The Urban Development in Relation to the Occurrence of Diseases in the Casa-Settat Region of Morocco during the Emergence of SARS-CoV-2.

The Casa-Settat region is experiencing very worrying environmental and epidemiological problems and challenges, namely, population growth, the significant development of unsupervised industrial activities, road traffic, the significant weight of the spread of diseases with high epidemiological potential such as SARS-CoV-2, the increase in hospital activities, and the significant discharge of hospital effluents highly contaminated and untreated. To understand and analyze the factors influencing the high prevalence of deaths and the occurrence of diseases under surveillance, among others SARS-CoV-2, on the quantitative data recorded relating to ten regions of Morocco, and informing, on the one hand, on intrinsic data linked to the urban development, and on the other hand, on the evolution of diseases under epidemiological surveillance, a multidimensional analysis was made. The results reveal the typological framework highlighted by the factorial map F1 × F2 which showed the individualization of the region of Casablanca explained by a large number of variables and diseases that affect it. Finally, these results call for a diagnosis that will make it possible to model new approaches and implement new actions promoting the dynamics of environmental and epidemiological change in one of the most polluted and infected regions of Morocco.

The role of the ubiquitin-proteasome pathway in skin cancer development: 26S proteasome-activated NF-κB signal transduction.

The Ubiquitin-Proteasome System plays a central role in signal transduction associated with stress, in the skin in particular by the control of NF-κB pathways. Under normal conditions, the inhibitory protein IκB is phosphorylated by kinases, then ubiquitinated and ends up at the proteasome to be degraded. The present short review discusses recent progress in the inhibition of NF-κB activation by proteasome inhibitors prevents the degradation of protein IκB, which accumulates in the cytosol, and there by the activation of NF-κB. Moreover, would not only limit the expression of adhesion molecules and cytokines involved in metastatic processes, but also increase the sensitivity of cancer cells to apoptosis. Considering this fact, the activity of NF-κB is regulated by the phosphorylation and proteasome-dependent degradation of its inhibitor Iκb. In this scenario, the use of a proteasome inhibitor might be an effective strategy in the treatment of skin cancer with constitutive activation of NF-κB.

Antitumor Effect of Inula viscosa Extracts on DMBA-Induced Skin Carcinoma Are Mediated by Proteasome Inhibition.

The aim of this work is to evaluate the antitumor effect mediated by the proteasome inhibitors of Inula viscosa extracts on skin carcinogenesis. Female Swiss albino mice were divided into five groups depending on the combination of skin cancer-inducing 7,12-dimethylbenz(a)anthracene (DMBA) and extract of Inula viscosa treatments. Histology of the affected skin and measurement of proteasome activity were performed to demonstrate the effect of Inula viscosa on mice. The identification of the molecules responsible for this inhibitory activity was carried out through the docking studies. The results showed that Inula viscosa extracts inhibit the development of papilloma in mice. Therefore, the best chemopreventive action of Inula viscosa was observed on mice in which extract treatment was performed before and after the induction of skin carcinogenesis. It was revealed that the ingestion of extracts Inula viscosa delays the formation of skin papillomas in animals and simultaneously decreases the size and number of papillomas, which is also reflected on the skin histology of the mice treated. Structure-activity relationship information obtained from component of Inula viscosa particularly tomentosin, inuviscolide, and isocosticacid demonstrated that distinct bonding modes in ß 1, ß 2, and ß 5 subunits determine its selectivity and potent inhibition for ß 5 subunit.

RET genetic screening in patients with medullary thyroid cancer: the Moroccan experience.

BACKGROUND: Germline RET gene mutations are well known to be the genetic causes of multiple endocrine neoplasia type 2 (MEN2) and may be identified by genetic screening. AIM: The purpose of the present study was to screen nine MTC patients for RET sequence changes. MATERIALS AND METHODS: In this study, our sample was composed of 30 individuals: 9 index patients with medullary thyroid carcinoma (MTC) corresponding either to 3 subjects with clinical evidence of MEN2, 6 with apparently sporadic MTC (sMTC), and 21 relatives have been investigated for RET mutations. After DNA extraction from peripheral blood leukocytes, RET exons 8, 10, 11, 13-16 and exon/intron boundaries were analyzed by direct PCR sequencing. RESULTS: Three different known RET germline mutations in exon 11 (codon 634), p.Cys634Arg (c1900 T-->C) (de novo case), p.Cys634Phe (c1901 G-->T), p.Cys634Trp (c1902 C-->G), were detected in three individuals with MEN2 phenotype. Of the 21 relatives, 2 cases presented mutation. Among the six probands with sMTC, none was found to carry mutation. There was no difference between RET polymorphisms detected among both MEN2 and sMTC patients. CONCLUSIONS: These preliminary data suggest that the RET mutation spectra observed in Moroccan patients with MEN2 are similar to those previously reported in other countries.

Pre-organized structure of viral DNA at the binding-processing site of HIV-1 integrase.

The integration of the human immunodeficiency virus type 1 DNA into the host cell genome is catalysed by the viral integrase (IN). The reaction consists of a 3'-processing [dinucleotide released from each 3' end of the viral long terminal repeat (LTR)] followed by a strand transfer (insertion of the viral genome into the human chromosome). A 17 base pair oligonucleotide d(GGAAAATCTCTAGCAGT), d(ACTGCTAGAGATTTTCC) reproducing the U5-LTR extremity of viral DNA that contains the IN attachment site was analysed by NMR using the classical NOEs and scalar coupling constants in conjunction with a small set of residual dipolar coupling constants (RDCs) measured at the 13C/15N natural abundance. The combination of these two types of parameters in calculations significantly improved the DNA structure determination. The well-known features of A-tracts were clearly identified by RDCs in the first part of the molecule. The binding/cleavage site at the viral DNA end is distinguishable by a loss of regular base stacking and a distorted minor groove that can aid its specific recognition by IN.