Introduction: Ionizing radiation (IR) causes not only acute tissue damage but also late effects in several cell generations after the initial exposure. The mechanism by which the radiation exposure is memorized and lead to delayed DNA breakage remains to be determined. Objectives: We investigated the mechanism by which IR induced ROS generation several days after irradiation. We focused on NADPH oxidases, which are specialized ROS-generating enzymes known as NOX/DUOX. Methodology: Human thyroid cell line, primary human thyroid cells and 35 frozen tissues (20 radio-induced thyroid tumors, 9 sporadic tumors and 6 normal tissues) were included in this study. Results: IR (10 Gy) induces a delayed NADPH oxidase DUOX1-dependent H2O2 production in a dose-dependent manner, which was sustained for several days. Pretreatment of cells with catalase, a scavenger of H2O2, or DUOX1 downregulation by siRNA abrogate IR-induced DNA-damage. Analysis of human thyroid tissues showed that DUOX1 is elevated in human radio-induced thyroid tumors. Conclusion: Our data reveal a key role of DUOX1-dependent H2O2 production in long-term persistent radio-induced DNA damage. Our data also show that DUOX1-dependent H2O2 production, which induces DNA double strand breaks, can cause genomic instability and promote generation of neoplastic cells through its mutagenic effect.

Nadph oxidase duox1 promotes long-term persistence of oxidative stress after an exposure to irradiation

https://www.mdpi.com/2076-393X/7/3/88/pdf

Immunoinformatics-Aided Design and Evaluation of a Potential Multi-Epitope Vaccine against Klebsiella Pneumoniae.

Multidrug-resistant Pseudomonas aeruginosa is one of the worldwide health problems involved in elevated mortality and morbidity. Therefore, it is important to find a therapeutic for this pathogen. In the present study, we have designed a chimeric vaccine against P. aeruginosa with the help of comparative proteomics and reverse vaccinology approaches. Using comparative subtractive proteomic analysis of 1,191 proteomes of P. aeruginosa, a total of twenty unique non-redundant proteomes were selected. In these proteomes, fifteen outer membrane proteins (OMPs) of P. aeruginosa were selected based on the basis of hydrophilicity, non-secretory nature, low transmembrane helix (<1), essentiality, virulence, pathway association, antigenic, and protein-protein network analysis. Reverse vaccinology approach was used to identify antigenic and immunogenic MHC class I, MHC class II and B cell epitopes present in the selected OMPs that can enhance T cell and B cell mediated immunogenicity. The selected epitopes were shortlisted based on their allergenicity, toxicity potentials, solubility, and hydrophilicity analysis. Immunogenic peptides were used to design a multi-epitope vaccine construct. Immune-modulating adjuvants and PADRE (Pan HLA-DR epitopes) sequence were added with epitopes sequence to enhance the immunogenicity. All the epitopes, adjuvants and PADRE sequence were joined by linkers. The designed vaccine constructs (VT1, VT2, VT3, and VT4) were analyzed by their physiochemical properties using different tools. Selected chimeric vaccine constructs (VT1, VT3, and VT4) were further shortlisted by their docking score with different HLA alleles. The final selected VT4 construct was docked with TLR4/MD2 complex and confirmed by molecular dynamics simulation studies. The final vaccine VT-4 construct was in-silico cloned in pET28a. Therefore, the designed construct VT4 may be studied to control the interaction of P. aeruginosa with host and infection caused by P. aeruginosa.

Prioritization of potential vaccine targets using comparative proteomics and designing of the chimeric multi-epitope vaccine against Pseudomonas aeruginosa.

Carbon brush electrodes have been used to provide high surface areas for bacterial growth and high power densities in microbial fuel cells (MFCs). A high-temperature ammonia gas treatment has been used to enhance power generation, but less energy-intensive methods are needed for treating these electrodes in practice. Three different treatment methods are examined here for enhancing power generation of carbon fiber brushes: acid soaking (CF-A), heating (CF-H), and a combination of both processes (CF-AH). The combined heat and acid treatment improve power production to 1370 mW m−2, which is 34% larger than the untreated control (CF-C, 1020 mW m−2). This power density is 25% higher than using only acid treatment (1100 mW m−2) and 7% higher than that using only heat treatment (1280 mW m−2). XPS analysis of the treated and untreated anode materials indicates that power increases are related to higher N1s/C1s ratios and a lower C–O composition. These findings demonstrate efficient and simple methods for improving power generation using graphite fiber brushes, and provide insight into reasons for improving performance that may help to further increase power through other graphite fiber modifications.

Treatment of carbon fiber brush anodes for improving power generation in air-cathode microbial fuel cells

https://research-information.bris.ac.uk/files/185726439/EJOPS_2019.pdf

Combating tigecycline resistant Acinetobacter baumannii: A leap forward towards multi-epitope based vaccine discovery.

Prediction of vaccine candidates against Pseudomonas aeruginosa: An integrated genomics and proteomics approach.

Flavonoids are tricyclic polyphenolic compounds naturally occurring in plants. Being nature’s antioxidants flavonoids have been shown to reduce the damages induced by oxidative stress in cells. Besides being an antioxidant, flavonols are demonstrated to have anti-infective properties, i.e., antiviral, antifungal, anti-angiogenic, anti-tumorigenic, and immunomodulatory bioproperties. Plants use them as one of their defense mechanisms against radiation-induced DNA damage and also for fungal infections. The use of flavonols for fabrication of new drugs has been underway with objectives to develop safer and effective therapeutic agents. This review covers 15 flavonols for their structure, biological properties, role in plant metabolisms, and current research focused on computational drug design using flavonols for searching drug leads.

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Flavonoids and Their Biological Secrets

Klebsiella pneumoniae and Mycobacterium tuberculosis coinfection is one of the most lethal combinations that has been becoming frequent yet, not diagnosed and reported properly. Due to the simultaneous occurrence of both infections, diagnosis is delayed leading to inadequate treatments and mortality. With the rise of MDR Klebsiella and Mycobacterium, a prophylactic and an immunotherapeutic vaccine has to be entailed for preemptive and adroit therapeutic approach. In this study, we aim to implement reverse vaccinology approach that encompasses a comprehensive evaluation of vital aspects of the pathogens to explore immunogenic epitopes against Omp A of Klebsiella and Rv1698, Rv1973 of Mtb that may help in vaccine development. The designed multi-epitopic vaccine was assessed for antigenicity, allergenicity and various physiochemical parameters. Molecular docking and simulations were executed to assess the immunogenicity and complex stability of the vaccine. The final multi-epitopic vaccine is validated to be highly immunogenic and can serve as a valuable proactive remedy for subject pathogens.

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Immunoinformatics Driven Prediction of Multiepitopic Vaccine Against Klebsiella pneumoniae and Mycobacterium tuberculosis Coinfection and Its Validation via In Silico Expression.

Pseudomonas aeruginosa produces Pyocyanin which serves as a good electron transport shuttle in Microbial Fuel Cells. Studies have implicated higher Microbial Fuel Cell energy yield with higher PCN production by P. aeruginosa thus improving energy output. For obtaining high pyocyanin producing strain of P. aeruginosa, sewage water samples were taken from various sites in Islamabad and were cultured in LB media at 37°C. Characterization was performed by both biochemically as well as genetically. For pyocyanin yield assessment R f value and λmax were determined. Pyocyanin was isolated via repeated chloroform and acidified water extraction and quantified. Physiochemical and nutritional conditions for pyocyanin production were optimized in the form of designed modified semisynthetic media. Optimized production was achieved and pyocyanin yield was increased to 3 folds than normal and control conditions. The designed pyocyanin yield media can be used to improve energy output in microbial fuel cells.

Pyocyanin yield improvement for enhancement of Pseudomonas aeruginosa inoculated Microbial Fuel Cell efficiency

Background Cholera, an acute enteric infection, is a serious health challenge in both the underdeveloped and the developing world. It is caused by Vibrio cholerae after ingestion of fecal contaminated food or water. Cholera outbreaks have recently been observed in regions facing natural calamities (i.e., earthquake in Haiti 2010) or war (i.e., ongoing civil war in Yemen 2016) where healthcare and sanitary setups have been disrupted as a consequence. Whole-cell oral cholera vaccines (OCVs) have been in market but their regimen efficacy has been questioned. A reverse vaccinology (RV) approach has been applied as a successful anti-microbial measure for many infectious diseases. Methodology With the aim of finding new protective antigens for vaccine development, the V. cholerae O1 (biovar eltr str. N16961) proteome was computationally screened in a sequential prioritization approach that focused on determining the antigenicity of potential vaccine candidates. Essential, accessible, virulent and immunogenic proteins were selected as potential candidates. The predicted epitopes were filtered for effective binding with MHC alleles and epitopes binding with greater MHC alleles were selected. Results In this study, we report lipoprotein NlpD, outer membrane protein OmpU, accessory colonization factor AcfA, Porin, putative and outer membrane protein OmpW as potential candidates qualifying all the set criteria. These predicted epitopes can offer a potential for development of a reliable peptide or subunit vaccine for V. cholerae.

Muhammad Ibrahim Rashid

Papers

Prediction of vaccine candidates against Pseudomonas aeruginosa: An integrated genomics and proteomics approach.

Flavonoids and Their Biological Secrets

Immunoinformatics Driven Prediction of Multiepitopic Vaccine Against Klebsiella pneumoniae and Mycobacterium tuberculosis Coinfection and Its Validation via In Silico Expression.

Pyocyanin yield improvement for enhancement of Pseudomonas aeruginosa inoculated Microbial Fuel Cell efficiency

Fishing for vaccines against Vibrio cholerae using in silico pan-proteomic reverse vaccinology approach