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1.
Cell Biol Toxicol ; 40(1): 49, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38922500

RESUMEN

OBJECTIVE: The primary objective of this investigation is to delve into the involvement of the long noncoding RNA (lncRNA) SPACA6P-AS in breast cancer (BC) development, focusing on its expression pattern, association with clinical-pathological features, impact on prognosis, as well as its molecular and immunological implications. METHODS: Bioinformatics analysis was conducted utilizing RNA sequencing data of 1083 BC patients from the TCGA database. Functional exploration of SPACA6P-AS was carried out through the construction of survival curves, GO and KEGG enrichment analysis, and single-sample gene set enrichment analysis (ssGSEA). Furthermore, its functionality was validated through in vitro cell experiments and in vivo nude mouse model experiments. RESULTS: SPACA6P-AS showed a remarkable increase in expression levels in BC tissues (p < 0.001) and demonstrated a close relationship to poor prognosis (overall survival HR = 1.616, progression-free interval HR = 1.40, disease-specific survival HR = 1.54). Enrichment analysis revealed that SPACA6P-AS could impact biological functions such as protease regulation, endopeptidase inhibitor activity, taste receptor activity, taste transduction, and maturity-onset diabetes of the young pathway. ssGSEA analysis indicated a negative correlation between SPACA6P-AS expression and immune cell infiltration like dendritic cells and neutrophils, while a positive correlation was observed with central memory T cells and T helper 2 cells. Results from in vitro and in vivo experiments illustrated that silencing SPACA6P-AS significantly inhibited the proliferation, migration, and invasion capabilities of BC cells. In vitro experiments also highlighted that dendritic cells with silenced SPACA6P-AS exhibited enhanced capabilities in promoting the proliferation of autologous CD3 + T cells and cytokine secretion. These discoveries elucidate the potential multifaceted roles of SPACA6P-AS in BC, including its potential involvement in modulating immune cell infiltration in the tumor microenvironment. CONCLUSION: The high expression of lncRNA SPACA6P-AS in BC is closely linked to poor prognosis and may facilitate tumor progression by influencing specific biological processes, signaling pathways, and the immune microenvironment. The regulatory role of SPACA6P-AS positions it as a prospective biomarker and target for therapeutic approaches for BC diagnosis and intervention.


Asunto(s)
Neoplasias de la Mama , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , ARN Largo no Codificante , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/inmunología , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Femenino , Ratones , Línea Celular Tumoral , Pronóstico , Proliferación Celular/genética , Ratones Endogámicos BALB C , Persona de Mediana Edad , Movimiento Celular/genética , Biología Computacional/métodos
2.
Biomed Chromatogr ; 37(10): e5709, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37533317

RESUMEN

Choulingdan mixture (CLDM) is an empirical clinical prescription for the adjuvant treatment of acute lung injury (ALI). CLDM has been used for almost 30 years in the clinic. However, its mechanism for improving ALI still needs to be investigated. In this study, high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) was applied to characterize the overall chemical composition of CLDM. A total of 93 ingredients were characterized, including 25 flavonoids, 20 organic acids, 11 saponins, nine terpenoids, seven tannins and 21 other compounds. Then network pharmacology was applied to predict the potential bioactive components, target genes and signaling pathways of CLDM in improving ALI. Additionally, molecular docking was performed to demonstrate the interaction between the active ingredients and the disease targets. Finally, animal experiments further confirmed that CLDM significantly inhibits pulmonary inflammation, pulmonary edema and oxidative stress in lipopolysaccharide-induced ALI mice by inhibiting the PI3K-AKT signaling pathway. This study enhanced the amount and accuracy of compounds of CLDM and provided new insights into CLDM preventing and treating ALI.


Asunto(s)
Lesión Pulmonar Aguda , Medicamentos Herbarios Chinos , Animales , Ratones , Cromatografía Líquida de Alta Presión , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Espectrometría de Masas en Tándem , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología
3.
Drug Chem Toxicol ; : 1-12, 2023 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-37434408

RESUMEN

This study employed computational modeling (in silico) methods, combined with ecotoxicological experiments (in vivo) to predict the persistence/biodegradability, bioaccumulation, mobility, and ecological risks of an antihistamine drug (Loratadine: LOR) in the aquatic compartment. To achieve these goals, four endpoints of the LOR were obtained from different open-source computational tools, namely: (i) "STP total removal"; (ii) Predicted ready biodegradability; (iii) Octanol-water partition coefficient (KOW); and (iv) Soil organic adsorption coefficient (KOC). Moreover, acute and chronic, ecotoxicological assays using non-target freshwater organisms of different trophic levels (namely, algae Pseudokirchneriella subcapitata; microcrustaceans Daphnia similis and Ceriodaphnia dubia; and fish Danio rerio), were used to predict the ecological risks of LOR. The main results showed that LOR: (i) is considered persistent (after a weight-of-evidence assessment) and highly resistant to biodegradation; (ii) is hydrophobic (LOG KOW = 5.20), immobile (LOG KOC = 5.63), and thus, it can potentially bioaccumulate and/or can cause numerous deleterious effects in aquatic species; and (iii) after ecotoxicological evaluation is considered "toxic" and/or "highly toxic" to the three trophic levels tested. Moreover, both the ecotoxicological assays and risk assessment (RQ), showed that LOR is more harmful for the crustaceans (RQcrustaceans = moderate to high risks) than for algae and fish. Ultimately, this study reinforces the ecological concern due to the indiscriminate disposal of this antihistamine drug in worldwide aquatic ecosystems.

4.
Molecules ; 28(21)2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37959820

RESUMEN

Venous thromboembolism is a serious problem because it significantly increases the risk of developing vascular complications in elderly patients with obesity or immobilization, cancer, and many other diseases. Thus, there is a need to study new therapeutic strategies, including new medicinal agents for the efficient and safe correction of thrombus disorders. In this work, we have synthesized a number of new amides and peptides of 4-amino-5-oxoprolines and studied their antiplatelet and antithrombotic activity in experiments in vitro and in vivo. It has been found that the newly obtained compounds slow down the process of thrombus formation in a model of arterial and venous thrombosis, without affecting plasma hemostasis parameters. (2S,4S)-4-Amino-1-(4-fluorophenyl)-5-oxoprolyl-(S)-phenylalanine proved to be the most efficient among the studied derivatives. The results obtained indicate the advisability of further studies on 5-oxoproline derivatives in order to design pharmaceutical agents for the prevention and treatment of the consequences of thrombosis.


Asunto(s)
Ácido Pirrolidona Carboxílico , Trombosis , Humanos , Anciano , Ácido Pirrolidona Carboxílico/química , Fibrinolíticos/farmacología , Fibrinolíticos/uso terapéutico , Amidas/farmacología , Trombosis/tratamiento farmacológico , Péptidos/farmacología , Péptidos/uso terapéutico , Inhibidores de Agregación Plaquetaria/química
5.
Zhongguo Zhong Yao Za Zhi ; 48(13): 3576-3588, 2023 Jul.
Artículo en Zh | MEDLINE | ID: mdl-37474991

RESUMEN

Network pharmacology, molecular docking, and in vivo and in vitro experiments were employed to study the molecular mechanism of Blaps rynchopetera Fairmaire in the treatment of non-small cell lung cancer(NSCLC). The components of B. rynchopetera were collected by literature review, and the active components were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). PharmMapper was used to obtain the targets of the active components. The targets of NSCLC were obtained from DrugBank, GeneCards, OMIM, TTD, and PharmGKB. The Venn diagram was drawn to identify the common targets shared by the active components of B. rynchopetera and NSCLC. The "drug component-target" network and protein-protein interaction(PPI) network were constructed by Cytoscape, and the key targets were screened by Centiscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the above key targets were performed by DAVID. AutoDock and PyMOL were used for the molecular docking between the key targets and corresponding active components. A total of 31 active components, 72 potential targets, and 11 key targets of B. rynchopetera against NSCLC were obtained. The active components of B. rynchopetera had good binding activity with key targets. Further, the serum containing B. rynchopetera was prepared and used to culture human lung adenocarcinoma A549 cells. The CCK-8 assay was employed to determine the inhibition rates on the growth of A549 cells in blank control group and those exposed to different concentrations of B. rynchopetera-containing serum, cisplatin, and drug combination(B. rynchopetera-containing serum+cisplatin) for different time periods. The cell migration and invasion of A549 cells were detected by cell scratch assay and Transwell assay, respectively. Western blot was employed to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), caspase-3, cell division cycle 42(CDC42), proto-oncogene tyrosine-protein kinase SRC, and vascular endothelial growth factor(VEGF) in A549 cells. C57BL/6 mice were inoculated with Lewis cells and randomly assigned into a model control group, a B. rynchopetera group, a cisplatin group, and a drug combination(B. rynchopetera+cisplatin) group, with 12 mice per group. The body weight and the long diameter(a) and short diameter(b) of the tumor were monitored every other day during treatment, and the tumor volume(mm~3) was calculated as 0.52ab~2. After 14 days of continuous medication, the mice were sacrificed for the collection of tumor, spleen, and thymus, and the tumor inhibition rate and immune organ indexes were calculated. The tissue morphology of tumors was observed by hematoxylin-eosin(HE) staining, and the positive expression of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF in the tumor tissue was detected by immunohistochemistry. The results indicated that B. rynchopetera and the drug combination regulated the expression levels of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF to inhibit the proliferation, migration, and invasion of A549 cells and Lewis cells, thus playing a role in the treatment of NSCLC via multiple ways.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Medicamentos Herbarios Chinos , Neoplasias Pulmonares , Humanos , Animales , Ratones , Ratones Endogámicos C57BL , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Caspasa 3 , Farmacología en Red , Factor A de Crecimiento Endotelial Vascular , Cisplatino , Simulación del Acoplamiento Molecular , Proteína X Asociada a bcl-2 , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Proliferación Celular , Medicamentos Herbarios Chinos/farmacología , Medicina Tradicional China
6.
Int J Hyperthermia ; 38(1): 1140-1148, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34353206

RESUMEN

PURPOSE: Microwave ablation (MWA) provides an effective treatment of lung and liver tumors but suffers from a lack of reproducibility of ablation size among currently available technologies. In-vitro evaluations are far removed from clinical practices because of uninfused tissue. This study is in-vivo preclinical testing of a new MWA system on swine lungs and liver. MATERIALS AND METHODS: All ablations were performed under CT guidance and multiple algorithms were tested with a power of 50, 75, and 100 W for durations of 3, 5, 8, 10, and 15 min. A 3 D-evaluation of the ablation zone was carried out using enhanced-CT. The sphericity index, coefficients of variation, and energy efficiency (which corresponds to the volume yield according to the power supplied) were calculated. RESULTS: Fifty liver and 48 lung ablations were performed in 17 swine. The sphericity index varies from 0.50 to 0.80 for liver ablations and from 0.40 to 0.69 for lung ablations. The coefficient of variation was below 15% for 4/5 and 4/8 protocols for lung and liver ablations, respectively. The energy efficiency seems to decrease with the duration of the ablation from 0.60 × 10-3 cm3/J (75 W, 3 min) to 0.26 × 10-3 cm3/J (100 W, 15 min) in the liver and from 0.57 × 10-3 cm3/J (50 W, 10 min) to 0.42 × 10-3 cm3/J (100 W, 12 min) in the lungs. CONCLUSION: A shorter treatment time provides the best energy efficiency, and the best reproducibility is obtained for a 10 min treatment duration. The system tested provides an interesting reproducibility in both lung and liver measurements. Our results may help interventional radiologists in the optimal selection of treatment parameters.


Asunto(s)
Técnicas de Ablación , Ablación por Catéter , Animales , Humanos , Hígado/diagnóstico por imagen , Hígado/cirugía , Pulmón/diagnóstico por imagen , Pulmón/cirugía , Microondas , Reproducibilidad de los Resultados , Porcinos , Tomografía Computarizada por Rayos X
7.
Sensors (Basel) ; 21(20)2021 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-34696147

RESUMEN

Thermal ablation is an acceptable alternative treatment for primary liver cancer, of which laser ablation (LA) is one of the least invasive approaches, especially for tumors in high-risk locations. Precise control of the LA effect is required to safely destroy the tumor. Although temperature imaging techniques provide an indirect measurement of the thermal damage, a degree of uncertainty remains about the treatment effect. Optical techniques are currently emerging as tools to directly assess tissue thermal damage. Among them, hyperspectral imaging (HSI) has shown promising results in image-guided surgery and in the thermal ablation field. The highly informative data provided by HSI, associated with deep learning, enable the implementation of non-invasive prediction models to be used intraoperatively. Here we show a novel paradigm "peak temperature prediction model" (PTPM), convolutional neural network (CNN)-based, trained with HSI and infrared imaging to predict LA-induced damage in the liver. The PTPM demonstrated an optimal agreement with tissue damage classification providing a consistent threshold (50.6 ± 1.5 °C) for the damage margins with high accuracy (~0.90). The high correlation with the histology score (r = 0.9085) and the comparison with the measured peak temperature confirmed that PTPM preserves temperature information accordingly with the histopathological assessment.


Asunto(s)
Aprendizaje Profundo , Terapia por Láser , Imágenes Hiperespectrales , Rayos Láser , Redes Neurales de la Computación
8.
Int J Mol Sci ; 22(14)2021 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-34298912

RESUMEN

The central nervous system (CNS) consists of a heterogeneous population of cells with highly specialized functions. For optimal functioning of the CNS, in disease and in health, intricate communication between these cells is vital. One important mechanism of cellular communication is the release and uptake of extracellular vesicles (EVs). EVs are membrane enclosed particles actively released by cells, containing a wide array of proteins, lipids, RNA, and DNA. These EVs can be taken up by neighboring or distant cells, and influence a wide range of processes. Due to the complexity and relative inaccessibility of the CNS, our current understanding of the role of EVs is mainly derived in vitro work. However, recently new methods and techniques have opened the ability to study the role of EVs in the CNS in vivo. In this review, we discuss the current developments in our understanding of the role of EVs in the CNS in vivo.


Asunto(s)
Sistema Nervioso Central/metabolismo , Vesículas Extracelulares/metabolismo , Animales , Comunicación Celular/fisiología , Humanos
9.
Chemistry ; 26(10): 2211-2221, 2020 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-31560142

RESUMEN

The synthesis, characterization and biological activity of molybdenum(IV) complexes containing Trofimenko's scorpionato ligand, hydrotris(3-isopropylpyrazolyl)borate (TpiPr ), in addition to varying biologically active as well as other conventional ligands is described. Ligands employed include (O,O-) (S,O-) (N,N-) donors that have been successfully coordinated to the molybdenum center by means of oxygen-atom transfer (OAT) reactions from the known MoVI starting material, TpiPr MoO2 Cl. The synthesized complexes were characterized by standard analytical methods and where possible by X-ray diffraction analysis. The aqueous stability of the compounds was studied by means of UV/Vis spectroscopy and the impact of the attached ligand scaffolds on the oxidation potentials (MoIV to MoV ) was studied by cyclic voltammetry. Utilizing polyvinylpyrrolidone (PVP) as a solubilizing agent, adequate aqueous solubility for biological tests was obtained. Anticancer activity tests and preliminary mode of action studies have been performed in vitro and in vivo.


Asunto(s)
Antineoplásicos/química , Boratos/química , Complejos de Coordinación/química , Molibdeno/química , Pirazoles/química , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Quelantes/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/uso terapéutico , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Estabilidad de Medicamentos , Humanos , Ligandos , Ratones , Ratones Endogámicos BALB C , Conformación Molecular , Neoplasias/tratamiento farmacológico , Nitrógeno/química , Oxígeno/química , Azufre/química
10.
Int J Hyperthermia ; 37(1): 879-886, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32689829

RESUMEN

PURPOSE: To evaluate microwave ablation (MWA) algorithms, comparing pulsed and continuous mode in an in vivo lung tumor mimic model. MATERIALS AND METHODS: A total of 43 lung tumor-mimic models of 1, 2 or 3 cm were created in 11 pigs through an intra-pulmonary injection of contrast-enriched minced muscle. Tumors were ablated under fluoroscopic and 3D-CBCT-guidance using a single microwave antenna. Continuous (CM) and pulsed mode (PM) were used. According to tumor size, 3 different algorithms for both continuous and pulsed mode were used. The ablation zones were measured using post-procedural 3D-CBCT and on pathologic specimens. RESULTS: Two radiologists measured the ablation zones on CBCT and they significantly correlated with macroscopic and microscopic pathological findings: r = 0.75 and 0.74 respectively (p < 0.0001) (inter-observer correlation r = 0.9). For 1, 2 and 3 cm tumors mimics lesions (TMLs), mean maximal and transverse ablation diameters were 3.6 [Formula: see text] 0.3 × 2.2 [Formula: see text] 0.3 cm; 4.1 [Formula: see text] 0.5 × 2.6 [Formula: see text] 0.3 cm and 4.8 [Formula: see text] 0.3 × 3.2 [Formula: see text] 0.3 cm respectively using CM; And, 3.0 [Formula: see text] 0.2 × 2.1 [Formula: see text] 0.2 cm; 4.0 [Formula: see text] 0.4 × 2.7 [Formula: see text] 0.4 cm and 4.6 [Formula: see text] 0.4 × 3.2 [Formula: see text] 0.4 cm respectively for PM, without any significant difference except for 1 cm TMLs treated by PM ablation which were significantly smaller (p = 0.009) The sphericity index was 1.6, 1.6, 1.5 and 1.4, 1.5, 1.4 at 1, 2 and 3 cm for CM and PM respectively, p = 0.07, 0.14 and 0.13 for 1, 2 and 3 cm tumors mimics. CONCLUSION: Microwave ablation for 1-3 cm lung tumors were successfully realized but with a moderate reproducibility rate, using either CM or PM. Immediate post ablation CBCT can accurately evaluate ablation zones.


Asunto(s)
Neoplasias Pulmonares , Ablación por Radiofrecuencia , Animales , Pulmón/diagnóstico por imagen , Pulmón/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Microondas , Reproducibilidad de los Resultados , Porcinos
11.
Molecules ; 24(5)2019 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-30832453

RESUMEN

3,4-dihydropyrimidin-2(1H)-one compounds (DHPMs) possess extensive biological activities and are mainly prepared via Biginelli reaction and N-alkylation. In the present study, selective alkylation of N¹ was investigated by using tetrabutylammonium hydroxide. In vitro cytotoxicity study on all synthesized compounds demonstrated that introduction of the aryl chain in the R³ as well as the low electron-donating group in the R¹ of DHPMs contributed to the anti-proliferative potency. A larger value of the partition coefficient (Log P) and suitable polar surface area (PSA) values were both found to be important in order to maintain the antitumor activity. The results from in vivo study indicated the great potential of compound 3d to serve as a lead compound for novel anti-tumor drugs to treat glioma. Pharmacophore study regarding the structure-activity relations of DHPMs were also conducted. Our results here could provide a guide for the design of novel bioactive 3,4-dihydropyrimidin-2(1H)-one compounds.


Asunto(s)
Antineoplásicos/farmacología , Glioma/tratamiento farmacológico , Pirimidinonas/farmacología , Alquilación , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Catálisis , Línea Celular Tumoral , Glioma/patología , Humanos , Ratones , Pirimidinonas/síntesis química , Pirimidinonas/química , Solventes/química , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de Xenoinjerto
12.
World J Microbiol Biotechnol ; 35(6): 85, 2019 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-31134456

RESUMEN

Surface properties like hydrophobicity, aggregation ability, adhesion to mucosal surfaces and epithelial cells and transit time are key features for the characterization of probiotic strains. In this study, we used two Lactobacillus paracasei subsp. paracasei strains (BGNJ1-64 and BGSJ2-8) strains which were previously described with very strong aggregation capacity. The aggregation promoting factor (AggLb) expressed in these strains showed high level of binding to collagen and fibronectin, components of extracellular matrix. The working hypothesis was that strains able to aggregate have an advantage to resist in intestinal tract. So, we assessed whether these strains and their derivatives (without aggLb gene) are able to bind or not to intestinal components and we compared the transit time of each strains in mice. In that purpose parental strains (BGNJ1-64 and BGSJ2-8) and their aggregation negative derivatives (BGNJ1-641 and BGSJ2-83) were marked with double antibiotic resistance in order to be tracked in in vivo experiments in mice. Comparative analysis of binding ability of WT and aggregation negative strains to different human intestinal cell lines and mucin revealed no significant difference among them, excluding involvement of AggLb in interaction with surface of intestinal cells and mucin. In vivo experiments showed that surviving and transit time of marked strains in mice did not drastically depend on the presence of the AggLb aggregation factor.


Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Células Epiteliales/microbiología , Intestinos/microbiología , Lacticaseibacillus paracasei/crecimiento & desarrollo , Lacticaseibacillus paracasei/fisiología , Unión Proteica , Animales , Adhesión Bacteriana/fisiología , Células CACO-2 , Moléculas de Adhesión Celular/fisiología , Colágeno/metabolismo , Fibronectinas/metabolismo , Células HT29 , Interacciones Microbiota-Huesped/fisiología , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Masculino , Ratones , Ratones Endogámicos C57BL , Mucinas/metabolismo , Probióticos , Análisis de la Onda del Pulso , Propiedades de Superficie
13.
J Clin Lab Anal ; 32(3)2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28703321

RESUMEN

PURPOSE: This study was aimed to investigate the relationship between miR-211-5p and SOX11, and the effects of their interaction on the proliferation, viability, and invasion of human thyroid cancer (TC) cells. METHODS: We used quantitative real-time PCR (qRT-PCR) to determine the expression of miR-211-5p and SOX11mRNA in the thyroid tumorous and the adjacent tissues. The target relationship between miR-211-5p and SOX11 was confirmed using dual luciferase reporter gene assay. Flow cytometry, colony formation assay, Transwell assay, and MTT assay were performed to determine the cell-cycle progression, cell apoptosis, proliferation and invasion, respectively. In addition, the tumor formation assay in nude mice was done to assess the effect of miR-211-5p on TC development in vivo. RESULTS: MiR-211-5p was underexpressed, whereas SOX11 was overexpressed in TC. The overexpression of miR-211-5p inhibited the expression of SOX11. The cell cycle was arrested and the proliferation as well as invasiveness was suppressed by exogenous miR-211-5p in TC cell line. The antitumor role of miR-211-5p was proved by the animal experiment. CONCLUSION: MiR-211-5p affected the viability, proliferation and invasion of TC by negatively regulating SOX11 expression.


Asunto(s)
Movimiento Celular/genética , Proliferación Celular/genética , MicroARNs/genética , Factores de Transcripción SOXC/genética , Neoplasias de la Tiroides/genética , Animales , Regulación hacia Abajo/genética , Humanos , Ratones , Ratones Desnudos , MicroARNs/metabolismo , Invasividad Neoplásica/genética , Reproducibilidad de los Resultados , Factores de Transcripción SOXC/metabolismo , Glándula Tiroides/química , Glándula Tiroides/metabolismo , Neoplasias de la Tiroides/química , Neoplasias de la Tiroides/metabolismo
14.
Br J Nutr ; 118(3): 169-178, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28831956

RESUMEN

Two types of diet - standard and atherogenic - were used to study the effect of wheat or wheat-rye breads supplemented with 20 % acid whey concentrate after ultrafiltration on the physiological response of growing rats. The acid whey concentrate after ultrafiltration used in rat diets caused reduced weight gain (for atherogenic diet with wheat bread); growth of caecum tissue and digesta weight; a decrease in the pH of caecum digesta (for atherogenic diet); reduced activity of bacterial glycolytic enzymes; and a significant increase in total SCFA for both types of diet with wheat-rye breads containing acid whey concentrate. For wheat bread with acid whey, in standard diet, a statistically significant increase was found in the population of bifidobacteria. The results showed that the acid whey concentrates could be used as a valuable food ingredient.


Asunto(s)
Pan/análisis , Ciego/metabolismo , Alimentos Fortificados , Suero Lácteo/química , Animales , Bifidobacterium/metabolismo , Peso Corporal , Ciego/microbiología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Recuento de Colonia Microbiana , Dieta Aterogénica , Dieta Alta en Grasa , Ácidos Grasos Volátiles/metabolismo , Fermentación , Microbioma Gastrointestinal , Masculino , Modelos Animales , Ratas , Ratas Wistar , Secale/química , Triglicéridos/sangre , Triticum/química
15.
Nanomedicine ; 11(2): 263-73, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25461293

RESUMEN

The present study deals with the preparation of albumin nanocapsules containing fenretinide and their evaluation in experimental models of human non-small cell lung cancer. These nanocapsules showed enhanced antitumor activity with respect to free fenretinide due to the solubilization effect of albumin on the hydrophobic drug, known to improve bioavailability. The high expression of caveolin-1 on the A549 cell surface further enhanced the antitumor activity of the nanoencapsulated fenretinide. Caveolin-1 favored albumin uptake and improved the efficacy of the fenretinide-loaded albumin nanocapsules, especially in 3-D cultures where the densely packed 3-D structures impaired drug diffusibility and severely reduced the activity of the free drug. The efficacy of the fenretinide albumin nanocapsules was further confirmed in tumor xenograft models of A549 by the significant delay in tumor progression observed with respect to control after intravenous administration of the novel formulation. FROM THE CLINICAL EDITOR: This study describes the preparation of fenretinide containing albumin nanocapsules and their evaluation in experimental models of non-small cell lung cancer, showing enhanced antitumor activity compared to free fenretinide.


Asunto(s)
Antineoplásicos/química , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Fenretinida/administración & dosificación , Nanocápsulas/administración & dosificación , Albúminas/administración & dosificación , Albúminas/química , Animales , Antineoplásicos/administración & dosificación , Disponibilidad Biológica , Línea Celular Tumoral , Humanos , Ratones , Nanocápsulas/química , Ensayos Antitumor por Modelo de Xenoinjerto
16.
J Microencapsul ; 31(5): 440-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24738486

RESUMEN

The cross-linking reaction in w/o emulsions of dextran (DEX) functionalised with methacrylic groups, having or not acid residues in side chain, can be used to easily prepare polysaccharide hydrogel microspheres with properties suitable for drug delivery applications. The formation of a chemical network within the obtained particles was evaluated with FT-IR spectroscopy, whereas morphology and dimensions of the microspheres were investigated with optical and scanning electron microscopy. At the same time, swelling measurements were carried out on freeze-dried particles in different aqueous media simulating biological fluids. Preliminary release experiments performed with ibuprofen, betamethasone and vitamin B12 chosen as model drugs, showed that these microspheres could be suitable as modified drug delivery systems in oral formulations. Finally, in vivo writhing experiments were carried out in mice in order to verify the antinociceptive activity of betamethasone loaded into the new polysaccharide hydrogel microspheres.


Asunto(s)
Analgésicos/administración & dosificación , Antiinflamatorios/administración & dosificación , Betametasona/administración & dosificación , Dextranos/química , Portadores de Fármacos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Analgésicos/farmacología , Animales , Antiinflamatorios/farmacología , Betametasona/farmacología , Emulsiones/química , Masculino , Ratones , Microesferas , Espectroscopía Infrarroja por Transformada de Fourier
17.
Int J Biol Macromol ; 261(Pt 1): 129478, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38237822

RESUMEN

Shigella flexneri is a prevalent foodborne and waterborne pathogen that threatens human health. Our previous research indicated that the Lactiplantibacillus plantarum Y12 exopolysaccharide (L-EPS) potentially inhibited the pathogenicity of S. flexneri. The in vitro results of this study demonstrated that L-EPS effectively mitigated the symptoms induced by S. flexneri in HT-29 cells, including inhibited gene expression levels of IL-1ß, IL-6, IL-8, TNF-α, TLR 2/4, and NOD1/2; decreased apoptosis ratio; and alleviated damage degree of intestinal barrier function (Zona occludens 1, Occludin, and Claudin-1). The in vivo results demonstrated that S. flexneri treated with L-EPS elicited mild adverse physiological manifestations, an inflammatory response, and tissue damage. The infection of S. flexneri caused significant alterations in the abundance of phylum (Firmicutes, Bacteroidota, Actinobacteriota, and Proteobacteria), family (Lachnospiraceae, Muribaculaceae, Rikenellaceae, Prevotellaceaea, Ruminococcaceae, and Lactobaillaceae), and genus (Escherichia Shigella and Lachnospirillaceae NK4A136 group) within the cecal microbiota. These changes were accompanied by perturbations in taurine and hypotaurine metabolism, tricarboxylic acid (TCA) cycle activity, arginine biosynthesis, and histidine metabolic pathways. However, intervention with L-EPS attenuated the dysbiosis of cecal microbiota and metabolic disturbances. In summary, our research suggested a potential application of L-EPS as a functional food additive for mitigating S. flexneri infection.


Asunto(s)
Shigella flexneri , Humanos , Virulencia , Células HT29 , Transporte Biológico
18.
Adv Mater ; : e2403038, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724029

RESUMEN

Perovskite solar cells (PSCs) are developed rapidly in efficiency and stability in recent years, which can compete with silicon solar cells. However, an important obstacle to the commercialization of PSCs is the toxicity of lead ions (Pb2+) from water-soluble perovskites. The entry of free Pb2+ into organisms can cause severe harm to humans, such as blood lead poisoning, organ failure, etc. Therefore, this work reports a "lead isolation-capture" dual detoxification strategy with calcium disodium edetate (EDTA Na-Ca), which can inhibit lead leakage from PSCs under extreme conditions. More importantly, leaked lead exists in a nontoxic aggregation state chelated by EDTA. For the first time, in vivo experiments are conducted in mice to systematically prove that this material has a significant inhibitory effect on the toxicity of perovskites. In addition, this strategy can further enhance device performance, enabling the optimized devices to achieve an impressive power conversion efficiency (PCE) of 25.19%. This innovative strategy is a major breakthrough in the research on the prevention of lead toxicity in PSCs.

19.
Artif Organs ; 37(11): 954-7, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24251773

RESUMEN

The Spiral Pump (SP), a centrifugal blood pump for cardiopulmonary bypass (CPB), has been developed at the Dante Pazzanese Institute of Cardiology/Adib Jatene Foundation laboratories, with support from Sintegra Company (Pompeia, Brazil). The SP is a disposable pump with an internal rotor-a conically shaped fuse with double entrance threads. This rotor is supported by two ball bearings, attached to a stainless steel shaft fixed to the housing base. Worm gears provide axial motion to the blood column, and the rotational motion of the conically shaped impeller generates a centrifugal pumping effect, improving pump efficiency without increasing hemolysis. In vitro tests were performed to evaluate the SP's hydrodynamic performance, and in vivo experiments were performed to evaluate hemodynamic impact during usual CPB. A commercially available centrifugal blood pump was used as reference. In vivo experiments were conducted in six male pigs weighing between 60 and 90 kg, placed on CPB for 6 h each. Blood samples were collected just before CPB (T0) and after every hour of CPB (T1-T6) for hemolysis determination and laboratory tests (hematological and biochemical). Values of blood pressure, mean flow, pump rotational speed, and corporeal temperature were recorded. Also, ergonomic conditions were recorded: presence of noise, difficulty in removing air bubbles, trouble in installing the pump in the drive module (console), and difficulties in mounting the CPB circuit. Comparing the laboratory and hemolysis results for the SP with those of the reference pump, we can conclude that there is no significant difference between the two devices. In addition, reports made by medical staff and perfusionists described a close similarity between the two devices. During in vivo experiments, the SP maintained blood flow and pressure at physiological levels, consistent with those applied in cardiac surgery with CPB, without presenting any malfunction. Also, the SP needed lower rotational speed to obtain average blood flow and pressure, compared with the reference pump.


Asunto(s)
Circulación Asistida/instrumentación , Puente Cardiopulmonar/instrumentación , Animales , Circulación Asistida/efectos adversos , Puente Cardiopulmonar/efectos adversos , Diseño de Equipo , Hemólisis , Hidrodinámica , Masculino , Porcinos
20.
Mar Pollut Bull ; 190: 114812, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36933356

RESUMEN

Plastic litter containing additives is potentially a major source of chemical contamination in remote areas. We investigated polybrominated diphenyl ethers (PBDEs) and microplastics in crustaceans and sand from beaches with high and low litter volumes on remote islands that were relatively free of other anthropogenic contaminants. Significant numbers of microplastics in the digestive tracts, and sporadically higher concentrations of rare congeners of PBDEs in the hepatopancreases were observed in coenobitid hermit crabs from the polluted beaches than in those from the control beaches. PBDEs and microplastics were detected in high amounts in one contaminated beach sand sample, but not in other beaches. Using BDE209 exposure experiments, similar debrominated products of BDE209 in field samples were detected in the hermit crabs. The results showed that when hermit crabs ingest microplastics containing BDE209, BDE209 leaches out and migrates to other tissues where it is metabolized.


Asunto(s)
Anomuros , Contaminantes Químicos del Agua , Animales , Éteres Difenilos Halogenados/análisis , Anomuros/metabolismo , Bioacumulación , Arena , Microplásticos , Plásticos/metabolismo , Contaminantes Químicos del Agua/análisis
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