An immunoinformatics approach for the design of a multi-epitope subunit vaccine for urogenital schistosomiasis

Discovery of T and B memory cells capable of eliciting long-term immunity against schistosomiasisis is important for people in endemic areas. Changes in schistosomes environment due to developmental cycle, induces up-regulation of Heat Shock Proteins (HSPs) which assist the parasite in coping with the hostile conditions associated with its life cycle. This study therefore focused on exploring the role of HSPs in urogenital schistosomiasis to develop new multi-epitope subunit vaccine against the disease using immunoinformatic approaches. The designed subunit vaccine was subjected to in silico antigenicity, immunogenicity, allergenicity and physicochemical parameters analysis. A 3D structure of the vaccine construct was predicted, followed by disulphide engineering for stability, codon adaptation and in silico cloning for proper expression and molecular protein–protein docking of vaccine construct in the vector against toll-like receptor 4 receptor, respectively. Consequently, a 493 amino acid multi-epitope vaccine construct of antigenicity probability of 0.91 was designed. This was predicted to be stable, non-allergenic in nature and safe for human use.

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Dermatopontin in Skeletal Muscle Extracellular Matrix Regulates Myogenesis

Cells ◽

10.3390/cells8040332 ◽

2019 ◽

Vol 8 (4) ◽

pp. 332 ◽

Cited By ~ 8

Author(s):

Kim ◽

Ahmad ◽

Shaikh ◽

Jan ◽

Seo ◽

...

Keyword(s):

Extracellular Matrix ◽

In Silico ◽

State Of The Art ◽

Myogenic Differentiation ◽

3D Structure ◽

Inhibitory Effect ◽

C2c12 Cells ◽

Myoblast Differentiation ◽

Protein Protein Interaction

Dermatopontin (DPT) is an extensively distributed non-collagenous component of the extracellular matrix predominantly found in the dermis of the skin, and consequently expressed in several tissues. In this study, we explored the role of DPT in myogenesis and perceived that it enhances the cell adhesion, reduces the cell proliferation and promotes the myoblast differentiation in C2C12 cells. Our results reveal an inhibitory effect with fibronectin (FN) in myoblast differentiation. We also observed that DPT and fibromodulin (FMOD) regulate positively to each other and promote myogenic differentiation. We further predicted the 3D structure of DPT, which is as yet unknown, and validated it using state-of-the-art in silico tools. Furthermore, we explored the in-silico protein-protein interaction between DPT-FMOD, DPT-FN, and FMOD-FN, and perceived that the interaction between FMOD-FN is more robust than DPT-FMOD and DPT-FN. Taken together, our findings have determined the role of DPT at different stages of the myogenic process.

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Cold Ischemic Organ Preservation: Lessons from Natural Systems

Journal of Investigative Medicine ◽

10.1136/jim-52-05-31 ◽

2004 ◽

Vol 52 (5) ◽

pp. 315-322 ◽

Cited By ~ 13

Author(s):

Kenneth B. Storey

Keyword(s):

Recovery Of Function ◽

Cdna Array ◽

Natural Systems ◽

Organ Specific ◽

Complementary Deoxyribonucleic Acid ◽

Biochemical Mechanisms ◽

New Research ◽

Shock Proteins

Mammalian hibernators offer natural models for investigating solutions to the metabolic injuries that accrue during cold ischemic storage of human organs removed for transplant. Knowledge of the biochemical mechanisms that regulate and stabilize metabolism to ensure long-term viability in the hypometabolic, hypothermic state of hibernation could lead to applied treatments that could increase the time that excised organs can be maintained in cold storage and/or improve recovery of function after implantation. New research has documented the widespread role of reversible protein phosphorylation control of metabolism in achieving the coordinated suppression of metabolic rate that greatly extends viability during torpor. Analysis of hibernation-induced gene expression is proving to be of crucial importance for identifying the genes and proteins that are up-regulated to address organ-specific concerns during torpor. In particular, the power of complementary deoxyribonucleic acid (cDNA) array screening is identifying families of proteins that are up-regulated during hibernation (eg, serpins, heat shock proteins, antioxidants, membrane transporters) and highlighting previously unrecognized areas of cellular metabolism as contributing to the hibernation phenotype. These offer new targets for innovative applied treatments that could enhance cytoprotection and cold ischemia survival of organ explants.

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PRIMING OF MICROGLIA ACTIVITY INCREASES SUSCEPTIBILITY TO DEPRESSION-LIKE BEHAVIORS

Innovation in Aging ◽

10.1093/geroni/igz038.359 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S95-S95

Author(s):

Tal Frolinger ◽

Umar Iqbal ◽

Giulio M Pasinetti

Keyword(s):

Gene Expression ◽

Depression And Anxiety ◽

Toll Like Receptor 4 ◽

Immune Priming ◽

Symptoms Of Depression ◽

Tlr4 Gene ◽

Induced Changes ◽

Increased Activity

Abstract This study investigates the role of microglia activity in stress-induced depression and anxiety and the mechanisms associated with the role of certain microbiome derived anti-inflammatory polyphenols in attenuating stress-induced microglia immune priming and symptoms of depression. We implemented a chronic unpredictable stress (CUS) paradigm to exhibit priming of microglia innate immunity in the context of the onset of depression and anxiety phenotypes. Mechanistic studies related to prophylactic treatment using dietary microbiome derived polyphenols were also investigated in this model. Depression and anxiety phenotypes, gene expression in microglia and protein expression in the cortex of mice were measured following a primary exposure to short-term unpredictable stress (US) followed by CUS. We examined the long-term, persistent CUS induced changes at 4-weeks of post-stress rest following a secondary US exposure. We found depression phenotypes resulted from US only following exposure to CUS. This was accompanied by an increase and persistent upregulation of toll-like receptor 4 (TLR4), RAGE, and HMGB1 gene expression in isolated cortical microglia. Priming by CUS also amplified gene expression of IL-1β in microglia and protein IL-1β in the cerebral cortex following US re-exposure. Increased activity of NF-kB was also noted in the period following CUS. Furthermore, polyphenol treatment prevented stress-induced phenotypes, upregulation of HMGB1, IL-1B, and TLR4 gene expression, as well as upregulation of IL-1β and NF-kB. The study suggests that latent activity of the TLR4-NFkB-IL1β pathway contributes to immune priming and increases susceptibility to depression-like behaviors. Anti-depressant effects of polyphenols may result from their ability to attenuate microglia priming.

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CREB in long-term potentiation in hippocampus: Role of post-translational modifications-studies In silico

Journal of Cellular Biochemistry ◽

10.1002/jcb.22909 ◽

2011 ◽

Vol 112 (1) ◽

pp. 138-146 ◽

Cited By ~ 7

Author(s):

Afshan Kaleem ◽

Daniel C. Hoessli ◽

Ikram-ul Haq ◽

Evelyne Walker-Nasir ◽

Asma Butt ◽

...

Keyword(s):

In Silico ◽

Long Term Potentiation ◽

Post Translational Modifications ◽

Term Potentiation

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Exploring the role of SoxA and SoxX in sulphur oxidation in Allochromatium vinosum through Protein-protein docking: An in silico approach

Pure and Applied Biology ◽

10.19045/bspab.2013.22003 ◽

2013 ◽

Vol 2 (2) ◽

pp. 53-56

Author(s):

Sujay Ray

Keyword(s):

In Silico ◽

Protein Docking ◽

Allochromatium Vinosum ◽

Sulphur Oxidation

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Role of Toll-like receptor-4 in renal graft ischemia-reperfusion injury

AJP Renal Physiology ◽

10.1152/ajprenal.00469.2013 ◽

2014 ◽

Vol 306 (8) ◽

pp. F801-F811 ◽

Cited By ~ 62

Author(s):

Hailin Zhao ◽

Jessica Santiváñez Perez ◽

Kaizhi Lu ◽

Andrew J. T. George ◽

Daqing Ma

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Graft Function ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Pharmacological Agents ◽

Renal Grafts

Toll-like receptor-4 (TLR-4) has been increasingly recognized as playing a critical role in the pathogenesis of ischemia-reperfusion injury (IRI) of renal grafts. This review provides a detailed overview of the new understanding of the involvement of TLR-4 in ischemia-reperfusion injury of renal grafts and its clinical significance in renal transplantation. TLR-4 not only responds to exogenous microbial motifs but can also recognize molecules which are released by stressed and necrotic cells, as well as degraded products of endogenous macromolecules. Upregulation of TLR-4 is found in tubular epithelial cells, vascular endothelial cells, and infiltrating leukocytes during renal ischemia-reperfusion injury, which is induced by massive release of endogenous damage-associated molecular pattern molecules such as high-mobility group box chromosomal protein 1. Activation of TLR-4 promotes the release of proinflammatory mediators, facilitates leukocyte migration and infiltration, activates the innate and adaptive immune system, and potentiates renal fibrosis. TLR-4 inhibition serves as the target of pharmacological agents, which could attenuate ischemia-reperfusion injury and associated delayed graft function and allograft rejection. There is evidence in the literature showing that targeting TLR-4 could improve long-term transplantation outcomes. Given the pivotal role of TLR-4 in ischemia-reperfusion injury and associated delayed graft function and allograft rejection, inhibition of TLR-4 using pharmacological agents could be beneficial for long-term graft survival.

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