Search results for: humanized mouse

Authors: Hyun Ji Hyun, Hyo Sun Suh, Min Kook Kim, Yong Chan Kwon, Byung-Mu Lee

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Scope: This study is focused on the effect of myristic acid on LPS-induced inflammation in RAW 264.7 macrophage cells. Methods and results: For the experiment, RAW 264.7 mouse macrophage cell line was used. Results showed that treatment with myristic acid can attenuate LPS-induced inflammation. Moreover, myristic acid significantly suppressed expression of inflammatory mediators and down-regulating UVB-induced intracellular ROS generation. Furthermore, myristic acid reduced the expression of NF-κB by inhibiting degradation of IκB-α and ERK, JNK, and p38 pathways by inhibiting phosphorylation in RAW 264.7 macrophage cells. Conclusion: Overall, these data suggest that the myristic acid could reduce LPS-induced inflammation. Acknowledgment: This research was supported by the Ministry of Trade, Industry & Energy(MOTIE), Korea Institute for Advancement of Technology(KIAT) through the Encouragement Program for The Industries of Economic Cooperation Region

Keywords: anti-inflammation, myristic acid, ROS, ultraviolet light

Procedia PDF Downloads 178

Authors: Mai M. Farid, Ximeng Yang, Tomoharu Kuboyama, Chihiro Tohda

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Trigonelline is a major alkaloid component derived from Trigonella foenum-graecum L. (fenugreek) and has been reported before as a potential neuroprotective agent, especially in Alzheimer’s disease (AD). However, the previous data were unclear and used model mice were not well established. In the present study, the effect of trigonelline on memory function was investigated in Alzheimer’s disease transgenic model mouse, 5XFAD which overexpresses the mutated APP and PS1 genes. Oral administration of trigonelline for 14 days significantly enhanced object recognition and object location memories. Plasma and cerebral cortex were isolated at 30 min, 1h, 3h, and 6 h after oral administration of trigonelline. LC-MS/MS analysis indicated that trigonelline was detected in both plasma and cortex from 30 min after, suggesting good penetration of trigonelline into the brain. In addition, trigonelline significantly ameliorated axonal and dendrite atrophy in Amyloid β-treated cortical neurons. These results suggest that trigonelline could be a promising therapeutic candidate for AD.

Keywords: alzheimer’s disease, cortical neurons, LC-MS/MS analysis, trigonelline

Procedia PDF Downloads 122

Authors: Gizem Kayar, Ramazan Bakir, M. Ilkay Koşar, Ceren U. Gencer, Alperen Ayyildiz

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Anatomy classes are crucial for general education of medical students, whereas learning anatomy is quite challenging and requires memorization of thousands of structures. In traditional teaching methods, learning materials are still based on books, anatomy mannequins, or videos. This results in forgetting many important structures after several years. However, more interactive teaching methods like virtual reality, augmented reality, gamification, and motion sensors are becoming more popular since such methods ease the way we learn and keep the data in mind for longer terms. During our study, we designed a virtual reality based digital head anatomy platform to investigate whether a fully interactive anatomy platform is effective to learn anatomy and to understand the level of teaching and learning optimization. The Head is one of the most complicated human anatomy structures, with thousands of tiny, unique structures. This makes the head anatomy one of the most difficult parts to understand during class sessions. Therefore, we developed a fully interactive digital tool with 3D model marking, quiz structures, 2D/3D puzzle structures, and VR support so as to integrate the power of VR and gamification. The project has been developed in Unity game engine with HTC Vive Cosmos VR headset. The head anatomy 3D model has been selected with full skeletal, muscular, integumentary, head, teeth, lymph, and vein system. The biggest issue during the development was the complexity of our model and the marking of it in the 3D world system. 3D model marking requires to access to each unique structure in the counted subsystems which means hundreds of marking needs to be done. Some parts of our 3D head model were monolithic. This is why we worked on dividing such parts to subparts which is very time-consuming. In order to subdivide monolithic parts, one must use an external modeling tool. However, such tools generally come with high learning curves, and seamless division is not ensured. Second option was to integrate tiny colliders to all unique items for mouse interaction. However, outside colliders which cover inner trigger colliders cause overlapping, and these colliders repel each other. Third option is using raycasting. However, due to its own view-based nature, raycasting has some inherent problems. As the model rotate, view direction changes very frequently, and directional computations become even harder. This is why, finally, we studied on the local coordinate system. By taking the pivot point of the model into consideration (back of the nose), each sub-structure is marked with its own local coordinate with respect to the pivot. After converting the mouse position to the world position and checking its relation with the corresponding structure’s local coordinate, we were able to mark all points correctly. The advantage of this method is its applicability and accuracy for all types of monolithic anatomical structures.

Keywords: anatomy, e-learning, virtual reality, 3D model marking

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Authors: Sai Charan Kamana, Harsha Vardhan Nakkina, B.R. Chandavarkar

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In a highly secure and robust key generation process, a key role is played by randomness and random numbers when current real-world cryptosystems are observed. Most of the present-day cryptographic protocols depend upon the Random Number Generators (RNG), Pseudo-Random Number Generator (PRNG). These protocols often use noisy channels such as Disk seek time, CPU temperature, Mouse pointer movement, Fan noise to obtain true random values. Despite being cost-effective, these noisy channels may need additional hardware devices to continuously communicate with them. On the other hand, Hash functions are Pseudo-Random (because of their requirements). So, they are a good replacement for these noisy channels and have low hardware requirements. This paper discusses, some of the key generation methodologies, and their drawbacks. This paper explains how hash functions can be used in key generation, how to combine Key Derivation Functions with hash functions.

Keywords: key derivation, hash based key derivation, password based key derivation, symmetric key derivation

Procedia PDF Downloads 133

Authors: Shahin Zanbaghi, Saeed Samet

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The internet has transformed the way we shop. Previously, most of our purchases came in the form of shopping trips to a nearby store. Now, it’s as easy as clicking a mouse. But with great convenience comes great responsibility. We have to be constantly vigilant about our personal information. In this work, our proposed approach is to encrypt the information printed on the physical packages, which include personal information in plain text, using a symmetric encryption algorithm; then, we store that encrypted information into a Blockchain network rather than storing them in companies or corporations centralized databases. We present, implement and assess a blockchain-based system using Ethereum smart contracts. We present detailed algorithms that explain the details of our smart contract. We present the security, cost, and performance analysis of the proposed method. Our work indicates that the proposed solution is economically attainable and provides data integrity, security, transparency, and data traceability.

Keywords: blockchain, Ethereum, smart contract, commit-reveal scheme

Procedia PDF Downloads 123

Authors: Sang Hun Park, Chul Gyu Song

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Artery and vein occlusion changes observed in patients and experimental animals are unexplainable symptoms. As the fat accumulated in cardiovascular ruptures, it causes vascular blocking. Likewise, early detection of cardiovascular disease can be useful for treatment. In this study, we used the mouse femoral occlusion model to observe the arterial and venous occlusion changes without darkroom. We observed the femoral arterial flow pattern changes by proposed fluorescent imaging system using an animal model of thrombosis. We adjusted the near-infrared light source current in order to control the intensity of the fluorescent substance light. We got the clear fluorescent images and femoral artery flow pattern were measured by a 5-minute interval. The result showed that the fluorescent substance flowing in the femoral arteries were accumulated in thrombus as time passed, and the fluorescence of other vessels gradually decreased.

Keywords: thrombus, fluorescence, femoral, arteries

Procedia PDF Downloads 319

Authors: Tong-Chien Wu, Ching-Liang Hsieh, Yi-Wen Lin

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There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). Local EA can reliably attenuate inflammatory pain in mouse with unclear mechanisms. However, the effect of EA on distal and contralateral acupoint for pain control has been rarely studied and the result was controversial. Here in our study, we found that inflammatory hindpaw pain in mouth, which was induced by injecting the complete Freund’s adjuvant (CFA) 2 days ago can be alleviated immediately after 2Hz 15mins EA treatment at contralateral forefoot acupoint LI4 through both mechanic and thermal behavior test, while sham acupoint group is not. The efficacy was observed to be more obvious after the second round of EA treatment on the following day. This analgesic effect is produced by applying EA to a site remote from the painful area. The present study provides a powerful experimental animal model that can be used for investigating the unique physiological mechanisms involved in acupuncture analgesia.

Keywords: remote electroacupuncture, distal EA, pain control, anti-inflammation

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Authors: Mengjiao Fan, Thomson W. L. Wong

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It is unavoidable that older adults may have to deal with aging-related motor problems. Aging is highly likely to affect motor learning and control as well. For example, older adults may suffer from poor motor function and quality of life due to age-related eye changes. These adverse changes in vision results in impairment of movement automaticity. Reaching is a fundamental component of various complex movements, which is therefore beneficial to explore the changes and adaptation in visuomotor behaviors. The current study aims to explore how aging affects visuomotor behaviors by comparing motor performance and gaze behaviors between two age groups (i.e., young and older adults). Visuomotor behaviors in reaching under providing or blocking online visual feedback (simulated visual deficiency) conditions were investigated in 60 healthy young adults (Mean age=24.49 years, SD=2.12) and 37 older adults (Mean age=70.07 years, SD=2.37) with normal or corrected-to-normal vision. Participants in each group were randomly allocated into two subgroups. Subgroup 1 was provided with online visual feedback of the hand-controlled mouse cursor. However, in subgroup 2, visual feedback was blocked to simulate visual deficiency. The experimental task required participants to complete 20 times of reaching to a target by controlling the mouse cursor on the computer screen. Among all the 20 trials, start position was upright in the center of the screen and target appeared at a randomly selected position by the tailor-made computer program. Primary outcomes of motor performance and gaze behaviours data were recorded by the EyeLink II (SR Research, Canada). The results suggested that aging seems to affect the performance of reaching tasks significantly in both visual feedback conditions. In both age groups, blocking online visual feedback of the cursor in reaching resulted in longer hand movement time (p < .001), longer reaching distance away from the target center (p<.001) and poorer reaching motor accuracy (p < .001). Concerning gaze behaviors, blocking online visual feedback increased the first fixation duration time in young adults (p<.001) but decreased it in older adults (p < .001). Besides, under the condition of providing online visual feedback of the cursor, older adults conducted a longer fixation dwell time on target throughout reaching than the young adults (p < .001) although the effect was not significant under blocking online visual feedback condition (p=.215). Therefore, the results suggested that different levels of visual feedback during movement execution can affect gaze behaviors differently in older and young adults. Differential effects by aging on visuomotor behaviors appear on two visual feedback patterns (i.e., blocking or providing online visual feedback of hand-controlled cursor in reaching). Several specific gaze behaviors among the older adults were found, which imply that blocking of visual feedback may act as a stimulus to seduce extra perceptive load in movement execution and age-related visual degeneration might further deteriorate the situation. It indeed provides us with insight for the future development of potential rehabilitative training method (e.g., well-designed errorless training) in enhancing visuomotor adaptation for our aging population in the context of improving their movement automaticity by facilitating their compensation of visual degeneration.

Keywords: aging effect, movement automaticity, reaching, visuomotor behaviors, visual degeneration

Procedia PDF Downloads 291

Authors: Leena Wanganoo

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In this digital age with the mushrooming of online companies across the globe has led to an unprecedented new business model. The frequency of online purchasing varies across the globe, but trend shows a steep upward movement. From Generation X to the Millennial the consumer not only wants to order the product with the click of mouse but also very demanding service quality during pre to post-transaction stage. The existing research examines the impact of website quality on the on behavioral intentions in e-services customers and has not adequately recognized the quality of e-commerce logistics perceived by the customer.In order to address this gap, this study examines the relationship among the logistics service quality, satisfaction, and loyalty. Drawing upon a sample of 350 millennial customers from various regions of UAE will work within the framework of structural equation modeling (SEM). Finally, the study would use Importance-Performance analysis (IPA) to discuss the relations of the level of customers’ expected logistics service quality and level of customers’ perceived logistics serviced quality.

Keywords: logistics service quality, customer satisfaction, loyalty, electronic commerce

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Authors: K. Yadamma, K. Rudrama Devi

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The protective effect of Ginger Extract against cyclophosphamide induced cytotoxicity was evaluated in in vivo animal model using analysis of chromosomal aberrations in somatic cells of mice. Three doses of Ginger Extract (150mg/kg, 200mg/kg, and 250mg/kg body weight) were selected for modulation and given to animals after priming. The animals were sacrificed 24, 48, 72 hrs after the treatment and slides were prepared for the incidence of chromosomal aberrations in bone marrow cells of mice. When animals were treated with cyclophosphamide 50mg/kg, showed cytogenetic damage in somatic cells. However, a significant decrease was observed in the percentage of chromosomal aberrations when animals were primed with various doses of Ginger Extract. The present results clearly indicate the protective nature of Ginger Extract against cyclophosphamide induced genetic damage in mouse bone marrow cells.

Keywords: ginger extract, protection, bone marrow cells, swiss albino mice

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Authors: Amy Heaps, Amy Burns, Una McMahon-Beattie

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Shock and fear tactics have been used to encourage consumer behaviour change within the UK regarding lifestyle choices such as smoking and alcohol abuse, yet such measures have not been applied to food labels to encourage healthier purchasing decisions. Obesity levels are continuing to rise within the UK, despite efforts made by government and charitable bodies to encourage consumer behavioural changes, which will have a positive influence on their fat, salt, and sugar intake. We know that taking extreme measures to shock consumers into behavioural changes has worked previously; for example, the anti-smoking television adverts and new standardised cigarette and tobacco packaging have reduced the numbers of the UK adult population who smoke or encouraged those who are currently trying to quit. The USA has also introduced new front-of-pack labelling, which is clear, easy to read, and includes concise health warnings on products high in fat, salt, or sugar. This model has been successful, with consumers reducing purchases of products with these warning labels present. Therefore, investigating if shock labels would have an impact on UK consumer behaviour and purchasing decisions would help to fill the gap within this research field. This study aims to develop an understanding of consumer’s initial responses to shock advertising with an interest in the perceived impact of long-term effect shock advertising on consumer food purchasing decisions, behaviour, and attitudes and will achieve this through a mixed methodological approach taken with a sample size of 25 participants ages ranging from 22 and 60. Within this research, shock mock labels were developed, including a graphic image, health warning, and get-help information. These labels were made for products (available within the UK) with large market shares which were high in either fat, salt, or sugar. The use of online focus groups and mouse-tracking experiments results helped to develop an understanding of consumer’s initial responses to shock advertising with interest in the perceived impact of long-term effect shock advertising on consumer food purchasing decisions, behaviour, and attitudes. Preliminary results have shown that consumers believe that the use of graphic images, combined with a health warning, would encourage consumer behaviour change and influence their purchasing decisions regarding those products which are high in fat, salt and sugar. Preliminary main findings show that graphic mock shock labels may have an impact on consumer behaviour and purchasing decisions, which will, in turn, encourage healthier lifestyles. Focus group results show that 72% of participants indicated that these shock labels would have an impact on their purchasing decisions. During the mouse tracking trials, this increased to 80% of participants, showing that more exposure to shock labels may have a bigger impact on potential consumer behaviour and purchasing decision change. In conclusion, preliminary results indicate that graphic shock labels will impact consumer purchasing decisions. Findings allow for a deeper understanding of initial emotional responses to these graphic labels. However, more research is needed to test the longevity of these labels on consumer purchasing decisions, but this research exercise is demonstrably the foundation for future detailed work.

Keywords: consumer behavior, decision making, labelling legislation, purchasing decisions, shock advertising, shock labelling

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Authors: Sang Hun Park, Moung Young Lee, Su Min Yu, Hyun Sang Jo, Ji Hyeon Kim, Chul Gyu Song

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A near-infrared light source used as a light source in the fluorescence imaging system is suitable for use in real-time during the operation since it has no interference in surgical vision. However, fluorescence images do not have depth information. In this paper, we configured the device with the research on molecular imaging systems for monitoring thrombus imaging using fluorescence and photoacoustic. Fluorescence imaging was performed using a phantom experiment in order to search the exact location, and the Photoacoustic image was in order to detect the depth. Fluorescence image obtained when evaluated through current phantom experiments when the concentration of the contrast agent is 25μg / ml, it was confirmed that it looked sharper. The phantom experiment is has shown the possibility with the fluorescence image and photoacoustic image using an indocyanine green contrast agent. For early diagnosis of cardiovascular diseases, more active research with the fusion of different molecular imaging devices is required.

Keywords: fluorescence, photoacoustic, indocyanine green, carotid artery

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Authors: Li Chen, Feng Zhang, Shizhong Zheng

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SaikosaponinD (SSD) is a major component of saikosaponins isolated from Bupleurumfalactum. Our current study was to examine the toxic effect of SSD on liver cells and explore the possible mechanism. The results demonstrated that SSD induced mouse liver injury and led to apoptosis in LO2 cells. HE staining and TUNEL analyses showed that SSD stimulated liver injury and hepatocyte apoptosis in vivo. Subsequent experiments showed that SSD down-regulated Bcl-2 but up-regulated Bax. In vitro, SSD-treated LO2 cells exhibited apparent down-regulated expression of p-p38. Moreover, PDGF-βR agonist PDGF-BB alone significantly upregulated p38 phosphorylation, while combined with SSD, p38 phosphorylation expression was reduced. Furthermore, shRNA-mediated PDGF-βR knockdown augmented the inactivation of p-p38 and Bcl2 but abrogated the activation of Bax, these results were more obvious when shRNA combined with SSD. These data indicated that SSD stimulated liver injury and apoptosis in hepatocytes and PDGF-βR /p38 pathway may be the potential mechanistic.

Keywords: saikosaponin D, hepatotoxicity, liver injury, apoptosis, platelet-derived growth factor-β receptor, p38

Procedia PDF Downloads 377

Authors: Eun-Joong Kim, Sankarprasad Bhuniya, Hyunseung Lee, Hyun Min Kim, Chaejoon Cheong, Su-khendu Maiti, Kwan Soo Hong, Jong Seung Kim

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Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential anti-metastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2 selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug 7 showed effective anti-tumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anti-cancer drug, SN-38.

Keywords: hydrogen peroxide, prodrug, metastatic tumors, fluorescence

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Authors: Hairin Taha, Aditya Arya, M. A. Hapipah, A. M. Mustafa

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Plants have been an important source of medicine since ancient times. Pseuduvaria monticola is a rare montane forest species from the Annonaceae family. Traditionally, the plant was used to cure symptoms of fever, inflammation, stomach-ache and also to reduce the elevated levels of blood glucose. Scientifically, we have evaluated the antidiabetic potential of the Pseuduvaria monticola bark methanolic extract on certain in vitro cell based assays, followed by in vivo study. Results from in vitro models displayed PMm upregulated glucose uptake and insulin secretion in mouse pancreatic β-cells. In vivo study demonstrated the PMm down-regulated hyperglycaemia, oxidative stress and elevated levels of pro-inflammatory cytokines in type 2 diabetic rat models. Altogether, the study revealed that Pseuduvaria monticola might be used as a potential candidate for the management of type 2 diabetes and its related complications.

Keywords: type 2 diabetes, Pseuduvaria monticola, insulin secretion, glucose uptake

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Authors: Jai Myung Yang, Na Young Kim, Sung Ho Shin

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The adverse reactions of current live smallpox vaccines and potential use of smallpox as a bioterror weapon have heightened the development of new effective vaccine for this infectious disease. In the present study, DNA vaccine vector was produced which was optimized for expression of the vaccinia virus L1 antigen in the mouse model. A plasmid IgM-tL1R, which contains codon-optimized L1R gene, was constructed and fused with an IgM signal sequence under the regulation of a SV40 enhancer. The expression and secretion of recombinant L1 protein was confirmed in vitro 293 T cell. Mice were administered the DNA vaccine by electroporation and challenged with vaccinia virus. We observed that immunization with IgM-tL1R induced potent neutralizing antibody responses and provided complete protection against lethal vaccinia virus challenge. Isotyping studies reveal that immunoglobulin G2 (IgG2) antibody predominated after the immunization, indicative of a T helper type 1 response. Our results suggest that an optimized DNA vaccine, IgM-tL1R, can be effective in stimulating anti-vaccinia virus immune response and provide protection against lethal orthopoxvirus challenge.

Keywords: DNA vaccine, electroporation, L1R, vaccinia virus

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Authors: Kuei-Chun Liu, Yu-Yu Lai, Ching-Hong Wu

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A good automated testing tool could reduce as much as possible the manual work done by testers. Traditional record-replay testing tool provides an automated testing solution by recording mouse coordinates as test scripts, but it will be easily broken if any change of resolutions. Therefore, more and more testers design multiple test scripts to automate the testing process for different devices. In order to improve the traditional record-replay approach and reduce the effort that the testers spending on writing test scripts, we propose an approach for generating the Android application test scripts based on accessibility service without connecting to a computer. This approach simulates user input actions and replays them correctly even at the different conditions such as the internet connection is unstable when the device under test, the different resolutions on Android devices. In this paper, we describe how to generate test scripts automatically and make a comparison with existing tools for Android such as Robotium, Appium, UIAutomator, and MonkeyTalk.

Keywords: accessibility service, Appium, automated testing, MonkeyTalk, Robotium, testing, UIAutomator

Procedia PDF Downloads 346

Authors: Yi-Hao Wong, Li-Li Chan, Chee-Onn Leong, Stephen Ambu, Joon-Wah Mak, Priyasashi Sahu

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Background: Acanthamoeba is a genus of amoebae which lives as a free-living in nature or as a human pathogen that causes severe brain and eye infections. Virulence potential of Acanthamoeba is not constant and can change with growth conditions. DNA methylation, an epigenetic process which adds methyl groups to DNA, is used by eukaryotic cells, including several human parasites to control their gene expression. We used qPCR, siRNA gene silencing, and RNA sequencing (RNA-Seq) to study DNA-methyltransferase gene family (DNMT) in order to indicate the possibility of its involvement in programming Acanthamoeba virulence potential. Methods: A virulence-attenuated Acanthamoeba isolate (designation: ATCC; original isolate: ATCC 50492) was subjected to mouse passages to restore its pathogenicity; a virulence-reactivated isolate (designation: AC/5) was generated. Several established factors associated with Acanthamoeba virulence phenotype were examined to confirm the succession of reactivation process. Differential gene expression of DNMT between ATCC and AC/5 isolates was performed by qPCR. Silencing on DNMT gene expression in AC/5 isolate was achieved by siRNA duplex. Total RNAs extracted from ATCC, AC/5, and siRNA-treated (designation: si-146) were subjected to RNA-Seq for comparative transcriptomic analysis in order to identify the genome-wide effect of DNMT in regulating Acanthamoeba gene expression. qPCR was performed to validate the RNA-Seq results. Results: Physiological and cytophatic assays demonstrated an increased in virulence potential of AC/5 isolate after mouse passages. DNMT gene expression was significantly higher in AC/5 compared to ATCC isolate (p ≤ 0.01) by qPCR. si-146 duplex reduced DNMT gene expression in AC/5 isolate by 30%. Comparative transcriptome analysis identified the differentially expressed genes, with 3768 genes in AC/5 vs ATCC isolate; 2102 genes in si-146 vs AC/5 isolate and 3422 genes in si-146 vs ATCC isolate, respectively (fold-change of ≥ 2 or ≤ 0.5, p-value adjusted (padj) < 0.05). Of these, 840 and 1262 genes were upregulated and downregulated, respectively, in si-146 vs AC/5 isolate. Eukaryotic orthologous group (KOG) assignments revealed a higher percentage of downregulated gene expression in si-146 compared to AC/5 isolate, were related to posttranslational modification, signal transduction and energy production. Gene Ontology (GO) terms for those downregulated genes shown were associated with transport activity, oxidation-reduction process, and metabolic process. Among these downregulated genes were putative genes encoded for heat shock proteins, transporters, ubiquitin-related proteins, proteins for vesicular trafficking (small GTPases), and oxidoreductases. Functional analysis of similar predicted proteins had been described in other parasitic protozoa for their survival and pathogenicity. Decreased expression of these genes in si146-treated isolate may account in part for Acanthamoeba reduced pathogenicity. qPCR on 6 selected genes upregulated in AC/5 compared to ATCC isolate corroborated the RNA sequencing findings, indicating a good concordance between these two analyses. Conclusion: To the best of our knowledge, this study represents the first genome-wide analysis of DNA methylation and its effects on gene expression in Acanthamoeba spp. The present data indicate that DNA methylation has substantial effect on global gene expression, allowing further dissection of the genome-wide effects of DNA-methyltransferase gene in regulating Acanthamoeba pathogenicity.

Keywords: Acanthamoeba, DNA methylation, RNA sequencing, virulence

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Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

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Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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Authors: Gani Pllana

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In the conditions of the rapid development of technics and technology in recent years, the cooperation of the scientific-technical language with the standard Albanian language is continuing with a higher intensity than before. We notice a vigor of enrichment in the vocabulary of technical terminology, due to the birth and formation of new fields and subfields of technics, technology, as computing, mechatronics, telemetry, a multitude of concepts many of which, on the one hand, are marked with names of the languages they come from, mainly from English, but on the other hand, they meet their needs with the lexical mother tongue composition (by common words being raised to terms) and with the activation of other layers, such as compound word terms. Thus, for example, in the field of computing, we notice in it the inclusion of the ordinary vocabulary for reproductive reasons, like mi, dritare, flamur, adresë, skedar (Engl: mouse, window, flag, address, file), and along with them, the compound word terms, serving to differentiate relevant concepts, like, adresë e hiperlidhjes, adresë e uebit, adresë relative, adresë virtuale (Engl. address hyperlink, web address, relative address, virtual address) etc.

Keywords: common words, Albanian language, technical terminology, standardization

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Authors: Hong Su, Qiuju Yan, Wei Du, En Hu, Zhaoyu Yang, Wei Zhang, Yusheng Li, Tao Tang, Wang yang, Shushan Zhao

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Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ATDC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Keywords: calycosin, osteoarthritis, network pharmacology, molecular docking, inflammatory, cyclooxygenase 2

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Authors: Chung-Young Lee, Se-Hee Ahn, Jun-Gu Choi, Youn-Jeong Lee, Hyuk-Joon Kwon, Jae-Hong Kim

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A/chicken/Korea/01310/2001 (H9N2) (01310) was passaged through embryonated chicken eggs (ECEs) by 20 times (01310-E20), and it has been used for an inactivated oil emulsion vaccine in Korea. After sequential passages, 01310-E20 showed higher pathogenicity in ECEs and acquired multiple mutations including a potential N-glycosylation at position 133 (H3 numbering) in HA and 18aa-deletion in NA stalk. To evaluate the effect of these mutations on the mammalian pathogenicity and resistance to non-specific inhibitors, we generated four PR8-derived recombinant viruses with different combinations of HA and NA from 01310-E2 and 01310-E20 (rH2N2, rH2N20, rH20N2, and rH20N20). According to our results, recombinant viruses containing 01310 E20 HA showed higher growth property in MDCK cells and higher virulence on mice than those containing 01310 E2 HA regardless of NA. The hemagglutination activity of rH20N20 was less inhibited by egg white and mouse lung extract than that of other recombinant viruses. Thus, the increased pathogenicity of 01310-E20 may be related to both higher replication efficiency and resistance to non-specific inhibitors in mice.

Keywords: avian influenza virus, egg adaptation, H9N2, N-glycosylation, stalk deletion of neuraminidase

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Authors: James Pietris

Abstract:

Glaucoma is a collection of irreversible optic neuropathies which, if left untreated, lead to severe visual field loss. These diseases are a leading cause of blindness across the globe and are estimated to affect approximately 80 million people, particularly women and people of Asian descent.1This represents a major burden on healthcare systems worldwide. Recently, there has been increasing interest in the potential of nicotinamide (vitamin B3) as a novel option in the management of glaucoma. This review aims to analyse the currently available literature to determine whether there is evidence of an association between nicotinamide adenine dinucleotide (NAD+) and glaucomatous optic neuropathy and whether nicotinamide has the potential to prevent or reverse these effects. The literature showed a strong connection between reduced NAD+ levels and retinal ganglion cell dysfunction through multiple different studies. There is also evidence of the positive effect of nicotinamide supplementation on retinal ganglion cell function in models of mouse glaucoma and in a study involving humans. Based on the literature findings, a recommendation has been made that more research into the efficacy, appropriate dosing, and potential side effects of nicotinamide supplementation is needed before it can be definitively determined whether it is appropriate for widespread prophylactic and therapeutic use against glaucoma in humans.

Keywords: glaucoma, nicotinamide, vitamin B3, optic neuropathy

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Authors: K. Żak, S. Przetocka, R. Kitel, K. Guzik, B. Musielak, S. Malicki, G. Dubin, T. A. Holak

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Studies on tumor genesis revealed a number of factors that may potentially serve as molecular targets for immunotherapies. One of such promising targets are PD1 and PDL1 proteins. PD1 (Programmed cell death protein 1) is expressed by activated T cells and plays a critical role in modulation of the host's immune response. One of the PD1 ligands -PDL1- is expressed by macrophages, monocytes and cancer cells which exploit it to avoid immune attack. The notion of the mechanisms used by cancer cells to block the immune system response was utilized in the development of therapies blocking PD1-PDL1 interaction. Up to date, human PD1-PDL1 complex has not been crystallized and structure of the mouse-human complex does not provide a complete view of the molecular basis of PD1-PDL1 interactions. The purpose of this study is to obtain crystal structure of the human PD1-PDL1 complex which shall allow rational design of small molecule inhibitors of the interaction. In addition, the study presents results of binding small-molecules to PD1 and fragment docking towards PD1 protein which will facilitate the design and development of small–molecule inhibitors of PD1-PDL1 interaction.

Keywords: PD1, PDL1, cancer, small molecule, drug discovery

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Authors: Ya-Ting Chuang, Krystle Leung, Ya-Jen Chang, Rosemarie H. DeKruyff, Paul B. Savage, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T. Umetsu

Abstract:

We examined characteristics of a Natural Killer T (NKT) cell subpopulation that developed during influenza infection in neonatal mice, and that suppressed the subsequent development of allergic asthma in a mouse model. This NKT cell subset expressed CD38 but not CD4, produced IFN-γ, but not IL-17, IL-4 or IL-13, and inhibited the development of airway hyperreactivity (AHR) through contact-dependent suppressive activity against helper CD4 T cells. The NKT subset expanded in the lungs of neonatal mice after infection with influenza, but also after treatment of neonatal mice with a Th1-biasing α-GalCer glycolipid analogue, Nu-α-GalCer. These results suggest that early/neonatal exposure to infection or to antigenic challenge can affect subsequent lung immunity by altering the profile of cells residing in the lung and that some subsets of NKT cells can have direct inhibitory activity against CD4+ T cells in allergic asthma. Importantly, our results also suggest a potential therapy for young children that might provide protection against the development of asthma.

Keywords: NKT subset, asthma, airway hyperreactivity, hygiene hypothesis, influenza

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Authors: Manea A. I. Alqrad, Alaa Sirwi, Sabrin R. M. Ibrahim, Hossam M. Abdallah, Gamal A. Mohamed

Abstract:

Phytochemical study of the methanolic extract of the air dried powdered of the parts of Viscum schemperi Engl. (Family: Viscaceae) using different chromatographic techniques led to the isolation of five compounds: -amyrenone (1), betulinic acid (2), (3β)-olean-12-ene-3,23-diol (3), -oleanolic acid (4), and α-oleanolic acid (5). Their structures were established based on physical, chemical, and spectral data. Anti-inflammatory and anti-apoptotic activities of oleanolic acid in a mouse model of acute hepatorenal damage were assessed. This study showed the efficacy of oleanolic acid to counteract thioacetamide-induced hepatic and kidney injury in mice through the reduction of hepatocyte oxidative damage, suppression of inflammation, and apoptosis. More importantly, oleanolic acid suppressed thioacetamide-induced hepatic and kidney injury by inhibiting NF-κB/TNF-α-mediated inflammation/apoptosis and enhancing SIRT1/Nrf2/Heme-oxygenase signalling pathway. These promising pharmacological activities suggest the potential use of oleanolic acid against hepatorenal damage.

Keywords: oleanolic acid, viscum schimperi, thioacetamide, SIRT1/Nrf2/NF-κB, hepatorenal damage

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Authors: Hailiang Liu, Yan Ni, Jie Zheng, Xiaoyan Jiang, Min Hong

Abstract:

Allergic contact dermatitis (ACD) is a commonly clinical type IV allergic skin disease, with the pathological features of infiltration by mononuclear cells and tissue necrosis. Traditional Chinese medicine Radix Saposhnikoviae (RS) is traditionally employed to treat exogenous evils, rubella, itching, rheumatism and tetanus. Meanwhile, it is an important component of the commonly used anti-allergy compound. It’s now widely used as an immuno-modulating agent in mixed herbal decoctions to treat inflammation. However, its mechanism of anti-allergy remains unknown. RS was found to reduce ear thickness, as well as the infiltration of eosinophils. The proliferation of T lymphocytes was inhibited significantly by RS, markedly decreased IFN-γ levels in the supernatant of cells cultured and serum were detected with the treatment of RS. RS significantly decreased the amount of DCs in the mouse lymph nodes, and inhibited the expression of CD4 0 and CD86. Meanwhile, T-bet mRNA expression was down remarkably regulated by RS. These results indicate that RS cures Th1-induced allergic skin inflammation by regulating Th1/Th2 balance with decreasing Th1 differentiation, which might be associated with DCs.

Keywords: allergic contact dermatitis, Radix saposhnikoviae, dendritic cells, T-bet, GATA-3, CD4+ CD25+ Foxp3+ treg cells

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Authors: Aika Umemuro, Mitsuru Sato, Mizuki Narita, Saya Hori, Saya Sakurai, Tomomi Nakayama, Ayano Nakazawa, Toshihiro Ogura

Abstract:

Mammography requires the detection of very small calcifications, and physicians search for microcalcifications by magnifying the images as they read them. The mouse is necessary to zoom in on the images, but this can be tiring and distracting when many images are read in a single day. Therefore, an image magnification system combining an eye-detector and a simple electroencephalograph (EEG) scanner was devised, and its operability was evaluated. Two experiments were conducted in this study: the measurement of eye-detection error using an eye-detector and the measurement of the time required for image magnification using a simple EEG scanner. Eye-detector validation showed that the mean distance of eye-detection error ranged from 0.64 cm to 2.17 cm, with an overall mean of 1.24 ± 0.81 cm for the observers. The results showed that the eye detection error was small enough for the magnified area of the mammographic image. The average time required for point magnification in the verification of the simple EEG scanner ranged from 5.85 to 16.73 seconds, and individual differences were observed. The reason for this may be that the size of the simple EEG scanner used was not adjustable, so it did not fit well for some subjects. The use of a simple EEG scanner with size adjustment would solve this problem. Therefore, the image magnification system using the eye-detector and the simple EEG scanner is useful.

Keywords: EEG scanner, eye-detector, mammography, observers

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Authors: Jana Tchekalarova, Stela Georgieva, Petia Peneva, Petar Todorov

Abstract:

In the present study, a series of bioconjugates of N-modified hemorphine analogs containing second pharmacophore cinnamic acids (CA) or caffeic acid (KA) were synthesized by a traditional solid-phase Fmoc chemistry method for peptide synthesis. Electrochemical and fluorometric analysis and in vivo anticonvulsant activity in mice were conducted on the compounds. The three CA (H4-CA, H5-CA, and H7-CA) and three KA (H4-KA, H5-KA, and H7-KA)-conjugated hemorphine derivatives showed dose-dependent anticonvulsant activity in the maximal electroshock test (MES) in mice. The KA-conjugated H5-KA derivate was the only compound that suppressed clonic seizures at the lowest dose of 0.5 µg/mouse in the scPTZ test. The activity against the psychomotor seizures in the 6-Hz test was detected only for the H4-CA (0.5 µg) and H4-KA (0.5 µg and 1 µg), respectively. The peptide derivates did not exhibit neurotoxicity in the rotarod test. Our findings suggest that conjugated CA and KA hemorphine peptides can be used as a background for developing hemorphin-related analogs with anticonvulsant activity. Acknowledgments: This study is funded by the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project № BG-RRP-2.004-0002, "BiOrgaMCT".

Keywords: hemorphins, SPSS, caffeic/cinnamic acid, anticonvulsant activity, electrochemistry, fluorimetry

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Authors: Shiva Emami, Jenny Persson, Bengt Johansson Lindbom

Abstract:

Group A streptococcus (GAS) is a prevalent human pathogen, causing a wide range of infections and diseases. One of the most well-known virulence factors in GAS is M protein, a surface protein that facilitates bacterial invasion. In this study, we used a recombinant GAS strain (GAS-2W) expressing M protein containing a hyper immunogenic peptide (2W). Mice were immunized three times with heat-killed-GAS subcutaneously at three weeks intervals. Three weeks post last immunization, mice were challenged intraperitoneally with a lethal dose of live GAS. In order to investigate the impact of IFN-ƴ and antibodies in protection against GAS infection, we used a mouse model knock-out for IFN-ƴ (IFN-ƴ KO). We observed immunization with GAS-2W strain can increase protection against GAS infection in mice compared with the original GAS strain. Higher levels of antibodies against M1 protein were measured in GAS-2W-immunized mice. There was also a significant increase in IgG2c response in mice immunized with GAS2W. By using IFN-ƴ KO mice, we showed that not a high level of total IgG, but IgG2c was correlated with protection through the i.p challenge. It also emphasizes the importance of IFN-ƴ cytokine to combat GAS by isotype switching to IgG2c (which is opsonic for phagocytosis). Our data indicate the crucial role of IFN-ƴ in the protective immune response that, together with IgG2c, can induce protection against GAS.

Keywords: Group A streptococcus, IgG2c, IFN-γ, protection

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