Delivery of SIRT1 by cancer-associated adipocyte-derived extracellular vesicles regulates immune response and tumorigenesis of ovarian cancer cells

Purpose This study intends to investigate the possible molecular mechanism of immune response and tumorigenesis in ovarian cancer cells, mediated by sirtuin 1 (SIRT1)-containing extracellular vesicles (EVs) derived from cancer-associated adipocytes (CAAs) (CAA-EVs). Methods Differentially expressed genes in EVs from CAAs were screened by RNA transcriptome sequencing, and the downstream pathway was predicted in silico. The binding between SIRT1 and CD24 was investigated by luciferase activity and ChIP-PCR assays. EVs were extracted from human ovarian cancer tissue-isolated CAAs, and the internalization of CCA-EVs by ovarian cancer cells was characterized. The ovarian cancer cell line was injected into mice to establish an animal model. Flow cytometry was performed to analyze the proportions of M1 and M2 macrophages, CD8+ T, T-reg, and CD4+ T cells. TUNEL staining was used to detect cell apoptosis in the mouse tumor tissues. ELISA detection was performed on immune-related factors in the serum of mice. Results CAA-EVs could deliver SIRT1 to ovarian cancer cells, thereby affecting the immune response of ovarian cancer cells in vitro and promoting tumorigenesis in vivo. SIRT1 could transcriptionally activate the expression of CD24, and CD24 could up-regulate Siglec-10 expression. CAA-EVs-SIRT1 activated the CD24/Siglec-10 axis and promoted CD8+ T cell apoptosis, thereby promoting tumorigenesis in mice. Conclusion CAA-EVs-mediated transfer of SIRT1 regulates the CD24/Siglec-10 axis to curb immune response and promote tumorigenesis of ovarian cancer cells (AU)

Formulation and evaluation of baclofen liposome vesicles using lecithin / Formulación y evaluación de vesículas de liposomas de baclofeno usando lecitina

INTRODUCTION: The main aim of present study was to prepare and characterize liposomal formulation of baclofen to improve the effectiveness of the topically applied formulation. METHOD: For the preparation of liposomes, different ratio of lecithin, cholesterol and ethanol were taken but ratio of drug and stearic acid were kept constant and prepared by ethanol injection method. Liposomes were characterized for vesicle size, vesicle shape, entrapment efficiency, in vitro studies, stability studies and in vivo studies. RESULTS: The average particle size of formulated liposome was in the range of 3.98 ± 0.45-4.24 ± 0.65 mim and small unilamellar vesicles with spherical in shape observed. Entrapment efficiency of optimized formulation was 58.67 ± 0.81 %. The maximum % cumulative drug release behaviours were 67.66 ± 5.32 % after 10 h. formulation stored in 4 ± 2 °C temperature shows better stability (64.19 ± 0.26) compared to elevated temperature. Swiss albino mice were used for the in vivo study and exhibit muscle relaxant activity in terms of no. of falls from rota rod apparatus (p value = 0.001). CONCLUSIONS: Baclofen loaded liposomal formulation have shown skeletal muscle relaxant activity in mice suggesting delivery of baclofen from liposomes in the therapeutic range

INTRODUCTION: the use of specific rules to correctly identify ingredients used in cosmetics was essential for their control. This paper analyses the complex process to adapt the INCI terminology between the 1960s and the 1990s. METHOD: analysis of the legislation published in Spain on the control of cosmetic products between the 1940s and the 1990s, focusing on cosmetic's registers and terminologies and nomenclatures used to identify their ingredients. Printed Primary sources, and periodical press have also been consulted. Primary sources have been discussed and contextualized with the help of more recent history of science publications. Results and CONCLUSIONS: The adoption of precise cosmetic nomenclature or terminology was required by health authorities registering these products, as well as for the labelling to inform consumer. The sanitary regulation of cosmetic products was very lax until the development of this industry and its market in Spain in the 1960s. The consolidation of the dermopharmaceutical sector occurred in the 1970s, in part due to the efforts of various pharmaceutical sectors. The gradual introduction of international cosmetic nomenclatures culminated in the 1990s with the official introduction of the INCI terminology in Spain

Decisiones razonables y razonadas sobre medicamentos convencionales y de uso tradicional. El Seguimiento Farmacoterapéutico, integrador de la perspectiva del paciente / Reasonable and reasoned decisions linked to conventional and traditional medicines. Pharmaceutical care practice as the integrator of patient’s perspective

Se presenta un caso de una paciente con síndrome metabólico y comorbilidades asociadas que acude a un consultorio farmacéutico del nivel primario de Atención en Salud en Bogotá (Colombia), donde recibe seguimiento farmacoterapéutico. La paciente usa tratamientos prescritos por sus médicos y se automedica con productos naturales, como son el extracto de balsamina para regular niveles de glucosa, el extracto de arándano azul europeo para problemas oculares y el uso de lecitina de soja para control de triglicéridos. Para la evaluación de la farmacoterapia, se localizó evidencia científica sobre el uso y conveniencia de cada producto en el tratamiento de sus problemas de salud, realizándose las siguientes intervenciones: continuar con la toma de la balsamina, el Bilberry y la lecitina de soja, ya que existen reportes de su utilidad como coadyuvantes en el control de las enfermedades que presenta y la elaboración de un plan de medicación para reforzar la adherencia a los tratamientos. Cuando se evalúan las intervenciones, encontramos que las cifras de glicemia, presión arterial y función hepática se encuentran dentro de objetivos terapéuticos. En este caso, el químico farmacéutico tiene una labor integradora de las terapias de los pacientes, basados en la valoración del riesgo-beneficio y a través del seguimiento farmacoterapéutico obtiene información clínica que permite tomar decisiones sustentadas para el futuro, más aún en el contexto de Latinoamérica, donde los productos naturales son ampliamente usados en la población

It is set out a case of a patient with metabolic syndrome and associated comorbidities. This patient goes to a Colombian primary care pharmacy service, where Pharmaceutical Care is offered to her. The patient uses medicines prescribed by her General Practitioner and natural products supported by popular knowledge, like bitter melon extract to control glucose levels, blueberry extract for ocular diseases and soy lecithin to control the triglycerides levels. During the pharmacotherapy assessment, it is done a clinical evidence search based on the use and convenience of each health product according to her clinical conditions. The results led to the following interventions: on the one hand, the continuation of the use of bitter melon, blueberry and soy lecithin, sustained in evidence of its use as coadjutant in the control of her diseases. On the other hand, it is designed a medication plan to reinforce the patient’s adherence to medical treatment. When interventions are evaluated, the blood glucose, blood pressure and hepatic functionality levels achieve the therapeutic targets. Therefore, Pharmacist can perform an integration role in patient’s therapies based on risk-benefit analysis. Furthermore, through Pharmaceutical Care, can be obtained clinical information that helps to make supported decisions for the future, especially in the Latin American context, where natural products are widely used by the population

LCAT cholesterol esterification is associated with the increase of ApoE/ApoA-I ratio during atherosclerosis progression in rabbit

Apolipoprotein A-I and Apolipoprotein E promote different steps of reverse cholesterol transport, including lecithin-cholesterol acyltransferase stimulation. Our aim was to study the changes in the levels of Apolipoprotein A-I, Apolipoprotein E, and lecithin-cholesterol acyltransferase activity during atherosclerosis progression in rabbits. Quantitative echocardiographic parameters were analyzed in order to evaluate, for the first time, whether atherosclerosis progression in rabbit is associated to apolipoproteins changes and alteration of indices of cardiac function, such as systolic strain and strain rate of the left ventricle. Atherosclerosis was induced by feeding rabbits for 8 weeks with 2 % cholesterol diet. The HDL levels of cholesterol and cholesteryl esters were measured by HPLC. The lecithin-cholesterol acyltransferase activity was evaluated both ex vivo, as cholesteryl esters/cholesterol molar ratio, and in vitro. Apolipoproteins levels were analyzed by ELISA. The HDL levels of cholesterol and cholesteryl esters increased, during treatment, up to 3.7- and 2.5-fold, respectively, compared to control animals. The lecithin-cholesterol acyltransferase activity in vitro was halved after 4 weeks. During cholesterol treatment, Apolipoprotein A-I level significantly decreased, whereas Apolipoprotein E concentration markedly increased. The molar ratio Apolipoprotein E/Apolipoprotein A-I was negatively correlated with the enzyme activity, and positively correlated with both increases in the intima-media thickness of common carotid wall and cardiac dysfunction signs, such as systolic strain and strain rate of the left ventricle (AU)

The homeostatic properties of the mannose receptor in health and disease

El estudio de la especificidad y distribución anatómica del Receptor de la Manosa (MR) y la caracterización fenotípica de ratones deficientes en el MR han permitido discernir la función de este receptor en condiciones fisiológicas normales y patológicas. En esta revisión se considera la biología del MR en tres contextos diferentes: A nivel molecular como miembro de la familia de receptores de manosa; como receptor de macrófagos y células dendríticas; y como un marcador de vasos linfáticos. Resultados recientes en estas tres áreas resaltan las propiedades únicas de este receptor y la necesidad de mantenerla mente abierta a la hora de establecer su función fisiológica (AU)

Research into the binding properties and anatomical distribution of the Mannose Receptor (MR), and the phenotypic characterization of MR deficient animals have provided highly valuable information regarding the role of the MR in health and disease. In this review, the biology of MR is considered in three different contexts: At the molecular level as a member of the mannose receptor family of proteins; as a macrophage and dendritic cell receptor; and as marker of lymphatic endothelia. Novel observations in these three areas highlight the unique properties of MR and the need to keep an open mind when assessing its physiological role (AU)