Search results for: gene delivery

Authors: Paola Modesto, Floriana Fruscione, Isabella Martini, Simona Perga, Federica Riccardo, Mariateresa Camerino, Davide Giacobino, Cecilia Gola, Luca Licenziato, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari

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Canine and human melanoma, osteosarcoma (OSA), and mammary carcinomas are aggressive tumors with common characteristics making dogs a good model for comparative oncology. Novel therapeutic strategies against these tumors could be useful to both species. In humans, chondroitin sulphate proteoglycan 4 (CSPG4) is a marker involved in tumor progression and could be a candidate target for immunotherapy. The anti-CSPG4 DNA electrovaccination has shown to be an effective approach for canine malignant melanoma (CMM) [1]. An immunohistochemistry evaluation of CSPG4 expression in tumour tissue is generally performed prior to electrovaccination. To assess the possibility to perform a rapid molecular evaluation and in order to validate these spontaneous canine tumors as the model for human studies, we investigate the CSPG4 gene expression by RT qPCR in CMM, OSA, and canine mammary tumors (CMT). The total RNA was extracted from RNAlater stored tissue samples (CMM n=16; OSA n=13; CMT n=6; five paired normal tissues for CMM, five paired normal tissues for OSA and one paired normal tissue for CMT), retro-transcribed and then analyzed by duplex RT-qPCR using two different TaqMan assays for the target gene CSPG4 and the internal reference gene (RG) Ribosomal Protein S19 (RPS19). RPS19 was selected from a panel of 9 candidate RGs, according to NormFinder analysis following the protocol already described [2]. Relative expression was analyzed by CFX Maestro™ Software. Student t-test and ANOVA were performed (significance set at P<0.05). Results showed that gene expression of CSPG4 in OSA tissues is significantly increased by 3-4 folds when compared to controls. In CMT, gene expression of the target was increased from 1.5 to 19.9 folds. In melanoma, although an increasing trend was observed, no significant differences between the two groups were highlighted. Immunohistochemistry analysis of the two cancer types showed that the expression of CSPG4 within CMM is concentrated in isles of cells compared to OSA, where the distribution of positive cells is homogeneous. This evidence could explain the differences in gene expression results.CSPG4 immunohistochemistry evaluation in mammary carcinoma is in progress. The evidence of CSPG4 expression in a different type of canine tumors opens the way to the possibility of extending the CSPG4 immunotherapy marker in CMM, OSA, and CMT and may have an impact to translate this strategy modality to human oncology.

Keywords: canine melanoma, canine mammary carcinomas, canine osteosarcoma, CSPG4, gene expression, immunotherapy

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Authors: Shashank Tiwari

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The most common method of drug delivery is the oral solid dosage form, of which tablets and capsules are predominant. The tablet is more widely accepted and used compared to capsules for a number of reasons, such as cost/price, tamper resistance, ease of handling and packaging, ease of identification, and manufacturing efficiency. Over the past several years, the issue of tamper resistance has resulted in the conversion of most over-the-counter (OTC) drugs from capsules to predominantly all tablets.

Keywords: capsule, drug delivery, dosages, solid, tablet

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Authors: Taus Muganda

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This research explores the intricate relationship between e-procurement adoption and effective service delivery in the Uganda Coffee Industry, focusing on the processes involved, key actors, and the impact of digital transformation. The study is guided by three prominent theories, Actor-Network Theory, Resource-Based View Theory, and Institutional Theory to comprehensively explore the dynamics of e-procurement in the context of the coffee sector. The primary aim of this project is to examine the e-procurement adoption process and its role in enhancing service delivery within the Uganda Coffee Industry. The research questions guiding this inquiry are: firstly, whether e-procurement adoption and implementation contribute to achieving quality service delivery; and secondly, how e-procurement adoption can be effectively realized within the Uganda Coffee Industry. To address these questions, the study has laid out specific objectives. Firstly, it seeks to investigate the impact of e-procurement on effective service delivery, analysing how the integration of digital processes influences the overall quality of services provided in the coffee industry. Secondly, it aims to critically analyse the measures required to achieve effective delivery outcomes through the adoption and implementation of e-procurement, assessing the strategies that can maximize the benefits of digital transformation. Furthermore, the research endeavours to identify and examine the key actor’s instrumental in achieving effective service delivery within the Uganda Coffee Industry. By utilizing Actor-Network Theory, the study will elucidate the network of relationships and collaborations among actors involved in the e-procurement process. The research contributes to addressing a critical gap in the sector. Despite coffee being the leading export crop in Uganda, constituting 16% of total exports, there is a recognized need for digital transformation, specifically in the realm of e-procurement, to enhance the productivity of producers and contribute to the economic growth of the country. The study aims to provide insights into transforming the Uganda Coffee Industry by focusing on improving the e-procurement services delivered to actors in the coffee sector. The three forms of e-procurement investigated in this research—E-Sourcing, E-Payment, and E-Invoicing—serve as focal points in understanding the multifaceted dimensions of digital integration within the Uganda Coffee Industry. This research endeavours to offer practical recommendations for policymakers, industry stakeholders, and the UCDA to strategically leverage e-procurement for the benefit of the entire coffee value chain.

Keywords: e-procurement, effective service delivery, actors, actor-network theory, resource-based view theory, institutional theory, e-invocing, e-payment, e-sourcing

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Authors: Rahul Malhotra, Anurag Sharma

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Fiber based access networks can deliver performance that can support the increasing demands for high speed connections. One of the new technologies that have emerged in recent years is Passive Optical Networks. This paper is targeted to show the simultaneous delivery of triple play service (data, voice, and video). The comparative investigation and suitability of various data rates is presented. It is demonstrated that as we increase the data rate, number of users to be accommodated decreases due to increase in bit error rate.

Keywords: FTTH, quad play, play service, access networks, data rate

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Authors: Thomas Geninatti, Bruno Giacomo, Alessandro Grattoni

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Nanofluidic devices have been investigated for over a decade as promising platforms for the controlled release of therapeutics. The nanochannel drug delivery system (nDS), a membrane fabricated with high precision silicon techniques, capable of zero-order release of drugs by exploiting diffusion transport at the nanoscale originated from the interactions between molecules with nanochannel surfaces, showed the flexibility of the sustained release in vitro and in vivo, over periods of time ranging from weeks to months. To improve the implantable bio nanotechnology, in order to create a system that possesses the key features for achieve the suitable release of therapeutics, the next generation of nDS has been created. Platinum electrodes are integrated by e-beam deposition onto both surfaces of the membrane allowing low voltage (<2 V) and active temporal control of drug release through modulation of electrostatic potentials at the inlet and outlet of the membrane’s fluidic channels. Hence, a tunable administration of drugs is ensured from the nanochannel drug delivery system. The membrane will be incorporated into a peek implantable capsule, which will include drug reservoir, control hardware and RF system to allow suitable therapeutic regimens in real-time. Therefore, this new nanotechnology offers tremendous potential solutions to manage chronic disease such as cancer, heart disease, circadian dysfunction, pain and stress.

Keywords: nanochannel membrane, drug delivery, tunable release, personalized administration, nanoscale transport, biomems

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Authors: Shiva Shakori Poshteh

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Lung cancer is a highly prevalent and devastating disease, representing a significant global health concern with profound implications for healthcare systems and society. Its high incidence, mortality rates, and late-stage diagnosis contribute to its formidable nature. To address these challenges, nanoparticle-based drug delivery has emerged as a promising therapeutic strategy. Curcumin (CUR), a natural compound derived from turmeric, has garnered attention as a potential nanomedicine for lung cancer treatment. Nanoparticle formulations of CUR offer several advantages, including improved drug delivery efficiency, enhanced stability, controlled release kinetics, and targeted delivery to lung cancer cells. CUR exhibits a diverse array of effects on cancer cells. It induces apoptosis by upregulating pro-apoptotic proteins, such as Bax and Bak, and downregulating anti-apoptotic proteins, such as Bcl-2. Additionally, CUR inhibits cell proliferation by modulating key signaling pathways involved in cancer progression. It suppresses the PI3K/Akt pathway, crucial for cell survival and growth, and attenuates the mTOR pathway, which regulates protein synthesis and cell proliferation. CUR also interferes with the MAPK pathway, which controls cell proliferation and survival, and modulates the Wnt/β-catenin pathway, which plays a role in cell proliferation and tumor development. Moreover, CUR exhibits potent antioxidant activity, reducing oxidative stress and protecting cells from DNA damage. Utilizing CUR as a standalone treatment is limited by poor bioavailability, lack of targeting, and degradation susceptibility. Nanoparticle-based delivery systems can overcome these challenges. They enhance CUR’s bioavailability, protect it from degradation, and improve absorption. Further, Nanoparticles enable targeted delivery to lung cancer cells through surface modifications or ligand-based targeting, ensuring sustained release of CUR to prolong therapeutic effects, reduce administration frequency, and facilitate penetration through the tumor microenvironment, thereby enhancing CUR’s access to cancer cells. Thus, nanoparticle-based CUR delivery systems promise to improve lung cancer treatment outcomes. This article provides an overview of lung cancer, explores CUR nanoparticles as a treatment approach, discusses the benefits and challenges of nanoparticle-based drug delivery, and highlights prospects for CUR nanoparticles in lung cancer treatment. Future research aims to optimize these delivery systems for improved efficacy and patient prognosis in lung cancer.

Keywords: lung cancer, curcumin, nanomedicine, nanoparticle-based drug delivery

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Authors: Agostinho Antunes

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The completion of the human genome sequencing in 2003 opened a new perspective into the importance of whole genome sequencing projects, and currently multiple species are having their genomes completed sequenced, from simple organisms, such as bacteria, to more complex taxa, such as mammals. This voluminous sequencing data generated across multiple organisms provides also the framework to better understand the genetic makeup of such species and related ones, allowing to explore the genetic changes underlining the evolution of diverse phenotypic traits. Here, recent results from our group retrieved from comparative evolutionary genomic analyses of varied species will be considered to exemplify how gene novelty and gene enhancement by positive selection might have been determinant in the success of adaptive radiations into diverse habitats and lifestyles.

Keywords: adaptation, animals, evolution, genomics

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Authors: Alaa Eddien Abdallah, Bajes Yousef Alskarnah

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Ant colony based routing algorithms are known to grantee the packet delivery, but they suffer from the huge overhead of control messages which are needed to discover the route. In this paper we utilize the network nodes positions to group the nodes in connected clusters. We use clusters-heads only on forwarding the route discovery control messages. Our simulations proved that the new algorithm has decreased the overhead dramatically without affecting the delivery rate.

Keywords: ad-hoc network, MANET, ant colony routing, position based routing

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Authors: Nirupama Dixit, Anyaa Mittal, Neeru Sood

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Alzheimer’s disease (AD) is a progressive form of dementia, contributing to up to 70% of cases, mostly observed in elderly but is not restricted to old age. The pathophysiology of the disease is characterized by specific pathological changes in brain. The changes (i.e. accumulation of metal ions in brain, formation of extracellular β-amyloid (Aβ) peptide aggregates and tangle of hyper phosphorylated Tau protein inside neurons) damage the neuronal connections irreversibly. The current issues in improvement of life quality of Alzheimer's patient lies in the fact that the diagnosis is made at a late stage of the disease and the medications do not treat the basic causes of Alzheimer's. The targeted delivery of drug through the blood brain barrier (BBB) poses several limitations via traditional approaches for treatment. To overcome these drug delivery limitation, nanoparticles provide a promising solution. This review focuses on current strategies for efficient targeted drug delivery using nanoparticles and improving the quality of therapy provided to the patient. Nanoparticles can be used to encapsulate drug (which is generally hydrophobic) to ensure its passage to brain; they can be conjugated to metal ion chelators to reduce the metal load in neural tissue thus lowering the harmful effects of oxidative damage; can be conjugated with drug and monoclonal antibodies against BBB endogenous receptors. Finally this review covers how the nanoparticles can play a role in diagnosing the disease.

Keywords: Alzheimer's disease, β-amyloid plaques, blood brain barrier, metal chelators, nanoparticles

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Authors: Saima Suleman, Kalsoom Sughra, Naeem Mahmood Ashraf

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Mycobacterium tuberculosis is a communicable chronic illness. This disease is being highly focused by researchers as it is present approximately in one third of world population either in active or latent form. The genetic makeup of a person plays an important part in producing immunity against disease. And one important factor association is single nucleotide polymorphism of relevant gene. In this study, we have studied association between single nucleotide polymorphism of CD-209 gene (encode DC-SIGN receptor) and patients of tuberculosis. Dry lab (in silico) and wet lab (RFLP) analysis have been carried out. GWAS catalogue and GEO database have been searched to find out previous association data. No association study has been found related to CD-209 nsSNPs but role of CD-209 in pulmonary tuberculosis have been addressed in GEO database.Therefore, CD-209 has been selected for this study. Different databases like ENSEMBLE and 1000 Genome Project has been used to retrieve SNP data in form of VCF file which is further submitted to different software to sort SNPs into benign and deleterious. Selected SNPs are further annotated by using 3-D modeling techniques using I-TASSER online software. Furthermore, selected nsSNPs were checked in Gujrat and Faisalabad population through RFLP analysis. In this study population two SNPs are found to be associated with tuberculosis while one nsSNP is not found to be associated with the disease.

Keywords: association, CD209, DC-SIGN, tuberculosis

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Authors: Odigie Veronica

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The paper focused on the application of Information and Communication Technology (ICT) in effective service delivery in view of the ongoing COVID-19 experience. It adopted the exploratory research method with three research objectives captured. Consequently, the objectives were to ascertain the meaning of online education, understand the concept of COVID-19 and to determine the relevance of online education in effective service delivery in institutions of learning. It is evident from the findings that through ICT, online mode of learning can be adopted in schools which helps greatly in promoting continual education. Online mode of education is practiced online; it brings both the teacher and learners from different places together, without any physical boundary/contact (at least 75%); and has helped greatly in human development in countries where it has been practiced. It is also a welcome development owing to its many benefits such as exposure to digital learning, having access to works of great teachers and educationists such as Socrates, Plato, Dewey, R.S. Peters, J. J. Rosseau, Nnamdi Azikwe, Carol Gilligan, J. I. Omoregbe, Jane Roland Martin, Jean Piaget, among others; and the facilitation of uninterrupted learning for class promotion and graduation of students. Developing the learners all round is part of human development which helps in developing a nation. These and many more are some benefits online education offers which make ICT very relevant in our contemporary society

Keywords: online education, COVID-19 pandemic, effective service delivery, human development

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Authors: Masoud Soltanialvar, Ali Bagherpour

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The aim of this study was to determinate the variety of Anaplasma species among sheep of khouzestan province, Iran. From April 2013 to June 2013, a total of 200 blood samples were collected via the jugular vein from healthy sheep (100), randomly. The extracted DNA from blood cells were amplified by Anaplasma-all primers, which amplify an approximately 1468bp DNA fragment from region of 16S rRNA gene from various members of the genus Anaplasma. For raising the test sensivity, the PCR products were amplified with the primers, which were designed from the region flanked by the first primers. The amplified nested PCR product had an expected PCR product with 345 nucleotides in length. In 100 sheep blood samples, 7 samples were Anaplasma spp. positive by first PCR and nested PCR. The results showed that 2 of total 100 blood samples (2%) were A.phagocytophilum positive by specific nested PCR based on 16S rRNA gene. The extracted DNA from positive Anaplasma spp. samples were amplified by Anaplasma ovis specific primers, which amplify an approximately 866bp DNA fragment from region of msp4 gene. 5 out of 100 sheep blood samples (5%) were positive for Anaplasma ovis. This study is the first molecular detection of A. ovis and A.phagocytophilum from sheep in Iran.

Keywords: Iran, anaplasma species, sheep, A. ovis, A. phagocytophilum, PCR

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Authors: Esther Kelechi Soyele

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Job satisfaction is the expression of an organisation's fulfillment of work output. In order to achieve effective job satisfaction, the motivation of employees is very essential in stimulating their obligation towards their work. The study examined the motivational strategies, job satisfaction as a correlation of library service delivery in some selected tertiary institutions in southwest Nigeria. The study adopted a descriptive survey research design. A simple random sampling method was employed to select 200 library staff consisting of both library professionals and para-professionals. Two hundred (200) questionnaires were given out, but only one hundred and twenty-nine 129 (96% response rate) were used for the study. Both simple percentage and one and two way ANOVA was used for data analysis. Findings revealed that 60.4% of the respondents were males while 39.6% were female; most of the respondents’ relatively belong to the age group of 31-40 and 41-50, 93.3% were within the age range of 21-50 years, and 43.2 % were M.Sc degree holders. The result revealed a (p < 0.05) significant relationship between work motivational strategies and library service delivery. The results also revealed that motivational development program strategies and job satisfaction have (p < 0.05) a positive significant relationship with library service delivery. It was concluded that work motivation strategies are essential for job satisfaction which is very important in any organization in the attainment of its goals and objectives and helps in maintaining a high standard. The study recommended that more incentive plans that will enhance job satisfaction should be put in place to encourage employees to be more active in carrying out their job effectively.

Keywords: job satisfaction, library, library services, motivational strategies

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Authors: Rahmi Yetri Kasri, Paulus Wirutomo

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Citizen engagement approach has become increasingly important in the rural water sector. However, the question remains as to what exactly is meant by citizen engagement and how this approach can lead to sustainable service delivery. To understand citizen engagement, this paper argues that we need to understand basic elements of social life that consist of social structure, process, and culture within the realm of community’s living environment. Extracting from empirical data from Pamsimas villages in rural West Java, Indonesia, this paper will identify basic elements of social life and environment that influence and form the engagement of citizen and government in delivering and sustaining rural water supply services in Indonesia. Pamsimas or the Water Supply and Sanitation for Low Income Communities project is the biggest rural water program in Indonesia, implemented since 1993 in more than 27,000 villages. The sustainability of this sector is explored through a rural water supply service delivery life-cycle, starts with capital investment, operational and maintenance, asset expansion or renewal, strategic planning for future services and matching cost with financing. Using mixed-method data collection in case study research, this paper argues that increased citizen engagement contributes to a more sustainable rural water service delivery.

Keywords: citizen engagement, rural water supply, sustainability, Indonesia

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Authors: Nipun Agarwal, David Paul, Fareed Un Din

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Strategy development and implementation is the key to an organization’s success in today’s competitive marketplace. Many organizations develop excellent strategy but are unable to implement this strategy in order to succeed. The difference between strategic goals and its implementation is called strategic error. Strategic error occurs when an organization does not have structures in place to implement their strategy. Strategy implementation happens through projects and having a project management method that provides certainty and agility will help an organization become more competitive in implementing strategy. Numerous project management methods exist in theory and practice. However, projects mainly used the Waterfall method in the past that provides certainty in terms of budget, delivery date and resourcing. It is common practice now to utilise Agile based methods. However, Agile based methods do not provide specific deadlines and budgets. But provide agility in product design and project delivery, which is useful to companies. Both Waterfall and Agile methods in some forms are the opposites of each other. Executive management prefer agility in delivery projects as the competitive landscape changes frequently. However, they also appreciate certainty in the projects being able to quantify budgets, deadlines and resources that is harder for an Agile based method to provide. This paper attempts to develop a hybrid project management method that attempts to merge these Waterfall and Agile methods to provide the positives from both these approaches.

Keywords: strategy, project management, strategy implementation, agile

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Authors: Yunfeng Shan, Xiaoliang Wang, Youjun Zhou

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Whole-genome data from two lungfish species, along with other species, present a valuable opportunity to reassess the longstanding debate regarding the evolutionary relationships among tetrapods, lungfishes, and coelacanths. However, the use of bootstrap support has become outdated for large-scale phylogenomic data. Without robust phylogenetic support, the phylogenetic trees become meaningless. Therefore, it is necessary to re-evaluate the phylogenies of tetrapods, lungfishes, and coelacanths using novel measures of phylogenetic support specifically designed for phylogenomic data, as the previous phylogenies were based on 100% bootstrap support. Our findings consistently provide strong evidence favoring lungfish as the closest living relative of tetrapods. This conclusion is based on high gene support confidence with confidence intervals exceeding 95%, high internode certainty, and high gene concordance factor. The evidence stems from two datasets containing recently deciphered whole genomes of two lungfish species, as well as five previous datasets derived from lungfish transcriptomes. These results yield fresh insights into the three hypotheses regarding the phylogenies of tetrapods, lungfishes, and coelacanths. Importantly, these hypotheses are not mere conjectures but are substantiated by a significant number of genes. Analyzing real biological data further demonstrates that the inclusion of additional taxa diminishes the number of orthologues and leads to more diverse tree topologies. Consequently, gene trees and species trees may not be identical even when whole-genome sequencing data is utilized. However, it is worth noting that many gene trees can accurately reflect the species tree if an appropriate number of taxa, typically ranging from six to ten, are sampled. Therefore, it is crucial to carefully select the number of taxa and an appropriate outgroup while excluding fast-evolving taxa as outgroups to mitigate the adverse effects of long-branch attraction (LBA) and achieve an accurate reconstruction of the species tree. This is particularly important as more whole-genome sequencing data becomes available.

Keywords: gene support confidence (GSC), origin of land vertebrates, coelacanth, two whole genomes of lungfishes, confidence intervals

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Authors: Mohammad Ahangari

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Schizophrenia is a psychiatric disorder with symptoms that include cognitive deficits and nicotine has been suggested to have an effect on cognition. In recent years, the advents of Genome-Wide Association Studies(GWAS) has evolved our understanding about the genetic causes of complex disorders such as schizophrenia and studying the role of genome-wide significant genes could potentially lead to the development of new therapeutic agents for treatment of cognitive deficits in schizophrenia. The current study identified six Single Nucleotide Polymorphisms (SNP) from schizophrenia and smoking GWAS that are located on or in close proximity to the nicotinic receptor gene cluster (CHRN) and studied their association with cognition in an Irish sample of 1297 cases and controls using linear regression analysis. Further on, the interaction between CHRN gene cluster and Dopamine receptor D2 gene (DRD2) during working memory was investigated. The effect of these polymorphisms on nicotinic and dopaminergic neurotransmission, which is disrupted in schizophrenia, have been characterized in terms of their effects on memory, attention, social cognition and IQ as measured by a neuropsychological test battery and significant effects in two polymorphisms were found across global IQ domain of the test battery.

Keywords: cognition, dopamine, GWAS, nicotine, schizophrenia, SNPs

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Authors: Mehrnaz Mostafavi

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Lung cancer is one of the most harmful forms of cancer. The long-term survival rate of lung cancer patients treated by conventional modalities such as surgical resection, radiation, and chemotherapy remains far from satisfactory. Systemic drug delivery is rarely successful because only a limited amount of the chemotherapeutic drug targets lung tumor sites, even when administered at a high dose. Targeted delivery of drug molecules to organs or special sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes, micelles and nanoparticles a new frontier was opened for improving drug delivery. Nanoparticles with their special characteristics such as small particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other delivery systems. Targeted nanoparticle delivery to the lungs is an emerging area of interest.Multimodal or combination therapy represents a promising new method to fight disease. Therefore, a combination of different therapeutic strategies may be the best alternative to improve treatment outcomes for lung cancer. Photothermal therapy was proposed as a novel approach to treatment. In this work, photothermal therapy with gold nanoparticles and near infrared laser (NIR) irradiation was investigated.Four types of small (<100nm), NIR absorbing gold nanoparticles (nanospheres, nanorods) were synthesized using wet chemical methods and characterized by transmission electron microscopy, dynamic light scattering and UV-vis spectroscopy. Their synthesis and properties were evaluated, to determine their feasibility as a photothermal agent for clinical applications. In vitro cellular uptake studies of the nanoparticles into lung cancer cell lines was measured using light scattering microscopy.Small gold nanorods had good photothermal properties and the greatest cellular uptake, and were used in photothermal studies. Under 4W laser irradiation, an increase in temperature of 10°C and decrease in cell viability of up to 80% were obtained.

Keywords: photothermal, therapy, cancer, gold nanorods

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Authors: Cenza Rhoda, Falone Sunda, Elvis Kidzeru, Nonhlanhla P. Khumalo, Afolake Arowolo

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Introduction: The human FAM111B gene mutations are associated with POIKTMP, a rare multi-organ fibrosing disease. Recent studies also reported the overexpression of FAM111B in specific cancers. However, the role of FAM111B in these pathologies, particularly fibrosarcoma, remains unknown. Materials and Methods: FAM111B RNA expression in some cancer cell lines was assessed in silico and validated in vitro in these cell lines and skin fibroblasts derived from the South African family member affected by POIKTMP with the heterozygous FAM111B gene mutation: NM_198947.4: c.1861T>G (p. Tyr621Asp or Y621D) by qPCR and western blot. The cellular function of FAM111B was also studied in HT1080 using various cell-based functional assays and a simple and cost-effective PCR-RFLP method for genotyping/screening FAM111B gene mutations described. Results: Expression studies showed upregulated FAM111B mRNA and protein in the cancer cells. High FAM111B expression with robust nuclear localization occurred in HT1080. Additionally, expression data and cell-based assays indicated that FAM111B led to the upregulation of cell migration and decreased cell apoptosis and cell proliferation modulation. FAM111B Y621D mutation showed similar effects on cell migration but minimal impact on cell apoptosis. FAM111B mRNA and protein expression were markedly downregulated (p ≤ 0.05) in the patient's skin-derived fibroblasts. Lastly, the PCR-RFLP method successfully genotyped FAM111B Y621D gene mutation. Discussion: FAM111B is a cancer-associated nuclear protein: Its modulation by mutations may enhance cell migration and proliferation and decrease apoptosis, as seen in cancers and POIKTMP/fibrosis, thus representing a viable therapeutic target in these disorders. Furthermore, the PCR-RFLP method could prove a valuable tool for FAM111B mutation validation or screening in resource-constrained laboratories.

Keywords: FAM111B, POIKTMP, cancer, fibrosis, PCR-RFLP

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Authors: Sunit Kumar Sahoo, Prakash Chandra Senapati

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The main drawback to design drug delivery systems with BCS class II drugs is their low bioavailabilty due to their inherent low permeability characteristics. So the present investigation aspire to develop a self-nanoemulsifying drug delivery system (SNEDDS) of BCS class II anti HIV drug efavirenz (EFZ) using mixtures of non-ionic surfactant mixtures with the main objective to improve the oral bioavailability of said drug. Results obtained from solubility studies of EFZ in various expients utilized for construction of the pseudo ternary phase diagram containing surfactant mixtures. Surfactants in 1:1 combination are used with different co-surfactants in different ratio to delineate the area of monophasic region of the pseudo ternary phase diagram. The formulations which offered positive results in different thermodynamic stability studies were considered for percentage transmittance and turbidity analysis. The various characterization studies like the TEM analysis of post diluted SNEDDS formulations r confirmed the size in nanometric range (below 50 nm) and FT-IR studies confirmed the intactness of the drug the in the preconcentrate. The in vitro dissolution profile of SNEDDS showed that 80% drug was released within 30 min in case of optimized SNEDDS while it was approximately 18.3 % in the case of plain drug powder.. The Pharmacokinetic study using rat model revealed a 2.63 fold increase in AUC (0-∞) in comparison to plain EFZ suspension. The designed delivery system illustrated the confidence in creating a formulation of EFZ with enhanced bioavailability for better HIV treatment.

Keywords: efavirenz, self-nanoemulsifying, surfactant mixture, bioavailability

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Authors: Zhen Ye, Maryam Zaroudi, Elizabeth Aisenbrey, Nicolynn E. Davis, Peng Gao

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Nanoparticles have been used as drug delivery systems in the treatment of life-threatening diseases for decades, but traditional formulation development methods are time consuming and labor intensive. Millipore Sigma has developed a platform¬¬– NanoFabTxTM¬¬– for rapid and reproducible formulation development and screening to ensure consistentnanoparticle characteristics. Reproducible and precise control of the development process for a range of nanoparticle formulations accelerates the introduction of novel formulations to the clinic.

Keywords: Bio platform, Formulation development, NanoFabTxTM, Drug delivery

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Authors: Dwarakanadha Reddy Peram, D. Swarnalatha, C. Gopinath

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The main aim of this research work was to design and development characterization of Pioglitazone transdermal drug delivery system by using various polymers such as Olibanum with different concentration by solvent evaporation technique. The prepared formulations were evaluated for different physicochemical characteristics like thickness, folding endurance, drug content, percentage moisture absorption, percentage moisture loss, percentage elongation break test and weight uniformity. The diffusion studies were performed by using modified Franz diffusion cells. The result of dissolution studies shows that formulation, F3 (Olibanum with 50 mg) showed maximum release of 99.95 % in 12hrs, whereas F1 (Olibanum and EC backing membrane) showed minimum release of 93.65% in 12 hr. Based on the drug release and physicochemical values obtained the formulation F3 is considered as an optimized formulation which shows higher percentage of drug release of 99.95 % in 12 hr. The developed transdermal patches increase the therapeutic efficacy and reduced toxic effect of pioglitazone.

Keywords: pioglitazone, olibanum, transdermal drug delivery system, drug release percantage

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Authors: Ayman K. El Essawy, Amal M. Hosny, Hala M. Abu Shady

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The rapid detection of TB and drug resistance, both optimizes treatment and improves outcomes. In the current study, respiratory specimens were collected from 155 patients. Conventional susceptibility testing and MIC determination were performed for rifampicin (RIF) and isoniazid (INH). Genotype MTBDRplus assay, which is a molecular genetic assay based on the DNA-STRIP technology and specific gene sequencing with primers for rpoB, KatG, and mab-inhA genes were used to detect mutations associated with resistance to rifampicin and isoniazid. In comparison to other categories, most of rifampicin resistant (61.5%) and isoniazid resistant isolates (47.1%) were from patients relapsed in treatment. The genotypic profile (using Genotype MTBDRplus assay) of multi-drug resistant (MDR) isolates showed missing of katG wild type 1 (WT1) band and appearance of mutation band katG MUT2. For isoniazid mono-resistant isolates, 80% showed katG MUT1, 20% showed katG MUT1, and inhA MUT1, 20% showed only inhA MUT1. Accordingly, 100% of isoniazid resistant strains were detected by this assay. Out of 17 resistant strains, 16 had mutation bands for katG distinguished high resistance to isoniazid. The assay could clearly detect rifampicin resistance among 66.7% of MDR isolates that showed mutation band rpoB MUT3 while 33.3% of them were considered as unknown. One mono-resistant rifampicin isolate did not show rifampicin mutation bands by Genotype MTBDRplus assay, but it showed an unexpected mutation in Codon 531 of rpoB by DNA sequence analysis. Rifampicin resistance in this strain could be associated with a mutation in codon 531 of rpoB (based on molecular sequencing), and Genotype MTBDRplus assay could not detect the associated mutation. If the results of Genotype MTBDRplus assay and sequencing were combined, this strain shows hetero-resistance pattern. Gene sequencing of eight selected isolates, previously tested by Genotype MTBDRplus assay, could detect resistance mutations mainly in codon 315 (katG gene), position -15 in inhA promotes gene for isoniazid resistance and codon 531 (rpoB gene) for rifampicin resistance. Genotyping techniques allow distinguishing between recurrent cases of reinfection or reactivation and supports epidemiological studies.

Keywords: M. tuberculosis, rpoB, KatG, inhA, genotype MTBDRplus

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Authors: Papon Thamvasupong, Kwanchanok Viravaidya-Pasuwat

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Osteoarthritis affects a lot of people worldwide. Local injection of glucosamine is one of the alternative treatment methods to replenish the natural lubrication of cartilage. However, multiple injections can potentially lead to possible bacterial infection. Therefore, a drug delivery system is desired to reduce the frequencies of injections. A hydrogel is one of the delivery systems that can control the release of drugs. Thermo-reversible hydrogels can be beneficial to the drug delivery system especially in the local injection route because this formulation can change from liquid to gel after getting into human body. Once the gel is in the body, it will slowly release the drug in a controlled manner. In this study, various formulations of Pluronic-based hydrogels were synthesized for the controlled release of glucosamine. One of the challenges of the Pluronic controlled release system is its fast dissolution rate. To overcome this problem, alginate and calcium sulfate (CaSO₄) were added to the polymer solution. The characteristics of the hydrogels were investigated including the gelation temperature, gelation time, hydrogel dissolution and glucosamine release mechanism. Finally, a mathematical model of glucosamine release from Pluronic-alginate-hyaluronic acid hydrogel was developed. Our results have shown that crosslinking Pluronic gel with alginate did not significantly extend the dissolution rate of the gel. Moreover, the gel dissolution profiles and the glucosamine release mechanisms were best described using the zeroth-order kinetic model, indicating that the release of glucosamine was primarily governed by the gel dissolution.

Keywords: controlled release, drug delivery system, glucosamine, pluronic, thermoreversible hydrogel

Procedia PDF Downloads 261

Authors: Mulata Haile Nega, Derebew Fikadu Berhe, Vera Ribeiro Marques

Abstract:

There is no epidemiologic data on this gene polymorphism in several countries. Therefore, this study aimed to assess the genotype and allele frequencies of the gene variant in three countries. This study involved healthy individuals from Colombia, Mozambique, and Portugal. Genomic DNA was isolated from blood samples using the Qiamp DNA Extraction Kit (Qiagen). The isolated DNA was genotyped using Polymerase Chain Reaction (PCR) - Restriction Fragment Length Polymorphism. Microstat and GraphPad quick cal software were used for the Chi-square test and evaluation of Hardy-Weinberg equilibrium, respectively. A total of 181 individuals’ blood sample was analyzed. Overall, TT (74.0%) genotype was the highest, and CC (7.8%) was the lowest. Country wise genotypic frequencies were Colombia 47(70.2%) TT, 12(17.9%) TC and 8(11.9%) CC; Mozambique 47(88.7%) TT, 5(9.4%) TC, and 1(1.9%) CC; and Portugal 40(65.6%) TT, 16(26.2%) TC, and 5(8.2%) CC. The reference (T) allele was highest among Mozambicans (93.4%) compared to Colombians (79.1%) and Portuguese (78.7%). Mozambicans showed statistically significant genotypic and allelic frequency differences compared to Colombians (p<0.01) and Portuguese (p <0.01). Overall and country-wise, the CC genotype was less frequent and relatively high for Colombians and Portuguese populations. This finding may imply statins risk-benefit variability associated with CC genotype among these populations that needs further understanding.

Keywords: c.521T>C, polymorphism, SLCO1B1, SNP, statins

Procedia PDF Downloads 116

Authors: M. Y. Abubakar, Ipinjolu J. K., Yuzine B. Esa, Magawata I., Hassan W. A., Turaki A. A.

Abstract:

Catfish (Heterobranchus spp.) is a major freshwater fish that are widely distributed in Nigeria waters and are gaining rapid aquaculture expansion. However, indiscriminate artificial crossbreeding of the species with others poses a threat to their biodiversity. There is a paucity of information about the genetic variability, hence this insight on the genetic variability is badly needed, not only for the species conservation but for aquaculture expansion. In this study, we tested the level of Genetic diversity, population differentiation and phylogenetic relationship analysis on 35 individuals of two populations of Heterobranchus bidorsalis and 29 individuals of three populations of Heterobranchus longifilis using the mitochondrial cytochrome c oxidase subunit I (mtDNA COI) gene sequence. Nucleotide sequences of 650 bp fragment of the COI gene of the two species were compared. In the whole 4 and 5 haplotypes were distinguished in the populations of H. bidorsalis & H. longifilis with accession numbers (MG334168 - MG334171 & MG334172 to MG334176) respectively. Haplotypes diversity indices revealed a range of 0.59 ± 0.08 to 0.57 ± 0.09 in H. bidorsalis and 0.000 to 0.001051 ± 0.000945 in H. longifilis population, respectively. Analysis of molecular variance (AMOVA) revealed no significant variation among H. bidorsalis population of the Niger & Benue Rivers, detected significant genetic variation was between the Rivers of Niger, Kaduna and Benue population of H. longifilis. Two main clades were recovered, showing a clear separation between H. bidorsalis and H. longifilis in the phylogenetic tree. The mtDNA COI genes studied revealed high gene flow between populations with no distinct genetic differentiation between the populations as measured by the fixation index (FST) statistic. However, a proportion of population-specific haplotypes was observed in the two species studied, suggesting a substantial degree of genetic distinctiveness for each of the population investigated. These findings present the description of the species character and accessions of the fish’s genetic resources, through gene sequence submitted in Genetic database. The data will help to protect their valuable wild resource and contribute to their recovery and selective breeding in Nigeria.

Keywords: AMOVA, genetic diversity, Heterobranchus spp., mtDNA COI, phylogenetic tree

Procedia PDF Downloads 128

Authors: Anurag Sharma, Dinesh Kumar, Rahul Malhotra, Manoj Kumar

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Fiber based access networks can deliver performance that can support the increasing demands for high speed connections. One of the new technologies that have emerged in recent years is Passive Optical Networks. This paper is targeted to show the simultaneous delivery of triple play service (data, voice and video). The comparative investigation and suitability of various data rates is presented. It is demonstrated that as we increase the data rate, number of users to be accommodated decreases due to increase in bit error rate.

Keywords: BER, PON, TDMPON, GPON, CWDM, OLT, ONT

Procedia PDF Downloads 716

Authors: Rasha Ahmadi

Abstract:

Glioblastoma is one of the most frequent brain malignancies, having a high mortality rate and limited survival in individuals with this malignancy. Despite different treatments and surgery, recurrence of glioblastoma cancer stem cells may arise as a subsequent tumor. For this reason, it is crucial to research the markers associated with glioblastoma stem cells and specifically their microenvironment. In this study, using bioinformatics analysis, we analyzed and nominated genes in the microenvironment pathways of glioblastoma stem cells. In this study, an appropriate database was selected for analysis by referring to the GEO database. This dataset comprised gene expression patterns in stem cells derived from glioblastoma patients. Gene clusters were divided as high and low expression. Enrichment databases such as Enrichr, STRING, and GEPIA were utilized to analyze the data appropriately. Finally, we extracted the potential genes 2700 high-expression and 1100 low-expression genes are implicated in the metabolic pathways of glioblastoma cancer progression. Cellular senescence, MAPK, TNF, hypoxia, zimosterol biosynthesis, and phosphatidylinositol metabolism pathways were substantially expressed and the metabolic pathways were downregulated. After assessing the association between protein networks, MSMP, SOX2, FGD4 ,and CNTNAP3 genes with high expression and DMKN and SBSN genes with low were selected. All of these genes were observed in the survival curve, with a survival of fewer than 10 percent over around 15 months. hsa-mir-192-5p, hsa-mir-129-5p, hsa-mir-215-5p, hsa-mir-335-5p, and hsa-mir-340-5p played key function in glioblastoma cancer stem cells microenviroments. We introduced critical genes through integrated and regular bioinformatics studies by assessing the amount of gene expression profile data that can play an important role in targeting genes involved in the energy and microenvironment of glioblastoma cancer stem cells. Have. This study indicated that hsa-mir-192-5p, and hsa-mir-129-5p are appropriate candidates for this.

Keywords: Glioblastoma, Cancer Stem Cells, Biomarker Discovery, Gene Expression Profiles, Bioinformatics Analysis, Tumor Microenvironment

Procedia PDF Downloads 124

Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Chi V. Phan, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le

Abstract:

Wilson’s disease is an autosomal recessive disorder of copper metabolism, which is caused by mutation in copper- transporting P-type ATPase (ATP7B). The mechanism of this disease is a failure of hepatic excretion of copper to the bile, and it leads to copper deposits in the liver and other organs. Most clinical symptoms of Wilson’s disease can present as liver disease and/or neurologic disease. Objective: The goal of the study is prenatal diagnosis for pregnant women at high risk of Wilson’s disease in Northern Vietnam. Material and method: Three probands with clinically diagnosed liver disease were detected in the mutations of 21 exons and exon-intron boundaries of the ATP7B gene by direct Sanger-sequencing. Prenatal diagnoses were performed by amniotic fluid sampling from pregnant women in the 16th-18th weeks of pregnancy after the genotypes of parents with the probands were identified. Result: A total of three different mutations of the probands, including of S105*, P1052L, P1273G, were detected. Among three fetuses which underwent prenatal genetic testing, one fetus was homozygote; two fetuses were carriers. Conclusion: Genetic testing provided a useful method for prenatal diagnosis, and is a basis for genetic counseling.

Keywords: ATP7B gene, genetic testing, prenatal diagnosis, pedigree, Wilson disease

Procedia PDF Downloads 442

Authors: Salina Y. Saddick

Abstract:

Mild gestational hyperglycemia (MGH) is a very common complication of pregnancy that is characterized by intolerance to glucose. The association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism to MGH has been previously reported. In this study, we evaluated the association between ACE polymorphism and the risk of MGH in a Saudi population. We conducted a case-control study in a population of 100 MGH patients and 100 control subjects. ACE gene polymorphism was analyzed by the novel approach of tetraprimer amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR). The frequency of ACE polymorphism was not associated with either alleles or genotypes in MGH patients. Glucose concentration was found to be significantly associated with the MGH group. Our study suggests that ACE genotypes were not associated with ACE polymorphism in a Saudi population.

Keywords: MGH, ACE, insertion polymorphism, deletion polymorphism

Procedia PDF Downloads 306