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PURPOSE: Increasing evidence suggested that microRNA plays an important role in ovarian cancer. In this study, the role of miR-92 in ovarian cancer was investigated. METHODS: In this study, miR-92 expression in clinical sample was evaluated, role of miR-92 was investigated in vitro, and underlying mechanism was investigated using Chip, co-IP, and western blot. RESULTS: In this study, we show that miR-92 is overexpressed in ovarian cancer tissue compared with normal cancer tissue. Transfection of miR-92 increased proliferation of ovarian cancer cell, and increased migration capacity and colony formation were observed after miR-92 transfection; we found that expression of LATS2 was decreased by miR-92, and this was further confirmed by luciferase assay, which proved that miR-92 is targeting 3' of the endogenous LATS2 gene. Downregulation of LATS2 resulted in increased translocation of YAP1 and upregulation of PD-L1, which subsequently suppressed NK cell function and promoted T cell apoptosis. Moreover, co-transfection of YAP1-targeted shRNA could relieve miR-92-induced immune suppression effect. Mechanically, immunoprecipitation (IP) was used to show that LATS2 interacted with YAP1 and subsequently limited nuclear translocation of YAP1; chromatin immunoprecipitation (ChIP) was used to confirm that YAP1 could bind to enhancer region of PD-L1 to enhance transcription activity of PD-L1. CONCLUSIONS: Our data revealed a novel mechanism which finally resulted in immune suppression in ovarian cancer.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antígeno B7-H1/metabolismo , Células Asesinas Naturales/inmunología , MicroARNs/metabolismo , Neoplasias Ováricas/inmunología , Proteínas Serina-Treonina Quinasas/metabolismo , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Núcleo Celular/metabolismo , Proliferación Celular , Regulación hacia Abajo , Elementos de Facilitación Genéticos , Femenino , Silenciador del Gen , Humanos , Inmunidad Celular , Inmunoprecipitación , Células Madre Neoplásicas , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Proteínas Serina-Treonina Quinasas/genética , ARN Interferente Pequeño , Transducción de Señal , Linfocitos T/fisiología , Proteínas Supresoras de Tumor/genética , Regulación hacia Arriba , Proteínas Señalizadoras YAPRESUMEN
The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included.
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Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Isoanticuerpos/inmunología , Trasplante de Hígado/efectos adversos , Aloinjertos , Humanos , Informe de InvestigaciónAsunto(s)
Investigación Biomédica/normas , Sujetos de Investigación/legislación & jurisprudencia , Donantes de Tejidos , Obtención de Tejidos y Órganos , Discusiones Bioéticas , Funcionamiento Retardado del Injerto/prevención & control , Humanos , Hipotermia Inducida/ética , Consentimiento Informado/ética , National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division , Defensa del Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto/ética , Obtención de Tejidos y Órganos/ética , Estados Unidos , United States Health Resources and Services AdministrationRESUMEN
Resonant Raman spectroscopy is a powerful tool for providing information about excitons and exciton-phonon coupling in two-dimensional materials. We present here resonant Raman experiments of single-layered WS2 and WSe2 using more than 25 laser lines. The Raman excitation profiles of both materials show unexpected differences. All Raman features of WS2 monolayers are enhanced by the first-optical excitations (with an asymmetric response for the spin-orbit related XA and XB excitons), whereas Raman bands of WSe2 are not enhanced at XA/B energies. Such an intriguing phenomenon is addressed by DFT calculations and by solving the Bethe-Salpeter equation. These two materials are very similar. They prefer the same crystal arrangement, and their electronic structure is akin, with comparable spin-orbit coupling. However, we reveal that WS2 and WSe2 exhibit quite different exciton-phonon interactions. In this sense, we demonstrate that the interaction between XC and XA excitons with phonons explains the different Raman responses of WS2 and WSe2, and the absence of Raman enhancement for the WSe2 modes at XA/B energies. These results reveal unusual exciton-phonon interactions and open new avenues for understanding the two-dimensional materials physics, where weak interactions play a key role coupling different degrees of freedom (spin, optic, and electronic).
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We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Fístula Arteriovenosa/complicaciones , Hipertensión Pulmonar/etiología , Diálisis Peritoneal/efectos adversos , Proteína C-Reactiva/análisis , China/epidemiología , Hipertensión Pulmonar/epidemiología , Incidencia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Péptido Natriurético Encefálico/sangre , Fósforo/sangre , Estudios Prospectivos , Factores de RiesgoRESUMEN
We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.
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Fístula Arteriovenosa/complicaciones , Hipertensión Pulmonar/etiología , Diálisis Peritoneal/efectos adversos , Anciano , Proteína C-Reactiva/análisis , China/epidemiología , Femenino , Humanos , Hipertensión Pulmonar/epidemiología , Incidencia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fósforo/sangre , Estudios Prospectivos , Factores de RiesgoRESUMEN
Klinefelter syndrome (KS) is the most common genetic cause of male infertility. Widespread development in assisted reproductive technology has provided non-mosaic KS patients with the opportunity of having biological children. Testosterone replacement therapy and micro-dissection testicular sperm extraction are effective sperm retrieval techniques for KS patients. Despite the success of sperm retrieval and intracytoplasmic sperm injection (ICSI), some areas of early aggressive hormonal spermatogenesis and appropriate management of KS remain controversial. Androgenotherapy, a common treatment for KS, carries a risk of decreasing focal spermatogenesis by lowering the gonadotropin content. Inadequately treated hypogonadism increases psychosocial morbidity in KS patients. Preventive care must be provided from the time of diagnosis, preferentially through a multidisciplinary approach. This indicates the need for improved genetic counseling of KS patients. The aim of this study was to report the prevalence of non-mosaic KS in a Chinese infertile male population. The rate of early diagnosis was lower in KS patients; most of these were diagnosed after rising concerns of reproductive capacity. The mean age of patients with sperm or germ cells was significantly lower, while the semen volume of these patients was significantly higher. However, the semen volume was negatively correlated with the age and ratio of luteinizing hormone/testosterone content in KS patients. Therefore, genetic counseling of KS patients should focus on early diagnosis and timely treatment, in addition to improving the quality of life of all KS patients. The use of testosterone replacement therapy and/ or micro-dissection testicular sperm extraction should be preferentially considered for fertility preservation.
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Asesoramiento Genético/métodos , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/terapia , Adulto , China , Terapia de Reemplazo de Hormonas , Humanos , Infertilidad Masculina/genética , Infertilidad Masculina/fisiopatología , Infertilidad Masculina/terapia , Cariotipo , Síndrome de Klinefelter/genética , Síndrome de Klinefelter/fisiopatología , Hormona Luteinizante/sangre , Masculino , Calidad de Vida , Técnicas Reproductivas Asistidas , Recuperación de la Esperma , Espermatogénesis/genética , Testosterona/administración & dosificación , Testosterona/sangreRESUMEN
Several previous studies have demonstrated that elevated levels of fibroblast growth factor-23 (FGF-23) may be involved in atherosclerosis and contribute to the high mortality rate of peritoneal dialysis (PD) patients. The aim of this study was to determine the precise role of FGF-23 in the pathogenesis of atherosclerosis in PD patients. Between April 2009 and January 2012, 62 PD patients and 25 control subjects were included in the study. An enzyme-linked immunosorbent assay was conducted to test for plasma FGF-23 levels. Carotid artery intima-media thickness (CIMT), left ventricular mass index (LVMI), and myocardial performance index (MPI) were determined by ultrasonography. Plasma Ca(2+), P(3+), calcium-phosphorus product, parathyroid hormone, N-terminal pro-brain natriuretic peptide, and cardiac troponin I were also detected. Plasma FGF-23 levels in PD patients were significantly higher than those in control subjects. PD patients with CIMT > 1.0 mm showed the highest levels of FGF-23. Plasma P(3+), calcium-phosphorous product, plasma parathyroid hormone, CIMT, LVMI, and MPI levels were positively associated with plasma FGF-23 levels. Multiple-stepwise regression analyses revealed that plasma P(3+), plasma parathyroid hormone, CIMT, LVMI, and MPI levels were strongly associated with plasma FGF-23 levels. However, no correlations were observed in plasma N-terminal pro-brain natriuretic hormone and cardiac troponin I levels. Plasma FGF- 23 levels may play an important role in the initiation and progression of atherosclerosis. Thus, detecting and defining plasma FGF-23 levels may be a promising biomarker for the early detection of atherosclerosis in PD patients.
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Aterosclerosis/genética , Biomarcadores/sangre , Factores de Crecimiento de Fibroblastos/sangre , Diálisis Peritoneal , Adulto , Anciano , Aterosclerosis/sangre , Aterosclerosis/patología , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Hormona Paratiroidea/sangre , Factores de Riesgo , Troponina I/sangreRESUMEN
PURPOSE: To explore the altered different expression of miRNAs and the mechanisms underlying the relapse and metastasis of pancreatic cancer. MATERIALS AND METHODS: The most differentially expressed miRNAs were analyzed by gene ontology (GO) term analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein interaction analysis. The potentially regulated target genes of the most differentially expressed miRNAs were also analyzed further by GO term analysis and KEGG pathway analysis, and quantitated by qRT-PCR. RESULTS: In total, we found 12 miRNAs displayed at least a 30-fold increase or decrease in expression of carcinoma and relapse vs. para-carcinoma human pancreatic cancer (C/R vs. P). In addition, our study found that pancreatic cancer was related to pathways in cancer, including Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway. CONCLUSIONS: The differential expressed miRNAs and their predicted target genes that involved in Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway indicating their potential roles in pancreatic carcinogenesis and progress.
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Carcinoma/genética , MicroARNs/genética , Recurrencia Local de Neoplasia/genética , Neoplasias Pancreáticas/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Ontología de Genes , Humanos , Quinasas Janus/genética , Sistema de Señalización de MAP Quinasas , Análisis de Secuencia por Matrices de Oligonucleótidos , Páncreas/química , Receptores Activados del Proliferador del Peroxisoma/genética , Factores de Transcripción STAT/genética , Transcriptoma , Regulación hacia ArribaRESUMEN
This meta-analysis was performed to evaluate the relationships between single-nucleotide polymorphisms (SNPs) in the immunity-related GTPase M (IRGM) gene and the risk of Crohn's disease (CD). Eleven case-control studies were included, for a total of 5183 CD patients and 5571 healthy controls. Three common SNPs (rs13361189 C>T, rs10065172 C>T, and rs4958847 A>G) in the IRGM gene were assessed. We found that the IRGM rs13361189 polymorphism was significantly associated with an increased risk of CD [C allele vs T allele: odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.05-1.61, P = 0.017; CC + CT vs TT: OR = 1.32, 95%CI = 1.06-1.64, P = 0.013]. However, we observed no correlation between the rs10065172 and rs4958847 polymorphisms in the IRGM gene with susceptibility to CD (all P > 0.05). Subgroup analysis by ethnicity revealed significant associations between IRGM genetic polymorphisms and an increased risk of CD among Caucasian populations (C allele vs T allele: OR = 1.22, 95%CI = 1.07-1.40, P = 0.004; CC + CT vs TT: OR = 1.22, 95%CI = 1.05-1.41, P = 0.009), but not among Asian populations (all P > 0.05). Meta-regression analysis also confirmed that ethnic differences may be an important source of heterogeneity (P = 0.003). Our meta-analysis results indicate that the IRGM rs13361189 polymorphism contributes to the susceptibility to CD. Thus, the IRGM rs13361189 polymorphism is promising as a biomarker for early diagnosis of CD. However, the IRGM rs10065172 and rs4958847 polymorphisms may not be the major determinants of CD risk.
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Enfermedad de Crohn/genética , Proteínas de Unión al GTP/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Anciano , Pueblo Asiatico , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Población Blanca , Adulto JovenRESUMEN
This study aimed to assess the relationship between the recurrence and prognosis of patients with acute middle cerebral artery infarction, atherosclerotic brain infarction, and the existence of microemboli. We continuously enrolled patients with acute atherosclerotic thrombotic cerebral infarction artery stenosis. We performed transcranial Doppler color ultrasound micro emboli monitoring, color Doppler ultrasound carotid artery tests, intracranial and carotid artery magnetic resonance angiography, impairment evaluation of nerve function, and registration of stroke recurrence and stroke mortality. Of the 49 patients enrolled in the study, 123 main arteries presented atherosclerotic stenosis or formed plaques, and 33 patients had symptomatic stenosis. Patients with symptomatic stenosis have a higher incidence of microemboli than patients with asymptomatic stenosis (P = 0.009). The microembolus-positive rate increased in patients with unstable plaques (P = 0.001). Patients who were microembolus-negative were more likely to show a neural function deficient NIHSS (National Institutes of Stroke Scale) score improvement than patients who were microembolus-positive at one week (P = 0.026). However, we found no significant difference between mRS (modified rankin scale) score (P = 0.319), relapse, and death (P = 0.179). The rate of microembolus-positivity increased in patients with atherosclerotic thrombotic cerebral infarction and unstable plaques. Patients who were microembolus-negative were more likely to show an improvement of neural function deficiency than patients with microembolus-positivity at one week (P = 0.026).
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Enfermedades Arteriales Cerebrales/diagnóstico por imagen , Embolia/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Arteriosclerosis Intracraneal/diagnóstico por imagen , Ultrasonografía Doppler Transcraneal/métodos , Anciano , Análisis de Varianza , Arterias Carótidas/diagnóstico por imagen , Enfermedades Arteriales Cerebrales/diagnóstico , Constricción Patológica/diagnóstico , Constricción Patológica/diagnóstico por imagen , Embolia/diagnóstico , Femenino , Humanos , Infarto de la Arteria Cerebral Media/diagnóstico , Arteriosclerosis Intracraneal/diagnóstico , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Examen Neurológico/métodos , Pronóstico , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/diagnósticoRESUMEN
Ginsenoside Rh2 (Rh2) is a ginseng derivative used in Chinese traditional medicine. We investigated whether Rh2 can help prevent Alzheimer's disease symptoms and examined underlying mechanisms. We injected Rh2 into tg2576 Alzheimer's disease model mice and looked for behavioral improvement and senile plaque reduction in brain slices. We measured amyloid precursor protein (APP) metabolism species changes, amyloid beta40 and 42 levels and ß, γ secretase activity in primary hippocampal neurons. By living cell staining, we detected surface and endocytosed APP. We also measured cholesterol and lipid rafts in primary neurons. Rh2 treatment significantly improved learning and memory performance at 14 months of age; it also reduced brain senile plaques at this age. Based on in vitro experiments, we found that Rh2 treatment increased soluble APPα (sAPPα) levels, increased CTFα/ß ratios, and reduced amyloid beta 40 and 42 concentrations. Surface APP levels dramatically increased. Based on living cell staining, we found that Rh2 inhibited APP endocytosis. Based on lipid removal and reload experiments, we found that Rh2 can modulate APP by reducing cholesterol and lipid raft levels. We concluded that Rh2 improves learning and memory function in Alzheimer's disease model mice, and that this improvement is accomplished by reducing amyloid beta secretion and APP endocytosis, which in turn is achieved by reducing cholesterol and lipid raft concentrations.
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Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/biosíntesis , Ginsenósidos/administración & dosificación , Fragmentos de Péptidos/biosíntesis , Enfermedad de Alzheimer/patología , Secretasas de la Proteína Precursora del Amiloide/biosíntesis , Animales , Colesterol/metabolismo , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Redes y Vías Metabólicas/efectos de los fármacos , Ratones , Neuronas/efectos de los fármacos , Neuronas/enzimologíaRESUMEN
Several novel bioactive components isolated from Chinese medicinal plants will be presented. These include novel maytansinoid tumor inhibitors, some new ent-kaurane and rosane diterpenoids from Mallotus anomalus Meer et Chun (Euphorbiaceae), as well as novel insecticide, stemona alkaloids from Stemona parviflora C. H. Wright (Stemonaceae). Both are native plants of Hainan island, China. 2D NMR techniques such as mono and hetero-COSY, NOESY, COLOC as well as 1H-NMR line broadening effect were utilized for structure elucidation. The separation techniques, structure elucidations and bioassay results will be reported.