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Nutrients are not only organic compounds fueling bioenergetics and biosynthesis, but also key chemical signals controlling growth and metabolism. Nutrients enormously impact the production of reactive oxygen species (ROS), which play essential roles in normal physiology and diseases. How nutrient signaling is integrated with redox regulation is an interesting, but not fully understood, question. Herein, we report that superoxide dismutase 1 (SOD1) is a conserved component of the mechanistic target of rapamycin complex 1 (mTORC1) nutrient signaling. mTORC1 regulates SOD1 activity through reversible phosphorylation at S39 in yeast and T40 in humans in response to nutrients, which moderates ROS level and prevents oxidative DNA damage. We further show that SOD1 activation enhances cancer cell survival and tumor formation in the ischemic tumor microenvironment and protects against the chemotherapeutic agent cisplatin. Collectively, these findings identify a conserved mechanism by which eukaryotes dynamically regulate redox homeostasis in response to changing nutrient conditions.
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Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Nutrientes/metabolismo , Fosforilación/fisiología , Superóxido Dismutasa-1/metabolismo , Animales , Línea Celular , Línea Celular Tumoral , Daño del ADN/fisiología , Metabolismo Energético/fisiología , Femenino , Células HEK293 , Humanos , Células MCF-7 , Ratones Endogámicos BALB C , Ratones Desnudos , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/fisiología , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Objective: To investigate the variation of reference ranges of hemodynamic parameters in normal pregnancy and their relation to maternal basic characteristics. Methods: A total of 598 healthy pregnant women who underwent regular prenatal examination at the Third Affiliated Hospital of Guangzhou Medical University from January to December 2023 were prospectively enrolled, and noninvasive hemodynamic monitors were used to detect changes in hemodynamic parameters of the pregnant women with the week of gestation, including cardiac output (CO), stroke volume (SV), thoracic fluid content (TFC), systemic vascular resistance (SVR), mean arterial pressure (MAP), and heart rate (HR). Relationships between hemodynamic parameters and maternal basic characteristics, including age, height, and weight, were analyzed using restricted cubic spline. Results: (1) CO (r=0.155, P<0.001), TFC (r=0.338, P<0.001), MAP (r=0.204, P<0.001), and HR (r=0.352, P<0.001) were positively correlated with the week of gestation, and SV was negatively correlated with the week of gestation (r=-0.158, P<0.001). There was no significant correlation between SVR and gestational age (r=-0.051, P=0.258). (2) CO exhibited a positive correlation with maternal height and weight (all P<0.001). The taller and heavier of pregnant women, the higher their CO. A linear relationship was observed between maternal weight and SV, MAP and HR (all P<0.01). As maternal weight increased, SV, MAP and HR showed an upward trend. Furthermore, there was an inverse association between maternal age and SVR (P<0.001). (3) There was a significant nonlinear association observed between TFC and body mass index during pregnancy (P<0.05). Additionally, a nonlinear relationship was found between SVR and MAP in relation to maternal age (all P<0.05). Notably, when the age exceeded 31 years old, there was an evident upward trend observed in both SVR and MAP. Conclusions: The hemodynamic parameters of normal pregnant women are influenced by their height, body weight, and age. It is advisable to maintain a reasonable weight during pregnancy and give birth at an appropriate age.
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Gasto Cardíaco , Frecuencia Cardíaca , Hemodinámica , Volumen Sistólico , Resistencia Vascular , Humanos , Femenino , Embarazo , Gasto Cardíaco/fisiología , Volumen Sistólico/fisiología , Resistencia Vascular/fisiología , Estudios Prospectivos , Frecuencia Cardíaca/fisiología , Edad Gestacional , Valores de Referencia , Adulto , Presión Sanguínea/fisiología , Presión Arterial/fisiología , Peso CorporalRESUMEN
BACKGROUND AND AIMS: Androgen receptor (AR) has been reported to play an important role in the development and progression of man's prostate cancer. Hepatocellular carcinoma (HCC) is also male-dominant, but the role of AR in HCC remains poorly understood. Mechanistic target of rapamycin complex 1 (mTORC1) also has been reported to be highly activated in HCC. In this study, we aimed to explore the role of AR phosphorylation and its relationship with mTORC1 in hepatocarcinogenesis. APPROACH AND RESULTS: In vitro experiment, we observed that mTORC1 interacts with hepatic AR and phosphorylates it at S96 in response to nutrient and mitogenic stimuli in HCC cells. S96 phosphorylation promotes the stability, nuclear localization, and transcriptional activity of AR, which enhances de novo lipogenesis and proliferation in hepatocytes and induces liver steatosis and hepatocarcinogenesis in mice independently and cooperatively with androgen. Furthermore, high ARS96 phosphorylation is observed in human liver steatotic and HCC tissues and is associated with overall survival and disease-free survival, which has been proven as an independent survival predictor for patients with HCC. CONCLUSIONS: AR S96 phosphorylation by mTORC1 drives liver steatosis and HCC development and progression independently and cooperatively with androgen, which not only explains why HCC is man-biased but also provides a target molecule for prevention and treatment of HCC and a potential survival predictor in patients with HCC.
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Carcinoma Hepatocelular , Hígado Graso , Neoplasias Hepáticas , Andrógenos , Animales , Carcinogénesis , Carcinoma Hepatocelular/patología , Transformación Celular Neoplásica , Humanos , Neoplasias Hepáticas/patología , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones , Fosforilación , Receptores Androgénicos/metabolismoRESUMEN
Objective: To investigate the mid-term clinical outcome of deep layer repair with the long head of the biceps autograft bridging for Kim classification type â A delaminated rotator cuff tear. Methods: A follow-up study. The clinical data of 42 consecutive patients with Kim classification type â A delaminated rotator cuff tear admitted to the First Affiliated Hospital of Jinan University from January 2018 to June 2019 were retrospectively included. All patients underwent shoulder arthroscopic surgery. During the operation, the autogenous long head of the biceps tendon was transferred to repair the deep layer of delaminated rotator cuff tear. The preoperative and postoperative (last follow-up) visual analogue scale (VAS) for pain, University of California Los Angeles (UCLA) score, Constant-Murley shoulder score, range of motion (ROM) of the shoulder and radiographic results were statistically analyzed. Results: A total of 42 patients were included in this study. There were 18 males and 24 females, with an average age of (64.5±15.2) years and a mean follow-up of (43.9±7.1) months. At the last follow-up, ROM of abduction increased from 80.8°±26.5° to 154.2°±14.3°, and ROM of external rotation increased from 18.2°±13.6° to 31.8°±7.8°; the VAS score of pain decreased from (5.5±1.3) points to (0.7±0.7) points, the UCLA score increased from (21.3±3.7) points to (29.9±2.1) points, and the Constant-Murley score increased from (45.4±10.0) points to (87.2±4.8) points; the differences were all statistically significant (all P<0.001). The X-ray films showed that there were no upward of the humeral head in all the patients. MRI results indicated that rotator cuff re-teared in one case (Sugaya classification type â ¢), and healed in other cases (Sugaya classification type â -â ¡). No complications such as upper limb nerve injury was found in all cases. Conclusion: Deep layer repair with the long head of the biceps autograft bridging can significantly alleviate the pain and improve the function of patients with Kim classification type â A delaminated rotator cuff tear, and the incidence of retear is low.
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Lesiones del Manguito de los Rotadores , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Lesiones del Manguito de los Rotadores/cirugía , Estudios de Seguimiento , Estudios Retrospectivos , Autoinjertos , Resultado del Tratamiento , Artroscopía/métodos , Dolor , Rango del Movimiento Articular , Imagen por Resonancia MagnéticaRESUMEN
Objective: To study the value of chromosome microarray analysis (CMA) application in children with developmental delay (DD), intellectual disability (ID), autistic spectrum disorder (ASD) and multiple congenital anomalies (MCA). Methods: Genomic DNA was extracted from peripheral blood samples. Array-based comparative genomic hybridization (array-CGH) analysis and single nucleotide polymorphism array (SNP-array) were performed in 1 320 children with DD/ID, ASD, with or without epilepsy and MCA who were admitted to Peking University First Hospital from 2014 to 2019. The results of genetic etiology test of CMA in children with mental retardation or global DD was summarized. Results: Of 1 320 samples, there were 10 cases of aneuploid abnormality, 6 cases of uniparental disomy and one case of mosaicism, respectively. Pathogenic copy number variations (CNVs) were found in 320 cases and pathogenic CNVs were detected in 23 cases, with a combined detection rate of 26% (343/1 320). CNVs of uncertain clinical significance occurred in 107 cases, accounting for 8.1% (107/1 320). There were 25 cases of possible benign CNVs, accounting for 2% (25/1 320), while benign CNVs were reported in 20 cases, accounting for 1.5% (20/1 320). The detection rate of MCA with DD/ID was 39.8% (130/327). Conclusions: CMA has the advantages of high resolution and covering the whole genome. It can detect the chromosomal abnormalities, microdeletions and duplications seen under the microscope, thus the genetic etiology of children with mental retardation or global DD can be diagnosed.
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Discapacidad Intelectual , Niño , Aberraciones Cromosómicas , Cromosomas , Hibridación Genómica Comparativa , Variaciones en el Número de Copia de ADN , Discapacidades del Desarrollo/genética , Humanos , Discapacidad Intelectual/genética , Análisis por MicromatricesRESUMEN
Objective: To evaluate the clinical impact of percutaneous coronary intervention (PCI) on left ventricular myocardial remodeling and main adverse cardiovascular and cerebrovascular events (MACE) in ischemic cardiomyopathy patients with different left ventricular ejection fraction and SYNTAX score≤22. Methods: A total of 191 ischemic cardiomyopathy patients who underwent PCI in Department of Cardiology from May 2017 to October 2018 were enrolled in this study, and they were divided into three groups according to preoperative left ventricular ejection fraction (≥50% group, 36%~49% group and ≤35% group). The main outcomes and left ventricular ejection fraction, left ventricular end-diastolic volume were analyzed at 12 months follow-up. The main outcomes were the recurrence of acute left ventricular failure, recurrent angina, restenosis, revascularization, non-fatal myocardial infarction, cardiovascular death and non-cardiovascular death. Results: The incidence of MACE was 32.6% (15 cases) in ≥50% group, 32.0% (31 cases) in 36%-49% group, 45.8% (22 cases) in ≤35% group, respectively, which was lower in the first two groups than in ≤35% group, but there was no statistically significant difference among the 3 groups (P=0.231). The incidence of acute left ventricular failure in the three groups was 2.2%, 12.4% and 22.9%, respectively, and there was statistically significant difference among the 3 groups (P= 0.01). Multivariate analysis indicated that preoperative left ventricular ejection fraction ≤35% was an independent predictor of acute left ventricular failure (OR=2.696, 95%CI: 1.099-6.612, P=0.030). Compared with baseline data, left ventricular end-diastolic volume ((62±4) mm vs (56±5) mm, P<0.001), left atrium ((42±6) mm vs (40±6) mm, P<0.001) decreased significantly 1 year after PCI. However, left ventricular ejection fraction ((43±10)% vs (51±13)%, P<0.001) increased significantly. At 1 year, left ventricular remodeling related parameters were detected in 3 groups, and there was statistically significant difference in left ventricular end-diastolic volume ((53.1±0.6) mm vs (55.1±0.5) mm vs (59.1±0.7) mm, P<0.001), left ventricular ejection fraction ((62.1±1.1)% vs (51.4±1.0)% vs (37.0±1.5)%, P<0.001) among the 3 groups. Conclusions: Coronary vascular reopening with PCI in patients with ischaemic cardiomyopathy and SYNTAX score≤22, can improve prognosis of patients with preoperative left ventricular ejection fraction>35% significantly, but not in those with preoperative left ventricular ejection fraction≤35%. Preoperative left ventricular ejection fraction may be an independent predictor of acute left ventricular failure in patients with ischemic cardiomyopathy and SYNTAX score≤22, postoperative left ventricular remodeling and left ventricular systolic function correlate with preoperative left ventricular ejection fraction.
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Cardiomiopatías , Intervención Coronaria Percutánea , Humanos , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
Objective: To investigate the effectiveness of an enhanced CT automatic recognition system based on Faster R-CNN for pancreatic cancer and its clinical value. Methods: In this study, 4 024 enhanced CT imaging sequences of 315 patients with pancreatic cancer from January 2013 to May 2016 at the Affiliated Hospital of Qingdao University were collected retrospectively, and 2 614 imaging sequences were input into the faster R-CNN system as training dataset to create an automatic image recognition model, which was then validated by reading 1 410 enhanced CT images of 135 cases of pancreatic cancer.In order to identify its effectiveness, 3 750 CT images of 150 patients with pancreatic lesions were read and a followed-up was carried out.The accuracy and recall rate in detecting nodules were recorded and regression curves were generated.In addition, the accuracy, sensitivity and specificity of Faster R-CNN diagnosis were analyzed, the ROC curves were generated and the area under the curves were calculated. Results: Based on the enhanced CT images of 135 cases, the area under the ROC curve was 0.927 calculated by Faster R-CNN. The accuracy, specificity and sensitivity were 0.902, 0.913 and 0.801 respectively.After the data of 150 patients with pancreatic cancer were verified, 893 CT images showed positive and 2 857 negative.Ninety-eight patients with pancreatic cancer were diagnosed by Faster R-CNN.After the follow-up, it was found that 53 cases were post-operatively proved to be pancreatic ductal carcinoma, 21 cases of pancreatic cystadenocarcinoma, 12 cases of pancreatic cystadenoma, 5 cases of pancreatic cyst, and 7 cases were untreated.During 5 to 17 months after operation, 6 patients died of abdominal tumor infiltration, liver and lung metastasis.Of the 52 patients who were diagnosed negative by Faster R-CNN, 9 were post-operatively proved to be pancreatic ductal carcinoma. Conclusion: Faster R-CNN system has clinical value in helping imaging physicians to diagnose pancreatic cancer.
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Interpretación de Imagen Asistida por Computador/métodos , Redes Neurales de la Computación , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Humanos , Neoplasias Pancreáticas/diagnóstico , Curva ROC , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Hepatocellular carcinoma (HCC) is a male-dominant cancer, and androgen receptor (AR) has been linked to the pathogenesis of HCC. However, AR expression and its precise role in HCC remain controversial. Moreover, previous antiandrogen and anti-AR clinical trials in HCC failed to demonstrate clinical benefits. In this study, we found that AR is overexpressed in the nucleus of approximately 37% of HCC tumors, which is significantly associated with advanced disease stage and poor survival. AR overexpression in HCC cells markedly alters AR-dependent transcriptome, stimulates oncogenic growth, and determines therapeutic response to enzalutamide, a second generation of AR antagonist. However, AR inhibition evokes feedback activation of AKT-mTOR (mechanistic target of rapamycin) signaling, a central regulator for cell growth and survival. On the other hand, mTOR promotes nuclear AR protein expression by restraining ubiquitin-dependent AR degradation and enhancing AR nuclear localization, providing a mechanistic explanation for nuclear AR overexpression in HCC. Finally, cotargeting AR and mTOR shows significant synergistic anti-HCC activity and decreases tumor burden by inducing apoptosis in vivo. CONCLUSION: Nuclear AR overexpression is associated with the progression and prognosis of HCC. However, enzalutamide alone has limited therapeutic utility attributed to feedback activation of the AKT-mTOR pathway. Moreover, mTOR drives nuclear AR overexpression. Cotargeting AR and mTOR is a promising therapeutic strategy for HCC. (Hepatology 2018;67:2271-2286).
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Receptor Cross-Talk , Receptores Androgénicos/fisiología , Serina-Treonina Quinasas TOR/fisiología , Animales , Benzamidas , Carcinoma Hepatocelular/tratamiento farmacológico , Núcleo Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Ratones , Nitrilos , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/uso terapéutico , Receptores Androgénicos/biosíntesis , Receptores Androgénicos/genética , Células Tumorales CultivadasRESUMEN
Tetanus consists of neonatal tetanus and non-neonatal tetanus. Although neonatal tetanus in China has been eliminated since 2012, non-neonatal tetanus remains a serious public health problem. Non-neonatal tetanus is a potential fatal disease, and the mortality rate of severe cases is almost 100% in the absence of medical intervention. Even with vigorous treatment, the mortality rate is still 30~50% globally. In order to standardize the diagnosis and treatment of non-neonatal tetanus in China, this specification is hereby formulated. This standard includes etiology, epidemiology, pathogenesis, clinical manifestations, laboratory tests, diagnosis, differential diagnosis, classification, grading and treatment of non-neonatal tetanus.
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Guías de Práctica Clínica como Asunto , Tétanos/diagnóstico , Tétanos/terapia , China , Humanos , Recién Nacido , Salud PúblicaRESUMEN
Mechanistic target of rapamycin (mTOR) is a conserved serine/threonine kinase that plays a critical role in the control of cellular growth and metabolism. Hyperactivation of mTOR pathway is common in human cancers, driving uncontrolled proliferation. MicroRNA (miRNA) is a class of short noncoding RNAs that regulate the expression of a wide variety of genes. Deregulation of miRNAs is a hallmark of cancer. Recent studies have revealed interplays between miRNAs and the mTOR pathway during cancer development. Such interactions appear to provide a fine-tuning of various cellular functions and contribute qualitatively to the behavior of cancer. Here we provide an overview of current knowledge regarding the reciprocal relationship between miRNAs and mTOR pathway: regulation of mTOR signaling by miRNAs and control of miRNA biogenesis by mTOR. Further research in this area may prove important for the diagnosis and therapy of human cancer.
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MicroARNs/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Animales , Carcinogénesis/genética , Regulación de la Expresión Génica , Humanos , MicroARNs/genética , Modelos Biológicos , Transducción de Señal/genéticaRESUMEN
SOX9 encodes a transcription factor that governs cell fate specification throughout development and tissue homeostasis. Elevated SOX9 is implicated in the genesis and progression of human tumors by increasing cell proliferation and epithelial-mesenchymal transition. We found that in response to UV irradiation or genotoxic chemotherapeutics, SOX9 is actively degraded in various cancer types and in normal epithelial cells, through a pathway independent of p53, ATM, ATR and DNA-PK. SOX9 is phosphorylated by GSK3ß, facilitating the binding of SOX9 to the F-box protein FBW7α, an E3 ligase that functions in the DNA damage response pathway. The binding of FBW7α to the SOX9 K2 domain at T236-T240 targets SOX9 for subsequent ubiquitination and proteasomal destruction. Exogenous overexpression of SOX9 after genotoxic stress increases cell survival. Our findings reveal a novel regulatory mechanism for SOX9 stability and uncover a unique function of SOX9 in the cellular response to DNA damage. This new mechanism underlying a FBW7-SOX9 axis in cancer could have implications in therapy resistance.
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Proteínas de Ciclo Celular/metabolismo , Daño del ADN , Proteínas F-Box/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Factor de Transcripción SOX9/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Antineoplásicos/farmacología , Muerte Celular , Línea Celular Tumoral , Daño del ADN/efectos de los fármacos , Daño del ADN/efectos de la radiación , Proteína 7 que Contiene Repeticiones F-Box-WD , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Modelos Biológicos , Fosforilación , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Proteolisis , Factor de Transcripción SOX9/química , Ubiquitinación , Rayos Ultravioleta/efectos adversosAsunto(s)
Lesión Renal Aguda , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Anticuerpos Monoclonales/uso terapéuticoRESUMEN
UNLABELLED: The phosphatidylinositol 3-kinase/phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase/protein kinase B/mammalian target of rapamycin (PI3K-PTEN-AKT-mTOR) pathway is a central controller of cell growth and a key driver for human cancer. MAF1 is an mTOR downstream effector and transcriptional repressor of ribosomal and transfer RNA genes. MAF1 expression is markedly reduced in hepatocellular carcinomas, which is correlated with disease progression and poor prognosis. Consistently, MAF1 displays tumor-suppressor activity toward in vitro and in vivo cancer models. Surprisingly, blocking the synthesis of ribosomal and transfer RNAs is insufficient to account for MAF1's tumor-suppressor function. Instead, MAF1 down-regulation paradoxically leads to activation of AKT-mTOR signaling, which is mediated by decreased PTEN expression. MAF1 binds to the PTEN promoter, enhancing PTEN promoter acetylation and activity. CONCLUSION: In contrast to its canonical function as a transcriptional repressor, MAF1 can also act as a transcriptional activator for PTEN, which is important for MAF1's tumor-suppressor function. These results have implications in disease staging, prognostic prediction, and AKT-mTOR-targeted therapy in liver cancer. (Hepatology 2016;63:1928-1942).
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Carcinoma Hepatocelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas Experimentales/metabolismo , Proteínas Represoras/metabolismo , Adulto , Anciano , Animales , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Humanos , Masculino , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Fosfohidrolasa PTEN/metabolismo , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Upregulation of CD137 on recently activated CD8+ T cells has been used to identify rare viral and tumour antigen-specific T cells from the peripheral blood. We aimed to evaluate the accuracy of CD137 for identifying Mycobacterium tuberculosis (Mtb)-reactive CD4+ T cells in the peripheral blood of infected individuals by flow cytometry and to investigate the characteristics of these CD137+ CD4+ T cells. We initially enrolled 31 active tuberculosis (TB) patients, 31 individuals with latent TB infection (LTBI) and 25 healthy donors. The intracellular CD137 and interferon-γ (IFN-γ) production by CD4+ T cells was simultaneously detected under unstimulated and CFP10-stimulated (culture filtrate protein 10, a Mtb-specific antigen) conditions. In unstimulated CD4+ T cells, we found that the CD137 expression in the TB group was significantly higher than that in the LTBI group. Stimulation with CFP10 largely increased the CD4+ T cell CD137 expression in both the TB and LTBI groups. After CFP10 stimulation, the frequency of CD137+ CD4+ T cells was higher than that of IFN-γ+ CD4+ T cells in both the TB and LTBI groups. Most of the CFP10-activated IFN-γ-secreting cells were CD137-positive, but only a small fraction of the CD137-positive cells expressed IFN-γ. An additional 20 patients with TB were enrolled to characterize the CD45RO+ CCR7+ , CD45RO+ CCR7- and CD45RO- subsets in the CD137+ CD4+ T cell populations. The Mtb-specific CD137+ CD4+ T cells were mainly identified as having an effector memory phenotype. In conclusion, CD137 is a useful marker that can be used for identifying Mtb-reactive CD4+ T cells by flow cytometry.
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Linfocitos T CD4-Positivos/inmunología , Tuberculosis Latente/inmunología , Mycobacterium tuberculosis/inmunología , Tuberculosis/inmunología , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Adulto , Biomarcadores/metabolismo , Linfocitos T CD4-Positivos/microbiología , Femenino , Citometría de Flujo , Interacciones Huésped-Patógeno/inmunología , Humanos , Interferón gamma/inmunología , Interferón gamma/metabolismo , Tuberculosis Latente/metabolismo , Tuberculosis Latente/microbiología , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/fisiología , Tuberculosis/metabolismo , Tuberculosis/microbiología , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismoRESUMEN
This study investigated the effects of FUT3 gene expression inhibition with miRNA on the proliferation, invasion and migration abilities of KATO-III cells. KATO-III cells were transfected with plasmid pcDNA™6.2-GW/EmGFP-FUT3-miR(FUT3-miRNA) and negative control plasmid in mediation of liposome, respectively, using untransfected cells as blank controls. Forty-eight hours after transfection, FUT3 mRNA levels were tested by RT-PCR. Levels of sLeA proteins were assayed by Western blot. The effects of FUT3-miRNA on the proliferation, invasion and migration of KATO-III cells were determined by CCK8 testing and Transwell assays, respectively. Results indicate that the transfection of FUT3-miRNA may down-regulate sLeA protein expression on the surface of KATO-III cells, and significantly inhibit cell proliferation (p<0.05). As compared to the negative and blank control groups, the number of invasion and migration cells in the FUT3-miRNA group decreased significantly (each p<0.05). Experimental results indicate that the miRNA expression vector which targets the FUT3 gene can effectively inhibit the proliferation, migration and invasion abilities of KATO-III cells.
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Movimiento Celular , Fucosiltransferasas/genética , Silenciador del Gen , MicroARNs/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Secuencia de Bases , Western Blotting , Línea Celular Tumoral , Proliferación Celular , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Invasividad Neoplásica , Plásmidos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Análisis de Secuencia de ADN , TransfecciónRESUMEN
Rapamycin and its analogs (rapalogs) are the first generation of mTOR inhibitors, which have the same molecular scaffold, but different physiochemical properties. Rapalogs are being tested in a wide spectrum of human tumors as both monotherapy and a component of combination therapy. Among them, temsirolimus and everolimus have been approved for the treatment of breast and renal cancer. However, objective response rates with rapalogs in clinical trials are modest and variable. Identification of biomarkers predicting response to rapalogs, and discovery of drug combinations with improved efficacy and tolerated toxicity are critical to moving this class of targeted therapeutics forward. This review focuses on the aberrations in the PI3K/mTOR pathway in human tumor cells or tissues as predictive biomarkers for rapalog efficacy. Recent results of combinational therapy using rapalogs and other anticancer drugs are documented. With the rapid development of next-generation genomic sequencing and precision medicine, rapalogs will provide greater benefits to cancer patients.
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Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Sirolimus/análogos & derivados , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/metabolismo , Animales , Antibióticos Antineoplásicos/farmacología , Biología Computacional/métodos , Humanos , Terapia Molecular Dirigida/métodos , Neoplasias/metabolismo , Medicina de Precisión/métodos , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacologíaRESUMEN
BACKGROUND: Little information about the occupational exposures to blood and body fluid (BBF) among blood service workers (BSWs) in blood stations in China is available currently. OBJECTIVES: To assess current status of occupational exposure to BBF and assess the knowledge about occupational blood-borne pathogen exposures and universal precaution among BSWs in blood donations in China. To understand the incidence of occupational exposure in five blood centres in China. METHODS: A cross-sectional study was conducted from January 2008 to December 2013. RESULTS: There were a total of 99 BBF exposures reported during the study period. The total incidence of BBF exposures was 4.4 per 100 person-years. Higher rates were observed for persons employed less than five years and persons less than 45 years old. Nurses have the highest percentage (49.5%) of BBF exposures. BBF exposures occurred most commonly during the afternoon (62.7%). Percutaneous injuries were the most common BBF exposures. Most incidents occurred during sharps use (73.4%). The major cause of occupational exposure was that there was no continuous training (48.4%) and improper use of equipment (23.2%). Only 56.6% of BBF exposures had appropriate first aid measures. During this research work, one staff member was reported to have seroconverted to syphilis after BBF exposure. CONCLUSIONS: To reduce BBF exposures, it is urgent to take several effective actions in China, including improved occupational health systems, adequate education, administrative support, increased use of standard precautions, better safety devices/products and work practices.
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Bancos de Sangre , Donantes de Sangre , Patógenos Transmitidos por la Sangre , Sangre , Enfermeras y Enfermeros , Exposición Profesional , Adulto , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Nelumbo nucifera is an important economic vegetable and traditional medicine, but available genetic resources remain limited. Next generation sequencing has proven to be a rapid and effective means of identifying genic simple sequence repeat (genic-SSR) markers. This study developed genic-SSRs for N. nucifera using Illumina sequencing technology to assess diversity across cultivated and wild lotus. A total of 105,834 uni-contigs were produced with an average read length of 722 bp. Exactly 11,178 genic-SSR loci were identified in 9523 uni-contigs. Di-nucleotide (64.5%) was the most abundant SSR, followed by tri-nucleotide (23%), tetra-nucleotide (8.9%), penta-nucleotide (2.5%), and hexa-nucleotide (1%) repeat types. The most common di- and tri-nucleotide repeat motifs were AG/CT (51%) and AAG/CTT (8%), respectively. Based on these SSRs sequences, 6568 primer pairs were designed, of which 72 primers were randomly selected for synthesis and validation, and 38 in-silico polymorphic primers were obtained using in-house perl scripts. A total of 110 primers were screened in the lotus samples and the results showed that 101 primers yielded amplification products, of which 80 were polymorphs. The number of alleles ranged from 2 to 17 and the PIC (polymorphism information content) ranged from 0.19 to 0.87 with a mean value of 0.55. An Unweighted Pair Group Method with Arithmetic Mean (UPGMA) dendrogram based on Jaccard's similarity coefficients showed that the correlation between geographical source and genotype was low. This study describes the distribution of genic-SSRs in the expressed portion of the lotus genome. These genic-SSRs have an important role to play in molecular mapping, diversity analysis, and marker-assisted selection strategies in Nelumbo.
Asunto(s)
Genoma de Planta , Nelumbo/genética , ARN de Planta/genética , Flores/genética , Frecuencia de los Genes , Sitios Genéticos , Marcadores Genéticos , Repeticiones de Microsatélite , Filogenia , Polimorfismo Genético , Rizoma/genética , Análisis de Secuencia de ARN , Especificidad de la EspecieRESUMEN
Water chestnut (Eleocharis dulcis) is an important aquatic crop in China; however, transcriptomic and genomic data in public databases are limited. To identify genes and development molecular markers, high-throughput transcriptome sequencing was applied to generate transcript sequences from water chestnut leaf. More than 24 million reads were obtained, trimmed, and assembled into 40,796 contigs with an average length of 616.6 bp. Sequence similarity analyses against 4 public databases (NR, GO, KEGG, KOG) revealed 17,628 contigs that could be annotated with gene descriptions, conserved protein domains, or gene ontology terms. Among the important metabolic pathways, 27 genes were related to starch synthesis and 13 genes were in the steroid synthetic pathway. In addition, 2570 cDNA simple sequence repeats were identified as potential molecular markers in our contigs. One hundred pairs of polymerase chain reaction primers were designed and used for validation of the amplification. The results revealed that 87 primer pairs were successfully amplified in initial screening tests. Overall, this transcriptome dataset and these markers can serve as a platform for further gene expression studies, functional genomic studies, and marker-assisted selection in E. dulcis.