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1.
Diseases ; 12(5)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38785761

RESUMO

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.

2.
Food Funct ; 14(16): 7489-7505, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37498560

RESUMO

Hyperlipidemia is the most well-known cause of metabolic complications and tissue toxicity such as liver steatosis, atherosclerosis and obesity. This study aims to evaluate the preventive effect of loquat fruit peel extract (PE) against tyloxapol-induced hyperlipidemia and related tissue lipotoxicity in mice. The in vivo study was conducted on mice injected daily with tyloxapol at 100 mg per kg B.W. and treated simultaneously with the PE at concentrations of 100 and 200 mg kg-1 or fenofibrate for 28 days. Plasma and tissue lipid biochemical analyses were undertaken using enzymatic methods. The antioxidative stress was revealed by measuring the malondialdehyde content and activities of superoxide dismutase and catalase as well as the scavenging activity against lipoperoxyl radicals. The PE significantly prevented oxidative stress and restored lipid metabolism, plasma glucose, body weight, organ relative mass and biomarkers of hepato-nephrotoxicity as well as the histological structure of the liver and kidneys. It contains five major polyphenols, namely, ferulic acid, caffeic acid, neochlorogenic acid, chlorogenic acid and quercetin. According to molecular docking analysis, these compounds and their circulating metabolites could interact with major proteins implicated in lipid metabolism and oxidative stress. Overall, the study suggests that PE could prevent hyperlipidemia and related toxic tissue complications.


Assuntos
Hiperlipidemias , Polifenóis , Camundongos , Animais , Polifenóis/química , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/prevenção & controle , Hiperlipidemias/metabolismo , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Fígado/metabolismo , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo
3.
Mol Genet Metab Rep ; 36: 100984, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37323222

RESUMO

Background: Wilson Disease (WD) is an autosomal recessive inherited metabolic disease caused by mutations in the ATP7B gene. WD is characterized by heterogeneous clinical presentations expressed by hepatic and neuropsychiatric phenotypes. The disease is difficult to diagnose, and misdiagnosed cases are commonly seen. Methods: In this study, the presented symptoms of WD, the biochemical parameters as well as its natural history are described based on cases collected in Mohammed VI Hospital University of Marrakech (Morocco). We screened and sequenced 21 exons of ATP7B gene from 12 WD patients that confirmed through biochemical diagnosis. Results: Mutational assessment of the ATP7B gene showed six homozygous mutations in 12 individuals however, 2 patients had no evidence of any mutation in promoter and exonic regions. All mutations are pathogenic and most were missense mutations. c.2507G > A (p.G836E), c.3694A > C (p.T1232P) and c.3310 T > C (p.C1104R) that were identified in 4 patients. The other mutations were a non-sense mutation (c.865C > T (p.C1104R)) detected in 2 patients, a splice mutation (c.51 + 4A > T) detected in 2 patients and a frameshift mutation (c.1746 dup (p.E583Rfs*25) detected in 2 patients. Conclusion: Our study is the first molecular analysis in Moroccan patients with Wilson's disease, the ATP7B mutational spectrum in the Moroccan population is diverse and still unexplored.

4.
Biomed Res Int ; 2021: 5553173, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34258267

RESUMO

Real-time genome monitoring of the SARS-CoV-2 pandemic outbreak is of utmost importance for designing diagnostic tools, guiding antiviral treatment and vaccination strategies. In this study, we present an accurate method for temporal and geographical comparison of mutational events based on GISAID database genome sequencing. Among 42523 SARS-CoV-2 genomes analyzed, we found 23202 variants compared to the reference genome. The Ti/Tv (transition/transversion) ratio was used to filter out possible false-positive errors. Transition mutations generally occurred more frequently than transversions. Our clustering analysis revealed remarkable hotspot mutation patterns for SARS-CoV-2. Mutations were clustered based on how their frequencies changed over time according to each geographical location. We observed some clusters showing a clear variation in mutation frequency and continuously evolving in the world. However, many mutations appeared in specific periods without a clear pattern over time. Various important nonsynonymous mutations were observed, mainly in Oceania and Asia. More than half of these mutations were observed only once. Four hotspot mutations were found in all geographical locations at least once: T265I (NSP2), P314L (NSP12), D614G (S), and Q57H (ORF3a). The current analysis of SARS-CoV-2 genomes provides valuable information on the geographical and temporal mutational evolution of SARS-CoV-2.


Assuntos
COVID-19 , Bases de Dados de Ácidos Nucleicos , Evolução Molecular , Genoma Viral , Mutação , Pandemias , Filogenia , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/genética , Humanos
5.
Z Naturforsch C J Biosci ; 62(5-6): 417-26, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17708449

RESUMO

We have compared the effect of toxic Cu and Cd concentrations on growth, metal accumulation, and chloroplast ultrastructure of willow (Salix purpurea L.) and reed [Phragmites australis (Cav.) Trin. ex Steud.]. After a 10-day treatment, both species have tolerated to some extent the lowest concentration of both metals; however, plant growth was strongly reduced at the highest Cu and Cd concentrations. These plants could be described as Cu-tolerant at the lowest concentration tested, showing a higher tolerance index in reed than in willow; in contrast, willow exhibited higher tolerance against Cd. Both plants appeared to be moderate root accumulators of Cu and Cd. Ultrastructural studies revealed special features that can provide some protection against heavy metals stress, such as ferritin aggregates in the stroma. In addition, Cu and Cd induced distortion of thylakoids, reduction of grana stacks, as well as an increased number and size of plastoglobuli and peripheral vesicles.


Assuntos
Cádmio/farmacologia , Cloroplastos/ultraestrutura , Cobre/farmacologia , Poaceae/crescimento & desenvolvimento , Salix/crescimento & desenvolvimento , Transporte Biológico , Cádmio/metabolismo , Cloroplastos/efeitos dos fármacos , Cobre/metabolismo , Tolerância a Medicamentos , Cinética , Lolium/efeitos dos fármacos , Lolium/crescimento & desenvolvimento , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/crescimento & desenvolvimento , Poaceae/efeitos dos fármacos , Salix/efeitos dos fármacos
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