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1.
Article in English | MEDLINE | ID: mdl-38960471

ABSTRACT

Acinetobacter baumannii is a gram-negative bacterium well known for its multidrug resistance and connection to nosocomial infections under ESKAPE pathogens. This opportunistic pathogen is ubiquitously associated with nosocomial infections, posing significant threats within healthcare environments. Its critical clinical symptoms, namely, meningitis, urinary tract infections, bloodstream infections, ventilator-associated pneumonia, and pneumonia, catalyze the imperative demand for innovative therapeutic interventions. The proposed research focuses on delineating the role of Zinc, a crucial metallo-binding protein and micronutrient integral to bacterial metabolism and virulence, to enhance understanding of the pathogenicity of A. baumannii. RNA sequencing and subsequent DESeq2 analytical methods were used to identify differential gene expressions influenced by zinc exposure. Exploiting the STRING database for functional enrichment analysis has demonstrated the complex molecular mechanisms underlying the enhancement of pathogenicity prompted by Zinc. Moreover, hub genes like gltB, ribD, AIL77834.1, sdhB, nuoI, acsA_1, acoC, accA, accD were predicted using the cytohubba tool in Cytoscape. This investigation underscores the pivotal role of Zinc in the virulence of A. baumannii elucidates the underlying molecular pathways responsible for its pathogenicity. The research further accentuates the need for innovative therapeutic strategies to combat A. baumannii infections, particularly those induced by multidrug-resistant strains.


Subject(s)
Acinetobacter baumannii , Drug Resistance, Multiple, Bacterial , Zinc , Acinetobacter baumannii/genetics , Acinetobacter baumannii/pathogenicity , Acinetobacter baumannii/metabolism , Zinc/metabolism , Drug Resistance, Multiple, Bacterial/genetics , Virulence/genetics , Humans , Gene Expression Profiling , Transcriptome , Acinetobacter Infections/microbiology , Acinetobacter Infections/metabolism , Acinetobacter Infections/drug therapy , Bacterial Proteins/genetics , Bacterial Proteins/metabolism
2.
Int J Biol Macromol ; 258(Pt 1): 128753, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38104690

ABSTRACT

Viruses transmitted by arthropods, such as Dengue, Zika, and Chikungunya, represent substantial worldwide health threats, particularly in countries like India. The lack of approved vaccines and effective antiviral therapies calls for developing innovative strategies to tackle these arboviruses. In this study, we employed immunoinformatics methodologies, incorporating reverse vaccinology, to design a multivalent vaccine targeting the predominant arboviruses. Epitopes of B and T cells were recognized within the non-structural proteins of Dengue, Zika, and Chikungunya viruses. The predicted epitopes were enhanced with adjuvants ß-defensin and RS-09 to boost the vaccine's immunogenicity. Sixteen distinct vaccine candidates were constructed, each incorporating epitopes from all three viruses. FUVAC-11 emerged as the most promising vaccine candidate through molecular docking and molecular dynamics simulations, demonstrating favorable binding interactions and stability. Its effectiveness was further evaluated using computational immunological studies confirming strong immune responses. The in silico cloning performed using the pET-28a(+) plasmid facilitates the future experimental implementation of this vaccine candidate, paving the way for potential advancements in combating these significant arboviral threats. However, further in vitro and in vivo studies are warranted to confirm the results obtained in this computational study, which highlights the effectiveness of immunoinformatics and reverse vaccinology in creating vaccines against major Arboviruses, offering a promising model for developing vaccines for other vector-borne diseases and enhancing global health security.


Subject(s)
Arboviruses , Chikungunya Fever , Dengue , Vaccines , Zika Virus Infection , Zika Virus , Humans , Molecular Docking Simulation , Chikungunya Fever/prevention & control , Vaccines, Combined , Vaccinology/methods , Epitopes, T-Lymphocyte/chemistry , Computational Biology/methods , Epitopes, B-Lymphocyte , Vaccines, Subunit
3.
Life Sci ; 337: 122360, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38135117

ABSTRACT

Triple-Negative Breast Cancer (TNBC) presents a significant challenge in oncology due to its aggressive behavior and limited therapeutic options. This review explores the potential of immunotherapy, particularly vaccine-based approaches, in addressing TNBC. It delves into the role of immunoinformatics in creating effective vaccines against TNBC. The review first underscores the distinct attributes of TNBC and the importance of tumor antigens in vaccine development. It then elaborates on antigen detection techniques such as exome sequencing, HLA typing, and RNA sequencing, which are instrumental in identifying TNBC-specific antigens and selecting vaccine candidates. The discussion then shifts to the in-silico vaccine development process, encompassing antigen selection, epitope prediction, and rational vaccine design. This process merges computational simulations with immunological insights. The role of Artificial Intelligence (AI) in expediting the prediction of antigens and epitopes is also emphasized. The review concludes by encapsulating how Immunoinformatics can augment the design of TNBC vaccines, integrating tumor antigens, advanced detection methods, in-silico strategies, and AI-driven insights to advance TNBC immunotherapy. This could potentially pave the way for more targeted and efficacious treatments.


Subject(s)
Triple Negative Breast Neoplasms , Vaccines , Humans , Triple Negative Breast Neoplasms/drug therapy , Multiomics , Artificial Intelligence , Epitopes , Vaccines/therapeutic use , Antigens, Neoplasm
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