Cytogenetic abnormalities correlate with clinico-biological characteristics in 30 Moroccan multiple myeloma patients.

Background: The nonrandom recurrence of chromosomal abnormalities in multiple myeloma (MM) raises the possibility that they play a role in the pathophysiology and development of the disease. Fluorescence in situ hybridization (FISH) can identify a high frequency of certain abnormalities without the need for the proliferative and infiltrative index of malignant plasma cells required for conventional cytogenetic analysis. In this study, we describe the association between clinico-biological characteristics and chromosomal abnormalities in 30 Moroccan patients. Methods: The analysis of cytogenetic data, conventional and molecular, of 30 cases of MM, obtained from our previously cytogenetic study, and correlation of the results with the clinico-biological data of these patients. Results: The bone marrow of 5 of 21 patients (23 %) contained a chromosomally abnormal clone, and all karyotypes were complicated (>3 abnormalities). Interphase FISH (iFISH) has detected aberrations in 14 out of 30 (46 %) of the total cases. The proportion of plasma cells in the bone marrow was higher in patients with chromosomal abnormalities (median 29 %) (p = 0.01917) than in patients without abnormalities (median 11 %). Although there was a difference in the median ß-2 microglobulin percentage (13.8 % versus 6.8 %), it was not statistically significant (p = 0.6818). We also, categorized patients into those with a complex clone and those with a sole abnormality. Patients with high bone marrow plasma cell rate (median 45 %) and high rate of ß-2 microglobulin (median 24 %) showed a complex karyotype and a higher iFISH detection rate than those with plasma cells count for (median 20 %) and ß-2 microglobulin count for (median 11 %) but without statistical significance (p = 0.4338 et p = 0.45 respectively). Furthermore, patients with aberrations had significantly shorter overall survival (100 % for 800 days versus 150 days only). Conclusion: Our research has shown that different subgroups of patients with MM can be classified based on the underlying genetic abnormalities. Chromosomal abnormalities (CA) may give the plasma cell a proliferative advantage, increasing the virulence of the disease and affecting overall survival.

In Silico Prediction of the Bioactive Profile and Metabolites of Satureja nepeta in Diseases Related to the Excessive Production of Interleukin-6.

Inflammatory bowel diseases are caused by an abnormal reaction of the immune system, which becomes hyperactive because the mechanisms responsible for regulating it get out of control. For an effective immune response, many proinflammatory cytokines are secreted, particularly interleukin-6 (IL-6) keystone cytokine inflammation. Many synthetic and natural compounds targeting IL-6 have been studied. The genus Satureja of the Lamiaceae family is generally known for its many virtues, in particular anti-inflammatory properties. However, the mechanism of action is unclear. This study aims to predict the impact of characterized bioactive molecules of Moroccan Satureja nepeta in the potential control of inflammatory response mediated by IL-6 cytokine. A list of 9 previously characterized natural compounds of S. nepeta was compiled, and a list of 6 potential protein targets involved in intestinal inflammation was made. The 2 lists of natural compound-target proteins were analyzed by the STITCH software (http://stitch.embl.de/) to develop protein-compound and protein-protein interaction networks (PPINs). An ontological enrichment (GO) analysis was performed by the Clue GO plugin to evaluate the PPIN generated by STITCH; finally, the molecular docking to predict the mode underlying the anti-inflammatory effects. STITCH results revealed direct and indirect interactions of S. nepeta chemical compounds with a key protein target IL-6. The array results by ClueGO showed that most compounds involved in the regulation of several biological processes related to IL-6 such as inflammation apoptosis, cell differentiation, and metabolic regulation. The targets directly related to IL-6 have been used for molecular docking. Quercetin, catechin, and gallic acid have a strong affinity with the IL-6 receptor (respectively -7.1; -6.1; -5.3). This study strongly suggests that the bioactive compounds of S. nepeta could constitute a new therapeutic alternative in the treatment of diseases related to IL-6. However, to validate the results obtained in this work, it is necessary to explore the mechanism of action of potential bioactive molecules by experimentation.

Multiple Myeloma: Bioinformatic Analysis for Identification of Key Genes and Pathways.

Multiple myeloma (MM) is a hematological malignancy in which monoclonal plasma cells multiply in the bone marrow and monoclonal immunoglobulins are overproduced in older people. Several molecular and cytogenetic advances allow scientists to identify several genetic and chromosomal abnormalities that cause the disease. The comprehension of the pathophysiology of MM requires an understanding of the characteristics of malignant clones and the changes in the bone marrow microenvironment. This study aims to identify the central genes and to determine the key signaling pathways in MM by in silico approaches. A list of 114 differentially expressed genes (DEGs) is important in the prognosis of MM. The DEGs are collected from scientific publications and databases (https://www.ncbi.nlm.nih.gov/). These data are analyzed by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) software (https://string-db.org/) through the construction of protein-protein interaction (PPI) networks and enrichment analysis of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, by CytoHubba, AutoAnnotate, Bingo Apps plugins in Cytoscape software (https://cytoscape.org/) and by DAVID database (https://david.ncifcrf.gov/). The analysis of the results shows that there are 7 core genes, including TP53; MYC; CDND1; IL6; UBA52; EZH2, and MDM2. These top genes appear to play a role in the promotion and progression of MM. According to functional enrichment analysis, these genes are mainly involved in the following signaling pathways: Epstein-Barr virus infection, microRNA pathway, PI3K-Akt signaling pathway, and p53 signaling pathway. Several crucial genes, including TP53, MYC, CDND1, IL6, UBA52, EZH2, and MDM2, are significantly correlated with MM, which may exert their role in the onset and evolution of MM.

Functional Prediction of Biological Profile During Eutrophication in Marine Environment.

In the marine environment, coastal nutrient pollution and algal blooms are increasing in many coral reefs and surface waters around the world, leading to higher concentrations of dissolved organic carbon (DOC), nitrogen (N), phosphate (P), and sulfur (S) compounds. The adaptation of the marine microbiota to this stress involves evolutionary processes through mutations that can provide selective phenotypes. The aim of this in silico analysis is to elucidate the potential candidate hub proteins, biological processes, and key metabolic pathways involved in the pathogenicity of bacterioplankton during excess of nutrients. The analysis was carried out on the model organism Escherichia coli K-12, by adopting an analysis pipeline consisting of a set of packages from the Cystoscape platform. The results obtained show that the metabolism of carbon and sugars generally are the 2 driving mechanisms for the expression of virulence factors.

Prediction of Anti-COVID 19 Therapeutic Power of Medicinal Moroccan Plants Using Molecular Docking.

The emerging pathogen SARS-CoV2 causing coronavirus disease 2019 (COVID-19) is a global public health challenge. To the present day, COVID-19 had affected more than 40 million people worldwide. The exploration and the development of new bioactive compounds with cost-effective and specific anti-COVID 19 therapeutic power is the prime focus of the current medical research. Thus, the exploitation of the molecular docking technique has become essential in the discovery and development of new drugs, to better understand drug-target interactions in their original environment. This work consists of studying the binding affinity and the type of interactions, through molecular docking, between 54 compounds from Moroccan medicinal plants, dextran sulfate and heparin (compounds not derived from medicinal plants), and 3CLpro-SARS-CoV-2, ACE2, and the post fusion core of 2019-nCoV S2 subunit. The PDB files of the target proteins and prepared herbal compounds (ligands) were subjected for docking to AutoDock Vina using UCSF Chimera, which provides a list of potential complexes based on the criteria of form complementarity of the natural compound with their binding affinities. The results of molecular docking revealed that Taxol, Rutin, Genkwanine, and Luteolin-glucoside have a high affinity with ACE2 and 3CLpro. Therefore, these natural compounds can have 2 effects at once, inhibiting 3CLpro and preventing recognition between the virus and ACE2. These compounds may have a potential therapeutic effect against SARS-CoV2, and therefore natural anti-COVID-19 compounds.

Integrative Analysis of the Genes Induced by the Intestine Microbiota of Infant Born to Term and Breastfed.

Nowadays, the integration of biological data is a major challenge for bioinformatics. Many studies have examined gene expression in the epithelial tissue in the intestines of infants born to term and breastfed, generating a large amount of data. The integration of these data is important to understand the biological processes involved during bacterial colonization of the newborns intestine, particularly through breast milk. This work aims to exploit the bioinformatics approaches, to provide a new representation and interpretation of the interactions between differentially expressed genes in the host intestine induced by the microbiota.