The maintenance effect of β-amyloid injection in the CA1 region of hippocampus on learning and spatial memory in adult male rats

Background: Alzheimer’s disease is one of the most common neurodegenerative diseases that lead to the progressive loss of mental, behavioral and learning abilities. The aim of this study was to investigate the maintenance effect of β-amyloid1-42 (Aβ) injection in the CA1 region of hippocampus on learning and spatial memory of adult male rats using the Morris water maze test. Materials and Methods: In this study, 42 adult male Wistar rats were randomly divided into control (intact), sham (Aβ solvent) and Aβ-injected groups (5 μg/μl). The β-amyloid and its solvent were bilaterally injected into the CA1 region of rats' hippocampus. The first recipient group of Aβ and its solvent after 6, the second group after 11 and the third groups after 31 days were trained by the Morris water maze test. Results: During 4 training days and also in probe and visible tests, there was no significant difference between control and sham groups. The results of the learning steps in Aβ groups showed that traveled distance and escape latency to find the hidden platform was significantly increased compared with the sham groups, but there was no significant difference in the probe and visible tests between these groups. Conclusion: It seems that long exposure to Aβ can lead to more memory and learning loss in animals with Alzheimer

The progress and research trends in oncolytic virotherapy: The bibliometric analysis from 2000 to 2019

Introduction: The objective of the present report is to perform the first comprehensive bibliometric analysis of oncolytic virotherapy research publications. Methods: Scopus was employed as a major database. The total number of publications was found to be 4369, majorly comprising of research articles (n=2895) and reviews (1082). The ANOVA F-test and Welch F-tests were performed to determine the significance (P=0.05). Results: In all publications (3751), the total numbers of authors were 11418 and 10480 different organizations, departments or institutes. We specifically selected seven different viral strains and provided details about the co-authorship network. We also provided details about the top 10 most cited documents. Conclusion: This may provide a quantitative overview about the trends and publications in oncolytic virotherapy research

Fiber manipulation and post-assembly nanobody conjugation for adenoviral vector retargeting through SpyTag-SpyCatcher protein ligation

For adenoviruses (Ads) to be optimally effective in cancer theranostics, they need to be retargeted toward target cells and lose their natural tropism. Typically, this is accomplished by either engineering fiber proteins and/or employing bispecific adapters, capable of bonding Ad fibers and tumor antigen receptors. This study aimed to present a simple and versatile method for generating Ad-based bionanoparticles specific to target cells, using the SpyTag-SpyCatcher system. The SpyTag peptide was inserted into the HI loop of fiber-knob protein, which could act as a covalent anchoring site for a targeting moiety fused to a truncated SpyCatcher (SpyCatcherΔ) pair. After confirming the presence and functionality of SpyTag on the Ad type-5 (Ad5) fiber knob, an adapter molecule, comprising of SpyCatcherΔ fused to an anti-vascular endothelial growth factor receptor 2 (VEGFR2) nanobody, was recombinantly expressed in Escherichia coli and purified before conjugation to fiber-modified Ad5 (fmAd5). After evaluating fmAd5 detargeting from its primary coxsackie and adenovirus receptor (CAR), the nanobody-decorated fmAd5 could be efficiently retargeted to VEGFR2-expressing 293/KDR and human umbilical vein endothelial (HUVEC) cell lines. In conclusion, a plug-and-play platform was described in this study for detargeting and retargeting Ad5 through the SpyTag-SpyCatcher system, which could be potentially applied to generate tailored bionanoparticles for a broad range of specific targets; therefore, it can be introduced as a promising approach in cancer nanotheranostics

Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant = Avaliação da potência terapêutica da vacina de DNA do papilomavírus humano-16 E7 isolada e com interleucina-18 como adjuvante genético

OBJETIVOS: Apesar da existência de vacinas preventivas eficazes contra o papilomavírus humano (HPV), são necessárias vacinas terapêuticas que desencadeiem respostas imunes mediadas por células para tratar infecções e malignidades estabelecidas. O objetivo deste estudo foi avaliar a potência terapêutica da vacina de ácido desoxirribonucleico (DNA) HPV-16 E7 isolada e com interleucina (IL)-18. MÉTODOS: Expressões in vitro de IL-18 foram realizadas em células renais embrionárias humanas 293 e confirmadas por Western blotting. A vacina de DNA foi disponibilizada em um estudo anterior. Um total de 45 camundongos fêmeas C57BL/6 divididos em cinco grupos (vacina de DNA, vacina de DNA adjuvada com IL-18, pcDNA3. 1 e solução salina tamponada com fosfato) e foram inoculados com linhagem murina-1 de carcinoma relacionado ao HPV, expressando antígenos E6 / E7 do HPV-16. Os animais foram então imunizados por via subcutânea duas vezes no intervalo de sete dias. A imunidade antitumoral e antígeno-celular específica foi avaliada pela proliferação de linfócitos (ensaio de brometo de 3- [4,5-dimetiltiazol-2-il] -2,5-difeniltetrazólio: MTT), ensaio de liberação de lactato desidrogenase, ensaio de IL-4 e ensaio de interferon-gama [IFN-γ]. O tamanho do tumor foi seguido por 62 dias. RESULTADOS: O ensaio MTT, que mede a proliferação de linfócitos em resposta ao antígeno específico, aumentou nos grupos de coadministração e de vacina de DNA em comparação aos grupos controle e adjuvante genético (p <0,001). Os camundongos imunizados com a coadministração geraram significativamente mais IFN-γ e IL-4 do que os outros camundongos imunizados (p<0,001) A redução do tamanho do tumor nos grupos de coadministração e de vacina de DNA foi significativamente mais acentuada do que nos grupos controle e adjuvante genético (p<0,001), mas não houve nenhuma diferença estatisticamente significativa entre os grupos vacina de DNA e coadministração (p=0,15). CONCLUSÕES: A IL-18 como adjuvante genético e a vacina de DNA E7 aumentaram as respostas imunes em sistemas modelo de camundongos contra o câncer cervical. No entanto, o uso de IL-18 como adjuvante genético com a vacina de DNA E7 não teve efeito sinérgico significativo nas respostas imunes in viv

In Silico Analysis of Six Known Leishmania major Antigens and In Vitro Evaluation of Specific Epitopes Eliciting HLA-A2 Restricted CD8 T Cell Response

Leishmaniasis is currently a serious health as well as economic problem in underdeveloped and developing countries in Africa, Asia, the Near and Middle East, Central and South America and the Mediterranean region. Cutaneous leishmaniasis is highly endemic in Iran, remarkably in Isfahan, Fars, Khorasan, Khozestan and Kerman provinces. Since effective prevention is not available and current curative therapy is expensive, often poorly tolerated and not always effective, alternative therapies including vaccination against leishmaniasis are of priority to overcome the problem. Although Th1 dominant response is so far considered as a pre-requisite for the immune system to overcome the infection, CD8+ T cell response could also be considered as a potent arm of immune system fighting against intracellular Leishmania. Polytope vaccine strategy may open up a new way in vaccine design against leishmaniasis, since they act as a potent tool to stimulate multi-CD8 T cell responses. Clearly there is a substantial need to evaluate the promising epitopes from different proteins of Leishmania parasite species. Some new immunoinformatic tools are now available to speed up this process, and we have shown here that in silico prediction can effectively evaluate HLA class I-restricted epitopes out of Leishmania proteins

Activating Natural Killer Cell Receptors, Selectins, and Inhibitory Siglecs Recognize Ebolavirus Glycoprotein

Expression of the extensively glycosylated Ebolavirus glycoprotein (EBOV-GP) induces physical alterations of surface molecules and plays a crucial role in viral pathogenicity. Here we investigate the interactions of EBOV-GP with host surface molecules using purified EBOV-GP, EBOV-GP-transfected cell lines, and EBOV-GP-pseudotyped lentiviral particles. Subsequently, we wanted to examine which receptors are involved in this recognition by binding studies to cells transfected with the EBOV-GP as well as to recombinant soluble EBOV-GP. As the viral components can also bind to inhibitory receptors of immune cells (e.g., Siglecs, TIM-1), they can even suppress the activity of immune effector cells. Our data show that natural killer (NK) cell receptors NKp44 and NKp46, selectins (CD62E/P/L), the host factors DC-SIGNR/DC-SIGN, and inhibitory Siglecs function as receptors for EBOV-GP. Our results show also moderate to strong avidity of homing receptors (P-, L-, and E-selectin) and DC-SIGNR/DC-SIGN to purified EBOV-GP, to cells transfected with EBOV-GP, as well as to the envelope of a pseudotyped lentiviral vector carrying the EBOV-GP. The concomitant activation and inhibition of the immune system exemplifies the evolutionary antagonism between the immune system and pathogens. Altogether these interactions with activating and inhibitory receptors result in a reduced NK cell-mediated lysis of EBOV-GP-expressing cells. Modulation of these interactions may provide new strategies for treating infections caused by this virus.publishedVersio

A novel medium-throughput biological assay system for HTLV-1 infectivity and drug discovery

Objective(s): Here, a reporter cell line containing two reporter vectors were developed, in order to monitor the Human T-Lymphotropic Virus type1(HTLV-1) infectivity and the cell viability simultaneously. Materials and Methods: The reporter cell line was constructed by stably transfected baby hamster's kidney cell line (BHK-21), with the genomes expressing two different reporters in separate plasmids.The first reporter gene is transactivated by the HTLV-1 tax protein, while the second reporter is continuously expressed when introduced into a mammalian cell. In order to show its functionality, the effect of the drug mix on HTLV-1 was assayed by this system and was compared to the results obtained by other methods. Results: HTLV-1 reporter cell line was found to produce high level of luciferase when co-cultured with MT-2 and Hut-102 cells but not with Jurkat cell. Moreover, the combination therapy against HTLV-1 can reduce luciferase expression of the cell when co-cultured with MT-2 and Hut-102 comparable to the ELISA (R=0.932, P-value =0.002). In addition, the results revealed the superiority of the present system over the molecular methods. Conclusion: The results demonstrated that the biological assay system is a beneficial tool for the medium-throughput anti-HTLV-1 drug screening and inhibitory effect

The maintenance effect of β-amyloid injection in the CA1 region of hippocampus on learning and spatial memory in adult male rats

Background: Alzheimer’s disease is one of the most common neurodegenerative diseases that lead to the progressive loss of mental, behavioral and learning abilities. The aim of this study was to investigate the maintenance effect of β-amyloid1-42 (Aβ) injection in the CA1 region of hippocampus on learning and spatial memory of adult male rats using the Morris water maze test. Materials and Methods: In this study, 42 adult male Wistar rats were randomly divided into control (intact), sham (Aβ solvent) and Aβ-injected groups (5 μg/μl). The β-amyloid and its solvent were bilaterally injected into the CA1 region of rats' hippocampus. The first recipient group of Aβ and its solvent after 6, the second group after 11 and the third groups after 31 days were trained by the Morris water maze test. Results: During 4 training days and also in probe and visible tests, there was no significant difference between control and sham groups. The results of the learning steps in Aβ groups showed that traveled distance and escape latency to find the hidden platform was significantly increased compared with the sham groups, but there was no significant difference in the probe and visible tests between these groups. Conclusion: It seems that long exposure to Aβ can lead to more memory and learning loss in animals with Alzheimer