Search results for: drug targeting

Authors: U. L. Fulco, E. L. Albuquerque, José X. Lima Neto, L. R. Da Silva

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The binding of the nonsteroidal anti-inflammatory drug ibuprofen (IBU) to human serum albumin (HSA) is investigated using density functional theory (DFT) calculations within a fragmentation strategy. Crystallographic data for the IBU–HSA supramolecular complex shows that the ligand is confined to a large cavity at the subdomain IIIA and at the interface between the subdomains IIA and IIB, whose binding sites are FA3/FA4 and FA6, respectively. The interaction energy between the IBU molecule and each amino acid residue of these HSA binding pockets was calculated using the Molecular Fractionation with Conjugate Caps (MFCC) approach employing a dispersion corrected exchange–correlation functional. Our investigation shows that the total interaction energy of IBU bound to HSA at binding sites of the fatty acids FA3/FA4 (FA6) converges only for a pocket radius of at least 8.5 °A, mainly due to the action of residues Arg410, Lys414 and Ser489 (Lys351, Ser480 and Leu481) and residues in nonhydrophobic domains, namely Ile388, Phe395, Phe403, Leu407, Leu430, Val433, and Leu453 (Phe206, Ala210, Ala213, and Leu327), which is unusual. Our simulations are valuable for a better understanding of the binding mechanism of IBU to albumin and can lead to the rational design and the development of novel IBU-derived drugs with improved potency.

Keywords: ibuprofen, human serum albumin, density functional theory, binding energies

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Authors: Asma Abdullah, Awais Khan, Reem Al-Ghumlasi, Pritam Kumari, Yasir Nawaz

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Introduction: This study verified the potential applications of two Oblique Wing configurations that were initiated by the Germans Aerodynamicists during the WWII. Due to the end of the war, this project was not completed and in this research is targeting the revival of German Oblique biplane configuration. The research draws upon the use of two Oblique wings mounted on the top and bottom of the fuselage through a single pivot. The wings are capable of sweeping at different angles ranging from 0° at takeoff to 60° at cruising Altitude. The top wing, right half, behaves like a forward swept wing and the left half, behaves like a backward swept wing. Vice Versa applies to the lower wing. This opposite deflection of the top and lower wing cancel out the rotary moment created by each wing and the aircraft remains stable. Problem to better understand or solve: The purpose of this research is to investigate the potential of achieving improved aerodynamic performance and efficiency of flight at a wide range of sweep angles. This will help examine the most accurate value for the sweep angle at which the aircraft will possess both stability and better aerodynamics. Explaining the methods used: The Aircraft configuration is designed using Solidworks after which a series of Aerodynamic prediction are conducted, both in the subsonic and the supersonic flow regime. Computations are carried on Ansys Fluent. The results are then compared to theoretical and flight data of different Supersonic fighter aircraft of the same category (AD-1) and with the Wind tunnel testing model at subsonic speed. Results: At zero sweep angle, the aircraft has an excellent lift coefficient value with almost double that found for fighter jets. In acquiring of supersonic speed the sweep angle is increased to maximum 60 degrees depending on the mission profile. General findings: Oblique biplane can be the future fighter jet aircraft because of its high value performance in terms of aerodynamics, cost, structural design and weight.

Keywords: biplane, oblique wing, sweep angle, supercritical airfoil

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

Procedia PDF Downloads 122

Authors: M. A. Ahmed, N. Basha, I. V. Nsahlai

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This study determined the effectiveness of selected anthementics (Ivermectin 1% (IVM), Closantel 7.5% (CST) and a combination Abamectin 0.08% and Praziquantel 1.5% (CAP) currently being used in SA. Gender, initial egg per gram (EPG) and initial live weight aided in blocking animals into groups, each group was randomly treated with one of four drug treatments comprising: the untreated control (D0), IVM, CST, and CAP. Animals grazed throughout on infested pasture. Rectal faeces were collected on days 0, 7, 14, and 21 for determining EPG. Faeces were mixed per group and incubated to identify and determine the abundance of larval forms of Haemonchus, Trichostrongylus, Strongyloides, Namatodirus, and Cooperia species. Differences between treatments changed over time. On day7 IVM, CST, and CAP depressed EPG to 0.66, 0.37 and 0.80 of their respective starting values whilst EPG increased 1.39 times for D0. Thereafter, EPG increased consistently for all drugs; CST recorded the lowest values. Haemonchus, Trichostrongylus, Strongyloides, Namatodirus and Coperia species contributed respectively 60%, 30%, 6%, 3%, and 1% of the larval forms on day 0; and 78%, 8%, 11%, 1%, 2% on day 21. Larval forms increased for Haemonchus species but decreased for Trichostrongylus species over time. Closantel was the most effective dewormer. Haemonchus Spp. were least affected whilst Trichostrongylus Spp. were the most affect by all drugs.

Keywords: anthementics, faecal egg count, L3 larvae, sheep

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Authors: Abhishekkumar Ramasamy, Parameshwari

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Chitosan is the deacyelitated derivative of chitin, the second most abundant biopolymer just after cellulose. Without doubt, its biomedical usages have gained more importance among the vast variety of chitosan applications owing to its good biocompatibility and biodegradability. In recent years, particular interest has been devoted to chitosan hydrogels as a promising alternative in competition with conventional sutures or bioadhesives. Different parameters such as acid type and concentration, and degree of deacetylation (DD%) of chitosan, were altered to modify hydrogel properties including viscosity, pH, cohesive strength, and tissue bioadhesiveness. In the current work, we have investigated the effectiveness of chitosan hydrogel encapsulated with tanexamic acid to stop bleeding. Chitosan film was obtained with solubilization of chitosan powder in aqueous acidic media. In vivo experiments have been conducted on rat and rabbit models that provide a convenient way to evaluate the efficacy of prepared samples. The arteries vein was punctured on the hind limb of the rat and the gauze was been applied on the punchered area. Bioadhesive strength as well as irritant effects were discussed. Samples with higher degree of deacetylation, including Chs-16 and Chs-19 that were dissolved in lactic media showed best sealing effect.

Keywords: chitosan, biocomaptibility, biodegradability, bioadhersive, deacetylation

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Authors: Sanjaykumar R. Patel, Parth R. Kayastha

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α-lactose monohydrate is widely used in the pharmaceutical industries as an inactive substance that acts as a vehicle or a medium for a drug or other active substance. It is a byproduct of dairy industries, and the recovery of lactose from whey not only boosts the improvement of the economics of whey utilization but also causes a reduction in pollution as lactose recovery can reduce the BOD of whey by more than 80%. In the present study, levels of process parameters were kept as initial lactose concentration (30-50% w/w), sonication amplitude (20-40%), sonication time (2-6 hours), and crystallization temperature (10-20 ^oC) for the recovery of lactose in ultrasound assisted cooling crystallization. In comparison with cooling crystallization, the use of ultrasound enhanced the lactose recovery by 39.17% (w/w). The parameters were optimized for the lactose recovery using Taguchi Method. The optimum conditions found were initial lactose concentration at level 3 (50% w/w), amplitude of sonication at level 2 (40%), the sonication time at level 3 (6 hours), and crystallization temperature at level 1 (10 °C). The maximum recovery was found to be 85.85% at the optimum conditions. Sonication time and the initial lactose concentration were found to be significant parameters for the lactose recovery.

Keywords: crystallization, lactose, Taguchi method, ultrasound

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Authors: Selamat Muliadi

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This study aimed to explain conceptual the role of Zakat on sustainable economic development by Rumah Zakat. Rumah Zakat is a philanthropic institution that manages zakat and other social funds through community empowerment programs. In running the program, including economic empowerment and socio health services are designed for these recipients. Rumah Zakat's connection with the establisment of Sustainable Development Goals (SDGs) which is to help impoverished recipients economically and socially. It’s an important agenda that the government input into national development, even the region. The primary goal of Zakat on sustainable economic development, not only limited to economic variables but based on Islamic principles, has comprehensive characteristics. The characteristics include moral, material, spiritual, and social aspects. In other words, sustainable economic development is closely related to improving people’s living standard (Mustahiq). The findings provide empiricial evidence regarding the positive contribution and effectiveness of zakat targeting in reducing poverty and improve the welfare of people related with the management of zakat. The purpose of this study was to identify the role of Zakat on sustainable economic development, which was applied by Rumah Zakat. This study used descriptive method and qualitative analysis. The data source was secondary data collected from documents and texts related to the research topic, be it books, articles, newspapers, journals, or others. The results showed that the role of zakat on sustainable economic development by Rumah Zakat has been quite good and in accordance with the principle of Islamic economics. Rumah Zakat programs are adapted to support intended development. The contribution of the productive program implementation has been aligned with four goals in the Sustainable Development Goals, i.e., Senyum Juara (Quality Education), Senyum Lestari (Clean Water and Sanitation), Senyum Mandiri (Entrepreneur Program) and Senyum Sehat (Free Maternity Clinic). The performance of zakat in the sustainable economic empowerment community at Rumah Zakat is taking into account dimensions such as input, process, output, and outcome.

Keywords: Zakat, social welfare, sustainable economic development, charity

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Authors: Amine Mezni, Merfat Algethami, Ali Aldalbahi, Arwa Alrooqi, Abel Santos, Dusan Losic, Sarah Alharthi, Tariq Altalhi

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In situ synthesis of carbon nanotubes featuring different diameters (10-200 nm), lengths (1 to 100 µm) and periodically nanostructured shape was performed in a custom designed chemical vapor deposition (CVD) system using nanoporous anodic alumina (NAA) under different conditions. The morphology of the resulting CNTs/NAA composites and free-standing CNTs were analyzed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The results confirm that highly ordered arrays of CNTs with precise control of nanotube dimensions in the range 20-200 nm with tube length in the range < 1 µm to > 100 μm and with periodically shaped morphology can be fabricated using nanostructured NAA templates prepared by anodization. This technique allows us to obtain tubes open at one / both ends with a uniform diameter along the pore length without using any metal catalyst. Our finding suggests that this fabrication strategy for designing new CNTs membranes and structures can be significant for emerging applications as molecular separation/transport, optical biosensing, and drug delivery.

Keywords: carbon nanotubes, CVD approach, composites membrane, nanoporous anodic alumina

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Authors: Slah Eddine Ben Fadhel

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Despite the development of new pedagogic methods, current teaching practices put more emphasis on the learning products than on the processes learners deploy. In school syllabi, for instance, very little time is devoted to both the explanation and analysis of strategies aimed at resolving problems by means of targeting students’ metacognitive procedures. Within a cognitive framework, teaching/learning contexts are conceived of in terms of cognitive, metacognitive and affective activities intended for the treatment of information. During these activities, learners come to develop an array of knowledge and strategies which can be subsumed within an active and constructive process. Through the investigation of strategies and metacognition concepts, the purpose is to reflect upon the modalities at the heart of the learning process and to demonstrate, similarly, the inherent significance of a cognitive approach to learning. The scope of this paper is predicated on a study where the population is a group of 76 primary school pupils who experienced difficulty with learning French. The population was divided into two groups: the first group was submitted during three months to a strategy-based training to learn French. All through this phase, the teachers centred class activities round making learners aware of the strategies the latter deployed and geared them towards appraising the steps these learners had themselves taken by means of a variety of tools, most prominent among which is the logbook. The second group was submitted to the usual learning context with no recourse whatsoever to any strategy-oriented tasks. The results of both groups point out the improvement of linguistic competences in the French language in the case of those pupils who were trained by means of strategic procedures. Furthermore, this improvement was noted in relation with the native language (Arabic), a fact that tends to highlight the importance of the interdisciplinary investigation of (meta-)cognitive strategies. These results show that strategic learning promotes in pupils the development of a better awareness of their own processes, which contributes to improving their general linguistic competences.

Keywords: constructive approach, cognitive strategies, metacognition, learning

Procedia PDF Downloads 207

Authors: Abdelhadi Adam Salih Denei

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Silver nanoparticles (AgNPs) have been used in cancer therapy, and the area of nanomedicine has made unheard-of strides in recent years. A thorough summary of the development and assessment of AgNPs for their possible use in the fight against cancer is the goal of this review. Targeted delivery methods have been designed to optimise therapeutic efficacy by using AgNPs' distinct physicochemical features, such as their size, shape, and surface chemistry. Firstly, the study provides an overview of the several synthesis routes—both chemical and green—that are used to create AgNPs. Natural extracts and biomolecules are used in green synthesis techniques, which are becoming more and more popular since they are biocompatible and environmentally benign. It is next described how synthesis factors affect the physicochemical properties of AgNPs, emphasising how crucial it is to modify these parameters for particular therapeutic uses. An extensive analysis is conducted on the anticancer potential of AgNPs, emphasising their capacity to trigger apoptosis, impede angiogenesis, and alter cellular signalling pathways. The analysis also investigates the potential benefits of combining AgNPs with currently used cancer treatment techniques, including radiation and chemotherapy. AgNPs' safety profile for use in clinical settings is clarified by a comprehensive evaluation of their cytotoxicity and biocompatibility.

Keywords: silver nanoparticles, cancer, nanocarrier system, targeted delivery

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Authors: Jiangang Shen

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Olfactory dysfunction is a common symptom companied by anxiety- and depressive-like behaviors in depressive patients. Chronic stress triggers hormone responses and inhibits the proliferation and differentiation of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ)-olfactory bulb (OB), contributing to depressive behaviors and olfactory dysfunction. However, the cellular signaling molecules to regulate chronic stress mediated olfactory dysfunction are largely unclear. Adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPLs) are multifunctional adaptor proteins. Herein, we tested the hypothesis that APPL2 could inhibit hippocampal neurogenesis by affecting glucocorticoid receptor (GR) signaling, subsequently contributing to depressive and anxiety behaviors as well as olfactory dysfunctions. The major discoveries are included: (1) APPL2 Tg mice had enhanced GR phosphorylation under basic conditions but had no different plasma corticosterone (CORT) level and GR phosphorylation under stress stimulation. (2) APPL2 Tg mice had impaired hippocampal neurogenesis and revealed depressive and anxiety behaviors. (3) GR antagonist RU486 reversed the impaired hippocampal neurogenesis in the APPL2 Tg mice. (4) APPL2 Tg mice displayed higher GR activity and less capacity for neurogenesis at the olfactory system with lesser olfactory sensitivity than WT mice. (5) APPL2 negatively regulates olfactory functions by switching fate commitments of NSCs in adult olfactory bulbs via interaction with Notch1 signaling. Furthermore, baicalin, a natural medicinal compound, was found to be a promising agent targeting APPL2/GR signaling and promoting adult neurogenesis in APPL2 Tg mice and chronic corticosterone-induced depression mouse models. Behavioral tests revealed that baicalin had antidepressant and olfactory-improving effects. Taken together, APPL2 is a critical therapeutic target for antidepressant treatment.

Keywords: APPL2, hippocampal neurogenesis, depressive behaviors and olfactory dysfunction, stress

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Authors: N. Nwachoko, E. B. Essien, E. O. Ayalogu

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Owing to the outbreak of different diseases and microbial resistance to some available drugs, proper identification, and evaluation of plants have been encouraged. There have been claims worldwide by the traditional system that some plants possessed medicinal properties. Plants and their components have been said to be source of large amount of drugs which comprise of distinct groups such as antispasmodics, anticancer and antimicrobials. Researchers have reported that chemicals in plants are responsible for the medicinal uses of plants. Thus this study evaluated the protective effect of Aframomun chrysanthum seed aqueous extract in acetaminophen-induced liver toxicity in rats. A suspension of 750 mg/kg acetaminophen was administered once every 72 hours to induce toxicity in the rats. Oral administration of 500, 1000 and 2000 mg/kg body weight of the extract and 100 mg/kg of silymarin (reference drug) were administered for 10 days. Biochemical analysis showed significant (p < 0.05) increase in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT)and alkaline phosphatase (ALP)as well as the concentrations of albumin (ALB) and total bilirubin (T.B.) levels in rats administered with acetaminophen only. The levels of these parameters were significantly (p < 0.05) decreased in the groups pretreated with the extract.

Keywords: Aframomun chrysanthum, silymarin, hepatoprotective, toxicity

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Authors: Yong-Hui Zheng

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Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.

Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress

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Authors: Hashaam Akhtar

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IFNλR1 and IL10R2 collectively construct a heterodimer, which is an acknowledged functional receptor for all type III interferons (IFNs). Expression of IFNλR1 is highly tissue specific, which can help in making type III IFNs a drug of choice as comparable to its analogue, type I IFNs, for treating hepatitis C in the near future. Although, expression of IFNλR1 also varies with the concentration of type I IFNs, but in this study it was shown that the expression of IFNλR1 varies with the protein titers of IFN-α, IFN-λ3 and the newly discovered IFN-λ4. High dosage of IFN-α reduces the expression of IFNλR1 in HepG2 cells, which can affect the antiviral activity of type III IFNs in vivo. We premeditated an experimental strategy to differentiate monocytes into dendritic cells (DCs), type I and type II macrophages in vitro and quantified the expression of the IFNλR1 by qPCR. The exposure of newly discovered IFN-λ4 to macrophages and DCs also raised the expression of its own receptor, which shows that expression of IFN-λ4 protein in hepatitis C patient may augment type I treatment and help ease off viral titers. The results of this study may contribute in some understanding towards the mechanisms involved in the selective expression of IFNLR1 and exceptionalities associated with the receptor.

Keywords: IFNLR1, Interferon Lambda 4 (IFN-λ4), Mononuclear Phagocyte Cells (MPCs), expression

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Authors: Inaam Khalaf, Nadin M. Abdel Razeq, Hamza Alduraidi, Suhaila Halasa, Omayyah S. Nassar, Eman Al-Horani, Jumana Shehadeh, Anna Talal

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Background: Nursing researchers are responsible for generating knowledge that corresponds to national and global research priorities in order to promote, restore, and maintain the health of individuals and societies. The objectives of this scoping review of Jordanian literature are to assess the existing research on pediatric nursing in terms of evolution, authorship and collaborations, funding sources, methodologies, topics of research, and pediatric subjects' age groups so as to identify gaps in research. Methodology: A search was conducted using related keywords obtained from national and international databases. The reviewed literature included pediatric health articles published through December 2019 in English and Arabic, authored by nursing researchers. The investigators assessed the retrieved studies and extracted data using a data-mining checklist. Results: The review included 265 articles authored by Jordanian nursing researchers concerning children's health, published between 1987 and 2019; 95% were published between 2009 and 2019. The most commonly applied research methodology was the descriptive non-experimental method (76%). The main generic topics were health promotion and disease prevention (23%), chronic physical conditions (19%), mental health, behavioral disorders, and forensic issues (16%). Conclusion: The review findings identified a grave shortage of evidence concerning nursing care issues for children below five years of age, especially those between ages two and five years. The research priorities identified in this review resonate with those identified in international reports. Implications: Nursing researchers are encouraged to conduct more research targeting topics of national-level importance in collaboration with clinically involved nurses and international scholars.

Keywords: Jordan, scoping review, children health nursing, pediatric, adolescents

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Authors: Hammed Tanimowo Aiyelabegan, Oluchukwu Franklin Aladi, Mutiu Adewumi Alabi, Raliat Abimbola Aladodo, Emmanuel Oladipupo Ajani, Abdulganiyu Giwa, Esther Owolabi

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The study aimed to evaluate the inhibitory activities of ligands from Enantia chlorantha stem bark on α-amylase and α-glucosidase. In silico pharmacokinetic properties and docking scores were employed to analyse the inhibition using SwissADME and Autodock4.2, respectively. Results revealed that drug-likeness, pharmacokinetics and bioavailability radar of all the ligands except jatrorrhizine and acarbose falls within the radar according to the Lipinski rule of 5. The binding energies of the protein-ligand interactions also show that the ligand fits into the active site. The results obtained from this study show that the chemical constituents from Enantia chlorantha stem bark may bring about positive physiological changes in a patient suffering from diabetes mellitus. Further in vitro studies on diabetes cell lines and in vivo studies on the animal may validate these compounds for diabetes treatment. These phytoconstituents could help in the development of novel anti-diabetic molecules.

Keywords: diabetes mellitus, ?-amylase, ?-glucosidase, in silico, Enantia chlorantha stem bark

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Authors: Sivakumar Singaravelu, Giriprasath Ramanathan, M. D. Raja, Uma Tirichurapalli Sivagnanam

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The goal of the present study was to develop and evaluate composite film for tissue engineering application. The keratin was extracted from bovine horn and used for preparation of keratin (HK), physiologically clotted fibrin (PCF) and gelatin (G) blend films in different stoichiometric ratios (1:1:1, 1:1:2 and 1:1:3) by using solvent casting method. The composite films (HK-PCF-G) were characterized physiochemically using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and Scanning Electron Microscopy (SEM). The mechanical properties of the composite films were analyzed. The results of tensile strength show that ultimate strength and elongation were 10.72 Mpa and 4.83 MPA respectively for 1:1:3 ratio combination. The SEM image showed a slight smooth surface for 1:1:3 ratio combination compared to other films. In order to impart antibacterial activities, the composite films were loaded with Mupirocin (MP) to act against infection. The composite films acted as a suitable carrier to protect and release the drug in a controlled manner. This developed composite film would be a suitable alternative material for tissue engineering application.

Keywords: bovine horn, keratin, fibrin, gelatin, tensile strength

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Authors: Amer Elgerwi, Abdelrazzag El-Magdoub, Abubakr El-Mahmoudy

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There are many bacterial infections affecting sheep that necessitates antibiotic intervention. Amoxicillin is among commonly used antibiotics in such case for its broad spectrum of activity. However, the side alterations in blood and organ function that may be associated during or after treatment are questionable. Therefore, the aim of the present study was to assess the possible alterations in blood parameters and organ function bio markers of sheep that may occur following intramuscular injection of amoxicillin. Amoxicillin has been administered intramuscularly to 10 sheep at a dosage regimen of 7 mg/kg of body weight for 5 successive days. Two types of blood samples (with and without anticoagulant) were collected from the jugular vein pre- and post-administration of the drug. Amoxicillin significantly (P < 0.001) increased total leukocyte count and (P < 0.05) absolute eosinophilic count when compared with those of the control samples. Aspartate aminotransferase, alkaline phosphatase and cholesterol were significantly (P < 0.05) higher than the corresponding control values. In addition, amoxicillin significantly (P < 0.05) increased blood urea nitrogen and creatinine but decreased phosphorus level when compared with those of prior-administration samples. These data may indicate that although the side changes caused by amoxicillin are minor in sheep, yet the liver and kidney functions should be monitored during its usage in therapy and it should be used with care for treatment of sheep with renal and/or hepatic impairments.

Keywords: amoxicillin, biogram, haemogram, sheep

Procedia PDF Downloads 455

Authors: Xiao Yang, Ji Zhang, Yingli Song, Hui Huang, Jing Zhang, Yan Wang, Rongrong Han, Zhixuan Xiang, Lu Chen, Lingling Gao

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Aim and Objectives: To examine physical activity self-efficacy, identify its predictors, and further explore the mechanism of action among the predictors in mainland Chinese pregnant women with high risk for gestational diabetes mellitus (GDM). Background: Physical activity could protect pregnant women from developing GDM. Physical activity self-efficacy was the key predictor of physical activity. Design: A cross-sectional study was conducted from October 2021 to May 2022 in Zhengzhou, China. Methods: 252 eligible pregnant women completed the Pregnancy Physical Activity Self-efficacy Scale, the Social Support for Physical Activity Scale, the Knowledge on Physical Activity Questionnaire, the 7-item Generalized Anxiety Disorder scale, the Edinburgh Postnatal Depression Scale, and a socio-demographic data sheet. Multiple linear regression was applied to explore the predictors of physical activity self-efficacy. Structural equation modeling was used to explore the mechanism of action among the predictors. Results: Chinese pregnant women with a high risk for GDM reported a moderate level of physical activity self-efficacy. The best-fit regression analysis revealed four variables explained 17.5% of the variance in physical activity self-efficacy. Social support for physical activity was the strongest predictor, followed by knowledge of the physical activity, intention to do physical activity, and anxiety symptoms. The model analysis indicated that knowledge of physical activity could release anxiety and depressive symptoms and then increase physical activity self-efficacy. Conclusion: The present study revealed a moderate level of physical activity self-efficacy. Interventions targeting pregnant women with high risk for GDM need to include the predictors of physical activity self-efficacy. Relevance to clinical practice: To facilitate pregnant women with high risk for GDM to engage in physical activity, healthcare professionals may find assess physical activity self-efficacy and intervene as soon as possible on their first antenatal visit. Physical activity intervention programs focused on self-efficacy may be conducted in further research.

Keywords: physical activity, gestational diabetes, self-efficacy, predictors

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Authors: Alyaa Ahmed Farid, Aida Ismail, Ibrahim Rabia, Azza Fahmy, Azza El Amir

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This study was designed for assessment of 3 types of Cysteine protease inhibitors (CPIs) fluromethylketone (FMK), vinyl sulfone (VS) and sodium nitro prussid (SNP), to define which of them is the best? The experiments aimed to define the protective power of each inhibitor alone or combined with PZQ for curing S. mansoni infection in mice. In vitro, treated S. mansoni adult worms recorded a mortality rate after 1 hr of exposure to 500 ppm of FMK, VS and SNP as 75, 70 and 60%, while, treated cercaria recorded 75, 60 and 50%, respectively. FMK+PZQ treatment recorded the maximum reduction in worm burden (97.2% at 5 wk PI). VS treatment alone or combined with PZQ increases IgM, total IgG, IgG2 and IgG4 levels. In EM study of worm tegument, while only detachment of spines was observed in PZQ treated group, the completely implanted spines were reported in the degenerated tegument of adult worms in all groups treated with CPIs. Treatment with VS+PZQ increased Igs levels but, its effect was different on worm reduction. So, it is not enough to eliminate the infection and FMK+PZQ considered the antischistosomicidal drug of choice.

Keywords: praziquantel, fluromethylketone, vinyl sulfone, worm burden, immunoglobulin pattern

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Authors: Reena Murali, David Peter S.

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The small interfering RNA (siRNA) alters the regulatory role of mRNA during gene expression by translational inhibition. Recent studies shows that up regulation of mRNA cause serious diseases like Cancer. So designing effective siRNA with good knockdown effects play an important role in gene silencing. Various siRNA design tools had been developed earlier. In this work, we are trying to analyze the existing good scoring second generation siRNA predicting tools and to optimize the efficiency of siRNA prediction by designing a computational model using Artificial Neural Network and whole stacking energy (ΔG), which may help in gene silencing and drug design in cancer therapy. Our model is trained and tested against a large data set of siRNA sequences. Validation of our results is done by finding correlation coefficient of experimental versus observed inhibition efficacy of siRNA. We achieved a correlation coefficient of 0.727 in our previous computational model and we could improve the correlation coefficient up to 0.753 when the threshold of whole tacking energy is greater than or equal to -32.5 kcal/mol.

Keywords: artificial neural network, double stranded RNA, RNA interference, short interfering RNA

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Authors: A. Shashank Tiwari, S. P. Mahapatra

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Scale-up is defined as the process of increasing batch size. Scale-up of a process viewed as a procedure for applying the same process to different output volumes. There is a subtle difference between these two definitions: batch size enlargement does not always translate into a size increase of the processing volume. In mixing applications, scale-up is indeed concerned with increasing the linear dimensions from the laboratory to the plant size. On the other hand, processes exist (e.g., tableting) where the term ‘scale-up’ simply means enlarging the output by increasing the speed. To complete the picture, one should point out special procedures where an increase of the scale is counterproductive and ‘scale-down’ is required to improve the quality of the product. In moving from Research and Development (R&D) to production scale, it is sometimes essential to have an intermediate batch scale. This is achieved at the so-called pilot scale, which is defined as the manufacturing of drug product by a procedure fully representative of and simulating that used for full manufacturing scale. This scale also makes it possible to produce enough products for clinical testing and to manufacture samples for marketing. However, inserting an intermediate step between R&D and production scales does not, in itself, guarantee a smooth transition. A well-defined process may generate a perfect product both in the laboratory and the pilot plant and then fail quality assurance tests in production.

Keywords: scale up, research, size, batch

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Authors: Neusa Fernanda Torres, Buyisile Chibi, Lyn E. Middleton, Vernon P. Solomon, Tivani P. Mashamba-Thompson

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Background: Self-medication with antibiotics (SMA) is a global concern, with a higher incidence in low and middle-income countries (LMICs). Despite intense world-wide efforts to control and promote the rational use of antibiotics, continuing practices of SMA systematically exposes individuals and communities to the risk of antibiotic resistance and other undesirable antibiotic side effects. Moreover, it increases the health systems costs of acquiring more powerful antibiotics to treat the resistant infection. This review thus maps evidence on the factors influencing self-medication with antibiotics in these settings. Methods: The search strategy for this review involved electronic databases including PubMed, Web of Knowledge, Science Direct, EBSCOhost (PubMed, CINAHL with Full Text, Health Source - Consumer Edition, MEDLINE), Google Scholar, BioMed Central and World Health Organization library, using the search terms:’ Self-Medication’, ‘antibiotics’, ‘factors’ and ‘reasons’. Our search included studies published from 2007 to 2017. Thematic analysis was performed to identify the patterns of evidence on SMA in LMICs. The mixed method quality appraisal tool (MMAT) version 2011 was employed to assess the quality of the included primary studies. Results: Fifteen studies met the inclusion criteria. Studies included population from the rural (46,4%), urban (33,6%) and combined (20%) settings, of the following LMICs: Guatemala (2 studies), India (2), Indonesia (2), Kenya (1), Laos (1), Nepal (1), Nigeria (2), Pakistan (2), Sri Lanka (1), and Yemen (1). The total sample size of all 15 included studies was 7676 participants. The findings of the review show a high prevalence of SMA ranging from 8,1% to 93%. Accessibility, affordability, conditions of health facilities (long waiting, quality of services and workers) as long well as poor health-seeking behavior and lack of information are factors that influence SMA in LMICs. Antibiotics such as amoxicillin, metronidazole, amoxicillin/clavulanic, ampicillin, ciprofloxacin, azithromycin, penicillin, and tetracycline, were the most frequently used for SMA. The major sources of antibiotics included pharmacies, drug stores, leftover drugs, family/friends and old prescription. Sore throat, common cold, cough with mucus, headache, toothache, flu-like symptoms, pain relief, fever, running nose, toothache, upper respiratory tract infections, urinary symptoms, urinary tract infection were the common disease symptoms managed with SMA. Conclusion: Although the information on factors influencing SMA in LMICs is unevenly distributed, the available information revealed the existence of research evidence on antibiotic self-medication in some countries of LMICs. SMA practices are influenced by social-cultural determinants of health and frequently associated with poor dispensing and prescribing practices, deficient health-seeking behavior and consequently with inappropriate drug use. Therefore, there is still a need to conduct further studies (qualitative, quantitative and randomized control trial) on factors and reasons for SMA to correctly address the public health problem in LMICs.

Keywords: antibiotics, factors, reasons, self-medication, low and middle-income countries (LMICs)

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Authors: Hind O. Osman, Tilal Elsaman, Bashir A. Yousef, Esraa Elhadi, Aimun A. E. Ahmed, Eyman Mohamed Eltayib, Malik Suliman Mohamed, Magdi Awadalla Mohamed

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Epilepsy is the most common neurological condition and cause of substantial morbidity and mortality. In the present study, the molecular hybridization tool was adopted to obtain six Schiff bases of isatin and adamantane-1-carbohydrazide (18–23). Then, their anticonvulsant activity was evaluated using a pentylenetetrazole- (PTZ-) induced seizure model using phenobarbitone as a positive control. Our findings showed that compounds 18–23 provided significant protection against PTZ-induced seizure, and maximum activities were associated with compound 23. Moreover, all investigated compounds increased the latency of induced convulsion and reduced the duration of epilepsy, with compound 23 being the best. Interestingly, most of the synthesized molecules showed a reduction in neurological symptoms and severity of the seizure. Molecular docking studies suggest GABA-A receptor as a potential target, and in silico ADME screening revealed that the pharmaceutical properties of compound 23 are within the specified limit. Thus, compound 23 was identified as a promising candidate that warrants further drug discovery processes.

Keywords: isatin and adamantane, anticonvulsant activity, PTZ-induced seizure, molecular docking

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Authors: Jan Bohata, Stanislav Zvanovec, Matej Komanec, Jakub Jaros, David Hruby

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Even though there is a rapid development in new optical networks, still optical communication infrastructures remain composed of thousands of kilometers of aging optical cables. Many of them are located in a harsh environment which contributes to an increased attenuation or induced birefringence of the fibers leading to the increase of polarization mode dispersion (PMD). In this paper, we report experimental results from environmental optical cable tests and characterization in the climate chamber. We focused on the evaluation of optical network reliability in a harsh environment. For this purpose, a special thermal chamber was adopted, targeting to the large temperature changes between -60 °C and 160 C° with defined humidity. Single mode optical cable 230 meters long, having six tubes and a total number of 72 single mode optical fibers was spliced together forming one fiber link, which was afterward tested in the climate chamber. The main emphasis was put to the polarization mode dispersion (PMD) changes, which were evaluated by three different PMD measuring methods (general interferometry technique, scrambled state-of-polarization analysis and polarization optical time domain reflectometer) in order to fully validate obtained results. Moreover, attenuation and chromatic dispersion (CD), as well as the PMD, were monitored using 17 km long single mode optical cable. Results imply a strong PMD dependence on thermal changes, imposing the exceeding 200 % of its value during the exposure to extreme temperatures and experienced more than 20 dB insertion losses in the optical system. The derived statistic is provided in the paper together with an evaluation of such as optical system reliability, which could be a crucial tool for the optical network designers. The environmental tests are further taken in context to our previously published results from long-term monitoring of fundamental parameters within an optical cable placed in a harsh environment in a special outdoor testbed. Finally, we provide a correlation between short-term and long-term monitoring campaigns and statistics, which are necessary for optical network safety and reliability.

Keywords: optical fiber, polarization mode dispersion, harsh environment, aging

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Authors: Oktavia Eka Puspita

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The possibility of using Solid Lipid Nanoparticles (SLN) for topical use is an interesting feature concerning this system has occlusive properties on the skin surface therefore enhance the penetration of drugs through the stratum corneum by increased hydration. This advantage can be used to enhance the drug penetration of topical delivery such as Diclofenac sodium for the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. The purpose of this study was focused on the preparation and physical characterization of Diclofenac sodium loaded SLN (D-SLN). D loaded SLN were prepared by hot homogenization followed by ultrasonication technique. Since the occlusion factor of SLN is related to its particle size the formulation of D-SLN in present study two formulations different in its surfactant contents were prepared to investigate the difference of the particle size resulted. Surfactants selected for preparation of formulation A (FA) were lecithin soya and Tween 80 whereas formulation B (FB) were lecithin soya, Tween 80, and Sodium Lauryl Sulphate. D-SLN were characterized for particle size and distribution, polydispersity index (PI), zeta potential using Beckman-Coulter Delsa™ Nano. Overall, the particle size obtained from FA was larger than FB. FA has 90% of the particles were above 1000 nm, while FB has 90% were below 100 nm.

Keywords: solid lipid nanoparticles, hot homogenization technique, particle size analysis, topical administration

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Authors: Dyah Larasati, Karishma Alize Huda, Sri Kusumastuti Rahayu, Martin Daniel Siyaranamual

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Indonesia continues to reform its social protection system to provide the needed protection for its citizen. Indonesia Social Protection consisted of social assistance programs (non-contributory/tax-financed) specifically targeted for the poor and at-risk and social security/insurance program (contributory system). The social assistance programs have mostly been implemented since 1998. The national health insurance has been implemented since 2014 and the employment social insurance since 2015. One major reform implemented has been improving the targeting performance of its major social assistance portfolios including (1) Food Assistance for the poor families (Rastra and BPNT/noncash foods assistance); (2) Education Assistance for poor children; (3) Conditional Cash Transfer for poor families (PKH); and (4) Subsidized beneficiaries of National Health Insurance (JKN-PBI) for the poor and at-risk individuals. For the Social Insurance (through BPJS Employment program), several initiatives have been implemented to expand the program contributing members, although it mostly benefits the formal sector workers. However, major gaps still exist especially for the emerging middle-income groups who typically work at the informal sectors. They have yet to get the protection needed to sustain their social and economic growth. Since 2017, TNP2K (the National Team for Poverty Reduction) under the Vice President office has led the social protection discourse as the government understands the need to address vulnerabilities across the lifecycle and prioritize support to the most at-risk population particularly the elderly, young children and people with disabilities. Discussion and advocacy to recommend for more investment is continuing in order for the government to establish a comprehensive social protection system in the near future (2020-2024) that protects children through an inclusive child benefit program; build a system to benefit more working-age adults (including individuals with disabilities) and a three-tier elderly protection as they reach 65 years.

Keywords: poverty reduction, social assistance, social insurance, social protection

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Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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Authors: Pattanapon Kayansamruaj, Ha Thanh Dong, Nopadon Pirarat, Channarong Rodkhum

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Streptococcus iniae (SI) is a devastating pathogenic bacteria causing heavy mortality in farmed fish. The application of commercialized bacterin vaccine has been reported failures as the outbreaks of the new serotype of SI were emerged in farms after vaccination and subsequently caused severe losses. In the present study, we attempted to develop effective DNA vaccines against SI infection using Nile tilapia (Oreochromis niloticus) as an animal model. Two monovalent DNA vaccines were constructed by the insertion of coding sequences of cell wall-associated virulence factors-encoding genes, comprised of eno (α-enolase) and mtsB (hydrophobic membrane protein), into cytomegalovirus expression vector (pCI-neo). In the animal trial, 30-g Nile tilapia were injected intramuscularly with 15 µg of each vaccine (mock vaccine group was injected by naked pCI-neo) and maintained for 35 days prior challenging with pathogenic SI at the dosage of 107 CFU/fish. At 13 days post-challenge, the relative percent survival of pEno, pMtsB and mock vaccine were 57%, 45% and 27%, respectively. The expression levels of immune responses-associated genes, namely, IL1β, TNF-α, TGF-β, COX2, IL-6, IL-12 and IL-13, were investigated from the spleen of experimental animal at 7 days post-vaccination (PV) and 7 days post-challenge (PC) using quantitative RT-PCR technique. Generally, at 7 days PV, the pEno vaccinated group exhibited highest level of up-regulation (1.7 to 2.9 folds) of every gene, but TGF-β, comparing to pMtsB and mock vaccine groups. However, at 7 days PC, pEno group showed significant up-regulation (1.4 to 8.5 folds) of immune-related genes as similar as mock vaccine group, while pMtsB group had lowest level of up-regulation (0.7 to 3.3 folds). Summarily, this study indicated that the pEno and pMtsB vaccines could elicit the immune responses of the fish and the magnitude of gene expression at 7 days PV was also consistent with the protection level conferred by the vaccine.

Keywords: gene expression, DNA vaccine, Nile tilapia, Streptococcus iniae

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Authors: Choi Younshick, Lee Wonseok, Lee Jaemeun, Park Sun-Hyun, Kim Sunwoung, Park Sua, Kim Eun Ho, Kim Jong-Ki

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Iron accumulation in the brain accelerates Alzheimer’s disease progression. To cure iron toxicity, we assessed the therapeutic effects of noncontact transcranial electric field stimulation to the brain on toxic iron deposits in either the Aβ-fibril structure or the Aβ plaque in a mouse model of Alzheimer’s disease (AD). A capacitive electrode-based alternating electric field (AEF) was applied to a suspension of magnetite (Fe₃O₄) to measure the field-sensitized electro-Fenton effect and resultant reactive oxygen species (ROS) generation. The increase in ROS generation compared to the untreated control was both exposure-time and AEF-frequency dependent. The frequency-specific exposure of AEF to 0.7–1.4 V/cm on a magnetite-bound Aβ-fibril or a transgenic Alzheimer’s disease (AD) mouse model revealed the removal of intraplaque ferrous magnetite iron deposit and Aβ-plaque burden together at the same time compared to the untreated control. The results of the behavioral tests show an improvement in impaired cognitive function following AEF treatment on the AD mouse model. Western blot assay found some disease-modifying biological responses, including down-regulating ferroptosis, neuroinflammation and reactive astrocytes that eventually made cognitive improvement feasible. Tissue clearing and 3D-imaging analysis revealed no induced damage to the neuronal structures of normal brain tissue following AEF treatment. In conclusion, our results suggest that the effective degradation of magnetite-bound amyloid fibrils or plaques in the AD brain by the electro-Fenton effect from electric field-sensitized magnetite offers a potential electroceutical treatment option for AD.

Keywords: electroceutical, intraplaque magnetite, alzheimer’s disease, transcranial electric field, electro-fenton effect

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