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1.
Molecules ; 28(1)2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36615630

RESUMEN

Catechins have been shown to display a great variety of biological activities, prominent among them are their chemo preventive and chemotherapeutic properties against several types of cancer. The amphiphilic nature of catechins points to the membrane as a potential target for their actions. 3,4,5-Trimethoxybenzoate of catechin (TMBC) is a modified structural analog of catechin that shows significant antiproliferative activity against melanoma and breast cancer cells. Phosphatidylglycerol is an anionic membrane phospholipid with important physical and biochemical characteristics that make it biologically relevant. In addition, phosphatidylglycerol is a preeminent component of bacterial membranes. Using biomimetic membranes, we examined the effects of TMBC on the structural and dynamic properties of phosphatidylglycerol bilayers by means of biophysical techniques such as differential scanning calorimetry, X-ray diffraction and infrared spectroscopy, together with an analysis through molecular dynamics simulation. We found that TMBC perturbs the thermotropic gel to liquid-crystalline phase transition and promotes immiscibility in both phospholipid phases. The modified catechin decreases the thickness of the bilayer and is able to form hydrogen bonds with the carbonyl groups of the phospholipid. Experimental data support the simulated data that locate TMBC as mostly forming clusters in the middle region of each monolayer approaching the carbonyl moiety of the phospholipid. The presence of TMBC modifies the structural and dynamic properties of the phosphatidylglycerol bilayer. The decrease in membrane thickness and the change of the hydrogen bonding pattern in the interfacial region of the bilayer elicited by the catechin might contribute to the alteration of the events taking place in the membrane and might help to understand the mechanism of action of the diverse effects displayed by catechins.


Asunto(s)
Catequina , Fosfatidilgliceroles , Fosfatidilgliceroles/química , Membrana Dobles de Lípidos/química , Catequina/química , Fosfolípidos , Transición de Fase , Rastreo Diferencial de Calorimetría
2.
J Membr Biol ; 255(2-3): 277-291, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35175383

RESUMEN

The antineoplastic drug Docetaxel is a second generation taxane which is used against a great variety of cancers. The drug is highly lipophilic and produces a great array of severe toxic effects that limit its therapeutic effectiveness. The study of the interaction between Docetaxel and membranes is very scarce, however, it is required in order to get clues in relation with its function, mechanism of toxicity and possibilities of new formulations. Using phosphatidylcholine biomimetic membranes, we examine the interaction of Docetaxel with the phospholipid bilayer combining an experimental study, employing a series of biophysical techniques like Differential Scanning Calorimetry, X-Ray Diffraction and Infrared Spectroscopy, and a Molecular Dynamics simulation. Our experimental results indicated that Docetaxel incorporated into DPPC bilayer perturbing the gel to liquid crystalline phase transition and giving rise to immiscibility when the amount of the drug is increased. The drug promotes the gel ripple phase, increasing the bilayer thickness in the fluid phase, and is also able to alter the hydrogen-bonding interactions in the interfacial region of the bilayer producing a dehydration effect. The results from computational simulation agree with the experimental ones and located the Docetaxel molecule forming small clusters in the region of the carbon 8 of the acyl chain palisade overlapping with the carbonyl region of the phospholipid. Our results support the idea that the anticancer drug is embedded into the phospholipid bilayer to a limited amount and produces structural perturbations which might affect the function of the membrane.


Asunto(s)
Fosfatidilcolinas , Fosfolípidos , 1,2-Dipalmitoilfosfatidilcolina/química , Rastreo Diferencial de Calorimetría , Docetaxel , Membrana Dobles de Lípidos/química , Membranas , Fosfatidilcolinas/química , Fosfolípidos/química
3.
Molecules ; 27(9)2022 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-35566261

RESUMEN

3,4,5-Trimethoxybenzoate of catechin (TMBC) is a semisynthetic catechin which shows strong antiproliferative activity against malignant melanoma cells. The amphiphilic nature of the molecule suggests that the membrane could be a potential site of action, hence the study of its interaction with lipid bilayers is mandatory in order to gain information on the effect of the catechin on the membrane properties and dynamics. Anionic phospholipids, though being minor components of the membrane, possess singular physical and biochemical properties that make them physiologically essential. Utilizing phosphatidylserine biomimetic membranes, we study the interaction between the catechin and anionic bilayers, bringing together a variety of experimental techniques and molecular dynamics simulation. The experimental data suggest that the molecule is embedded into the phosphatidylserine bilayers, where it perturbs the thermotropic gel to liquid crystalline phase transition. In the gel phase, the catechin promotes the formation of interdigitation, and in the liquid crystalline phase, it decreases the bilayer thickness and increases the hydrogen bonding pattern of the interfacial region of the bilayer. The simulation data agree with the experimental ones and indicate that the molecule is located in the interior of the anionic bilayer as monomer and small clusters reaching the carbonyl region of the phospholipid, where it also disturbs the intermolecular hydrogen bonding between neighboring lipids. Our observations suggest that the catechin incorporates well into phosphatidylserine bilayers, where it produces structural changes that could affect the functioning of the membrane.


Asunto(s)
Catequina , Fosfolípidos , Catequina/química , Catequina/farmacología , Membrana Dobles de Lípidos/química , Transición de Fase , Fosfatidilserinas/química , Fosfolípidos/química
4.
Rev Chil Pediatr ; 87(6): 442-448, 2016.
Artículo en Español | MEDLINE | ID: mdl-26925502

RESUMEN

Coeliac disease (CD) is a systemic autoimmune disorder triggered by gluten consumption in genetically susceptible individuals. It exhibits several clinical features, such as blood auto-antibodies (anti-endomysial antibodies EMA, anti-transglutaminase antibodies tTG, anti-deamidated gliadin peptides PGD), plus variable degrees of damage in the small intestinal mucosa. In Chile, tTG is positive in 0.76% in individuals >15 years, with the prevalence of CD being estimated at 0.6%. Approximately17% of first-degree relatives of coeliac patients have been reported tTG positive. To date, the gluten free diet (GFD) is the only known treatment for CD. To be effective, this must be lifelong, permanent, and strict. Gluten content in the GFD is not zero, but is limited to a cut-off of 3ppm (ormg/kg of product) in Chile. Mortality higher than that of the general population has been reported among coeliac patients, and poor adherence to GFD is associated with complications (mainly autoimmune processes and cancer). GFD is difficult to maintain strictly and poor adherence is by far the main cause of lack of response to treatment. Follow-up of adherence is also difficult because there are no objective measurements to assess it. In clinical practice determination of serum EMA, tTG and PGD is routinely used for these purposes, although more recently, the interview by an expert dietitian, validated questionnaires and measurement of faecal 33-mer peptide are being assessed as alternatives or complements to measure adherence to GFD. A review is presented with the current concepts on the available tools to follow up patients on GFD, emphasising those available in Chilel.


Asunto(s)
Enfermedad Celíaca/dietoterapia , Dieta Sin Gluten , Cooperación del Paciente , Autoanticuerpos/análisis , Enfermedad Celíaca/inmunología , Chile , Glútenes/administración & dosificación , Glútenes/efectos adversos , Humanos , Encuestas y Cuestionarios
5.
Rev. chil. pediatr ; 87(6): 442-448, Dec. 2016. tab
Artículo en Español | LILACS | ID: biblio-844563

RESUMEN

La enfermedad celíaca (EC) es un trastorno sistémico inmune mediado por la ingesta de gluten en individuos genéticamente susceptibles. Se caracteriza por manifestaciones clínicas variables, auto anticuerpos anti-endomisio, anti-transglutaminasa (tTG) y/o anti-péptidos de gliadina deamidados (PGD) en sangre, más daño variable de la mucosa intestinal. En Chile el 0,76% de los mayores de 15 años tiene IgA-tTG positiva y la prevalencia de EC se estima en ~0,6%. En familiares de primer grado de celíacos se ha identificado ~17% de casos tTG positivos. Hasta hoy el único tratamiento es la dieta libre de gluten (DLG), que para ser efectiva debe ser estricta, permanente y durante toda la vida. La DLG no contiene cero gluten, sino que lo disminuye hasta un «punto de corte¼, que en Chile es 3 ppm (o mg/kg de producto). La mortalidad de la EC es mayor que la de la población general, y la falta de adherencia al tratamiento se asocia a complicaciones (procesos autoinmunes y cáncer principalmente). La DLG es difícil de mantener estrictamente, y las transgresiones son por lejos la principal causa de falta de respuesta al tratamiento. El seguimiento también es difícil, porque no existen marcadores objetivables que midan la adherencia. En la práctica clínica se utiliza la medición de auto anticuerpos anti-endomisio, tTG y/o PGD; más recientemente se están evaluando las entrevistas por una nutricionista especializada, cuestionarios validados y la medición de péptidos 33-mer en heces como alternativas o complementos de la evaluación de adherencia. En este artículo se revisan las herramientas de seguimiento actualmente utilizadas, poniendo énfasis en aquellas disponibles en Chile.


Coeliac disease (CD) is a systemic autoimmune disorder triggered by gluten consumption in genetically susceptible individuals. It exhibits several clinical features, such as blood auto-antibodies (anti-endomysial antibodies EMA, anti-transglutaminase antibodies tTG, anti-deamidated gliadin peptides PGD), plus variable degrees of damage in the small intestinal mucosa. In Chile, tTG is positive in 0.76% in individuals >15 years, with the prevalence of CD being estimated at 0.6%. Approximately17% of first-degree relatives of coeliac patients have been reported tTG positive. To date, the gluten free diet (GFD) is the only known treatment for CD. To be effective, this must be lifelong, permanent, and strict. Gluten content in the GFD is not zero, but is limited to a cut-off of 3 ppm (or mg/kg of product) in Chile. Mortality higher than that of the general population has been reported among coeliac patients, and poor adherence to GFD is associated with complications (mainly autoimmune processes and cancer). GFD is difficult to maintain strictly and poor adherence is by far the main cause of lack of response to treatment. Follow-up of adherence is also difficult because there are no objective measurements to assess it. In clinical practice determination of serum EMA, tTG and PGD is routinely used for these purposes, although more recently, the interview by an expert dietitian, validated questionnaires and measurement of faecal 33-mer peptide are being assessed as alternatives or complements to measure adherence to GFD. A review is presented with the current concepts on the available tools to follow up patients on GFD, emphasising those available in Chilel.


Asunto(s)
Humanos , Enfermedad Celíaca/dietoterapia , Cooperación del Paciente , Dieta Sin Gluten , Autoanticuerpos/análisis , Enfermedad Celíaca/inmunología , Chile , Encuestas y Cuestionarios , Glútenes/administración & dosificación , Glútenes/efectos adversos
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