is a highly successful pathogen infecting various body parts and forming biofilms on natural and artificial surfaces resulting in difficult-to-treat and chronic infections. We investigated the ...secreted cytokines and proteomes of isolated peripheral blood mononuclear cells (PBMCs) from healthy volunteers exposed to methicillin-resistant
(MRSA) biofilms or planktonic bacteria. Additionally, the cytokine profiles in sera from patients with community-acquired pneumonia (CAP) caused by
were investigated. The aim was to gain insights into the immune response involved and differentiate between the planktonic and sessile MRSA forms. We identified 321 and 298 targets that were significantly differently expressed in PBMCs when exposed to planktonic or biofilm-embedded bacteria, respectively. PBMCs exposed to planktonic MRSA cells secreted increased levels of TNF-α, while IL-18 was elevated when exposed to the biofilm. The machine-learning analyses of the cytokine profiles obtained for the
PBMCs and CAP sera distinguished between the two types of bacteria forms based on cytokines IL-18, IL12, and IL-17, and with a lower importance IL-6. Particularly, IL-18 which has not been correlated with
biofilms so far might represent a suitable marker for monitoring chronification during MRSA infection to individualize the therapy, but this hypothesis must be proved in clinical trials.
Human brain development is a complex process that follows sequential orchestration of gene expression, begins at conceptual stages, and continues into adulthood. Altered profile of gene expression ...drives many cellular and molecular events required for development. Here, the molecular events during development of human prefrontal cortex (PFC) (as an important executive part of the brain) were investigated. First, the RNA-sequencing data of BrainSpan were used to obtain differentially expressed genes between each two developmental stages and then, the relevant biological processes and signaling pathways were deduced by gene set enrichment analysis. In addition, the changes in transcriptome landscape of PFC during development were analyzed and the potential biological processes underlie the changes were found. Comparison of the four regions of PFC based on their biological processes showed that additional to common biological processes and signaling pathways, each PFC region had its own molecular characteristics, conforming their previously reported functional roles in brain physiology. The most heterogeneity in transcriptome between the PFC regions was observed at the time of birth which was concurrent with the activity of some region-specific regulatory systems such as DNA methylation, transcription regulation, RNA splicing, and presence of different transcription factors and microRNAs. In conclusion, this study used bioinformatics to present a comprehensive molecular overview on PFC development which may explain the etiology of brain neuropsychiatric disorders originated from malfunctioning of PFC.
Liver cirrhosis is a major public health problem, accounting for high rates of morbidity and mortality worldwide. The cirrhosis etiology is a broad and essential step in planning a treatment ...strategy. Many recent studies have documented that gut microbiome alterations play a vital role in the development and progression of cirrhosis and its complications. Nevertheless, there is insufficient data on the correlation between liver cirrhosis and gut phageome alterations in patients with advanced liver diseases. This study aimed to analyze the taxonomic structure and functional attributes of the gut phageome in six different etiologies of advanced liver cirrhosis.
We first retrieved metagenomic sequencing data from three datasets of fecal samples taken from cirrhotic patients with various etiologies. Subsequently, several bioinformatics pipelines were used to analyze bacteriophage composition and determine their functionality.
A gene catalog of 479,425 non-redundant genes was developed as a reference to measure gene prevalence. The results of the analysis revealed a few significant differences among the cohorts at the phage species level. However, the alternations were more evident as there were more in-depth analyses of the functional resolution of the gut phageome.
Our findings suggest that the functional analysis of the gut phageome would provide meaningful markers to predict the progression of liver cirrhosis and facilitate the development of novel treatment approaches.
Intercellular interactions and cell–cell communication are critical to regulating cell functions, especially in normal immune cells and immunotherapies. Ligand–receptor pairs mediating these ...cell–cell interactions can be identified using diverse experimental and computational approaches. Here, we reconstructed the intercellular interaction network between Mus musculus immune cells using publicly available receptor–ligand interaction databases and gene expression data from the immunological genome project. This reconstructed network accounts for 50,317 unique interactions between 16 cell types between 731 receptor–ligand pairs. Analysis of this network shows that cells of hematopoietic lineages use fewer communication pathways for interacting with each other, while nonhematopoietic stromal cells use the most network communications. We further observe that the WNT, BMP, and LAMININ pathways are the most significant contributors to the overall number of cell–cell interactions among the various pathways in the reconstructed communication network. This resource will enable the systematic analysis of normal and pathologic immune cell interactions, along with the study of emerging immunotherapies.
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