Search results for: viral mutation

Authors: Selena Ferrian, Erin Mccaffrey, Toshie Saito, Aiqin Cao, Noah Greenwald, Mark Robert Nicolls, Trevor Bruce, Roham T. Zamanian, Patricia Del Rosario, Marlene Rabinovitch, Michael Angelo

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Recent experimental and clinical observations are advancing immunotherapies to clinical trials in pulmonary arterial hypertension (PAH). However, comprehensive mapping of the immune landscape in pulmonary arteries (PAs) is necessary to understand how immune cell subsets interact to induce pulmonary vascular pathology. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to interrogate the immune landscape in PAs from idiopathic (IPAH) and hereditary (HPAH) PAH patients. Massive immune infiltration in I/HPAH was observed with intramural infiltration linked to PA occlusive changes. The spatial context of CD11c+DCs expressing SAMHD1, TIM-3 and IDO-1 within immune-enriched microenvironments and neutrophils were associated with greater immune activation in HPAH. Furthermore, CD11c-DC3s (mo-DC-like cells) within a smooth muscle cell (SMC) enriched microenvironment were linked to vessel score, proliferating SMCs, and inflamed endothelial cells. Experimental data in cultured cells reinforced a causal relationship between neutrophils and mo-DCs in mediating pulmonary arterial SMC proliferation. These findings merit consideration in developing effective immunotherapies for PAH.

Keywords: pulmonary arterial hypertension, vascular remodeling, indoleamine 2-3-dioxygenase 1 (IDO-1), neutrophils, monocyte-derived dendritic cells, BMPR2 mutation, interferon gamma (IFN-γ)

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Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

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Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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Authors: Yudi Zhao, Ziyun Zhou, Yueting Yao, Shuying Dai, Zhiling Yan, Longyu Yang, Chuanyin Li, Li Shi, Yufeng Yao

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HPV16 E4 gene plays an important role in viral genome amplification and release. Therefore, a variation of the E4 gene nucleic acid sequence may affect the carcinogenicity of HPV16. In order to understand the relationship between the variation of HPV16 E4 gene and cervical cancer, this study was to amplify and sequence the DNA sequences of E4 genes in 118 HPV16-positive cervical cancer patients and 151 HPV16-positive asymptomatic individuals. After obtaining E4 gene sequences, the phylogenetic trees were constructed by the Neighbor-joining method for gene variation analysis. The results showed that: 1) The distribution of HPV16 variants between the case group and the control group differed greatly (P = 0.015)，and the Asian-American（AA）variant was likely to relate to the occurrence of cervical cancer. 2) DNA sequence analysis showed that there were significant differences in the distribution of 8 variants between the case group and the control group (P < 0.05). And 3) In European (EUR) variant, two variations, C3384T (L18L) and A3449G (P39P), were associated with the initiation and development of cervical cancer. The results suggested that the variation of HPV16 E4 gene may be a contributor affecting the occurrence as well as the development of cervical cancer, and different HPV16 variants may have different carcinogenic capability.

Keywords: cervical cancer, HPV16, E4 gene, variations

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Authors: T. Toathom, M. Munlin, P. Sugunnasil

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The traveling salesman problem (TSP) is one of the best-known problems in optimization problem. There are many research regarding the TSP. One of the most usage tool for this problem is the genetic algorithm (GA). The chromosome of the GA for TSP is normally encoded by the order of the visited city. However, the traditional chromosome encoding scheme has some limitations which are twofold: the large solution space and the inability to encapsulate some information. The number of solution for a certain problem is exponentially grow by the number of city. Moreover, the traditional chromosome encoding scheme fails to recognize the misplaced correct relation. It implies that the tradition method focuses only on exact solution. In this work, we relax some of the concept in the GA for TSP which is the exactness of the solution. The proposed work exploits the relation between cities in order to reduce the solution space in the chromosome encoding. In this paper, a second order GA is proposed to solve the TSP. The term second order refers to how the solution is encoded into chromosome. The chromosome is divided into 2 types: the high order chromosome and the low order chromosome. The high order chromosome is the chromosome that focus on the relation between cities such as the city A should be visited before city B. On the other hand, the low order chromosome is a type of chromosome that is derived from a high order chromosome. In other word, low order chromosome is encoded by the traditional chromosome encoding scheme. The genetic operation, mutation and crossover, will be performed on the high order chromosome. Then, the high order chromosome will be mapped to a group of low order chromosomes whose characteristics are satisfied with the high order chromosome. From the mapped set of chromosomes, the champion chromosome will be selected based on the fitness value which will be later used as a representative for the high order chromosome. The experiment is performed on the city data from TSPLIB.

Keywords: genetic algorithm, traveling salesman problem, initial population, chromosomes encoding

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Authors: Mahawish Masud, Muhammad Iqbal, M. U. Khan, Farooque Azam

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Manual writing of test cases from functional requirements is a time-consuming task. Such test cases are not only difficult to write but are also challenging to maintain. Test cases can be drawn from the functional requirements that are expressed in natural language. However, manual test case generation is inefficient and subject to errors.  In this paper, we have presented a systematic procedure that could automatically derive test cases from user stories. The user stories are specified in a restricted natural language using a well-defined template.  We have also presented a detailed methodology for writing our test ready user stories. Our tool “Test-o-Matic” automatically generates the test cases by processing the restricted user stories. The generated test cases are executed by using open source Selenium IDE.  We evaluate our approach on a case study, which is an open source web based application. Effectiveness of our approach is evaluated by seeding faults in the open source case study using known mutation operators.  Results show that the test case generation from restricted user stories is a viable approach for automated testing of web applications.

Keywords: automated testing, natural language, restricted user story modeling, software engineering, software testing, test case specification, transformation and automation, user story, web application testing

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Authors: Shuo Mu, Guangzhi Jiang, Jinsa Chen

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The analysis of Indel for RNA sequencing of clinical samples is easily affected by sequencing experiment errors and software selection. In order to improve the efficiency and accuracy of analysis, we developed an automatic reporting system for Indel recognition and annotation based on image snapshot of transcriptome reads alignment. This system includes sequence local-assembly and realignment, target point snapshot, and image-based recognition processes. We integrated high-confidence Indel dataset from several known databases as a training set to improve the accuracy of image processing and added a bioinformatical processing module to annotate and filter Indel artifacts. Subsequently, the system will automatically generate data, including data quality levels and images results report. Sanger sequencing verification of the reference Indel mutation of cell line NA12878 showed that the process can achieve 83% sensitivity and 96% specificity. Analysis of the collected clinical samples showed that the interpretation accuracy of the process was equivalent to that of manual inspection, and the processing efficiency showed a significant improvement. This work shows the feasibility of accurate Indel analysis of clinical next-generation sequencing (NGS) transcriptome. This result may be useful for RNA study for clinical samples with microsatellite instability in immunotherapy in the future.

Keywords: automatic reporting, indel, next-generation sequencing, NGS, transcriptome

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Authors: Zerrin Orbak, Busra Demir

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Osteopetrosis is a rare genetic disease characterized by impaired bone resorption and increased bone sclerosis. Clinical presentation is very different in osteopetrosis. It can be asymptomatic or can be seen with typical symptoms. Here, a case of osteopetrosis was presented when evaluated for nystagmus. She was 10 months old. Parents were second-degree relatives. On physical examination, pigeon chest deformity and horizontal nystagmus were observed. There was a failure of thrive but no fracture. The cardiovascular examination was normal. Cranial, vertebral and long bone roentgenograms revealed characteristic deformities of osteopetrosis and diffuse sclerosis. The diagnosis was confirmed by genetic testing. A Homozygous mutation was detected in the TNFRSF11A gene (c.508A>G p.(Arg170Gly)). RANKL is encoded by the tumor necrosis factor ligand superfamily member 11 (TNFSF11) gene, and the binding to its receptor RANK, encoded by the TNFRSF11A gene, determines the activation of the downstream pathway that drives osteoclast differentiation and activation (51). The complete absence of osteoclasts is the key feature of the osteoclast-poor form of osteopetrosis (46). Patients are characterized by the absence of TRAP-positive osteoclasts in bone biopsies. The osteoclast-poor subtype of osteopetrosis caused by mutations in TNFSF11 gene is ultra-rare in humans. Clinical presentation is usually severe, with onset in early infancy or in fetal life. But here, a case was presented with horizontal nystagmus. A case presented with horizontal nystagmus, which was evaluated by neurology and diagnosed incidentally, was shared.

Keywords: osteopetrosis, nystagmus, bone, osteoclast-poor

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Authors: Vanja Misic, Mohamed El-Mogy, Yousef Haj-Ahmad

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Endonuclease G (EndoG) is a well conserved mitochondrio-nuclear nuclease with dual lethal and vital roles in the cell. The aim of our study was to examine whether EndoG exerts its nuclease activity on exogenous DNA substrates such as plasmid DNA (pDNA), considering their importance in gene therapy applications. The effects of EndoG knockdown on pDNA stability and levels of encoded reporter gene expression were evaluated in the cervical carcinoma HeLa cells. Transfection of pDNA vectors encoding short-hairpin RNAs (shRNAs) reduced levels of EndoG mRNA and nuclease activity in HeLa cells. In physiological circumstances, EndoG knockdown did not have an effect on the stability of pDNA or the levels of encoded transgene expression as measured over a four day time-course. However, when endogenous expression of EndoG was induced by an extrinsic stimulus, targeting of EndoG by shRNA improved the perceived stability and transgene expression of pDNA vectors. Therefore, EndoG is not a mediator of exogenous DNA clearance, but in non-physiological circumstances it may non-specifically cleave intracellular DNA regardless of its origin. These findings make it unlikely that targeting of EndoG is a viable strategy for improving the duration and level of transgene expression from non-viral DNA vectors in gene therapy efforts.

Keywords: EndoG, silencing, exogenous DNA stability, HeLa cells

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Authors: D. J. Kalita

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Cancer is one of the prime causes of early death worldwide. Mutation of the gene involve in DNA repair and damage, like BRCA2 (Breast cancer gene two) genes, can be detected efficiently by PCR-RFLP to early breast cancer diagnosis and adopt the suitable method of treatment. Host Defense Peptide can be used as blueprint for the design and synthesis of novel anticancer drugs to avoid the side effect of conventional chemotherapy and chemo resistance. The change at nucleotide position 392 of a -› c in the cancer sample of dog mammary tumour at BRCA2 (exon 7) gene lead the creation of a new restriction site for SsiI restriction enzyme. This SNP may be a marker for detection of canine mammary tumour. Support vector machine (SVM) algorithm was used to design and predict the anticancer peptide from the mature functional peptide. MTT assay of MCF-7 cell line after 48 hours of post treatment showed an increase in the number of rounded cells when compared with untreated control cells. The ability of the synthesized peptide to induce apoptosis in MCF-7 cells was further investigated by staining the cells with the fluorescent dye Hoechst stain solution, which allows the evaluation of the nuclear morphology. Numerous cells with dense, pyknotic nuclei (the brighter fluorescence) were observed in treated but not in control MCF-7 cells when viewed using an inverted phase-contrast microscope. Thus, PCR-RFLP is one of the attractive approach for early diagnosis, and synthetic cationic peptide can be used for the treatment of canine mammary tumour.

Keywords: cancer, cationic peptide, host defense peptides, Breast cancer genes

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Authors: Arunima Verma, Padmabati Mondal

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Serotonin-receptor binding plays a key role in several neurological and biological processes, including mood, sleep, hunger, cognition, learning, and memory. In this article, we performed molecular dynamics simulation to examine the key residues that play an essential role in the binding of serotonin to the G-protein-coupled 5-HT₁ᴮ receptor (5-HT₁ᴮ R) via electrostatic interactions. An end-point free energy calculation method (MM-PBSA) determines the stability of the 5-HT1B R due to serotonin binding. The single-point mutation of the polar or charged amino acid residues (Asp129, Thr134) on the binding sites and the calculation of binding free energy validate the importance of these residues in the stability of the serotonin-receptor complex. Principal component analysis indicates the serotonin-bound 5-HT1BR is more stabilized than the apo-receptor in terms of dynamical changes. The difference dynamic cross-correlations map shows the correlation between the transmembrane and mini-Go, which indicates signal transduction happening between mini-Go and the receptor. Allosteric communication reveals the key nodes for signal transduction in 5-HT1BR. These results provide useful insights into the signal transduction pathways and mutagenesis study to regulate the functionality of the complex. The developed protocols can be applied to study local non-covalent interactions and long-range allosteric communications in any protein-ligand system for computer-aided drug design.

Keywords: allostery, CADD, MD simulations, MM-PBSA

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Authors: Ogbonnaya O. Iroanya, Samson T. Fakorede, Osamudiamen J. Edosa, Hadiat A. Azeez

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The human mitochondrial DNA (mtDNA) is about 17 kbp circular DNA fragments found within the mitochondria together with smaller fragments of 1200 bp known as the control region. Knowledge of variation within populations has been employed in forensic and molecular anthropology studies. The study was aimed at investigating the polymorphic nature of the two hypervariable segments (HVS) of the mtDNA, i.e., HVS1 and HVS2, and to determine the haplogroup distribution among individuals resident in Lagos, Southwestern Nigeria. Peripheral blood samples were obtained from sixty individuals who are not related maternally, followed by DNA extraction and amplification of the extracted DNA using primers specific for the regions under investigation. DNA amplicons were sequenced, and sequenced data were aligned and compared to the revised Cambridge Reference Sequence (rCRS) GenBank Accession number: NC_012920.1) using BioEdit software. Results obtained showed 61 and 52 polymorphic nucleotide positions for HVS1 and HVS2, respectively. While a total of three indels mutation were recorded for HVS1, there were seven for HVS2. Also, transition mutations predominate nucleotide change observed in the study. Genetic diversity (GD) values for HVS1 and HVS2 were estimated to be 84.21 and 90.4%, respectively, while random match probability was 0.17% for HVS1 and 0.89% for HVS2. The study also revealed mixed haplogroups specific to the African (L1-L3) and the Eurasians (U and H) lineages. New polymorphic sites obtained from the study are promising for human identification purposes.

Keywords: hypervariable region, indels, mitochondrial DNA, polymorphism, random match probability

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Authors: Fern Baedyananda, Arkom Chaiwongkot, Somchai Niruthisard, Nakarin Kitkumthorn, Parvapan Bhattarakosol

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High-risk human papillomavirus (HPV) infections cause transformation of the host cells by down-regulating and inhibiting host regulatory proteins such as p53 and pRb by overexpressing the viral oncoproteins E6 and E7. However, the E1 protein which is the only enzyme encoded by HPV has also been shown to cause DNA instability leading to the integration of the virus into the host genome and triggering carcinogenic events. A 63bp duplication in the E1 helicase region has been detected in European patients. However, the clinical prognosis of these patients is still controversial. This study was performed to determine the presence of the HPV-16 E1 63bp duplication in patient cervical samples in Thai women and determine the sequence of the variant in the Thai population. Detection of the HPV-16 E1 duplication in the helicase region was performed in 90 patient cell samples across normal, cervical intraepithelial neoplasia I-III, and squamous cervical carcinoma stages by PCR. The PCR products were purified and sequenced to determine the presence of duplication variants.The variant form was found in 10% of all CIN 1 patients. In this study, the presence of the 63 bp duplication variant in the Thai population was found to be present and was further characterized. Interestingly, all samples that exhibited the variant form of HPV-16 E1 were classified as CIN I. Presence of the variant, constricted to mild dysplasia signifies the importance of HPV-16 E1 in carcinogenesis.

Keywords: carcinogenesis, cervical cancer, human papillomavirus, HPV-16 E1

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Authors: Tariq Abbas, Younus Muhammad, Sayyad Aun Muhammad

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Background : Crimean Congo hemorrhagic fever (CCHF) is a tick born viral zoonotic disease that has been notified from almost all regions of Pakistan. The aim of this study was to investigate spatial distribution of CCHF cases reported to National Institue of Health , Islamabad during year 2013. Methods : Spatial statistics tools were applied to detect extent spatial auto-correlation and clusters of the disease based on adjusted cumulative incidence per million population for each district. Results : The data analyses revealed a large multi-district cluster of high values in the uplands of Balochistan province near Afghanistan border. Conclusion : The cluster included following districts: Pishin; Qilla Abdullah; Qilla Saifullah; Quetta, Sibi; Zhob; and Ziarat. These districts may be given priority in CCHF surveillance, control programs, and further epidemiological research . The location of the cluster close to border of Afghanistan and Iran highlight importance of the findings for organizations dealing with disease at national, regional and global levels.

Keywords: Crimean Congo hemorrhagic fever, Pakistan, spatial autocorrelation, clusters , adjusted cumulative incidence

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Authors: Roshika Tyagi, Shuvomoy Banerjee

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Among various diseases, cancer has become a huge threat to human beings globally. In the context of viral infection, Epstein–Barr virus (EBV) infection is ubiquitous in nature world-wide as well as in India. Recepteur d’Origine Nantais (RON) receptor tyrosine kinase is overexpressed in Lymphoblastoid cell lines (LCLs) but undetectable in primary B-cells. Biologically, RON expression was found to be essential for EBV transformed LCLs proliferation. In our study, we investigated whether EBV latent antigen EBNA3C is playing a crucial role in regulating RON receptor tyrosine kinase function in EBV-induced malignancies. Interestingly, we observed that expression pattern of RON was modulated by EBNA3C in EBV transformed LCLs compared with EBV negative BJAB cell line by PCR and western blot analysis. Moreover, in the absence of EBNA3C, RON expression was found low in western blot and immunofluorescence analysis and cell proliferation rate was significantly reduced in LCLs by cell viability assays. Therefore, our study clearly indicating the potential role of EBNA3C expressed in EBV-infected B-cells for modulating the functions of oncogenic kinases that leads to EBV induced B-cell transformation.

Keywords: apoptosis, cell proliferation, Epstein–barr virus, receptor tyrosine kinase

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Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell

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Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.

Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers

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Authors: Pugazhenthan Thangaraju

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Background: Since the pandemic began, more than millions of people have become infected with COVID-19. Globally, researchers are working for safe and effective treatments for this disease. Remdesivir is a drug that has been approved for the treatment of COVID-19. Many aspects are still being considered that may influence the future use of remdesivir. Aim: To assess the safety and efficacy of Remdesivir in hospitalized adult patients diagnosed with moderate and severe COVID-19. Methods: It was a record-based retrospective cohort study conducted between April 1st, 2020 and June 30th, 2021 at the tertiary care teaching hospital All India Institutes of Medical Sciences (AIIMS), Raipur Results: There were a total of 10,559 medical records of COVID-19 patients of which 1034 records were included in this study. Overall, irrespective of the survival status, there was statistical significant difference observed between the WHO score at the time of admission and discharge. Clinical improvement among the survivors was found to be statistically significant. Conclusion: Remdesivir's potential efficacy against coronaviruses has so far been limited to in vitro studies and animal models. However, information about COVID-19 is rapidly expanding. Several clinical trials for the treatment of COVID-19 with remdesivir are now underway. However, the findings of this study support remdesivir as a promising agent in the fight against SARS-CoV-2.

Keywords: Remdesivir, COVID-19, SARS-CoV-2, antiviral, RNA-dependent RNA polymerase, viral pneumonia

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially the John Cunningham virus (JCV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on JCV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", " John Cunningham virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2019 and 2022 were searched, and 12 articles were chosen, studied, and analyzed. Results: MS patients are candidates for natalizumab therapy, which inhibits lymphocyte migration and increases the risk of progressive multifocal leukoencephalopathy (PML), a rare lytic infection of glial cells caused by JCV. Oligodendrocytes may be the target of JCV infection in the central nervous system (CNS). Conclusion: There is a high expression of JCV during the natalizumab treatment period for MS patients, suggesting that the virus may play a role in the development of MS by inducing an inflammatory state. Therefore, it is necessary to evaluate anti-JCV antibody serum as an important risk factor for the development of PML before deciding on the treatment course for these patients.

Keywords: multiple sclerosis, John Cunningham virus, central nervous system, autoimmunity

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Authors: Osama H. Elsayed, Mohsen M. S. Asker, Mahmoud A. Swelim, Ibrahim H. Abbas, Aziza I. Attwa, Mohamed E. El Awady

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Hydroxy marilone C is a bioactive metabolite was produced from the culture broth of Streptomyces badius isolated from Egyptian soil. hydroxy marilone C was purified and fractionated by silica gel column with a gradient mobile phase dicloromethane (DCM) : Methanol then Sephadex LH-20 column using methanol as a mobile phase. It was subjected to many instruments as Infrared (IR), nuclear magnetic resonance (NMR), Mass spectroscopy (MS) and UV spectroscopy to the elucidation of its structure. It was evaluated for antioxidant, cytotoxicity against human alveolar basal epithelial cell line (A-549) and human breast adenocarcinoma cell line (MCF-7) and antiviral activities; showed that the maximum antioxidant activity was 78.8 % at 3000 µg/ml after 90 min. and the IC50 value against DPPH radical found about 1500 µg/ml after 60 min. By Using MTT assay the effect of the pure compound on the proliferation of A-549 cells and MCF-7 cells were 443 µg/ml and 147.9 µg/ml, respectively. While for detection of antiviral activity using Madin-Darby canine kidney (MDCK) cells the maximum cytotoxicity was at 27.9% and IC50 was 128.1µg/ml. The maximum concentration required for protecting 50% of the virus-infected cells against H1N1 viral cytopathogenicity (EC50) was 33.25% for 80 µg/ml. This results indicated that the hydroxy marilone C has a potential antitumor and antiviral activities.

Keywords: hydroxy marilone C, production, bioactive compound, Streptomyces badius

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Authors: Sina Mahdavi

Abstract:

Background and Objective: Multiple sclerosis (MS) is an 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 Herpesvirus 6 (HHV-6), and MS is one potential cause that is not well understood. In this study, we aim to summarize the available data on HHV-6 infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", " Human Herpesvirus 6 ", and "central nervous system" in the databases PubMed and Google Scholar between 2017 and 2022 were searched, and 12 articles were chosen, studied, and analyzed. Results: HHV 6 tends towards TCD 4+ lymphocytes and enters the CNS due to the weakening of the blood-brain barrier due to inflammatory damage. Following the observation that the HHV-6 U24 protein has a seven amino acid sequence with myelin basic protein, which is one of the main components of the myelin sheath, it could cause a molecular mimicry mechanism followed by cross-reactivity. Reactivation of HHV-6 in the CNS can cause the release of proinflammatory cytokines, including TNF-α, leading to immune-mediated demyelination in patients with MS. Conclusion: There is a high expression of endogenous retroviruses during the course of MS, which indicates the relationship between HHV-6 and MS, and that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of HHV-6 may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human herpesvirus 6, central nervous system, autoimmunity

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Authors: Samira Khalaji, , Fenneke Klein Jan, Kay-E. Gottschalk, Eugenia Makrantonaki, Karin Scharffetter-Kochanek

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Biological aging is a multi-dimensional process that takes place over a whole range of scales from the nanoscopic alterations within individual cells, over transformations in tissues and organs and to changes of the whole organism. On the single cell level, aging involves mutation of genes, differences in gene expression levels as well as altered posttranslational modifications of proteins. A variety of proteins is affected, including proteins of the cell cytoskeleton and migration machinery. Previous work quantified the expression of cytoskeleton proteins on the gene and protein levels in senescent and young fibroblasts. Their results show that senescent skin fibroblasts have an upregulated expression of the intermediate filament (IF) protein vimentin in contrast to actin and tubulin, which are downregulated. IFs play an important role in providing mechanical stability of cells. However, the mechanical properties of IFs depending on cellular senescence or age of the donor has not been studied so far. Hence, we employed passive microrheology on primary human dermal fibroblasts from female donors with age of 28 years (young) and 86 years (old) as model of in vivo aging and human normal dermal fibroblast from 11-year old male with CPD 17-35 (young) and CPD 58-59 (senescence) as a model of in vitro replicative senescence. In contrast to the expectations, our primary results show no significant differences in the viscoelastic properties of fibroblasts depending on age of the donor or cellular replicative senescence.

Keywords: aging, cytoskeleton, fibroblast, mechanical properties

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Authors: Imeobong Joseph Inyang, Aniekan-Augusta Okon Eyo, Abel William Essien

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Hepatitis B virus (HBV) is one of the known human carcinogens. The presence of HBsAg in liver tissues indicates active viral replication. More than 85% of Hepatocellular Carcinoma (HCC) cases occur in countries with increased rates of chronic HBV infection. An evaluation study to determine the relationship between positivity for HBsAg and development of HCC and its distribution between age and gender of subjects was done. Shikata Orcein and Haematoxylin and Eosin (H&E) staining techniques were performed on liver sections. A total of 50 liver tissue specimens comprising 38 biopsy and 12 post-mortem specimens were processed. Thirty-five of the 50 specimens were positive for HBsAg with Orcein stain whereas only 16 were positive with H&E stain, and these were also positive with Orcein stain, giving an HBsAg prevalence of 70.0% (35/50). The prevalence of HCC in the study was 56.0% (28/50), of which 21 (75.0%) cases were positive for HBsAg, 18 (64.3%) were males while 10 (35.7%) were females distributed within the age range of 20-70 years. The highest number of HBsAg positive HCC cases, 7/21 (33.3%) occurred in the age group 40-49 years. There was no relationship in the pattern of distribution of HCC between age and gender using the Pearson correlation coefficient (r = 0.0474; P < 0.05). HBV infection predisposed to HCC. Orcein technique was more specific and is therefore recommended for screening of liver tissues where facilities for immunohistochemistry are inaccessible.

Keywords: Hepatitis B. surface antigen, hepatocellular carcinoma, orcein, pathology

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Authors: Giang Tran Thi Huong, Hieu Dong Van, Tung Dao Duy, Saadanov Iskender, Isakeev Mairambek, Tsutomu Omatsu, Yukie Katayama, Tetsuya Mizutani, Yuki Ozeki, Yohei Takeda, Haruko Ogawa, Kunitoshi Imai

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Newcastle disease virus (NDV) is a contagious viral disease of the poultry industry and other birds throughout the world. At present, very little is known about molecular epidemiological data regarding the causes of ND outbreak in commercial poultry farms in Kyrgyzstan. In the current study, the NDV isolated from the one out of three samples from the unvaccinated flock was confirmed as NDV. Phylogenetic analysis indicated that this NDV strain is clustered in the Class II subgenotype VIId, and closely related to the Chinese NDV isolate. Phylogenetic analyses revealed that the isolated NDV strain has an origin different from the 4 NDV strains previously identified in Kyrgyzstan. According to the mean death time (MDT: 61.1 h) and a multibasic amino acid (aa) sequence at the F0 proteolytic cleavage site (¹¹²R-R-Q-K-R-F¹¹⁷), the NDV isolate was determined as mesogenic strain. Several mutations in the neutralizing epitopes (notably, ³⁴⁷E→K) and the global head were observed in the hemagglutinin-neuraminidase (HN) protein of the current isolate. The present study represents the molecular characterization of the coding gene region of NDV in Kyrgyzstan. Additionally, further study will be investigated on the antigenic characterization using monoclonal antibody.

Keywords: Kyrgyzstan, Newcastle disease, genotype, genome characterization

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Authors: Susmiati, Ingrid S. Surono, Jamsari, Nur Indrawati Lipoeto

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There are two contradicting opinions on the relationship between fat mass obesity associated (FTO) rs 9939609 variants and obesity on various ethnics and races. The first opinion agrees that there is an association between the two variables, yet another one disagree. Minangkabau ethnic had a different dietary pattern with other ethnics in Indonesia. They had higher fat and low fiber intakes compared to the other ethnics groups. There is little research in genetic factors that influence eating behavior (food preference or food selection). The objective of this study was to investigate the association between FTO rs 9939609 variants with obesity and eating behavior in adolescent girls of Minangkabau Ethnic. The research design was case control study. A total of 275 adolescent girls aged 12-15 years old (130 obese and 145 normal) were randomly chosen from four districts at West Sumatera (Padang, Padang Pariaman, Padang Panjang and Tanah Datar). Genetic variants of FTO rs 9939609 were analyzed with Tetra-primer Amplification Refractory Mutation System-Polimerase Chain Reaction (AMRS PCR), eating behavior were gathered using eating habits questionnaire, and Body Mass Index (BMI) was calculated according to BMI Z-score (WHO). The result showed that genetic variants of FTO rs 9939609 (TT, TA and AA genotype) had associated with obesity (p = 0,013), whereas subject with An Allele was significantly associated with obesity (odds ratio 1,62 [95% confidential interval, 1,00-2,60]). Subjects with An Allele carrier reported a higher consumption of fried food (p < 0.05) as compared to TT genotypes carriers. There is no association between genetic variants and meal frequency, fruit and fiber intakes p > 0.05. The genetic variants of FTO rs 9939609 are associated with obesity and eating behavior in adolescent of Minangkabau Ethics.

Keywords: FTO rs9939609, obesity, eating behavior, adolescents

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Authors: Mohammed Qutishat, Loai Abu Sharour, Kholoud Al-Damery, Ibtisam Al Harthy, Sulaiman Al-Sabei

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Background: The 2019 coronavirus outbreak (COVID-19) has been declared a pandemic and has greatly affected both patients and healthcare workers. This study was conducted to explore the extent of posttraumatic stress disorder (PTSD) experiences among nurses as a result of the COVID-19 pandemic in Jordan. Method: This study used a cross-sectional study design with a convenience sampling approach. A sample of 259 participants completed the study questionnaires, including a sociodemographic questionnaire and the posttraumatic stress disorder checklist for DSM‐5, between May and July 2020. Result: The prevalence of PTSD among the study participants was 37.1%. The majority of study participants who exhibited PTSD symptoms presented the lowest level of PTSD (17%). The results indicated significant differences in overall COVID-19-related PTSD according to the participant’s age (F = 14.750, P = .000), gender (F = 30.340, P = .000), level of education (F = 51.983, P =.000), years of experience (F = 52.33, P = .000), place of work (F = 19.593, P = .000), and working position (F = 11.597, P = .000), as determined by one-way ANOVA. Conclusion: Nurses must be qualified and accredited to cope with reported PTSD cases and their consequences in relation to COVID-19 outbreaks. Close collaboration with a multidisciplinary team is required to recognise, manage, and encourage safety literacy among health care professionals and individuals diagnosed with or suspected of PTSD due to COVID-19 outbreaks or any other viral outbreaks.

Keywords: PTSD, nursing, coronavirus, pandemic, infectious disease

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Authors: Mark Osborn

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Clustered, regularly interspaced short palindromic repeat (CRISPR/Cas) proteins can be designed to bind specified DNA and RNA sequences and hold great promise for the accurate detection of nucleic acids for diagnostics. Commercially available reagents were integrated into a CRISPR/Cas9-based lateral flow assay that can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences with single-base specificity. This approach requires minimal equipment and represents a simplified platform for field-based deployment. A rapid, multiplex fluorescence CRISPR/Cas9 nuclease cleavage assay capable of detecting and differentiating SARS-CoV-2, influenza A and B, and respiratory syncytial virus in a single reaction was also developed. These findings provide proof of principle for CRISPR/Cas9 point-of-care diagnosis that can detect specific SARS-CoV-2 strain(s). Further, Cas9 cleavage allows for a scalable fluorescent platform for identifying respiratory viral pathogens with overlapping symptomology. Collectively, this approach is a facile platform for diagnostics with broad application to user-defined sequence interrogation and detection.

Keywords: CRISPR/Cas9, lateral flow assay, SARS-Co-V2, single-nucleotide resolution

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Authors: Husham Bayazed

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The infant immune system has a reputation for being weak and underdeveloped when compared to the adult immune system, but the comparison isn’t quite fair. At the start, as the COVID-19 pandemic drags on and evolves, many Pediatricians and kids' parents have been left with renewed questions about the consequences and sequel of infection on children and the steps to be taken if their child, has the symptoms of COVID-19 or tests positive. Recent Findings: Literature reviews and recent studies revealed that children are better than adults at controlling SARS-CoV-2. There was conflicting evidence on age-related differences in ACE2 expression in the nose and lungs. But scientists who measured the ‘viral load’ in children's upper airways have seen no clear difference between children and adults. Moreover, the hypothesis is that kids might be more exposed to other coronaviruses common cold with a production of ready protective antibodies to lock on to the pandemic coronavirus. But the evidence suggests that adults also have this immunity too. Strikingly, these ‘cross-reactive’ antibodies don’t offer any special protection. Summary: One of the few silver linings of the Covid-19 pandemic is that children are relatively spared. The kid's Innate Immunity is hardly the whole story, the innate immune response against SARS-CoV-2 infection is early initiative calm with low immunological tone to prevent an overactive immunity and with rapidly repair damage to the lungs in contrast to stormy waves in adults. Therefore, Kids are at much lower risk of Covid-19 infection and they are still winning the battle against Covid-19 with their innate immunity.

Keywords: kids, Covid-19, immunity, ACT2

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Authors: Shizra Waris, Bilal Shoaib, Munib Ahmad

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Background; The using of clinical decision support systems (CDSSs) may recover unceasing disease organization, which requires regular visits to multiple health professionals, treatment monitoring, disease control, and patient behavior modification. The objective of this survey is to determine if these CDSSs improve the processes of unceasing care including diagnosis, treatment, and monitoring of diseases. Though artificial intelligence is not a new idea it has been widely documented as a new technology in computer science. Numerous areas such as education business, medical and developed have made use of artificial intelligence Methods: The survey covers articles extracted from relevant databases. It uses search terms related to information technology and viral hepatitis which are published between 2000 and 2016. Results: Overall, 80% of studies asserted the profit provided by information technology (IT); 75% of learning asserted the benefits concerned with medical domain;25% of studies do not clearly define the added benefits due IT. The CDSS current state requires many improvements to hold up the management of liver diseases such as HCV, liver fibrosis, and cirrhosis. Conclusion: We concluded that the planned model gives earlier and more correct calculation of hepatitis B and it works as promising tool for calculating of custom hepatitis B from the clinical laboratory data.

Keywords: detection, hapataties, observation, disesese

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Authors: S. Tebibel, C. Mechati, S. Messaoudi

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Algeria is currently experiencing the same rate of cancer progression as that registered these last years in the western countries. Colorectal cancer, constituting increasingly a major public health problem, is the most common form of cancer after breast and Neck-womb cancer at the woman and prostate cancer at the man. Our work is based on a retrospective study to determine the cases of colorectal cancer through eastern Algeria. Our goal is to carry out an epidemiological, histological and immune- histochemical study to investigate different techniques for the diagnosis of colorectal cancer and their interests and specific in detecting the disease. The study includes 110 patients (aged between 20 to 87 years) with colorectal cancer where the inclusions and exclusions criteria were established. In our study, colorectal cancer, expresses a male predominance, with a sex ratio of 1, 99 and the most affected age group is between 50 and 59 years. We noted that the colon cancer rate is higher than rectal cancer rate, whose frequencies are respectively 60,91 % and 39,09 %. In the series of colon cancer, the ADK lieberkunien is histological the most represented type, or 85,07 % of all cases. In contrast, the proportion of ADK mucinous (colloid mucous) is only 1,49% only. Well-differentiated ADKS, are very significant in our series, they represent 83,58 % of cases. Adenocarcinoma moderately and poorly differentiated, whose proportions are respectively 2,99 % and 0.05 %. For histological varieties of rectal ADK, we see in our workforce that ADK lieberkunien represent the most common histological form, or 76,74%, while the mucosal colloid is 13,95 %. Research of the mutation on the gene encoding K-ras, a major step in the targeted therapy of colorectal cancers, is underway in our study. Colorectal cancer is the subject of much promising research concern: the evaluation of new therapies (antiangiogenic monoclonal antibodies), the search for predictors of sensitivity to chemotherapy and new prognostic markers using techniques of molecular biology and proteomics.

Keywords: adenocarcinoma, age, colorectal cancer, epidemiology, histological section, sex

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Authors: Neha Singh, Anuj Ranjan, Tanu Jindal

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Over the last decade, the exponential growth of mobile communication has been accompanied by a parallel increase in density of electromagnetic fields (EMF). The continued expansion of mobile phone usage raises important questions as EMF, especially radio frequency (RF), have long been suspected of having biological effects. In the present experiments, we studied the effects of RF-EMF on cell death (apoptosis) and DNA damage of a well- tested biological model, Drosophila melanogaster exposed to 2400 MHz frequency for different time duration i.e. 2 hrs, 4 hrs, 6 hrs,8 hrs, 10 hrs, and 12 hrs each day for five continuous days in ambient temperature and humidity conditions inside an exposure chamber. The flies were grouped into control, sham-exposed, and exposed with 100 flies in each group. In this study, well-known techniques like Comet Assay and TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) Assay were used to detect DNA damage and for apoptosis studies, respectively. Experiments results showed DNA damage in the brain cells of Drosophila which increases as the duration of exposure increases when observed under the observed when we compared results of control, sham-exposed, and exposed group which indicates that EMF radiation-induced stress in the organism that leads to DNA damage and cell death. The process of apoptosis and mutation follows similar pathway for all eukaryotic cells; therefore, studying apoptosis and genotoxicity in Drosophila makes similar relevance for human beings as well.

Keywords: cell death, apoptosis, Comet Assay, DNA damage, Drosophila, electromagnetic fields, EMF, radio frequency, RF, TUNEL assay

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Authors: Ana Corberan-Vallet, Karen C. Florez, Ingrid C. Marino, Jose D. Bermudez

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In 2016, the Region of the Americas was declared free of measles, a viral disease that can cause severe health problems. However, since 2017, measles has reemerged in Venezuela and has subsequently reached neighboring countries. In 2018, twelve American countries reported confirmed cases of measles. Governmental and health authorities in Colombia, a country that shares the longest land boundary with Venezuela, are aware of the need for a strong response to restrict the expanse of the epidemic. In this work, we apply a Bayesian hierarchical Poisson model with an underlying cluster structure to describe disease incidence in Colombia. Concretely, the proposed methodology provides relative risk estimates at the department level and identifies clusters of disease, which facilitates the implementation of targeted public health interventions. Socio-demographic factors, such as the percentage of migrants, gross domestic product, and entry routes, are included in the model to better describe the incidence of disease. Since the model does not impose any spatial correlation at any level of the model hierarchy, it avoids the spatial confounding problem and provides a suitable framework to estimate the fixed-effect coefficients associated with spatially-structured covariates.

Keywords: Bayesian analysis, cluster identification, disease mapping, risk estimation

Procedia PDF Downloads 151