Search results for: inhibition of cancer cells
3815 Synthesis of Highly Stable Multi-Functional Iron Oxide Nanoparticles for Active Mitochondrial Targeting in Immunotherapy
Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour
Abstract:
Mitochondria- targeting immunogenic cell death inducers (MT-ICD) have been designed to trigger intrinsic apoptosis signalling pathway in malignant cells and revive the antitumour immune system. MT-ICD inducers have considered to be non-specific, which can deteriorate the ability to initiate mitochondria-selective oxidative stress, causing high toxicity. Iron oxide nanoparticles (IONPs) can be an ideal candidate as vehicles for utilizing in immunotherapy due to their biocompatibility, modifiable surface chemistry, magnetic characteristics and multi-functional applications in single platform. These types of NPs can facilitate a real time imaging which can provide an effective strategy to analyse pharmacokinetic parameters of nano-formula, including blood circulation time, targeted and controlled release at tumour microenvironment. To our knowledge, the conjugation of IONPs with MT-ICD and oxaliplatin (a chemotherapeutic agent used for the treatment of colorectal cancer) for immunotherapy have not been investigated. Herein, IONPs were generated via co-precipitation reaction at high temperatures, followed by coating the colloidal suspension with tetraethyl orthosilicate and 3-aminopropyltriethoxysilane to optimize their bio-compatibility, preventing aggregation and maintaining stability at physiological pH, then functionalized with (3-carboxypropyl) triphenyl phosphonium bromide for mitochondrial delivery. Analytical results demonstrated the successful process of IONPs functionalization. In particular, the colloidal particles of doped IONPs exhibited an excellent stability and dispersibility. The resultant particles were also successfully loaded with the oxaliplatin for an active mitochondrial targeting in immunotherapy, resulting in well-maintained super-paramagnetic characteristics and stable structure of the functionalized IONPs with nanoscale particle sizes.Keywords: Immunotherapy, mitochondria, cancer, iron oxide nanoparticle
Procedia PDF Downloads 753814 iPSCs More Effectively Differentiate into Neurons on PLA Scaffolds with High Adhesive Properties for Primary Neuronal Cells
Authors: Azieva A. M., Yastremsky E. V., Kirillova D. A., Patsaev T. D., Sharikov R. V., Kamyshinsky R. A., Lukanina K. I., Sharikova N. A., Grigoriev T. E., Vasiliev A. L.
Abstract:
Adhesive properties of scaffolds, which predominantly depend on the chemical and structural features of their surface, play the most important role in tissue engineering. The basic requirements for such scaffolds are biocompatibility, biodegradation, high cell adhesion, which promotes cell proliferation and differentiation. In many cases, synthetic polymers scaffolds have proven advantageous because they are easy to shape, they are tough, and they have high tensile properties. The regeneration of nerve tissue still remains a big challenge for medicine, and neural stem cells provide promising therapeutic potential for cell replacement therapy. However, experiments with stem cells have their limitations, such as low level of cell viability and poor control of cell differentiation. Whereas the study of already differentiated neuronal cell culture obtained from newborn mouse brain is limited only to cell adhesion. The growth and implantation of neuronal culture requires proper scaffolds. Moreover, the polymer scaffolds implants with neuronal cells could demand specific morphology. To date, it has been proposed to use numerous synthetic polymers for these purposes, including polystyrene, polylactic acid (PLA), polyglycolic acid, and polylactide-glycolic acid. Tissue regeneration experiments demonstrated good biocompatibility of PLA scaffolds, despite the hydrophobic nature of the compound. Problem with poor wettability of the PLA scaffold surface could be overcome in several ways: the surface can be pre-treated by poly-D-lysine or polyethyleneimine peptides; roughness and hydrophilicity of PLA surface could be increased by plasma treatment, or PLA could be combined with natural fibers, such as collagen or chitosan. This work presents a study of adhesion of both induced pluripotent stem cells (iPSCs) and mouse primary neuronal cell culture on the polylactide scaffolds of various types: oriented and non-oriented fibrous nonwoven materials and sponges – with and without the effect of plasma treatment and composites with collagen and chitosan. To evaluate the effect of different types of PLA scaffolds on the neuronal differentiation of iPSCs, we assess the expression of NeuN in differentiated cells through immunostaining. iPSCs more effectively differentiate into neurons on PLA scaffolds with high adhesive properties for primary neuronal cells.Keywords: PLA scaffold, neurons, neuronal differentiation, stem cells, polylactid
Procedia PDF Downloads 853813 Consolidated Predictive Model of the Natural History of Breast Cancer Considering Primary Tumor and Secondary Distant Metastases Growth
Authors: Ella Tyuryumina, Alexey Neznanov
Abstract:
This study is an attempt to obtain reliable data on the natural history of breast cancer growth. We analyze the opportunities for using classical mathematical models (exponential and logistic tumor growth models, Gompertz and von Bertalanffy tumor growth models) to try to describe growth of the primary tumor and the secondary distant metastases of human breast cancer. The research aim is to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoMPaS and corresponding software. We are interested in: 1) modelling the whole natural history of the primary tumor and the secondary distant metastases; 2) developing adequate and precise CoMPaS which reflects relations between the primary tumor and the secondary distant metastases; 3) analyzing the CoMPaS scope of application; 4) implementing the model as a software tool. The foundation of the CoMPaS is the exponential tumor growth model, which is described by determinate nonlinear and linear equations. The CoMPaS corresponds to TNM classification. It allows to calculate different growth periods of the primary tumor and the secondary distant metastases: 1) ‘non-visible period’ for the primary tumor; 2) ‘non-visible period’ for the secondary distant metastases; 3) ‘visible period’ for the secondary distant metastases. The CoMPaS is validated on clinical data of 10-years and 15-years survival depending on the tumor stage and diameter of the primary tumor. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer growth models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. The CoMPaS model and predictive software: a) fit to clinical trials data; b) detect different growth periods of the primary tumor and the secondary distant metastases; c) make forecast of the period of the secondary distant metastases appearance; d) have higher average prediction accuracy than the other tools; e) can improve forecasts on survival of breast cancer and facilitate optimization of diagnostic tests. The following are calculated by CoMPaS: the number of doublings for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases; tumor volume doubling time (days) for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases. The CoMPaS enables, for the first time, to predict ‘whole natural history’ of the primary tumor and the secondary distant metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on the primary tumor sizes. Summarizing: a) CoMPaS describes correctly the primary tumor growth of IA, IIA, IIB, IIIB (T1-4N0M0) stages without metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and inception of the secondary distant metastases.Keywords: breast cancer, exponential growth model, mathematical model, metastases in lymph nodes, primary tumor, survival
Procedia PDF Downloads 3413812 Incidence of Vulval, Vaginal and Cervical Disease in Rapid Access Clinic in a London Tertiary Hospital Setting
Authors: Kieren Wilson, Gulnaz Majeed
Abstract:
NHS constitution gives rights to the patient with suspected cancer to be seen by a cancer specialist within 2 weeks of referral. Guys and St Thomas Hospital (GSTT) is one of the largest cancer centres in London. NICE guidelines have provided guidance for health professionals to refer patients appropriately to RAC. In GSTT suspected gynae cancer referrals are mostly by NHS e-Referral Service with some fax, emails as well as paper referrals. The objective of this study was to evaluate compliance with 2-week referral pathway with emphasis on one stop diagnostic service with supporting efficient pathways. A prospective evaluation over 3 months (1 Jan 2017 to 31 Mar 2017) was undertaken. There were 26 clinics, 761 patients were booked in the clinics with a DNA rate of 13% (n=101) hence 606 patients were seen. Majority of referrals were for post menopausal bleeding (PMB) 25% (n=194) followed by cervical, vaginal, vulval reasons 23% (n=179) (abnormal cytology excluded as patients directly referred to colposcopy unit in GSTT), ovarian 7% (n=54) and endometrial 5% (n=41). Women with new or previous established diagnosis of cancer were 24, cervical (n=17), vulva (n=6) and vagina (n=1). Multifocal preinvasive disease vulva (VIN), vagina (VAIN) and cervix (CIN) was confirmed in twenty-six patients 4% (high prevalence in HIV patients). Majority of cervical referrals: PCB (n=14), cervical erosion (n=7), polyps (n=9) and cervical cyst were benign. However, two women with PMB had cervical cancer. Only 2 out of 13 referrals with vaginal concerns had VAIN. One case with non-cervical glandular cytology was confirmed to have endometrial cancer. One stop service based on the diagnostic support of ultrasound, colposcopy and hysteroscopy was achieved in 54% (n=359). Patients were discharged to GP, benign gynaecology, endometriosis, combined vulval/dermatology clinic or gynae oncology. 33% (n=202) required a second visit, 12% (n=70) third visit, 3% (n=19) fourth visit, 1% (n=4) fifth visit and 1% (n=6) sixth visit. Main reasons for follow ups were the unavailability of diagnostic slots, patient choice, need for interpreters, the discussion following gynae MDM review for triage to benign gynae, delay in availability of diagnostic results like histology/MRI/CT. Recommendations following this study are multi disciplinary review of pathways with the availability of additional diagnostic procedure slots to aim for one stop service. Furthermore, establishment of virtual and telephone consultations to reduce follow ups.Keywords: multifocal disease, post menopausal bleeding, preinvasive disease, rapid access clinic
Procedia PDF Downloads 1883811 Identification of Potent and Selective SIRT7 Anti-Cancer Inhibitor via Structure-Based Virtual Screening and Molecular Dynamics Simulation
Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi
Abstract:
Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation
Procedia PDF Downloads 793810 In vitro Cytotoxicity Study on Silver Powders Synthesized via Different Routes
Authors: Otilia Ruxandra Vasile, Ecaterina Andronescu, Cristina Daniela Ghitulica, Bogdan Stefan Vasile, Roxana Trusca, Eugeniu Vasile, Alina Maria Holban, Carmen Mariana Chifiriuc, Florin Iordache, Horia Maniu
Abstract:
Engineered powders offer great promise in several applications, but little information is known about cytotoxicity effects. The aim of the current study was the synthesis and cytotoxicity examination of silver powders using pyrosol method at temperatures of 600°C, 650°C and 700°C, respectively sol-gel method and calcinations at 500°C, 600°C, 700°C and 800°C. We have chosen to synthesize and examine silver particles cytotoxicity due to its use in biological applications. The synthesized Ag powders were characterized from the structural, compositional and morphological point of view by using XRD, SEM, and TEM with SAED. In order to determine the influence of the synthesis route on Ag particles cytotoxicity, different sizes of micro and nanosilver synthesized powders were evaluated for their potential toxicity. For the study of their cytotoxicity, cell cycle and apoptosis have been done analysis through flow cytometry on human colon carcinoma cells and mesenchymal stem cells and through the MTT assay, while the viability and the morphological changes of the cells have been evaluated by using cloning studies. The results showed that the synthesized silver nanoparticles have displayed significant cytotoxicity effects on cell cultures. Our synthesized silver powders were found to present toxicity in a synthesis route and time-dependent manners for pyrosol synthesized nanoparticles; whereas a lower cytotoxicity has been measured after cells were treated with silver nanoparticles synthesized through sol-gel method.Keywords: Ag, cytotoxicity, pyrosol method, sol-gel method
Procedia PDF Downloads 5943809 MAGE-A3 and PRAME Gene Expression and EGFR Mutation Status in Non-Small-Cell Lung Cancer
Authors: Renata Checiches, Thierry Coche, Nicolas F. Delahaye, Albert Linder, Fernando Ulloa Montoya, Olivier Gruselle, Karen Langfeld, An de Creus, Bart Spiessens, Vincent G. Brichard, Jamila Louahed, Frédéric F. Lehmann
Abstract:
Background: The RNA-expression levels of cancer-testis antigens MAGE A3 and PRAME were determined in resected tissue from patients with primary non-small-cell lung cancer (NSCLC) and related to clinical outcome. EGFR, KRAS and BRAF mutation status was determined in a subset to investigate associations with MAGE A3 and PRAME expression. Methods: We conducted a single-centre, uncontrolled, retrospective study of 1260 tissue-bank samples from stage IA-III resected NSCLC. The prognostic value of antigen expression (qRT-PCR) was determined by hazard-ratio and Kaplan-Meier curves. Results: Thirty-seven percent (314/844) of tumours expressed MAGE-A3, 66% (723/1092) expressed PRAME and 31% (239/839) expressed both. Respective frequencies in squamous-cell tumours and adenocarcinomas were 43%/30% for MAGE A3 and 80%/44% for PRAME. No correlation with stage, tumour size or patient age was found. Overall, no prognostic value was identified for either antigen. A trend to poorer overall survival was associated with MAGE-A3 in stage IIIB and with PRAME in stage IB. EGFR and KRAS mutations were found in 10.1% (28/311) and 33.8% (97/311) of tumours, respectively. EGFR (but not KRAS) mutation status was negatively associated with PRAME expression. Conclusion: No clear prognostic value for either PRAME or MAGE A3 was observed in the overall population, although some observed trends may warrant further investigation.Keywords: MAGE A3, PRAME, cancer-testis gene, NSCLC, survival, EGFR
Procedia PDF Downloads 3823808 Electrodeposition of NiO Films from Organic Solvent-Based Electrolytic Solutions for Solar Cell Application
Authors: Thierry Pauporté, Sana Koussi, Fabrice Odobel
Abstract:
The preparation of semiconductor oxide layers and structures by soft techniques is an important field of research. Higher performances are expected from the optimizing of the oxide films and then use of new methods of preparation for a better control of their chemical, morphological, electrical and optical properties. We present the preparation of NiO by electrodeposition from pure polar aprotic medium and mixtures with water. The effect of the solvent, of the electrochemical deposition parameters and post-deposition annealing treatment on the structural, morphological and optical properties of the films is investigated. We remarkably show that the solvent is inserted in the deposited layer and act as a blowing agent, giving rise to mesoporous films after elimination by thermal annealing. These layers of p-type oxide have been successfully used, after sensitization by a dye, in p-type dye-sensitized solar cells. The effects of the solvent on the layer properties and the application of these layers in p-type dye-sensitized solar cells are described.Keywords: NiO, layer, p-type sensitized solar cells, electrodeposition
Procedia PDF Downloads 2973807 How OXA GENE Expression is Implicated in the Treatment Resistance and Poor Prognosis in Glioblastoma
Authors: Naomi Seidu, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan
Abstract:
The current poor prognosis of glioblastoma has called for the need for an improvement in treatment methods in order to improve its survival rate. Despite the different interventions currently available for this tumor, the average survival is still only a few months. (12-15). The aim is to create a more favorable prognosis and have a reduction in the resistance to treatment currently being experienced, even with surgical interventions and chemotherapy. From the available literature, there is a relationship between the presence of HOX genes (Homeobox genes) and glioblastoma, which could be attributable to the increasing treatment resistance. Hence silencing these genes can be a key to improving survival rates of glioblastoma. A series of studies have highlighted the role that HOX genes play in glioblastoma prognosis. Promotion of human glioblastoma initiation, aggressiveness, and resistance to Temozolomide has been associated with HOXA9. The role of HOX gene expression in cancer stem cells should be studied as it could provide a means of designing CSC-targeted therapies, as CSCs play a part in the initiation and progression of solid tumors.Keywords: GBM- glioblastoma, HOXA gene- homeobox genes cluster, signaling pathways, temozolomide
Procedia PDF Downloads 1053806 Antibacterial Activity of Rosmarinus officinalis (Rosemary) and Murraya koenigii (Curry Leaves) against Multidrug Resistant S. aureus and Coagulase Negative Staphylococcus Species
Authors: Asma Naim, Warda Mushtaq
Abstract:
Staphylococcus species are the most versatile and adaptive organism. They are widespread and naturally found on the skin, mucosa and nose in humans. Among these, Staphylococcus aureus is the most important species. These organisms act as opportunistic pathogens and can infect various organs of the host, causing minor skin infection to severe toxin mediated diseases, and life threatening nosocomial infections. Staphylococcus aureus has acquired resistance against β-lactam antibiotics by the production of β-lactamase, and Methicillin-Resistant Staphylococcus aureus (MRSA) strains have also been reported with increasing frequency. MRSA strains have been associated with nosocomial as well as community acquired infections. Medicinal plants have enormous potential as antimicrobial substances and have been used in traditional medicine. Search for medicinally valuable plants with antimicrobial activity is being emphasized due to increasing antibiotic resistance in bacteria. In the present study, the antibacterial potential of Rosmarinus officinalis (Rosemary) and Murraya koenigii (curry leaves) was evaluated. These are common household herbs used in food as enhancer of flavor and aroma. The crude aqueous infusion, decoction and ethanolic extracts of curry leaves and rosemary and essential oil of rosemary were investigated in the present study for antibacterial activity against multi-drug resistant Staphylococcus strains using well diffusion method. In the present study, 60 Multi-drug resistant clinical isolates of S. aureus (43) and Coagulase Negative Staphylococci (CoNS) (17) were screened against different concentrations of crude extracts of Rosmarinus officinalis and Murraya koenigii. Out of these 60 isolates, 43 were sensitive to the aqueous infusion of rosemary; 23 to aqueous decoction and 58 to ethanolic extract whereas, 24 isolates were sensitive to the essential oil. In the case of the curry leaves, no antibacterial activity was observed in aqueous infusion and decoction while only 14 isolates were sensitive to the ethanolic extract. The aqueous infusion of rosemary (50% concentration) exhibited a zone of inhibition of 21(±5.69) mm. against CoNS and 17(±4.77) mm. against S. aureus, the zone of inhibition of 50% concentration of aqueous decoction of rosemary was also larger against CoNS 17(±5.78) mm. then S. aureus 13(±6.91) mm. and the 50% concentrated ethanolic extract showed almost similar zone of inhibition in S. aureus 22(±3.61) mm. and CoNS 21(±7.64) mm. whereas, the essential oil of rosemary showed greater zone of inhibition against S. aureus i.e., 16(±4.67) mm. while CoNS showed 15(±6.94) mm. These results show that ethanolic extract of rosemary has significant antibacterial activity. Aqueous infusion and decoction of curry leaves revealed no significant antibacterial potential against all Staphylococcal species and ethanolic extract also showed only a weak response. Staphylococcus strains were susceptible to crude extracts and essential oil of rosemary in a dose depend manner, where the aqueous infusion showed highest zone of inhibition and ethanolic extract also demonstrated antistaphylococcal activity. These results demonstrate that rosemary possesses antistaphylococcal activity.Keywords: antibacterial activity, curry leaves, multidrug resistant, rosemary, S. aureus
Procedia PDF Downloads 2483805 A Novel Bio-ceramic Using Hyperthermia for Bone Cancer Therapy, Ferro-substituted Silicate Calcium Materials
Authors: hassan gheisari
Abstract:
Ferro silicate calcium nano particles are prepared through the sol-gel method using polyvinyl alcohol (PVA) as a chelating agent. The powder, as prepared, is annealed at three different temperatures (900 ºC, 1000 ºC, and 1100 ºC) for 3 h. The XRD patterns of the samples indicate broad peaks, and the full width at half maximum decreased with increasing annealing temperature. FTIR spectra of the samples confirm the presence of metal - oxygen complexes within the structure. The average particle size obtained from PSA curve demonstrates ultrafine particles. SEM micrographs indicate the particles synthesized have spherical morphology. The saturation magnetization (Ms) and remnant magnetization (Mr) of the samples show dependence on particle size and crystallinity of the samples. The highest saturation magnetization is achieved for the sample annealed at 1100 ºC having maximum average particle size. The high saturation magnetization of the samples suggests the present method is suitable for obtaining nano particles magnetic ferro bioceramic, which is desirable for practical applications such as hyperthermia bone cancer therapy.Keywords: hyperthermia, bone cancer, bio ceramic; magnetic materials; sol– gel, silicate calcium
Procedia PDF Downloads 733804 Ferro-Substituted Silicate Calcium Materials, a Novel Bio-Ceramic Using Hyperthermia for Bone Cancer Therapy
Authors: Hassan Gheisari
Abstract:
Ferro silicate calcium nano particles are prepared through the sol-gel method using polyvinyl alcohol (PVA) as a chelating agent. The powder as prepared is annealed at three different temperatures (900 ºC, 1000 ºC and 1100 ºC) for 3 h. The XRD patterns of the samples indicate broad peaks and the full width at half maximum decreased with increasing annealing temperature. FTIR spectra of the samples confirm the presence of metal - oxygen complexes within the structure. The average particle size obtained from PSA curve demonstrates ultrafine particles. SEM micrographs indicate the particles synthesized have spherical morphology. The saturation magnetization (Ms) and remnant magnetization (Mr) of the samples show dependence on particle size and crystallinity of the samples. The highest saturation magnetization is achieved for the sample annealed at 1100 ºC having maximum average particle size. The high saturation magnetization of the samples suggests the present method is suitable for obtaining nano particles magnetic ferro bioceramic which is desirable for practical applications such as hyperthermia bone cancer therapy.Keywords: hyperthermia, bone cancer, bio ceramic, magnetic materials, sol– gel, silicate calcium
Procedia PDF Downloads 3083803 Cloning, Expression and N-Terminal Pegylation of Human Interferon Alpha-2b Analogs and Their Cytotoxic Evaluation against Cancer Cell Lines
Authors: Syeda Kiran Shahzadi, Nasir Mahmood, Muhammad Abdul Qadir
Abstract:
In the current research, three recombinant human interferon alpha-2b proteins (two modified and one normal form) were produced and Pegylated with an aim to produce more effective drugs against viral infections and cancers. The modified recombinant human interferon alpha-2b proteins were produced by site-directed modifications of interferon alpha 2b gene, targeting the amino acids at positions ‘R23’ and ‘H34’. The resulting chemically modified and unmodified forms of human interferon alpha 2b were conjugated with methoxy-polyethylene glycol propanealdehyde (400 KDa) and methoxy-polyethylene glycol succinimidyl succinate (400 KDa). Pegylation of normal and modified forms of Interferon alpha-2b prolong their release time and enhance their efficacy. The conjugation of PEG with modified and unmodified human interferon alpha 2b protein drugs was also characterized with 1H-NMR, HPLC, and SDS-PAGE. Antiproliferative assays of modified and unmodified forms of drugs were performed in cell based bioassays using MDBK cell lines. The results indicated that experimentally produced recombinant human interferon alpha-2b proteins were biologically active and resulted in significant inhibition of cell growth.Keywords: protein refolding, antiproliferative activities, biomedical applications, human interferon alpha-2b, pegylation, mPEG-propionaldehyde, site directed mutagenesis, E. coli expression
Procedia PDF Downloads 1773802 Effect of Radiotherapy/Chemotherapy Protocol on the Gut Microbiome in Pediatric Cancer Patients
Authors: Nourhan G. Sahly, Ahmed Moustafa, Mohamed S. Zaghloul, Tamer Z. Salem
Abstract:
The gut microbiome plays important roles in the human body that includes but not limited to digestion, immunity, homeostasis and response to some drugs such as chemotherapy and immunotherapy. Its role has also been linked to radiotherapy and associated gastrointestinal injuries, where the microbial dysbiosis could be the driving force for dose determination or the complete suspension of the treatment protocol. Linking the gut microbiota alterations to different cancer treatment protocols is not easy especially in humans. However, enormous effort was exerted to understand this complex relationship. In the current study, we described the gut microbiota dysbiosis in pediatric sarcoma patients, in the pelvic region, with regards to radiotherapy and antibiotics. Fecal samples were collected as a source of microbial DNA for which the gene encoding for V3-V5 regions of 16S rRNA was sequenced. Two of the three patients understudy had experienced an increase in alpha diversity post exposure to 50.4 Gy. Although phylum Firmicutes overall relative abundance has generally decreased, six of its taxa increased in all patients. Our results may indicate the possibility of radiosensitivity or enrichment of the antibiotic resistance of the elevated taxa. Further studies are needed to describe the extent of radiosensitivity with regards to antibiotic resistance.Keywords: combined radiotherapy and chemotherapy, gut microbiome, pediatric cancer, radiosensitivity
Procedia PDF Downloads 1513801 Fabrication of Silicon Solar Cells Using All Sputtering Process
Authors: Ching-Hua Li, Sheng-Hui Chen
Abstract:
Sputtering is a popular technique with many advantages for thin film deposition. To fabricate a hydrogenated silicon thin film using sputtering process for solar cell applications, the ion bombardment during sputtering will generate microstructures (voids and columnar structures) to form silicon dihydride bodings as defects. The properties of heterojunction silicon solar cells were studied by using boron grains and silicon-boron targets. Finally, an 11.7% efficiency of solar cell was achieved by using all sputtering process.Keywords: solar cell, sputtering process, pvd, alloy target
Procedia PDF Downloads 5803800 [Keynote Talk]: Bioactive Cyclic Dipeptides of Microbial Origin in Discovery of Cytokine Inhibitors
Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan
Abstract:
Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha
Procedia PDF Downloads 2123799 Design of a Controlled BHJ Solar Cell Using Modified Organic Vapor Spray Deposition Technique
Authors: F. Stephen Joe, V. Sathya Narayanan, V. R. Sanal Kumar
Abstract:
A comprehensive review of the literature on photovoltaic cells has been carried out for exploring the better options for cost efficient technologies for future solar cell applications. Literature review reveals that the Bulk Heterojunction (BHJ) Polymer Solar cells offer special opportunities as renewable energy resources. It is evident from the previous studies that the device fabricated with TiOx layer shows better power conversion efficiency than that of the device without TiOx layer. In this paper, authors designed a controlled BHJ solar cell using a modified organic vapor spray deposition technique facilitated with a vertical-moving gun named as 'Stephen Joe Technique' for getting a desirable surface pattern over the substrate to improving its efficiency over the years for industrial applications. We comprehended that the efficient processing and the interface engineering of these solar cells could increase the efficiency up to 5-10 %.Keywords: BHJ polymer solar cell, photovoltaic cell, solar cell, Stephen Joe technique
Procedia PDF Downloads 5433798 Suppression of Immunostimulatory Function of Dendritic Cells and Prolongation of Skin Allograft Survival by Dryocrassin
Authors: Hsin-Lien Lin, Ju-Hui Fu
Abstract:
Dendritic cells (DCs) are the major professional antigen-presenting cells for the development of optimal T-cell immunity. DCs can be used as pharmacological targets to screen novel biological modifiers for the treatment of harmful immune responses, such as transplantation rejection. Dryopteris crassirhizoma Nakai (Aspiadaceae) is used for traditional herbal medicine in the region of East Asia. The root of this fern plant has been listed for treating inflammatory diseases. Dryocrassin is the tetrameric phlorophenone component derived from Dryopteris. Here, we tested the immunomodulatory potential of dryocrassin on lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs in vitro and in skin allograft transplantation in vivo. Results demonstrated that dryocrassin reduced the secretion of tumor necrosis factor-α, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also blocked by dryocrassin. Moreover, LPS-stimulated DC-elicited allogeneic T-cell proliferation was lessened by dryocrassin. In addition, dryocrassin inhibited LPS-induced activation of IϰB kinase, JNK/p38 mitogen-activated protein kinase, as well as the translocation of NF-ϰB. Treatment with dryocrassin obviously diminished 2,4-dinitro-1-fluorobenzene- induced delayed-type hypersensitivity and prolonged skin allograft survival. Dryocrassin may be one of the potent immunosuppressive agents for transplant rejection through the destruction of DC maturation and function.Keywords: dryocrassin, dendritic cells, immunosuppression, skin allograft
Procedia PDF Downloads 3863797 Hydrogel Based on Cellulose Acetate Used as Scaffold for Cell Growth
Authors: A. Maria G. Melero, A. M. Senna, J. A. Domingues, M. A. Hausen, E. Aparecida R. Duek, V. R. Botaro
Abstract:
A hydrogel from cellulose acetate cross linked with ethylenediaminetetraacetic dianhydride (HAC-EDTA) was synthesized by our research group, and submitted to characterization and biological tests. Cytocompatibility analysis was performed by confocal microscopy using human adipocyte derived stem cells (ASCs). The FTIR analysis showed characteristic bands of cellulose acetate and hydroxyl groups and the tensile tests evidence that HAC-EDTA present a Young’s modulus of 643.7 MPa. The confocal analysis revealed that there was cell growth at the surface of HAC-EDTA. After one day of culture the cells presented spherical morphology, which may be caused by stress of the sequestration of Ca2+ and Mg2+ ions at the cell medium by HAC-EDTA, as demonstrated by ICP-MS. However, after seven days and 14 days of culture, the cells present fibroblastoid morphology, phenotype expected by this cellular type. The results give efforts to indicate this new material as a potential biomaterial for tissue engineering, in the future in vivo approach.Keywords: cellulose acetate, hydrogel, biomaterial, cellular growth
Procedia PDF Downloads 1953796 Corrosion Inhibition of AA2024 Alloy with Graphene Oxide Derivative: Electrochemical and Surface Analysis
Authors: Nisrine Benzbiria, Abderrahmane Thoume, Mustapha Zertoubi
Abstract:
The goal of this research is to investigate the corrosion inhibition potential of functionalized graphene oxide (GO) with oxime derivative on AA2024-T3 surface in synthetic seawater. The utilization of functionalized graphene oxide is creating a category of corrosion inhibitors known as organically modified nanomaterials. In our work, the functionalization of GO by chalcone oxime enables graphene oxide to have enhanced water solubility and a good corrosion mitigation capacity. Fourier-transform infrared (FT-IR) spectroscopy was utilized to evaluate the main functional groups of the inhibitor. Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization curves (PDP) showed that the inhibitor acts as a mixed-type inhibitor. The inhibitory efficiency (IE) improved as the concentration increased to a value of 96% after one hour of exposure to a medium containing 60 mg/L ppm of the inhibitor. According to thermodynamic calculations, the adsorption of the inhibitor on the AA2024-T3 surface in 3% NaCl followed the Langmuir isotherm. The formation of a barrier layer was further confirmed by surface analysis. The protective film prevented the alloy dissolution and limited the accessibility of attacking ions, as evinced by solution analysis techniques.Keywords: AA2024-T3, NaCl, electrochemical methods, FT-IR, SEM/AFM, DFT, MC simulation
Procedia PDF Downloads 603795 Energy Management Method in DC Microgrid Based on the Equivalent Hydrogen Consumption Minimum Strategy
Authors: Ying Han, Weirong Chen, Qi Li
Abstract:
An energy management method based on equivalent hydrogen consumption minimum strategy is proposed in this paper aiming at the direct-current (DC) microgrid consisting of photovoltaic cells, fuel cells, energy storage devices, converters and DC loads. The rational allocation of fuel cells and battery devices is achieved by adopting equivalent minimum hydrogen consumption strategy with the full use of power generated by photovoltaic cells. Considering the balance of the battery’s state of charge (SOC), the optimal power of the battery under different SOC conditions is obtained and the reference output power of the fuel cell is calculated. And then a droop control method based on time-varying droop coefficient is proposed to realize the automatic charge and discharge control of the battery, balance the system power and maintain the bus voltage. The proposed control strategy is verified by RT-LAB hardware-in-the-loop simulation platform. The simulation results show that the designed control algorithm can realize the rational allocation of DC micro-grid energy and improve the stability of system.Keywords: DC microgrid, equivalent minimum hydrogen consumption strategy, energy management, time-varying droop coefficient, droop control
Procedia PDF Downloads 3033794 Development of Cationic Gelatin Nanoparticles as an Antigen-Carrier for Mucosal Immunization
Authors: Ping-Lun Jiang, Hung-Jun Lin, Shen-Fu Lin, Mei-Yin Chien, Ting-Wei Li, Chun-Han Lin, Der-Zen Liu
Abstract:
Mucosal vaccine induces both mucosal (secretory IgA) and systemic immune responses and it is considered an ideal vaccination strategy for prevention of infectious diseases. One important point to be considered in mucosal vaccination is effective antigen delivery system which can manage effective delivery of antigen to antigen-presenting cells (APCs) of mucosal. In the present study, cationic gelatin nanoparticles were prepared as ideal carriers for more efficient antigen delivery. The average diameter of cationic gelatin nanoparticle was approximate 190 nm, and the zeta potential was about +45 mV, then ovalbumin (OVA) was physically absorbed onto cationic gelatin nanoparticle. The OVA absorption rate was near 95% the zeta potential was about +20 mV. We show that cationic gelatin nanoparticle effectively facilitated antigen uptake by mice bone marrow-derived dendritic cells (mBMDCs) and RAW264.7 cells and induced higher levels of pro-inflammatory cytokines. C57BL/6 mice twice immunized intranasally with OVA-absorbed cationic gelatin nanoparticle induced high levels of OVA-specific IgG in the serum and IgA in their in the nasal and lung wash fluid. These results indicate that nasal administration of cationic gelatin nanoparticles induced both mucosal and systemic immune responses and cationic gelatin nanoparticles might be a potential antigen delivery carrier for further clinical applications.Keywords: antigen delivery, antigen-presenting cells, gelatin nanoparticle, mucosal vaccine
Procedia PDF Downloads 3593793 In Vivo Maltase and Sucrase Inhibitory Activities of Five Underutilized Nigerian Edible Fruits
Authors: Mohammed Auwal Ibrahim, Isa Yunusa, Nafisa Kabir, Shazali Ali Baba, Amina Muhammad Yushau, Suraj Suraj Ibrahim, Zaharaddeen Idris Bello, Suleiman Haruna Suleiman, Murtala Bindawa Isah
Abstract:
Background: Inhibition of intestinal maltase and sucrase prevents postprandial blood glucose excursions which are beneficial in ameliorating diabetes-associated complications. Objective: In this study, the inhibitory effects of fruit extracts of Parinari macrophylla, Detarium microcarpum, Ziziphus spina-christi, Z. mairei and Parkia biglobosa were investigated against intestinal maltase and sucrase. Methods: Rats were given co-administration of the fruit extracts with maltose or sucrose and blood glucose levels were measured at 0, 30, 90 and 120 min. Results: The glucose-time curves indicated that all the fruits had the most potent inhibitory effects on both maltase and sucrase within the first 30 min. The computed Area Under the Curves (AUC0-120)for all the fruits indicated more potent inhibitory effects against intestinal maltase than sucrase.The ED50 range for the fruits extract against maltase and sucrase were 647.15-1118.35 and 942.44-1851.94 mg/kg bw respectively. Conclusion: The data suggests that the fruits could prevent postprandial hyperglycemia via inhibition of intestinal maltase and sucrase.Keywords: diabetes mellitus, fruits, α-glucosidases, maltase, sucrase
Procedia PDF Downloads 3853792 A Left Testicular Cancer with Multiple Metastases Nursing Experience
Authors: Syue-Wen Lin
Abstract:
Objective:This article reviews the care experience of a 40-year-old male patient who underwent a thoracoscopic right lower lobectomy following a COVID-19 infection. His complex medical history included multiple metastases (lungs, liver, spleen, and left kidney) and lung damage from COVID-19, which complicated the weaning process from mechanical ventilation. The care involved managing cancer treatment, postoperative pain, wound care, and palliative care. Methods:Nursing care was provided from August 16 to August 17, 2024. Challenges included difficulty with sputum clearance, which exacerbated the patient's anxiety and fear of reintubation. Pain management strategies combined analgesic drugs, non-drug methods, essential oil massages with family members, and playing the patient’s favorite music to reduce pain and anxiety. Progressive rehabilitation began with stabilizing vital signs, followed by assistance with sitting on the edge of the bed and walking within the ward. Strict sterile procedures and advanced wound care technology were used for daily dressing changes, with meticulous documentation of wound conditions and appropriate dressing selection. Holistic cancer care and palliative measures were integrated to address the patient’s physical and psychological needs. Results:The interdisciplinary care team developed a comprehensive plan addressing both physical and psychological aspects. Respiratory therapy, lung expansion exercises, and a high-frequency chest wall oscillation vest facilitated sputum expulsion and assisted in weaning from mechanical ventilation. The integration of cancer care, pain management, wound care, and palliative care led to improved quality of life and recovery. The collaborative approach between nursing staff and family ensured that the patient received compassionate and effective care. Conclusion: The complex interplay of emergency surgery, COVID-19, and advanced cancer required a multifaceted care strategy. The care team’s approach, combining critical care with tailored cancer and palliative care, effectively improved the patient’s quality of life and facilitated recovery. The comprehensive care plan, developed with family collaboration, provided both high-quality medical care and compassionate support for the terminally ill patient.Keywords: multiple metastases, testicular cancer, palliative care, nursing experience
Procedia PDF Downloads 223791 Targeting Basic Leucine Zipper Transcription Factor ATF-Like Mediated Immune Cells Regulation to Reduce Crohn’s Disease Fistula Incidence
Authors: Mohammadjavad Sotoudeheian, Soroush Nematollahi
Abstract:
Crohn’s disease (CD) is a chronic gastrointestinal segment inflammation encompassing immune dysregulation in a genetically susceptible individual in response to the environmental triggers and interaction between the microbiome and immune system. Uncontrolled inflammation leads to long-term complications, including fibrotic strictures and enteric fistulae. Increased production of Th1 and Th17-cell cytokines and defects in T-regulatory cells have been associated with CD. Th17-cells are essential for protection against extracellular pathogens, but their atypical activity can cause autoimmunity. Intrinsic defects in the control of programmed cell death in the mucosal T-cell compartment are strongly implicated in the pathogenesis of CD. The apoptosis defect in mucosal T-cells in CD has been endorsed as an imbalance of the Bcl-2 and the Bax. The immune system encounters foreign antigens through microbial colonization of mucosal surfaces or infections. In addition, FOSL downregulated IL-26 expression, a cytokine that marks inflammatory Th17-populations in patients suffering from CD. Furthermore, the expression of IL-23 is associated with the transcription factor primary leucine zipper transcription factor ATF-like (Batf). Batf-deficiency demonstrated the crucial role of Batf in colitis development. Batf and IL-23 mediate their effects by inducing IL-6 production. Strong association of IL-23R, Stat3, and Stat4 with IBD susceptibility point to a critical involvement of T-cells. IL-23R levels in transfer fistula were dependent on the AP-1 transcription factor JunB that additionally controlled levels of RORγt by facilitating DNA binding of Batf. T lymphocytes lacking JunB failed to induce IL-23- and Th17-mediated experimental colitis highlighting the relevance of JunB for the IL-23/ Th17 pathway. The absence of T-bet causes unrestrained Th17-cell differentiation. T-cells are central parts of immune-mediated colon fistula. Especially Th17-cells were highly prevalent in inflamed IBD tissues, as RORγt is effective in preventing colitis. Intraepithelial lymphocytes (IEL) contain unique T-cell subsets, including cells expressing RORγt. Increased activated Th17 and decreased T-regulatory cells in inflamed intestinal tissues had been seen. T-cells differentiate in response to many cytokines, including IL-1β, IL-6, IL-23, and TGF-β, into Th17-cells, a process which is critically dependent on the Batf. IL-23 promotes Th17-cell in the colon. Batf manages the generation of IL-23 induced IL-23R+ Th17-cells. Batf is necessary for TGF-β/IL-6-induced Th17-polarization. Batf-expressing T-cells are the core of T-cell-mediated colitis. The human-specific parts of three AP-1 transcription factors, FOSL1, FOSL2, and BATF, are essential during the early stages of Th17 differentiation. BATF supports the Th17 lineage. FOSL1, FOSL2, and BATF make possession of regulatory loci of genes in the Th17 lineage cascade. The AP1 transcription factor Batf is identified to control intestinal inflammation and seems to regulate pathways within lymphocytes, which could theoretically control the expression of several genes. It shows central regulatory properties over Th17-cell development and is intensely upregulated within IBD-affected tissues. Here, we demonstrated that targeting Batf in IBD appears as a therapeutic approach that reduces colitogenic T-cell activities during fistula formation while aiming to affect inflammation in the gut epithelial cells.Keywords: immune system, Crohn’s Disease, BATF, T helper cells, Bcl, interleukin, FOSL
Procedia PDF Downloads 1453790 The Effect of SIAH1 on PINK1 Homeostasis in Parkinson Disease
Authors: Fatimah Abd Elghani, Raymonde Szargel, Vered Shani, Hazem Safory, Haya Hamza, Mor Savyon, Ruth Rott, Rina Bandopadhyay, Simone Engelender
Abstract:
Background: PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. Down regulation of PINK1 results in abnormal mitochondrial morphology and altered membrane potential. Although PINK1 has a predicted mitochondrial import sequence, it’s cellular, and submitochondrial localization remains unclear, in part because it is rapidly degraded. In this work, we investigated the mechanisms involved in PINK1 degradation and how this may affect PINK1 stability and function, with implications for mitochondrial function in PD. In addition, pharmacological inhibition of proteasome activity was shown to lead to PINK1 accumulation, indicating that PINK1 degradation depends on the ubiquitin-proteasome system (UPS). Methods: Using co-immunoprecipitation assays, we identified E3 ubiquitin ligase SIAH1 as a PINK1-interacting protein in HEK293 cells as well as on rat brain tissues. In addition, we determined the effect of SIAH 1, SIAH2 and Parkin on PINK1 steady-state levels by Western blot analysis, and checked their possibility to ubiquitinate and mediate PINK1 degradation through the proteasome carried out in vivo ubiquitination experiments. Results: We have obtained results showing that SIAH-1 interacts with and ubiquitinates PINK1. The ubiquitination promoted by SIAH-1 leads to the proteasomal degradation of PINK1. We confirmed these findings by knocking down SIAH-1 and observing important accumulation of PINK1 in cells. Besides, we found that SIAH-1 decreases PINK1 steady-state levels but not the E3 ligase Parkin. We also investigated the interaction of SIAH-1 with PINK1 disease mutants and its ability to promote their ubiquitination and degradation. Although, no clear difference in the ability of SIAH-1 to promote the degradation of PINK1 disease mutants was observed. It is possible that dysfunction of proteasomal activity in the disease may lead to the accumulation and aggregation of ubiquitinated PINK1 in patients with PINK1 mutations, with possible implications to the pathogenesis of PD. Conclusions: Here, we demonstrated that SIAH-1 ubiquitinates and promotes the degradation of PINK1. In addition, SIAH-1 represents now a target that may help the improvement of mitophagy in PD. Further investigations needed to understand how mitophagy is regulated by PINK1-SIAH-1 axis to provide targets for future therapeutics.Keywords: PD, Parkinson's disease, PINK1, PTEN-induced kinase1, SIAH, seven in absentia homolog, SN, substantia nigra
Procedia PDF Downloads 1423789 Solid Lipid Nanoparticles of Levamisole Hydrochloride
Authors: Surendra Agrawal, Pravina Gurjar, Supriya Bhide, Ram Gaud
Abstract:
Levamisole hydrochloride is a prominent anticancer drug in the treatment of colon cancer but resulted in toxic effects due poor bioavailability and poor cellular uptake by tumor cells. Levamisole is an unstable drug. Incorporation of this molecule in solid lipids may minimize their exposure to the aqueous environment and partly immobilize the drug molecules within the lipid matrix-both of which may protect the encapsulated drugs against degradation. The objectives of the study were to enhance bioavailability by sustaining drug release and to reduce the toxicities associated with the therapy. Solubility of the drug was determined in different lipids to select the components of Solid Lipid Nanoparticles (SLN). Pseudoternary phase diagrams were created using aqueous titration method. Formulations were subjected to particle size and stability evaluation to select the final test formulations which were characterized for average particle size, zeta potential, and in-vitro drug release and percentage transmittance to optimize the final formulation. SLN of Levamisole hydrochloride was prepared by Nanoprecipitation method. Glyceryl behenate (Compritol 888 ATO) was used as core comprising of Tween 80 as surfactant and Lecithin as co-surfactant in (1:1) ratio. Entrapment efficiency (EE) was found to be 45.89%. Particle size was found in the range of 100-600 nm. Zeta potential of the formulation was -17.0 mV revealing the stability of the product. In-vitro release study showed that 66 % drug released in 24 hours in pH 7.2 which represent that formulation can give controlled action at the intestinal environment. In pH 5.0 it showed 64% release indicating that it can even release drug in acidic environment of tumor cells. In conclusion, results revealed SLN to be a promising approach to sustain the drug release so as to increase bioavailability and cellular uptake of the drug with reduction in toxic effects as dose has been reduced with controlled delivery.Keywords: SLN, nanoparticulate delivery of levamisole, pharmacy, pharmaceutical sciences
Procedia PDF Downloads 4313788 Positive Effects of Aerobic Exercise after Bone Marrow Stem Cell Transplantation on Recovery of Dopaminergic Neurons and Promotion of Angiogenesis Markers in the Striatum of Parkinsonian Rats
Authors: S. A. Hashemvarzi, A. Heidarianpour, Z. Fallahmohammadi, M. Pourghasem, M. Kaviani
Abstract:
Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative in the central nervous system characterized by the loss of dopaminergic neurons in the substantia nigra resulting in loss of dopamine release in the striatum. Non-drug treatment options such as Stem cell transplantation and exercise have been considered for treatment of Parkinson's disease. Purpose: The purpose of this study was to evaluate the effect of aerobic exercise after bone marrow stem cells transplantation on recovery of dopaminergic neurons and promotion of angiogenesis markers in the striatum of parkinsonian rats. Materials and Methods: 42 male Wistar rats were divided randomly into six groups: Normal (N), Sham (S), Parkinson’s (P), Stem cells transplanted Parkinson’s (SP), Exercised Parkinson’s (EP) and Stem cells transplanted + Exercised Parkinson’s (SEP). To create a model of Parkinson's, the striatum was destroyed by injection of 6-hydroxy-dopamine into the striatum through stereotaxic apparatus. Stem cells were derived from the bone marrow of femur and tibia of male rats with 6-8 weeks old. After cultivation, approximately 5×105 cells in 5 microliter of medium were injected into the striatum of rats through the channel. Aerobic exercise was included 8 weeks of running on the treadmill with a speed of 15 meters per minute. At the end, all subjects were decapitated and striatum tissues were separately isolated for measurement of vascular endothelial growth factor (VEGF), dopamine (DA) and tyrosine hydroxylase (TH) levels. Results: VEGF, DA and TH levels in the striatum of parkinsonian rats significantly increased in treatment groups (SP, EP and SEP), especially in SEP group compared to P group after treatment (P<0.05). Conclusion: The findings implicate that the BMSCs transplantation in combination with exercise would have synergistic effects leading to functional recovery, dopaminergic neurons recovery and promotion of angiogenesis marker in the striatum of parkinsonian rats.Keywords: stem cells, treadmill training, neurotrophic factors, Parkinson
Procedia PDF Downloads 3423787 Pegylated Liposomes of Trans Resveratrol, an Anticancer Agent, for Enhancing Therapeutic Efficacy and Long Circulation
Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh
Abstract:
Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes
Procedia PDF Downloads 5893786 Microbial Fuel Cells and Their Applications in Electricity Generating and Wastewater Treatment
Authors: Shima Fasahat
Abstract:
This research is an experimental research which was done about microbial fuel cells in order to study them for electricity generating and wastewater treatment. These days, it is very important to find new, clean and sustainable ways for energy supplying. Because of this reason there are many researchers around the world who are studying about new and sustainable energies. There are different ways to produce these kind of energies like: solar cells, wind turbines, geothermal energy, fuel cells and many other ways. Fuel cells have different types one of these types is microbial fuel cell. In this research, an MFC was built in order to study how it can be used for electricity generating and wastewater treatment. The microbial fuel cell which was used in this research is a reactor that has two tanks with a catalyst solution. The chemical reaction in microbial fuel cells is a redox reaction. The microbial fuel cell in this research is a two chamber MFC. Anode chamber is an anaerobic one (ABR reactor) and the other chamber is a cathode chamber. Anode chamber consists of stabilized sludge which is the source of microorganisms that do redox reaction. The main microorganisms here are: Propionibacterium and Clostridium. The electrodes of anode chamber are graphite pages. Cathode chamber consists of graphite page electrodes and catalysts like: O2, KMnO4 and C6N6FeK4. The membrane which separates the chambers is Nafion117. The reason of choosing this membrane is explained in the complete paper. The main goal of this research is to generate electricity and treating wastewater. It was found that when you use electron receptor compounds like: O2, MnO4, C6N6FeK4 the velocity of electron receiving speeds up and in a less time more current will be achieved. It was found that the best compounds for this purpose are compounds which have iron in their chemical formula. It is also important to pay attention to the amount of nutrients which enters to bacteria chamber. By adding extra nutrients in some cases the result will be reverse. By using ABR the amount of chemical oxidation demand reduces per day till it arrives to a stable amount.Keywords: anaerobic baffled reactor, bioenergy, electrode, energy efficient, microbial fuel cell, renewable chemicals, sustainable
Procedia PDF Downloads 227