Dataset Information

Sequencing Analysis and Identification of the Primary Peptide Component of the Dialyzable Leukocyte Extract “Transferon Oral”: The Starting Point to Understand Its Mechanism of Action

ABSTRACT: “Transferon Oral” is a peptide-derived product with immunomodulatory properties obtained from the lysis and dialysis of human buffy coat. Its active pharmaceutical ingredient, generically known as Dialyzable Leucocyte Extract, is a mixture of peptide populations with reproducible proportions among batches. “Transferon Oral” modulates IFN-?, TNF-?, and IL-6 and increases the survival rate in a herpes infection murine model when oropharyngeally (ORO) administered, which correlate with clinical observations where “Transferon Oral” is used as a therapeutic auxiliary in inflammatory diseases. Notwithstanding, how a peptide-derived product elicits systemic modulation of cytokines when ORO administered remains unclear. To shed light on the pharmacology of “Transferon Oral” its peptide components must be known. Ten “Transferon Oral” batches were sequenced by mass spectrometry and the intact peptides were identified. The most abundant peptides were the monomeric human Ubiquitin (Ub), a globular low-molecular mass protein, and an Ub variant which lacks the two-terminal Gly (Ub-GG). Recombinant Ub prevented murine death when ORO administered in a herpes infection murine model. Besides, the percentage of survival increased in groups treated with Transferon Oral+Ub and decreased in groups treated with Ub-depleted “Transferon Oral” respect to the group treated with “Transferon Oral” only. Our findings indicate that the biological properties of “Transferon Oral” are partially associated to the Ub content. They suggest that Ub may activate its extracellular receptor (CXCR-4) in the stomach eliciting systemic immunomodulatory effects via vagus nerve. This is the first report that identifies an active component of “Transferon Oral” with the potential for the development of oral peptide immunomodulators.

SUBMITTER: Vallejo-Castillo L

PROVIDER: S-EPMC7577238 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:Influenza constitutes a major challenge to world health authorities due to high transmissibility and the capacity to generate large epidemics. This study aimed to characterize the diffusion process of influenza A (H1N1) by identifying the starting point of the epidemic as well as climatic and sociodemographic factors associated with the occurrence and intensity of transmission of the disease. The study was carried out in the Brazilian state of Paraná, where H1N1 caused the largest impact. The units of spatial and temporal analysis were the municipality of residence of the cases and the epidemiological weeks of the year 2009, respectively. Under the Bayesian paradigm, parametric inference was performed through a two-part spatiotemporal model and the integrated nested Laplace approximation (INLA) algorithm. We identified the most likely starting points through the effective distance measure based on mobility networks. The proposed estimation methodology allowed for rapid and efficient implementation of the spatiotemporal model, and provided evidence of different patterns for chance of occurrence and risk of influenza throughout the epidemiological weeks. The results indicate the capital city of Curitiba as the probable starting point, and showed that the interventions that focus on municipalities with greater migration and density of people, especially those with higher Human Development Indexes (HDIs) and the presence of municipal air and road transport, could play an important role in mitigation of effects of future influenza pandemics on public health. These results provide important information on the process of introduction and spread of influenza, and could contribute to the identification of priority areas for surveillance as well as establishment of strategic measures for disease prevention and control. The proposed model also allows identification of epidemiological weeks with high chance of influenza occurrence, which can be used as a reference criterion for creating an immunization campaign schedule.

Dataset Information

Sequencing Analysis and Identification of the Primary Peptide Component of the Dialyzable Leukocyte Extract “Transferon Oral”: The Starting Point to Understand Its Mechanism of Action

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