivity was 0.599 ± 0.122 gbiomass.Lmedium-1.day-1. While TIS RITA® bioreactor produced the lowest yield and productivity, 0.182 ± 0.024 gbiomass.gsubstrate-1 and 0.041 ± 0.0002 gbiomass.Lmedium-1.day-1 respectively. The yield of bubble column bioreactor was 0.354 ± 0.204 gbiomass.gsubstrate-1 and the productivity was 0,099 ± 0,009 gbiomass.Lmedium-1.day-1. The stevioside content from the highest to the lowest was obtained from stevia shoot which was cultivated on TLC, TIS RITA® bioreactor, and bubble column bioreactor; the content was 93,44 μg/g, 42,57 μg/g, and 23,03 μg/g respectively. All three systems could be used to produce stevia shoot biomass, but optimization on the number of nutrition and oxygen intake was required in each system.Keywords: bubble column, growth medium efficiency, Stevia rebaudiana, stevioside, TIS RITA®, TLC
Procedia PDF Downloads 259404 Ameliorative Effects of Ganoderma lucidum Extracts on Testosterone Induced Prostatic Hyperplasia in Rats
Authors: Alok Nahata
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Introduction: Nowadays, androgen-mediated diseases such as prostate cancer, hirsutism, acne, androgenic alopecia and benign prostatic hyperplasia (BPH) have become serious problems. The aim of the present study was to find out whether Ganoderma lucidum (GL) can be used as a clinically effective medicine for the management of prostatic hyperplasia. Methodology: In vitro studies were conducted to assess the 5α-reductase inhibitory potential of GL. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts (10, 20 and 50 mg/kg p.o for a period of 28 days. Finasteride was used as a positive control (1 mg/kg p.o.). Major Findings: GL extracts attenuated the increase in the prostate/body weight ratio (P/BW) induced by testosterone. Most of the values were significant when compared to testosterone-treated group and finasteride treated groups. Petroleum ether extract (50 mg/kg p.o.) exhibited the best activity (P < 0.01). Ethanolic extract (20 and 50 mg/kg p.o.) also exhibited significant activity (P < 0.01). The urine output also improved significantly (P < 0.01 in all groups as compared to standard finasteride), which emphasize the clinical implications of the study. Testosterone levels measured weekly and prostate-specific antigen (PSA) levels measured at the end of the study also support the findings. Histological studies suggested improvement in prostatic histoarchitecture in extract-treated groups as compared to the testosterone-treated group. Conclusion: Study clearly reflects the utility of extracts in BPH. Because of conversion of testosterone to dihydrotestosterone, the prostate size is increased, thereby causing obstruction in urinary output. The observed effect that extracts do not allow the increase as reflected by urinary output, P/BW ratios and histoarchitecture showed that activity of administered testosterone was blocked by the extract and resulted in recovery.Keywords: benign prostatic hyperplasia, Ganoderma lucidum, prostate-specific antigen, 5α-reductase, testosterone
Procedia PDF Downloads 163403 Re-Differentiation Effect of Sesquiterpene Farnesol on De-Differentiated Rabbit Chondrocytes
Authors: Chun Hsien Wu, Guan Xuan Wu, Hsia Ying Cheng, Shyh Ming Kuo
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Articular cartilage is composed of chondrocytes and extracellular matrix, such as collagen fibers, glycosaminoglycans, etc., which play an important role in lubricating and cushion joint activities. The phenotypic expression and metabolic activity of chondrocytes are extremely important in maintaining the functions of articular cartilage. In in vitro passaged culture of chondrocytes, chondrocytes gradually lose their original cell phenotype and morphology, which is called dedifferentiation. After continuous passaged culture of chondrocytes or induction by inflammatory factor IL-1, chondrocytes changed their phenotype and morphology. Also, the extracellular matrix type II collagen and GAG secretion were significantly reduced, while type I and X collagen were synthesized. Farnesol is an anti-inflammatory and antioxidant sesquiterpene compound that has the specific property of promoting collagen production. The purpose of this study was to investigate whether farnesol could restore the original type II collagen synthesis and, furthermore, the mechanisms of farnesol on the synthesis of type II collagen from the de-differentiated chondrocytes. The obtained results showed that the de-differentiated chondrocytes significantly restored to secret type II collagen and GAG (2.5-folds increases), and the secretion of collagen I and X and PGE2 synthesis were also significantly reduced after being treated with farnesol, indicating that farnesol had a restoration/re-differentiation effect on de-differentiated chondrocytes. The de-differentiated chondrocytes exhibited decreased expression of PPAR-γ and upregulated TGF-β expression to increase the MMP-13 expression. Higher expression of MMP-13 caused chondrocytes to secret type X collagen. On the contrary, increasing the expression of PPAR-γ would benefit the production of type II collagen. As shown, the PPAR-γ expression increased, and MMP-13 expression decreased after being treated with farnesol, indicating a possible signal pathway of farnesol to restore the production of type II collagen. However, more detailed mechanisms still need to evaluate.Keywords: chondrocytes, de-differentiation, farnesol, re-differentiation
Procedia PDF Downloads 114402 Evaluation of Entomopathogenic Fungi Strains for Field Persistence and Its Relationship to in Vitro Heat Tolerance
Authors: Mulue Girmay Gebreslasie
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Entomopathogenic fungi are naturally safe and eco-friendly biological agents. Their potential of host specificity and ease handling made them appealing options to substitute synthetic pesticides in pest control programs. However, they are highly delicate and unstable under field conditions. Therefore, the current experiment was held to search out persistent fungal strains by defining the relationship between invitro heat tolerance and field persistence. Current results on leaf and soil persistence assay revealed that strains of Metarhizium species, M. pingshaense (F2685), M. pingshaense (MS2) and M. brunneum (F709) exhibit maximum cumulative CFUs count, relative survival rate and least percent of CFUs reductions showed significant difference at 7 days and 28 days post inoculations (dpi) in hot seasons from sampled soils and leaves and in cold season from soil samples. Whereas relative survival of B. brongniartii (TNO6) found significantly higher in cold weather leaf treatment application as compared to hot season and found as persistent as other fungal strains, while higher deterioration of fungal conidia seen with M. pingshaense (MS2). In the current study, strains of Beauveria brongniartii (TNO6) and Cordyceps javanica (Czy-LP) were relatively vulnerable in field condition with utmost colony forming units (CFUs) reduction and least survival rates. Further, the relationship of the two parameters (heat tolerance and field persistence) was seen with strong linear positive correlations elucidated that heat test could be used in selection of field persistent fungal strains for hot season applications.Keywords: integrated pest management, biopesticides, Insect pathology and microbial control, entomology
Procedia PDF Downloads 81401 Survival and Retention of the Probiotic Properties of Bacillus sp. Strains under Marine Stress Starvation Conditions and Their Potential Use as a Probiotic for Aquaculture Objectives
Authors: Abdelkarim Mahdhi, Fdhila Kais, Faouzi Lamari, Zeineb Hmila, Fathi Kamoun, Maria Ángeles Esteban, Amina Bakhrouf
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Aquaculture is the world’s fastest growing food-production sector. However, one of the most serious problems regarding the culture of marine fishes is the mortality associated with pathogenic bacteria that occurs in the critical phases of larval development. Conventional approaches, such as the use of antimicrobial drugs to control diseases, have had limited success in the prevention or cure of aquatic diseases. Promising alternatives to antibiotics are probiotics, which are food supplements consisting of live microorganisms that benefit the host organism. In the search for more effective and environmentally friendly treatments with probionts against pathogenic species in shrimp larval culture, the probiotic properties of Bacillus strains isolated from Artemia culture such as antibacterial activity, adhesion, pathogenicity, toxicity and the effect of marine stress on viability and survival were investigated, as well as the changes occurring in their properties. Analyses showed that these bacteria corresponded to the genus Bacillus sp. Antagonism and adherence assays revealed that these strains have an inhibitory effect against pathogenic bacteria in vitro and in vivo conditions and are fairly adherent. Challenge tests performed with Artemia larvae provided evidence that the tested Bacillus strains were neither pathogenic nor toxic to the host. The tested strains maintained their viability and their probiotic properties during the period of study. The results suggest that the tested strains have suffered changes allowing them to survive in seawater in the absence of nutrients and outside their natural host, identifying them as potential probiotic candidates for Artemia culture.Keywords: bacillus, probiotic, cell viability, stress response
Procedia PDF Downloads 377400 Emerging Therapeutic Approach with Dandelion Phytochemicals in Breast Cancer Treatment
Authors: Angel Champion, Sadia Kanwal, Rafat Siddiqui
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Harnessing phytochemicals from plant sources presents a novel opportunity to prevent or treat malignant diseases, including breast cancer. Chemotherapy lacks precision in targeting cancerous cells while sparing normal cells, but a phytopharmaceutical approach may offer a solution. Dandelion, a common weed plant, is rich in phytochemicals and provides a safer, more cost-effective alternative with lower toxicity than traditional pharmaceuticals for conditions such as breast cancer. In this study, an in-vitro experiment will be conducted using the ethanol extract of Dandelion on triple-negative MDA-231 breast cancer cell lines. The polyphenolic analysis revealed that the Dandelion extract, particularly from the root and leaf (both cut and sifted), had the most potent antioxidant properties and exhibited the most potent antioxidation activity from the powdered leaf extract. The extract exhibits prospective promising effects for inducing cell proliferation and apoptosis in breast cancer cells, highlighting its potential for targeted therapeutic interventions. Standardizing methods for Dandelion use is crucial for future clinical applications in cancer treatment. Combining plant-derived compounds with cancer nanotechnology holds the potential for effective strategies in battling malignant diseases. Utilizing liposomes as carriers for phytoconstituent anti-cancer agents offers improved solubility, bioavailability, immunoregulatory effects, advancing anticancer immune function, and reducing toxicity. This integrated approach of natural products and nanotechnology has significant potential to revolutionize healthcare globally, especially in underserved communities where herbal medicine is prevalent.Keywords: apoptosis, antioxidant activity, cancer nanotechnology, phytopharmaceutical
Procedia PDF Downloads 46399 Mixed Hydrotropic Zaleplon Oral Tablets: Formulation and Neuropharmacological Effect on Plasma GABA Level
Authors: Ghada A. Abdelbary, Maha M. Amin, Mostafa Abdelmoteleb
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Zaleplon (ZP) is a non-benzodiazepine poorly soluble hypnotic drug indicated for the short term treatment of insomnia having a bioavailability of about 30%. The aim of the present study is to enhance the solubility and consequently the bioavailability of ZP using hydrotropic agents (HA). Phase solubility diagrams of ZP in presence of different molar concentrations of HA (Sodium benzoate, Urea, Ascorbic acid, Resorcinol, Nicotinamide, and Piperazine) were constructed. ZP/Sodium benzoate and Resorcinol microparticles were prepared adopting melt, solvent evaporation and melt-evaporation techniques followed by XRD. Directly compressed mixed hydrotropic ZP tablets of Sodium benzoate and Resorcinol in different weight ratios were prepared and evaluated compared to the commercially available tablets (Sleep aid® 5 mg). The effect of shelf and accelerated stability storage (40°C ± 2°C/75%RH ± 5%RH) on the optimum tablet formula (F5) for six months were studied. The enhancement of ZP solubility follows the order of: Resorcinol > Sodium benzoate > Ascorbic acid > Piperazine > Urea > Nicotinamide with about 350 and 2000 fold increase using 1M of Sodium benzoate and Resorcinol respectively. ZP/HA microparticles exhibit the order of: Solvent evaporation > melt-solvent evaporation > melt > physical mixture which was further confirmed by the complete conversion of ZP into amorphous form. Mixed hydrotropic tablet formula (F5) composed of ZP/(Resorcinol: Sodium benzoate 4:1w/w) microparticles prepared by solvent evaporation exhibits in-vitro dissolution of 31.7±0.11% after five minutes (Q5min) compared to 10.0±0.10% for Sleep aid® (5 mg) respectively. F5 showed significantly higher GABA concentration of 122.5±5.5mg/mL in plasma compared to 118±1.00 and 27.8±1.5 mg/mL in case of Sleep aid® (5 mg) and control taking only saline respectively suggesting a higher neuropharmacological effect of ZP following hydrotropic solubilization.Keywords: zaleplon, hydrotropic solubilization, plasma GABA level, mixed hydrotropy
Procedia PDF Downloads 437398 In Vitro Antibacterial Activity of Selected Tanzania Medicinal Plants
Authors: Mhuji Kilonzo, Patrick Ndakidemi, Musa Chacha
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Objective: To evaluate antibacterial activity from four selected medicinal plants namely Mystroxylon aethiopicum, Lonchocarpus capassa, Albizia anthelmentica and Myrica salicifolia used for management of bacterial infection in Tanzania. Methods: Minimum Inhibitory Concentration (MIC) of plants extracts against the tested bacterial species was determined by using 96 wells microdilution method. In this method, 50 μL of nutrient broth were loaded in each well followed by 50 μL of extract (100 mg/mL) to make a final volume of 100 μL. Subsequently, 50 μL were transferred from first rows of each well to the second rows and the process was repeated down the columns to the last wells from which 50 μL were discarded. Thereafter, 50 μL of the selected bacterial suspension were added to each well thus making a final volume of 100 μL. The lowest concentration which showed no bacterial growth was considered as MIC. Results: It was revealed that L. capassa leaf ethyl acetate extract exhibited antibacterial activity against Salmonella kisarawe and Salmonella typhi with MIC values of 0.39 and 0.781 mg/mL respectively. Likewise, L. capassa root bark ethyl acetate extracts inhibited growth of S. typhi and E. coli with MIC values of 0.39 and 0.781 mg/mL respectively. The M. aethiopicum leaf and root bark chloroform extracts displayed antibacterial activity against S. kisarawe and S. typhi respectively with MIC value of 0.781 mg/mL. The M. salicifolia stem bark ethyl acetate exhibited antibacterial activity against P. aeruginosa with MIC value of 0.39 mg/mL whereas the methanolic stem and root bark of the same plant inhibited the growth of Proteus mirabilis and Klebsiella pneumoniae with MIC value of 0.781 mg/mL. Conclusion: It was concluded that M. aethiopicum, L. capassa, A. anthelmentica and M. salicifolia are potential source of antibacterial agents. Further studies to establish structures of antibacterial and evaluate active ingredients are recommended.Keywords: Albizia anthelmentica, Lonchocarpus capassa, Mystroxylon aethiopicum, Myrica salicifolia
Procedia PDF Downloads 214397 Peptidoglycan Vaccine-On-Chip against a Lipopolysaccharide-Induced Experimental Sepsis Model
Authors: Katerina Bakela, Ioanna Zerva, Irene Athanassakis
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Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression (incretion of MDSCs cells and Tregs, imbalance of inflammatory/anti-inflammatory cytokines) and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the protective role of Micrococcus luteus peptidoglycan (PG) pre-activated vaccine-on chip in endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2mg/g LPS. Such protocol allowed longer survival, necessary in the prospect of the therapeutic treatment application. The so-called vaccine-on-chip consists of a 3-dimensional laser micro-texture Si-scaffold loaded with BALB/c mouse macrophages and activated in vitro with 1μg/ml PG, which exert its action upon subcutaneous implantation. The LPS treatment significantly decreased CD4+, CD8+, CD3z+, and CD19+ cells, while increasing myeloid-derived suppressor cells (MDSCs), CD25+, and Foxp3+ cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and production of IL-6, TNF-a, and IL-18 while acquiring severe sepsis phenotype as defined by the murine sepsis scoring. The in vivo application of PG pre-activated vaccine-on chip significantly decreased the percent of CD11b+, Gr1+, CD25+, Foxp3+ cells, and arginase-1 activity in the spleen of LPS-treated animals, while decreasing IL-6 and TNF-a in the serum, allowing survival to all animals tested and rescuing the severity of sepsis phenotype. In conclusion, these results reveal a promising mode of action of PG pre-activated vaccine-on chip in LPS endotoxemia, strengthening; thus, the use of treatment is septic patients.Keywords: myeloid-derived suppressor cells, peptidoglycan, sepsis, Si-scaffolds
Procedia PDF Downloads 126396 Radiation Skin Decontamination Formulation
Authors: Navneet Sharma, Himanshu Ojha, Dharam Pal Pathak, Rakesh Kumar Sharma
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Radio-nuclides decontamination is an important task because any extra second of deposition leads to deleterious health effects. We had developed and characterise nanoemulsion of p-tertbutylcalix[4]arens using phase inversion temperature (PIT) method and evaluate its decontamination efficacy (DE). The solubility of the drug was determined in various oils and surfactants. Nanoemulsion developed with an HLB value of 11 and different ratios of the surfactants 10% (7:3, w/w), oil (20%, w/w), and double distilled water (70%) were selected. Formulation was characterised by multi-photon spectroscopy and parameters like viscosity, droplet size distribution, zeta potential and stability were optimised. In vitro and Ex vivo decontamination efficacy (DE) was evaluated against Technetium-99m, Iodine-131, and Thallium-201 as radio-contaminants applied over skin of Sprague-Dawley rat and human tissue equivalent model. Contaminants were removed using formulation soaked in cotton swabs at different time intervals and whole body imaging and static counts were recorded using SPECT gamma camera before and after decontamination attempt. Data were analysed using one-way analysis of variance (ANOVA) and was found to be significant (p <0.05). DE of the nanoemulsion loaded with p-tertbutylcalix[4]arens was compared with placebo and recorded to be 88±5%, 90±3% and 89±3% for 99mTc, 131I and 201Tl respectively. Ex-vivo complexation study of p-tertbutylcalix[4]arene nanoemulsion with surrogate nuclides of radioactive thallium and Iodine, were performed on rat skin mounted on Franz diffusion cell using high-resolution sector field inductively coupled plasma mass spectroscopy (HR-SF-ICPMS). More than 90% complexation of the formulation with these nuclides was observed. Results demonstrate that the prepared nanoemulsion formulation was found efficacious for the decontamination of radionuclides from a large contaminated population.Keywords: p-tertbutylcalix[4]arens, skin decontamination, radiological emergencies, nanoemulsion, iodine-131, thallium-201
Procedia PDF Downloads 391