Search results for: drug discovery

Authors: Ravi Kiran Pothamsetty, Radha Rani Ghosh, Baby Paul Thaliath

Abstract:

Radiation therapy has undergone many advancements and evloved from 2D to 3D. Recently, with rapid pace of drug discoveries, cutting edge technology, and clinical trials has made innovative advancements in computer technology and treatment planning and upgraded to intensity modulated radiotherapy (IMRT) which delivers in homogenous dose to tumor and normal tissues. The present study was a hospital-based experience comparing two different conformal radiotherapy techniques for brain tumors. This analytical study design has been conducted at Regional Cancer Centre, India from January 2014 to January 2015. Ten patients have been selected after inclusion and exclusion criteria. All the patients were treated on Artiste Siemens Linac Accelerator. The tolerance level for maximum dose was 6.0 Gyfor lenses and 54.0 Gy for brain stem, optic chiasm and optical nerves as per RTOG criteria. Mean and standard deviation values of PTV98%, PTV 95% and PTV 2% in IMRT were 93.16±2.9, 95.01±3.4 and 103.1±1.1 respectively; for 3DCRT were 91.4±4.7, 94.17±2.6 and 102.7±0.39 respectively. PTV max dose (%) in IMRT and 3D-CRT were 104.7±0.96 and 103.9±1.0 respectively. Maximum dose to the tumor can be delivered with IMRT with acceptable toxicity limits. Variables such as expertise, location of tumor, patient condition, and TPS influence the outcome of the treatment.

Keywords: brain tumors, intensity modulated radiotherapy (IMRT), three dimensional conformal radiotherapy (3D-CRT), radiation therapy oncology group (RTOG)

Procedia PDF Downloads 218

Authors: Karen Butler

Abstract:

Johnson C. Smith University, one of the nation’s oldest Historically Black Colleges and Universities, has a strong history of service learning and community service. We first integrated service learning and peer education into health education courses in the spring of 2000. Students enrolled in the classes served as peer educators for the semester. Since then, the program has evolved and expanded but remains an integral part of several courses. The purpose of this session is to describe our program in terms of development, successes, and obstacles, and feedback received. A detailed description of the service learning component in HED 235: Drugs and Drug Education and HED 337: Environmental Health will be provided. These classes are required of our Community Health majors but are also popular electives for students in other disciplines. Three sources of student feedback were used to evaluate and continually modify the component: the SIR II course evaluation, service learning reflection papers, and focus group interviews. Student feedback has been largely positive. When criticism was given, it was thoughtful and constructive – given in the spirit of making it better for the next group. Students consistently agreed that the service learning program increased their awareness of pertinent health issues; that both the service providers and service recipients benefited from the project; and that the goals/issues targeted by the service learning component fit the objectives of the course. Also, evidence of curriculum and learning enhancement was found in the reflection papers and focus group sessions. Service learning sets up a win-win situation. It provides a way to respond to campus and community health needs while enhancing the curriculum, as students learn more by doing things that benefit the health and wellness of others. Service learning is suitable for any health education course and any target audience would welcome the effort.

Keywords: black colleges, community health, health education, service learning

Procedia PDF Downloads 311

Authors: Redouane Krini, Lutz Nuhn, Hicham El Mard Cheol Woo Ha, Yoondeok Han, Kwang-Sup Lee, Dong-Yol Yang, Jinsoo Joo, Rudolf Zentel

Abstract:

To use Quantum Dots (QDs) in the two photon initiated polymerization technique (TPIP) for 3D patternings, QDs were modified on the surface with photosensitive end groups which are able to undergo a photopolymerization. We were able to fabricate fluorescent 3D lattice structures using photopatternable QDs by TPIP for photonic devices such as photonic crystals and metamaterials. The QDs in different diameter have different emission colors and through mixing of RGB QDs white light fluorescent from the polymeric structures has been created. Metamaterials are capable for unique interaction with the electrical and magnetic components of the electromagnetic radiation and for manipulating light it is crucial to have a negative refractive index. In combination with QDs via TPIP technique polymeric structures can be designed with properties which cannot be found in nature. This makes these artificial materials gaining a huge importance for real-life applications in photonic and optoelectronic. Understanding of interactions between nanoparticles and biological systems is of a huge interest in the biomedical research field. We developed a synthetic strategy of polymer functionalized nanoparticles for biomedical studies to obtain hybrid systems of QDs and copolymers with a strong binding network in an inner shell and which can be modified in the end through their poly(ethylene glycol) functionalized outer shell. These hybrid systems can be used as models for investigation of cell penetration and drug delivery by using measurements combination between CryoTEM and fluorescence studies.

Keywords: biomedical study models, lithography, photo induced polymerization, quantum dots

Procedia PDF Downloads 497

Authors: Kenji Gwee

Abstract:

In Singapore, the death penalty remains in active use for murder and drug trafficking of controlled drugs such as heroin. As such, the psychological assessment of defendants can often be of high stakes. The Test of Memory Malingering (TOMM) is employed by government psychologists to determine the degree of effort invested by defendants, which in turn inform on the veracity of overall psychological findings that can invariably determine the life and death of defendants. The purpose of this study was to find out if defendants facing the death penalty were more likely to invest less effort during psychological assessment (to fake bad in hopes of escaping the death sentence) compared to defendants facing lesser penalties. An archival search of all forensic cases assessed in 2012-2013 by Singapore’s designated forensic psychiatric facility yielded 186 defendants’ TOMM scores. Offence severity, coded into 6 rank-ordered categories, was analyzed in a one-way ANOVA with TOMM score as the dependent variable. There was a statistically significant difference (F(5,87) = 2.473, p = 0.038). A Tukey post-hoc test with Bonferroni correction revealed that defendants facing lower charges (Theft, shoplifting, criminal breach of trust) invested less test-taking effort (TOMM = 37.4±12.3, p = 0.033) compared to those facing the death penalty (TOMM = 46.2±8.1). The surprising finding that those facing death penalties actually invested more test taking effort than those facing relatively minor charges could be due to higher levels of cooperation when faced with death. Alternatively, other legal avenues to escape the death sentence may have been preferred over the mitigatory chance of a psychiatric defence.

Keywords: capital sentencing, offence severity, Singapore, Test of Memory Malingering

Procedia PDF Downloads 411

Authors: Arzu Karahan, Loriano Ballarin, Baruch Rinkevich

Abstract:

Marine invertebrates, the highly diverse phyla of multicellular organisms, represent phenomena that are either not found or highly restricted in the vertebrates. These include phenomena like budding, fission, a fusion of ramets, and high regeneration power, such as the ability to create whole new organisms from either tiny parental fragment, many of which are controlled by totipotent, pluripotent, and multipotent stem cells. Thus, there is very much that can be learned from these organisms on the practical and evolutionary levels, further resembling Darwin's words, “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change”. The ‘stem cell’ notion highlights a cell that has the ability to continuously divide and differentiate into various progenitors and daughter cells. In vertebrates, adult stem cells are rare cells defined as lineage-restricted (multipotent at best) with tissue or organ-specific activities that are located in defined niches and further regulate the machinery of homeostasis, repair, and regeneration. They are usually categorized by their morphology, tissue of origin, plasticity, and potency. The above description not always holds when comparing the vertebrates with marine invertebrates’ stem cells that display wider ranges of plasticity and diversity at the taxonomic and the cellular levels. While marine/aquatic invertebrates stem cells (MISC) have recently raised more scientific interest, the know-how is still behind the attraction they deserve. MISC, not only are highly potent but, in many cases, are abundant (e.g., 1/3 of the entire animal cells), do not locate in permanent niches, participates in delayed-aging and whole-body regeneration phenomena, the knowledge of which can be clinically relevant. Moreover, they have massive hidden potential for the discovery of new bioactive molecules that can be used for human health (antitumor, antimicrobial) and biotechnology. The MARISTEM COST action (Stem Cells of Marine/Aquatic Invertebrates: From Basic Research to Innovative Applications) aims to connect the European fragmented MISC community. Under this scientific umbrella, the action conceptualizes the idea for adult stem cells that do not share many properties with the vertebrates’ stem cells, organizes meetings, summer schools, and workshops, stimulating young researchers, supplying technical and adviser support via short-term scientific studies, making new bridges between the MISC community and biomedical disciplines.

Keywords: aquatic/marine invertebrates, adult stem cell, regeneration, cell cultures, bioactive molecules

Procedia PDF Downloads 136

Authors: Mahsa Taghavi

Abstract:

In the treatment of breast cancer, tamoxifen is a regularly prescribed medication. The effect of tamoxifen on breast cancer patients' EMT pathways was studied. In this study to see if it had any effect on the cancer cells' resistance to tamoxifen and to look for specific miRNAs associated with EMT. In this work, we used continuous and integrated bioinformatics analysis to choose the optimal GEO datasets. Once we had sorted the gene expression profile, we looked at the mechanism of signaling, the ontology of genes, and the protein interaction of each gene. In the end, we used the GEPIA database to confirm the candidate genes. after that, I investigated critical miRNAs related to candidate genes. There were two gene expression profiles that were categorized into two distinct groups. Using the expression profile of genes that were lowered in the EMT pathway, the first group was examined. The second group represented the polar opposite of the first. A total of 253 genes from the first group and 302 genes from the second group were found to be common. Several genes in the first category were linked to cell death, focal adhesion, and cellular aging. Two genes in the second group were linked to cell death, focal adhesion, and cellular aging. distinct cell cycle stages were observed. Finally, proteins such as MYLK, SOCS3, and STAT5B from the first group and BIRC5, PLK1, and RAPGAP1 from the second group were selected as potential candidates linked to tamoxifen's influence on the EMT pathway. hsa-miR-1204 and hsa-miR-639 have a very close relationship with the candidates genes according to the node degrees and betweenness index. With this, the action of tamoxifen on the EMT pathway was better understood. It's important to learn more about how tamoxifen's target genes and proteins work so that we can better understand the drug.

Keywords: tamoxifen, breast cancer, bioinformatics analysis, EMT, miRNAs

Procedia PDF Downloads 105

Authors: Xi Liu, Fan Yuan

Abstract:

In the evolving landscape of physics-based machine learning (PBML), particularly within fluid dynamics and its applications in electromechanical engineering, robot vision, and robot learning, achieving precision and alignment with researchers' specific needs presents a formidable challenge. In response, this work proposes a methodology that integrates neural transformation with a modified smoothed particle hydrodynamics model for generating transformed 3D fluid simulations. This approach is useful for nanoscale science, where the unique and complex behaviors of viscoelastic medium demand accurate neurally-transformed simulations for materials understanding and manipulation. In electromechanical engineering, the method enhances the design and functionality of fluid-operated systems, particularly microfluidic devices, contributing to advancements in nanomaterial design, drug delivery systems, and more. The proposed approach also aligns with the principles of PBML, offering advantages such as multi-fluid stylization and consistent particle attribute transfer. This capability is valuable in various fields where the interaction of multiple fluid components is significant. Moreover, the application of neurally-transformed hydrodynamical models extends to manufacturing processes, such as the production of microelectromechanical systems, enhancing efficiency and cost-effectiveness. The system's ability to perform neural transfer on 3D fluid scenes using a deep learning algorithm alongside physical models further adds a layer of flexibility, allowing researchers to tailor simulations to specific needs across scientific and engineering disciplines.

Keywords: physics-based machine learning, robot vision, robot learning, hydrodynamics

Procedia PDF Downloads 38

Authors: Danish Idrees, Vijay Kumar, Samudrala Gourinath

Abstract:

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by misfolding and aggregation of Cu, Zn superoxide dismutase (SOD1). The use of small molecules has been shown to stabilize the SOD1 dimer and preventing its dissociation and aggregation. In this study, we employed molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR) to study the interactions between SOD1 and natural polyphenolic compounds. In order to explore the noncovalent interaction between SOD1 and natural polyphenolic compounds, molecular docking and molecular dynamic (MD) simulations were employed to gain insights into the binding modes and free energies of SOD1-polyphenolic compounds. MM/PBSA methods were used to calculate free energies from obtained MD trajectories. The compounds, Hesperidin, Ergosterol, and Rutin showed the excellent binding affinity in micromolar range with SOD1. Ergosterol and Hesperidin have the strongest binding affinity to SOD1 and was subjected to further characterization. Biophysical experiments using Circular Dichroism and Thioflavin T fluorescence spectroscopy results show that the binding of these two compounds can stabilize SOD1 dimer and inhibit the aggregation of SOD1. Molecular simulation results also suggest that these compounds reduce the dissociation of SOD1 dimers through direct interaction with the dimer interface. This study will be helpful to develop other drug-like molecules which may have the effect to reduce the aggregation of SOD1.

Keywords: amyotrophic lateral sclerosis, molecular dynamics simulation, surface plasmon resonance, superoxide dismutase

Procedia PDF Downloads 114

Authors: Ioana Simina Frincu

Abstract:

As institutional initiatives often fail to provide good practices when it comes to heritage management or to adapt to the changing environment in which they function and to the audiences they address, private actions represent viable strategies for sustainable knowledge acquisition. Information dissemination to future generations is one of the key aspects in preserving cultural heritage and is successfully feasible even in the absence of original artifacts. Combined with the (re)discovery of natural landscape, open-air exploratory approaches (archeoparks) versus an enclosed monodisciplinary rigid framework (traditional museums) are more likely to 'speak the language' of a larger number of people, belonging to a variety of categories, ages, and professions. Interactive sites are efficient ways of stimulating heritage awareness and increasing the number of visitors of non-interactive/static cultural institutions owning original pieces of history, delivering specialized information, and making continuous efforts to preserve historical evidence (relics, manuscripts, etc.). It is high time entrepreneurs took over the role of promoting cultural heritage, bet it under a more commercial yet more attractive form (business). Inclusive, participatory type of activities conceived by experts from different domains/fields (history, anthropology, tourism, sociology, business management, integrative sustainability, etc.) have better chances to ensure long term cultural benefits for both adults and children, especially when and where the educational discourse fails. These unique self-experience leisure activities, which offer everyone the opportunity to recreate history by him-/her-self, to relive the ancestors’ way of living, surviving and exploring should be regarded not as pseudo-scientific approaches but as important pre-steps to museum experiences. In order to support this theory, focus will be laid on two different examples: one dynamic, in the outdoors (the Boario Terme Archeopark from Italy) and one experimental, held indoor (the reconstruction of the Neolithic sanctuary of Parta, Romania as part of a transdisciplinary academic course) and their impact on young generations. The conclusion of this study shows that the increasingly lower engagement of youth (students) in discovering and understanding history, archaeology, and heritage can be revived by entrepreneurial projects.

Keywords: archeopark, educational tourism, open air museum, Parta sanctuary, prehistory

Procedia PDF Downloads 106

Authors: E. M. Vieira, C. S. Vieira, L. P. Bonifácio, L. M. de Oliveira Ciabati, A. C. A. Franzon, F. S. Zaratini, J. A. C. Sanchez, M. S. Andrade, J. P. Dias de Souza

Abstract:

The quality of prenatal care is key to reduce maternal morbidity and mortality. Communication between the health service and users can stimulate prevention and care. M-health has been an important and low cost strategy to health education. The PRENACEL programme (prenatal in the cell phone) was developed. It consists of a programme of information via SMS from the 20^th week of pregnancy up to 12^th week after delivery. Messages were about prenatal care, birth, contraception and breastfeeding. Communication of the pregnant woman asking questions about their health was possible. The objective of this study was to evaluate the implementation of PRENACEL as a useful complement to the standard prenatal care. Twenty health clinics were selected and randomized by cluster, 10 as the intervention group and 10 as the control group. In the intervention group, women and their partner were invited to participate. The control group received the standard prenatal care. All women were interviewed in the immediate post-partum and in the 12^th and 24^th week post-partum. Most women were married, had more than 8 years of schooling and visit the clinic more than 6 times during prenatal care. The intervention group presented lowest percentage of higher economic participants (5.6%), less single mothers and no drug user. It also presented more prenatal care visits than the control group and it was less likely to present Severe Acute Maternal Mortality when compared to control group as well as higher percentage of partners (75.4%) was present at the birth compared to control group. Although the study is still being carried out, preliminary data are showing positive results of the compliance of women to prenatal care.

Keywords: cellphone, health technology, prenatal care, prevention

Procedia PDF Downloads 369

Authors: A. M. Malagon Escandon, J. A. Arenas Alatorre, C. P. Chaires Rosas, N. A. Vazquez Torres, B. Hernandez Tellez, G. Pinon Zarate, M. Herrera Enriquez, A. E. Castell Rodriguez

Abstract:

The current approach to the treatment of bone defects involves the use of scaffolds that provide a biological and mechanically stable niche to favor tissue repair. Despite the significant progress in the field of bone tissue engineering, several main problems associated are attributed to giving a low biodegradation degree, does not promote osseointegration and regeneration, if the bone is not healing as well as expected or fails to heal, will not be given a proper ossification or new bone formation. The actual approaches of bone tissue regeneration are directed to the use of decellularized native extracellular matrices, which are able of retain their own architecture, mechanic properties, biodegradability and promote new bone formation because they are capable of conserving proteins and other factors that are founded in physiological concentrations. Therefore, we propose an extracellular matrix-based bioscaffolds derived from bovine cancellous bone, which is processed by decellularization, demineralization, and hydrolysis of the collagen protein, these protocols have been successfully carried out in other organs and tissues; the effectiveness of its biosafety has also been previously evaluated in vivo and Food and Drug Administration (FDA) approved. In the specific case of bone, a more complex treatment is needed in comparison with other organs and tissues because is necessary demineralization and collagen denaturalization. The present work was made in order to obtain a temporal scaffold that succeed in degradation in an inversely proportional way to the synthesis of extracellular matrix and the maturation of the bone by the cells of the host.

Keywords: bioactive, biodegradable, bone, extracellular matrix-based bioscaffolds, stem cells, tissue engineering

Procedia PDF Downloads 125

Authors: Danielle Page

Abstract:

Foregoing studies, statistics, and medical evaluations have established a relationship between Posttraumatic stress disorder (PTSD) and criminal justice involvement in Vietnam veterans. War is highly trauma inducing and can leave combat veterans with mental disorders ranging from psychopathic thoughts to suicidal ideation. The majority of those suffering are unaware that they have PTSD, and as a coping mechanism, they often turn to self isolation. Beyond isolation, many veterans with symptomatic PTSD turn to aggression and substance abuse to cope with their internal agony. The most common crimes committed by veterans with PTSD fall into the assault and drug/alcohol abuse categories. Thus, a relationship is established between veteran populations and the criminal justice system. This research aims to define the relationship between PTSD and criminal justice involvement in veterans, explore the mediating factors in this relationship, and analyze numerous court cases in this subject area. Further, it will examine the ways in which crime rates can be reduced for veterans with symptoms of PTSD. This ranges from the improvement of healthcare systems to the implementation of special courts to handle veteran cases. The contribution of this work to the field of forensic psychology will be significant, as it will analyze preexisting case studies and experimental data in an effort to improve the ways in which veteran cases are handled in the criminal justice system. Military personnel involved in the criminal justice system are a vulnerable population in need of healthcare and legislative attention, and this work will bring us one step closer to providing them with just that.

Keywords: forensic psychology, psychotraumatology, PTSD, veterans

Procedia PDF Downloads 67

Authors: Ozlem Temiz Arpaci, Meryem Tasci, Hakan Goker

Abstract:

Benzimidazole, a structural isostere of indol and purine nuclei that can interact with biopolymers, can be identified as master key. So that benzimidazole compounds are important fragments in medicinal chemistry because of their wide range of biological activities including antimicrobial activity. We planned to synthesize some benzimidazole compounds for developing new antimicrobial drug candidates. In this study, we put some heterocyclic rings on second position and an amidine group on the fifth position of benzimidazole ring and synthesized them using a multiple step procedure. For the synthesis of the compounds, as the first step, 4-chloro-3-nitrobenzonitrile was reacted with cyclohexylamine in dimethyl formamide. Imidate esters (compound 2) were then prepared with absolute ethanol saturated with dry HCl gas. These imidate esters which were not too stable were converted to compound 3 by passing ammonia gas through ethanol. At the Pd / C catalyst, the nitro group is reduced to the amine group (compound 4). Finally, various aldehyde derivatives were reacted with sodium metabisulfite addition products to give compound 5-20. Melting points were determined on a Buchi B-540 melting point apparatus in open capillary tubes and are uncorrected. Elemental analyses were done a Leco CHNS 932 elemental analyzer. 1H-NMR and 13C-NMR spectra were recorded on a Varian Mercury 400 MHz spectrometer using DMSO-d6. Mass spectra were acquired on a Waters Micromass ZQ using the ESI(+) method. The structures of them were supported by spectral data. The 1H-NMR, 13C NMR and mass spectra and elemental analysis results agree with those of the proposed structures. Antimicrobial activity studies of the synthesized compounds are under the investigation.

Keywords: benzimidazoles, synthesis, structure elucidation, antimicrobial

Procedia PDF Downloads 134

Authors: Shekher Kummari, V. Sunil Kumar, K. Vengatajalabathy Gobi

Abstract:

A simple, cost-effective, reusable and reagent-free electrochemical biosensor is developed with functionalized multiwall carbon nanotube paste electrode (f-CNTPE) for the sensitive and selective determination of the important chemotherapeutic drug methotrexate (MTX), which is widely used for the treatment of various cancer and autoimmune diseases. The electrochemical response of the fabricated electrode towards the detection of MTX is examined by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV). CV studies have shown that f-CNTPE electrode system exhibited an excellent electrocatalytic activity towards the oxidation of MTX in phosphate buffer (0.2 M) compared with a conventional carbon paste electrode (CPE). The oxidation peak current is enhanced by nearly two times in magnitude. Applying the DPV method under optimized conditions, a linear calibration plot is achieved over a wide range of concentration from 4.0×10⁻⁷ M to 5.5×10⁻⁶ M with the detection limit 1.6×10⁻⁷ M. further, by applying the SWV method a parabolic calibration plot was achieved starting from a very low concentration of 1.0×10⁻⁸ M, and the sensor could detect as low as 2.9×10⁻⁹ M MTX in 10 s and 10 nM were detected in steady state current-time analysis. The f-CNTPE shows very good selectivity towards the specific recognition of MTX in the presence of important biological interference. The electrochemical biosensor detects MTX in-vitro directly from pharmaceutical sample, undiluted urine and human blood serum samples at a concentration range 5.0×10⁻⁷ M with good recovery limits.

Keywords: amperometry, electrochemical detection, human blood serum, methotrexate, MWCNT, SWV

Procedia PDF Downloads 288

Authors: Si Yin Tee

Abstract:

Bimetallic nanostructures have received tremendous interests as a new class of nanomaterials which may have better technological usefulness with distinct properties from those of individual atoms and molecules or bulk matter. They excelled over the monometallic counterparts because of their improved electronic, optical and catalytic performances. The properties and the applicability of these bimetallic nanostructures not only depend on their size and shape, but also on the composition and their fine structure. These bimetallic nanostructures are potential candidates for bio-applications such as biosensing, bioimaging, biodiagnostics, drug delivery, targeted therapeutics, and tissue engineering. Herein, gold-incorporated copper (Cu/Au) nanostructures were synthesized through the controlled disproportionation of Cu⁺-oleylamine complex at 220 ºC to form copper nanowires and the subsequent reaction with Au³⁺ at different temperatures of 140, 220 and 300 ºC. This is to achieve their synergistic effect through the combined use of the merits of low-cost transition and high-stability noble metals. Of these Cu/Au nanostructures, Cu/Au nanotubes display the best performance towards electrochemical non-enzymatic glucose sensing, originating from the high conductivity of gold and the high aspect ratio copper nanotubes with high surface area so as to optimise the electroactive sites and facilitate mass transport. In addition to high sensitivity and fast response, the Cu/Au nanotubes possess high selectivity against interferences from other potential interfering species and excellent reproducibility with long-term stability. By introducing gold into copper nanostructures at a low level of 3, 1 and 0.1 mol% relative to initial copper precursor, a significant electrocatalytic enhancement of the resulting bimetallic Cu/Au nanostructures starts to occur at 1 mol%. Overall, the present fabrication of stable Cu/Au nanostructures offers a promising low-cost platform for sensitive, selective, reproducible and reusable electrochemical sensing of glucose.

Keywords: bimetallic, electrochemical sensing, glucose oxidation, gold-incorporated copper nanostructures

Procedia PDF Downloads 496

Authors: S. Jaramillo, Y. Montoya, W. Agudelo, J. Bustamante

Abstract:

Cardiovascular diseases (CVD) are related to affectations of the heart and blood vessels, within these are pathologies such as coronary or peripheral heart disease, caused by the narrowing of the vessel wall (atherosclerosis), which is related to the accumulation of Low-Density Lipoproteins (LDL) in the arterial walls that leads to a progressive reduction of the lumen of the vessel and alterations in blood perfusion. Currently, the main therapeutic strategy for this type of alteration is drug treatment with statins, which inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), responsible for modulating the rate of cholesterol production and other isoprenoids in the mevalonate pathway. This enzyme induces the expression of LDL receptors in the liver, increasing their number on the surface of liver cells, reducing the plasma concentration of cholesterol. On the other hand, when the blood vessel presents stenosis, a surgical procedure with vascular implants is indicated, which are used to restore circulation in the arterial or venous bed. Among the materials used for the development of vascular implants are Dacron® and Teflon®, which perform the function of re-waterproofing the circulatory circuit, but due to their low biocompatibility, they do not have the ability to promote remodeling and tissue regeneration processes. Based on this, the present research proposes the development of a hydrolyzed collagen and polyethylene oxide electrospun membrane reinforced with medium and high-intensity statins, so that in future research it can favor tissue remodeling processes from its microarchitecture.

Keywords: atherosclerosis, medium and high-intensity statins, microarchitecture, electrospun membrane

Procedia PDF Downloads 107

Authors: Mehrnaz Mostafavi, Alireza Azani, Mahtab Shabani, Fatemeh Ghafari

Abstract:

While filled with promise and wonder, space exploration also presents significant challenges, one of the foremost being the threat of cosmic radiation to astronaut health. Recent advancements in assessing these risks and developing protective strategies have shed new light on this issue. Cosmic radiation encompasses a variety of high-energy particles originating from sources like solar particle events, galactic cosmic rays, and cosmic rays from beyond the solar system. These particles, composed of protons, electrons, and heavy ions, pose a substantial threat to human health in space due to the lack of Earth's protective atmosphere and magnetic field. Researchers have made significant progress in assessing the risks associated with cosmic radiation exposure. By employing advanced dosimetry techniques and conducting biological studies, they have gained insights into how cosmic radiation affects astronauts' health, including increasing the risk of cancer and radiation sickness. This research has led to personalized risk assessment methods tailored to individual astronaut profiles. Distinctive protection strategies have been proposed to combat the dangers of cosmic radiation. These include developing spacecraft shielding materials and designs to enhance radiation protection. Additionally, researchers are exploring pharmacological interventions such as radioprotective drugs and antioxidant therapies to mitigate the biological effects of radiation exposure and preserve astronaut well-being. The findings from recent research have significant implications for the future of space exploration. By advancing our understanding of cosmic radiation risks and developing effective protection strategies, we pave the way for safer and more sustainable human missions beyond Earth's orbit. This is especially crucial for long-duration missions to destinations like Mars, where astronauts will face prolonged exposure to cosmic radiation. In conclusion, recent research has marked a milestone in addressing the challenges posed by cosmic radiation in space exploration. By delving into the complexities of cosmic radiation exposure and developing innovative protection strategies, scientists are ensuring the health and resilience of astronauts as they venture into the vast expanse of the cosmos. Continued research and collaboration in this area are essential for overcoming the cosmic radiation challenge and enabling humanity to embark on new frontiers of exploration and discovery in space.

Keywords: Space exploration, cosmic radiation, astronaut health, risk assessment, protective strategies

Procedia PDF Downloads 10

Authors: Samir Kumar Pal

Abstract:

Background: Targeted rapid degradation of bilirubin has the potential to thwart incipient bilirubin encephalopathy. Uncontrolled hyperbilirubinemia is a potential problem in developing countries, including India, because of the lack of reliable healthcare institutes for conventional phototherapy. In India, most of the rural subjects duel in the exchange limit during transport, leading to a risk of kernicterus when they arrive at the treatment centre. Thus, an alternative pharmaceutical agent is needed for the hours. Objective: Exploration of a distinct therapeutic strategy for the control of neonatal hyperbilirubinemia compared to conventional phototherapy in a clinical setting. Method: We synthesized, characterized and investigated a spinel-structured Manganese citrate nanocomplex (C-Mn₃O₄ NC, the nanodrug) along with conventional phototherapy in neonatal subjects. We have also observed BIND scores in order to assess neurological dysfunctions. Results: Our observational study clearly reveals that the rate of declination of bilirubin in neonatal subjects with nanodrug oral administration and phototherapy is faster compared to that in the case of phototherapy only. The associated neural dysfunctions were also found to be significantly lower in the case of combined therapy. Conclusion: This study demonstrates that combined therapy works better than conventional phototherapy only for the control of hyperbilirubinemia. We have observed that a significant portion of neonatal subjects requiring blood exchange has been prevented with the combined therapeutic strategy. Further compilation of a drug-safety-dossier is warranted to translate this novel therapeutic chemo preventive approach to clinical settings.

Keywords: nanodrug, nanoparticle, Neonatal hyperbilirubinemia, alternative to phototherapy, redox modulation, redox medicine

Procedia PDF Downloads 30

Authors: M. Sangeetha, D. Chamundeeswari, C. Saravanababu, C. Rose, V. Gopal

Abstract:

Rheumatoid arthritis (RA) is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis that leads to joint destruction, which is responsible for the deformity and disability. Despite improvements in the treatment of RA over the past decade, there still is a need for new therapeutic agents that are efficacious, less expensive, and free of severe adverse reactions. The present study aimed to investigate role of inflammatory markers in arthritic rats treated with ethanolic bark extract of Albizia procera. The protective effect of ethanolic bark extract of Albizia procera against complete Freund’s adjuvant (CFA) induced arthritis in rats. Arthritis was induced by an intradermal injection of 0.1 ml FCA in the foot pad of left hind limb of rats. ETBE (100 and 200 mg/kg b.wt./p.o) and the reference drug diclofenac (25 mg/kg b.wt./p.o) were administered to arthritic rats. Paw volume was measured for all the animals before inducing arthritis and thereafter once in seven days by using plethysmometer for 42 days. Gene expression of inflammatory markers such as IL-1β and IL-10 were investigated in paw tissues. Up regulation of IL-1β and Down regulation IL-10 were observed in CFA injected rats when compared to normal rats. ETBE attenuated these alterations dose dependently when compared to the vehicle treated rats. These results provide insights into the mechanism of anti-arthritic activity, and unravel potential therapeutic use of Albizia procera in arthritis.

Keywords: CFA-Complete Freund’s adjuvant, ETBE – ethanolic bark extract, IL- interleukins, RA-rheumatoid arthritis

Procedia PDF Downloads 256

Authors: Martin Cai, Khadijah B. Hashim, Leng Leo, Edmund F. Tian

Abstract:

Analysis of traditional Chinese medicinal (TCM) supplements has always been a laborious task, particularly in the case of multi‐ingredient formulations. Traditionally, herbal extracts are analysed using one or few markers compounds. In the recent years, however, pharmaceutical companies are introducing health supplements of TCM active ingredients to cater to the needs of consumers in the fast-paced society in this age. As such, new problems arise in the aspects of composition identification as well as quality analysis. In most cases of products or supplements formulated with multiple TCM herbs, the chemical composition, and nature of each raw material differs greatly from the others in the formulation. This results in a requirement for individual analytical processes in order to identify the marker compounds in the various botanicals. Thin-layer Chromatography (TLC) is a simple, cost effective, yet well-regarded method for the analysis of natural products, both as a Pharmacopeia-approved method for identification and authentication of herbs, and a great analytical tool for the discovery of chemical compositions in herbal extracts. Recent technical advances introduced High-Performance TLC (HPTLC) where, with the help of automated equipment and improvements on the chromatographic materials, both the quality and reproducibility are greatly improved, allowing for highly standardised analysis with greater details. Here we report an industrial consultancy project with ONI Global Pte Ltd for the analysis of LAC Liver Protector, a TCM formulation aimed at improving liver health. The aim of this study was to identify 4 key components of the supplement using HPTLC, following protocols derived from Chinese Pharmacopeia standards. By comparing the TLC profiles of the supplement to the extracts of the herbs reported in the label, this project proposes a simple and cost-effective analysis of the presence of the 4 marker compounds in the multi‐ingredient formulation by using 4 different HPTLC methods. With the increasing trend of small and medium-sized enterprises (SMEs) bringing natural products and health supplements into the market, it is crucial that the qualities of both raw materials and end products be well-assured for the protection of consumers. With the technology of HPTLC, science can be incorporated to help SMEs with their quality control, thereby ensuring product quality.

Keywords: traditional Chinese medicine supplement, high performance thin layer chromatography, active ingredients, product quality

Procedia PDF Downloads 252

Authors: Benchouala Amira, Bojic Clement, Poupin Pascal, Cossu Leguille-carole

Abstract:

The objective of this study is to evaluate in vitro the cytotoxic and androgenic potential of several antifungal molecules (amphotericin B, econazole, ketoconazole and miconazole) on MDA-Kb2 cell lines. This biological model is an effective tool for the detection of endocrine disruptors because it responds well to the main agonist of the androgen receptor (testosterone) and also to an antagonist: flutamide. The cytotoxicity of each chemical compound tested was measured using an MTT assay (tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) which measures the activity of the reductase function of mitochondrial succinate dehydrogenase enzymes of cultured cells. This complementary cytotoxicity test is essential to ensure that the effects of reduction in luminescence intensity observed during androgenic tests are only attributable to the anti-androgenic action of the compounds tested and not to their possible cytotoxic properties. Tests of the androgenic activity of antifungals show that these compounds do not have the capacity to induce transcription of the luciferase gene. These compounds do not exert an androgenic effect on MDA-Kb2 cells in culture for the environmental concentrations tested. The addition of flutamide for the same tested concentrations of antifungal molecules reduces the luminescence induced by amphotericin B, econazole and miconazole, which is explained by a strong interaction of these molecules with flutamide which may have a greater toxic effect than when tested alone. The cytotoxicity test shows that econazole and ketoconazole can cause cell death at certain concentrations tested. This cell mortality is perhaps induced by a direct or indirect action on deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or proteins necessary for cell division.

Keywords: cytotoxicity, androgenic potential, antifungals, MDA-Kb2

Procedia PDF Downloads 11

Authors: Ibrahim Iddrisu, Joseph Ayariga, Junhuan Xu, Ayomide Adebanjo, Boakai K. Robertson, Michelle Samuel-Foo, Olufemi Ajayi

Abstract:

The rise of antimicrobial resistance is a global public health crisis that threatens the effective control and prevention of infections. Due to the emergence of pan drug-resistant bacteria, most antibiotics have lost their efficacy. Bacteriophages or their components are known to target bacterial cell walls, cell membranes, and lipopolysaccharides (LPS) and hydrolyze them. Bacteriophages, being the natural predators of pathogenic bacteria, are inevitably categorized as ‘human friends’, thus fulfilling the adage that ‘the enemy of my enemy is my friend’. Leveraging on their lethal capabilities against pathogenic bacteria, researchers are searching for more ways to overcome the current antibiotic resistance challenge. In this study, we expressed and purified epsilon 34 phage tail spike protein (E34 TSP) from the E34 TSP gene, then assessed the ability of this bacteriophage protein in the killing of two CBD-resistant strains of Salmonella spp. We also assessed the ability of the tail spike protein to cause bacteria membrane disruption and dehydrogenase depletion. We observed that the combined treatment of CBD-resistant strains of Salmonella with CBD and E34 TSP showed poor killing ability, whereas the mono treatment with E34 TSP showed considerably higher killing efficiency. This study demonstrates that the inhibition of the bacteria by E34 TSP was due in part to membrane disruption and dehydrogenase inactivation by the protein. The results of this work provide an interesting background to highlight the crucial role phage proteins such as E34 TSP could play in pathogenic bacterial control.

Keywords: cannabidiol, resistance, Salmonella, antimicrobials, phages

Procedia PDF Downloads 31

Authors: Sushil Kumar Singh, Ashok Kumar, Ankit Ganeshpurkar, Ravi Singh, Devendra Kumar

Abstract:

In spectrum of neurodegenerative diseases, Alzheimer’s disease (AD) is characterized by the presence of amyloid β plaques and neurofibrillary tangles in the brain. It results in cognitive and memory impairment due to loss of cholinergic neurons, which is considered to be one of the contributing factors. Donepezil, an acetylcholinesterase (AChE) inhibitor which also inhibits butyrylcholinesterase (BuChE) and improves the memory and brain’s cognitive functions, is the most successful and prescribed drug to treat the symptoms of AD. The present work is based on designing of the selective BuChE inhibitors using computational techniques. In this work, machine learning models were trained using classification algorithms followed by screening of diverse chemical library of compounds. The various molecular modelling and simulation techniques were used to obtain the virtual hits. The amide derivatives of 4-(phenylsulfonamido) benzoic acid were synthesized and characterized using 1H & 13C NMR, FTIR and mass spectrometry. The enzyme inhibition assays were performed on equine plasma BuChE and electric eel’s AChE by method developed by Ellman et al. Compounds 31, 34, 37, 42, 49, 52 and 54 were found to be active against equine BuChE. N-(2-chlorophenyl)-4-(phenylsulfonamido)benzamide and N-(2-bromophenyl)-4-(phenylsulfonamido)benzamide (compounds 34 and 37) displayed IC50 of 61.32 ± 7.21 and 42.64 ± 2.17 nM against equine plasma BuChE. Ortho-substituted derivatives were more active against BuChE. Further, the ortho-halogen and ortho-alkyl substituted derivatives were found to be most active among all with minimal AChE inhibition. The compounds were selective toward BuChE.

Keywords: Alzheimer disease, butyrylcholinesterase, machine learning, sulfonamides

Procedia PDF Downloads 116

Authors: H. Aldewachi, M. Hines, M. McCulloch, N. Woodroofe, P. Gardiner

Abstract:

DPP-IV is an enzyme whose expression is affected in a variety of diseases, therefore, has been identified as possible diagnostic or prognostic marker for various tumours, immunological, inflammatory, neuroendocrine, and viral diseases. Recently, DPP-IV enzyme has been identified as a novel target for type II diabetes treatment where the enzyme is involved. There is, therefore, a need to develop sensitive and specific methods that can be easily deployed for the screening of the enzyme either as a tool for drug screening or disease marker in biological samples. A variety of assays have been introduced for the determination of DPP-IV enzyme activity using chromogenic and fluorogenic substrates, nevertheless these assays either lack the required sensitivity especially in inhibited enzyme samples or displays low water solubility implying difficulty for use in vivo samples in addition to labour and time-consuming sample preparation. In this study, novel strategies based on exploiting the high extinction coefficient of gold nanoparticles (GNPs) are investigated in order to develop fast, specific and reliable enzymatic assay by investigating synthetic peptide sequences containing a DPP IV cleavage site and coupling them to GNPs. The DPP IV could be detected by colorimetric response of peptide capped GNPs (P-GNPS) that could be monitored by a UV-visible spectrophotometer or even naked eyes, and the detection limit could reach 0.01 unit/ml. The P-GNPs, when subjected to DPP IV, showed excellent selectivity compared to other proteins (thrombin and human serum albumin) , which led to prominent colour change. This provided a simple and effective colorimetric sensor for on-site and real-time detection of DPP IV.

Keywords: gold nanoparticles, synthetic peptides, colorimetric detection, DPP-IV enzyme

Procedia PDF Downloads 279

Authors: Rajnarayan Damor, Gayatri Swarnakar

Abstract:

Fasciola gigantica are present in the biliary ducts of liver and gall bladder of domestic buffaloes. They are very harmful and causes significant lose to live stock owners, on account of poor growth and lower productivity of domestic buffaloes. Synthetic veterinary drugs have been used to eliminate parasites from cattle but these drugs are unaffordable and inaccessible for poor cattle farmers. The in vitro anthelmintic effect of Citrullus colocynthis fruit extract against Fasciola gigantica parasites were observed by light and scanning electron microscopy. Fruit extracts of C. colocynthis exhibit highest mortality 100% at 50 mg/ml in 15th hour of exposure. The oral and ventral sucker appeared to be slightly more swollen than control and synthetic drug albendazole. The tegument showed submerged spines by the swollen tegument around them. The tegument of the middle region showed deep furrows, folding and submerged spines which either lied very flat against the surface or had become submerged in the tegument by the swollen tegument around them leaving deep furrows. Posterior region showed with deep folding in the tegument, completely disappearance of spines and swelling of the tegument led to completely submerged spines leaving spine socket. The present study revealed that fruit extracts of Citrullus colocynthis found to be potential sources for novel anthelmintic and justify their ethno-veterinary use.

Keywords: anthelmintic, buffalo, Citrullus colocynthis, Fasciola gigantica, mortality, tegument

Procedia PDF Downloads 212

Authors: Fisseha Shiferie (Bpharm, Mpharm)

Abstract:

Diarrhea is a common gastrointestinal disorder characterized by an increase in stool frequency and a change in stool consistency. Inspite of the availability of many drugs as antidiarrheal agents, the search for a drug with affordable cost and better efficacy is essential to overcome diarrheal problems. The root extract of Echinops kebericho, is used by traditional practitioners for the treatment of diarrhea. However, the scientific basis for this usage has not been yet established. The purpose of the present study was to evaluate the antidiarrheal and spasmolytic activities of the aqueous extract of the roots of E. kebericho in rodents and isolated guinea-pig ileum preparations. In the castor oil induced intestinal transit test, E. kebericho produced a significant (p < 0.01) dose dependent decrease in propulsion with peristaltic index values of 45.05±3.3, 42.71±2.25 and 33.17±3.3%, respectively at doses of 100, 200 and 400 mg/kg compared with 63.43±7.3% for control. In the castor oil-induced diarrhea test, the mean defecation was reduced from 1.81±0.18 to 0.99 ± 0.21 compared with 2.59 ±0.81 for control. The extract (at doses stated above) significantly decreased the volume of intestinal fluid secretion induced by castor oil (2.31±0.1 to 2.01±0.2) in relation to 3.28±0.3 for control. When tested on a guinea-pig ileum, root extract of Echinops kebericho exhibited a dose dependent spasmolytic effect, 23.07 % being its highest inhibitory effect. The results obtained in this study give some scientific support to the use of Echinops kebericho as an antidiarrheal agent due to its inhibitory effects on the different diarrheal parameters used in this study.

Keywords: antidiarrheal activity, E. kebericho, traditional medicine, diarrhea, enteropooling, and intestinal transit

Procedia PDF Downloads 285

Authors: Alaa E. El-sisi, Sherin Zakaria

Abstract:

Rebamipide is an antiulcer drug with unique properties such as anti-inflammatory action. It induces endogenous prostaglandin e2 (PGE2). PGE2 is considered as a potent physiological suppressor of liver fibrosis. Aim of study: This study investigated the effect of rebamipide on hepatic fibrosis. Material and Method: Hepatic fibrosis was induced by intraperitoneal injections (IP) injection of CCl4 (0.45 mL/kg) in corn oil 1:5 twice a week for 4 weeks. Rats were divided into four groups as follow: Group 1 treated with CCL4 only, group 2 and 3 treated with CCL4 and rebamipide 60 mg/kg/day (group2) or 100 mg/kg/day (group3), and the fourth group was considered as control group and treated with vehicles. ALT, AST, and Bilirubin were assayed in serum. Antioxidant markers such as malondialdhyde (MDA) and superoxide dismutase (SOD) and fibrotic markers such as hyaluronic acid (HA) and procollagen-III (procol-III) were evaluated in liver tissues. IL-10 as well as PGE2 were also assayed in liver tissues. Pathologic changes in the liver were detected by hematoxylin and eosin staining. Collagen precipitation in liver tissues was visualized using masson trichrom stain. Results: Rebamipide inhibit CCL4 induced increase in ALT and AST significantly (p < 0.05). Rebamipide exerted an antioxidant effect as it inhibits CCL4 induced increased MDA level and decreased SOD activity. Fibrotic markers assay revealed that repamipide (60 or 100 mg/kg/day) decreased the level of procol-III and HA compared to CCl4 (p < 0.05). Oral administration of Rebamipide was associated with a significant increase (p < 0.05) of PGE2 and IL-10. Rebamipide especially at the dose of (100 mg/kg/day) restores liver histology structure and abolish collagen precipitation in liver tissues. Conclusion: Rebamipide retards hepatic fibrosis induced by CCL4 may be through the induction of PGE2 level.

Keywords: fibrotic markers, hepatic fibrosis, PGE2, rebamipide

Procedia PDF Downloads 462

Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

Abstract:

Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

Procedia PDF Downloads 147

Authors: Eman M. Morgan, Hayam M. Lotfy, Yasmin M. Fayez, Mohamed Abdelkawy, Engy Shokry

Abstract:

Two simple, selective, economic, safe, accurate, precise and environmentally friendly methods were developed and validated for the quantitative determination of valaciclovir (VAL) in the presence of its related substances R1 (acyclovir), R2 (guanine) in bulk powder and in the commercial pharmaceutical product containing the drug. Method A is a colorimetric method where VAL selectively reacts with ferric hydroxamate and the developed color was measured at 490 nm over a concentration range of 0.4-2 mg/mL with percentage recovery 100.05 ± 0.58 and correlation coefficient 0.9999. Method B is a reversed phase ultra performance liquid chromatographic technique (UPLC) which is considered superior in technology to the high-performance liquid chromatography with respect to speed, resolution, solvent consumption, time, and cost of analysis. Efficient separation was achieved on Agilent Zorbax CN column using ammonium acetate (0.1%) and acetonitrile as a mobile phase in a linear gradient program. Elution time for the separation was less than 5 min and ultraviolet detection was carried out at 256 nm over a concentration range of 2-50 μg/mL with mean percentage recovery 100.11±0.55 and correlation coefficient 0.9999. The proposed methods were fully validated as per International Conference on Harmonization specifications and effectively applied for the analysis of valaciclovir in pure form and tablets dosage form. Statistical comparison of the results obtained by the proposed and official or reported methods revealed no significant difference in the performance of these methods regarding the accuracy and precision respectively.

Keywords: hydroxamic acid, related substances, UPLC, valaciclovir

Procedia PDF Downloads 223

Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

Abstract:

The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

Procedia PDF Downloads 52