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To detect redox potential evolution during the initial stage of an acute wound, a redox-sensitive SERS-active optical fiber was fabricated by integrating redox-sensitive SERS probes in a hole of an optical fiber. The redox-sensitive SERS-active optical fibers carried redox-sensitive SERS probes into the inside of a wound to sense its redox potential. The laser was transmitted to the redox-sensitive SERS probes in the body by optical fibers, and the SERS signals of the redox-sensitive SERS probes were transferred out of the body by optical fibers to indicate the redox potentials in the wound. The redox-sensitive SERS probes dynamically sensed the redox potential in vivo, and their SERS signals were collected constantly to indicate the redox potentials. The assessments in vivo and in vitro proved the responsiveness of redox-sensitive SERS-active optical fibers. The redox potential evolution during the initial stage of an acute wound with the treatments of different concentrations of glucose was detected to verify the feasibility of redox-sensitive SERS-active optical fibers to dynamically detect redox potentials in vivo. The redox-sensitive SERS-active optical fiber would be a versatile tool to explore the roles of redox potentials in living organisms.
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Espectrometría Raman , Oxidación-Reducción , Espectrometría Raman/instrumentación , Espectrometría Raman/métodos , Masculino , Animales , Ratas , Ratas Sprague-Dawley , Enfermedad Aguda , Heridas y Lesiones/diagnósticoRESUMEN
Sex estimation based on teeth could help to narrow the scope for individual identification. According to the different teeth morphology among both genders, we plan to establish a sex estimation method for the northern Chinese population through mesiodistal diameter and teeth volume measurements and compare the accuracy of the two methods. In this study, measurements were taken from cone-beam computed tomography images collected from 142 males and 140 females aged 21-59 years. The mesiodistal diameter and volume of the left canines and the first molars in both upper and lower jaws were measured and analyzed for suitable coefficients. We selected 80% samples as the training set to set up the logistic regression formulas and 20% as the test set to obtain accuracy. The accuracy of sex estimation by mesiodistal diameter can reach 87.50%, and the volume is up to 78.57%. The measurement of mesiodistal diameter is less time-consuming. This work established and tested a method to estimate sex for the northern Chinese population. Results showed that sex estimation based on the mesiodistal diameter of teeth has higher accuracy than the method based on teeth volume.
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The influence of spin-orbit coupling on the cooling of NH molecular laser is investigated based on the ab initio theory. The potential energy curves (PECs) and spectral constants for four Λ-S states (X3Σ-, a1Δ, b1Σ+ and A3Π) and eight Ω states [Formula: see text] a1Δ2, [Formula: see text] and [Formula: see text] ) of NH molecule are obtained by the multi-reference configuration interaction (MRCI) plus Davidson correction. The spectroscopic constants (Re, ωe, ωeχe, Be, De) are obtained by solving the one dimensional radial Schrödinger equation, and the results are almost the same as the previously reported data. In addition, the transition dipole moment, permanent dipole moment, Franck-Condon factors, and radiative lifetime of NH molecule are also acquired. Also, the effects of the intermediate state on the [Formula: see text] , [Formula: see text] and [Formula: see text] transitions are considered. The feasible laser cooling schemes using a single laser are formulated. In the proposed cooling scheme, there wavelengths for the [Formula: see text] are used, the main pump lasers are λ00 = 335.74 nm. The feasible transition is based on this. It is found that spin-orbit coupling has a significant effect on potential energy curves, permanent dipole moments, transition dipole moments and vibration energy levels.
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Photothermal therapy is a very promising treatment method in the field of cancer therapy. The photothermal nanomaterials in near-infrared region (NIR-I, 750-900 nm) attracts extensive attention in recent years because of the good biological penetration of NIR light. However, the penetration depth is still not enough for solid tumors due to high tissue scattering. The light in the second near-infrared region (NIR-II, 1000-1700 nm) allows deeper tissue penetration, higher upper limit of radiation and greater tissue tolerance than that in the NIR-I, and it shows greater application potential in photothermal conversion. This review summarizes the photothermal properties of Au nanomaterials, two-dimensional materials, metal oxide sulfides and polymers in the NIR-II and their application prospects in photothermal therapy. It will arouse the interest of scientists in the field of cancer treatment as well as nanomedicine.
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BACKGROUND: Poor physical functioning (PF) is a common issue among critically ill patients. It was suggested that reasonable nutrition accelerates PF recovery. However, the details and types of nutritional interventions on the PF of different intensive care unit (ICU) patients at present have not been well analyzed yet. This study aimed to systematically synthesize nutritional interventions on PF in different ICU populations. METHODS: Whittemore and Knafl's framework was employed. PubMed, EMBASE, Web of Science, CINAHL Plus with Full Text, and Cochrane Library were searched to obtain studies from January 2010 to September 2020, with a manual search of the included studies' references. Record screening, data extraction, and quality appraisal were conducted independently by each reviewer before reaching an agreement after discussion. RESULTS: Twelve studies were included reporting the effects of early parenteral nutrition, early enteral nutrition, early goal-directed nutrition, early adequate nutrition, higher protein delivery, higher energy delivery, low energy delivery, energy and protein delivery, intermittent enteral feeding on PF like muscle mass, muscle strength, and function. Function was the most common outcome but showed little improvements. Muscle strength outcomes improved the most. The mechanically ventilated were the most popular target ICU population. The commenced time of the interventions is usually within 24 to 48 hours after ICU admission. CONCLUSION: Research on nutritional interventions on critically ill patients' PF is limited, but most are of a high level of evidence. Few intervention studies specified their evidence basis. Qualitative studies investigating timeframe of initiating feeding, perspectives of the patients' perspectives and caregivers are warranted to advance research and further discuss this topic.
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Lips are the main part of the lower facial soft tissue and are vital to forensic facial approximation (FFA). Facial soft tissue thickness (FSTT) and linear measurements in three dimensions are used in the quantitative analysis of lip morphology. With most FSTT analysis methods, the surface of soft tissue is unexplicit. Our study aimed to determine FSTT and explore the relationship between the hard and soft tissues of lips in different skeletal occlusions based on cone-beam CT (CBCT) and 3dMD images in a Chinese population. The FSTT of 11 landmarks in CBCT and 29 lip measurements in CBCT and 3dMD of 180 healthy Chinese individuals (90 males, 90 females) between 18 and 30 years were analyzed. The subjects were randomly divided into two groups with different skeletal occlusions distributed equally: 156 subjects in the experimental group to establish the prediction regression formulae of lip morphology and 24 subjects in the test group to assess the accuracy of the formulae. The results indicated that FSTT in the lower lip region varied among different skeletal occlusions. Furthermore, sex discrepancy was noted in the FSTT in midline landmarks and linear measurements. Measurements showing the highest correlation between soft and hard tissues were between total upper lip height and Ns-Pr (0.563 in males, 0.651 in females). The stepwise multiple regression equations were verified to be reliable with an average error of 1.246 mm. The method of combining CBCT with 3dMD provides a new perspective in predicting lip morphology and expands the database for FFA.
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Tomografía Computarizada de Haz Cónico , Imagenología Tridimensional , Labio/anatomía & histología , Labio/diagnóstico por imagen , Adulto , Puntos Anatómicos de Referencia , Pueblo Asiatico/etnología , Pesos y Medidas Corporales , Cara/anatomía & histología , Cara/diagnóstico por imagen , Femenino , Humanos , Masculino , Análisis de Regresión , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
AIM: This study aimed to develop a patient classification system that stratifies patients admitted to the intensive care unit based on their disease severity and care needs. BACKGROUND: Classifying patients into homogenous groups based on clinical characteristics can optimize nursing care. However, an objective method for determining such groups remains unclear. METHODS: Predictors representing disease severity and nursing workload were considered. Patients were clustered into subgroups with different characteristics based on the results of a clustering algorithm. A patient classification system was developed using a partial least squares regression model. RESULTS: Data of 300 patients were analysed. Cluster analysis identified three subgroups of critically patients with different levels of clinical trajectories. Except for blood potassium levels (p = .29), the subgroups were significantly different according to disease severity and nursing workload. The predicted value ranges of the regression model for Classes A, B and C were <1.44, 1.44-2.03 and >2.03. The model was shown to have good fit and satisfactory prediction efficiency using 200 permutation tests. CONCLUSIONS: Classifying patients based on disease severity and care needs enables the development of tailored nursing management for each subgroup. IMPLICATIONS FOR NURSING MANAGEMENT: The patient classification system can help nurse managers identify homogeneous patient groups and further improve the management of critically ill patients.
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Unidades de Cuidados Intensivos , Carga de Trabajo , Adulto , Enfermedad Crítica , Estudios Transversales , Humanos , Aprendizaje AutomáticoRESUMEN
Dentition is an individualizing structure in humans that may be potentially utilized in individual identification. However, research on the use of three-dimensional (3D) digital models for personal identification is rare. This study aimed to develop a method for individual identification based on a 3D image registration algorithm and assess its feasibility in practice. Twenty-eight college students were recruited; for each subject, a dental cast and an intraoral scan were taken at different time points, and digital models were acquired. The digital models of the dental casts and intraoral scans were assumed as antemortem and postmortem dentition, respectively. Additional 72 dental casts were extracted from a hospital database as a suspect pool together with 28 antemortem models. The dentition images of all of the models were extracted. Correntropy was introduced into the traditional iterative closest point algorithm to compare each postmortem 3D dentition with 3D dentitions in the suspect pool. Point-to-point root mean square (RMS) distances were calculated, and then 28 matches and 2772 mismatches were obtained. Statistical analysis was performed using the Mann-Whitney U test, which showed significant differences in RMS between matches (0.18±0.03mm) and mismatches (1.04±0.67mm) (P<0.05). All of the RMS values of the matched models were below 0.27mm. The percentage of accurate identification reached 100% in the present study. These results indicate that this method for individual identification based on 3D superimposition of digital models is effective in personal identification.
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Dentición , Odontología Forense/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional , Modelos Dentales , Adulto , Algoritmos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Higher relevance may increase older adults' engagement in cognitively demanding activities; however, whether this effect will maintain when available cognitive resources are limited? Consequently, we investigated the joint impact of task relevance and cognitive load on older and younger adults' decision search behaviors. We adopted a 2 (age: young/old) × 2 (cognitive load: without load/with load) × 2 (task relevance: high/low) mixed design. Sixty-one younger and 63 older adults completed high-relevance and low-relevance decisions. Our results revealed that older (vs. younger) adults took more time and more alternative-based search before decision-making. Both age groups sampled less information with an additional memory task. Additionally, they spent more time and effort to sample more information on high-relevance (vs. low-relevance) decisions; however, such differences disappeared when with an additional memory task. Task relevance promoted both age groups' search engagement, but this effect was subjected to their available cognitive resources.
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Cognición , Toma de Decisiones , Conducta en la Búsqueda de Información , Adolescente , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Entrevistas como Asunto , Juicio , Masculino , Persona de Mediana Edad , Reconocimiento en Psicología , Adulto JovenRESUMEN
The nose is the most prominent part of the face and is a crucial factor for facial esthetics as well as facial reconstruction. Although some studies have explored the features of external nose and predicted the relationships between skeletal structures and soft tissues in the nasal region, the reliability and applicability of methods used in previous studies have not been reproduced. In addition, the majority of previous studies have focused on the sagittal direction, whereas the thickness of the soft tissues was rarely analyzed in three dimensions. A few studies have explained the specific characteristics of the nose of Chinese individuals. The aim of this study was to investigate the relationship between the hard nasal structures and soft external nose in three dimensions and to predict the morphology of the nose based on hard-tissue measurements. To eliminate the influence of low resolution of CBCT and increase the accuracy of measurement, three-dimensional (3D) images captured by cone-beam computed tomography (CBCT) and 3dMD photogrammetry system were used in this study. Twenty-six measurements (15 measurements for hard tissue and 11 measurements for soft tissue) based on 5 craniometric and 5 capulometric landmarks of the nose of 120 males and 120 females were obtained. All of the subjects were randomly divided into an experimental group (180 subjects consisting of 90 males and 90 females) and a test group (60 subjects consisting of 30 males and 30 females). Correlation coefficients between hard- and soft-tissue measurements were analyzed, and regression equations were obtained based on the experimental group and served as predictors to estimate nasal morphology in the test group. Most hard- and soft-tissue measurements appeared significantly different between genders. The strongest correlation was found between basis nasi protrusion and nasospinale protrusion (0.499) in males, and nasal height and nTr-nsTr (0.593) in females. For the regression equations, the highest value of R2 was observed in the nasal bridge length in males (0.257) and nasal tip protrusion in females (0.389). The proportion of subjects with predicted errors < 10% was over 86.7% in males and 70.0% in females. Our study proved that a combined CBCT and 3dMD photogrammetry system is a reliable method for nasal morphology estimation. Further research should investigate other influencing factors such as age, skeletal types, facial proportions, or population variance in nasal morphology estimation.
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Tomografía Computarizada de Haz Cónico/métodos , Cara/anatomía & histología , Cara/diagnóstico por imagen , Imagenología Tridimensional , Nariz/anatomía & histología , Nariz/diagnóstico por imagen , Fotogrametría/métodos , Adulto , Puntos Anatómicos de Referencia , Pueblo Asiatico/etnología , Cefalometría , Femenino , Ciencias Forenses , Humanos , Masculino , Proyectos Piloto , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
MicroRNAs (miRNAs or miRs) are critical regulators in various diseases. In the current study, the role of miR30c5p in the formation of sodium oxalateinduced kidney stones was investigated. For this purpose, human renal tubular epithelial cells (HK2 cells) were incubated with sodium oxalate at the concentrations of 100, 250, 500, 750 and 1,000 µM. Cell viability and the miR30c5p expression level were respectively measured by CCK8 assay and RTqPCR. After separately transfecting miR30c5p mimic and inhibitor into the HK2 cells, the cell apoptotic rate, the levels of mitochondrial membrane potential (MMP) and ROS were determined by flow cytometry. The levels of oxidative stress indicators [lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT)] were determined using commercial kits. Crystalcell adhesion assay was performed to evaluate the crystal adhesion capacity in vitro. miR30c5p binding at autophagy related 5 (ATG5) was predicted by TargetScan7.2 and further verified by dualluciferase reporter assay. Rescue experiments were performed to confirm the molecular mechanisms underlying sodium oxalateinduced kidney formation in HK2 cells. The results revealed that sodium oxalate decreased the viability of HK2 cells in a concentrationdependent manner, and that miR30c5p expression was significantly downregulated by exposure to 750 µM sodium oxalate. In addition, the increase in cell apoptosis and crystal number, and the upregulated levels of LDH, MDA and ROS were reversed by the overexpression of miR30c5p. Moreover, the overexpression of miR30c5p upregulated the levels of SOD, CAT and MMP induced by sodium oxalate. ATG5 was directly regulated by miR30c5p, and the inhibition of cell cytotoxicity and crystalcell adhesion induced by miR30c5p mimic was blocked by ATG5. These data indicated that the overexpression of miR30c5p alleviated cell cytotoxicity and crystalcell adhesion induced by sodium oxalate through ATG5. Thus, the current study provides a better understanding of the role of miR30c5p in sodium oxalateinduced kidney stones.
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Proteína 5 Relacionada con la Autofagia/genética , Cálculos Renales/genética , MicroARNs/genética , Regulación hacia Arriba , Apoptosis , Proteína 5 Relacionada con la Autofagia/metabolismo , Línea Celular , Regulación de la Expresión Génica , Humanos , Riñón/metabolismo , Riñón/patología , Cálculos Renales/metabolismo , Cálculos Renales/patología , Ácido Oxálico/metabolismo , Estrés OxidativoRESUMEN
Facial reconstruction is a classical technique in forensic anthropology to reestablish the contours of the soft tissues over the skull. The accurate facial soft tissue data plays an essential role in forensic facial reconstruction. However, according to previous studies, various skeletal types might relate to different thickness in facial soft tissue. Until now, there are few publications focusing on the relationship between facial soft tissue thickness (FSTT) and different skeletal types, and none of them analyze the FSTT according to various sagittal and vertical skeletal types. The aim of this study was to testify the possible existence of correlations between FSTT and different skeletal types. In order to exclude interference from age, sex, ethnicity and body mass index (BMI) factors, we collected lateral projection X-rays data of 270 Chinese female aged 19-26 years with nomal BMI and divided them into various skeletal groups. Soft tissue thickness measurements were mainly based on 10 anthropological landmarks of the skull and statistics were analyzed on the basis of different skeletal types. The greatest differences were observed in the upper lip region of maxilla and the mental region of mandible. The concave and hypodivergent skull types showed the thickest soft tissue in maxillary region, and the convex and hypedivergent skull types showed the thickest soft tissue in the mental region. This study provided a database for FSTT according to various skeletal types in Chinese female population, and our current studies demonstrated that considering various skeletal types will improve the accuracy of facial reconstruction.
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Tejido Conectivo/anatomía & histología , Cráneo/anatomía & histología , Adulto , Pueblo Asiatico , Cara/anatomía & histología , Femenino , Antropología Forense , Humanos , Mandíbula/anatomía & histología , Maxilar/anatomía & histologíaRESUMEN
This study investigated the relationship between cognitive abilities and age differences in information search and the moderating role of task self-relevance by measuring the decision-making processes of participants in both high and low self-relevance decision-making tasks. The sample included 57 young and 65 older adults. They viewed five-alternative × five-attribute decision matrices that required them to open, with a mouse click, the information cells that interested them. Processing speed, verbal fluency, working memory, and vocabulary were measured as cognitive abilities. The dependent variables were search engagement (including time-related engagement and frequency-related engagement) and search pattern (calculated based on alternative-based or attribute-based search). The results from structured equation modeling showed that age negatively predicted these cognitive abilities (processing speed, verbal fluency, working memory, and vocabulary) and positively predicted information search engagement. Processing speed mediated the effect of age on study time per cell under tasks with both high and low self-relevance. Verbal fluency, meanwhile, mediated the total search time and checking time per cell when the task was highly self-related but not when the task had low self-relevance. These results suggest that self-relevance can moderate the mediation effect of verbal fluency on the relationship between age and information search time; this means that older adults whose verbal fluency was limited require relatively more time to search information to make an informed decision. However, this effect is only sufficient when the decision-making task is highly self-related and provokes more engagement motivation toward it.
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OBJECTIVE: This study aims to determine the mediating effects of psychological empowerment on abusive supervision and turnover intention as perceived by nurses to provide information to change the status of nurse turnover. METHODS: A cross-sectional survey (a questionnaire examining perceptions of abusive supervision, measurement of psychological empowerment, and questionnaire for turnover intention) was used to collect data. A total of 1127 clinical nurses, who were recruited through convenience sampling, participated in the survey. RESULTS: Nurses' average perceived abusive supervision, psychological empowerment, and turnover intention scores were 1.62⯱â¯0.95, 3.24⯱â¯0.83, and 14.17⯱â¯3.78, respectively. Psychological empowerment was found to mediate the relationship between abusive supervision and turnover intention (Pâ¯<â¯0.01). Turnover intention tends to be stronger and psychological empowerment reduced when nurse managers adopt an abusive leadership style. CONCLUSIONS: Nurses' psychological empowerment is an intermediary variable that predicts the relationship between abusive supervision and turnover intention. Nurse managers should manage abusive supervision to increase nurses' psychological empowerment and decrease turnover intention.
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BACKGROUND: Sensory function, processing speed, and working memory are considered to be mechanisms that play important explanatory roles in age-related decline of cognitive abilities. As individuals age, sensory function declines along with other cognitive abilities, including processing speed and working memory. Moreover, the relationship between sensory function, processing speed, and working memory, which represent the most basic mechanism, is one of the important issues in the field of cognitive aging. METHODS: To explore the role of sensory function, especially visual function, in processing speed and working memory aging, the present study adopted a 2 (age: young and old) × 4 (visual perceptual stress: high, medium, low, and non-stress) mixed design and explored age differences in tasks testing processing speed and working memory. To generate different levels of visual perceptual stress, test materials were masked with Gaussian noise according to each individual's visual function. RESULTS: The results indicated that age differences in processing speed were not influenced by different levels of visual perceptual stress, while age differences in working memory performance decreased gradually with the increase of visual perceptual stress. CONCLUSION: Visual function affected age differences in working memory rather than in processing speed. The common-cause hypothesis and information-degradation hypothesis were applied to interpret the relationships between visual function and processing speed and between visual function and working memory, respectively. Moreover, sensory function may not directly affect working memory function, which was also consistent with a resource decrement model of aging.
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Envejecimiento/psicología , Memoria a Corto Plazo , Sensación , Percepción Visual , Adulto , Anciano , Cognición , Femenino , Humanos , Masculino , Estrés Psicológico , Adulto JovenRESUMEN
This study examined age differences in daily life events related to different types of social goals based on the socioemotional selectivity theory (SST), and determined whether the positivity effect existed in the context of social goals in older adults' daily lives. Over a course of 14 days, 49 older adults and 36 younger adults wrote about up to three life events daily and rated the valence of each event. The findings indicated that (1) although both older and younger adults recorded events related to both emotional and knowledge-acquisition goals, the odds ratio for reporting a higher number of events related to emotional goals compared to the number of events related to knowledge-acquisition goals was 2.12 times higher in older adults than that observed in younger adults. (2) Considering the number of events, there was an age-related positivity effect only for knowledge-related goals, and (3) older adults' ratings for events related to emotional and knowledge-acquisition goals were significantly more positive compared to those observed in younger adults. These findings supported the SST, and to some extent, the positivity effect was demonstrated in the context of social goals.
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PURPOSE: The current study was carried out to assess the effects of chronic intermittent hypoxia (CIH) on the kidney, the intervention roles of adiponectin (Ad), and the associated mechanisms. METHODS: Sixty Wistar rats were randomly divided into four groups: the normal control (NC), normal control plus Ad supplement (NC + Ad), CIH, and CIH plus Ad supplement (CIH + Ad) groups. The rats in both CIH and CIH + Ad groups were submitted to a CIH environment for 4 months, while the rats in NC and NC + Ad groups were housed with the normal air for 4 months. In addition, the rats in NC + Ad and CIH + Ad groups were treated with an intravenous injection of Ad at a dosage of 10 µg per injection, twice a week, for four successive months. RESULTS: The production level of reactive oxygen species (ROS) and the protein levels of endoplasmic reticulum (ER) stress, as well as the cell apoptosis level in kidney, were all higher in the CIH group than in the NC and NC + Ad groups (all p < 0.05). However, the ROS production, the protein of ER stress, and cell apoptosis levels in kidney were all lower in the CIH + Ad group than those in the CIH group (all p < 0.05). CONCLUSION: Ad could protect against CIH-induced renal cell apoptosis through inhibiting ROS-related ER stress.
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Adiponectina/fisiología , Retículo Endoplásmico/fisiología , Hipoxia/fisiopatología , Riñón/irrigación sanguínea , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/fisiología , Riñón/citología , Ratas , Ratas WistarRESUMEN
The association between the temporal activation of Wnt/ß-catenin pathway and the spontaneous hepatocellular carcinoma (HCC) development in Farnesoid X receptor (FXR) knockout mice is not well understood. We found that Huh7 cells depleted with FXR by RNAi showed enhanced cell growth, migration and invasion in vitro and accelerated tumor xenografts formation in nude mice. And these phenotypes were attenuated by simultaneous knockdown of ß-catenin with RNAi. Furthermore, we identified that FXR could bind with ß-Catenin through AF1 domain, and disrupt the assembly of the core ß-Catenin/TCF4 complex. Activation of FXR attenuated the DNA-binding activity of ß-Catenin/TCF4, and subsequently, its targeting gene-cyclin D1 expression. Importantly, FXR expression was markedly reduced in human HCC, an event which correlated with aberrant activation of ß-Catenin. These data identified FXR as a negative regulator of HCC development through direct suppression of Wnt/ß-catenin pathway.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , beta Catenina/metabolismo , Animales , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Células Hep G2 , Xenoinjertos , Humanos , Neoplasias Hepáticas/genética , Ratones , Ratones Noqueados , Receptores Citoplasmáticos y Nucleares/genética , Transducción de Señal , Factores de Transcripción , TransfecciónRESUMEN
The genes that encode inhibitor of apoptosis proteins (IAPs) are frequently overexpressed in human cancers. However, the expression pattern and clinical significance of BIRC6, a member of IAPs, in hepatocellular carcinoma (HCC) remains unclear. Here we investigated the role of BIRC6 in hepatocellular carcinogenesis. We used immunoblot and immunochemical analyses to determine the levels of BIRC6 in 7 hepatoma cell lines and 160 HCC specimens. We evaluated the proognostic value of BIRC6 expression and its association with clinical parameters. A lentivirus-mediated silencing method was used to knockdown BIRC6, and the biological consequences of BIRC6 silencing in three hepatoma cell lines were investigated in vitro and in vivo. We found that BIRC6 overexpression was significantly correlated with serum ALT level and HCC vascular invasion. Patients with positive BIRC6 expression in tumor tissue had a poor survival and a high rate of recurrence. BIRC6 knockdown remarkably suppressed cell proliferation, caused G1/S arrest and sensitized hepatoma cells to sorafenib-induced apoptosis in hepatoma cells, which was partly reversed by RNA interference targeting p53. The mechanistic study revealed that BIRC6 interacted with p53 and facilitated its degradation. The in vivo study showed that BIRC6 knockdown inhibited xenograft tumor growth and increased the sensitivity of tumor cells to sorafenib in nude mice. Taken together, these findings demonstrate that BIRC6 overexpression in HCC specimens is indicative of poor prognosis and that its interaction with p53 facilitates the degradation of p53, leading to carcinogenesis and an anti-apoptotic status.
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Carcinoma Hepatocelular/patología , Proteínas Inhibidoras de la Apoptosis/fisiología , Neoplasias Hepáticas/patología , Proteína p53 Supresora de Tumor/metabolismo , Animales , Apoptosis , Carcinogénesis , Ciclo Celular , Proliferación Celular , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Niacinamida/análogos & derivados , Niacinamida/farmacología , Niacinamida/uso terapéutico , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Pronóstico , Sorafenib , UbiquitinaciónRESUMEN
Fructose is a key dietary factor in the development of nonalcoholic fatty liver disease (NAFLD). Here we investigated whether WAY-362450 (WAY), a potent synthetic and orally active FXR agonist, protects against fructose-induced steatosis and the underlying mechanisms. C57BL/6J mice, fed 30% fructose for 8 weeks, were treated with or without WAY, 30 mg/kg, for 20 days. The elevation of serum and hepatic triglyceride in mice fed 30% fructose was reversed by WAY treatment. Histologically, WAY significantly reduced triglyceride accumulation in liver, attenuated microphage infiltration and protected the junction integrity in intestine. Moreover, WAY remarkably decreased portal endotoxin level, and lowered serum TNFα concentration. In lipopolysaccharide (LPS)-induced NAFLD model, WAY attenuated serum TNFα level. Moreover, WAY suppressed LPS-induced expression of hepatic lipid droplet protein adipose differentiation-related protein (ADRP), down-regulation of it in mice fed 30% fructose. Furthermore, WAY repressed lipid accumulation and ADRP expression in a dose-dependent manner in palmitic acid (PA)-treated HepG2 and Huh7 cells. WAY suppressed TNFα-induced ADRP up-regulation via competing with AP-1 for ADRP promoter binding region. Together, our findings suggest that WAY, an FXR agonist, attenuates liver steatosis through multiple mechanisms critically involved in the development of hepatosteatosis, and represents a candidate for NAFLD treatment.