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1.
Int J Mol Sci ; 25(10)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38791506

RESUMEN

Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets is more necessary than ever to tackle this pathology. Heat-Shock Protein 90 (HSP90), a chaperone protein, is implicated in breast cancer pathogenesis, rendering it an appealing target. Looking for alternative approach such as Plant-based compounds and natural HSP90 inhibitors offer promising prospects for innovative therapeutic strategies. This study aims to identify plant-based compounds with anticancer effects on breast cancer models and elucidate their mechanism of action in inhibiting the HSP90 protein. A systematic review was conducted and completed in January 2024 and included in vitro, in vivo, and in silico studies that investigated the effectiveness of plant-based HSP90 inhibitors tested on breast cancer models. Eleven studies were included in the review. Six plants and 24 compounds from six different classes were identified and proved to be effective against HSP90 in breast cancer models. The studied plant extracts showed a dose- and time-dependent decrease in cell viability. Variable IC50 values showed antiproliferative effects, with the plant Tubocapsicum anomalum demonstrating the lowest value. Withanolides was the most studied class. Fennel, Trianthema portulacastrum, and Spatholobus suberectus extracts were shown to inhibit tumor growth and angiogenesis and modulate HSP90 expression as well as its cochaperone interactions in breast cancer mouse models. The identified plant extracts and compounds were proven effective against HSP90 in breast cancer models, and this inhibition showed promising effects on breast cancer biology. Collectively, these results urge the need of further studies to better understand the mechanism of action of HSP90 inhibitors using comparable methods for preclinical observations.


Asunto(s)
Neoplasias de la Mama , Proteínas HSP90 de Choque Térmico , Animales , Femenino , Humanos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/metabolismo , Extractos Vegetales/farmacología , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología
2.
BMC Cancer ; 22(1): 1142, 2022 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-36344948

RESUMEN

BACKGROUND: Our review discuss (i) the findings from analyzed data that have examined KRAS, NRAS and BRAF mutations in patients with colorectal cancer (CRC) in North Africa and to compare its prevalence with that shown in other populations and (ii) the possible role of dietary and lifestyle factors with CRC risk.  METHODS: Using electronic databases, a systematic literature search was performed for the KRAS, NRAS, and BRAF mutations in CRC patients from Morocco, Tunisia, Algeria and Lybia.  RESULTS: Seventeen studies were identified through electronic searches with six studies conducted in Morocco, eight in Tunisia, two in Algeria, and one in Libya. A total of 1843 CRC patients were included 576 (31.3%) in Morocco, 641 (34.8%) in Tunisia, 592 (32.1%) in Algeria, and 34 (1.8%) in Libya. Overall, the average age of patients was 52.7 years old. Patients were predominantly male (56.6%). The mutation rates of KRAS, NRAS and BRAF were 46.4%, 3.2% and 3.5% of all patients, respectively. A broad range of reported KRAS mutation frequencies have been reported in North Africa countries. The KRAS mutation frequency was 23.9% to 51% in Morocco, 23.1% to 68.2% in Tunisia, 31.4% to 50% in Algeria, and 38.2% in Libya. The G12D was the most frequently identified KRAS exon 2 mutations (31.6%), followed by G12V (25.4%), G13D (15.5%), G12C (10.2%), G12A (6.9%), and G12S (6.4%). G12R, G13V, G13C and G13R are less than 5%. There are important differences among North Africa countries. In Morocco and Tunisia, there is a higher prevalence of G12D mutation in KRAS exon 2 (≈50%). The most frequently mutation type in KRAS exon 3 was Q61L (40%). A59T and Q61E mutations were also found. In KRAS exon 4, the most common mutation was A146T (50%), followed by K117N (33.3%), A146P (8.3%) and A146V (8.3%). CONCLUSION: KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.


Asunto(s)
Neoplasias Colorrectales , Proteínas Proto-Oncogénicas B-raf , Humanos , Masculino , Persona de Mediana Edad , Femenino , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Prevalencia , Mutación , Sistema de Señalización de MAP Quinasas , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Túnez/epidemiología
3.
BMC Infect Dis ; 18(1): 680, 2018 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-30567502

RESUMEN

BACKGROUND: The widespread use of an effective and safe vaccine to measles has substantially decreased morbidity and mortality from this epidemic. Nevertheless, HIV-infected children vaccinated against measles may develop an impaired vaccine response and remain susceptible to this disease. In Morocco, infants are routinely vaccinated against measles, regardless of their HIV serostatus. An evaluation of the immunization of these children may be of paramount importance to implement timely measures aimed at preventing measles transmission. METHODS: In this study, we have enrolled 114 children vaccinated against measles, 50 children prenatally infected with HIV and 64 HIV-uninfected children. For all children, blood samples were taken to measure anti-measles IgG by EIA and CD4 count by flow cytometry. Additionally, HIV viral load was determined by automated real time PCR, for HIV-infected children. RESULTS: The seroprotective rate of IgG anti-measles antibodies was significantly lower among HIV-infected children (26%) compared with HIV-uninfected children (73%) (p < 0.001). Within HIV-infected children group, the comparison of variables between children without seroprotective seroconversion to measles and those with seroprotective immunity, displayed that sex and age were not statistically different, p > 0.999 and p = 0.730, respectively. However, CD4 count was lower among children with negative serostatus to measles (23% versus 32%, p < 0.001). Furthermore, viral load was higher, with 2.91 log10 ± 2.24 versus 1.7 log10 ± 1.5 (p = 0.042). Finally, 62% of children with a negative vaccine response to measles were under HAART therapy, versus 92% (p = 0.008). CONCLUSION: The majority of HIV-infected children vaccinated against measles develop a suboptimal seroprotective titer, and therefore remain at risk for this highly infectious disease. These data in combination with international recommendations, including recent WHO guidance on vaccination of HIV-infected children, suggest there is a need for national measures to prevent these children from measles.


Asunto(s)
Anticuerpos Antivirales/sangre , Formación de Anticuerpos , Infecciones por VIH/epidemiología , Transmisión Vertical de Enfermedad Infecciosa , Vacuna Antisarampión/uso terapéutico , Sarampión/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Femenino , VIH , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Masculino , Sarampión/sangre , Sarampión/complicaciones , Vacuna Antisarampión/inmunología , Virus del Sarampión/inmunología , Marruecos/epidemiología , Estudios Seroepidemiológicos , Vacunación
4.
BMC Public Health ; 17(1): 752, 2017 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-28962610

RESUMEN

BACKGROUND: Since its development in the early 1980s, Hepatitis B virus (HBV) vaccine has been proven to be highly protective. However, its immunogenicity may be ineffective among HIV-infected children. In Morocco, HBV vaccine was introduced in 1999, and since then all infants, including vertically HIV-infected infants, have been following the vaccination schedule, implemented by the Moroccan ministry of health. An assessment of the immunization of these children is important to optimize efforts aimed at tackling Hepatitis B coinfection, within the country. METHODS: Forty-nine HIV-infected children (HIV group) and 112 HIV uninfected children (control group) were enrolled in this study. Samples were tested by Elisa (Monolisa Anti-HBs, Biorad) to quantify the anti-HBs antibodies. The % of lymphocyte subsets i.e. CD4+ T cells, CD8+ T cells, B cells, and NK, was determined by flow cytometry, using CellQuest Pro software (Becton-Dickinson), and for HIV group, HIV viral load was measured by real time PCR assay (Abbott). All variables were statistically compared in the two groups. RESULTS: The median age was 51 ± 35 months for the HIV group and 50 ± 36 months (p > 0.05) for the control group. Female represented 63% and 41% (p = 0.01), among the HIV group and the control group, respectively. Among HIV-infected children, 71.4% (35/49) were under HAART therapy at the enrollment in the study. Seroprotection titer i.e. anti-HBs ≥10mUI/ml among control group was 76% (85/112), and only 29% (14/49) among the perinatally HIV-infected children (p < 0.0001). Lower % of CD4 + T cells was observed in HIV-infected children with a poor anti-HBs response. CONCLUSION: In this studied group, we have shown that despite the vaccination of HIV-children with HBV vaccine, 71% did not show any seroprotective response. These findings support the need for monitoring HBV vaccine response among HIV-infected children in Morocco, in order to revaccinate non-immunized children.


Asunto(s)
Infecciones por VIH/inmunología , Anticuerpos contra la Hepatitis B/análisis , Vacunas contra Hepatitis B/administración & dosificación , Hepatitis B/prevención & control , Terapia Antirretroviral Altamente Activa , Estudios de Casos y Controles , Niño , Preescolar , Coinfección/prevención & control , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hepatitis B/epidemiología , Humanos , Esquemas de Inmunización , Lactante , Masculino , Marruecos/epidemiología
5.
Nutr Cancer ; 68(1): 131-43, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26771897

RESUMEN

Telomerase is activated in human papillomavirus (HPV) positive cervical cancer and targeting telomeres offers a novel anticancer therapeutic strategy. In this study, the telomere targeting properties, the cytotoxic as well as the pro-apoptotic effects of hexane (IV-HE) and dichloromethane (IV-DF) fractions from Inula viscosa L. extracts were investigated on human cervical HeLa and SiHa cancer cells. Our data demonstrate that IV-HE and IV-DF extracts were able to inhibit cell growth in HeLa and SiHa cells in a dose-dependent manner and studied resistant cell lines exhibited a resistance factor less than 2 when treated with the extracts. IV-HE and IV-DF extracts were able to inhibit telomerase activity and to induce telomere shortening as shown by telomeric repeat amplification protocol and TTAGGG telomere length assay, respectively. The sensitivity of fibroblasts to the extracts was increased when telomerase was expressed. Finally, IV-HE and IV-DF were able to induce apoptosis as evidenced by an increase in annexin-V labeling and caspase-3 activity. This study provides the first evidence that the IV-HE and IV-DF extracts from Inula viscosa L. target telomeres induce apoptosis and overcome drug resistance in tumor cells. Future studies will focus on the identification of the molecules involved in the anticancer activity.


Asunto(s)
Apoptosis/efectos de los fármacos , Inula , Extractos Vegetales/farmacología , Acortamiento del Telómero/efectos de los fármacos , Anexina A5/análisis , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Humanos , Telomerasa/metabolismo
6.
Nutrients ; 14(22)2022 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-36432545

RESUMEN

It is with great interest that we read the article entitled "Hydroxybenzoic Acids as Acetylcholinesterase Inhibitors: Calorimetric and Docking Simulation Studies" published in Nutrients 2022, 14, 2476 [...].


Asunto(s)
Acetilcolinesterasa , Inhibidores de la Colinesterasa , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Acetilcolinesterasa/química , Hidroxibenzoatos/farmacología , Simulación por Computador , Nutrientes
8.
Pediatr Hematol Oncol ; 26(4): 216-31, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19437324

RESUMEN

CD10 and CD34 expression in 86 Moroccan children with acute lymphoblastic leukemias (ALL) and the relevance to prognosis, diagnosis, and outcome during a 5-year follow-up were examined. At diagnosis, 57% of patients had CD10(+) blasts, while 35% had CD34(+) blasts. The CD10(+) blast frequency was much higher (80%) in B-ALL than in T-ALL (20%). The frequency of CD34(+) blasts was higher in B-ALL (48%) compared to T-ALL (16%). The 5-year survival curves showed that children with CD10(+) B-ALL had a significantly longer survival rate than those with CD10(-), as observed for T-ALL. The survival rate of B-ALL expressing CD34 was higher than that of CD34(-). Thus, CD34 and CD10 expression may have prognostic value and is associated with a better clinical outcome.


Asunto(s)
Antígenos CD34/inmunología , Biomarcadores de Tumor/inmunología , Neprilisina/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Leucemia-Linfoma Linfoblástico de Células T Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Adolescente , Linfocitos B/inmunología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Estimación de Kaplan-Meier , Masculino , Marruecos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Tasa de Supervivencia , Linfocitos T/inmunología
9.
Therapie ; 64(2): 121-7, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19664406

RESUMEN

Extracts of Withania adpressa Coss. (Solanaceae), a medicinal plant endemic to Moroccan Sahara, were tested for their cytotoxicity towards a panel of cancer cell lines (Hep2, HT29, RD, Vero and MDCK), using the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) [MTT assay, Sigma-Aldrich]. The bioassay-guided fractionation of this plant extracts results a novel withanolide 14alpha,15alpha,17beta ,20beta-tetrahydroxy-1-oxo-(22R)-witha-2,5,24-trienolide and the already identified withanolides F and J extract, semi-purified fractions and pure compounds exhibits potent cytotoxicity against human cancer cell lines tested, in dose-dependent manner. Morphological features of treated Hep2 cells with the novel withanolide and characteristic DNA fragmentation revealed that the cytotoxicity was due to induction of apoptosis. Taken together, the results suggest that withanolides from W. adpressa Coss. hold potential as antiproliferative agents.


Asunto(s)
Antineoplásicos Fitogénicos , Proliferación Celular/efectos de los fármacos , Withania/química , Witanólidos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Colorantes , Fragmentación del ADN/efectos de los fármacos , Humanos , Extractos Vegetales/farmacología , Hojas de la Planta/química , Sales de Tetrazolio , Tiazoles
10.
Therapie ; 63(1): 49-54, 2008.
Artículo en Francés | MEDLINE | ID: mdl-18387276

RESUMEN

Atractylis gummifera L., a poisonous thistle responsible for frequent and sometimes mortal poisonings is known in Mediterranean region and in occident as this plant is used in alternative medicine. The clinical and biological data of four cases of poisoning in Morocco by Atractylis gummifera L. reported and discussed in this study will have to help to review this poisoning in order to inform better and to take care of the poisoned persons. Also this study may contribute to prevent the use of this plant in traditional medicine.


Asunto(s)
Atractylis/envenenamiento , Intoxicación por Plantas/terapia , Adolescente , Glucemia/metabolismo , Presión Sanguínea/fisiología , Niño , Femenino , Escala de Coma de Glasgow , Humanos , Marruecos , Intoxicación por Plantas/metabolismo , Intoxicación por Plantas/patología
11.
Enzyme Microb Technol ; 114: 1-6, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29685347

RESUMEN

The present work describes a method for detecting the ingress of gas phase oxygen into packed food. It uses the enzyme polyphenol oxidase (PPO)from Mushroom and Mediterranean dwarf palm. The PPO is incorporated into an indubiose film along with a non-toxic polyphenol such as gallic acid or chlorogenic acid. If exposed to oxygen, the test spot undergoes an irreversible and visible color change from pale to deep brown due to the PPO catalyzed oxidation of the respective polyphenol by oxygen. The color change can be detected visually or by spectrophotometry at 470 nm. The effect of the amount of oxygen or substrate, type of enzyme substrate, enzyme source, temperature and duration of storage on the response were studied. Air oxygen can be detected within 30 min under optimized condition. The smallest amount of oxygen that can be detected with acceptable response time (120 min) is 5%. The test is highly selective for oxygen and the detector is stable over time. The detector may be used in any application as long as the presence or absence of oxygen in a sealed space is determined prior to the application using the detector.


Asunto(s)
Agaricales/enzimología , Arecaceae/enzimología , Técnicas Biosensibles/métodos , Catecol Oxidasa/química , Proteínas Fúngicas/química , Oxígeno/análisis , Proteínas de Plantas/química , Biocatálisis , Técnicas Biosensibles/instrumentación , Color , Cinética , Espectrofotometría , Especificidad por Sustrato , Temperatura
12.
Eur J Intern Med ; 18(6): 474-83, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17822659

RESUMEN

BACKGROUND: Hyperhomocyteinemia (HHcy) is a risk factor for coronary artery disease (CAD), and methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) polymorphisms may contribute to plasma total homocysteine (tHcy) variation. We investigated the association of polymorphisms 1298A-->C in the MTHFR gene, 2756A-->G in the MTR gene, and 66A-->G in the MTRR gene with tHcy levels and with CAD in patients undergoing coronary angiography. METHODS: CAD patients (n=151) and control subjects (n=79) were compared regarding the prevalence of the polymorphisms, risk factors, and biochemical parameters. RESULTS: The mean tHcy concentration was significantly higher in CAD patients than in control subjects (P<0.001). HHcy (tHcy>/=15 mumol/l) conferred an OR of CAD of 4.1 (95% CI 2.2-7.5, P<0.001). In both cases and controls, smokers had a higher tHcy level than non-smokers and demonstrated a markedly increased risk for CAD (OR=2.5, 95% CI 1.7-3.3, P<0.001). The allele frequencies of the MTHFR 1298A-->C, MTR 2756A-->G, and MTRR 66A-->G mutations were 36.7%, 15.7%, and 36.6%, respectively. The 1298C allele frequency was significantly higher in the CAD group than in controls (P<0.05) and showed a significant association with CAD in heterozygote carriers. There was no statistically significant difference between cases and controls in the frequencies of the A2756G alleles/genotypes in the MTR gene and of the A66G alleles/genotypes in the MTRR gene. The contributions to tHcy levels of the three common mutations were statistically significant. The heterozygosity of the MTHFR 1298AC genotype, MTR 2756G allele, and MTRR 66G allele yielded an OR of 3.4, 2.0, and 2.1, respectively, for having HHcy. CONCLUSION: We suggest that HHcy confers a risk for CAD, and smokers with tHcy are at a greatly increased risk. Our finding supports an important role of the MTHFR gene in CAD and provides evidence of polygenic regulation of tHcy.

13.
Acta Cardiol ; 61(1): 51-61, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16485733

RESUMEN

BACKGROUND: Elevated plasma total homocysteine (tHcy) is increasingly being recognized as a risk factor for coronary artery disease (CAD) and other defects. Recent genetic studies have characterized molecular determinants contributing to altered homocysteine metabolism. Our objectives were therefore to confirm the relationship of tHcy with CAD and to examine the importance of genetic influence on tHcy in the coronary angiograms and conventional cardiovascular risk factors recorded in 230 subjects. We also determined the genotype frequencies distribution of the A2756G transition of the B12-dependent methionine synthase (MTR) gene and the A66G mutation of the methionine synthase reductase (MTRR) gene. RESULTS: Patients with CAD (n=151) had significantly higher tHcy concentrations than control subjects (15.49 +/- 2.75 micromol/l vs. 11.21 +/- 3.54 micromol/l, P < 0.001). Hyperhomocysteinaemia (tHcy > or =15 micromol/l) was a risk factor for CAD [RR = 4.07, 95% CI: 2.21 - 7.47, P < 0.001]. The homocysteine concentrations were significantly different between smokers and non-smokers, at 15.63 +/- 3.10 vs. 12.45 +/- 3.84 micromol/l, P < 0.05. In addition, smokers with hyperhomocysteinaemia demonstrated a markedly increased risk of CAD (OR = 2.50, 95% CI: 1.67 - 3.32, P < 0.05) compared with non-smokers with normal homocysteine.The 2756G and the 66G allele contribute to a moderate increase in homocysteine levels (P = 0.008 and P = 0.007, respectively), but not to CAD (P > 0.05). Combined MTR and MTRR polymorphisms, the 2756AG + 66AG and the 2756AG + 66GG were the combined genotypes that were a significant risk factor for having hyperhomocysteinaemia (14.4 +/- 2.8 micromol/l, OR = 2.75, IC 95% = 1.21 - 6.24, P=0.016 and 17.9 +/- 4.1 micromol/l, OR = 6.28, IC 95% = 1.46 - 12.1, P = 0.021, respectively). Statistic analysis using the UniANOVA test shows that these two polymorphisms have an interactive effect circulating homocysteine levels (P < 0.05). CONCLUSION: Our data suggest that moderately elevated tHcy levels are prevalent in our population and are associated with an increased risk for CAD. This study provides evidence that the MTR A2756G and MTRR A66G polymorphisms significantly influence the circulating homocysteine concentration. In addition, the MTR and MTRR genes may interact to increase the risk for having hyperhomocysteinaemia.


Asunto(s)
5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , Enfermedad de la Arteria Coronaria/sangre , Ferredoxina-NADP Reductasa/genética , Homocisteína/sangre , Hiperhomocisteinemia/genética , Polimorfismo Genético , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/sangre , Adulto , Anciano , Análisis de Varianza , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/enzimología , Femenino , Ferredoxina-NADP Reductasa/sangre , Genotipo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Mutación , Factores de Riesgo , Estadísticas no Paramétricas
14.
Nat Commun ; 7: 12203, 2016 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-27417143

RESUMEN

The accumulation of lipid droplets (LD) is frequently observed in hepatitis C virus (HCV) infection and represents an important risk factor for the development of liver steatosis and cirrhosis. The mechanisms of LD biogenesis and growth remain open questions. Here, transcriptome analysis reveals a significant upregulation of septin 9 in HCV-induced cirrhosis compared with the normal liver. HCV infection increases septin 9 expression and induces its assembly into filaments. Septin 9 regulates LD growth and perinuclear accumulation in a manner dependent on dynamic microtubules. The effects of septin 9 on LDs are also dependent on binding to PtdIns5P, which, in turn, controls the formation of septin 9 filaments and its interaction with microtubules. This previously undescribed cooperation between PtdIns5P and septin 9 regulates oleate-induced accumulation of LDs. Overall, our data offer a novel route for LD growth through the involvement of a septin 9/PtdIns5P signalling pathway.


Asunto(s)
Hepacivirus/patogenicidad , Gotas Lipídicas/metabolismo , Microtúbulos/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Septinas/metabolismo , Línea Celular Tumoral , Regulación de la Expresión Génica , Hepacivirus/fisiología , Hepatitis C/metabolismo , Interacciones Huésped-Patógeno/fisiología , Humanos , Gotas Lipídicas/efectos de los fármacos , Metabolismo de los Lípidos/fisiología , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/virología , Microtúbulos/virología , Ácido Oléico/farmacología , Septinas/genética , Replicación Viral
15.
J Immunol Methods ; 266(1-2): 53-65, 2002 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-12133622

RESUMEN

Development of specifically labeled chemokines that retain their biological properties should be useful for analyzing their mechanisms of action both under physiological and pathological conditions. Here, we report the chemical synthesis and characterization of RANTES (regulated upon activation normal T cell expressed and secreted) derivatives that were biotinylated at residues 1, 25, 33, 45, or 67. Gel filtration and ultracentrifugation experiments showed that biotinylation at position 45 or 67 decreased the aggregation tendency of the chemokine to a dimeric state. Competition experiments, using a stably transfected CHO-K1 cell line overexpressing human CCR5, a RANTES receptor, indicated that derivatives biotinylated at positions 1, 25, and 67 bound to CCR5 with the same affinity as native RANTES. Flow cytometry analysis showed that RANTES biotinylated at residue 67 (B67-RANTES) bound more efficiently to primary macrophages than the other derivatives. Such binding was dependent on cell surface glycosaminoglycans (GAGs) since it was reduced when macrophages or HeLa cells expressing or not CCR5 were first treated with GAG-specific enzymes. In addition, B67-RANTES modulated CCR5 expression on lymphocytes and elicited chemotaxis of monocytes in the same manner as unmodified RANTES. Thus, B67-RANTES acts as a CCR5 agonist and may be useful to study the role of RANTES in pathologies such as, for example, human immunodeficiency virus (HIV) infection and inflammatory disorders.


Asunto(s)
Quimiocina CCL5/análogos & derivados , Quimiocina CCL5/farmacología , Animales , Unión Competitiva , Biotinilación , Células CHO , Células Cultivadas , Quimiocina CCL5/química , Quimiocina CCL5/fisiología , Quimiotaxis , Cricetinae , Glicosaminoglicanos/metabolismo , Células HeLa , Humanos , Macrófagos/metabolismo , Monocitos/fisiología , Receptores CCR5/metabolismo , Linfocitos T/metabolismo
16.
AIDS Res Hum Retroviruses ; 18(2): 103-13, 2002 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-11839143

RESUMEN

Activating cells of the immune system may stimulate human immunodeficiency virus type 1 (HIV-1) replication and contribute to select pathogenic variants in vivo. Here, we examined the possible effect of a major pathway of immune activation, CD40 interaction with its ligand (CD40L), on the susceptibility of monocyte-derived macrophages (MDMs) to various HIV-1 strains. Stimulation of MDMs with CD40L led to reduced replication of R5 HIV-1(Ba-L), whereas this strongly enhanced the replication of X4 HIV-1(Lai) as well as of X4 primary isolates, and this was associated with strong cytopathic effects. The replication of X4 strains was inhibited by stromal cell-derived factor 1, an indication of the restricted usage of CXCR4 as virus coreceptor in this case. CD40L induced the activation of mitogen-activated protein kinases ERK1/ERK2 and stimulated MDMs to secrete RANTES (regulated on activation, normal T cell expressed and secreted), macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, interleukin 6 (IL-6), IL-1beta, and tumor necrosis factor alpha. From this data, it may be hypothesized that activated macrophages represent a favorable environment for the replication of classically T lymphocyte-tropic X4 variants and, thus, may contribute significantly to the selection of such variants at late stages of clinical HIV-1 infection.


Asunto(s)
Antígenos CD40/inmunología , VIH-1/inmunología , Activación de Macrófagos/inmunología , Macrófagos/inmunología , Ligando de CD40/farmacología , Células Cultivadas , Citocinas/biosíntesis , Activación Enzimática , VIH-1/efectos de los fármacos , VIH-1/aislamiento & purificación , VIH-1/fisiología , Humanos , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/virología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fenotipo , Replicación Viral
17.
Therapie ; 58(6): 531-4, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-15058498

RESUMEN

Extracts from a new chemotype of Mentha longifolia, a mint species that grows spontaneously and widely in the Moroccan mountains, were tested against human immunodeficiency virus type 1 (HIV-1). We observed that non-toxic concentrations (10 microg/mL) of extracts from this plant, in particular methanol (Ext-1) and ethyl acetate (Ext-3) extracts, significantly inhibit (p < 0.01) HIV-1BaL infection by about 40% and 55%, respectively. In addition, only Ext-3 shows significant (p < 0.008) inhibitory activity (50% inhibition) against HIV-1 reverse transcriptase. It is noteworthy that chemical analysis of these extracts suggests that flavonoids, mainly flavones of M. longifolia, may be the major inhibitors of HIV infection. In conclusion, these in vitro data suggest that components of M. longifolia may represent potential anti-HIV agents; the identification of such components is in progress.


Asunto(s)
Fármacos Anti-VIH/farmacología , VIH-1/efectos de los fármacos , Mentha/química , Inhibidores de la Transcriptasa Inversa/farmacología , Línea Celular , Supervivencia Celular , Transcriptasa Inversa del VIH/efectos de los fármacos , Células HeLa , Humanos , Marruecos , Extractos Vegetales/farmacología
18.
J Infect Dev Ctries ; 8(4): 430-40, 2014 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-24727508

RESUMEN

INTRODUCTION: Toll-like receptors (TLRs) 2, 4, and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis (Mtb). TLR2, TLR4, and VDR polymorphisms were previously associated with tuberculosis (TB) and were here investigated as candidates for pulmonary TB (PTB) susceptibility in a Moroccan population group. METHODOLOGY: Genomic DNA from 343 PTB patients and 203 healthy controls were analyzed for 12 single nucleotide polymorphisms (SNPs) located in TLR2, TLR4, and VDR genes using polymerase chain reaction-based restriction fragment length polymorphism and TaqMan SNP genotyping assays. RESULTS: The TLR2 +597 CT genotype was associated with protection against PTB (corrected p [pc] = 0.04; odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.45 - 0.94), and the TLR4 +7263 C allele was significantly associated with PTB susceptibility (pc = 0.04; OR = 1.63; CI = 1.06 - 2.57). The VDR [f,b,a,T] haplotype was found to confer protection (pc < 0.00001; OR = 0.18; CI = 0.09 - 0.35), while the TLR2 [-16934T,+597C,+1349T] haplotype seemed to be at risk (p = 0.03; OR = 1.52; CI = 1.01 - 2.30), but statistical significance was not reached. Finally, cross-analysis between polymorphisms of the three studied genes revealed significant interaction between TLR2 +597 and TLR4 +4434 SNPs towards protection against PTB (pc = 0.036), suggesting that the functionally relevant TLR4 +4434 SNP may act synergistically with TLR2 SNPs. CONCLUSIONS: TLR2 and TLR4 interaction and a specific VDR haplotype influence protection against PTB in Moroccans patients.


Asunto(s)
Receptores de Calcitriol/genética , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/genética , Tuberculosis Pulmonar/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Marruecos , Polimorfismo de Nucleótido Simple , Adulto Joven
20.
Adv Pharmacol Sci ; 2012: 270824, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22162677

RESUMEN

We evaluate the sedative and hypnotic activities of the methanolic and aqueous extract of Lavandula officinalis L. on central nervous system (CNS). In this study, the effect of the methanolic and aqueous extracts of this plant was investigated in a battery of behavioural models in mice. Stems and flowers of Lavandula officinalis L. have several therapeutic applications in folk medicine in curing or managing a wide range of diseases, including insomnia. The methanolic extract produced significant sedative effect at the doses of 200, 400, and 600 mg/kg (by oral route), compared to reference substance diazepam (DZP), and an hypnotic effect at the doses of 800 and 1000 mg/kg while the treatment of mice with the aqueous extract at the doses of 200 and 400 mg/kg via oral pathway significantly reduced in both the reestablishment time and number of head dips during the traction and hole-board tests. In conclusion, these results suggest that the methanolic and aqueous extracts of Lavandula officinalis possess potent sedative and hypnotic activities, which supported its therapeutic use for insomnia.

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