Search results for: hepatitis B core-related antigen
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 329

Search results for: hepatitis B core-related antigen

89 Salon-Associated Infections: Customer’s Knowledge and Practice Measures

Authors: Esraa Elaraby, Dania Abu Zahra, Ghidaa Maswadah, Osama Amira, Mohamed Alshoura, Nihar Dash

Abstract:

Background: Human being uses salon for a variety of purposes, from trimming of hair and shaving to a range of beauty treatments such as manicure and pedicure. Salon activities involve use of several instruments including scissors, scalpels and razors, materials such as soaps, solutions, creams and gels on human skin and body. Besides, salon customers also use chair, bed and many other common shared utensils and appliances. These salons related activities create a suitable environment for the transmission of several diseases and pathogens including hepatitis B and C, scabies, tuberculosis, staphylococcus and MRSA etc. The transmission of these pathogens can be prevented by maintenance of adequate hygiene and standard preventive measures. Aim: To assess the customer’s level of knowledge about salon-acquired infections and practices taken to prevent their transmission. Methods: A cross-sectional study was conducted among 500 participants across the Emirates. Moreover, self-administered questionnaires (in English and Arabic) were distributed through convenience sampling methods between February and April 2017. Results: The study included 500 participants of which 250 were females. The mean age of the study population was 33 years (SD=4.77). The participants were from several nationalities including 325 Arabs (Non-GCC) (66.2%), 108 Non-Arabs (22%), and 59 Arabs (GCC) (11.8%). The majority of the participants 421 (84.4%) had required knowledge about salon-associated infections with a mean knowledge score of 6/10 (60%). However, when it comes down to preventive practices, only 73 of the 500 participants (14.6%) did carry their own equipment. Thus, there was insufficient correlation between the level of knowledge and preventive practices (p=0.139) of salon-associated infections. Conclusion: People’s knowledge about the salon-associated infections among UAE residents was good, but only a small number practically took the required preventative measures towards this issue. Therefore, a public awareness program is recommended to enhance the deficiencies in knowledge and practices to prevent salon-acquired infections among the users. Up to our knowledge, this is the first study of this kind in the UAE targeting the salon customers about this important issue.

Keywords: awareness, knowledge, practices, salon-associated infections

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88 The Effectiveness of Copegus (Ribavirin) Placed in a Field of Unexplored Properties of Low-Level Laser Radiation in the Treatment of Long-Covid Syndrome

Authors: Naylya Djumaeva

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Since the end of 2019, the world has been shaken by an infection that has claimed the lives of more than six and a half million patients. Currently, SARS-CoV-2 not only causes acute damage but has long-term consequences affecting every organ and has brought a wave of a new chronic disabling condition called Long-Covid..This preliminary study describes an application of un-explored properties of low-level laser radiation with laser- light emitter in the field of which is placed Copegus (Ribavirin) with the aim of treatment of patients with Long-Covid syndrome. The difference from the traditional use of the drug is that Copegus was not prescribed to the patient by the traditional method - orally or intravenously, and the medicinal properties of the drug were introduced into the patient’s body using the un-explored properties of low-power laser radiation. Ninety eight patients with Long- Covid syndrome were observed. The obtained findings suggest that under the influence of the field formed into the laser- light emitter with a Copegus placed inside the field, the remote transfer of pharmacological properties of Сopegus occurs. Conclusions about the produced effect of exposure were made based on improvement in the condition of patients, the disappearance of complaints, and positive changes in various diagnostic tests performed by the patients. Biography: Djumaeva N completed her PhD from the Institute of Epidemiology, Microbiology and Infectious Diseases in 2000. In her dissertation work devoted to the treatment of patients with chronic hepatitis B virus infection, she presented data on the possible influence of Complex Homeopathic Preparations on the organization of bound intracellular water in the cells of the body. She is the Consultant (Neurologist) at the Scientific-Research Institute for Virology, Uzbekistan, and an expert in “medicament testing” method (30 years). She has published 43 papers, including 2 patents.

Keywords: long covid, low level laser, copegus, laser- light emmiter

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87 Identification of Promiscuous Epitopes for Cellular Immune Responses in the Major Antigenic Protein Rv3873 Encoded by Region of Difference 1 of Mycobacterium tuberculosis

Authors: Abu Salim Mustafa

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Rv3873 is a relatively large size protein (371 amino acids in length) and its gene is located in the immunodominant genomic region of difference (RD)1 that is present in the genome of Mycobacterium tuberculosis but deleted from the genomes of all the vaccine strains of Bacillus Calmette Guerin (BCG) and most other mycobacteria. However, when tested for cellular immune responses using peripheral blood mononuclear cells from tuberculosis patients and BCG-vaccinated healthy subjects, this protein was found to be a major stimulator of cell mediated immune responses in both groups of subjects. In order to further identify the sequence of immunodominant epitopes and explore their Human Leukocyte Antigen (HLA)-restriction for epitope recognition, 24 peptides (25-mers overlapping with the neighboring peptides by 10 residues) covering the sequence of Rv3873 were synthesized chemically using fluorenylmethyloxycarbonyl chemistry and tested in cell mediated immune responses. The results of these experiments helped in the identification of an immunodominant peptide P9 that was recognized by people expressing varying HLA-DR types. Furthermore, it was also predicted to be a promiscuous binder with multiple epitopes for binding to HLA-DR, HLA-DP and HLA-DQ alleles of HLA-class II molecules that present antigens to T helper cells, and to HLA-class I molecules that present antigens to T cytotoxic cells. In addition, the evaluation of peptide P9 using an immunogenicity predictor server yielded a high score (0.94), which indicated a greater probability of this peptide to elicit a protective cellular immune response. In conclusion, P9, a peptide with multiple epitopes and ability to bind several HLA class I and class II molecules for presentation to cells of the cellular immune response, may be useful as a peptide-based vaccine against tuberculosis.

Keywords: mycobacterium tuberculosis, PPE68, peptides, vaccine

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86 Induction of Cellular and Humoral Immune Responses in BALB/c Mice Immunized With rB2L and rF1L Proteins of Orf Virus Adjuvanted With Alumina Nanoparticles

Authors: Alhaji Modu Bukar, Faez Firdaus Abdullah Jesse, Che Azurahanim Che Abdullah, Mustapha M. Noordin, Mohd-Lila Mohd Azmia

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Orf virus (ORFV) is the causative agent of a proliferative skin lesion known as contagious ecthyma in sheep and goats. Currently used live attenuated vaccines against ORFV infection have been reported to cause severe outbreaks in vaccinated animals. In this study, we investigated the immunogenicity of the B2L and F1L proteins of the virus, which are thought to elicit a protective immune response The 6-week-old 50 female mice were divided into 8 groups: seven experimental groups and one control group. Each animal in the experimental group received an initial immunisation with the nanoparticles or proteins coated with the nanoparticles, followed by two booster immunizations with the same products 14 days apart. Ten days after the last booster inoculation, the mice were either humanely killed or lethally challenged with UPM /HSN-2-ORFV at a dose of 106 TCID50/mL in a volume of 50 μl. The spleen was examined for histopathological changes and quantification of T cells by flow cytometry. On the other hand, the degree of protection of mice from the lethal virus was evaluated by lesion size, weight loss, and histopathological examination of skin and liver. The results showed that mice immunised with rB2L alone, rB2L-Al₂O₃-NPs, rB2L/rF1L, and rB2L/rF1L-Al₂O₃-NPs elicited statistically higher levels of anti-rB2L and/or rF1L-specific IgA/IgG and CD4/CD8 cell immune responses than mice in the control groups (p < 0.01). The vaccine candidate did not exhibit severe skin damage after monitoring histopathology, morbidity, and mortality. Overall, the results suggest that recombinant rB2L and rF1L antigens may be useful universal vaccine candidates against ORFV infections.

Keywords: orf virus, antigen nanoparticles, virus, nanoparticles

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85 A New Cytoprotective Drug on the Basis of Cytisine: Phase I Clinical Trial Results

Authors: B. Yermekbayeva, A. Gulyayaev, T. Nurgozhin, C. Bektur

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Cytisine aminophosphonate under the name "Cytafat" was approved for clinical trials in Republic of Kazakhstan as a putative liver protecting drug for the treatment of acute toxic hepatitis. A method of conducting the clinical trial is a double blind study. Total number of patients -71, aged from 16 to 56 years. Research on healthy volunteers determined the maximal tolerable doze of "Cytafat" as 200 mg/kg. Side effects when administered at high dozes (100-200 mg/kg) are tachycardia and increase of arterial blood pressure. The drug is tested in the treatment of 28 patients with a syndrome of hepatocellular failure (a poisoning with substitutes of alcohol, rat poison, or medical products). "Cytafat" was intravenously administered at a dose of 10 mg/kg in 200 ml of 5 % glucose solution once daily. The number of administrations: 1-3. In the comparison group, 23 patients were treated intravenously once a day with “Essenciale H” at a dose of 10 ml. 20 patients received a placebo (10 ml of glucose intravenously). In all cases of toxic hepatopathology the significant positive clinical effect of the testing drug distinguishable from placebo and surpassing the alternative was observed. Within a day after administration a sharp reduction of cytolitic syndrome parameters (ALT, AST, alkaline phosphatase, thymol turbidity test, GGT) was registered, a reduction of the severity of cholestatic syndrome (bilirubin decreased) was recorded, significantly decreased indices of lipid peroxidation. The following day, in all cases the positive dynamics was determined with ultrasound study (reduction of diffuse changes and events of reactive pancreatitis), hepatomegaly disappeared. Normalization of all parameters occurred in 2-3 times faster, than when using the drug "Essenciale H" and placebo. Average term of elimination of toxic hepatopathy when using the drug "Cytafat" -2,8 days, "Essenciale H" -7,2 days, and placebo -10,6 days. The new drug "Cytafat" has expressed cytoprotective properties.

Keywords: cytisine, cytoprotection, hepatopathy, hepatoprotection

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84 Detection of JC Virus DNA and T-Ag Expression in a Subpopulation of Tunisian Colorectal Carcinomas

Authors: Wafa Toumi, Alessandro Ripalti, Luigi Ricciardiello, Dalila Gargouri, Jamel Kharrat, Abderraouf Cherif, Ahmed Bouhafa, Slim Jarboui, Mohamed Zili, Ridha Khelifa

Abstract:

Background & aims: Colorectal cancer (CRC) is one of the most common malignancies throughout the world. Several risk factors, both genetic and environmental, including viral infections, have been linked to colorectal carcinogenesis. A few studies report the detection of human polyomavirus JC (JCV) DNA and transformation antigen (T-Ag) in a fraction of the colorectal tumors studied and suggest an association of this virus with CRC. In order to investigate whether such an association of JCV with CRC will hold in a different epidemiological setting, we looked for the presence of JCV DNA and T-Ag expression in a group of Tunisian CRC patients. Methods: Fresh colorectal mucosa biopsies were obtained from 17 healthy volunteers and from both colorectal tumors and adjacent normal tissues of 47 CRC patients. DNA was extracted from fresh biopsies or from formalin-fixed, paraffin-embedded tissue sections using the Invitrogen Purelink Genomic DNA mini Kit. A simple PCR and a nested PCR were used to amplify a region of the T-Ag gene. The obtained PCR products revealed a 154 bp and a 98 bp bands, respectively. Specificity was confirmed by sequencing of the PCR products. T-Ag expression was determined by immunohistochemical staining using a mouse monoclonal antibody (clone PAb416) directed against SV40 T-Ag that cross reacts with JCV T-Ag. Results: JCV DNA was found in 12 (25%) and 22 (46%) of the CRC tumors by simple PCR and by nested PCR, respectively. All paired adjacent normal mucosa biopsies were negative for viral DNA. Sequencing of the DNA amplicons obtained confirmed the authenticity of T-Ag sequences. Immunohistochemical staining showed nuclear T-Ag expression in all 22 JCV DNA- positive samples and in 3 additional tumor samples which appeared DNA-negative by PCR. Conclusions: These results suggest an association of JCV with a subpopulation of Tunisian colorectal tumors.

Keywords: colorectal cancer, immunohistochemistry, Polyomavirus JC, PCR

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83 Combining in vitro Protein Expression with AlphaLISA Technology to Study Protein-Protein Interaction

Authors: Shayli Varasteh Moradi, Wayne A. Johnston, Dejan Gagoski, Kirill Alexandrov

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The demand for a rapid and more efficient technique to identify protein-protein interaction particularly in the areas of therapeutics and diagnostics development is growing. The method described here is a rapid in vitro protein-protein interaction analysis approach based on AlphaLISA technology combined with Leishmania tarentolae cell-free protein production (LTE) system. Cell-free protein synthesis allows the rapid production of recombinant proteins in a multiplexed format. Among available in vitro expression systems, LTE offers several advantages over other eukaryotic cell-free systems. It is based on a fast growing fermentable organism that is inexpensive in cultivation and lysate production. High integrity of proteins produced in this system and the ability to co-express multiple proteins makes it a desirable method for screening protein interactions. Following the translation of protein pairs in LTE system, the physical interaction between proteins of interests is analysed by AlphaLISA assay. The assay is performed using unpurified in vitro translation reaction and therefore can be readily multiplexed. This approach can be used in various research applications such as epitope mapping, antigen-antibody analysis and protein interaction network mapping. The intra-viral protein interaction network of Zika virus was studied using the developed technique. The viral proteins were co-expressed pair-wise in LTE and all possible interactions among viral proteins were tested using AlphaLISA. The assay resulted to the identification of 54 intra-viral protein-protein interactions from which 19 binary interactions were found to be novel. The presented technique provides a powerful tool for rapid analysis of protein-protein interaction with high sensitivity and throughput.

Keywords: AlphaLISA technology, cell-free protein expression, epitope mapping, Leishmania tarentolae, protein-protein interaction

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82 Molecular Detection of Tuberculosis in Dogs in the Three North-Eastern States Assam, Mizoram and Nagaland of India

Authors: A. G. Barua, Uttam Rajkhowa, Pranjal Moni Nath, Nur Abdul Kadir

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Mycobacterium tuberculosis (MTB) is one of the most closely-related intracellular bacterial pathogens, grouped as the M. tuberculosis complex (MTC). MTB, the primary agent of human tuberculosis (TB), can develop clinical TB in animals as 75 percent of canine mycobacterial infection is caused by close contact with an infected human being. In the present study, molecular detection of TB in dogs in three North-eastern states of India, Assam Mizoram, and Nagaland was carried out. So far, there has been a lack of systematic study in these regions, hampered by slow diagnostic methods and poor infrastructure. In an attempt to rectify this situation, molecular epidemiology was carried out for nine months to detect canine TB in a sample of 340 dogs. Isolation of DNA was done with swabs (throat/nasal), nodules of lungs and fluids from 100 suspected dogs and the molecular study were carried out with the help of conventional and real-time PCR. Post-mortem study was also carried out. Our results showed that the prevalence of clinical TB in dogs from a high-risk setting was 1 percent. However, the prevalence of immunological sensitization to M. tuberculosis antigen in dogs living in contact with sputum smeared positive TB cases was almost 50 percent. The latter setting had the maximum impact in terms of TB transmission. During the study period, a survey with a standard questionnaire was carried out in the TB hospitals to study reverse zoonosis. It was observed that an infected human being was one of the major risk factors for dogs to contract the infection. This observation was drawn by examining the probable airborne transmission from humans to their pets or strays. The present study helped to discover the nuances of TB transmission more clearly and systematically as compared to other sporadic tests to detect MTB in canine.

Keywords: Assam and Nagaland, canine TB, India, molecular detection, tuberculosis

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81 Hesperidin through Acting on Proliferating Cell Nuclear Antigen and Follicle Stimulating Hormone Receptor Expression Decreased Ovarian Toxicity Induced by Malathion

Authors: Mahnaz Zarein, Hamed Shoorei

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Background: Malathion is one of the most toxic agents widely used in agriculture throughout the world. This agent has adverse effects on the functions of multiple organs such as the reproductive system in both male and female genders. On the one hand, daily use of antioxidant supplementations such as hesperidin is capable to neutralize the deleterious impacts of malathion. Therefore, in this experimental study, the protective effects of hesperidin against ovarian toxicity induced by malathion were investigated. Material & Methods: Balb/c adult mice (n=32) were randomly divided into 4 groups including 1) the control group, treated with normal saline, 2) the Mal group, treated with 30mg/kg malathion, daily for 1 month, 3) Mal + Hes group, treated with 20 mg/kg malathion and 20 mg/kg hesperidin, daily for 1 month, and 5) Hes group, treated with 20 mg/kg hesperidin. At the end of the experimental period, mice were anesthetized and their drops of blood were collected to the assessment of some hormones such as LH, FSH, E2, and P4. Also, the right ovaries were used to H&E staining, and the left ovaries were used for IHC staining (PCNA and FSHR). Results: Histopathological assessments showed that the number of follicles, i.e. primordial, primary, and secondary, significantly decreased, while the atretic follicle counts remarkably increased compared to the control group (p<0.05). Hormonal levels revealed that the production of all mentioned hormones decreased in the Mal group in comparison with the control group (p<0.05). The expression of PCNA, as a proliferative marker, and FHSR, as a marker showing maturation, decreased when mice received malathion compared to the control group (p<0.05). Interestingly, treatment with hesperidin significantly neutralized the adverse effects of malathion on all mentioned parameters. Conclusion: Daily use of antioxidant supplementations such as hesperidin could alleviate the ovarian toxicity induced by malathion.

Keywords: malathion, ovary, antioxidant hesperidin, FSHR PCNA, ovary

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80 Angiogenic and Immunomodulatory Properties and Phenotype of Mesenchymal Stromal Cells Can Be Regulated by Cytokine Treatment

Authors: Ekaterina Zubkova, Irina Beloglazova, Iurii Stafeev, Konsyantin Dergilev, Yelena Parfyonova, Mikhail Menshikov

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Mesenchymal stromal cells from adipose tissue (MSC) currently are widely used in regenerative medicine to restore the function of damaged tissues, but that is significantly hampered by their heterogeneity. One of the modern approaches to overcoming this obstacle is the polarization of cell subpopulations into a specific phenotype under the influence of cytokines and other factors that activate receptors and signal transmission to cells. We polarized MSC with factors affecting the inflammatory signaling and functional properties of cells, followed by verification of their expression profile and ability to affect the polarization of macrophages. RT-PCR evaluation showed that cells treated with LPS, interleukin-17, tumor necrosis factor α (TNF α), primarily express pro-inflammatory factors and cytokines, and after treatment with polyninosin polycytidic acid and interleukin-4 (IL4) anti-inflammatory factors and some proinflammatory factors. MSC polarized with pro-inflammatory cytokines showed a more robust pro-angiogenic effect in fibrin gel bead 3D angiogenesis assay. Further, we evaluated the possibility of paracrine effects of MSCs on the polarization of intact macrophages. Polarization efficiency was assesed by expression of M1/M2 phenotype markers CD80 and CD206. We showed that conditioned media from MSC preincubated in the presence of IL-4 cause an increase in CD206 expression similar to that observed in M2 macrophages. Conditioned media from MSC polarized in the presence of LPS or TNF-α increased the expression of CD80 antigen in macrophages, similar to that observed in M1 macrophages. In other cases, a pronounced paracrine effect of MSC on the polarization of macrophages was not detected. Thus, our study showed that the polarization of MSC along the pro-inflammatory or anti-inflammatory pathway allows us to obtain cell subpopulations that have a multidirectional modulating effect on the polarization of macrophages. (RFBR grants 20-015-00405 and 18-015-00398.)

Keywords: angiogenesis, cytokines, mesenchymal, polarization, inflammation

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79 Design and Synthesis of Some Pyrimidine Derivatives as Bruton’s Tyrosine Kinase Inhibitors for Hematologic Malignancies

Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

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Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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78 Development of Innovative Nuclear Fuel Pellets Using Additive Manufacturing

Authors: Paul Lemarignier, Olivier Fiquet, Vincent Pateloup

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In line with the strong desire of nuclear energy players to have ever more effective products in terms of safety, research programs on E-ATF (Enhanced-Accident Tolerant Fuels) that are more resilient, particularly to the loss of coolant, have been launched in all countries with nuclear power plants. Among the multitude of solutions being developed internationally, carcinoembryonic antigen (CEA) and its partners are investigating a promising solution, which is the realization of CERMET (CERamic-METal) type fuel pellets made of a matrix of fissile material, uranium dioxide UO2, which has a low thermal conductivity, and a metallic phase with a high thermal conductivity to improve heat evacuation. Work has focused on the development by powder metallurgy of micro-structured CERMETs, characterized by networks of metallic phase embedded in the UO₂ matrix. Other types of macro-structured CERMETs, based on concepts proposed by thermal simulation studies, have been developed with a metallic phase with a specific geometry to optimize heat evacuation. This solution could not be developed using traditional processes, so additive manufacturing, which revolutionizes traditional design principles, is used to produce these innovative prototype concepts. At CEA Cadarache, work is first carried out on a non-radioactive surrogate material, alumina, in order to acquire skills and to develop the equipment, in particular the robocasting machine, an additive manufacturing technique selected for its simplicity and the possibility of optimizing the paste formulations. A manufacturing chain was set up, with the pastes production, the 3D printing of pellets, and the associated thermal post-treatment. The work leading to the first elaborations of macro-structured alumina/molybdenum CERMETs will be presented. This work was carried out with the support of Framatome and EdF.

Keywords: additive manufacturing, alumina, CERMET, molybdenum, nuclear safety

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77 Inhibition of Mixed Infection Caused by Human Immunodeficiency Virus and Herpes Virus by Fullerene Compound

Authors: Dmitry Nosik, Nickolay Nosik, Elli Kaplina, Olga Lobach, Marina Chataeva, Lev Rasnetsov

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Background and aims: Human Immunodeficiency Virus (HIV) infection is very often associated with Herpes Simplex Virus (HSV) infection but HIV patients are treated with a cocktail of antiretroviral drugs which are toxic. The use of an antiviral drug which will be active against both viruses like ferrovir found in our previous studies is rather actual. Earlier we had shown that Fullerene poly-amino capronic acid (FPACA) was active in case of monoinfection of HIV-1 or HSV-1. The aim of the study was to analyze the efficiency of FPACA against mixed infection of HIV and HSV. Methods: The peripheral blood lymphocytes, CEM, MT-4 cells were simultaneously infected with HIV-1 and HSV-1. FPACA was added 1 hour before infection. Cells viability was detected by MTT assay, virus antigens detected by ELISA, syncytium formation detected by microscopy. The different multiplicity of HIV-1/HSV-1 ratio was used. Results: The double viral HIV-1/HSV-1 infection was more cytopathic comparing with monoinfections. In mixed infection by the HIV-1/HSV-1 concentration of HIV-1 antigens and syncytium formations increased by 1,7 to 2,3 times in different cells in comparison with the culture infected with HIV-1 alone. The concentration of HSV-1 increased by 1,5-1,7 times, respectively. Administration of FPACA (1 microg/ml) protected cells: HIV-1/HSV-1 (1:1) – 80,1%; HIV-1/HSV-1 (1:4) – 57,2%; HIV-1/HSV-1 (1:8) – 46,3 %; HIV-1/HSV-1 (1:16) – 17,0%. Virus’s antigen levels were also reduced. Syncytium formation was totally inhibited in all cases of mixed infection. Conclusion: FPACA showed antiviral activity in case of mixed viral infection induced by Human Immunodeficiency Virus and Herpes Simplex Virus. The effect of viral inhibition increased with the multiplicity of HIV-1 in the inoculum. The mechanism of FPACA action is connected with the blocking of the virus particles adsorption to the cells and it could be suggested that it can have an antiviral activity against some other viruses too. Now FPACA could be considered as a potential drug for treatment of HIV disease complicated with opportunistic herpes viral infection.

Keywords: antiviral drug, human immunodeficiency virus (hiv), herpes simplex virus (hsv), mixed viral infection

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76 The Multiple Sclerosis condition and the Role of Varicella-zoster virus in its Progression

Authors: Sina Mahdavi, Mahdi Asghari Ozma

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Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human Varicella-zoster virus (VZV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on VZV retrovirus infection in MS disease progression. For this study, the keywords "Multiple sclerosis", " Human Varicella-zoster virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles were chosen, studied, and analyzed. Analysis of the amino acid sequences of HNRNPA1 with VZV proteins has shown a 62% amino acid sequence similarity between VZV gE and the PrLD/M9 epitope region (TNPO1 binding domain) of mutant HNRNPA1. A heterogeneous nuclear ribonucleoprotein (hnRNP), which is produced by HNRNPA1, is involved in the processing and transfer of mRNA and pre-mRNA. Mutant HNRNPA1 mimics gE of VZV as an antigen that leads to autoantibody production. Mutant HnRNPA1 translocates to the cytoplasm, after aggregation is presented by MHC class I, followed by CD8 + cells. Of these, antibodies and immune cells against the gE epitopes of VZV remain due to the memory immune response, causing neurodegeneration and the development of MS in genetically predisposed individuals. VZV expression during the course of MS is present in genetically predisposed individuals with HNRNPA1 mutation, suggesting a link between VZV and MS, and that this virus may play a role in the development of MS by inducing an inflammatory state. Therefore, measures to modulate VZV expression may be effective in reducing inflammatory processes in demyelinated areas of MS patients in genetically predisposed individuals.

Keywords: multiple sclerosis, varicella-zoster virus, central nervous system, autoimmunity

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75 Initiation of Paraptosis-Like PCD Pathway in Hepatocellular Carcinoma Cell Line by Hep88 mAb through the Binding of Mortalin (HSPA9) and Alpha-Enolase

Authors: Panadda Rojpibulstit, Suthathip Kittisenachai, Songchan Puthong, Sirikul Manochantr, Pornpen Gamnarai, Sasichai Kangsadalampai, Sittiruk Roytrakul

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Hepatocellular carcinoma (HCC) is the most primary hepatic cancer worldwide. Nowadays a targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is continually developed in HCC treatment. In this regard, after establishing and consequently exploring Hep88 mAb’s tumoricidal effect on hepatocellular carcinoma cell line (HepG2 cell line), the Hep88 mAb’s specific Ag from both membrane and cytoplasmic fractions of HepG2 cell line was identified by 2-D gel electrophoresis and western blot analysis. After in-gel digestion and subsequent analysis by liquid chromatography-mass spectrometry (LC-MS), mortalin (HSPA9) and alpha-enolase were identified. The recombinant proteins specific to Hep88 mAb were cloned and expressed in E.coli BL21 (DE3). Moreover, alteration of HepG2 and Chang liver cell line after being induced by Hep88 mAb for 1-3 days was investigated using a transmission electron microscope. The result demonstrated that Hep88 mAb can bind to the recombinant mortalin (HSPA9) andalpha-enolase. In addition, gradual appearance of mitochondria vacuolization and endoplasmic reticulum dilatation were observed. Taken together, paraptosis-like programmed cell death (PCD) of HepG2 is induced by binding of mortalin (HSPA9) and alpha-enolase to Hep88 mAb. Mortalin depletion by formation of Hep88 mAb-mortalin (HSPA9) complex might initiate transcription-independent of p53-mediated apoptosis. Additionally, Hep88 mAb-alpha-enolase complex might initiate HepG2 cells energy exhaustion by glycolysis pathway obstruction. These results imply that Hep88 mAb might be a promising tool for development of an effective treatment of HCC in the next decade.

Keywords: Hepatocellular carcinoma, Monoclonal antibody, Paraptosis-like program cell death, Transmission electron microscopy, mortalin (HSPA9), alpha-enolase

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74 Pathogenic Effects of IgG and IgM Apoptotic Cell-Reactive Monoclonal Auto-Antibodies on Innate and Adaptive Immunity in Lupus

Authors: Monika Malik, Pooja Arora, Ruchi Sachdeva, Vishnampettai G. Ramachandran, Rahul Pal

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Apoptotic debris is believed to be the antigenic trigger in lupus. Whether such debris and autoantibodies induced in lupus-prone mice which specifically recognize its constituents can mediate differential effects on innate and humoral responses in such mice was assessed. The influence of apoptotic blebs and apoptotic cell-reactive monoclonal antibodies on phenotypic markers expressed on bone marrow-derived dendritic cells (BMDCs) and secreted cytokines were evaluated. Sera from lupus-prone and healthy mice immunized with the antibodies were analyzed for anti-self reactivity. Apoptotic blebs, as well as somatically-mutated IgG and non-mutated IgM apoptotic-cell reactive monoclonal antibodies, induced the preferential maturation of BMDCs derived from lupus-prone mice relative to BMDCs derived from healthy mice; antibody specificity and cell genotype both influenced the secretion of inflammatory cytokines. Immunization of lupus-prone mice with IgM and IgG antibodies led to hypergammaglobulinemia; elicited antibodies were self-reactive, and exhibited enhanced recognition of lupus-associated autoantigens (dsDNA, Ro60, RNP68, and Sm) in comparison with adjuvant-induced sera. While ‘natural’ IgM antibodies are believed to contribute to immune homeostasis, this study reveals that apoptotic cell-reactive IgM antibodies can promote inflammation and drive anti-self responses in lupus. Only in lupus-prone mice did immunization with IgG auto-antibodies enhance the kinetics of humoral anti-self responses, resulting in advanced-onset glomerulosclerosis. This study reveals that preferential innate and humoral recognition of the products of cell death in an autoimmune milieu influences the indices associated with lupus pathology.

Keywords: antigen spreading, apoptotic cell-reactive pathogenic IgG, and IgM autoantibodies, glomerulosclerosis, lupus

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73 Aire-Dependent Transcripts have Shortened 3’UTRs and Show Greater Stability by Evading Microrna-Mediated Repression

Authors: Clotilde Guyon, Nada Jmari, Yen-Chin Li, Jean Denoyel, Noriyuki Fujikado, Christophe Blanchet, David Root, Matthieu Giraud

Abstract:

Aire induces ectopic expression of a large repertoire of tissue-specific antigen (TSA) genes in thymic medullary epithelial cells (MECs), driving immunological self-tolerance in maturing T cells. Although important mechanisms of Aire-induced transcription have recently been disclosed through the identification and the study of Aire’s partners, the fine transcriptional functions underlied by a number of them and conferred to Aire are still unknown. Alternative cleavage and polyadenylation (APA) is an essential mRNA processing step regulated by the termination complex consisting of 85 proteins, 10 of them have been related to Aire. We evaluated APA in MECs in vivo by microarray analysis with mRNA-spanning probes and RNA deep sequencing. We uncovered the preference of Aire-dependent transcripts for short-3’UTR isoforms and for proximal poly(A) site selection marked by the increased binding of the cleavage factor Cstf-64. RNA interference of the 10 Aire-related proteins revealed that Clp1, a member of the core termination complex, exerts a profound effect on short 3’UTR isoform preference. Clp1 is also significantly upregulated in the MECs compared to 25 mouse tissues in which we found that TSA expression is associated with longer 3’UTR isoforms. Aire-dependent transcripts escape a global 3’UTR lengthening associated with MEC differentiation, thereby potentiating the repressive effect of microRNAs that are globally upregulated in mature MECs. Consistent with these findings, RNA deep sequencing of actinomycinD-treated MECs revealed the increased stability of short 3’UTR Aire-induced transcripts, resulting in TSA transcripts accumulation and contributing for their enrichment in the MECs.

Keywords: Aire, central tolerance, miRNAs, transcription termination

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72 Effects of Different Types of Perioperative Analgesia on Minimal Residual Disease Development After Colon Cancer Surgery

Authors: Lubomir Vecera, Tomas Gabrhelik, Benjamin Tolmaci, Josef Srovnal, Emil Berta, Petr Prasil, Petr Stourac

Abstract:

Cancer is the second leading cause of death worldwide and colon cancer is the second most common type of cancer. Currently, there are only a few studies evaluating the effect of postoperative analgesia on the prognosis of patients undergoing radical colon cancer surgery. Postoperative analgesia in patients undergoing colon cancer surgery is usually managed in two ways, either with strong opioids (morphine, piritramide) or epidural analgesia. In our prospective study, we evaluated the effect of postoperative analgesia on the presence of circulating tumor cells or minimal residual disease after colon cancer surgery. A total of 60 patients who underwent radical colon cancer surgery were enrolled in this prospective, randomized, two-center study. Patients were randomized into three groups, namely piritramide, morphine and postoperative epidural analgesia. We evaluated the presence of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20) mRNA positive circulating tumor cells in peripheral blood before surgery, immediately after surgery, on postoperative day two and one month after surgery. The presence of circulating tumor cells was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). In the priritramide postoperative analgesia group, the presence of CEA mRNA positive cells was significantly lower on a postoperative day two compared to the other groups (p=0.04). The value of CK-20 mRNA positive cells was the same in all groups on all days. In all groups, both types of circulating tumor cells returned to normal levels one month after surgery. Demographic and baseline clinical characteristics were similar in all groups. Compared with morphine and epidural analgesia, piritramide significantly reduces the amount of CEA mRNA positive circulating tumor cells after radical colon cancer surgery.

Keywords: cancer progression, colon cancer, minimal residual disease, perioperative analgesia.

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71 Clinical Efficacy of Nivolumab and Ipilimumab Combination Therapy for the Treatment of Advanced Melanoma: A Systematic Review and Meta-Analysis of Clinical Trials

Authors: Zhipeng Yan, Janice Wing-Tung Kwong, Ching-Lung Lai

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Background: Advanced melanoma accounts for the majority of skin cancer death due to its poor prognosis. Nivolumab and ipilimumab are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocytes antigen 4 (CTLA-4). Nivolumab and ipilimumab combination therapy has been proven to be effective for advanced melanoma. This systematic review and meta-analysis are to evaluate its clinical efficacy and adverse events. Method: A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 21 June 2020. Search keywords were nivolumab, ipilimumab, melanoma, and randomised controlled trials. Clinical trials fulfilling the inclusion criteria were selected to evaluate the efficacy of combination therapy in terms of prolongation of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The odd ratios and distributions of grade 3 or above adverse events were documented. Subgroup analysis was performed based on PD-L1 expression-status and BRAF-mutation status. Results: Compared with nivolumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR in combination therapy were 0.64 (95% CI, 0.48-0.85; p=0.002), 0.84 (95% CI, 0.74-0.95; p=0.007) and 1.76 (95% CI, 1.51-2.06; p < 0.001), respectively. Compared with ipilimumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR were 0.46 (95% CI, 0.37-0.57; p < 0.001), 0.54 (95% CI, 0.48-0.61; p < 0.001) and 6.18 (95% CI, 5.19-7.36; p < 0.001), respectively. In combination therapy, the odds ratios of grade 3 or above adverse events were 4.71 (95% CI, 3.57-6.22; p < 0.001) compared with nivolumab monotherapy, and 3.44 (95% CI, 2.49-4.74; p < 0.001) compared with ipilimumab monotherapy, respectively. High PD-L1 expression level and BRAF mutation were associated with better clinical outcomes in patients receiving combination therapy. Conclusion: Combination therapy is effective for the treatment of advanced melanoma. Adverse events were common but manageable. Better clinical outcomes were observed in patients with high PD-L1 expression levels and positive BRAF-mutation.

Keywords: nivolumab, ipilimumab, advanced melanoma, systematic review, meta-analysis

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70 Management of Blood Exposure Risk: Knowledge and Attitudes of Caregivers in Pediatric Dapartments

Authors: Hela Ghali, Oumayma Ben Amor, Salwa Khefacha, Mohamed Ben Rejeb, Sirine Frigui, Meriam Tourki Dhidah, Lamine Dhidah, Houyem Said Laatiri

Abstract:

Background: Blood exposure accidents are the most common problem in hospitals that threaten healthcare professionals with a high risk of infectious complications which weighs heavily on health systems worldwide. Paramedics are the highest risk group due to the nature of their daily activities. We aimed to determine knowledge and attitudes about the management of blood-exposure accidents among nurses and technicians in two pediatric departments. Materials/Methods: This is a cross-sectional descriptive study conducted on March 2017, carried out with the care staff of the pediatric ward of the Farhat Hached Teaching Hospital of Sousse and pediatric surgery of the Fattouma Bourguiba University Hospital in Monastir, using a pre- tested and self-administered questionnaire. Data entry and analysis were performed using Excel software. Results: The response rate was 85.1%. A female predominance (82.5%) was reported among respondents with a sex ratio of 0.21. 80% of the participants were under 35 years old. Seniority of less than 10 years was found in 77.5% of respondents. Only 22.5% knew the definition of a blood- exposure accident. 100% and 95% of participants reported the relative risk, respectively, to hepatitis and AIDS viruses. However, only 15% recognized the severity factors of a blood-exposure accident. Hygiene compliance was the most important dimension for almost the entire population for the prevention. On the other hand, only 12.5% knew the meaning of 'standard precautions' and ¼ considered them necessary for at-risk patients only. 40% reported being exposed at least once, among them, 87.5% used betadine, and 77.5% said that anti-infectious chemoprophylaxis is necessary regardless of the patient's serological status. However, 52.5% did not know the official reporting circuit of management of blood-exposure accident in their institutions. Conclusion: For better management of risks in hospitals and an improvement of the safety of the care, a reinforcement of the sensibilization of the caregivers with regard to the risks of blood exposure accident is necessary, while developing their knowledge to act in security.

Keywords: attitudes, blood-exposure accident, knowledge, pediatric department

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69 Molecular Mechanisms of Lipid Metabolism and Obesity Modulation by Caspase-1/11 and nlrp3 Inflammasome in Mice

Authors: Lívia Pimentel Sant'ana Dourado, Raquel Das Neves Almeida, Luís Henrique Costa Corrêa Neto, Nayara Soares, Kelly Grace Magalhães

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Introduction: Obesity and high-fat diet intake have a crucial impact on immune cells and inflammatory profile, highlighting an emerging realization that obesity is an inflammatory disease. In the present work, we aimed to characterize the role of caspase-1/11 and NLRP3 inflammasome in the establishment of mice obesity and modulation of inflammatory lipid metabolism induced by high fat diet intake. Methods and results: Wild type, caspase-1/11 and NLRP3 knockout mice were fed with standard fat diet (SFD) or high fat diet (HFD) for 90 days. The weight of animals was measured weekly to monitor the weight gain. After 90 days, the blood, peritoneal lavage cells, heart and liver were collected from mice studied here. Cytokines were measured in serum by ELISA and analyzed in spectrophotometry. Lipid antigen presentation molecule CD1d expression, reactive oxygen species (ROS) generation and lipid droplets biogenesis were analyzed in cells from mice peritoneal cavity by flow cytometry. Liver histopathology was performed for morphological evaluation of the organ. The absence of caspase-1/11, but not NLRP3, in mice fed with HFD favored the mice weight gain, increased liver size, induced development of hepatic steatosis and IL-12 secretion in mice compared to mice fed with SFD. In addition, caspase-1/11 knockout mice fed with HFD presented an increased CD1d molecule expression, as well as higher levels of lipid droplets biogenesis and ROS generation compared to wild type mice also fed with HFD. Conclusion: Our data suggest that caspase-1/11 knockout mice have greater susceptibility to obesity as well as increased activation of lipid metabolism and inflammatory markers.

Keywords: caspase 1, caspase 11, inflamassome, obesity, lipids

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68 Autoimmune Diseases Associated with Celiac Disease in Adults

Authors: Soumaya Mrabet, Taieb Ach, Imen Akkari, Amira Atig, Neirouz Ghannouchi, Koussay Ach, Elhem Ben Jazia

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Introduction: Celiac disease (CD) is an immune-mediated small intestinal disorder that occurs in genetically susceptible people. It is significantly associated with other autoimmune disorders represented mainly by type 1 diabetes and autoimmune dysthyroidism. The aim of our study is to determine the prevalence and the type of the various autoimmune diseases associated with CD in adult patients. Material and methods: This is a retrospective study including patients diagnosed with CD, explored in Internal Medicine, Gastroenterology and Endocrinology and Diabetology Departments of the Farhat Hached University Hospital, between January 2005 and January 2016. The diagnosis of CD was confirmed by serological tests and duodenal biopsy. The screening of autoimmune diseases was based on physical examination, biological and serological tests. Results: Sixty five patients with a female predominance were included, 48women (73.8%) and 17 men (26.2%). The mean age was 31.8 years (17-75). A family history of CD or other autoimmune diseases was present in 5 and 10 patients respectively. Clinical presentation of CD was made by recurrent abdominal pain in 49 cases, diarrhea in 29 cases, bloating in 17 cases, constipation in 25 cases and vomiting in 8 cases. Autoimmune diseases associated with CD were found in 30 cases (46.1%): type 1 diabetes in 15 patients attested by the positivity of anti-GAD antibodies in 11 cases and anti-IA2 in 4 cases, Hashimoto thyroiditis in 8 cases confirmed by the positivity of anti-TPO antibodies, Addison's disease in 2 patients, Anemia of Biermer in 2 patients, autoimmune hepatitis, Systemic erythematosus lupus, Gougerot Sjögren syndrome, rheumatoid arthritis, Vitiligo and antiphospholipid syndrome in one patient each. CD was associated with more than one autoimmune disease defining multiple autoimmune syndrome in 2 female patients. The first patient had Basedow disease, Addison disease and type 1 diabetes. The second patient had systemic erythematosus lupus and Gougerot Sjögren syndrome. Conclusion: In our study autoimmune diseases were associated with CD in 46.1% of cases and were dominated by diabetes and dysthroidism. After establishing the diagnosis of CD the search of associated autoimmune diseases is necessary in order to avoid any therapeutic delay which can alter the prognosis of the patient.

Keywords: association, autoimmune thyroiditis, celiac disease, diabetes

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67 Results of the Safety Evaluation of Cancer Vaccines Dealing with Novel Targets for Cancer Immunotherapy

Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

Abstract:

Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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66 Electrochemical Biosensor Based on Chitosan-Gold Nanoparticles, Carbon Nanotubes for Detection of Ovarian Cancer Biomarker

Authors: Parvin Samadi Pakchin, Reza Saber, Hossein Ghanbari, Yadollah Omidi

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Ovarian cancer is one of the leading cause of mortality among the gynecological malignancies, and it remains the one of the most prevalent cancer in females worldwide. Tumor markers are biochemical molecules in blood or tissues which can indicates cancers occurrence in the human body. So, the sensitive and specific detection of cancer markers typically recruited for diagnosing and evaluating cancers. Recently extensive research efforts are underway to achieve a simple, inexpensive and accurate device for detection of cancer biomarkers. Compared with conventional immunoassay techniques, electrochemical immunosensors are of great interest, because they are specific, simple, inexpensive, easy to handling and miniaturization. Moreover, in the past decade nanotechnology has played a crucial role in the development of biosensors. In this study, a signal-off electrochemical immunosensor for the detection of CA125 antigen has been developed using chitosan-gold nanoparticles (CS-AuNP) and multi-wall carbon nanotubes (MWCNT) composites. Toluidine blue (TB) is used as redox probe which is immobilized on the electrode surface. CS-AuNP is synthesized by a simple one step method that HAuCl4 is reduced by NH2 groups of chitosan. The CS-AuNP-MWCNT modified electrode has shown excellent electrochemical performance compared with bare Au electrode. MWCNTs and AuNPs increased electrochemical conductivity and accelerate electrons transfer between solution and electrode surface while excessive amine groups on chitosan lead to the effective loading of the biological material (CA125 antibody) and TB on the electrode surface. The electrochemical, immobilization and sensing properties CS-AuNP-MWCNT-TB modified electrodes are characterized by cyclic voltammetry, electrochemical impedance spectroscopy, differential pulse voltammetry and square wave voltammetry with Fe(CN)63−/4−as an electrochemical redox indicator.

Keywords: signal-off electrochemical biosensor, CA125, ovarian cancer, chitosan-gold nanoparticles

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65 Application of Gamma Frailty Model in Survival of Liver Cirrhosis Patients

Authors: Elnaz Saeedi, Jamileh Abolaghasemi, Mohsen Nasiri Tousi, Saeedeh Khosravi

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Goals and Objectives: A typical analysis of survival data involves the modeling of time-to-event data, such as the time till death. A frailty model is a random effect model for time-to-event data, where the random effect has a multiplicative influence on the baseline hazard function. This article aims to investigate the use of gamma frailty model with concomitant variable in order to individualize the prognostic factors that influence the liver cirrhosis patients’ survival times. Methods: During the one-year study period (May 2008-May 2009), data have been used from the recorded information of patients with liver cirrhosis who were scheduled for liver transplantation and were followed up for at least seven years in Imam Khomeini Hospital in Iran. In order to determine the effective factors for cirrhotic patients’ survival in the presence of latent variables, the gamma frailty distribution has been applied. In this article, it was considering the parametric model, such as Exponential and Weibull distributions for survival time. Data analysis is performed using R software, and the error level of 0.05 was considered for all tests. Results: 305 patients with liver cirrhosis including 180 (59%) men and 125 (41%) women were studied. The age average of patients was 39.8 years. At the end of the study, 82 (26%) patients died, among them 48 (58%) were men and 34 (42%) women. The main cause of liver cirrhosis was found hepatitis 'B' with 23%, followed by cryptogenic with 22.6% were identified as the second factor. Generally, 7-year’s survival was 28.44 months, for dead patients and for censoring was 19.33 and 31.79 months, respectively. Using multi-parametric survival models of progressive and regressive, Exponential and Weibull models with regard to the gamma frailty distribution were fitted to the cirrhosis data. In both models, factors including, age, bilirubin serum, albumin serum, and encephalopathy had a significant effect on survival time of cirrhotic patients. Conclusion: To investigate the effective factors for the time of patients’ death with liver cirrhosis in the presence of latent variables, gamma frailty model with parametric distributions seems desirable.

Keywords: frailty model, latent variables, liver cirrhosis, parametric distribution

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64 Angiogenic, Cytoprotective, and Immunosuppressive Properties of Human Amnion and Chorion-Derived Mesenchymal Stem Cells

Authors: Kenichi Yamahara, Makiko Ohshima, Shunsuke Ohnishi, Hidetoshi Tsuda, Akihiko Taguchi, Toshihiro Soma, Hiroyasu Ogawa, Jun Yoshimatsu, Tomoaki Ikeda

Abstract:

We have previously reported the therapeutic potential of rat fetal membrane(FM)-derived mesenchymal stem cells (MSCs) using various rat models including hindlimb ischemia, autoimmune myocarditis, glomerulonephritis, renal ischemia-reperfusion injury, and myocardial infarction. In this study, 1) we isolated and characterized MSCs from human amnion and chorion; 2) we examined their differences in the expression profile of growth factors and cytokines; and 3) we investigated the therapeutic potential and difference of these MSCs using murine hindlimb ischemia and acute graft-versus-host disease (GVHD) models. Isolated MSCs from both amnion and chorion layers of FM showed similar morphological appearance, multipotency, and cell-surface antigen expression. Conditioned media obtained from amnion- and chorion-derived MSCs inhibited cell death caused by serum starvation or hypoxia in endothelial cells and cardiomyocytes. Amnion and chorion MSCs secreted significant amounts of angiogenic factors including HGF, IGF-1, VEGF, and bFGF, although differences in the cellular expression profile of these soluble factors were observed. Transplantation of human amnion or chorion MSCs significantly increased blood flow and capillary density in a murine hindlimb ischemia model. In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced T-lymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of GVHD disease. Our results highlight that human amnionand chorion-derived MSCs, which showed differences in their soluble factor secretion and angiogenic/immuno-suppressive function, could be ideal cell sources for regenerative medicine.

Keywords: amnion, chorion, fetal membrane, mesenchymal stem cells

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63 Magnetic Bio-Nano-Fluids for Hyperthermia

Authors: Z. Kolacinski, L. Szymanski. G. Raniszewski, D. Koza, L. Pietrzak

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Magnetic Bio-Nano-Fluid (BNF) can be composed of a buffer fluid such as plasma and magnetic nanoparticles such as iron, nickel, cobalt and their oxides. However iron is one of the best elements for magnetization by electromagnetic radiation. It can be used as a tool for medical diagnosis and treatment. Radio frequency (RF) radiation is able to heat iron nanoparticles due to magnetic hysteresis. Electromagnetic heating of iron nanoparticles and ferro-fluids BNF can be successfully used for non-invasive thermal ablation of cancer cells. Moreover iron atoms can be carried by carbon nanotubes (CNTs) if iron is used as catalyst for CNTs synthesis. Then CNTs became the iron containers and they screen the iron content against oxidation. We will present a method of CNTs addressing to the required cells. For thermal ablation of cancer cells we use radio frequencies for which the interaction with human body should be limited to minimum. Generally, the application of RF energy fields for medical treatment is justified by deep tissue penetration. The highly iron doped CNTs as the carriers creating magnetic fluid will be presented. An excessive catalyst injection method using electrical furnace and microwave plasma reactor will be presented. This way it is possible to grow the Fe filled CNTs on a moving surface in continuous synthesis process. This also allows producing uniform carpet of the Fe filled CNTs carriers. For the experimental work targeted to cell ablation we used RF generator to measure the increase in temperature for some samples like: solution of Fe2O3 in BNF which can be plasma-like buffer, solutions of pure iron of different concentrations in plasma-like buffer and in buffer used for a cell culture, solutions of carbon nanotubes (MWCNTs) of different concentrations in plasma-like buffer and in buffer used for a cell culture. Then the targeted therapies which can be effective if the carriers are able to distinguish the difference between cancerous and healthy cell’s physiology are considered. We have developed an approach based on ligand-receptor or antibody-antigen interactions for the case of colon cancer.

Keywords: cancer treatment, carbon nano tubes, drag delivery, hyperthermia, iron

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62 In Silico Study of Cell Surface Structures of Parabacteroides distasonis Involved in Its Maintain Within the Gut Microbiota and Its Potential Pathogenicity

Authors: Jordan Chamarande, Lisiane Cunat, Corentine Alauzet, Catherine Cailliez-Grimal

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Gut microbiota (GM) is now considered a new organ mainly due to the microorganism’s specific biochemical interaction with its host. Although mechanisms underlying host-microbiota interactions are not fully described, it is now well-defined that cell surface molecules and structures of the GM play a key role in such relation. The study of surface structures of GM members is also fundamental for their role in the establishment of species in the versatile and competitive environment of the digestive tract and as a potential virulence factor. Among these structures are capsular polysaccharides (CPS), fimbriae, pili and lipopolysaccharides (LPS), all well-described for their central role in microorganism colonization and communication with host epithelium. The health-promoting Parabacteroides distasonis, which is part of the core microbiome, has recently received a lot of attention, showing beneficial properties for its host and as a new potential biotherapeutic product. However, to the best of the authors’ knowledge, the cell surface molecules and structures of P. distasonis that allow its maintain within the GM are not identified. Moreover, although P. distasonis is strongly recognized as intestinal commensal species with benefits for its host, it has also been recognized as an opportunistic pathogen. In this study, we reported gene clusters potentially involved in the synthesis of the capsule, fimbriae-like and pili-like cell surface structures in 26 P. distasonis genomes and applied the new RfbA-Typing classification in order to better understand and characterize the beneficial/pathogenic behaviour related to P. distasonis strains. In context, 2 different types of fimbriae, 3 of pilus and up to 14 capsular polysaccharide loci, have been identified over the 26 genomes studied. Moreover, the addition of data to the rfbA-Type classification modified the outcome by rearranging rfbA genes and adding a fifth group to the classification. In conclusion, the strain variability in terms of external proteinaceous structure could explain the inter-strain differences previously observed in P. distasonis adhesion capacities and its potential pathogenicity.

Keywords: gut microbiota, Parabacteroides distasonis, capsular polysaccharide, fimbriae, pilus, O-antigen, pathogenicity, probiotic, comparative genomics

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61 Correlative Study of Serum Interleukin-18 and Disease Activity, Functional Disability and Quality of Life in Rheumatoid Arthritis Patients

Authors: Hamdy Khamis Korayem, Manal Yehia Tayel, Abeer Shawky El Hadedy, Emmanuel Kamal Aziz Saba, Shimaa Badr Abdelnaby Badr

Abstract:

The aim of the current study was to demonstrate whether serum Interleukin-18 (IL-18) is increased in rheumatoid arthritis (RA) and its correlation with disease activity, functional disability and quality of life in RA patients. The study included 30 RA patients and 20 healthy normal control subjects. The RA patients were diagnosed according to the 2010 ACR/EULAR classification criteria for RA with the exclusion of those who had diabetes mellitus, endocrine disorders, associated rheumatologic diseases, viral hepatitis B or C and other diseases with increased serum IL-18 level. All patients were subjected to clinical evaluation of the musculoskeletal system. Disease activity was assessed by disease activity score 28 with 4 variables (DAS 28). Functional disability was assessed by health assessment questionnaire disability index (HAQ-DI). The quality of life was assessed by Short form-36 (SF-36) questionnaire. Radiological assessment of both hands and feet by Sharp/van der Heijde (SvH) scoring method. Laboratory parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were assessed in patients and serum level of IL-18 in both patients and control subjects. There was no statistically significant difference between patient and control group as regards age and sex. Among patients, 29 % were females and the age range was between 25 to 55 years. Extra-articular manifestations were presented in 56.7% of the patients. The mean of DAS 28 score was 5.73±1.46 and that of HAQ-DI was 1.22±0.72 while that of SF-36 was 40.03±13.96. The level of serum IL-18 was significantly higher in patients than in the control subjects (P= 0.030). Serum IL-18 was correlated with ACPA among the patient group. There were no statistically significant correlations between serum IL-18 and DAS28, HAQ-DI, SF-36, total SvH score and the other laboratory results. In conclusion, IL-18 is significantly higher in RA patient than in healthy control subjects and positively correlated with ACPA level. IL-18 is associated with extra-articular manifestations. However, it is not correlated with other laboratory parameters, disease activity, functional disability, quality of life nor radiological severity.

Keywords: disease activity score, Interleukin-18, quality of life assessment, rheumatoid arthritis

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60 Overview of Cage Aquaculture Practices, Benefits and Challenges on Africa Waters Bodies

Authors: Mekonen Hailu, Liu Liping

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Cage aquaculture is highly preferred due to higher production per unit volume of water, lower costs of investment, and simpler routine farm management procedures compared to pond systems. In the 1980s, cage culture was first used on a trial basis in sub-Saharan Africa. Over the past 20 years, a small number of prosperous freshwater cage culture operations have started to emerge in Egypt, Rwanda, Kenya, Uganda, Tanzania, Ghana, Malawi, Zambia and Zimbabwe. Brackish and marine cage culture also offers a lot of potential, although this subsector hasn't seen any significant commercial growth to date. In 2019, 263 cage aquaculture installations on the African inland waters on 18 water bodies within eight countries with an estimated 20,114 cages were reported. The lakes Victoria, Kariba, Volta, and River Volta, which together account for 82.9% of all cage aquaculture installations regarded as sub-Saharan Africa's principal cage aquaculture regions (Fig 1). Except few small-scale trials with North African catfish (Clarias gariepinus), almost all farms in Sub-Saharan Africa and Egypt grow Nile tilapia (Oreochromis niloticus). More than 247,398 tonnes of fish are produced yearly from ten African countries through cage aquaculture. The expansion of cage culture in Africa provides job opportunities for both skilled and unskilled workers, nutritious food and foreign currency. The escaping non-native strains of tilapia in Lake Volta and the occurrence of a risky Tilapia lake virus (syncytial hepatitis), which has the potential to wipe out entire populations in both wild and farmed Nile tilapia on Lake Victoria, are threats coming with the expansion of cage aquaculture in Africa. In addition, the installations of 138 cage aquacultures were found in contrary to best cage culture practices. To sustain cage aquaculture development and maintain harmony with other water uses, developers must strictly abide by best practices. Hence, the exclusion of protected areas and small lakes (average depth 5 m or less) should be done, as well an Environmental Impact Assessment should be conducted before establishing the cage farms.

Keywords: Africa, cage aquaculture, production, threats

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