Association study of the JAK/STAT signaling pathway with susceptibility to COVID-19 in moroccan patient and in-silico analysis of rare variants.

The goal of our study was to explore the association of the polymorphisms in the JAK/STAT pathway among Moroccan COVID-19 patients, using a case-control approach. Next-generation sequencing was employed to investigate the IFNAR1, IFNAR2, JAK1, TYK2, STAT2, and IRF9 genes within the JAK/STAT pathway. We also performed an in silico study to examine the rare variants in this pathway.

A post-irradiation-induced replication stress promotes RET proto-oncogene breakage.

Objective: Ionizing radiation generates genomic instability by promoting the accumulation of chromosomal rearrangements. The oncogenic translocation RET/PTC1 is present in more than 70% of radiation-induced thyroid cancers. Both RET and CCDC6, the genes implicated in RET/PTC1, are found within common fragile sites - chromosomal regions prone to DNA breakage during slight replication stress.

, and Mutational Profile of Colorectal Cancer in a Series of Moroccan Patients.

Objectives: The present study aimed to evaluate the frequencies of , and mutations and their possible associations with clinicopathological features in 249 Moroccan patients with colorectal cancer (CRC).

Methods: A retrospective investigation of a cohort of formalin-fixed paraffin-embedded tissues of 249 patients with CRC was screened for // mutations using Idylla™ technology and pyrosequencing.

Results: , and mutations were revealed in 46.

Pre-pandemic antibodies screening against SARS-CoV-2 and virus detection among children diagnosed with eruptive fevers.

Objectives: This study aims to assess the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies against the spike (S) and nucleocapsid (NP) proteins, as well as neutralizing antibodies against the receptor-binding domain (RBD). Additionally, it aims to detect viral RNA of SARS-CoV-2 in pre-pandemic archival pediatric specimens collected before the announcement of the COVID-19 pandemic spread on March 20, 2020, in Morocco. The objective is to investigate the existence of pre-pandemic immunity to SARS-CoV-2.

Alteration of glucose metabolism and expression of glucose transporters in ovarian cancer.

Aerobic glycolysis also known as the Warburg effect, remains a hallmark of various cancers, including ovarian cancer. Cancer cells undergo metabolic changes to sustain their tumorigenic properties and adapt to environmental conditions, such as hypoxia and nutrient starvation. Altered metabolic pathways not only facilitate ovarian cancer cells' survival and proliferation but also endow them to metastasize, develop resistance to chemotherapy, maintain cancer stem cell phenotype, and escape anti-tumor immune responses.

Methods for detection of mitochondrial reactive oxygen species in senescent cells.

Cellular senescence is a pathophysiological process with multifaceted effects. It is involved in wound healing, aging and age-related diseases as well as cancer. On the one hand, senescence is considered as barrier against tumorigenesis by inducing an irreversible/prolonged cell cycle arrest.

The Tumor Suppressor BRCA1/2, Cancer Susceptibility and Genome Instability in Gynecological and Mammary Cancers.

BRCA1 and BRCA2 germline alterations highly predispose women to breast and ovarian cancers. They are mostly found within the TNBC (Triple-Negative Breast Cancer) and the HGSOC (High-Grade Serous Ovarian Carcinoma) subsets, known by an aggressive phenotype, the lack of therapeutic targets and poor prognosis. Importantly, there is an increased risk for cervical cancer in BRCA1 and BRCA2 mutation carriers that raises questions about the link between the HPV-driven genome instability and BRCA1 and BRCA2 germline mutations.

BRCA1 Promoter Hypermethylation in Malignant Breast Tumors and in the Histologically Normal Adjacent Tissues to the Tumors: Exploring Its Potential as a Biomarker and Its Clinical Significance in a Translational Approach.

The hypermethylation status of the promoter region of the breast cancer 1 (, a well-known tumor suppressor gene, has been extensively investigated in the last two decades as a potential biomarker for breast cancer. In this retrospective study, we investigated the prevalence of promoter methylation in 84 human breast tissues, and we correlated this epigenetic silencing with the clinical and histopathological parameters of breast cancer. We used methylation-specific PCR (MSP) to analyze BRCA1 promoter hypermethylation in 48 malignant breast tumors (MBTs), 15 normal adjacent tissues (NATs), and 21 benign breast lesions (BBLs).

A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid Tumors.

The comparative analysis of the expression of the reactive oxygen species-generating NADPH oxidase NOX4 from TCGA data shows that the NOX4 transcript is upregulated in papillary thyroid carcinomas (PTC)-BRAF tumors compared to PTC-BRAF tumors. However, a comparative analysis of NOX4 at the protein level in malignant and non-malignant tumors is missing. We explored NOX4 protein expression by immunohistochemistry staining in malignant tumors (28 classical forms of PTC (C-PTC), 17 follicular variants of PTC (F-PTC), and three anaplastic thyroid carcinomas (ATCs)) and in non-malignant tumors (six lymphocytic thyroiditis, four Graves' disease, ten goiters, and 20 hyperplasias).

BRAF hot spot mutation in thyroid carcinomas: first Moroccan experience from a single-institution retrospective study.

Background: The incidence of thyroid cancer is increasing worldwide at an alarming rate. BRAF mutation is described to be associated with a worse prognostic of thyroid carcinomas, as well as extrathyroidal invasion and increased mortality.

Objective: To our knowledge, there are no reported studies neither from Morocco nor from other Maghreb countries regarding the prevalence of BRAF mutation in thyroid carcinomas.

NADPH oxidase DUOX1 sustains TGF-β1 signalling and promotes lung fibrosis.

Interstitial lung fibroblast activation coupled with extracellular matrix production is a pathological signature of pulmonary fibrosis, and is governed by transforming growth factor (TGF)-β1/Smad signalling. TGF-β1 and oxidative stress cooperate to drive fibrosis. Cells can produce reactive oxygen species through activation and/or induction of NADPH oxidases, such as dual oxidase (DUOX1/2).

Oxidative stress in thyroid carcinomas: biological and clinical significance.

At physiological concentrations, reactive oxygen species (ROS), including superoxide anions and H2O2, are considered as second messengers that play key roles in cellular functions, such as proliferation, gene expression, host defence and hormone synthesis. However, when they are at supraphysiological levels, ROS are considered potent DNA-damaging agents. Their increase induces oxidative stress, which can initiate and maintain genomic instability.

Conformation of the N-Terminal Ectodomain Elicits Different Effects on DUOX Function: A Potential Impact on Congenital Hypothyroidism Caused by a HO Production Defect.

Background: Dual oxidases (DUOX1 and DUOX2) were initially identified as HO sources involved in thyroid hormone synthesis. Congenital hypothyroidism (CH) resulting from inactivating mutations in the DUOX2 gene highlighted that DUOX2 is the major HO provider to thyroperoxidase. The role of DUOX1 in the thyroid remains unknown.

Detection of Reactive Oxygen Species in Cells Undergoing Oncogene-Induced Senescence.

Reactive oxygen species (ROS) derive from molecular oxygen and present higher reactivity. ROS designation comprehends free radicals such as superoxide radical (O°), hydroxyl radical (OH°); but also nonradical molecule like hydrogen peroxide (HO). ROS play a critical role in several physiological functions like proliferation and signalling pathways.

NADPH Oxidase NOX4 Is a Critical Mediator of BRAF-Induced Downregulation of the Sodium/Iodide Symporter in Papillary Thyroid Carcinomas.

Aims: The BRAF oncogene, reported in 40%-60% of papillary thyroid cancer (PTC), has an important role in the pathogenesis of PTC. It is associated with the loss of thyroid iodide-metabolizing genes, such as sodium/iodide symporter (NIS), and therefore with radioiodine refractoriness. Inhibition of mitogen-activated protein kinase (MAPK) pathway, constitutively activated by BRAF, is not always efficient in resistant tumors suggesting that other compensatory mechanisms contribute to a BRAF adaptive resistance.

NADPH oxidases: new actors in thyroid cancer?

Hydrogen peroxide (H2O2) is a crucial substrate for thyroid peroxidase, a key enzyme involved in thyroid hormone synthesis. However, as a potent oxidant, H2O2 might also be responsible for the high level of oxidative DNA damage observed in thyroid tissues, such as DNA base lesions and strand breakages, which promote chromosomal instability and contribute to the development of tumours. Although the role of H2O2 in thyroid hormone synthesis is well established, its precise mechanisms of action in pathological processes are still under investigation.

NADPH oxidase DUOX1 promotes long-term persistence of oxidative stress after an exposure to irradiation.

Ionizing radiation (IR) causes not only acute tissue damage, but also late effects in several cell generations after the initial exposure. The thyroid gland is one of the most sensitive organs to the carcinogenic effects of IR, and we have recently highlighted that an oxidative stress is responsible for the chromosomal rearrangements found in radio-induced papillary thyroid carcinoma. Using both a human thyroid cell line and primary thyrocytes, we investigated the mechanism by which IR induces the generation of reactive oxygen species (ROS) several days after irradiation.

When an Intramolecular Disulfide Bridge Governs the Interaction of DUOX2 with Its Partner DUOXA2.

Aims: The dual oxidase 2 (DUOX2) protein belongs to the NADPH oxidase (NOX) family. As H2O2 generator, it plays a key role in both thyroid hormone biosynthesis and innate immunity. DUOX2 forms with its maturation factor, DUOX activator 2 (DUOXA2), a stable complex at the cell surface that is crucial for the H2O2-generating activity, but the nature of their interaction is unknown.

Human papillomavirus detection in Moroccan patients with bladder cancer.

Introduction: Human papillomavirus (HPV) is associated with more human cancers than any other virus. Many studies have investigated the association between bladder cancer and HPV but the results remain controversial. The aim of the present study is to evaluate whether HPV have an etiological role in bladder carcinogenesis among Moroccan patients.

Functional consequences of dual oxidase-thyroperoxidase interaction at the plasma membrane.

Context: Thyroperoxidase (TPO) and dual oxidase (DUOX) are present at the apical membrane of thyrocytes, where TPO catalyzes thyroid hormone biosynthesis in the presence of H2O2 produced by DUOX. Both enzymes are colocalized and associated, but the consequences of this interaction remain obscure.

Objective: The objective of this study was to evaluate the functional consequences of TPO-DUOX interaction at the plasma membrane.

Role of H2O2 in RET/PTC1 chromosomal rearrangement produced by ionizing radiation in human thyroid cells.

During childhood, the thyroid gland is one of the most sensitive organs to the carcinogenetic effects of ionizing radiation that may lead to papillary thyroid carcinoma (PTC) associated with RET/PTC oncogene rearrangement. Exposure to ionizing radiation induces a transient "oxidative burst" through radiolysis of water, which can cause DNA damage and mediates part of the radiation effects. H(2)O(2) is a potent DNA-damaging agent that induces DNA double-strand breaks, and consequently, chromosomal aberrations.

Intracellular expression of reactive oxygen species-generating NADPH oxidase NOX4 in normal and cancer thyroid tissues.

NADPH oxidase 4 (NOX4) belongs to the NOX family that generates reactive oxygen species (ROS). Function and tissue distribution of NOX4 have not yet been entirely clarified. To date, in the thyroid gland, only DUOX1/2 NOX systems have been described.

Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity.

Duox2 (and probably Duox1) is a glycoflavoprotein involved in thyroid hormone biosynthesis, as the thyroid H2O2 generator functionally associated with Tpo (thyroperoxidase). So far, because of the impairment of maturation and of the targeting process, transfecting DUOX into nonthyroid cell lines has not led to the expression of a functional H2O2-generating system at the plasma membrane. For the first time, we investigated the H2O2-generating activity in the particulate fractions from DUOX2- and DUOX1-transfected HEK293 and Chinese hamster ovary cells.

Dual oxidase2 is expressed all along the digestive tract.

The dual oxidase (Duox)2 flavoprotein is strongly expressed in the thyroid gland, where it plays a critical role in the synthesis of thyroid hormones by providing thyroperoxidase with H2O2. DUOX2 mRNA was recently detected by RT-PCR and in-situ hybridization experiments in other tissues, such as rat colon and rat and human epithelial cells from the salivary excretory ducts and rectal glands. We examined Duox2 expression at the protein level throughout the porcine digestive tract and in human colon.