Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 85
Filtrar
Más filtros

Intervalo de año de publicación
1.
J Am Chem Soc ; 146(11): 7159-7164, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38467030

RESUMEN

Here, we report the synthesis of BCN-93, a meltable, functionalized, and permanently porous metal-organic polyhedron (MOP) and its subsequent transformation into amorphous or crystalline, shaped, self-standing, transparent porous films via melting and subsequent cooling. The synthesis entails the outer functionalization of a MOP with meltable polymer chains: in our model case, we functionalized a Rh(II)-based cuboctahedral MOP with poly(ethylene glycol). Finally, we demonstrate that once melted, BCN-93 can serve as a porous matrix into which other materials or molecules can be dispersed to form mixed-matrix composites. To illustrate this, we combined BCN-93 with one of various additives (either two MOF crystals, a porous cage, or a linear polymer) to generate a series of mixed-matrix films, each of which exhibited greater CO2 uptake relative to the parent film.

2.
Ann Surg Oncol ; 30(12): 7236-7239, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37626252

RESUMEN

INTRODUCTION: After extensive small and colon resections, quality of life can be affected. We propose the antiperistaltic transverse coloplasty as a solution that allows for preservation of the transverse colon after both right and left colectomies while achieving a tension-free colorectal anastomosis slowing the transit and increasing the absorption time, resulting in better stool consistency and quality of life compared with an ileorectal anastomosis. METHODS: This technique was performed in a 41-year-old woman with Goblet cell adenocarcinoma of the appendix with peritoneal metastasis. The transverse colon is rotated anticlockwise over the axis of the middle colic vessels toward the left parietocolic flank and relocated to the usual position of the descending colon. RESULTS: After 1 year of follow-up, the patient led a normal life without parenteral nutrition with five bowel movements per day and a weight gain of 15%. CONCLUSIONS: The use of an antiperistaltic transverse coloplasty may be worthwhile to perform in cases of extensive bowel resections during cytoreductive surgery leading to short-bowel syndrome to avoid a permanent stoma or intestinal failure and improve patient outcomes.


Asunto(s)
Neoplasias Colorrectales , Insuficiencia Intestinal , Femenino , Humanos , Adulto , Colon/cirugía , Antidiarreicos , Calidad de Vida , Colectomía/métodos , Anastomosis Quirúrgica/métodos , Neoplasias Colorrectales/cirugía , Resultado del Tratamiento
3.
Environ Geochem Health ; 45(12): 9891-9901, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37882916

RESUMEN

Exposure to heavy metals may cause the overproduction of reactive oxygen species, generating oxidative stress and consequently, various harms to human health. The soil surrounding the Ventanas Industrial Complex, in Puchuncaví and Quintero municipal districts on the central Chilean coast, contains heavy metal concentrations (As, Cu, Pb, Zn, among others) that far exceed the maximum permissible levels established by Italian soil standards (used as a reference). This study aimed to investigate the potential association between heavy metal exposure in humans and the levels of oxidative stress biomarkers in inhabitants of these locations. We took blood samples from 140 adults living in sites with high concentrations of heavy metals in the soil and compared them with blood samples from 140 adults living in areas with normal heavy metal concentrations. We assessed lipid peroxidation, damage to genetic material, and Total Antioxidant Capacity in these blood samples. Our results indicate an association between oxidative damage and heavy metal exposure, where the inhabitants living in exposed areas have a higher level of DNA damage compared with those living in control areas. Given that DNA damage is one of the main factors in carcinogenesis, these results are of interest, both for public health and for public policies aimed at limiting human exposure to environmental pollution.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Adulto , Humanos , Chile , Monitoreo del Ambiente/métodos , Metales Pesados/toxicidad , Metales Pesados/análisis , Estrés Oxidativo , Suelo , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Medición de Riesgo , China
4.
Addict Biol ; 27(5): e13223, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36001424

RESUMEN

The use of areca nuts (areca) in the form of betel quids constitutes the fourth most common addiction in the world, associated with high risk for oral disease and cancer. Areca is a complex natural product, making it difficult to identify specific components associated with the addictive and carcinogenic properties. It is commonly believed that the muscarinic agonist arecoline is at the core of the addiction. However, muscarinic receptor activation is not generally believed to support drug-taking behaviour. Subjective accounts of areca use include descriptions of both sedative and stimulatory effects, consistent with the presence of multiple psychoactive agents. We have previously reported partial agonism of α4-containing nicotinic acetylcholine receptors by arecoline and subsequent inhibition of those receptors by whole areca broth. In the present study, we report the inhibition of nicotinic acetylcholine receptors and other types of neurotransmitter receptors with compounds of high molecular weight in areca and the ability of low molecular weight areca extract to activate GABA and glutamate receptors. We confirm the presence of a high concentration of GABA and glutamate in areca. Additionally, data also indicate the presence of a dopamine and serotonin transporter blocking activity in areca that could account for the reported stimulant and antidepressant activity. Our data suggest that toxic elements of high molecular weight may contribute to the oral health liability of betel quid use, while two distinct low molecular weight components may provide elements of reward, and the nicotinic activity of arecoline contributes to the physical dependence of addiction.


Asunto(s)
Conducta Adictiva , Receptores Nicotínicos , Areca , Arecolina/farmacología , Ácido gamma-Aminobutírico
5.
Public Health Nutr ; : 1-7, 2022 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-35356855

RESUMEN

OBJECTIVE: The purpose of the current study was to cross-culturally adapt and validate an online questionnaire to assess eating habits and physical activity of university students under confinement due to coronavirus disease (COVID-19). DESIGN: Generation of a cross-sectional online survey to university students conducted during confinement due to COVID-19. The study was divided into two phases. SETTINGS: Students, Chile. PARTICIPANTS: Phase 1 considered the process of translation and back translation, expert panel, cultural adaptation and the generation of a pilot to validate a preliminary format of the questionnaire. In Phase 2, information from the instrument was collected from two hundred and sixty-eight university students, ages 16 to 30 years old, with a mean age of 21·6 (3·3) The major proportion of participants were female (82 %). RESULTS: The adapted questionnaire was statistically validated in three dimensions: (A) eating habits and behaviours during quarantine, (B) perception of risk and (C) physical activity changes during the quarantine. The reliability of Cronbach's α for dimensions A, B and C was 0·59, 0·85 and 0·97, respectively. The complete questionnaire obtained 0·61 in internal consistency and 0·61 (0·58-0·67) ICC reliability. A statistically significant positive correlation matrix was observed. CONCLUSIONS: This questionnaire is a practical tool to obtain accurate information about the relation of COVID-19 confinement on people's eating habits and physical activity. Therefore, it could contribute to establishing appropriate strategies to prevent negative effects on people's health.

6.
Sensors (Basel) ; 21(5)2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33800166

RESUMEN

Foot traffic, conversion rate, and total sales during a period of time may be considered to be important indicators of store performance. Forecasting them may allow for business managers plan stores operation in the near future in an efficient way. This work presents a regression method that is able to predict these three indicators based on previous data. The previous data includes values for the indicators in the recent past; therefore, it is a requirement to have gathered them in a suitable manner. The previous data also considers other values that are easily obtained, such as the day of the week and hour of the day of the indicators. The novelty of the approach that is presented here is that it provides a confidence interval for the predicted information and the importance of each parameter for the predicted output values, without additional processing or analysis. Real data gathered by Follow Up, a customer experience company, was used to test the proposed method. The method was tried for making predictions for up to one month in the future. The results of the experiments show that the proposed method has a comparable performance to the best methods proposed in the past that do not provide confidence intervals or parameter rankings. The method obtains RMSE of 0.0713 for foot traffic prediction, 0.0795 for conversion rate forecasting, and 0.0757 for sales prediction.

7.
Rev Esp Enferm Dig ; 113(12): 848-849, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34315217

RESUMEN

Gastrointestinal melanoma metastases are not uncommon, with the jejunum and ileum being the most common locations (58 %), followed by the stomach (26 %), colon (22 %), duodenum (12 %), and rectum (5 %).


Asunto(s)
Colon Transverso , Melanoma , Colon , Duodeno , Humanos , Íleon , Yeyuno , Melanoma/diagnóstico por imagen , Melanoma/patología , Estómago/patología
8.
J Biol Chem ; 294(17): 6957-6971, 2019 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-30824538

RESUMEN

The dopamine transporter (DAT) regulates dopamine neurotransmission via reuptake of dopamine released into the extracellular space. Interactions with partner proteins alter DAT function and thereby dynamically shape dopaminergic tone important for normal brain function. However, the extent and nature of these interactions are incompletely understood. Here, we describe a novel physical and functional interaction between DAT and the voltage-gated K+ channel Kv2.1 (potassium voltage-gated channel subfamily B member 1 or KCNB1). To examine the functional consequences of this interaction, we employed a combination of immunohistochemistry, immunofluorescence live-cell microscopy, co-immunoprecipitation, and electrophysiological approaches. Consistent with previous reports, we found Kv2.1 is trafficked to membrane-bound clusters observed both in vivo and in vitro in rodent dopamine neurons. Our data provide evidence that clustered Kv2.1 channels decrease DAT's lateral mobility and inhibit its internalization, while also decreasing canonical transporter activity by altering DAT's conformational equilibrium. These results suggest that Kv2.1 clusters exert a spatially discrete homeostatic braking mechanism on DAT by inducing a relative increase in inward-facing transporters. Given recent reports of Kv2.1 dysregulation in neurological disorders, it is possible that alterations in the functional interaction between DAT and Kv2.1 affect dopamine neuron activity.


Asunto(s)
Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Endocitosis , Canales de Potasio Shab/metabolismo , Animales , Dopamina/metabolismo , Femenino , Masculino , Mesencéfalo/citología , Mesencéfalo/metabolismo , Ratones , Ratones Endogámicos C57BL , Neuronas/metabolismo , Ratas , Ratas Sprague-Dawley
9.
Sensors (Basel) ; 20(16)2020 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-32781680

RESUMEN

Although many authors have highlighted the importance of predicting people's health costs to improve healthcare budget management, most of them do not address the frequent need to know the reasons behind this prediction, i.e., knowing the factors that influence this prediction. This knowledge allows avoiding arbitrariness or people's discrimination. However, many times the black box methods (that is, those that do not allow this analysis, e.g., methods based on deep learning techniques) are more accurate than those that allow an interpretation of the results. For this reason, in this work, we intend to develop a method that can achieve similar returns as those obtained with black box methods for the problem of predicting health costs, but at the same time it allows the interpretation of the results. This interpretable regression method is based on the Dempster-Shafer theory using Evidential Regression (EVREG) and a discount function based on the contribution of each dimension. The method "learns" the optimal weights for each feature using a gradient descent technique. The method also uses the nearest k-neighbor algorithm to accelerate calculations. It is possible to select the most relevant features for predicting a patient's health care costs using this approach and the transparency of the Evidential Regression model. We can obtain a reason for a prediction with a k-NN approach. We used the Japanese health records at Tsuyama Chuo Hospital to test our method, which included medical examinations, test results, and billing information from 2013 to 2018. We compared our model to methods based on an Artificial Neural Network, Gradient Boosting, Regression Tree and Weighted k-Nearest Neighbors. Our results showed that our transparent model performed like the Artificial Neural Network and Gradient Boosting with an R2 of 0.44.


Asunto(s)
Algoritmos , Costos de la Atención en Salud , Redes Neurales de la Computación , Análisis por Conglomerados , Femenino , Humanos , Masculino
10.
Sensors (Basel) ; 19(22)2019 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-31752331

RESUMEN

Preparing a plan for reaction to a grave emergency is a significant first stage in disaster management. A group of experts can do such preparation. Best results are obtained with group members having diverse backgrounds and access to different relevant data. The output of this stage should be a plan as comprehensive as possible, taking into account various perspectives. The group can organize itself as a collaborative decision-making team with a process cycle involving modeling the process, defining the objectives of the decision outcome, gathering data, generating options and evaluating them according to the defined objectives. The meeting participants may have their own evidences concerning people's location at the beginning of the emergency and assumptions about people's reactions once it occurs. Geographical information is typically crucial for the plan, because the plan must be based on the location of the safe areas, the distances to move people, the connecting roads or other evacuation links, the ease of movement of the rescue personnel, and other geography-based considerations. The paper deals with this scenario and it introduces a computer tool intended to support the experts to prepare the plan by incorporating the various viewpoints and data. The group participants should be able to generate, visualize and compare the outcomes of their contributions. The proposal is complemented with an example of use: it is a real case simulation in the event of a tsunami following an earthquake at a certain urban location.


Asunto(s)
Conducta Cooperativa , Planificación en Desastres , Urgencias Médicas , Tecnología , Algoritmos , Chile , Toma de Decisiones , Geografía
11.
J Biol Chem ; 291(34): 17510-22, 2016 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-27365397

RESUMEN

We previously reported that the vesicular monoamine transporter 2 (VMAT2) is physically and functionally coupled with Hsc70 as well as with the dopamine synthesis enzymes tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase, providing a novel mechanism for dopamine homeostasis regulation. Here we expand those findings to demonstrate that Hsc70 physically and functionally interacts with TH to regulate the enzyme activity and synaptic vesicle targeting. Co-immunoprecipitation assays performed in brain tissue and heterologous cells demonstrated that Hsc70 interacts with TH and aromatic amino acid decarboxylase. Furthermore, in vitro binding assays showed that TH directly binds the substrate binding and carboxyl-terminal domains of Hsc70. Immunocytochemical studies indicated that Hsc70 and TH co-localize in midbrain dopaminergic neurons. The functional significance of the Hsc70-TH interaction was then investigated using TH activity assays. In both dopaminergic MN9D cells and mouse brain synaptic vesicles, purified Hsc70 facilitated an increase in TH activity. Neither the closely related protein Hsp70 nor the unrelated Hsp60 altered TH activity, confirming the specificity of the Hsc70 effect. Overexpression of Hsc70 in dopaminergic MN9D cells consistently resulted in increased TH activity whereas knockdown of Hsc70 by short hairpin RNA resulted in decreased TH activity and dopamine levels. Finally, in cells with reduced levels of Hsc70, the amount of TH associated with synaptic vesicles was decreased. This effect was rescued by addition of purified Hsc70. Together, these data demonstrate a novel interaction between Hsc70 and TH that regulates the activity and localization of the enzyme to synaptic vesicles, suggesting an important role for Hsc70 in dopamine homeostasis.


Asunto(s)
Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Proteínas del Choque Térmico HSC70/metabolismo , Vesículas Sinápticas/metabolismo , Tirosina 3-Monooxigenasa/metabolismo , Animales , Línea Celular , Chaperonina 60/genética , Chaperonina 60/metabolismo , Dopamina/genética , Neuronas Dopaminérgicas/citología , Proteínas del Choque Térmico HSC70/genética , Homeostasis/fisiología , Masculino , Ratones , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Unión Proteica/fisiología , Dominios Proteicos , Ratas , Ratas Sprague-Dawley , Vesículas Sinápticas/genética , Tirosina 3-Monooxigenasa/genética
12.
Pharm Res ; 34(12): 2735-2748, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28913790

RESUMEN

PURPOSE: HSP90 (Heat shock protein 90kD) has been validated as a therapeutic target in Castrate Resistant Prostate Cancer. Unfortunately, HSP90 inhibitors suffer from dose-limiting toxicities that hinder their clinical applications. Previously developed polymeric delivery systems for HSP90 inhibitors had either low drug content or low biological activity suggesting the need for better delivery system for HSP90 inhibitors. METHODS: We developed a simplified synthetic strategy to prepare polyethylene glycol based water-soluble polymeric system for model HSP90 inhibitor geldanamycin (GDM). We then investigated the effect of cathepsin B degradable linker and drug content in polymeric conjugates on their growth inhibitory property using DU145 (androgen independent) and LNCaP (androgen dependent) cell lines. RESULTS: Water-soluble polymeric conjugates were synthesized with GDM content ranging from 9 to 30% wt/wt. We demonstrated the importance of cathepsin B degradable linker from the context of drug content and different prostate cancer cell lines. The most active conjugate against DU145 cells exhibited IC50 value of 2.9 µM. This was similar to the IC50 (2.1 µM) of small molecular drug aminohexane geldanamycin. CONCLUSION: Water-soluble polymeric conjugate with high drug content was synthesized that exhibited in-vitro growth inhibitory activity similar to small molecular weight HSP90 inhibitor. Graphical Abstract Water soluble degradable polymeric conjugate for the delivery of Geldanamycin.


Asunto(s)
Antineoplásicos/administración & dosificación , Benzoquinonas/administración & dosificación , Portadores de Fármacos/química , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Lactamas Macrocíclicas/administración & dosificación , Polímeros/química , Antineoplásicos/farmacología , Benzoquinonas/farmacología , Línea Celular Tumoral , Humanos , Lactamas Macrocíclicas/farmacología , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Solubilidad , Agua/química
13.
BMC Complement Altern Med ; 15: 254, 2015 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-26219933

RESUMEN

BACKGROUND: Reactive Oxygen Species (ROS) impair the physiological functions of Retinal Pigment Epithelial (RPE) cells, which are known as one major cause of age-related macular degeneration and retinopathy diseases. The purpose of this study is to explore the cytoprotective effects of the antioxidant Bucida buceras extract in co-treatment with hydrogen peroxide (H2O2) delivery as a single addition or with continuous generation using glucose oxidase (GOx) in ARPE-19 cell cultures. The mechanism of Bucida buceras extract is believed to be associated with their antioxidant capacity to protect cells against oxidative stress. METHODS: A comparative oxidative stress H2O2-induced was performed by addition and enzymatic generation using glucose oxidase on human retinal pigment epithelial cells line. H2O2-induced injury was measured by toxic effects (cell death and apoptotic pathway) and intracellular redox status: glutathione (GSH), antioxidant enzymes (catalase and glutathione peroxidase) and reducing power (FRAP). The retino-protective effect of co-treatment with Bucida buceras extract on H2O2-induced human RPE cell injury was investigated by cell death (MTT assay) and oxidative stress biomarkers (H2O2, GSH, CAT, GPx and FRAP). RESULTS: Bucida buceras L. extract is believed to be associated with the ability to prevent cellular oxidative stress. When added as a pulse, H2O2 is rapidly depleted and the cytotoxicity analyses show that cells can tolerate short exposure to high peroxide doses delivered as a pulse but are susceptible to lower chronic doses. Co-treatment with Bucida buceras was able to protect the cells against H2O2-induced injury. In addition to preventing cell death treatment with antioxidant plant could also reverse the significant decrease in GSH level, catalase activity and reducing power caused by H2O2. CONCLUSION: These findings suggest that Bucida buceras could protect RPE against ocular pathogenesis associated with oxidative stress induced by H2O2-delivered by addition and enzymatic generation.


Asunto(s)
Antioxidantes , Combretaceae/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales , Epitelio Pigmentado de la Retina/citología , Antioxidantes/química , Antioxidantes/farmacología , Línea Celular , Humanos , Peróxido de Hidrógeno/toxicidad , Oxidorreductasas/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología
14.
Cir Esp ; 93(9): 594-8, 2015 Nov.
Artículo en Inglés, Español | MEDLINE | ID: mdl-26025065

RESUMEN

Endoscopic retrograde cholangiopancreatography may be difficult in patients that have undergone Roux-en-Y gastric bypass. Due to the fact that prevalence of morbid obesity is increasing, and laparoscopic procedures for its treatment have increased, the incidence of biliary tract problems in patients of altered anatomy is also growing. We describe a laparoscopic technique to access the biliary tree by endoscope, through the excluded stomach.


Asunto(s)
Laparoscopía , Desviación Biliopancreática , Colangiopancreatografia Retrógrada Endoscópica , Derivación Gástrica , Humanos , Obesidad Mórbida/cirugía
15.
Cir Esp ; 93(8): 509-15, 2015 Oct.
Artículo en Inglés, Español | MEDLINE | ID: mdl-26072690

RESUMEN

BACKGROUND: Enhanced recovery after surgery (ERAS) has demonstrated in colorectal surgery a reduction in morbidity and length of stay without compromising security. Experience with ERAS programs in pancreatoduodenectomy (PD) is still limited. The aims of this study were first to evaluate the applicability of an ERAS program for PD patients in our hospital, and second to analyze the postoperative results. METHODS: A retrospective study using a prospectively maintained database identified 41 consecutive PD included in an ERAS program. Key elements studied were early removal of tubes and drainages, early oral feeding and early mobilization. Variables studied were mortality, morbidity, perioperative data, length of stay, re-interventions and inpatient readmission. This group of patients was compared with an historic control group of 44 PD patients with a standard postoperative management. RESULTS: A total of 85 pancreatoduodenectomies were analyzed (41 patients in the ERAS group, and 44 patients in the control group. General mortality was 2.4% (2 patients) belonging to the control group. There were no statistical differences in mortality, length of stay in intensive care, reoperationss, and readmissions. ERAS group had a lower morbidity rate than the control group (32 vs. 48%; P=.072), as well as a lower length of stay (14.2 vs. 18.7 days). All the key ERAS proposed elements were achieved. CONCLUSIONS: ERAS programs may be implemented safely in pancreaticoduodenectomy. They may reduce the length of stay, unifying perioperative care and diminishing clinical variability and hospital costs.


Asunto(s)
Pancreaticoduodenectomía/rehabilitación , Cuidados Posoperatorios/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
16.
Oncol Rep ; 51(2)2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38131223

RESUMEN

Patients with end­stage metastatic disease have limited treatment options and those diagnosed with triple negative breast cancer (Her2, Estrogen receptor, Progesterone receptor) have a poor prognosis. Using a triple negative mammary tumor model selected for brain metastasis (4T1Br4) in the mouse, treatment options that may increase survival when therapeutics are applied at post­metastasis were assessed. Anti­parasitic benzimidazoles (BZs) destabilize microtubules, inhibit metabolic pathways, reduce cell proliferation, and induce apoptosis in tumor cells. Co­administration of two BZs was selected, oxfendazole (OFZ) and parbendazole (PBZ), shown to overcome resistance development in anthelmintic effects by imposing metabolic delay to assess if multiple BZ approach is also suitable to enhance anticancer effects. It has been previously reported that treatment of mammary tumor­bearing mice at an early stage with chitin microparticles (CMPs) decreased tumor growth and metastases by enhancing both innate M1 macrophage and TH1 adaptive immune response. Oral administration of CMPs was previously revealed to affect the gut in intestinal inflammation. A combination BZ (OFZ/PBZ) and CMP treatment was tested to target tumor development and metastasis and effects were compared in response to monotherapies of the same compounds or to untreated mice. The results demonstrated increased survival, decreased tumor cell proliferation, decreased metastasis in lungs and brain, increased levels of fecal SCFAs butyric, acetic, propionic and valeric acids with increased butyric and propionic acid levels in brain biopsies in combination treated compared with untreated mice. At the primary tumor, SCFA receptor FFAR2 expression was increased in combination treatment compared with untreated mice, suggestive of a non­invasive cancer phenotype. The superior cytotoxic effects of OFZ/PBZ were confirmed as opposed to single treatment with OFZ or PBZ using 3D spheroids generated from a human breast cancer cell line, MDA­MB­468. These data are compelling for treatment option possibility even at late stages of metastasized breast cancer.


Asunto(s)
Antihelmínticos , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Antihelmínticos/metabolismo , Macrófagos/metabolismo , Línea Celular Tumoral
17.
Reproduction ; 145(2): 203-12, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23241345

RESUMEN

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) like superoxide and nitric oxide are produced by testis and spermatogenic cells in response to heat stress. However, the magnitude and mechanisms of this production in spermatogenic cells have not been described. In this work, we evaluated ROS/RNS production, its pharmacology, mitochondrial oxidative metabolism, membrane potential and antioxidant capacity at different temperatures in isolated rat pachytene spermatocytes and round spermatids. Our results showed an increment in ROS/RNS production by pachytene spermatocytes when increasing the temperature to 40 °C. Instead, ROS/RNS production by round spermatids did not change at temperatures higher than 33 °C. ROS/RNS production was sensitive to NADPH oxidase inhibitor diphenylene iodonium or the mitochondrial complex I inhibitor rotenone. No additive effects were observed for these two compounds. Our results suggest an important mitochondrial ROS/RNS production in spermatogenic cells. Oligomycin-insensitive oxygen consumption (uncoupled oxygen consumption) increased with temperature and was significantly larger in round spermatids than pachytene spermatocytes, indicating a likely round spermatid mitochondrial uncoupling at high temperatures. A similar conclusion can be reached by measuring the mitochondrial membrane potential using rhodamine 123 fluorescence in permeabilized cells or JC-1 fluorescence in intact cells. The antioxidant capacity was higher in round spermatids than pachytene spermatocytes at 40 °C. Our results strongly suggest that at high temperatures (40 °C) pachytene spermatocytes are more susceptible to oxidative stress, but round spermatids are more protected because of a temperature-induced mitochondrial uncoupling together with a larger antioxidant capacity.


Asunto(s)
Frío , Calor , Fase Paquiteno/fisiología , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Espermátides/metabolismo , Espermatocitos/metabolismo , Animales , Antioxidantes/metabolismo , Temperatura Corporal/fisiología , Células Cultivadas , Respuesta al Choque Térmico/fisiología , Masculino , Ratas , Ratas Sprague-Dawley , Espermátides/fisiología , Espermatocitos/fisiología , Espermatogénesis/fisiología
18.
Foods ; 12(4)2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36832775

RESUMEN

Cereal ß-glucans are beneficial health ingredients that reduce cholesterolemia and postprandial glycaemia. However, their impact on digestive hormones and gut microbiota is not yet fully established. Two randomized, double-blind, controlled studies were conducted. In the first study, 14 subjects ingested a breakfast with or without ß-glucan from oats (5.2 g). Compared to the control, ß-glucan increased orocecal transit time (p = 0.028) and decreased mean appetite score (p = 0.014) and postprandial plasma ghrelin (p = 0.030), C-peptide (p = 0.001), insulin (p = 0.06), and glucose (p = 0.0006). ß-glucan increased plasma GIP (p = 0.035) and PP (p = 0.018) without affecting leptin, GLP-1, PYY, glucagon, amylin, or 7α-hydroxy-4-cholesten-3-one, a biomarker of bile acid synthesis. In the second study, 32 subjects were distributed into 2 groups to ingest daily foods with (3 g/day) or without ß-glucan for 3 weeks; stools were collected before/after treatment. No changes in fecal microbiota composition/diversity (deep sequencing) were detected with ß-glucans. These results indicate that acute intake of 5 g ß-glucan slows transit time and decreases hunger sensation and postprandial glycaemia without affecting bile-acid synthesis, these changes being associated with decreased plasma insulin, C-peptide, and ghrelin, and increased plasma GIP and PP. However, regular daily intake of 3 g ß-glucan is not sufficient to have an effect on fecal microbiota composition.

19.
J Inorg Biochem ; 246: 112291, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37352655

RESUMEN

The water-soluble ruthenium complex cis-[Ru(dcbpyH)2(PTAH)2]Cl2·3H2O (1) (dcbpy = 4,4'-dicarboxy-2,2'-bipyridine; PTA = 1,3,5-triaza-7-phosphaadamantane) has been synthesized and characterised by NMR, IR spectroscopy, elemental analysis, and single-crystal X-ray diffraction. The optical properties of 1 were studied, including photoactivation under visible light, as well as its biological properties, together with those of the previously published Ru complexes cis-[Ru(bpy)2(PTA)2]Cl2 (2), trans-[Ru(bpy)2(PTA)2](CF3SO3)2 (3) and cis-[Ru(bpy)2(H2O)(PTA)](CF3SO3)2 (4) (bpy = 2,2'-bipyridine). Anticancer activities of the complexes against human lung (A549), cervical (HeLa) and prostate (PC3) carcinoma cells were evaluated under dark conditions and upon photoactivation with visible light. None of the complexes exhibited cytotoxic activity in the absence of light irradiation (IC50 > 100 µM). However, after photoactivation, the cytotoxicity of complexes 1, 2 and 3 against the three cell lines markedly increased, resulting in IC50 values between 25.3 µM and 9.3 µM. Notably, these complexes did not show toxicity against red blood cells. These findings show the potential of complexes 1, 2 and, particularly, 3 for selective and controlled cancer photochemotherapy. The reactivity of the Ru complexes against DNA under UV-Vis irradiation was studied by analysing plasmid mobility. Experimental data shows that 4 unfolds supercoiled DNA (SC DNA) both in the dark and under visible irradiation, while 1 and 3 are only active under light, being 2 inactive in either case. The unfolding activities of complexes 3 and 4 were dependent on the air present in the reaction. The measured intracellular levels of reactive oxygen species (ROS) upon irradiation with complexes 1, 2 and 3 suggest that their mechanism of action is related to oxidative stress.


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Rutenio , Humanos , 2,2'-Dipiridil/química , Compuestos Organofosforados/farmacología , Compuestos Organofosforados/química , Antineoplásicos/farmacología , Antineoplásicos/química , ADN/química , Rutenio/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química
20.
Chem Commun (Camb) ; 59(50): 7803-7806, 2023 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-37272083

RESUMEN

Metal-organic frameworks (MOFs) based on high-connected nets are generally very attractive due to their combined robustness and porosity. Here, we describe the synthesis of BCN-348, a new high-connected Zr-MOF built from an 8-connected (8-c) cubic Zr-oxocluster and an 8-c organic linker. BCN-348 contains a minimal edge-transitive 3,4,8-c eps net, and combines mesoporosity with thermal and hydrolytic stability. Encouraging results from preliminary studies on its use as a catalyst for hydrolysis of a nerve-agent simulant suggest its potential as an agent for detoxification of chemical weapons and other pernicious compounds.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA