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This study evaluated the presence of the three pesticides methomyl (MET), carbendazim (CBZ) and chlorpyrifos-ethyl (CPE), as well as the degradation product of CPE (3,5,6-trichloro-2-pyridinol; TCP), in 44 honey samples from all 12 regions of Morocco. With a validated HPLC-UV method occurrence frequencies of 63.6% for MET, 54.5% for CBZ, 95.1% for CPE and 34.1% for TCP were obtained, even at concentrations higher than the maximum residue limits for MET, CPE and TCP. Based on the predominant pesticide, principal component analysis separated sampling regions into three groups. Risk assessment indicated that ingestion of these pesticides, alone or in combination, in honey did not pose a risk to consumers (HQ and HI < 1).
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Contaminación de Alimentos , Miel , Residuos de Plaguicidas , Miel/análisis , Marruecos , Residuos de Plaguicidas/análisis , Contaminación de Alimentos/análisis , Humanos , Medición de Riesgo , Cromatografía Líquida de Alta Presión , Análisis de Componente Principal , Carbamatos/análisis , Cloropirifos/análisis , BencimidazolesRESUMEN
Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide, accounting for 24.5% of total new cancer cases and 15.5% of total cancer deaths. Similarly, BC is the most common cancer among Moroccan women, comprising a noteworthy percentage of 40% of all cancers in women. Globally, 15% of cancers are attributable to infections; among them, viruses play a significant role. The present study aimed to explore the presence of a wide range of viral DNA in samples recovered from 76 Moroccan patients with BC and 12 controls using Luminex technology. The explored viruses were as follows: 10 polyomaviruses (PyVs): BKV, KIV, JCV, MCV, WUV, TSV, HPyV6, HPyV7, HPyV9, and SV40; and 5 Herpesviruses (HHVs): CMV, EBV1, EBV2, HSV1, and HSV2. Our results revealed the presence of PyVs DNA in both control (16.7%) and BC tissues (18.4%). Nonetheless, HHV DNA was detected exclusively in BC tissues (23.7%), with a predominance of Epstein-Barr virus (EBV) (21%). In conclusion, our study highlights the presence of EBV in human BC tissues, which may play an important role in its development and/or progression. Further investigations are needed to confirm the presence/co-presence of these viruses in BC.
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PROPOSAL: A distinct epidemiology, etiology, clinical characteristics, and therapeutic outcomes characterize nasopharyngeal carcinoma (NPC) from other head and neck cancers. An actualized analysis of NPC patients' features enables a global view of NPC management. Accordingly, the current study investigated the epidemiological and clinical characteristics of Moroccan patients with NPC, as well as their 4-years survival outcomes and influencing prognostic factors. METHODS: We prospectively analyzed data of 142 histologically confirmed Moroccan patients with NPC between October 2016 and February 2019. Kaplan-Meier and Cox regression analyses were used to assess predictive prognostic factors related to NPC. All analyses were conducted using SPSS version 21 statistical software. RESULTS: In the present study, a net male predominance was found, with a mean age of 44±16.3 years old. Advanced stages of NPC were observed in 64.1% of patients, and 32.4% of patients presented with distant metastasis at diagnosis. The 4-years overall survival, locoregional relapse-free survival, distant metastasis-free survival and progression-free survival were 68.0%, 63.0%, 53.9%, and 39.9%, respectively. Age, N category and distant metastasis were identified as the most important independent prognosis factors for NPC in this cohort (p<0.05). CONCLUSION: In conclusion, NPC affects young adults and is frequently diagnosed at advanced disease stages, impacting therefore negatively patients survival; which is in line with data from endemic areas for NPC. The current study clearly highlights that a greater attention should be directed to improving the management of this aggressive malignancy.
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Neoplasias Nasofaríngeas , Adulto Joven , Humanos , Masculino , Adulto , Persona de Mediana Edad , Femenino , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/epidemiología , Recurrencia Local de Neoplasia , PronósticoRESUMEN
Vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2) are the most important tissue factors involved in tumor growth and angiogenesis. The aim of this study was to evaluate the promoter mutational status of VEGFA and the expression levels of VEGFA, VEGFR1, and VEGFR2 in bladder cancer (BC) tissues and to correlate the results with the clinical-pathological parameters of BC patients. A total of 70 BC patients were recruited at the Urology Department of the Mohammed V Military Training Hospital in Rabat, Morocco. Sanger sequencing was performed to investigate the mutational status of VEGFA, and RT-QPCR was used to evaluate the expression levels of VEGFA, VEGFR1, and VEGFR2. Sequencing of the VEGFA gene promoter revealed the presence of -460T/C, -2578C/A, and -2549I/D polymorphisms, and statistical analyses showed a significant correlation between -460T/C SNP and smoking (p = 0.02). VEGFA and VEGFR2 expressions were significantly up-regulated in patients with NMIBC (p = 0.003) and MIBC (p = 0.03), respectively. Kaplan-Meier analyses showed that patients with high VEGFA expression had significantly longer disease-free survival (p = 0.014) and overall survival (p = 0.009). This study was very informative, showing the implication of VEGF alterations in BC, suggesting that VEGFA and VEGFR2 expressions could be promising biomarkers for the better management of BC.
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BACKGROUND: Direct anthropometric measurements to assess body composition have limited precision and/or specificity. OBJECTIVES: The study aimed to develop a prediction equation based on anthropometric measurements for estimating total body water (TBW) in a healthy population. METHODS: TBW was assessed using the deuterium dilution method in 398 Moroccan participants (235 women and 163 men) aged 11.6-88 y, then compared to the estimations made by previously published anthropometric equations. By sex, participants were randomly assigned into development (n = 199) and validation subgroups (n = 199). A new anthropometric equation was developed in the development subgroup from data obtained on body volume (BV), weight, and sex, where the BV was calculated from participants' height. Then the equation was validated in the validation subgroup using the Bland and Altman procedure, bias, and pure error. External validation was performed using a sample from Tunisia (n = 220, 51.8% female, 18-65 y). RESULTS: Bias in predicting TBW showed unacceptable value for all previously published equations as it was significantly overestimated. The following new equation using anthropometric measurements [TBW (kg) = -5.249 + 107.502 BV (L) + 0.289 weight (kg) + 2.015 sex (male: 1, female: 0); (R2 = 0.91, RMSE = 1.885 kg)] was developed, and its internal validation was confirmed. The generated bias and pure error values were 0.047 kg (95% CI: -0.235, 0.330) and 2.02 kg (95% CI: 1.73, 2.31), respectively. The external validation of the new TBW prediction equation on a Tunisian sample showed a bias and pure error values of 0.07 kg (95% CI: -0.289, 0.429) and 2.36 kg, respectively. CONCLUSIONS: The results indicate that the new anthropometric-based prediction equation provides a good estimation of TBW and other body composition compartments. It could be recommended as an alternative method to assess body composition for epidemiological and clinical studies.
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Composición Corporal , Agua Corporal , Humanos , Masculino , Femenino , Impedancia Eléctrica , Antropometría/métodos , Técnicas de Dilución del IndicadorRESUMEN
BACKGROUND: Assessment of protein quality is necessary to satisfy the nutritional needs of populations across the world. In addition to indispensable amino acid (IAAs) composition, protein digestibility is a major component of IAA bioavailability, playing a crucial role in human health and affecting the linear growth of children. OBJECTIVES: This study aimed to evaluate IAA digestibility of fava beans, a legume widely consumed in Morocco using the dual-tracer method. METHODS: 2H-intrinsically labeled Fava beans supplemented with 12 mg/kg BW of 13C spirulina were given to 5 healthy volunteers (3 men and 2 women), aged 25.8 ± 3.3 y, with a mean BMI of 20.0 kg/m2. The meal was spread in small portions and was given hourly throughout 7 h. Blood was sampled at baseline and hourly from 5 to 8 h after meal ingestion. IAA digestibility was evaluated by gas chromatography-combustion-isotope ratio mass spectrometry using the 2H/13C ratio in plasma IAA. Digestible indispensable amino acid ratios (DIAAR) were calculated using the scoring pattern for people older than 3 y. RESULTS: Fava beans had an adequate level of lysine but were limiting in several IAAs, especially methionine. Under our experimental conditions, the average IAA digestibility of fava bean was 61.1% ± 5.2%. Valine had the highest digestibility (68.9% ± 4.3%) and threonine had the lowest (43.7% ± 8.2%). In consequence, the lowest DIAAR was 67% for threonine and only 47% for sulfur amino acids (SAA). CONCLUSIONS: The present study is the first to determine the digestibility of fava bean amino acids in humans. The mean IAA digestibility was moderate, and consequently, we conclude that fava bean provides a limited amount of several IAAs, especially SAA, but adequately for lysine. Preparation and cooking methods of fava beans should be improved to increase digestibility. This study was registered at ClinicalTrials.gov as NCT04866927.
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Fabaceae , Vicia faba , Adulto , Femenino , Humanos , Masculino , Aminoácidos/metabolismo , Digestión , Fabaceae/química , Isótopos , Lisina , Treonina , Vicia faba/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: Nasopharyngeal carcinoma (NPC) is a severe malignant disease. Despite its low frequency, NPC is very common in North African population. Radiotherapy is the standard therapeutic treatment of NPC. However, radioresistance hampers the success of treatment. At the molecular scale, radioresistance is due to genetic variations involved in DNA repair pathways in NPC patients. Several studies reported that single nucleotide polymorphisms (SNPs) in excision repair cross complementing group 1 (ERCC1) could be associated with radioresistance. In this optic, the present study aimed to evaluate the association between DNA repair gene polymorphisms ERCC1 C8092A and ERCC1 C118T and radiotherapy response of patients with NPC. METHODS: A total of 95 patients with confirmed NPC were recruited at the Mohammed VI Center for Cancer Treatment, Casablanca - Morocco between 2016 and 2018. Two single nucleotide polymorphisms in ERCC1 gene were genotyped. Multiple analysis software was used to assess the correlation between these SNPs and radio-therapeutic response. RESULTS: Sequencing of ERCC1 C8092A polymorphism revealed that CC and CA genotypes were found in 51.6% and 45.3% of cases, respectively, whereas the homozygote AA genotype was reported in only 3.1% of cases. For ERCC1 C118T polymorphism, the heterozygote CT genotype was identified in 49.5% of cases. Homozygotes genotypes CC and TT were detected in 17.9% and 32.6% respectively of NPC cases. Of note, no significant association was found between the ERCC1 C8092A polymorphism and response to radiation therapy (p=0.81). Similarly, there was no significant association between the response to radiotherapy and allelic distribution (p=0.56). Likewise, no correlation was observed neither with genotypes (p=0.07) nor with alleles (p=0.09) of ERCC1 C118T polymorphism and response to radiation therapy. CONCLUSION: Our results clearly showed that ERCC1 C8092A and ERCC1 C118T polymorphisms were not associated with response to radiotherapy in Moroccan NPC patients. Large studies are warranted to confirm the role of these SNPs in therapeutic response of NPC patients.
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Proteínas de Unión al ADN , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/radioterapia , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Polimorfismo de Nucleótido Simple/genética , Genotipo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Endonucleasas/genéticaRESUMEN
In this work, three isoxazoline-thiazolidine-2,4-dione derivatives were synthesized and characterized by FT-IR, 1H-NMR, 13C-NMR and ESI-MS spectrometry. All compounds have been investigated for their α-amylase and α-glucosidase inhibitory activities. In vitro enzymatic evaluation revealed that all compounds were inhibitory potent against α-glucosidase with IC50 values varied from 40.67 ± 1.81 to 92.54 ± 0.43 µM, and α-amylase with IC50 in the range of 07.01 ± 0.02 to 75.10 ± 1.06 µM. One of the tested compounds were found to be more potent inhibitor compared to other compounds and standard drug Acarbose (IC50 glucosidase= 97.12 ± 0.35 µM and IC50 amylase= 2.97 ± 0.01 µM). All compounds were then evaluated for their acute toxicity in vivo and shown their safety at a high dose with LD > 2000mg/kg BW. A cell-based toxicity evaluation was performed to determine the safety of compounds on liver cells, using the MTT assay against HepG2 cells, and the results shown that all compounds have non-toxic impact against cell viability and proliferation compared to reference drug (Pioglitazone). Furthermore, the molecular homology analysis, SAR and the molecular binding properties of compound with the active site of α-amylase and α-glucosidase were confirmed through computational analysis. This study has identified the inhibitory potential of a new class of synthesized isoxazoline-thiazolidine-2,4-dione derivatives in controlling both hyperglycemia and type 2 diabetes mellitus without any hepatic toxicity.Communicated by Ramaswamy H. Sarma.
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Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Humanos , Simulación del Acoplamiento Molecular , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , alfa-Glucosidasas/química , Espectroscopía Infrarroja por Transformada de Fourier , alfa-Amilasas/metabolismo , Estructura Molecular , Relación Estructura-ActividadRESUMEN
The main purpose of this study was to investigate the protective effect of Rosmarinus officinalis, Origanum compactum, Lavandula angustifolia, and Eucalyptus globulus essential oils (EOs) against gamma-radiation-induced damages on Tetrahymena pyriformis growing in presence of cobalt-60 source. The chemical composition of the 4 EOs was analyzed by gas chromatography-mass spectrometry. The protective effects of EOs on growth, on morphology, and on some metabolic enzymes and antioxidant markers have been evaluated. Thus, addition of EOs significantly improves the growth parameters (generation number and time) in irradiating conditions. All EOs allowed restoring growth parameters over more than 90% compared to the controls. The morphological analysis indicated that T. pyriformis cells growing in irradiating conditions were able to regain their normal form in presence of the different EOs. Our results indicate that the 4 EOs also have protective effects on some metabolic enzymes. They allowed recovering totally or partially the glyceraldehyde 3-phosphate dehydrogenase and the succinate dehydrogenase activities compared to the controls. Moreover, the addition of EOs reduced the lipid peroxidation level and decreased the activities of catalase and superoxide dismutase induced by the gamma-radiation exposure. A more pronounced protective effect was found for O. compactum and L. angustifolia EOs compared to R. officinalis and E. globulus EOs. These results suggest that the studied EOs are efficient natural antioxidants that could offer protection against gamma-radiation-induced damages and can therefore be useful in clinical medicine.
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Aceites Volátiles , Rosmarinus , Tetrahymena pyriformis , Antioxidantes/química , Antioxidantes/farmacología , Radioisótopos de Cobalto , Aceites Volátiles/química , Aceites Volátiles/farmacología , Rosmarinus/químicaRESUMEN
OBJECTIVE: The present study aimed to assess the prognostic interest of metabolic and anatomic parameters derived from 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) and head and neck magnetic resonance imaging (HN-MRI) for better management of nasopharyngeal carcinoma (NPC). METHODS: In this study, pre-treatment [18F]FDG PET/CT and HN-MRI parameters of NPC patients diagnosed between January 2017 and December 2018, were prospectively investigated. Correlation between those parameters and 4-year patient's survival outcomes was evaluated using Kaplan-Meier and Cox-regression analyses. RESULTS: Our results revealed a significant association between pre-treatment nodal-maximum standardized uptake value (N-SUV max) and N categories (p = 0.01), between pre-treatment node-to-tumor SUV ratio (NTR) and both tumor size (p = 0.01) and N categories (p = 0.009), as well as between metabolic tumor volume (MTV) and both tumor size and NPC overall stage (p < 0.000). In multivariate analyses, pre-treatment N-SUV max, NTR and MTV were significant independent predictors of overall survival, distant metastasis-free survival, and progression-free survival (PFS) (p < 0.05). N-SUV max and MTV were also found to be significant independent predictors of loco-regional recurrence-free survival (p < 0.05), whereas HN-MRI detection of skull-base bone invasion was an independent factor associated with worse PFS in NPC (p = 0.03). CONCLUSIONS: The present study highlights N-SUV max, NTR and MTV derived from [18F]FDG PET/CT, and skull-base bone invasion defined by HN-MRI, as promising metabolic and anatomic prognosis biomarkers for NPC.
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Fluorodesoxiglucosa F18 , Neoplasias Nasofaríngeas , Biomarcadores , Fluorodesoxiglucosa F18/metabolismo , Glucosa , Humanos , Imagen por Resonancia Magnética , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/terapia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Pronóstico , Radiofármacos , Estudios RetrospectivosRESUMEN
BACKGROUND: Iodine deficiency disorders (IDD) affects nearly 1.9 million people worldwide. Iodine deficiency (ID) remains a public health concern not only for pregnant women, but for women of reproductive age (WRA) as well. This study was planned to evaluate the iodine status and the prevalence of iodine deficiency in a nationally representative sample of Moroccan WRA according to their socio-economic data and living areas. METHODS: This study is a cross-sectional national survey conducted on 1652 WRA aged between 18 and 49 years. Iodine status was assessed by the evaluation of the urinary iodine concentration (UIC) on spot urinary samples, using the Sandell-Kolthoff reaction, and by the estimation of iodine-rich food consumption, using a food frequency questionnaire. The World Health Organization cutoff of a median UIC of < 100 µg/l was used to define ID in the population. RESULTS: The median UIC [20th- 80th] was 71.3 µg/l [37.5-123.1] and 71% of participants had UIC < 100 µg/L, indicating insufficient iodine status and mild iodine deficiency. WRA from urban and rural areas showed an UIC median of 75.94 µg/l [41.16-129.97] and 63.40 µg/l [33.81-111.68], respectively. Furthermore, ID prevalence was significantly higher in rural areas (75.6%) as compared to urban areas (67.9%) (p < 0.05). Food frequency questionnaires analyses highlighted that dairy products are the most commonly consumed iodine-rich food, reported to be consumed daily by 43.1% of WRA. Of particular interest, 83.5% of WRA reported a weekly consumption of fish. CONCLUSION: ID is still a public health problem in Morocco highlighting the necessity to implement effective national program, including efficient salt iodization, effective nutritional education and awareness, to control iodine deficiency and prevent IDD development.
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Introduction: in cancer cells, activating mutations in PIK3CA and AKT1 genes, major players of PI3K-AKT-mTOR signalling pathway, are widely reported in many cancers and present attractive targets for the identification of new therapeutics and better cancer management. The present study was planned to evaluate the mutational status of PIK3CA and AKT1 genes in bladder cancer patients and to assess the association between these mutations and patients´ clinico-pathological features. Methods: in this prospective study, bladder cancer biopsies and matched urine sediments samples were collected form 70 patients. Mutations were assessed by deoxyribonucleic acid (DNA) sequencing and correlation with clinico-pathological data was performed using SPSS software. Results: AKT1 alterations were poorly detected. Only one patient with pT1 stage and high-grade tumour carried the E17K mutation. In PIK3CA exon 9, 2 point mutations, E545K and Q546E, and a SNP (E547E) were reported, whereas in exon 20, 2 point mutations (L989V and H1047R) and 2 SNPs (I1022I and T1025T) were detected. PIK3CA mutations were mainly observed in early stages and high-grade tumours. Statistical analysis showed no significant association between the studied AKT1 and PIK3CA mutations and patients´ clinico-pathological parameters (p > 0.05). Detection of these mutations in voided urine samples showed a high specificity (100%) for both genes and a moderate sensitivity: 100% for AKT1 and 66.7% for PIK3CA genes. Conclusion: this study shows clearly that mutations in AKT1 and PIK3CA are rare events and could not be considered as valuable biomarkers for bladder cancer management.
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Fosfatidilinositol 3-Quinasa Clase I , Proteínas Proto-Oncogénicas c-akt , Neoplasias de la Vejiga Urinaria , Biopsia , Fosfatidilinositol 3-Quinasa Clase I/genética , Humanos , Mutación , Estudios Prospectivos , Proteínas Proto-Oncogénicas c-akt/genética , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
The present meta-analysis was conducted to evaluate the prognostic value of pre and post-Epstein Barr Virus (EBV) DNA load testing and to assess the clinical benefit of using this molecular approach in the prognosis for a better nasopharyngeal carcinoma (NPC) management. Relevant studies were searched in different database until May 2020. Patient´s outcomes overall survival (OS), disease free survival (DFS), progression-free survival (PFS), distant-metastasis-free survival (DMFS), and local-regional-failure-free survival (LRFS), hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted from selected studies. The association of pre and post-EBV DNA load and survival outcomes was assessed using review manager and the pooled HRs with 95% CIs were calculated. Twenty-six eligible studies were included in this meta-analysis, with a total of 9966 patients. Pooled HRs showed that EBV DNA levels before and after treatment are significantly associated with survival outcomes, with HR (95% CI) of 2.09 [1.74, 2.51] for OS, 1.77 [1.19, 2.62] for DFS, 2.53 [2.18, 2.92] for DMFS, 1.78 [1.45, 2.19] for LRFS and 2.17 [1.91, 2.47] for PFS in pre-EBV DNA, and an HR (95%) of 4.52 [2.44, 8.36], 4.08 [2.38, 6.99], 5.59 [ 3.58, 8.71] and 8.88 [5.29, 14.90] for OS, DFS and PFS and DMFS in post-EBV DNA, respectively. High pre and post-EBV DNA levels were significantly associated with poor NPC patient´s survival outcomes; which clearly confirm the high interest to introduce viral EBV DNA load as a prognostic biomarker for NPC management.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , ADN Viral , Supervivencia sin Enfermedad , Herpesvirus Humano 4/genética , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/terapia , PronósticoRESUMEN
This study investigated the effects of gamma-radiation on Tetrahymena pyriformis. The experimental approach consists of exposing T. pyriformis growing in presence of Cesium-137 (137Cs) at dose rates of 1, 2, 4, and 6 cGy h-1 and Cobalt-60 (60Co) at dose rates of 8, 10, 15, and 20 cGy h-1. The radiation doses effects on growth, morphology, some metabolic enzymes, and reactive oxygen species (ROS) markers have been evaluated. When cells were growing in irradiating conditions at dose rates beyond 4 cGy h-1, a decreasing of cells and generation numbers with a prolongation of generation time and a change of morphological aspect with rounding-off of cells were observed compared to the control. The 50%-inhibitory dose (ID50) for radiation was estimated at 1568.72 ± 158.45 cGy. The gamma-radiation at dose rates more than 6 cGy h-1, affected both glyceraldehyde 3-phosphate dehydrogenase and succinate dehydrogenase by inhibiting their activities. All of these effects were more pronounced when cells were irradiated at the dose rate of 20 cGy h-1 using 60Co source. For ROS markers generated by gamma-radiation in T. pyriformis, the results showed an increase of the lipid peroxidation in cells grown in presence of gamma-radiation at dose rates more than 6 cGy h-1 and an enhancement in catalase and superoxide dismutase activities from the dose rate of 1 cGy h-1. These encouraging results suggested the use of T. pyriformis as a unicellular model cell to investigate other aspects of the response to ionizing radiation.
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Tetrahymena pyriformis , Radioisótopos de Cesio , Radioisótopos de Cobalto , Relación Dosis-Respuesta en la Radiación , Rayos gammaRESUMEN
PURPOSE: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme of the glycolytic pathway, can play a physiological regulatory role and vital other roles in metabolism. This study investigated the effects of gamma radiation generated by Cobalt-60 source on GAPDH activity and protein levels in Pichia pastoris as an eukaryotic organism model. MATERIALS AND METHODS: After purification of the GAPDH from P. pastoris, in vitro effects of irradiation to the dose of 2 Gy, using Cobalt-60 at the dose rate of 0.25 Gy/min, on activity and kinetic parameters were investigated. In vivo effects of gamma exposition (dose of 5 Gy) on P. pastoris GAPDH and on reactive oxygen species (ROS) markers were also explored. RESULTS AND CONCLUSIONS: The in vitro irradiation of the purified GAPDH reduces the specific activity and the maximum velocity (Vmax) without alteration of substrates binding (Km). No changes occurred in the specific activity and in kinetic parameters when P. pastoris cells were exposed to Cobalt-60 source. However, this in vivo irradiation of cells produced a significant increase of the GAPDH protein level. The changes of GAPDH activity and the increase of the enzyme population as a target for gamma radiation exposure will play a role in cells adaptation under stress conditions. On the other hand, the increase of malondialdehyde and carbonyl contents and the enhancement of catalase and superoxide dismutase in irradiated cells have been noticed. The antioxidant system can play an important role in the protection of P. pastoris GAPDH against the gamma induced-ROS damage. This is the first report of the P. pastoris GAPDH as a physiological target of gamma exposition.
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Gliceraldehído-3-Fosfato Deshidrogenasas , Radioisótopos de Cobalto , Rayos gamma , Gliceraldehído-3-Fosfato Deshidrogenasas/metabolismo , Especies Reactivas de Oxígeno , SaccharomycetalesRESUMEN
Promoter hypermethylation have been reported to play a key role in bladder cancer development and progression. The aim of this study is to evaluate the methylation status of hTERT, TWIST1, VIM and NID2 genes in bladder cancer. The methylation status was evaluated using the Methylation-Specific PCR (MSP) approach on 70 tumour biopsies from Moroccan bladder cancer patients. Overall, methylation frequencies of hTERT, TWIST1, VIM and NID2 genes, were 90%, 85.71%, 67.14% and 67.14%, respectively. Hypermethylation of all studied genes was found in all pathological grades and stages of bladder cancer. Nevertheless, statistical analysis showed no significant association between promoter methylation of hTERT, TWIST1, VIM and NID2 genes and tumours stage/grade (p value >0.05). Moreover, we have investigated the association between the methylation pattern of selected genes and the treatment outcome in a sub-group of non-muscle-invasive bladder cancer cases (52/70). Hypermethylation of hTERT, TWIST1, VIM and NID2 was detected in 83.34%; 66.67%; 83.34% and 58.34% of recurrent cases, respectively, and in 80%; 80%; 80% and 60% of progressive cases, respectively. Statistical analysis highlighted a significant association between TWIST1 hypermethylation and tumour recurrence (p = 0.041<0.05). Our results indicate that hypermethylation of hTERT, TWIST1, VIM and NID2 genes is a frequent epigenetic event in bladder cancer and could be a promising therapeutic target to prevent bladder cancer progression and metastasis.
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Proteínas de Unión al Calcio/genética , Moléculas de Adhesión Celular/genética , Metilación de ADN , Proteínas Nucleares/genética , Telomerasa/genética , Proteína 1 Relacionada con Twist/genética , Neoplasias de la Vejiga Urinaria/patología , Vimentina/genética , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Marruecos , Clasificación del Tumor , Estadificación de Neoplasias , Regiones Promotoras Genéticas , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
The current study was designed to investigate the changes in the circulating Epstein−Barr virus DNA load (EBV DNA) at various time points before and after treatment and its clinical significance in nasopharyngeal carcinoma (NPC). A total of 142 patients with NPC were prospectively enrolled in this study. The plasma EBV DNA concentration was measured before and after treatment using qPCR. The prognostic values of the EBV DNA load were analyzed using the Kaplan−Meier and Cox regression tests. Following multivariate analysis, our data showed that high pre-EBV DNA loads were associated with significantly poorer distant metastasis free survival (DMFS) and progression free survival (PFS); detectable end-EBV DNA loads were associated with significantly worse loco-regional recurrence free survival (LRRFS) and PFS, and the detecTable 6 months-post-EBV DNA loads were associated with significantly poorer overall survival (OS), DMFS and PFS (p < 0.05). Additionally, combining the pre-EBV DNA load and the stage of the disease, our results showed that patients at stage III-IVA with a low pre-EBV DNA load had similar survival rates as patients at stage II with a low or high pre-EBV DNA load, but had better survival rates than those at stage III-IVA with a high pre-EBV DNA load. Taken together, we showed that the change of the EBV DNA load measured at several time points was more valuable than at any single time point for predicting patients' survival for NPC. Furthermore, combining the pre-EBV DNA load and the TNM classification could help to formulate an improved prognostic model for this cancer.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Herpesvirus Humano 4/genética , Estudios de Seguimiento , Neoplasias Nasofaríngeas/diagnóstico , ADN Viral/genética , PronósticoRESUMEN
The major roles of vitamin D in the genesis of breast cancer and as an immunomodulator against acute and chronic infections have been the subject of much research in recent years. A low vitamin D status could decrease the function of blocking the cell multiplication cycle of the cancer process and weaken the immune system. In this context, we were interested in the implication of vitamin D status in women with human papilloma virus (HPV)-induced breast cancer. Our study included 63 women, 53 with breast cancer and 10 healthy women, and we measured the plasma 25(OH)D3 level and looked for the presence of HPV by PCR in our population. 90.6% had low serum 25(OH)D3 levels and HPV was found in 41% of cases. In this regard, the data in the literature are discordant. Vitamin D status could explain the concomitance of the two conditions, breast cancer and HPV; it would be desirable to broaden the sample in order to better define its impact.
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Neoplasias de la Mama , Infecciones por Papillomavirus , Deficiencia de Vitamina D , Humanos , Femenino , Vitamina D , Virus del Papiloma Humano , Infecciones por Papillomavirus/complicaciones , VitaminasRESUMEN
Vitamin D deficiency is a hot topic as it affects about 50% of the world's population. Beyond its extra-osseous effects, notably on the cardiovascular system. In recent years many epidemiological studies have looked at the role of vitamin D status in modulating blood pressure. It appears that there is an inverse association between serum vitamin D levels and blood pressure. It is in this context that our prospective study on the Moroccan population allows having global knowledge of the association between vitamin D and arterial hypertension. This is a descriptive study of vitamin D status in Moroccan hypertensive patients in whom blood samples were taken for serum 25(OH)D determination. The data collected were anonymised and entered into SPSS software. X2 and ANOVA tests were used to investigate the existence of correlations between vitamin D status and age, age at menopause, body mass index, sex and hypertension. 1015 hypertensive patients were included in this study with a female predominance of 84.2%, mainly over 50 years old in 80.8%, of whom 31.5% were overweight or obese, 13.2% had a hypertensive parent and 70.8% had vitamin D deficiency. Vitamin D regulates at least 3% of the human genome with receptors throughout the body, including vascular smooth muscle cells, vascular endothelium and cardiomyocytes, where it acts by vasodilation and by blocking the renin-angiotensin-aldosterone system (RAAS) to lower blood pressure. There is a relationship between low serum vitamin D levels and high blood pressure. Our study concluded that there is an association between hypovitaminosis D and the pathology of hypertension. However, further randomised studies are needed and in the meantime, clinicians could propose it in the therapeutic arsenal of Moroccan hypertensive patients.
Asunto(s)
Hipertensión , Deficiencia de Vitamina D , Humanos , Femenino , Persona de Mediana Edad , Masculino , Vitamina D , Marruecos/epidemiología , Estudios Prospectivos , Vitaminas/uso terapéutico , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Presión SanguíneaRESUMEN
INTRODUCTION: Viral hepatitis B is a global scourge affecting millions of people worldwide. In Morocco, hepatitis B is considered a public health problem, and available data converge to consider Morocco as a country with intermediate endemicity. In the present study, we have planned to evaluate the HBV prevalence in Morocco on a large scale and to assess the prevalence of different serological markers for better management of this infection in Morocco. METHODS: This study was conducted on 18,877 patients referring to the Ibn Sina University Hospital Center of Rabat, Morocco. HBV serological markers including HBsAg, HBsAb, HBeAg, HBeAb, and total HBcAb were assessed by immune-enzymatic assays. The quantification of HBV DNA was performed by real-time PCR. RESULTS: The overall prevalence of positive cases for HBsAg, HBsAb, and total HBcAb was 2.47%, 27.66%, and 21.2%, respectively. From 141 patients with an isolated HBcAb serological profile (HBcAb+/HBsAb-/HBsAg-), HBV DNA was detected in 10 patients, representing a rate of 7.09%. In the present study, up to 95.78% of HBV chronic carriers were negative for HBeAg. CONCLUSION: This study highlights a higher prevalence of HBsAg in the hospital-based population than the general population reported previously in Morocco and a very low HBV immunization coverage. Of particular interest, detectable HBV DNA levels in isolated HBcAb patients show that exclusive HBsAg screening cannot eliminate the risk of HBV transmission in certain cases. Many efforts are then mandatory to promote serological testing and increase the vaccination rate to limit viral dissemination for better management of this disease in Morocco.