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1.
Int J Immunogenet ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563185

RESUMEN

Chronic inflammation triggered by hepatitis B (HBV) and hepatitis C (HCV) viruses elevates interleukin 6 (IL-6) levels, activating pathways that cause liver damage and contribute to hepatocellular carcinoma (HCC) development. In this study, we assessed IL-6 levels and explored the correlation between the rs1800795 and rs1800797 variants of the IL-6 gene and the risk of developing HCC. We conducted a case-control study involving 314 participants. Among them, 157 were HCC patients (94 anti-HCV, 22 HBsAg and 41 metabolic dysfunction-associated steatotic liver disease [MASLD]) and 157 controls. Genotyping for IL-6 rs1800795 and rs1800797 polymorphisms was performed using real-time polymerase chain reaction (PCR). Additionally, plasma IL-6 levels were determined using enzyme-linked immunosorbent assay. The IL-6 levels were notably higher in patients compared to controls (p < .0001). Among HCC patients, those with MASLD exhibited higher plasma IL-6 levels than those with HCV and HBV (p = .003). In male HCC patients, IL-6 levels were significantly elevated compared to controls (p < .0001). Similarly, female patients showed significantly higher IL-6 levels compared to female controls, though still lower than in male HCC patients (p = .023). However, no significant difference was observed in IL-6 levels between male and female HCC patients (p = .129). Contrastingly, the genotype and allele distributions of the rs1800795 and rs1800797 polymorphisms in the IL-6 gene displayed no association with HCC development (all p > .005). In Moroccan HCC patients, chronic liver inflammation is characterized by elevated levels of IL-6, potentially playing a role in the progression of liver disease and tumourigenesis.

2.
Asian Pac J Cancer Prev ; 24(11): 3689-3696, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-38019226

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignancy. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) plays a crucial role in regulating the biogenesis of mitochondria. We aimed to assess the association between PPARGC1A polymorphisms and HCC risk in a Moroccan population. METHODS: In this case-control study, 147 patients with HCC and 147 controls without pre-existing liver disease were matched for ethnicity. TaqMan SNP allelic discrimination assays were used for genotyping of PPARGC1A rs8192678 and rs12640088 polymorphisms. RESULTS: The result revealed that individuals with the GA/AA genotypes for rs8192678 had a significantly higher risk of HCC compared to those with the GG genotype (OR=6.68; P<0.0001, and OR=9.78; P<0.0001, respectively). In particular, the A allele of rs8192678 was over-represented in HCC patients compared to controls (40% versus 12%, P<0.0001, respectively). With respect to PPARGC1A rs12640088 variant, two genetic models (codominant and dominant) were tested to explore any potential variations in the distribution of SNP A>C among HCC cases and control subjects group. Overall, no significant association between rs12640088 and HCC was found (P>0.05). Interestingly, a significantly higher level of aspartate aminotransferase was observed in HCC patients with GG-GA genotypes (280 IU/L) compared to those with GG genotype (164 IU/L) at rs8192678 (P=0.0019). CONCLUSION: Our results suggest that the PPARGC1A rs8192678 polymorphism is associated with an increased risk of HCC in Moroccan population and may serve as a prognostic marker for liver cancer.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Humanos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/genética , Estudios de Casos y Controles , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética
3.
Infect Dis (Lond) ; 55(9): 614-624, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37376899

RESUMEN

BACKGROUND: Chronic hepatitis B virus (CHB) infection is still incurable a major public health problem. It is yet unclear how host genetic factors influence the development of HBV infection. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) has been shown to regulate hepatitis B virus (HBV). Several reports found that PPARGC1A variants are involved in a number of distinct liver diseases. Here we investigate whether the PPARGC1A rs8192678 (Gly482Ser) variant is involved in the spontaneous clearance of acute HBV infection and if it participates in chronic disease progression in Moroccan patients. METHODS: Our study included 292 chronic hepatitis B (CHB) patients and 181 individuals who spontaneously cleared-HBV infection. We genotyped the rs8192678 SNP using a TaqMan allelic discrimination assay and then explored its association with spontaneous HBV clearance and CHB progression. RESULTS: Our data showed that individuals carrying CT and TT genotypes were more likely to achieve spontaneous clearance (OR = 0.48, 95% CI (0.32-0.73), p = 0.00047; OR = 0.28, 95% CI (0.15-0.53), p = 0.00005, respectively). Subjects carrying the mutant allele T were more likely to achieve spontaneous clearance (OR = 0.51, 95% CI (0.38-0.67), P = 2.68E-06). However, when we investigated the impact of rs8192678 on the progression of liver diseases, we neither observe any influence (p > 0.05) nor found any significant association between ALT, AST, HBV viral loads, and the PPARGC1A rs8192678 genotypes in patients with CHB (p > 0.05). CONCLUSION: Our result suggests that PPARGC1A rs8192678 may modulate acute HBV infection, and could therefore represent a potential predictive marker in the Moroccan population.


Asunto(s)
Virus de la Hepatitis B , Hepatitis B Crónica , Humanos , Genotipo , Virus de la Hepatitis B/genética , Hepatitis B Crónica/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Polimorfismo de Nucleótido Simple , PPAR gamma/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
4.
Nucleosides Nucleotides Nucleic Acids ; 42(12): 986-1003, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37330637

RESUMEN

Hepatocellular carcinoma (HCC) is the fifth most common human malignancy and the fourth most frequent cause of cancer-related deaths worldwide. Toll-like receptors (TLRs), are known to play a key role in hepatocarcinogenesis through induction of inflammation. We aimed to investigate the association between TLR2 rs3804099, TLR4 rs4986790, rs4986791, and rs11536889 and TLR5 rs5744174 and HCC risk in a total of 306 Moroccan subjects, including 152 HCC patient and 154 controls using a TaqMan allelic discrimination assay. Our result showed that the frequency of TLR4 rs11536889 C allele was higher in control group than in HCC patients (OR = 0.52, 95% CI = 0.30-0.88, p = 0.01). Moreover, under the dominant model, we observed that CG/CC genotypes were protective factors against HCC risk (OR = 0.51, 95% CI = 0.28-0.91, p = 0.02). However, no significant differences were found in the allele and genotype frequencies of TLR4 rs4986790 and rs4986791, between HCC patients and controls. Similarly, genotypic frequencies of TLR2 and TLR5 polymorphisms did not differ significantly between HCC patients and controls. However, TLR4 haplotype analysis revealed that ACC haplotype may be protective of HCC risk in patients with HCC (OR = 0.53, 95% CI = 0.31-0.92, p = 0.02). In conclusion, our result suggest that TLR4 rs11536889 polymorphism and ACC haplotype may decrease risk of hepatocellular carcinoma in Moroccan population.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Neoplasias Hepáticas/genética , Polimorfismo de Nucleótido Simple , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/genética , Receptor Toll-Like 5/genética
5.
Clin Immunol ; 252: 109648, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37209806

RESUMEN

Helicobacter pylori infection is involved in development of diverse gastro-pathologies. Our aim is to investigate potential signature of cytokines-chemokine levels (IL-17A, IL-1ß, and CXCL-8) in H. pylori-infected patients and their impact on immune response in both corpus and antrum. Multivariate level analysis with machine learning model were carried out using cytokines/chemokine levels of infected Moroccan patients. In addition, Geo dataset was used to run enrichment analysis following CXCL-8 upregulation. Our analysis showed that combination of cytokines-chemokine levels allowed prediction of positive H. pylori density score with <5% of miss-classification error, with fundus CXCL-8 being the most important variable for this discrimination. Furthermore, CXCL-8 dependent expression profile was mainly associated to IL6/JAK/STAT3 signaling in the antrum, interferons alpha and gamma responses in the corpus and commonly induced transcriptional /proliferative activities. To conclude, CXCL-8 level might be a signature of Moroccan H. pylori-infected patients and an inducer of regional-dependent immune response at the gastric level. Larger trials must be carried out to validate the relevance of these results for diverse populations.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Citocinas/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/patología , Helicobacter pylori/metabolismo , Inmunidad , Estómago/patología
6.
Microorganisms ; 11(2)2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36838318

RESUMEN

Genetic polymorphisms at the IL-1 cluster are associated with increased Helicobacter pylori (H. pylori)-associated disease risk in an ethnically dependent manner. Due to the corroborated role of IL-1ß in H. pylori infection progression, our aim is to depict the impact of IL1B rs1143627 and rs16944 as well as the IL1RN variable number of identical tandem repeats (VNTR) on the clinical and biological features of Moroccan H. pylori-infected patients. A total of 58 patients with epigastralgic pain were referred to the gastroenterology department for histopathological and clinical analysis. DNA extraction from antrum and fundus biopsies and PCR-RFLP were performed to detect polymorphisms. As a result, VNTR was significantly associated with IL-1ß antrum levels (p-value = 0.029), where the *1/*4 genotype showed a positive association with upregulated cytokine levels in the antrum and was clustered with H. pylori-infected patients' features and higher levels of IL-1ß in the antrum and fundus. Likewise, *1/*1 genotype carriers clustered with severe gastritis activity and H. pylori density scores along with low levels of IL-1ß in the antrum and fundus, while the *1/*2 genotype was clustered with non-infected-patient features and normal IL-1ß levels. In conclusion, VNTR might be an interesting predictor to identify patients at risk of developing H. pylori-associated pathologies.

7.
Pan Afr Med J ; 42: 286, 2022.
Artículo en Francés | MEDLINE | ID: mdl-36405668

RESUMEN

Common variable immune deficiency (CVID) is the most common symptomatic immunodeficiency in adults, but it remains rare. It is characterized by its extremely heterogeneous phenotypic spectrum. We here report the case of a 39-year-old patient presenting with chronic diarrhoea with anal fistula. Laboratory tests showed inflammatory syndrome and malabsorption syndrome, hypogammaglobulinemia on serum protein electrophoresis, global hypogammaglobulinemia in weight-based assignments for immunoglobulin and a low level of lymphocytes in the analysis of lymphocyte subpopulations, thus confirming the diagnosis of common variable immune deficiency (CVID) complicated by systemic AA amyloidosis identified by amyloid deposits in the biopsies. This study highlights the importance of paying attention to common gastrointestinal symptoms of immune deficiency and to suspect it in patients with treatment-resistant symptoms.


Asunto(s)
Agammaglobulinemia , Amiloidosis , Inmunodeficiencia Variable Común , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Humanos , Adulto , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/diagnóstico , Agammaglobulinemia/complicaciones , Amiloidosis/diagnóstico , Amiloidosis/etiología
8.
Asian Pac J Cancer Prev ; 23(8): 2755-2761, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-36037131

RESUMEN

OBJECTIVE: Knowledge of local antibiotic resistance is crucial to the adaption of the effective empirical first-line treatment for Helicobacter Pylori (H. pylori) infection. This study aimed to evaluate the prevalence of H. pylori resistance to clarithromycin and compare it with that of metronidazole, and highlight the impact of epidemiological factors and gastric lesions severity on H. pylori resistance. METHODS: The susceptibility to clarithromycin of 96 isolates was determined by PCR-RFLP and the susceptibility to metronidazole of 185 isolates was determined by classic PCR. RESULT: Our results showed that the prevalence of H. pylori resistance to clarithromycin ( 14.6%) was low compared to that recorded with metronidazole ( 62.7%). Moreover, we remarked that 7.3% of isolates were co-resistant to both antibiotics. The assessment of epidemiological factors' impact on the resistance to studied antibiotics has revealed no association. Besides, our results had demonstrated that the metronidazole and clarithromycin resistance was not related to the severity of gastric lesions. CONCLUSION: In our population, clarithromycin seems to be an effective antibiotic as long as the resistance rate of H. pylori is low. In contrast to metronidazole, it appears that this antibiotic will lose its efficacy, due to the high rate of resistance among our population. Therefore, each population must conduct their epidemiologic studies separately to survey the resistance profile of strains and choose the appropriate antibiotic, in order to avoid the failure of H. pylori eradication and the development of severe gastric diseases.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Amoxicilina , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Claritromicina/farmacología , Farmacorresistencia Bacteriana/genética , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Humanos , Metronidazol/farmacología , Pruebas de Sensibilidad Microbiana
9.
Cureus ; 14(4): e23967, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35541289

RESUMEN

Sarcoidosis is a systemic granulomatous disease of unknown etiology, characterized by the presence of non-caseating granulomas. Gastrointestinal involvement in sarcoidosis is extremely rare. However, hepatic sarcoidosis occurs in 70% of cases. This is a case report of multisystemic sarcoidosis revealed by hepatosplenomegaly. The patient presented initially with asthenia, anorexia, and weight loss. An abdominal computed tomography scan revealed hepatosplenomegaly and lumbo-aortic adenopathy. During hospitalization, the patient presented an extended erythematous cutaneous lesion in the peri-auricular area. The diagnosis of sarcoidosis was confirmed by salivary, cutaneous, and bronchoscopic biopsy, which revealed the presence of epithelioid granuloma without necrosis. Consequently, the patient was treated with oral corticosteroids with good improvement.

10.
Pan Afr Med J ; 43: 75, 2022.
Artículo en Francés | MEDLINE | ID: mdl-36590998

RESUMEN

Embolization of gastric varices with cyanoacrylate glue is the treatment of choice for digestive bleeding due to rupture of gastric varices. Gastrointestinal bleeding due to the expulsion of cyanoacrylate glue after gluing of gastric varices is a rare complication. We here report the case of a 65-year-old female patient on cirrhosis and decompensation treatment, undergoing cyanoacrylate glue of gastric varices 3 months before her admission for upper gastrointestinal bleeding; oesogastroduodenal fibroscopy objectified oesophageal varices grade 2 with ulcerated gastric varices and active bleeding due to the expulsion of cyanoacrylate glue. The patient received blood transfusion and sandostatin as well as cyanoacrylate gluing of GOV2 with no complications. Gastrointestinal bleeding after expulsion of cyanoacrylate glue is a serious complication of gluing. Few cases have been described in the literature that required, most often, endoscopic hemostasis.


Asunto(s)
Enbucrilato , Várices Esofágicas y Gástricas , Humanos , Femenino , Anciano , Cianoacrilatos/efectos adversos , Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Endoscopía , Resultado del Tratamiento
11.
J Infect Dev Ctries ; 15(8): 1124-1132, 2021 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-34516420

RESUMEN

INTRODUCTION: Helicobacter pylori infection is the major risk factor of atrophic gastritis and intestinal metaplasia. The vacA gene is one of the most virulence factors of H. pylori and genetic diversity in its s, m, i, and d regions is associated with gastric lesions severity. This study aimed to investigate the association of vacA s, m, i, and d regions with the risk of atrophic gastritis and intestinal metaplasia in a Casablanca population. METHODOLOGY: A total of 210 patients suffering from gastric lesions (chronic gastritis, atrophic gastritis, and intestinal metaplasia) were enrolled. The type of lesion was diagnosed by histological examination. Detection of H. pylori infection and genotyping of vacA regions were carried out by PCR. RESULTS: The prevalence of H. pylori was 95%. The most common vacA genotypes were s2 (51.5%), m2 (77%), i2 (60.5%), and d2 (58.5%). VacA s1, m1, and i1 genotypes were associated with a high risk of intestinal metaplasia, while the vacA d1 genotype increases the risk of atrophic gastritis and intestinal metaplasia. The most common vacA combination was s2/m2/i2/d2 (52%), and it was more detected in chronic gastritis. The moderate virulent vacA combination (s1/m2/i1/d1) increases the risk of atrophic gastritis, while the most virulent vacA combination (s1/m1/i1/d1) increases the risk of intestinal metaplasia. CONCLUSIONS: Genotyping of vacA d region might be a reliable marker for the identification of vacA virulent strains that represent a high risk of developing precancerous lesions (atrophic gastritis and intestinal metaplasia).


Asunto(s)
Proteínas Bacterianas/aislamiento & purificación , Gastritis Atrófica/etiología , Infecciones por Helicobacter/genética , Lesiones Precancerosas/etiología , Adulto , Anciano , Proteínas Bacterianas/metabolismo , Biomarcadores/análisis , Femenino , Genotipo , Infecciones por Helicobacter/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Marruecos , Polimorfismo Genético , Factores de Virulencia/genética
12.
Ann Med Surg (Lond) ; 65: 102323, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33996056

RESUMEN

The Video Capsule Diagnostic Imaging is a technique for exploring the digestive tract, particularly the small bowel. It is indicated for any unexplained digestive bleeding or as a means of monitoring intestinal polyposis or inflammatory diseases. This videocapsule is not digestible, and the risk of its retention, symptomatic or not, is not negligible following an inflammatory, anastomatous or tumoral stenosis. This retention or blockage is defined by the presence of the Video Capsule in the digestive tract at least two weeks after ingestion. Surgical approach is considered effective to retrieve the retained capsule, treat the pathology responsible and prevent acute complications. We report the case of retention of a video capsule in a young patient with severe anaemia due to inflammatory polyposis of the small bowl, whose removal required surgery to extract the capsule and resect the segment of the small intestine stenosis by the polyps.

13.
Microbes Infect ; 23(4-5): 104802, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33607264

RESUMEN

OBJECTIVES: The interferon (IFN) is known to bridge innate and adaptive immune responses, and to play a critical role particularly against hepatitis B virus (HBV) infection. Defects in IFN signals may result, therefore, in attenuated responses against HBV. Accordingly, polymorphisms in genes coding for immune response effectors may affect the clinical outcome of HBV infection. We analyzed the putative association between IFNL4 rs12979860 polymorphism and the outcome of HBV infection in Moroccan patients. METHODS: In this study, 237 chronic HBV (CHB) patients and 129 spontaneously resolved HBV (SRB) individuals were enrolled and genotyped using a predesigned Taqman allelic discrimination assay. RESULTS: Our data show a significant increase of HBV DNA loads in patients with IFNL4 rs12979860 CC genotype compared to patients with CT and TT genotypes (p = 0.0008). However, there was no consistent association between IFNL4 rs12979860 polymorphism and the outcome of HBV infection. CONCLUSIONS: Although IFNL4 rs12979860 polymorphism seems to modulate circulating HBV DNA levels, it is disconnected from chronic disease progression. This observation suggests that the role of rs12979860 in liver disease is restricted to viral control and inactive in the deleterious immune pathology that affects liver tissue. Taken together, our data suggest that rs12979860 CC genotypes could be useful as a predictor of success or failure of IFN-based therapy in chronic HBV-infected patients.


Asunto(s)
ADN Viral/sangre , Hepatitis B/genética , Polimorfismo Genético , Carga Viral/genética , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Hepatitis B/virología , Virus de la Hepatitis B , Hepatitis B Crónica/genética , Hepatitis B Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Marruecos/epidemiología
14.
Pan Afr Med J ; 37: 77, 2020.
Artículo en Francés | MEDLINE | ID: mdl-33244340

RESUMEN

Non-alphabetical hepatitis (Epstein Barr virus -EBV-, cytomegalovirus -CMV-, Herpes simplex virus -HSV-, varicella zoster virus -VZV-etc.) may be a mode of revelation of several underlying chronic liver diseases including autoimmune hepatitis (HAI). We report a peculiar case of acute EBV hepatitis, revealing type I autoimmune hepatitis confirmed by liver biopsy through puncture in a female patient on breast cancer treatment. The study involved a 29-year-old female patient on breast cancer treatment scheduled to receive radiotherapy and chemotherapy, hospitalized for acute severe hepatitis (fever with jaundice, hypertransaminasemia (normal AST level 47 and normal ALT level 23 and prothrombin activity 25%). The test for viral hepatitis A, B, C, and E was negative and subhepatic veins were free on doppler. Non-alphabetical hepatitis was suspected based on fever with jaundice. Patient's assessment showed recent EBV infection diagnosed on the basis of the presence of anti-VAC IgM/G and anti-EBNA Ab IgG. The patient received acyclovir for 10 days. Progression was marked by ascites. The diagnosis of autoimmune hepatitis was retained based on laboratory tests (gamma peak on serum protein electrophoresis and positive anti-nuclear antibodies) and histological examination. Clinical-biological remission was obtained with corticosteroid therapy. EBV infections should be investigated in immunocompromised patients with fever in the clinical course of acute hepatitis. Practitioners should also suspect it in patients with persistent cytolysis following an infectious episode in order to prevent the occurrence of autoimmune hepatitis, in particular in female patients, in a context of self-immunity and negative serological tests for alphabetical viral hepatitis.


Asunto(s)
Infecciones por Virus de Epstein-Barr/diagnóstico , Hepatitis Autoinmune/diagnóstico , Hepatitis Viral Humana/diagnóstico , Enfermedad Aguda , Aciclovir/administración & dosificación , Adulto , Antivirales/administración & dosificación , Ascitis/diagnóstico , Ascitis/etiología , Neoplasias de la Mama/terapia , Progresión de la Enfermedad , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/virología , Femenino , Glucocorticoides/administración & dosificación , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Viral Humana/tratamiento farmacológico , Hepatitis Viral Humana/virología , Humanos , Índice de Severidad de la Enfermedad
15.
Biomed Res Int ; 2020: 2451854, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33029495

RESUMEN

Chronic inflammation due to H. pylori infection is the risk factor of gastric cancer (GC). Through its receptor (TNFR1), TNF-α plays a fundamental role in inflammatory, infectious, and tumor processes. Dysregulation of TNFR1 gene expression could impact many biological processes that can lead to cancer. This study is aimed at evaluating the association of TNFR1 promoter gene polymorphisms (-580 A/G and -609 G/T) and TNFR1 serum levels with GC and precancerous lesion susceptibility. Patients suffering from gastric lesions (65 chronic gastritis, 50 precancerous lesions, and 40 GC) related to H. pylori infection and 63 healthy controls (HC) were involved in this study. Individuals are genotyped by TNFR1 gene promoter sequencing, and TNFR1 serum levels were measured by the ELISA quantitative method. Concerning TNFR1 -609 G/T locus, we noticed that the T allele was associated with an attenuated susceptibility to GC (OR = 0.4; p value = 0.02). At the genotypic level and under the recessive model, the TNFR1 -609 TT genotype showed a decreased risk of GC (OR = 0.3, p value = 0.03) compared to the combined (GG/GT) genotypes. TNFR1 serum levels have been increased together with gastric lesion severity (p value < 0.05). The TNFR1 -609 TT genotype seemed linked to a low level of sTNFR1 compared to GT and GG genotypes (p value = 0.07). Concerning TNFR1 -580 A/G locus, no significant relation was noticed between this polymorphism and GC susceptibility, as well as with the TNFR1 serum level. Our results suggest that the TNFR1 -609 T allele appears to have a protective effect against GC. High levels of TNFR1 serum levels seemed to be associated with the aggressiveness of gastric lesions. Therefore, our results suggest that TNFR1 -609 T/G polymorphism and the TNFR1 serum levels may be related to GC susceptibility.


Asunto(s)
Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Infecciones por Helicobacter/genética , Polimorfismo de Nucleótido Simple/genética , Lesiones Precancerosas/genética , Regiones Promotoras Genéticas , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Neoplasias Gástricas/genética , Adulto , Helicobacter pylori/fisiología , Humanos , Persona de Mediana Edad , Marruecos , Lesiones Precancerosas/sangre , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Índice de Severidad de la Enfermedad , Neoplasias Gástricas/sangre , Neoplasias Gástricas/microbiología
16.
Asian Pac J Cancer Prev ; 21(6): 1623-1629, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-32592356

RESUMEN

OBJECTIVE: Helicobacter pylori (H. pylori) induces the production of tumor necrosis factor-alpha (TNF-α), which is closely related to a gastric epithelial injury. TNF-α gene polymorphism and TNF-α serum levels are associated with various malignant conditions. Identification of the ideal marker for gastric cancer (GC) is still the leading aim of several trials. Physio-pathological considerations of GC led us to investigate the association of two TNF-α promoter polymorphisms (-308G>A and -238G>A), and TNF-α serum levels with the susceptibility to gastric precancerous (PL) and GC. METHODS: Patients suffering from gastric lesions (65 chronic gastritis, 50 PL, 40 GC) related to H. pylori infection , and 63 healthy controls (HC) were involved in this study. Individuals are genotyped by TNF-α gene promoter sequencing and TNF-α serum levels are measured by ELISA quantitative method. RESULTS: Regarding TNF-α-308 G/A locus, we noticed higher risk for GC (OR=4.3, CI 1.5-11.9, p-value=0.005)  and PL (OR=3.4, CI 1.2-9.2, p-value=0.01) for individuals with AA/GA genotypes compared to GG genotype. Concerning TNF-α-238 G/A locus, we noticed higher  risk for GC (OR=5.9, CI 1.2-27.5, p-value=0.01) and PL (OR=4.8, CI 1.3-18, p-value=0.01) for individuals with GG genotype compared to AA/GA genotypes. We noticed that TNF-α serum levels have been increased together with gastric lesions severity. Moreover, TNF-α-308 and TNF-α-238 A alleles seemed to, respectively, upregulate and downregulate TNF-α serum levels. CONCLUSION: The TNF-α -308 A allele has a promotive effect for GC progression, whereas the TNF-α -238 A allele has a protective function against GC progression. High levels of TNF-α seemed to be associated with the aggressiveness of gastric lesions. TNF-α gene polymorphisms and TNF-α serum levels might be helpful to select those patients who are at high risk for GC.


Asunto(s)
Infecciones por Helicobacter/complicaciones , Polimorfismo de Nucleótido Simple , Lesiones Precancerosas/epidemiología , Regiones Promotoras Genéticas , Neoplasias Gástricas/epidemiología , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Adulto , Biomarcadores de Tumor/análisis , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Infecciones por Helicobacter/virología , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Marruecos/epidemiología , Lesiones Precancerosas/sangre , Lesiones Precancerosas/genética , Lesiones Precancerosas/virología , Pronóstico , Neoplasias Gástricas/sangre , Neoplasias Gástricas/genética , Neoplasias Gástricas/virología
17.
Virol Sin ; 35(5): 566-574, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32297157

RESUMEN

Hepatitis C virus (HCV) is still one of the main causes of liver disease worldwide. Metabolic disorders, including non-alcoholic fatty liver disease (NAFLD), induced by HCV have been shown to accelerate the progression of fibrosis to cirrhosis and to increase the risk of hepatocellular carcinoma. An optimal peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) activity is crucial to prevent NAFLD installation. The present study aims to investigate the associations between two common PPARGC1A polymorphisms (rs8192678 and rs12640088) and the outcomes of HCV infection in a North African context. A series of 592 consecutive Moroccan subjects, including 292 patients with chronic hepatitis C (CHC), 100 resolvers and 200 healthy controls were genotyped using a TaqMan allelic discrimination assay. PPARGC1A variations at rs8192678 and rs12640088 were not associated with spontaneous clearance of HCV infection (adjusted ORs = 0.76 and 0.79 respectively, P > 0.05, for both). Furthermore, multivariable logistic regression analysis showed that both SNPs were not associated with fibrosis progression (OR = 0.71; 95% CI 0.20-2.49; P = 0.739; OR = 1.28; 95% CI 0.25-6.54; P = 0.512, respectively). We conclude that, in the genetic context of South Mediterranean patients, rs8192678 and rs12640088 polymorphisms of PPARGC1A are neither associated with spontaneous clearance nor with disease progression in individuals infected with HCV.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis C , Neoplasias Hepáticas , Femenino , Hepacivirus , Hepatitis C Crónica , Humanos , Recién Nacido , Cirrosis Hepática , Masculino , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Receptores Activados del Proliferador del Peroxisoma , Polimorfismo de Nucleótido Simple
18.
Int J Cancer ; 146(5): 1333-1345, 2020 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-31525258

RESUMEN

The current study aimed to investigate the relationship between red and white meat subtypes, processed meat (divided into traditional "Khlii, Kaddid" and industrially processed meat) and colorectal cancer (CRC) risk, considering CRC subsites, in Moroccan adults. A case-control study was conducted including 2,906 matched case-control pairs recruited from the five largest university hospitals in Morocco. Dietary data were collected through a validated Food Frequency Questionnaire (FFQ). Multivariable odds ratios (OR) and 95% confidence intervals (CI), for the association of CRC risk with meat consumption (high vs. low intake), were estimated using conditional logistic regression models, adjusted for relevant confounding variables. Overall, consumption of red meat was positively associated with colon cancer and CRC risk (OR = 1.23, 95% CI = 1.05-1.44; OR = 1.14, 95% CI = 1.02-1.27), respectively. In contrast, no significant association was observed between the consumption of red meat and rectal cancer risk (OR = 1.05, 95% = 0.90-1.23). Interestingly, while processed meat from industrial processes was positively associated with colon cancer, rectal cancer and CRC (OR = 1.61, 95% CI = 1.27-2.04; OR = 1.73, 95% CI = 1.34-2.23; OR = 1.67, 95% CI = 1.41-1.98), processed meat prepared using traditional methods was inversely associated with colon cancer and CRC risk (OR = 0.74, 95% CI = 0.57-0.98; OR = 0.77, 95% CI = 0.64-0.93), respectively. Furthermore, positive associations were observed between poultry intake and colon cancer risk among men (OR = 1.27, 95% CI = 1.01-1.59). Our study showed similar associations between the consumption of red meat and CRC risk in Morocco as in developed countries, while inverse associations were found for traditionally processed meat products. This is the first study to investigate the differential effects of traditional vs. westernized processed meat products in a developing country. Other studies are needed to confirm these findings and to understand the physiological pathways underlying these associations.


Asunto(s)
Neoplasias Colorrectales/epidemiología , Productos de la Carne/estadística & datos numéricos , Carne/estadística & datos numéricos , Animales , Estudios de Casos y Controles , Neoplasias Colorrectales/etiología , Femenino , Humanos , Modelos Logísticos , Masculino , Marruecos/epidemiología , Aves de Corral , Carne Roja/estadística & datos numéricos , Riesgo , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos
19.
Cytokine ; 126: 154893, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31877554

RESUMEN

INTRODUCTION: Helicobacter pylori induces acute gastritis that can progress to serious diseases such as gastric cancer. H. pylori interacts with host cells within the gastric mucosa, resulting in activation of multiple innate immune signalling pathways, leading to pro-inflammatory cytokines production and immune cells recruitment. Various studies have shown that there are ethnic- and population-related differences in the expression of these cytokines. Although the H. pylori infection is a major public health problem in Morocco, to our knowledge, no study has been carried out in gastric cytokine expression from H. pylori-infected Moroccan patients. Thus we aimed to (i) determine the IL-1ß, IL-8 and IL-17A gene expression in gastric biopsies from Moroccan patients infected with H. pylori, and (ii) to determine the cytokine signature of each pathological stages associated with this infection. MATERIAL AND METHODS: 71 patients with epigastralgic pain were included in this study. The H. pylori detection on gastric biopsies was performed by histopathological and PCR analysis. The IL-1ß, IL-8 and IL-17A mRNA expression in the antrun and fundus biopsies was performed by RT-qPCR. RESULTS: The histopathological and PCR analyses revealed that 87.32% of the patients were infected with H. pylori. IL-1ß mRNA expression was significantly lower in the antral mucosa of H. pylori-infected patients (p = 0.0038) than in the uninfected while there was no significant difference in the expression of IL-8 and IL-17A mRNA. The expression of the three cytokines was higher in the fundic mucosa of H. pylori-infected patients than in the uninfected patients, but only IL-8 and IL-17A expression reached statistical significance (p = 0.042 and p = 0.0179 respectively). Furthermore, the multivariate predictive analysis highlighted a cytokine signature that may predict metaplasia during the infection progression that involves a specific down-regulation of IL17A and an up-regulation of IL1ß in antral and fundic metaplasia respectively.


Asunto(s)
Gastritis/patología , Infecciones por Helicobacter/patología , Helicobacter pylori/inmunología , Interleucina-17/análisis , Interleucina-1beta/análisis , Interleucina-8/análisis , Adulto , Femenino , Mucosa Gástrica/inmunología , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/diagnóstico , Gastritis/microbiología , Infecciones por Helicobacter/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Marruecos , Transducción de Señal/inmunología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología
20.
Pan Afr Med J ; 34: 106, 2019.
Artículo en Francés | MEDLINE | ID: mdl-31934248

RESUMEN

Krukenberg tumours are rare, often bilateral ovarian malignant tumours secondary to muco-secreting gastric cancer, in 90% of cases. We collected data from patients' medical records over a period of 17years, between January 2002 and January 2019. These patients had Krukenberg tumors for which they were treated in the Department of Hepato-Gastro-Enterology at the Ibn Rochd Hospital University. The purpose of this retrospective, descriptive study was to update the current understanding of this type of neoplasm characterized by poor prognosis, in order to improve diagnostic performance and therapeutic treatment. The average age of our patients was 42 years, ranging between 25 and 61 years. Ascites was the most common manifestation and was reported in 80% of cases. Radiological assessment highlighted ovarian tumor of variable size and echo structure, unilateral in 60% of cases. Oeso-gastroduodenal fibroscopy showed gastric process in 4 patients. Surgical exploration and immunohistochemical examination of biopsic specimens resulted in the correct diagnosis of cancer of the transverse colon with massive locoregional extension and gastric infiltration in one case. The fifth patient underwent exploratory laparotomy which revealed metastatic colonic neoplasia. Radical surgery could be performed only in two patients, in the other two cases only biopsies were performed due to the late stage of the disease. One patient had profoundly altered general state and was at high-risk for anaesthetic, then surgical procedure could not be performed. Only two patients received postoperative chemotherapy. Fatal outcome was reported in 100% of cases. This study reconfirms the catastrophic prognosis of Krukenberg tumor based on its insidious evolution often leading to late diagnosis and to a clear misunderstanding of its etiopathogenesis. We conclude that the improvement of survival chances is based on systematic assessment of ovaries in patients with digestive neoplasia. Some authors also affirm that prophylactic ovariectomy should be performed in women older than 40 years who have undergone gastrointestinal cancer surgery.


Asunto(s)
Neoplasias Gastrointestinales/diagnóstico , Tumor de Krukenberg/diagnóstico , Neoplasias Ováricas/diagnóstico , Adulto , Resultado Fatal , Femenino , Neoplasias Gastrointestinales/patología , Humanos , Tumor de Krukenberg/patología , Tumor de Krukenberg/secundario , Laparotomía , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias Ováricas/secundario , Pronóstico , Estudios Retrospectivos
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