YBX-1 alleviates sepsis-stimulated lung epithelial cell injury

Objective: To explore the role of Y-box binding protein 1 (YBX-1) in the lipopolysaccharide (LPS)-stimulated inflammation and oxidative stress of BEAS-2B cell line and clarify the underlying mechanism. Methods: LPS-stimulated BEAS-2B cells were used as a cell model of sepsis-stimulated acute lung injury (ALI). Immunoblot and quantitative polymerase chain reaction assays were used to detect the expression of YBX-1 in LPS-stimulated BEAS-2B cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, TdT-mediated dUTP nick end labeling, and immunoblot assays were conducted to determine the effects of YBX-1 on cell survival. JC-1 staining and adenosine triphosphate production were used to detect the effects of YBX-1 on mitochondrial function. Immunostaining and enzyme-linked immunosorbent serologic assay were performed to examine the effects of YBX-1 on the inflammation and oxidative stress of cells. Immunoblot assay was conducted to confirm the mechanism. Results: YBX-1 was lowly expressed in LPS-stimulated BEAS-2B cells and enhanced the survival of LPS-stimulated lung epithelial cells. In addition, YBX-1 improved mitochondrial function of LPS-stimulated BEAS-2B cells. YBX-1 inhibited the inflammation and oxidative stress of LPS-stimulated BEAS-2B cells. Mechanically, YBX-1 inhibited mitogen-activated protein kinase (MAPK) axis, thereby alleviating sepsis-stimulated ALI. Conclusion: YBX-1 alleviated inflammation and oxidative stress of LPS-stimulated BEAS-2B cells via MAPK axis. (AU)

Pulsed magnetic field increases the effect of ultraviolet C radiation and thermal shock in aged yeasts / El campo magnético pulsado aumenta el efecto de la radiación ultravioleta C y el choque térmico en levaduras envejecidas

The study of the effects of the magnetic field (MF) on living matter continues to be a dilemma. Until now, the interaction mechanisms of MF with living matter that explain the observed phenomena are unknown. Despite the existing literature and the multiple effects described to date, there are few published articles that study the combined effect of MF with other physical agents during the cellular aging process. In this sense, the aim of this work is to study whether low frequency and intensity pulsed and sinusoidal MF exposure produce alterations in the cell killing effect of ultraviolet C (UVC) radiation and thermal shock during the chronological aging of S. cerevisiae. Yeast cells were exposed to 2.45 mT (50 Hz) sinusoidal MF and 1.5 mT (25 Hz) pulsed MF, during 40 days of aging, in combination with UVC radiation (50 J/m2) and/or thermal shock (52°C). Cell survival was evaluated by clonogenic assay. The exposure of yeast to pulsed MF produces an acceleration of aging, which is not observed in cells exposed to sinusoidal MF. The pulsed MF modifies the cellular response to damaging agents only in aged S. cerevisiae cells. In this sense, the pulsed MF applied increases the damage induced by UVC radiation and by thermal shock. In contrast, the sinusoidal MF used has no effect.(AU)

STAT3 inhibitor BBI608 reduces patient-specific primary cell viability of cervical and endometrial cancer at a clinical-relevant concentration

Aberrant activation of STAT3 signal pathway promotes tumor progression in many solid tumor types, including cervical cancer and endometrial cancer. BBI608, the STAT3 inhibitor had been reported in previous studies for restraining cancer stem cells. However, whether BBI608 is available for inhibiting the proliferation of cervical cancer or endometrial cancer remains poorly understood. This study investigated the anti-tumor effect and molecular mechanism of BBI608 on the patient-specific primary cells (PSPC) generated from cervical and endometrial cancer in vitro. Methods PSPCs were obtained from four patients via biopsy. The cell viability was analyzed by the CCK8 assay. The PSPCs were treated with various concentrations of BBI608 or/and paclitaxel; and then, western blot was applied to investigate the expression of phosphorylated STAT3 (pSTAT3). Results The PSPCs cell viability was reduced after treated with BBI608 at a lower concentration. Western blot results showed a reduction trend of pSTAT3 after PSPCs treated with BBI608. Our results demonstrated that BBI608 at the certain concentrations worked well in reducing the cell viability of PSPC from the patients who suffered from cervical cancer and endometrial cancer. Conclusions In this study, the patient-specific primary cell (PSPC) was used as the pre-clinical model for investigating the efficiency of BBI608 in reducing cancer cells viability. BBI608, at a clinical-relevant concentration, had valid efficiency in PSPCs from the patients. The dose of drugs treatment and the measured results were more valuable for further guiding clinical trials (AU)

Enhanced anticancer activity and endocytic mechanisms by polymeric nanocarriers of n-butylidenephthalide in leukemia cells

Purpose The purpose of this study was to investigate the antitumor mechanisms of n-butylidenephthalide (BP) and to further examine the delivery efficacy of polycationic liposome containing PEI and polyethylene glycol complex (LPPC)-encapsulated BP in leukemia cells. Method MTS, flow cytometric and TUNEL assays were performed to assess cell viability and apoptosis. BP and BP/LPPC complex delivery efficiency was analyzed by full-wavelength fluorescent scanner and fluorescence microscope. The expressions of cell cycle- and apoptosis-related proteins were conducted by Western blotting. Results The results showed that BP inhibited leukemia cell growth by inducing cell cycle arrest and cell apoptosis. LPPC-encapsulated BP rapidly induced endocytic pathway activation, resulting in the internalization of BP into leukemia cells, causing cell apoptosis within 1 h. Conclusions LPPC encapsulation enhanced the cytotoxic activity of BP and did not influence the effects of BP induction that suggested LPPC-encapsulated BP might be developed as anti-leukemia drugs in future (AU)

Combination therapy with TiO2 nanoparticles and cisplatin enhances chemotherapy response in murine melanoma models

Background Despite recent progressions in the treatment of melanoma, the response to conventional therapies and the long-term survival in melanoma patients still remain poor. Recently, the use of nanoparticles (NPs) has been highlighted for promoting the chemotherapeutic effects of cytotoxic drugs in melanoma. The aim of this study is to mechanistically evaluate the potential of titanium dioxide (TiO2) nanoparticles (NPs) for enhancing chemotherapy effects in in vitro and in vivo models of murine melanoma. Methods The F10 melanoma cells were exposed to different concentrations of TiO2 NPs and/or cisplatin, then cell growth, cell viability, and cell death were evaluated. In parallel, C57BL/6 syngeneic melanoma mice were treated by TiO2 NPs and/or cisplatin, and then drug responses, tumor size and mice’s organs were studied pathologically. Autophagy was examined by evaluating the formation of autophagosomes and gene expression levels of autophagy markers (ATG5 and ATG6) by fluorescent microscopy and qPCR, respectively. Results Nontoxic concentrations of TiO2 NPs (50 µg/ml) promote anti-proliferative and cytotoxic effects of cisplatin in F10 melanoma cells, which is mediated through the induction of autophagy and necrotic cell death. Whereas TiO2 NPs have no cytotoxic or metastatic effects in melanoma mice, its combination with cisplatin enhances drug responses (up to 50%), leading to higher inhibition of tumor growth compared with each monotherapy. Conclusion The combination of TiO2 NP with cisplatin enhances chemotherapy response in both in vitro and in vivo melanoma models. In addition, autophagy plays an essential role during sensitizing melanoma cells to chemotherapy (AU)

CDKN2A inhibits cell proliferation and invasion in cervical cancer through LDHA-mediated AKT/mTOR pathway

Purpose The current study aims to explore the effects of CDKN2A on cell proliferation and cycle, and investigate the underlying mechanisms. Methods Expression of CDKN2A in cervical cancer cell lines was evaluated by real-time quantitative PCR (RT-qPCR) and western blotting. Apoptotic rate was detected by Annexin V assay. MTT assay, Transwell assay and cell cycle assay kit were applied to examine the effect of CDKN2A on cell viability, invasion and cell cycle. Co-immunoprecipitation and western blotting were devoted to explore the mechanism by which CDKN2A contributes to cell function. Results CDKN2A was expressed at a low level in cervical cancer cell lines. Overexpression of CDKN2A inhibited cell proliferation and invasion, and caused cell cycle arrest in the G1 phase. CDKN2A mediates the AKT–mTOR signaling pathway by suppressing lactate dehydrogenase (LDHA). Taken together, our data revealed that CDKN2A can be applied as a therapeutic target for the treatment of cervical cancer in future. Conclusions CDKN2A inhibits cell proliferation and invasion in cervical cancer through LDHA-mediated AKT–mTOR pathway (AU)

miR-22 suppresses cell viability and EMT of ovarian cancer cells via NLRP3 and inhibits PI3K/AKT signaling pathway

Purpose miR-22 plays a great role in inhibiting cell growth, metastasis and enhanced cell apoptosis in several cancers. The purpose of this study was to investigate the functions of miR-22 in ovarian cancer. Methods The proliferative ability was measured using CCK-8 assay. The protein expression associated with EMT and PI3K/AKT signaling biomarkers were measured by western blot. Luciferase assay applied to measure the luciferase activity. Kaplan–Meier method was performed to evaluate the overall survival rate of ovarian cancers. Results miR-22 was low expressed and NLRP3 was overexpressed in ovarian cancer tissues and cells, and downregulation of miR-22 was associated with poor prognosis. The expression of NLRP3 had a negative correlation with miR-22 expression in ovarian cancer. miR-22 promoted cell viability and EMT through directly binding to the 3′-UTR of NLRP3 mRNA and inhibited PI3K/AKT signaling pathway. NLRP3 partially restored functions of miR-22 on cell proliferation and EMT in ovarian cancer. Conclusion miR-22 impaired cell viability and EMT by NLRP3 and inhibited PI3K/AKT signaling pathway in ovarian cancer. The newly identified miR-22/NLRP3/PI3K/AKT axis provides novel insight into the pathogenesis of ovarian cancer (AU)

Estudio de biocompatibilidad y osteointegración de nuevos materiales protésicos / Biocompatibility and osseointegration study of new prosthetic materials

OBJETIVO: Los implantes óseos son utilizados cada vez con mayor frecuencia en la práctica clínica y, entre los materiales, el Ti o sus aleaciones son los de mejor rendimiento por sus propiedades fisicoquímicas. Aleaciones como TiNbTa han demostrado mejorar las características biomecánicas del Ti puro comercial (c.p.), sin embargo, su capacidad osteointegradora necesita ser evaluada. El objetivo del presente estudio fue valorar la citotoxicidad y la capacidad de adhesión, proliferación y diferenciación de células osteoblásticas en cultivo, influida por discos de material TiNbTa frente a Ti c.p. MATERIALES Y MÉTODOS: Analizamos a los 4 y 7 días del cultivo la línea celular MC3T3, la viabilidad celular (AlamarBlue Cell Viability Reagent. Invitrogen, España), así como la proliferación y diferenciación celular (actividad de fosfatasa alcalina (ALP) y microscopía electrónica de barrido (Fijación para SEM). Se realizó la prueba t de Student para determinar diferencias estadísticamente significativas entre los dos grupos de discos de estudio. RESULTADOS: Los resultados obtenidos demuestran muy buena viabilidad celular durante el periodo de estudio, sin diferencias significativas para ambos materiales. Así mismo, detectamos una caída en los niveles de ALP que fue significativa para ambos componentes entre los días 4 y 7 del estudio (p < 0,05). Las imágenes de microscopía electrónica revelaron buena capacidad de adhesión al material, así como diferenciación celular frente a ambos tipos de discos. CONCLUSIONES: La aleación de TiNbTa como material para implantes óseos cuenta con una buena capacidad osteointegradora, además de resolver problemas de biomecánica que presenta el titanio puro como componente

OBJETIVE: Bone implants are increasingly used in clinical practice and, among the materials, Ti or its alloys are offer the best performance given their physicochemical properties. Alloys such as TiNbTa have been shown to improve the biomechanical characteristics of commercial pure Ti (c.p.), however, its osseointegration capacity needs to be evaluated. The objective of the present study was to assess the cytotoxicity and the adhesion, proliferation and differentiation capacity of osteoblastic cells in culture, influenced by discs of TiNbTa material versus Ti c.p. MATERIAL AND METHODS: At 4 and 7 days after culture, we analyzed the MC3T3 cell line, cell viability (AlamarBlue Cell Viability Reagent. Invitrogen, Spain), as well as cell proliferation and differentiation (alkaline phosphatase activity (ALP) and scanning electron microscopy (Fixation for SEM) Student's t test was performed to determine statistically significant differences between the two groups of study discs. RESULTS: The results obtained show very good cell viability during the study period, with no significant differences for both materials. Likewise, we detected a drop in ALP levels that was significant for both components between days 4 and 7 of the study (p < 0.05). Electron microscopy images revealed good adhesion capacity to the material, as well as cell differentiation against both types of discs. CONCLUSIONS: The TiNbTa alloy as a material for bone implants offers good osseointegrative capacity, in addition to solving biomechanical problems that pure titanium presents as a component

Repercusión de la radioterapia sobre la situación nutricional del paciente oncogeriátrico. ¿Puede el oncólogo radioterápico minimizar el impacto de la radioterapia sobre el estado nutricional del enfermo mayor? / Nutritional impact of radiotherapy in oncogeriatric patients. Can radiation oncologists minimize the radiotherapy impact on the nutritional status of the elderly patient?

El cáncer en pacientes ancianos representa un reto de salud a escala mundial debido al aumento de su incidencia y su mortalidad asociada. En nuestro país es la segunda causa de muerte en mayores de 65 años. En años venideros el problema irá en aumento, con un pronóstico de personas mayores de 65 años del 35% en el año 2050. La radioterapia supone una parte fundamental del tratamiento multidisciplinar del cáncer en los pacientes ancianos, donde unas veces se plantea como primera opción terapéutica y otras, como alternativa a la cirugía y/o la quimioterapia si estas plantean demasiado riesgo. El desarrollo tecnológico de la Oncología Radioterápica en los últimos años ha permitido optimizar los tratamientos y disminuir las toxicidades en los pacientes de edad avanzada, que suelen presentar mayor incidencia de comorbilidades. Es fundamental que los profesionales implicados en el tratamiento multidisciplinar del cáncer conozcan la posible toxicidad y su manejo en los pacientes oncogeriátricos, ya que, de lo contrario, disminuyen las probabilidades de que pacientes con indicación adecuada de este tratamiento lo reciban. En este sentido, es imprescindible el reconocimiento de aquellos pacientes que puedan sufrir desnutrición o estén en riesgo de sufrirla, para iniciar una intervención nutricional que minimice una pérdida de peso que altere o incluso haga suspender el tratamiento planificado

Cancer in elderly patients represents a global health challenge due to the increase in its incidence and its associated mortality. In our country it is the second leading cause of death in people over 65 years. In the coming years, the problem will increase, with a prognosis of people over 65 years of 35% in 2050. Radiotherapy is an essential part of the multidisciplinary treatment of cancer in elderly patients, where sometimes it is considered as the first therapeutic option and others, as an alternative to surgery and/or chemotherapy if they pose too much risk. The technological development of Radiation Oncology in recent years has allowed optimizing treatments and reducing side effects in elderly patients, who tend to have a higher incidence of comorbidities. It is essential that professionals involved in the multidisciplinary treatment of cancer know the possible toxicity and its management in oncogeriatric patients; otherwise, the percentage of patients who do not receive radiotherapy despite of an adequate indication will not decrease. In this sense, it is necessary to recognize those patients who may suffer from malnutrition or are at risk of suffering it, to initiate a nutritional intervention that minimizes weight loss that alters or even causes the suspension of the planned treatment

Efecto comparativo del método de fractura mecánica y el método de corte en la viabilidad de las células de la pulpa dental humana de las 24 horas postexodoncia / Comparative effect of the mechanical fracture method and the cutting method on the viability of human dental pulp cells from teeth extracted within 24 hours

OBJETIVO: En los estudios sobre biomateriales e ingeniería de tejidos se emplean células de la pulpa dental para regenerar o sustituir las deficiencias de tejido óseo en la cavidad oral. Para evaluar su potencial clínico se utilizan modelos de cultivo celular, en los cuales se aplican diversos métodos de extracción de la pulpa dental. Pero aún no está claro qué método es el más conveniente. Por ello, el propósito de este estudio fue comparar el método de fractura mecánica y el método de corte en la viabilidad celular. MATERIAL Y MÉTODOS: Se extrajo el tejido pulpar de dientes completamente desarrollados y sanos de 32 pacientes de entre 18 y 40 años mediante dos técnicas: el método de fractura mecánica (grupo 1) y el método de corte (grupo 2). Para determinar la viabilidad celular se usó el colorante azul de tripán. Las células teñidas de azul (muertas) y las células birrefringentes (vivas) fueron contabilizadas en el microscopio óptico. RESULTADOS: Al emplear el método de fractura mecánica se obtuvo un 87,72 % de viabilidad celular, mientras que al aplicar el método de corte se logró una menor viabilidad: 83,59 %. Al analizar los datos (n = 16 por grupo) bajo la prueba t de Student se obtuvo una diferencia significativa (p = 0,006). CONCLUSIONES: El método de fractura mecánica permite obtener una viabilidad celular más alta en comparación al método de corte, empleado en dientes extraídos dentro de las 24 horas

AIM: In biomaterials and tissue engineering studies, dental pulp cells are used to regenerate or replace deficiencies of bone tissue in the oral cavity. To evaluate its clinical potential, cell culture models are employed, in which different extraction methods of the dental pulp are applied. Mainly, the tooth is broken by fracture mechanics and the cutting method to obtain the dental pulp. However, it is not clear yet which method is the most convenient. Therefore, the purpose of this study was to compare the effect of two methods of fracture mechanical and cutting methods on the dental pulp cell viability. METHODOLOGY: Dental pulp tissue was removed of fully developed and healthy teeth of 32 patients between 18 to 40 years, through two techniques: the methods of fracture mechanics (group 1) and cutting (group 2). To determine the cell viability, trypan blue dye was used. The cells were counted in the microscope, blue stained cells (dead) and birefringent (living). RESULTS: Using the mechanical fracture method, 87.72 % of cell viability was obtained. While with the cutting method was achieved a lower viability 83.59 %. There was a significant difference (p = 0.006) when analyzing the data (n = 16 per group) under t-Student test. CONCLUSIONS: The use of mechanical fracture method for the extraction of the dental pulp tissue allows to obtain higher percentages of cell viability compared to cutting method

Response of Anaerobic Protozoa to Oxygen Tension in Anaerobic System

The effect of oxygen on anaerobic protozoa was studied in anaerobic batch reactors inoculated with sludge and protozoa cultures. Among the protozoa genera, Metopus, Brachonella, Plagiopyla, Trepomonas, and Vanella were more sensitive to oxygen compared to other genera. Protozoa genera Menoidium, Rhynchomonas, Cyclidium, Spathidium, and Amoeba were found to survive under aerobic conditions, and the growth rate was slightly higher or similar to anaerobic condition. O2 tension resulted in the loss of free and endosymbiotic methanogens in anaerobic system, while methanogens were observed inside the protozoan cysts. Survival of anaerobic protozoa declined considerably when the O2 tension exceeded 1% atm. sat. and showed chemosensory behavior in response to O2 exposure. Superoxide dismutase activity was detected in survived protozoa cells under O2 tension. Facultative anaerobic protozoa with SOD activity can provide a mechanism to overcome possible occurrence of oxygen toxicity in the treatment of wastewater in anaerobic reactor

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Efectos biológicos de los cementos MTA Repair HP y ProRoot MTA tras ser expuestos a diferentes pH sobre células madre de ligamento periodontal / Biological effects of MTA Repair HP and ProRoot MTA exposed to different pH on human periodontal ligament stem cells

Objetivos. El propósito de este trabajo fue evaluar los efectos biológicos de MTA Repair HP y ProRoot MTA en células madre procedentes de ligamento periodontal (hPDLSCs) tras ser ex-puestos los cementos a ambiente ácido y neutro. Material y Métodos: Discos de cada material (n=30) fueron ex-puestos a un tampón fosfato-salino (pH 7.4) o a ácido butírico (pH 5.2) durante 7 días, posteriormente se realizaron pruebas biológicas in vitro usando hPDLSCs. A partir de eluatos de los diferentes materiales de obturación a retro, se analizaron pruebas de viabilidad celular y apoptosis. Para evaluar la adhesión celular, hPDLSCs se sembraron directamente sobre la superficie de los materiales y se observaron bajo microscopio electrónico de barrido. Para analizar estadísticamente los resultados se usaron los test ANOVA y Tukey test (p < 0.05). Resultados: Los cementos endodónticos expuestos a ambiente ácido mostraron un similar grado de adhesión celular, y sorprendentemente, MTA Repair HP a pH 5.2 exhibió una mayor viabilidad celular que ProRootMTA (p<0.05). A pH 7.4, ProRooT MTA obtuvo una tasa mayor de viabilidad celular que con MTA Repair HP. Conclusiones: Los materiales ProRoot MTA y MTA Repair HP presentaron adecuadas propiedades biológicas en los diferentes ambientes, en términos de viabilidad celular, apoptosis y adhesión

Objectives: The purpose of this work was to evaluate the biolo-gical effects of MTA Repair HP and ProRoot MTA on stem cells from periodontal ligament (hPDLSCs) after exposure to acidic and neutral environments. Material and Methods: Discs of each material (n=30) were ex-posed to phosphate buffered saline (pH = 7.4) or butyric acid (pH = 5.2) for 7 days, and biological testing was carried out in vitro on hPDLSCs. Cell viability and apoptosis assays were performed using eluates of each root-end filling material. To evaluate cell attachment to the different materials, hPDLSCs were directly seeded onto the material surfaces and analyzed by scanning electron microscopy. Statistical differences were assessed by ANOVA and Tukey test (p < 0.05).Results: Endodontic cements exposure to an acidic environment showed a similar degree of cell adherence, and, surprisingly, MTA Repair HP exhibited higher cell viability rates at pH 5.2 than Pro-Root MTA, whereas ProRoot MTA 7.4 showed higher cell viability rates than MTA Repair HP. Conclusions: Adequate biological properties of ProRoot MTA and MTA Repair HP in terms of cell viability, cell death and cell attach-ment were observed in both environments

Osteoprotegerin mediate RANK/RANKL signaling inhibition eases asthma inflammatory reaction by affecting the survival and function of dendritic cells

Introduction: Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Dendritic cells (DCs) are considered the most important antigen-presenting cell in asthma airway inflammatory reaction. But whether osteoprotegerin (OPG) mediate RANK/RANKL signaling inhibition influences asthma development by affecting the survival and function of DCs remains unclear. In this study, we assessed the effects of OPG on DCs and asthma. Material and methods: BALB/c mice immunized with ovalbumin (OVA) were challenged thrice with an aerosol of OVA every second day for eight days. Dexamethasone (1.0mg/kg) or OPG (50 mig/kg) was administered intraperitoneally to OVA-immunized BALB/c mice on day 24 once a day for nine days. Mice were analyzed for effects of OPG on asthma, inflammatory cell infiltration and cytokine levels in lung tissue. The expression of RANK and β-actin was detected by Western Blot. DCs were isolated from mouse bone morrow. Cell survival was assessed by cell counting. The content of IL-12 was detected by ELISA. Results: Results showed that OVA increased the number of inflammatory factors in BALF, elevated lung inflammation scores in mice. OPG reversed the alterations induced by OVA in the asthmatic mice. OPG inhibited the survival and function of DC via inhibition of RANK/RANKL signaling. Conclusions: This research proved inhibition of RANK/RANKL signaling by OPG could ease the inflammatory reaction in asthma, providing new evidence for the application of OPG on asthma

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Effects of reactive oxygen species and interplay of antioxidants during physical exercise in skeletal muscles

A large number of researches have led to a substantial growth of knowledge about exercise and oxidative stress. Initial investigations reported that physical exercise generates free radical-mediated damages to cells; however, in recent years, studies have shown that regular exercise can upregulate endogenous antioxidants and reduce oxidative damage. Yet, strenuous exercise perturbs the antioxidant system by increasing the reactive oxygen species (ROS) content. These alterations in the cellular environment seem to occur in an exercise type-dependent manner. The source of ROS generation during exercise is debatable, but now it is well established that both contracting and relaxing skeletal muscles generate reactive oxygen species and reactive nitrogen species. In particular, exercises of higher intensity and longer duration can cause oxidative damage to lipids, proteins, and nucleotides in myocytes. In this review, we summarize the ROS effects and interplay of antioxidants in skeletal muscle during physical exercise. Additionally, we discuss how ROS-mediated signaling influences physical exercise in antioxidant system

Silymarin prevents diabetes-induced hyperpermeability in human retinal endothelial cells / La silimarina previene la hiperpermeabilidad inducida por la diabetes en células endoteliales de retina humana

Introduction: Vascular endothelial growth factor (VEGF) plays an essential role in development of diabetic macular edema (DME). While there is evidence suggesting that silymarin, a flavonoid extracted from Silybum marianum, could be useful for prevention and treatment of diabetic nephropathy, no studies have been conducted in diabetic retinopathy (DR). The aim of this study was to assess the effect of silymarin on disruption of inner blood retinal barrier (BRB), the primary cause of DME. Materials and methods: Human retinal endothelial cells (HRECs) were cultured under standard (5.5mM D-glucose) and diabetogenic conditions (25mM D-glucose and 25mM D-glucose + recombinant vascular endothelial growth factor [rVEGF, 25mg/mL]). To assess cell viability, three concentrations of silymarin were tested (2, 4 and 10μg/mL). The effect of silymarin on HREC disruption was determined using a dextran (70kD) permeability asssay. Results: No differences were found in the viability of HRECs treated with 2 or 4μg/mL of silymarin as compared to untreated cells, but viability significantly decreased after using 10 μg/mL. The concentration of 4 μg/mL was therefore selected. Silymarin (4μg/mL) caused a significant decrease in VEGF-induced permeability in both media with 5.5nM (422±58 vs. 600±72 ng/mL/cm2; p<0.03) and 25nM of D-glucose (354 ± 28 vs. 567 ± 102 ng/mL/cm2; p<0.04). Discussion: Our results show that silymarin is effective for preventing hyperpermeability induced by diabetic conditions in HRECs. Further studies are needed to assess whether silymarin could be useful to treat DME (AU)

Introducción: El Vascular endothelial growth factor (VEGF) juega un papel esencial en el desarrollo del edema macular diabético (EMD). Existe evidencia que indica que el uso de la silimarina, extracto flavonoide del Silybum marianum, podría ser útil en la prevención y el tratamiento de la nefropatía diabética pero no se dispone de datos en retinopatía diabética (RD). El objetivo del estudio es evaluar el efecto de la silimarina sobre la disrupción de la barrera hematorretininana, que es la causa primaria del EMD. Material y métodos: Células endoteliales de retina humana (HRECs) se cultivaron en condiciones estándar (5.5mM de D-glucosa) y en condiciones suprafisiológicas de glucosa (25mM de D-glucosa y 25mM de D-glucosa + VEGF 25mg/dl). Para evaluar la viabilidad de las células se probaron 3 concentraciones de silimarina (2, 4 y 10μg/ml). El efecto de la silimarina sobre la disrupción de las HRECs se determinó mediante análisis de permeabilidad a dextrano (70kD). Resultados: No se observaron diferencias en la viabilidad de las HRECs tratadas con 2 o 4μg/ml de silimarina en comparación con las células no tratadas, pero se observó una reducción de la viabilidad con la concentración de 10μg/ml. Por consiguiente, se seleccionó la concentración de 4μg/ml de silimarina. La silimarina (4μg/ml) produjo un descenso significativo de la permeabilidad inducida por VEGF tanto en medio con 5.5mM de D-glucosa (422 ±58 vs. 600 ±72 ng/ml/cm2; p<0.03) como en medio con 25mM de D-glucosa (354±28 vs. 567±102 ng/ml/cm2; p<0.04). Discusión: Nuestros resultados demuestran que la silimarina es efectiva para prevenir la hiperpermeabilidad inducida por condiciones suprafisiológicas de glucosa en HRECs. Son necesarios más estudios para evaluar si la silimarina podría ser útil para el tratamiento del EMD (AU)

Unicca(R): nueva superficie de implantes para acelerar la oseointegración / Unicca(R): new surface implants to accelerate the osseointegration

La superficie de los implantes dentales es un parámetro fundamental a considerar para mejorar la regeneración ósea basada en implantes. Junto con las técnicas quirúrgicas y los materiales y herramientas empleados, las modificaciones superficiales de los implantes han ido evolucionando con el tiempo para permitir acortar los tiempos de tratamiento y abordar reconstrucciones cada vez más complejas. La superficie unicCa® resulta de la incorporación a la superficie multirrugosa optima® de una capa de iones de calcio. Las modificaciones realizadas en el desarrollo de esta nueva superficie hacen que presente ventajas como: impedimento del envejecimiento del óxido de titanio, mejora de la unión hueso-implante y aceleración de la fase de la osteointegración. Para demostrar las propiedades de esta nueva superficie se realizaron estudios en cóndilo femoral de conejo y en tibia de oveja. En ambos casos se demostró un incremento y aceleración de la osteointegración. El calcio, presente en la superficie unicCa®, asegura la estimulación celular desde los primeros momentos tras la implantación hasta la consolidación de los tejidos y la formación de la capa calcificada de osteointegración de la que es el constituyente principal. Esto implica una regeneración peri-implante más rápida y de mejor calidad

The surface of the dental implants is a fundamental parameter to consider for improving bone regeneration based on implants. Together with the surgical techniques and materials and tools used, surface modifications of the implants have evolved over time to allow to shorten treatment times and address increasingly complex reconstructions. The unicCa® surface is the result of the addition to the optima® surface of a layer of calcium ions. The modifications made in the development of this new surface make this advantages such as: impairment of the aging of the titanium oxide, improvement of the union bone-implant and acceleration of the phase of the osseointegration. To demonstrate the properties of this new area studies were performed in rabbit femoral condyle and in tibia of sheep. In both cases showed an increase and acceleration of the osseointegration. The calcium, present on the the unicCa® surface ensures the cellular stimulation from the first moments after implantation until the consolidation of the tissues and the formation of the osseointegration of calcified layer which is the main constituent. This implies a regeneration peri-implant faster and of better quality

The effect of therapeutic ultrasound on fibroblast cells in vitro: the systematic review / Efecto del ultrasonido terapéutico en células fibroblásticas in vitro: revisión sistemática

Introduction: Therapeutic ultrasound is one of the most used physical resources in the area of physiotherapy for the treatment of injuries. However, the multiplicity of dosimetry used in clinical practice points to its indiscriminate use for pathologies that surround skeletal muscle and expresses the limitation of the available literature on the ideal dosimetric standardization to the tissue restoration, mechanism of action and its real effects on the treatment in question. Objective: The objective of this study was to promote a systematic review about the different effects and the dosimetric parameters of therapeutic ultrasonic irradiation on the process of restoration of fibroblast cells in vitro. Methods: To select the articles, three electronic data banks were consulted, with publication from January 2000 to September 2016. The studies were tracked by three freestanding reviewers, according to inclusion and exclusion criteria. Results: 669 articles were selected and after the application of inclusion and exclusion criteria, 647 were excluded. Among the exclusions reasons there are: the utilization of another physical method, exclusive focus on another type of cell line, other experimental models or the use of another language, reaching at the end 22 studies directed to qualitative analysis. Conclusion: The results of this study showed that the scientific basis is not enough to stablish real effects and dosimetric parameters of therapeutic ultrasonic on the process of restoration of fibroblast cells in vitro, due to the lack of generalization and conflict of found results

Introducción: El ultrasonido terapéutico es uno de los recursos físicos más utilizados en el área de fisioterapia para el tratamiento de lesiones. Sin embargo, la gran cantidad de dosimetrías utilizadas en la práctica clínica muestra su uso indiscriminado para patologías que circundan el músculo esquelético y además expresa la limitación de la literatura sobre la estandarización dosimétrica ideal para la restauración del tejido, mecanismo de acción y sus efectos reales sobre el tratamiento en cuestión. Objetivos: El objetivo de este estudio fue realizar una revisión sistemática sobre los diferentes efectos y parámetros dosimétricos de la irradiación ultrasónica terapéutica en el proceso de reparación de células fibroblásticas in vitro. Material y método: Para la selección de los artículos fueron consultadas tres bases de datos para buscar publicaciones entre enero de 2000 y septiembre de 2016. La búsqueda de trabajos se realizó por tres revisores independientes, conforme a los criterios de inclusión y exclusión. Resultados: Se seleccionaron 669 artículos y tras la aplicación de los criterios de inclusión, se excluyeron 647 estudios. Entre los motivos de exclusión están la utilización de otro medio físico, enfoque exclusivo de otro tipo de línea celular, otros modelos experimentales o el uso de otro idioma, quedando 22 estudios para el análisis cualitativo. Conclusión: Los hallazgos de este estudio mostraron que la base científica todavía es insuficiente para el establecimiento de los efectos reales y parámetros dosimétricos de la irradiación ultrasónica terapéutica en el proceso de reparación de células fibroblásticas in vitro, por la falta de generalización y conflicto de los resultados encontrados

Comparacion de un nuevo agente basado en nanotecnología con el talco convencional para el control de los derrames pleurales malignos / Comparison between a new nanotechnology-based agent and conventional talc in the control of malignant pleural effusions

En este trabajo usamos dióxido de titanio (TiO2), fabricado mediante nanotecnología. Para demostrar su superioridad respecto al talco, realizamos un estudio in vitro comparando la respuesta pro-inflamatoria de ambos agentes sobre células malignas y mesoteliales benignas; investigando la posible inducción de apoptosis y la posible inhibición de angiogénesis también por ambos agentes. Realizamos cultivo de líneas celulares derivadas de mesotelio humano, procedente de mesotelioma bifásico humano y adenocarcinoma bronquial humano. Las células se co-cultivaron con diferentes dosis de talco y de nanopartículas de TiO2. En todas las muestras de sobrenadantes de los cultivos se analizaron los niveles de diferentes mediadores inflamatorios. La tasa de apoptosis se analizó por la expresión de Caspasa-3. Para el estudio de angiostasis se determinaron los niveles de endostatina mediante técnica ELISA. Observamos que la viabilidad de las células mesoteliales benignas es mucho menor al emplear TiO2. En el caso de las células mesoteliales malignas, se observó el mismo efecto con dosis alta de TiO2. En el adenocarcinoma de pulmón, la viabilidad de estas células expuestas al talco fue netamente inferior a la que se observó en la línea celular benigna. La producción de IL-8 fue mucho mayor por parte de las células mesoteliales neoplásicas que por las benignas y aumentó siguiendo un patrón dosis dependiente frente al talco, mientras que cayó con el TiO2. Según estos resultados, se demuestra que el talco es superior al TiO2 en su capacidad de producir mediadores que favorecerían la pleurodesis para el control del derrame pleural maligno

For this study, we used titanium dioxide (TiO2), produced using nanotechnology. To show its superiority with respect to talc, we completed an in vitro study comparing the pro-inflammatory response of both agents towards malignant and benign mesothelial cells; researching the possible apoptosis induction and possible inhibition of angiogenesis for both agents. We took a culture of cell lines derived from human mesothelioma, originating from human biphasic mesothelioma and human bronchial adenocarcinoma. The cells were cocultured with different doses of talc and TiO2 nanoparticles. The levels of different inflammatory mediators were analyzed for each culture supernatant sample. The apoptosis rate was analyzed using caspase-3 expression. The endostatin levels were determined for the angiostasis study using the ELISA technique. We observed that the viability of the benign mesothelial cells is much lower after using TiO2. In the case of malignant mesothelial cells, the same effect was observed with a high dose of TiO2. In adenocarcinoma of the lung, the viability of these cells exposed to talc was distinctly lower than that which was observed in the benign cell line. IL-8 production was much higher in neoplastic mesothelial cells than in benign cells and increased following a dose-dependent pattern with talc, while it decreased with TiO2. According to these results, we can see that talc is superior to TiO2 in its ability to produce mediators which favor pleurodesis for the control of malignant pleural effusions

Production of bone mineral material and BMP-2 in osteoblasts cultured on double acid-etched titanium

Background: The study of osteoblasts and their osteogenic functions is essential in order to understand them and their applications in implantology. In this sense, this study try to study BMP-2 production and bone matrix deposition, in addition to other biological variables, in osteoblasts cultured on a rough double acid-etched titanium surface (Osseotite®, Biomet 3i, Palm Beach Garden, Florida, USA) in comparison to a smooth titanium surface (machined) and a control Petri dish. Material and Methods: An in vitro prospective study. NHOst human osteoblasts from the femur were cultured on three different surfaces: Control group: 25-mm methacrylate dish (n = 6); Machined group: titanium discs with machined surface (n = 6) and Experimental group: titanium discs with a double acid-etched nitric and hydrofluoric Osseotite® acid surface (n = 6). A quantification of the mitochondrial membrane potential, and studies of apoptosis, mobility and adhesion, bone productivity (BMP-2) and cellular bone synthesis were carried out after culturing the three groups for forty-eight hours. Results: A statistically significant difference was observed in the production of BMP-2 between the experimental group and the other two groups (22.33% ± 11.06 vs. 13.10% ± 5.51 in the machined group and 3.88% ± 3.43 in the control group). Differences in cellular bone synthesis were also observed between the groups (28.34% ± 14.4% in the experimental group vs. 20.03% ± 6.79 in the machined group and 19.34% ± 15.93% in the control group). Conclusions: In comparison with machined surfaces, Osseotite® surfaces favor BMP-2 production and bone synthesis as a result of the osteoblasts in contact with it (AU)

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Protective role of downregulated MLK3 in myocardial adaptation to chronic hypoxia

A series of protective responses could be evoked to achieve compensatory adaptation once cardiomyocytes are subjected to chronic hypoxia. MLK3/JNK/c-jun signaling pathway was previously demonstrated to be involved in this process. In the present study, we aim to further examine the performance of MLK3 in hypoxic H9C2 cells and potential mechanism. Myocardial samples of patients with congenital heart disease (CHD) were collected. H9C2 cells were cultured in hypoxic conditions for various durations. MLK3 was silenced by transfection of shRNA to evaluate its role in cell viability. We found expression of MLK3 protein was lower in patients with cyanotic CHD. In hypoxic H9C2 cells, its expression was gradually decreased in a time-dependent manner. However, there was no significant difference about expression of MLK3 mRNA. According to the results of MTT, LDH, and TUNEL, faster cell growth curve, lower death rate, and less apoptotic cells could be observed in MLK-shRNA group compared with scramble-shRNA group. Silencing of MLK3 significantly reduced expression of cleaved caspase-3, cleaved PARP, Bad, and Bax, together with increased expression of Bcl-2 and ration of Bcl-2/Bax. Both ratio of phospho-JNK/total JNK and ratio of phospho-c-jun/total c-jun were significantly decreased once MLK3 was silenced. At various reoxygenation time, MLK3 shRNA could significantly promote cell survival and decrease cell death according to MTT and LDH. Our results suggested that chronic hypoxia could reduce MLK3 expression in a posttranscriptional regulatory manner. Downregulation of MLK3 protects H9C2 cells from hypoxia-induced apoptosis and H/R injury via blocking the activation of JNK and c-jun