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Authors = Manoj Khokhar ORCID = 0000-0001-7106-8545

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14 pages, 4516 KiB  
Article
Designing a Multi-Epitope Subunit Vaccine against VP1 Major Coat Protein of JC Polyomavirus
by Sukhada Kanse, Mehak Khandelwal, Rajan Kumar Pandey, Manoj Khokhar, Neetin Desai and Bajarang Vasant Kumbhar
Vaccines 2023, 11(7), 1182; https://doi.org/10.3390/vaccines11071182 - 30 Jun 2023
Cited by 10 | Viewed by 4777
Abstract
The JC polyomavirus virus (JCPyV) affects more than 80% of the human population in their early life stage. It mainly affects immunocompromised individuals where virus replication in oligodendrocytes and astrocytes may lead to fatal progressive multifocal encephalopathy (PML). Virus protein 1 (VP1) is [...] Read more.
The JC polyomavirus virus (JCPyV) affects more than 80% of the human population in their early life stage. It mainly affects immunocompromised individuals where virus replication in oligodendrocytes and astrocytes may lead to fatal progressive multifocal encephalopathy (PML). Virus protein 1 (VP1) is one of the major structural proteins of the viral capsid, responsible for keeping the virus alive in the gastrointestinal and urinary tracts. VP1 is often targeted for antiviral drug and vaccine development. Similarly, this study implied immune-informatics and molecular modeling methods to design a multi-epitope subunit vaccine targeting JCPyV. The VP1 protein epitopic sequences, which are highly conserved, were used to build the vaccine. This designed vaccine includes two adjuvants, five HTL epitopes, five CTL epitopes, and two BCL epitopes to stimulate cellular, humoral, and innate immune responses against the JCPyV. Furthermore, molecular dynamics simulation (100 ns) studies were used to examine the interaction and stability of the vaccine protein with TLR4. Trajectory analysis showed that the vaccine and TLR4 receptor form a stable complex. Overall, this study may contribute to the path of vaccine development against JCPyV. Full article
(This article belongs to the Special Issue Design of Multi-Epitope Subunit Vaccine and Immunization Strategies)
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50 pages, 3231 KiB  
Review
Mechanism of Immune Evasion in Mosquito-Borne Diseases
by Swagato Bhattacharjee, Debanjan Ghosh, Rounak Saha, Rima Sarkar, Saurav Kumar, Manoj Khokhar and Rajan Kumar Pandey
Pathogens 2023, 12(5), 635; https://doi.org/10.3390/pathogens12050635 - 23 Apr 2023
Cited by 11 | Viewed by 14068
Abstract
In recent decades, mosquito-borne illnesses have emerged as a major health burden in many tropical regions. These diseases, such as malaria, dengue fever, chikungunya, yellow fever, Zika virus infection, Rift Valley fever, Japanese encephalitis, and West Nile virus infection, are transmitted through the [...] Read more.
In recent decades, mosquito-borne illnesses have emerged as a major health burden in many tropical regions. These diseases, such as malaria, dengue fever, chikungunya, yellow fever, Zika virus infection, Rift Valley fever, Japanese encephalitis, and West Nile virus infection, are transmitted through the bite of infected mosquitoes. These pathogens have been shown to interfere with the host’s immune system through adaptive and innate immune mechanisms, as well as the human circulatory system. Crucial immune checkpoints such as antigen presentation, T cell activation, differentiation, and proinflammatory response play a vital role in the host cell’s response to pathogenic infection. Furthermore, these immune evasions have the potential to stimulate the human immune system, resulting in other associated non-communicable diseases. This review aims to advance our understanding of mosquito-borne diseases and the immune evasion mechanisms by associated pathogens. Moreover, it highlights the adverse outcomes of mosquito-borne disease. Full article
(This article belongs to the Special Issue Advances in Mosquito-Borne Pathogens and Diseases)
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18 pages, 8723 KiB  
Article
PTEN, MMP2, and NF-κB and Regulating MicroRNA-181 Aggravate Insulin Resistance and Progression of Diabetic Nephropathy: A Case-Control Study
by Manoj Khokhar, Purvi Purohit, Sojit Tomo, Riddhi G. Agarwal, Ashita Gadwal, Nitin Kumar Bajpai, Gopal Krishna Bohra and Ravindra Kumar Shukla
Kidney Dial. 2023, 3(1), 121-138; https://doi.org/10.3390/kidneydial3010011 - 15 Mar 2023
Cited by 7 | Viewed by 2921
Abstract
Diabetic nephropathy (DN) is characterized by an increase in urinary albumin excretion, diabetic glomerular lesions, and a decline in glomerular filtration rate (GFR). We assessed the expression of phosphatase and tensin homolog (PTEN), nuclear factor kappa-β (NF-κB), matrix metalloproteinase-2 (MMP2), and microRNA-181 in [...] Read more.
Diabetic nephropathy (DN) is characterized by an increase in urinary albumin excretion, diabetic glomerular lesions, and a decline in glomerular filtration rate (GFR). We assessed the expression of phosphatase and tensin homolog (PTEN), nuclear factor kappa-β (NF-κB), matrix metalloproteinase-2 (MMP2), and microRNA-181 in healthy controls (HC), individuals with type 2 diabetes mellitus (T2DM) without nephropathy, and those with DN. Our study investigated the association between these genes, insulin resistance (IR), and eGFR to gain insight into their roles in the pathogenesis and progression of DN. Anthropometric measurements and biochemical tests were conducted on HC (N = 36), T2DM (N = 38) patients, and DN (N = 35) patients. We used real-time polymerase chain reaction (RT-PCR) for whole blood gene expression analysis and performed bioinformatics analyses, including protein–protein interaction, gene ontology, and co-expression networks. We compared our expression data with other GEO-Microarray datasets. Our study highlights the role of IR in the progression of nephropathy in T2DM via the PTEN-Akt-mTOR signalling pathway. We also observed a decreasing trend in the expression of MMP2 and PTEN and an increasing trend in the expression of NF-κB and miR-181b-5p with the progression of nephropathy to the severe stage. The dysregulated expression of MMP2, PTEN, NF-κB, and miR-181b-5p in patients with T2DM contributes to the progression of T2DM to DN by aggravating IR, inflammation, accelerating basement membrane thickening, mesangial matrix expansion, and renal fibrosis. Full article
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