Search results for: pathways
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 650

Search results for: pathways

410 The Internet of Healthcare Things: A European Perspective and a Review of Ethical Concerns

Authors: M. Emmanouilidou

Abstract:

The Internet of Things (IoT) is a disruptive technological paradigm that is at the center of the digital evolution by integrating physical and virtual worlds leading to the creation of extended interconnected ecosystems that are characterized as smart environments. The concept of the IoT has a broad range of applications in different industries including the healthcare sector. The Internet of Healthcare Things (IoHT), a branch of the IoT, is expected to bring promising benefits to all involved stakeholders and accelerate the revolution of the healthcare sector through a transition towards preventive and personalized medicine. The socio-economic challenges that the healthcare sector is facing further emphasize the need for a radical transformation of healthcare systems in both developed and developing countries with the role of pervasive technological innovations, such as IoHT, recognized as key to counteract the relevant challenges. Besides the number of potential opportunities that IoHT presents, there are fundamental ethical concerns that need to be considered and addressed in relation to the application of IoHT. This paper contributes to the discussion of the emerging topic of IoHT by providing an overview of the role and potential of IoHT, highlighting the characteristics of the current and future healthcare landscape, reporting on the up-to-date status of IoHT in Europe and reflecting upon existing research in the ethics of IoHT by incorporating additional ethical dimensions that have been ignored which can provide pathways for future research in the field.

Keywords: ethics, Europe, healthcare, Internet of Things

Procedia PDF Downloads 106
409 The Discovery of Competitive Glca Inhibitors That Inhibits the Human Pathogenic Fungi Aspergillus Fumigatus and Candida Albicans

Authors: Reem Al-Shidhani, Isabelle S. R. Storer, Michael J. Bromley, Lydia Tabernero

Abstract:

Invasive fungal diseases are an increasing global health concern that contributes to the high mortality rates in immunocompromised patients. The rising of antifungal resistance severely lowers the efficacy of the limited antifungal agents available. New antifungal drugs that target new mechanisms are necessary to tackle the current shortfalls. Amongst post- modifications, phosphorylation is a predominant and an outstanding protein alteration in all eukaryotes. In fungi, protein phosphorylation plays a vital role in many signal transduction pathways, including cell cycle, cell growth, metabolism, transcription, differentiation, proliferation, and virulence. The investigation of Aspergillus fumigatus phosphatases revealed seven genes essential for viability. Inhibiting one of these phosphatases is a new interesting route to develop novel antifungal drugs. In this study, we carried out an early drug discovery process targeting oneessential phosphatase, GlcA. Here, we report the identification of new GlcA inhibitors that show antifungal activity. These important finding open a new avenue to the development of novel antifungals to expand the current narrow arsenal of clinical candidates.

Keywords: invasive fungal diseases, phosphatases, GlcA, competitive inhibitors

Procedia PDF Downloads 76
408 The Symbiotic Relation of Mythical Stories in Transforming Human Lives

Authors: Gayatri Kanwar

Abstract:

The purpose of this research paper is to explore the power of myth in changing human lives; it establishes patterns in the human psyche, affects the way of thinking, as myths unveil various subjects, ideas, and challenges. Through mythological stories one comes to understand the images behind the emotions and feelings, they influence him as it changes his thought patterns, their therapeutic sets the individual on the path of healing and transforms human lives. Every civilization in the olden times had a vast source of myths which they lived by. They were not ordinary stories of everyday life, but exemplary cases narrated through oral traditions in a sacred manner revealed the 'way to live life'. The mythical stories have a spiritual touch which brought him to the acceptance of suffering or finding a solution to his life problems. In modern times, the significance of the age old myth has lost their touch. Each one of us bears countless stories inside ourselves of our own lives and all its happenings. Therefore, each being is a natural narrator. Everybody tells stories about their lives; hence, one tends to know oneself as well as seeks understanding of others through them. When one remembers their stories they speak in narratives. As stated by Jung, these narratives grow into a personal mythology one lives by. Nonetheless, there are times when one becomes stuck in their own stories or myths. Hence, mythology can change one’s perception and can open pathways to other ways of discovering, feeling and experiencing one’s lives.

Keywords: Power of Myths, Significance of myths in modern times, Transforming human lives, Benefits to Society

Procedia PDF Downloads 373
407 Cardioprotective Effects of Grape Seed Extract against Lipo-toxicity and Energy Metabolism Alterations in High-Fat-Diet-Induced Obese Rats

Authors: Thouraya Majoul

Abstract:

Obesity is now a real public health issue throughout the world, and it is well-established that obesity leads to cardiovascular diseases. The prevention and treatment of obesity using nutritional supplements has become a realistic and effective approach. This study was carried out to analyze the incidence of a high-fat diet on rat heart metabolism as well as on fatty acids composition, then to investigate the eventual protective effects of a grape seed extract (GSE). The experimental design consisted of three rat groups subjected to three different conditions; standard (SD), high-fat diet (HFD) and HFD+GSE (HG). We showed that GSE counteracted the effect of HFD on fatty acid composition, namely, docosapentaenoic acid, docosahexaenoic acid, arachidonic acid (ARA), palmitic acid (PA) and palmitoleic acid. Besides, GSE treatment restored HFD-altered metabolic pathways through the recovery of some cardiac enzyme activities such as lipase, glucose 6 phosphate dehydrogenase and pyruvate dehydrogenase. The cardiac lactate level and lactate dehydrogenase activity were also analyzed in relation to HFD and GSE administration. To our knowledge, this is the first study showing the anti-obesity and cardioprotective effects of GSE in relation to fatty acid composition and some cardiac enzymes, supporting its role as a therapeutic agent of obesity.

Keywords: Grape seed extract, phenolic, obesity, cardioprotective, lipotoxicity, energy metabolism

Procedia PDF Downloads 49
406 Insulin Secretory Actions of Spirulina platensis in Perfused Rat Pancreas, Isolated Mouse Islets, and Clonal Pancreatic Β-Cells

Authors: Jma Hannan, Prawej Ansari, Yasser H. A. Abdel-Wahab, Peter R. Flatt

Abstract:

Spirulina platensis (SP, Blue-green algae) have been accepted as a supplement for the treatment of pre and post-diabetes. The present study investigated the effects of butanol fraction from ethanol extract of S. platensis on insulin release from BRIN BD11 cells, isolated mouse islets, and perfused rat pancreas, as well as glucose homeostasis in type 2 diabetic rats and their molecular pathways. In a dose-dependent manner, S. platensis increased insulin release from mouse islets and pancreatic β-cells. The extract also elevated insulin release in perfused rat pancreas. Glucose, isobutylmethylxanthine, tolbutamide, and a depolarizing concentration of KCl significantly potentiated insulin release from BRIN BD11 cells. The effect of diazoxide and verapamil, as well as the absence of extracellular Ca2+ showed a reduction in insulin secretion. When administered orally together with glucose (2.5g/kg bw), S. platensis extract improved fasting and postprandial blood glucose in type 2 diabetes. These data suggest that the anti-diabetic activity of S. platensis is partly mediated by insulin secretion via the KATP channel-dependent pathway/the intracellular cAMP pathway.

Keywords: Insulin, glucose, S. platensis, type 2 diabetes, medicinal plants

Procedia PDF Downloads 73
405 Sema4D/Plexin-B1 Signaling Regulates Osteo/Odontogenic Differentiation of Dental Pulp Stem Cells

Authors: Ting Zou, Chengfei Zhang

Abstract:

Objectives: The purpose of this study was to investigate the role of Semaphorin 4D (Sema4D)/Plexin-B1 signaling on osteo/odontogenic differentiation of human dental pulp stem cells (DPSCs) and uncover its molecular mechanism. Methods: DPSCs were cultured in osteo/odontogenic medium. After treatment with Sema4D (10μg/mL), osteo/odontogenic differentiation and mineralization was evaluated by measuring alkaline phosphatase (ALP) activity and alizarin red S staining respectively. The expression of osteo/odontogenic genes (ALP, Col1A1, BSP, and Runx2) was determined by real-time polymerase chain reaction. p-Plexin-B1, Plexin-B1, Col1A1, RhoA, and ErbB2 were analyzed by western. Results: ALP activity and mineralization formation of DPSCs were significantly decreased after treatment with Sema4D (P<0.05). Sema4D significantly down-regulated osteo/odontogenic-related genes expression (ALP, Col1A1, BSP, and Runx2). p-Plexin-B1, Plexin-B1 and RhoA protein expression levels increased after stimulated with Sema4D, while the expression of Col1A1 decreased. Pretreatment with Plexin-B1 antibody blocked Sema4D induced p-Plexin-B1 expression. Conclusion: Sema4D suppressed osteo/odontogenic differentiation of DPSCs via RhoA-mediated pathways.

Keywords: Sema4D/Plexin-B1, dental pulp stem cells, osteo/odontogenic differentiation, alkaline phosphatase (ALP)

Procedia PDF Downloads 226
404 Gut-Microbiota-Brain-Axis, Leaky Gut, Leaky Brain: Pathophysiology of Second Brain Aging and Alzheimer’s Disease- A Neuroscientific Riddle

Authors: Bilal Ahmad

Abstract:

Alzheimer’s disease (AD) is one of the most common neurodegenerative illnesses. However, how Gut-microbiota plays a role in the pathogenesis of AD is not well elucidated. The purpose of this literature review is to summarize and understand the current findings that may elucidate the gut microbiota's role in the development of AD. Methods: A literature review of all the relevant papers known to the author was conducted. Relevant articles, abstracts and research papers were collected from well-accepted web sources like PubMed, PMC, and Google Scholar. Results: Recent studies have shown that Gut-microbiota has an important role in the progression of AD via Gut-Microbiota-Brain Axis. The onset of AD supports the ‘Hygiene Hypothesis’, which shows that AD might begin in the Gut, causing dysbiosis, which interferes with the intestinal barrier by releasing pro-inflammatory cytokines and making its way up to the brain via the blood-brain barrier (BBB). Molecular mechanisms lipopolysaccharides and serotonin kynurenine (tryptophan) pathways have a direct association with inflammation, the immune system, neurodegeneration, and AD. Conclusion: The studies helped to analyze the molecular basis of AD, other neurological conditions like depression, autism, and Parkinson's disease and how they are linked to Gut-microbiota. Further, studies to explore the therapeutic effects of probiotics in AD and cognitive enhancement should be warranted to provide significant clinical and practical value.

Keywords: gut-microbiota, Alzheimer’s disease, second brain aging, lipopolysaccharides, short-chain fatty acids

Procedia PDF Downloads 13
403 Legal Regulation of Personal Information Data Transmission Risk Assessment: A Case Study of the EU’s DPIA

Authors: Cai Qianyi

Abstract:

In the midst of global digital revolution, the flow of data poses security threats that call China's existing legislative framework for protecting personal information into question. As a preliminary procedure for risk analysis and prevention, the risk assessment of personal data transmission lacks detailed guidelines for support. Existing provisions reveal unclear responsibilities for network operators and weakened rights for data subjects. Furthermore, the regulatory system's weak operability and a lack of industry self-regulation heighten data transmission hazards. This paper aims to compare the regulatory pathways for data information transmission risks between China and Europe from a legal framework and content perspective. It draws on the “Data Protection Impact Assessment Guidelines” to empower multiple stakeholders, including data processors, controllers, and subjects, while also defining obligations. In conclusion, this paper intends to solve China's digital security shortcomings by developing a more mature regulatory framework and industry self-regulation mechanisms, resulting in a win-win situation for personal data protection and the development of the digital economy.

Keywords: personal information data transmission, risk assessment, DPIA, internet service provider, personal information data transimission, risk assessment

Procedia PDF Downloads 21
402 Real-Time Recognition of Dynamic Hand Postures on a Neuromorphic System

Authors: Qian Liu, Steve Furber

Abstract:

To explore how the brain may recognize objects in its general,accurate and energy-efficient manner, this paper proposes the use of a neuromorphic hardware system formed from a Dynamic Video Sensor~(DVS) silicon retina in concert with the SpiNNaker real-time Spiking Neural Network~(SNN) simulator. As a first step in the exploration on this platform a recognition system for dynamic hand postures is developed, enabling the study of the methods used in the visual pathways of the brain. Inspired by the behaviours of the primary visual cortex, Convolutional Neural Networks (CNNs) are modeled using both linear perceptrons and spiking Leaky Integrate-and-Fire (LIF) neurons. In this study's largest configuration using these approaches, a network of 74,210 neurons and 15,216,512 synapses is created and operated in real-time using 290 SpiNNaker processor cores in parallel and with 93.0% accuracy. A smaller network using only 1/10th of the resources is also created, again operating in real-time, and it is able to recognize the postures with an accuracy of around 86.4% -only 6.6% lower than the much larger system. The recognition rate of the smaller network developed on this neuromorphic system is sufficient for a successful hand posture recognition system, and demonstrates a much-improved cost to performance trade-off in its approach.

Keywords: spiking neural network (SNN), convolutional neural network (CNN), posture recognition, neuromorphic system

Procedia PDF Downloads 438
401 Pathways and Mechanisms of Lymphocytes Emigration from Newborn Thymus

Authors: Olena Grygorieva

Abstract:

Nowadays mechanisms of thymocytes emigration from the thymus to the periphery are investigated actively. We have proposed a hypothesis of thymocytes’ migration from the thymus through lymphatic vessels during periodical short-term local edema. By morphological, hystochemical methods we have examined quantity of lymphocytes, epitelioreticulocytes, mast cells, blood and lymphatic vessels in morpho-functional areas of rats’ thymuses during the first week after birth in 4 hours interval. In newborn and beginning from 8 hour after birth every 12 hours specific density of the thymus, absolute quantity of microcirculatory vessels, especially of lymphatic ones, lymphcyte-epithelial index, quantity of mast cells and their degranulative forms increase. Structure of extracellular matrix, intrathymical microenvironment and lymphocytes’ adhesive properties change. Absolute quantity of small lymphocytes in thymic cortex changes wavy. All these changes are straightly expressed from 0 till 2, from 12 till 16, from 108 till 120 hours of postnatal life. During this periods paravasal lymphatic vessels are stuffed with lymphocytes, i.e. discrete migration of lymphocytes from the thymus occurs. After rapid edema reduction, quantity of lymphatic vessels decrease, they become empty. Therefore, in the thymus of newborn periodical short-term local edema is observed, on its top discrete migration of lymphocytes from the thymus occurs.

Keywords: lymphocytes, lymphatic vessels, mast cells, thymus

Procedia PDF Downloads 199
400 Mechanism of Action of Troxerutin in Reducing Oxidative Stress

Authors: Nasrin Hosseinzad

Abstract:

Troxerutin, a trihydroxyethylated derived of rutin, is a flavonoid existing in tea, coffee, cereal grains, various fruits and vegetables have been conveyed to display radioprotective, antithrombotic, nephron-protective and hepato-protective possessions. Troxerutin, has been well-proved to utilize hepatoprotective assets. Troxerutin could upturn the resistance of hippocampal neurons alongside apoptosis by lessening the action of AChE and oxidative stress. Consequently, troxerutin may have advantageous properties in the administration of Alzheimer's disease and cancer. Troxerutin has been testified to have several welfares and medicinal stuffs. It could shelter the mouse kidney against d-gal-induced damage by refining renal utility, decreasing histopathologic changes, dropping ROS construction, reintroducing the activities of antioxidant enzymes and reducing DNA oxidative destruction. The DNA cleavage study clarifies that troxerutin showed DNA protection against hydroxyl radical persuaded DNA mutilation. Troxerutin uses anti-cancer effect in HuH-7 hepatocarcinoma cells conceivably through synchronized regulation of the molecular signalling pathways, Nrf2 and NF-κB. DNA binding at slight channel by troxerutin may have donated to feature breaks leading to improved radiation brought cell death. Furthermore, the mechanism principal the observed variance in the antioxidant activities of troxerutin and its esters was qualified to equally their free radical scavenging capabilities and dissemination on the cell membrane outward.

Keywords: troxerutin, DNA, oxidative stress, antioxidant, free radical

Procedia PDF Downloads 130
399 An Exploration of the Pancreatic Cancer miRNome during the Progression of the Disease

Authors: Barsha Saha, Shouvik Chakravarty, Sukanta Ray, Kshaunish Das, Nidhan K. Biswas, Srikanta Goswami

Abstract:

Pancreatic Ductal Adenocarcinoma is a well-recognised cause of cancer death with a five-year survival rate of about 9%, and its incidence in India has been found to be increased manifold in recent years. Due to delayed detection, this highly metastatic disease has a poor prognosis. Several molecular alterations happen during the progression of the disease from pre-cancerous conditions, and many such alterations could be investigated for their biomarker potential. MicroRNAs have been shown to be prognostic for PDAC patients in a variety of studies. We hereby used NGS technologies to evaluate the role of small RNA changes during pancreatic cancer development from chronic pancreatitis. Plasma samples were collected from pancreatic cancer patients (n=16), chronic pancreatitis patients (n=8), and also from normal individuals (n=16). Pancreatic tumour tissue (n=5) and adjacent normal tissue samples (n=5) were also collected. Sequencing of small RNAs was carried out after small RNAs were isolated from plasma samples and tissue samples. We find that certain microRNAs are highly deregulated in pancreatic cancer patients in comparison to normal samples. A combinatorial analysis of plasma and tissue microRNAs and subsequent exploration of their targets and altered molecular pathways could not only identify potential biomarkers for disease diagnosis but also help to understand the underlying mechanism.

Keywords: small RNA sequencing, pancreatic cancer, biomarkers, tissue sample

Procedia PDF Downloads 62
398 Caring for the Carers: A Qualitative Study to Evaluate the Perspective of Mental Health Carers on the Effectiveness of Community Services in the Illawarra Region (NSW)

Authors: Mona Nikidehaghani, Freda Hui

Abstract:

In Australia, one-third of mental health carers provide 40 hours or more of unpaid care per week. These hidden workers contribute significantly to the Australian mental health workforce by providing unpaid services both direct and indirect to people in their care. However, carers are often neglected in the healthcare system because Government services focus on those with a mental health condition rather than those supporting them. The aim of this study is to evaluate the perceptions of mental health carers on the effectiveness of community services designed for carers and how these services could be improved. We collaborated with One Door Mental Health, a community organisation that supports mental health carers. Through semi-structured interviews with 27 mental health carers residing in the Illawarra region (NSW), we documented their daily challenges and evaluated outcomes of the current programs for carers. Our findings demonstrate that services such as education programs enable capacity building and improve the social life and mental health of carers. Drawing on the perceptions of mental health carers, this study maps pathways for making meaningful changes in the lives of carers and proposes an outcome framework to evaluate the impact of a community organisation on the lives of their clients. The framework prepared by this project would be replicable, allowing other community organisations to measure the outcomes and improve their services.

Keywords: capacity building, community development, community service, mental health carers

Procedia PDF Downloads 128
397 Peripheral Inflammation and Neurodegeneration; A Potential for Therapeutic Intervention in Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

Authors: Lourdes Hanna, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan, Grace Imaguezegie

Abstract:

Background: Degeneration of the central nervous system (CNS), also known as neurodegeneration, describes an age-associated progressive loss of the structure and function of neuronal materials, leading to functional and mental impairments. Main body: Neuroinflammation contributes to the continuous worsening of neurodegenerative states which are characterised by functional and mental impairments due to the progressive loss of the structure and function of neu-ronal materials. Some of the most common neurodegenerative diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Whilst neuroinflammation is a key contributor to the progression of such disease states, it is not the single cause as there are multiple factors which contribute. Theoretically, non-steroidal anti-inflammatory drugs (NSAIDs) have potential to target neuroinflammation to reduce the severity of disease states. Whilst some animal models investigating the effects of NSAIDs on the risk of neurodegenerative diseases have shown a beneficial effect, this is not the same finding. Conclusion: Further investigation using more advanced research methods is required to better understand neuroinflammatory pathways and understand if there is still a potential window for NSAID efficacy.

Keywords: intervention, central nervous system, neurodegeneration, neuroinflammation

Procedia PDF Downloads 49
396 Assessing the Impact of Pharmacist-Led Medication Therapy Management on Treatment Adherence and Clinical Outcomes in Cancer Patients: A Prospective Intervention Study

Authors: Omer Ibrahim Abdallh Omer

Abstract:

Cancer patients often face complex medication regimens, leading to challenges in treatment adherence and clinical outcomes. Pharmacist-led medication therapy management (MTM) has emerged as a potential solution to optimize medication use and improve patient outcomes in oncology settings. In this prospective intervention study, we aimed to evaluate the impact of pharmacist-led MTM on treatment adherence and clinical outcomes among cancer patients. Participants were randomized to receive either pharmacist-led MTM or standard care, with assessments conducted at baseline and follow-up visits. Pharmacist interventions included medication reconciliation, adherence counseling, and personalized care plans. Our findings reveal that pharmacist-led MTM significantly improved medication adherence rates and clinical outcomes compared to standard care. Patients receiving pharmacist interventions reported higher satisfaction levels and perceived value in pharmacist involvement in their cancer care. These results underscore the critical role of pharmacists in optimizing medication therapy and enhancing patient-centered care in oncology settings. Integration of pharmacist-led MTM into routine cancer care pathways holds promise for improving treatment outcomes and quality of life for cancer patients.

Keywords: cancer, medications adherence, medication therapy management, pharmacist

Procedia PDF Downloads 27
395 Cybernetic Modeling of Growth Dynamics of Debaryomyces nepalensis NCYC 3413 and Xylitol Production in Batch Reactor

Authors: J. Sharon Mano Pappu, Sathyanarayana N. Gummadi

Abstract:

Growth of Debaryomyces nepalensis on mixed substrates in batch culture follows diauxic pattern of completely utilizing glucose during the first exponential growth phase, followed by an intermediate lag phase and a second exponential growth phase consuming xylose. The present study deals with the development of cybernetic mathematical model for prediction of xylitol production and yield. Production of xylitol from xylose in batch fermentation is investigated in the presence of glucose as the co-substrate. Different ratios of glucose and xylose concentrations are assessed to study the impact of multi substrate on production of xylitol in batch reactors. The parameters in the model equations were estimated from experimental observations using integral method. The model equations were solved simultaneously by numerical technique using MATLAB. The developed cybernetic model of xylose fermentation in the presence of a co-substrate can provide answers about how the ratio of glucose to xylose influences the yield and rate of production of xylitol. This model is expected to accurately predict the growth of microorganism on mixed substrate, duration of intermediate lag phase, consumption of substrate, production of xylitol. The model developed based on cybernetic modelling framework can be helpful to simulate the dynamic competition between the metabolic pathways.

Keywords: co-substrate, cybernetic model, diauxic growth, xylose, xylitol

Procedia PDF Downloads 299
394 Genetic Approach to Target Putative PKS Genes Involved in Ochratoxin a Biosynthesis within Aspergillus Section Nigri, As a Main Cause of Human Nephropathy

Authors: Sabah Ben Fredj Melki, Yves Brygoo, Ahmed Mliki

Abstract:

A 700 pb PCR-derived DNA fragment was isolated from Aspergillus carbonarius, Aspergillus niger, and Aspergillus tubingensis using degenerated primers (LC1-LC2c) and two newly designed primer pairs (KSLB-LC6) for Aspergillus niger and (AFl1F-LC2) for Aspergillus tubingensis developed for the acyl transferase (AT) and the KS domains of fungal PKSs. DNA from the most of black Aspergillus species currently recognized was tested. Herein, we report on the identification and characterisation of a part of the novel putative OTA-polyketide synthase gene in A. carbonarius “ACPks”, A. niger “ANPks” and A. tubingenis “ATPks”. The sequences were aligned and analyzed using phylogenetic methods. Primers used in this study showed general applicability and other Aspergillus species belonging to section Nigri were successfully amplified especially in A. niger and A. tubingenis. The predicted amino acid sequences “ACPks” displayed 66 to 81% similarities to different polyketide synthase genes while “ANPks” similarities varied from 68 to 71% and “ATPks” were from 81 to 97%. The AT and the KS domains appeared to be specific for a particular type of fungal PKSs and were related to PKSs involved in different mycotoxin biosynthesis pathways, including ochratoxin A. The sequences presented in this work have a high utility for the discovery of novel fungal PKS gene clusters.

Keywords: Pks genes, OTA Biosynthesis, Aspergillus Nigri, sequence analysis

Procedia PDF Downloads 41
393 Simultaneous Targeting of MYD88 and Nur77 as an Effective Approach for the Treatment of Inflammatory Diseases

Authors: Uzma Saqib, Mirza S. Baig

Abstract:

Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

Procedia PDF Downloads 278
392 The Regulation of the Pro-inflammatory Cytokine Interleukin 6 (IL6) by Epstein-Barr Virus (EBV)

Authors: Liu Xiaohan

Abstract:

Epstein–Barr virus (EBV) is a human herpesvirus and is closely related to many malignancies of lymphocyte and epithelial origins, such as gastric cancer, Burkitt’s lymphoma, and nasopharyngeal carcinoma (NPC). NPC is a malignant epithelial tumor which is 100% associated with EBV latent infection. Most of the NPC cases are densely populated in southern China, especially in Guangdong and Hong Kong. To our knowledge, overexpression of pro-inflammatory cytokines may result in a loss of balance of the immune system and cause damage to human bodies. Interleukin-6 (IL6) is a pro-inflammatory cytokine which plays an important role in tumor progression. In addition, gene expression is regulated by both transcriptional and post-transcriptional pathways, while post-transcriptional regulation is an important mechanism to modulate the mature mRNA level in mammalian cells. AU-rich element binding factor 1 (AUF1)/heterogeneous nuclear RNP D (hnRNP D) is known for its function in destabilizing mRNAs, including cytokines and cell cycle regulators. Previous studies have found that overexpression of hnRNP D would lead to tumorigenesis. In this project, our aim is to determine the role played by hnRNP D in EBV-infected cells and how our anti-EBV agents can affect the function of hnRNP D. The results of this study will provide a new insight into how the pro-inflammatory cytokine expression can be regulated by EBV.

Keywords: interleukin 6 (IL6), epstein-barr virus (EBV), nasopharyngeal carcinoma (NPC, epstein-barr nuclear antigen-1 (EBNA1)

Procedia PDF Downloads 33
391 Genome-Wide Functional Analysis of Phosphatase in Cryptococcus neoformans

Authors: Jae-Hyung Jin, Kyung-Tae Lee, Yee-Seul So, Eunji Jeong, Yeonseon Lee, Dongpil Lee, Dong-Gi Lee, Yong-Sun Bahn

Abstract:

Cryptococcus neoformans causes cryptococcal meningoencephalitis mainly in immunocompromised patients as well as immunocompetent people. But therapeutic options are limited to treat cryptococcosis. Some signaling pathways including cyclic AMP pathway, MAPK pathway, and calcineurin pathway play a central role in the regulation of the growth, differentiation, and virulence of C. neoformans. To understand signaling networks regulating the virulence of C. neoformans, we selected the 114 putative phosphatase genes, one of the major components of signaling networks, in the genome of C. neoformans. We identified putative phosphatases based on annotation in C. neoformans var. grubii genome database provided by the Broad Institute and National Center for Biotechnology Information (NCBI) and performed a BLAST search of phosphatases of Saccharomyces cerevisiae, Aspergillus nidulans, Candida albicans and Fusarium graminearum to Cryptococcus neoformans. We classified putative phosphatases into 14 groups based on InterPro phosphatase domain annotation. Here, we constructed 170 signature-tagged gene-deletion strains through homologous recombination methods for 91 putative phosphatases. We examined their phenotypic traits under 30 different in vitro conditions, including growth, differentiation, stress response, antifungal resistance and virulence-factor production.

Keywords: human fungal pathogen, phosphatase, deletion library, functional genomics

Procedia PDF Downloads 333
390 Locally Crafted Sustainability: A Scoping Review for Nesting Social-Ecological and Socio-Technical Systems Towards Action Research in Agriculture

Authors: Marcia Figueira

Abstract:

Context: Positivist transformations in agriculture were responsible for top-down – often coercive – mechanisms of uniformed modernization that weathered local diversities and agency. New development pathways need to now shift according to comprehensive integrations of knowledge - scientific, indigenous, and local, and to be sustained on political interventions, bottom-up change, and social learning if climate goals are to be met – both in mitigation and adaptation. Objectives The objectives of this research are to understand how social-ecological and socio-technical systems characterisation can be nested to bridge scientific research/knowledge into a local context and knowledge system; and, with it, stem sustainable innovation. Methods To do so, we conducted a scoping review to explore theoretical and empirical works linked to Ostrom’s Social-Ecological Systems framework and Geels’ multi-level perspective of socio-technical systems transformations in the context of agriculture. Results As a result, we were able to identify key variables and connections to 1- understand the rules in use and the community attributes influencing resource management; and 2- how they are and have been shaped and shaping systems innovations. Conclusion Based on these results, we discuss how to leverage action research for mutual learning toward a replicable but highly place-based agriculture transformation frame.

Keywords: agriculture systems innovations, social-ecological systems, socio-technical systems, action research

Procedia PDF Downloads 64
389 Creative Potential of Children with Learning Disabilities

Authors: John McNamara

Abstract:

Growing up creative is an important idea in today’s classrooms. As education seeks to prepare children for their futures, it is important that the system considers traditional as well as non-traditional pathways. This poster describes the findings of a research study investigating creative potential in children with learning disabilities. Children with learning disabilities were administered the Torrance Test of Creative Problem Solving along with subtests from the Comprehensive Test of Phonological Processing. A quantitative comparative analysis was computed using paired-sample t-tests. Results indicated statistically significant difference between children’s creative problem-solving skills and their reading-based skills. The results lend support to the idea that children with learning disabilities have inherent strengths in the area of creativity. It can be hypothesized that the success of these children may be associated with the notion that they are using a type of neurological processing that is not otherwise used in academic tasks. Children with learning disabilities, a presumed left-side neurological processing problem, process information with the right side of the brain – even with tasks that should be processed with the left side (i.e. language). In over-using their right hemisphere, it is hypothesized that children with learning disabilities have well-developed right hemispheres and, as such, have strengths associated with this type of processing, such as innovation and creativity. The current study lends support to the notion that children with learning disabilities may be particularly primed to succeed in areas that call on creativity and creative thinking.

Keywords: learning disabilities, educational psychology, education, creativity

Procedia PDF Downloads 47
388 Health Benefit and Mechanism from Green Open Space: A Pathway to Connect Health to Design and Planning

Authors: Ming Ma, Rui Li

Abstract:

In the highly urbanized district, green open space is playing an important role in human’s health and wellbeing as a physical, aesthetic and natural environment resources. The aim of this paper is to close this gap through providing a comprehensive, qualitative meta-analysis of existing studies related to this issue. A systematic scoping of current quantitative research is conducted which mostly focused on cross-sectional survey and experimental studies. Health benefits from contact with green open space could be categorized into physical health, psychological health and social wellbeing. Mechanism for the health related to green open space could be clearly identified with the regard to natural restoration, physical activities and social capital. These results indicate a multiple pathways framework between the health benefits and mechanism. In order to support design and planning, the most evident relationship was picked up that people could psychologically benefit from green open space through outdoors physical activities. Additionally, three design and planning strategies are put forward. Various and multi-level contacts with green open space would be considered as an explanation of the pathway results and tie to bridge the health to design and planning. There is a need to carry out long-term research emphasizing on causal relationship between health and green open space through excluding cofounding factors such as self-selection.

Keywords: urban green open space, planning and design, health benefit, mechanism, pathway framework

Procedia PDF Downloads 279
387 A Novel Protein Elicitor Extracted From Lecanicillium lecanii Induced Resistance Against Whitefly, Bemisia tabaci in Cotton

Authors: Yusuf Ali Abdulle, Azhar Uddin Keerio

Abstract:

Background: Protein elicitors play a key role in signaling or displaying plant defense mechanisms and emerging as vital tools for bio-control of insects. This study was aimed at the characterization of the novel protein elicitor isolated from entomopathogenic fungi Lecanicillium lecanii (V3) strain and its activity against Whitefly, Bemisia tabaci in cotton. The sequence of purified elicitor protein showed 100% similarity with hypothetical protein LEL_00878 [Cordyceps confragosa RCEF 1005], GenBank no (OAA81333.1). This novel protein elicitor has 253 amino acid residues and 762bp with a molecular mass of 29 kDa. The protein recombinant was expressed in Escherichia coli using pET‐28a (+) plasmid. Effects of purified novel protein elicitor on Bemisia tabaci were determined at three concentrations of protein (i.e., 58.32, 41.22, 35.41 μg mL⁻¹) on cotton plants and were exposed to newly molted adult B.tabaci. Bioassay results showed a significant effect of the exogenous application of novel protein elicitor on B. tabaci in cotton. In addition, the gene expression analysis found a significant up-regulation of the major genes associated with salicylic acid (SA) and jasmonic acid (JA) linked plant defense pathways in elicitor protein-treated plants. Our results suggested the potential application of a novel protein elicitor derived from Lecanicillium lecanii as a future bio-intensive controlling approach against the whitefly, Bemisia tabaci.

Keywords: resistance, Lecanicillium lecanii, secondary metabolites, whitefly

Procedia PDF Downloads 145
386 Muscle Relaxant Dantrolene Repurposed to Treat Alzheimer's Disease

Authors: Huafeng Wei

Abstract:

Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

Procedia PDF Downloads 182
385 Academic Skills Enhancement in Secondary School Students Undertaking Tertiary Studies

Authors: Richard White, Anne Drabble, Maureen O’Neill

Abstract:

The University of the Sunshine Coast (USC) offers secondary school students in the final two years of school (Years 11 and 12, 16 – 18 years of age) an opportunity to participate in a program which provides an accelerated pathway to tertiary studies. Whilst still at secondary school, the students undertake two first year university subjects that are required subjects in USC undergraduate degree programs. The program is called Integrated Learning Pathway (ILP) and offers a range of disciplines, including business, design, drama, education, and engineering. Between 2010 and 2014, 38% of secondary students who participated in an ILP program commenced undergraduate studies at USC following completion of secondary school studies. The research reported here considers “before and after” literacy and numeracy competencies of students to determine what impact participation in the ILP program has had on their academic skills. Qualitative and quantitative data has been gathered via numeracy and literacy testing of the students, and a survey asking the students to self-evaluate their numeracy and literacy skills, and reflect on their views of these academic skills. The research will enable improved targeting of teaching strategies so that students will acquire not only course-specific learning outcomes but also collateral academic skills. This enhancement of academic skills will improve undergraduate experience and improve student retention.

Keywords: academic skills enhancement, accelerated pathways, improved teaching, student retention

Procedia PDF Downloads 284
384 Akt: Isoform-Specific Regulation of Cellular Signaling in Cancer

Authors: Bhumika Wadhwa, Fayaz Malik

Abstract:

The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.

Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition

Procedia PDF Downloads 231
383 Caecotrophy Behaviour of the Rabbits (Oryctolagus cuniculus)

Authors: Awadhesh Kishore

Abstract:

One of the most unique characteristics of rabbit feeding behaviour is caecotrophy, which involves the excretion and immediate consumption of specific faeces known as soft faeces. Caecotrophy in rabbits is the instinctual behaviour of eating soft faeces; reduced caecotrophy decreases rabbit growth and lipid synthesis in the liver. Caecotroph ingestion is highest when rabbits are fed a diet high in indigestible fibre. The colon produces two types of waste: hard and soft pellets. The hard pellets are expelled, but the soft pellets are re-ingested by the rabbit directly upon being expelled from the anus by twisting itself around and sucking in those pellets as they emerge from the anus. The type of alfalfa hay in the feed of the rabbits does not affect volatile fatty acid concentration, the pattern of fermentation, or pH in the faeces. The cecal content and the soft faeces contain significant amounts of retinoids and carotenoids, while in the tissues (blood, liver, and kidney), these pigments do not occur in substantial amounts. Preventing caecotrophy reduced growth and altered lipid metabolism, depressing the development of new approaches for rabbit feeding and production. Relative abundance is depressed for genes related to metabolic pathways such as vitamin C and sugar metabolism, vitamin B2 metabolism, and bile secretion. The key microorganisms that regulate the rapid growth performance of rabbits may provide useful references for future research and the development of microecological preparations.

Keywords: caecocolonic microorganisms, caecotrophy, fasting caecotrophy, rabbits, soft pellets

Procedia PDF Downloads 19
382 MXene Quantum Dots Decorated Double-Shelled Ceo₂ Hollow Spheres for Efficient Electrocatalytic Nitrogen Oxidation

Authors: Quan Li, Dongcai Shen, Zhengting Xiao, Xin Liu Mingrui Wu, Licheng Liu, Qin Li, Xianguo Li, Wentai Wang

Abstract:

Direct electrocatalytic nitrogen oxidation (NOR) provides a promising alternative strategy for synthesizing high-value-added nitric acid from widespread N₂, which overcomes the disadvantages of the Haber-Bosch-Ostwald process. However, the NOR process suffers from the limitation of high N≡N bonding energy (941 kJ mol− ¹), sluggish kinetics, low efficiency and yield. It is a prerequisite to develop more efficient electrocatalysts for NOR. Herein, we synthesized double-shelled CeO₂ hollow spheres (D-CeO₂) and further modified with Ti₃C₂ MXene quantum dots (MQDs) for electrocatalytic N₂ oxidation, which exhibited a NO₃− yield of 71.25 μg h− ¹ mgcat− ¹ and FE of 31.80% at 1.7 V. The unique quantum size effect and abundant edge active sites lead to a more effective capture of nitrogen. Moreover, the double-shelled hollow structure is favorable for N₂ fixation and gathers intermediate products in the interlayer of the core-shell. The in-situ infrared Fourier transform spectroscopy confirmed the formation of *NO and NO₃− species during the NOR reaction, and the kinetics and possible pathways of NOR were calculated by density functional theory (DFT). In addition, a Zn-N₂ reaction device was assembled with D-CeO₂/MQDs as anode and Zn plate as cathode, obtaining an extremely high NO₃− yield of 104.57 μg h− ¹ mgcat− ¹ at 1 mA cm− ².

Keywords: electrocatalytic N₂ oxidation, nitrate production, CeO₂, MXene quantum dots, double-shelled hollow spheres

Procedia PDF Downloads 16
381 Therapeutic Application of Light and Electromagnetic Fields to Reduce Hyper-Inflammation Triggered by COVID-19

Authors: Blanche Aguida, Marootpong Pooam, Nathalie Jourdan, Margaret Ahmad

Abstract:

COVID-19-related morbidity is associated with exaggerated inflammation and cytokine production in the lungs, leading to acute respiratory failure. The cellular mechanisms underlying these so-called ‘cytokine storms’ are regulated through the Toll-like receptor 4 (TLR4) signaling pathway and by reactive oxygen species (ROS). Both light (photobiomodulation) and magnetic fields (e.g., pulsed electromagnetic field) stimulation are non-invasive therapies known to confer anti-inflammatory effects and regulate ROS signaling pathways. Here we show that daily exposure to two 10-minute intervals of moderate-intensity infra-red light significantly lowered the inflammatory response induced via the TLR4 receptor signaling pathway in human cell cultures. Anti-inflammatory effects were likewise achieved by electromagnetic field exposure of cells to daily 10-minute intervals of either pulsed electromagnetic fields (PEMF) or to low-level static magnetic fields. Because current illumination and electromagnetic field therapies have no known side effects and are already approved for some medical uses, we have here developed protocols for verification in clinical trials of COVID 19 infection. These treatments are affordable, simple to implement, and may help to resolve the acute respiratory distress of COVID 19 patients both in the home and in the hospital.

Keywords: COVID 19, electromagnetic fields therapy, inflammation, photobiomodulation therapy

Procedia PDF Downloads 118