The emergence of new omics approaches, such as genomic algorithms to identify tumor mutations and molecular modeling tools to predict the three-dimensional structure of proteins, has facilitated the understanding of the dynamic mechanisms involved in the pathogenesis of low-grade gliomas including oligodendrogliomas and astrocytomas.In this study, we targeted known mutations involved in low-grade gliomas, starting with the sequencing of genomic regions encompassing exon 4 of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) and the four exons (5-6 and 7-8) of TP53 from 32 samples, followed by computational analysis to study the impact of these mutations on the structure and function of 3 proteins IDH1, IDH2, and p53.We obtain a mutation that has an effect on the catalytic site of the protein IDH1 as R132H and on the catalytic site of the protein IDH2 as R172M. Other mutations at p53 have been identified as K305N, which is a pathogenic mutation; R175 H, which is a benign mutation; and R158G, which disrupts the structural conformation of the tumor suppressor protein.In low-grade gliomas, mutations in IDH1, IDH2, and TP53 may be the key to tumor progression because they have an effect on the function of the protein such as mutations R132H in IDH1 and R172M in IDH2, which change the function of the enzyme alpha-ketoglutarate, or R158G in TP53, which affects the structure of the generated protein, thus their importance in understanding gliomagenesis and for more accurate diagnosis complementary to the anatomical pathology tests.
Blastocystosis is an infection caused by Blastocystis sp., which colonizes the digestive tract of various hosts, including humans, although its pathogenicity is debated. It is crucial to detect and distinguish the different forms of Blastocystis to understand better its impact on human health and its epidemiological evolution. This study evaluated three diagnostic methods on 105 stool samples: direct examination, culture in Jones’ medium, and conventional PCR. PCR is considered the gold standard and revealed a high prevalence of Blastocystis (67.62%) compared to direct examination (20.95%) and culture in Jones’ medium (51.43%). Although the sensitivity of direct examination and culture was 31% and 76.1%, respectively, their specificity was 100%. No significant risk factors were identified. A statistically significant association was observed between Blastocystis infection and abdominal pain. Microscopic analysis revealed various morphological forms. Molecular diagnosis is an essential tool to determine the true prevalence of Blastocystis , and studying the different forms of this microorganism will contribute to a better understanding of its biological cycle and, therefore, the impact of this emerging infection on human health.
The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains. From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from 24 December 2019, to 13 May 2020, according to the GISAID database. Our analysis revealed the presence of 3206 variant sites, with a uniform distribution of mutation types in different geographic areas. Remarkably, a low frequency of recurrent mutations has been observed; only 169 mutations (5.27%) had a prevalence greater than 1% of genomes. Nevertheless, fourteen non-synonymous hotspot mutations (>10%) have been identified at different locations along the viral genome; eight in ORF1ab polyprotein (in nsp2, nsp3, transmembrane domain, RdRp, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein, and one in each of three proteins: Spike, ORF3a, and ORF8. Moreover, 36 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human ACE2 receptor. These results along with intra-genomic divergence of SARS-CoV-2 could indicate that unlike the influenza virus or HIV viruses, SARS-CoV-2 has a low mutation rate which makes the development of an effective global vaccine very likely.
In Morocco two waves of SARS-CoV-2 infections have been recorded. The first one occurred from March 02, 2020 with infections mostly imported from Europe and the second one dominated by local infections. At the time of writing, the genetic diversity of Moroccan isolates of SARS-CoV-2 has not yet been reported. The present study aimed to analyze first the genomic variation of the twenty-eight Moroccan strains of SARS-CoV-2 isolated from March 03, 2020 to May 15, 2020, to compare their distributions with twelve other viral genomes from North Africa as well as to identify their possible sources. Our finding revealed 61 mutations in the Moroccan genomes of SARS-CoV-2 compared to the reference sequence Wuhan-Hu-1/2019, of them 23 (37.7%) were present in two or more genomes. Focusing on non-synonymous mutations, 29 (47.54%) were distributed in five genes (ORF1ab, spike, membrane, nucleocapsid and ORF3a) with variable frequencies. The non-structural protein coding regions nsp3-Multi domain and nsp12-RdRp of the ORF1ab gene harbored more mutations, with six for each. The comparison of genetic variants of fourty North African strains revealed that two non-synonymous mutations D614G (in spike) and Q57H (in ORF3a) were common in four countries (Morocco, Tunisia, Algeria and Egypt), with a prevalence of 92.5% (n = 37) and 42.5% (n = 17), respectively, of the total genomes. Phylogenetic analysis showed that the Moroccan SARS-CoV-2 strains were closely related to those from different origins (Africa, Asia, Europe, North and South America) and distributed in different distinct subclades. This could indicate different sources of infection with no specific strain dominating yet in Morocco. These results have the potential to lead to new comprehensive investigations combining genomic data, epidemiological information and the clinical characteristics of patients with SARS-CoV-2. Keywords: SARS-CoV-2, Morocco, North African strains, mutations, spike protein, RdRp, Phylogeny.
Diffuse intrinsic pontine glioma (DIPG) also referred as paediatric high-grade glioma (pHGG) is a fast-growing and aggressive type of childhood brain cancer. Recent studies investigating the molecular pathogenesis of DIPG have identified new therapeutic targets, paving the way for a new line of drugs mainly HDAC inhibitors. However, despite long years of trials, no significant results have been generated yet. Panobinostat is a HDAC inhibitor that has shown promising preclinical cytotoxicity in DIPG but failed so far in clinical trials. This study aims to re-evaluate the efficacy of Panobinostat in DIPG in vitro using patient-derived DIPG cell cultures obtained directly from patients. ONC21 is another potentially effective drug in DIPG. This apoptotic agent has been considered in a few clinical trials in diffuse glioma including DIPG. Herein, we performed a preclinical evaluation, in patient-derived DIPG cultures along with an overview and discussion of clinical trials in DIPG patients to confirm and compare the potential efficacy of these drugs and also to understand the inconsistent outcomes of Panobinostat between preclinical and clinical trials. Our results reveal a dose-dependent response to Pabinostat and ONC201 in cultured DIPG cells. However, Panobinostat caused a significant reduction in the mean percentage cell viability at a lower concentration compared to ONC201. Panobinostat caused significant decreases in DIPG cell viability at concentrations greater than or equal to 0.002μM (p<0.05), the response reached a plateau after 0.1μM. ONC201 only significantly induced apoptosis at concentrations equal or higher than 0.01 μM (p<0.05), with its effect plateauing after 0.2 μM.
Among the numerous variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that have been reported worldwide, the emergence of the Omicron variant has drastically changed the landscape of the coronavirus disease (COVID-19) pandemic. Here, we analyzed the genetic diversity of Moroccan SARS-CoV-2 genomes with a focus on Omicron variant after one year of its detection in Morocco in order to understand its genomic dynamics, features and its potential introduction sources. From 937 Omicron genomes, we identified a total of 999 non-unique mutations distributed across 92 Omicron lineages, of which 13 were specific to the country. Our findings suggest multiple introductory sources of the Omicron variant to Morocco. In addition, we found that four Omicron clades are more infectious in comparison to other Omicron clades. Remarkably, a clade of Omicron is particularly more transmissible and has become the dominant variant worldwide. Moreover, our assessment of Receptor-Binding Domain (RBD) mutations showed that the Spike K444T and N460K mutations enabled a clade higher ability of immune vaccine escape. In conclusion, our analysis highlights the unique genetic diversity of the Omicron variant in Moroccan SARS-CoV-2 genomes, with multiple introductory sources and the emergence of highly transmissible clades. The distinctiveness of the Moroccan strains compared to global ones underscores the importance of ongoing surveillance and understanding of local genomic dynamics for effective response strategies in the evolving COVID-19 pandemic.
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