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Hepatitis C virus (HCV) infection is one of the major health burdens worldwide. Its course depends on the virus itself and the host’s immune responses. The latter are conditioned by immunogenetic factors, in particular human leukocyte antigens (HLAs), whose role in determining the outcome of infection varies according to populations and ethnic groups. The current study attempted to investigate the possible relationship between HLA-A and HLA-B allele polymorphism and its impacts on the clinical outcome of HCV for a better understanding of disease susceptibility and clearance. A cross-sectional and comparative study was carried out on 40 patients with hepatitis C and 100 ethnically matched healthy control subjects originating from southern Morocco. HLA class I alleles were typed using the high-resolution PCR-SSO method. The prevalence of certain HLA class I alleles differed significantly between HCV-infected individuals and healthy controls. In particular, HLA-A*02:01 was less prevalent in chronic HCV infection (p = 0.002), indicating a potential protective effect, while the higher prevalence of HLA-A*68:02, A*66:01 B*15:03, B*41:02, B*44:03, and B*50:01 in patients could indicate a predisposing factor. These findings support the association of these immunogenetic markers with HCV infection, indicating their possible role in determining clinical and genotype forms as well as the outcome of HCV infection. Thus, an in-depth analysis of these alleles could lead to a better understanding of HCV pathogenesis and potential targeted interventions.

Precision Medicine is being increasingly used in the developed world to improve health care. While several Precision Medicine (PM) initiatives have been launched worldwide, their implementations have proven to be more challenging particularly in low- and middle-income countries. To address this issue, the “Personalized Medicine in North Africa” initiative (PerMediNA) was launched in three North African countries namely Tunisia, Algeria and Morocco. PerMediNA is coordinated by Institut Pasteur de Tunis together with the French Ministry for Europe and Foreign Affairs, with the support of Institut Pasteur in France. The project is carried out along with Institut Pasteur d’Algérie and Institut Pasteur du Maroc in collaboration with national and international leading institutions in the field of PM including Institut Gustave Roussy in Paris. PerMediNA aims to assess the readiness level of PM implementation in North Africa, to strengthen PM infrastructure, to provide workforce training, to generate genomic data on North African populations, to implement cost effective, affordable and sustainable genetic testing for cancer patients and to inform policy makers on how to translate research knowledge into health products and services. Gender equity and involvement of young scientists in this implementation process are other key goals of the PerMediNA project.In this paper, we are describing PerMediNA as the first PM implementation initiative in North Africa. Such initiatives contribute significantly in shortening existing health disparities and inequities between developed and developing countries and accelerate access to innovative treatments for global health.

Introduction: Autism spectrum disorder (ASD) is characterized by aberrations in social interaction and communication associated with repetitive behaviors and interests, with strong clinical heterogeneity. Genetic factors play an important role in ASD, but about 75% of ASD cases have an undetermined genetic risk.Methods: We extensively investigated an ASD cohort made of 102 families from the Middle Eastern population of Qatar. First, we investigated the copy number variations (CNV) contribution using genome-wide SNP arrays. Next, we employed Next Generation Sequencing (NGS) to identify de novo or inherited variants contributing to the ASD etiology and its associated comorbid conditions in families with complete trios (affected child and the parents).Results: Our analysis revealed 16 CNV regions located in genomic regions implicated in ASD. The analysis of the 88 ASD cases identified 41 genes in 39 ASD subjects with de novo (n = 24) or inherited variants (n = 22). We identified three novel de novo variants in new candidate genes for ASD (DTX4, ARMC6, and B3GNT3). Also, we have identified 15 de novo variants in genes that were previously implicated in ASD or related neurodevelopmental disorders (PHF21A, WASF1, TCF20, DEAF1, MED13, CREBBP, KDM6B,SMURF1, ADNP, CACNA1G, MYT1L, KIF13B, GRIA2, CHM, and KCNK9). Additionally, we defined eight novel recessive variants (RYR2, DNAH3, TSPYL2, UPF3B KDM5C, LYST, and WNK3), four of which were X-linked.Conclusion: Despite the ASD multifactorial etiology that hinders ASD genetic risk discovery, the number of identified novel or known putative ASD genetic variants was appreciable. Nevertheless, this study represents the first comprehensive characterization of ASD genetic risk in Qatar's Middle Eastern population.

Hepatitis C Virus (HCV) infection represents a significant global health challenge, with its natural course largely influenced by the host’s immune response. Human Leukocyte Antigen (HLA) molecules, particularly HLA class I and II, play a crucial role in the adaptive immune response against HCV. The polymorphism of HLA molecules contributes to the variability in immune response, affecting the outcomes of HCV infection. This study aims to investigate the frequency of HLA A, B, DR, and DQ alleles known to be associated with HCV clearance or persistence in a healthy Moroccan population. Conducted at the University Hospital Center Mohammed VI, Marrakech, this study spanned from 2015 to 2022 and included 703 healthy Moroccan individuals. HLA class I and II typing was performed using complement-dependent cytotoxicity and polymerase chain reaction-based methodologies. The results revealed the distinct patterns of HLA-A, B, DRB1, and DQB1 alleles in the Moroccan population. Notably, alleles linked to favorable HCV outcomes, such as HLA-DQB1*0301, DQB1*0501, and DRB1*1101, were more prevalent. Conversely, alleles associated with increased HCV susceptibility and persistence, such as HLA-DQB1*02 and DRB1*03, were also prominent. Gender-specific variations in allele frequencies were observed, providing insights into genetic influences on HCV infection outcomes. The findings align with global trends in HLA allele associations with HCV infection outcomes. The study emphasizes the role of host genetics in HCV infection, highlighting the need for further research in the Moroccan community, including HCV-infected individuals. The prevalence of certain HLA alleles, both protective and susceptibility-linked, underscores the potential for a national HLA data bank in Morocco.

Insulin resistance (IR) is type 2 diabetes’ hallmark. MiRNAs regulate many target genes that makes them attractive candidates for regulating insulin production, secretion and action. Therefore, we anticipate a change in the circulatory profile of miRNAs in IR subjects compared to normal glucose tolerance subjects. In the present study, we sought to identify the circulating miRNAs associated with IR as biomarkers in Qatari population. The circulating miRNA profile was assessed in a pilot study of healthy volunteers (n = 22) whose insulin sensitivity was quantitated by euglycemic hyperinsulemic clamp. Moreover, in the validation phase (n = 40) subjects were added including lean and obese T2D. MiR-186 showed a consistent significant increase in insulin resistance subjects compared to NGT in the discovery and validation phase analysis. In addition, intergroup comparison of circulating miRNA pinpointed 2 miRNAs: MiR-122 increased substantially in obese T2D subjects, with diagnostic value to predict obesity in T2D subjects, and let-7b increased significantly in lean T2D subjects. Our results suggest that circulating miRNAs serve as biomarkers for IR, T2D and obesity in Qatari population. Further functional studies are warranted to better identify the targets of these miRNAs and understand the underlying molecular and cellular mechanisms.

Cercospora beticola Sacc. is an ascomycete pathogen that causes Cercospora leaf spot in sugar beets (Beta vulgaris L.) and other related crops. It can lead to significant yield losses if not effectively managed. This study aimed to assess rhizosphere bacteria from sugar beet soil as a biological control agent against C. beticola and evaluate their effect on B. vulgaris. Following a dual-culture screening, 18 bacteria exhibiting over 50% inhibition were selected, with 6 of them demonstrating more than 80% control. The bacteria were identified by sequencing the 16S rRNA gene, revealing 12 potential species belonging to 6 genera, including Bacillus, which was represented by 4 species. Additionally, the biochemical and molecular properties of the bacteria were characterized in depth, as well as plant growth promotion. PCR analysis of the genes responsible for producing antifungal metabolites revealed that 83%, 78%, 89%, and 56% of the selected bacteria possessed bacillomycin-, iturin-, fengycin-, and surfactin-encoding genes, respectively. Infrared spectroscopy analysis confirmed the presence of a lipopeptide structure in the bacterial supernatant filtrate. Subsequently, the bacteria were assessed for their effect on sugar beet plants in controlled conditions. The bacteria exhibited notable capabilities, promoting growth in both roots and shoots, resulting in significant increases in root length and weight and shoot length. A field experiment with four bacterial candidates demonstrated good performance against C. beticola compared to the difenoconazole fungicide. These bacteria played a significant role in disease control, achieving a maximum efficacy of 77.42%, slightly below the 88.51% efficacy attained with difenoconazole. Additional field trials are necessary to verify the protective and growth-promoting effects of these candidates, whether applied individually, combined in consortia, or integrated with chemical inputs in sugar beet crop production.

Abstract Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide. Agonists of the glucagon-like peptide-1 receptor (GLP-1R), currently approved to treat type 2 diabetes, hold promise to improve steatosis and even steatohepatitis. However, due to their pleiotropic effects, the mechanisms underlying their protective effect on NAFLD remain elusive. We aimed to investigate these mechanisms using an in vitro model of steatosis treated with the GLP-1R agonist Exendin-4 (Ex-4). We established steatotic HepG2 cells by incubating the cells with 400 µM oleic acid (OA) overnight. Further treatment with 200 nM Ex-4 for 3 h significantly reduced the OA-induced lipid accumulation (p

Abstract Elevated serum ferritin (SFer) levels are implicated in many energy metabolism abnormalities. The association between SFer levels and metabolic disorders has not been studied in Middle Eastern populations. We aimed at exploring the association between SFer levels and serum lipids, diabetes determinants, and metabolic syndrome in a sample of Qatari adults. This study used biochemical parameters obtained from 1928 participants from the Qatar Biobank cohort. We utilized adjusted multivariable logistic regression analysis to estimate the odds ratios (ORs) for dyslipidemia, type 2 diabetes, the homeostasis model assessment of insulin resistance (HOMA-IR), and metabolic syndrome (MetS) according to sex-specific SFer quartiles (Q1 to Q4). Results revealed that the ORs for dyslipidemia increased progressively and significantly across the SFer quartiles, up to two folds in Q4 for women (OR 2.47 (1.68–3.62)) and men (OR 2.24 (1.41–3.55)) versus Q1 (OR:1). Exclusively in women, the ORs for IR (HOMA-IR > 3.58) increased significantly in Q4 (OR 1.79 (1.19–2.70)) versus OR 1 in Q1 as did the ORs for diabetes (OR: 2.03 (1.15–3.57) in Q4 versus OR 1 in Q1). We observed the same result when we pooled the participants with prediabetes and diabetes in one group. The OR for MetS also increased significantly across the Sfer Quartiles from OR: 1 in Q1 to 1.92 (1.06–3.02) in Q4 for women and to 2.07 (1.08–3.98) in Q4 in men. Our results suggest the elevated Sfer levels as a potential risk biomarker for dyslipidemia and MetS in adult Qatari men and women, and diabetes and IR in women only.

Abstract Background and aims The hallmark of non-alcoholic fatty liver disease (NAFLD) is the excessive hepatic lipid accumulation. Currently, no pharmacotherapy exists for NAFLD. However, the glucagon-like peptide-1 receptor agonists have recently emerged as potential therapeutics. Here, we sought to identify the long non-coding RNAs (LncRNAs) associated with the steatosis improvement induced by the GLP-1R agonist Exendin-4 (Ex-4) in vitro. Methods Steatosis was induced in HepG2 cells with oleic acid. The transcriptomic profiling was performed using total RNA extracted from untreated, steatotic, and Ex-4-treated steatotic cells. We validated a subset of differentially expressed LncRNAs with qRT-PCR and identified the most significantly enriched cellular functions associated with the relevant LncRNAs. Results We confirm that Ex-4 improves steatosis in HepG2 cells. We found 379 and 180 differentially expressed LncRNAs between untreated and steatotic cells and between steatotic and Ex-4-treated steatotic cells, respectively. Interestingly, 22 upregulated LncRNAs in steatotic cells became downregulated with Ex-4 exposure, while 50 downregulated LncRNAs in steatotic cells became upregulated in the presence of Ex-4. Although some LncRNAs, such as MALAT1, H19, and NEAT1, were previously associated with NAFLD, the association of others with steatosis and the positive effect of Ex-4 is being reported for the first time. Functional enrichment analysis identified many critical pathways, including fatty acid and pyruvate metabolism, and insulin, PPAR, Wnt, TGF-β, mTOR, VEGF, NOD-like, and Toll-like receptors signaling pathways. Conclusion Our results suggest that LncRNAs may play essential roles in the mechanisms underlying steatosis improvement in response to GLP-1R agonists and warrant further functional studies.

Abstract Aims/Introduction The progression from prediabetes to type 2 diabetes is preventable by lifestyle intervention and/or pharmacotherapy in a large fraction of individuals with prediabetes. Our objective was to develop a risk score to screen for prediabetes in the Middle East, where diabetes prevalence is one of the highest in the world. Materials and Methods In this cross‐sectional, case–control study, we used data of 4,895 controls and 2,373 prediabetic adults obtained from the Qatar Biobank cohort. Significant risk factors were identified by logistic regression and other machine learning methods. The receiver operating characteristic was used to calculate the area under curve, cut‐off point, sensitivity, specificity, positive and negative predictive values. The prediabetes risk score was developed from data of Qatari citizens, as well as long‐term (≥15 years) residents. Results The significant risk factors for the Prediabetes Risk Score in Qatar were age, sex, body mass index, waist circumference and blood pressure. The risk score ranges from 0 to 45. The area under the curve of the score was 80% (95% confidence interval 78–83%), and the cut‐off point of 16 yielded sensitivity and specificity of 86.2% (95% confidence interval 82.7–89.2%) and 57.9% (95% confidence interval 65.5–71.4%), respectively. Prediabetes Risk Score in Qatar performed equally in Qatari nationals and long‐term residents. Conclusions Prediabetes Risk Score in Qatar is the first prediabetes screening score developed in a Middle Eastern population. It only uses risk factors measured non‐invasively, is simple, cost‐effective, and can be easily understood by the general public and health providers. Prediabetes Risk Score in Qatar is an important tool for early detection of prediabetes, and can help tremendously in curbing the diabetes epidemic in the region.

Abstract Although many factors have been identified and used to enhance the iPSC reprogramming process, its efficiency remains quite low. In addition, reprogramming efficacy has been evidenced to be affected by disease mutations that are present in patient samples. In this study, using RNA-seq platform we have identified and validated the differential gene expression of five transcription factors (TFs) (GBX2, NANOGP8, SP8, PEG3, and ZIC1) that were associated with a remarkable increase in the number of iPSC colonies generated from a patient with Parkinson's disease. We have applied different bioinformatics tools (Gene ontology, protein–protein interaction, and signaling pathways analyses) to investigate the possible roles of these TFs in pluripotency and developmental process. Interestingly, GBX2, NANOGP8, SP8, PEG3, and ZIC1 were found to play a role in maintaining pluripotency, regulating self-renewal stages, and interacting with other factors that are involved in pluripotency regulation including OCT4, SOX2, NANOG, and KLF4. Therefore, the TFs identified in this study could be used as additional transcription factors that enhance reprogramming efficiency to boost iPSC generation technology.

No therapy exists for non-alcoholic fatty liver disease (NAFLD). However, glucagon-like peptide receptor agonists (GLP-1RAs) showed a beneficial effect on NAFLD, although the underpinning mechanisms remain unclear due to their pleiotropic effects. We examined the implicated signaling pathways using comparative transcriptomics in a cell model of steatosis to overcome pleiotropy. We treated steatotic HepG2 cells with the GLP-1RA Exendin-4 (Ex-4). We compared the transcriptome profiles of untreated steatotic, and Ex-4-treated steatotic cells, and used Ingenuity Pathway Analysis (IPA) to identify the signaling pathways and associated genes involved in the protective effect of Ex-4. Ex-4 treatment significantly reduces steatosis. RNA-seq analysis revealed 209 differentially expressed genes (DEGs) between steatotic and untreated cells, with farnesoid X receptor/retinoid X receptor (FXR/RXR) (p = 8.9 × 10−7) activation being the top regulated canonical pathway identified by IPA. Furthermore, 1644 DEGs were identified between steatotic cells and Ex-4-treated cells, with liver X receptor/retinoid X receptor (LXR/RXR) (p = 2.02 × 10−7) and FXR/RXR (p = 3.28 × 10−7) activation being the two top canonical pathways. The top molecular and cellular functions between untreated and steatotic cells were lipid metabolism, molecular transport, and small molecular biochemistry, while organismal injury and abnormalities, endocrine system disorders, and gastrointestinal disease were the top three molecular and cellular functions between Ex-4-treated and steatotic cells. Genes overlapping steatotic cells and Ex-4-treated cells were associated with several lipid metabolism processes. Unique transcriptomic differences exist between steatotic cells and Ex-4-treated steatotic cells, providing an important resource for understanding the mechanisms that underpin the protective effect of GLP-1RAs on NAFLD and for the identification of novel therapeutic targets for NAFLD.