RESUMEN
We have reported previously that during hypoxia exposure, the expression of mature miR-17â¼92 was first upregulated and then downregulated in pulmonary artery smooth muscle cells (PASMC) and in mouse lungs in vitro and in vivo. Here, we investigated the mechanisms regulating this biphasic expression of miR-17â¼92 in PASMC in hypoxia. We measured the level of primary miR-17â¼92 in PASMC during hypoxia exposure and found that short-term hypoxia exposure (3% O2, 6 h) induced the level of primary miR-17â¼92, whereas long-term hypoxia exposure (3% O2, 24 h) decreased its level, suggesting a biphasic regulation of miR-17â¼92 expression at the transcriptional level. We found that short-term hypoxia-induced upregulation of miR-17â¼92 was hypoxia-inducible factor 1α (HIF1α) and E2F1 dependent. Two HIF1α binding sites on miR-17â¼92 promoter were identified. We also found that long-term hypoxia-induced suppression of miR-17â¼92 expression could be restored by silencing of p53. Mutation of the p53-binding sites in the miR-17â¼92 promoter increased miR-17â¼92 promoter activity in both normoxia and hypoxia. Our findings suggest that the biphasic transcriptional regulation of miR-17â¼92 during hypoxia is controlled by HIF1/E2F1 and p53 in PASMC: during short-term hypoxia exposure, stabilization of HIF1 and induction of E2F1 induce the transcription of miR-17â¼92, whereas during long-term hypoxia exposure, hyperphosphorylation of p53 suppresses the expression of miR-17â¼92.NEW & NOTEWORTHY We showed that the biphasic transcriptional regulation of miR-17â¼92 during hypoxia is controlled by two distinct mechanisms: during short-term hypoxia exposure, induction of HIF1 and E2F1 upregulates miR-17â¼92. Longer hypoxia exposure induces hyperphosphorylation of p53 at ser15, which leads to its binding to miR-17â¼92 promoter and inhibition of its expression. Our findings provide novel insights into the spatiotemporal regulation of miR-17â¼92 that may play a role in the development of human lung diseases including pulmonary hypertension (PH).
Asunto(s)
Factor de Transcripción E2F1 , Subunidad alfa del Factor 1 Inducible por Hipoxia , MicroARNs , Arteria Pulmonar , Proteína p53 Supresora de Tumor , MicroARNs/genética , MicroARNs/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Fosforilación , Humanos , Animales , Factor de Transcripción E2F1/metabolismo , Factor de Transcripción E2F1/genética , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Transcripción Genética , Hipoxia de la Célula/genética , Miocitos del Músculo Liso/metabolismo , Regiones Promotoras Genéticas/genética , Ratones , Hipoxia/metabolismo , Hipoxia/genética , Serina/metabolismo , Regulación de la Expresión Génica , Células CultivadasRESUMEN
OBJECTIVES: Genetic variation has been a major contributor to interindividual variability of warfarin dosage requirement. The specific genetic factors contributing to warfarin bleeding complications are largely unknown, particularly in Chinese patients. In this study, 896 Chinese patients were enrolled to explore the effect of CYP2C9 and VKORC1 genetic variations on both the efficacy and safety of warfarin therapy. METHODS AND RESULTS: Univariate analyses unveiled significant associations between two specific single nucleotide polymorphisms rs1057910 in CYP2C9 and rs9923231 in VKORC1 and stable warfarin dosage ( P â <â 0.001). Further, employing multivariate logistic regression analysis adjusted for age, sex and height, the investigation revealed that patients harboring at least one variant allele in CYP2C9 exhibited a heightened risk of bleeding events compared to those with the wild-type genotype (odds ratioâ =â 2.16, P â =â 0.04). Moreover, a meta-analysis conducted to consolidate findings confirmed the associations of both CYP2C9 (rs1057910) and VKORC1 (rs9923231) with stable warfarin dosage. Notably, CYP2C9 variant genotypes were significantly linked to an increased risk of hemorrhagic complications ( P â <â 0.00001), VKORC1 did not demonstrate a similar association. CONCLUSION: The associations found between specific genetic variants and both stable warfarin dosage and bleeding risk might be the potential significance of gene detection in optimizing warfarin therapy for improving patient efficacy and safety.
Asunto(s)
Anticoagulantes , Pueblo Asiatico , Citocromo P-450 CYP2C9 , Polimorfismo de Nucleótido Simple , Vitamina K Epóxido Reductasas , Warfarina , Humanos , Citocromo P-450 CYP2C9/genética , Vitamina K Epóxido Reductasas/genética , Warfarina/efectos adversos , Warfarina/administración & dosificación , Femenino , Masculino , Persona de Mediana Edad , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Anciano , Pueblo Asiatico/genética , Hemorragia/inducido químicamente , Hemorragia/genética , China , Adulto , Genotipo , Estudios de Asociación Genética , Pueblos del Este de AsiaRESUMEN
Gastrointestinal stromal tumors (GISTs) are predominately induced by KIT mutants. In this study, we found that four and a half LIM domains 2 (FHL2) was highly expressed in GISTs and KIT signaling dramatically increased FHL2 transcription while FHL2 inhibited KIT transcription. In addition, our results showed that FHL2 associated with KIT and increased the ubiquitination of both wild-type KIT and primary KIT mutants in GISTs, leading to decreased expression and activation of KIT although primary KIT mutants were less inhibited by FHL2 than wild-type KIT. In the animal experiments, loss of FHL2 expression in mice carrying germline KIT/V558A mutation which can develop GISTs resulted in increased tumor growth, but increased sensitivity of GISTs to imatinib treatment which is used as the first-line targeted therapy of GISTs, suggesting that FHL2 plays a role in the response of GISTs to KIT inhibitor. Unlike wild-type KIT and primary KIT mutants, we further found that FHL2 didn't alter the expression and activation of drug-resistant secondary KIT mutants. Taken together, our results indicated that FHL2 acts as the negative feedback of KIT signaling in GISTs while primary KIT mutants are less sensitive and secondary KIT mutants are resistant to the inhibition of FHL2.
Asunto(s)
Tumores del Estroma Gastrointestinal , Proteínas con Homeodominio LIM , Proteínas Musculares , Proteínas Proto-Oncogénicas c-kit , Transducción de Señal , Factores de Transcripción , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/metabolismo , Animales , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Proteínas con Homeodominio LIM/genética , Proteínas con Homeodominio LIM/metabolismo , Humanos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Ratones , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Mutación , Carcinogénesis/genética , Regulación Neoplásica de la Expresión Génica , Mesilato de Imatinib/farmacología , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/metabolismo , Línea Celular Tumoral , UbiquitinaciónRESUMEN
BACKGROUND AND OBJECTIVES: The psychological problems of hemodialysis (HD) patients are prominent, and benefit finding (BF) have been proven beneficial to physical and mental health, fewer researchers explored BF in HD patients. The aim of this study was to investigate the current status of BF in patients with chronic kidney disease and to analyze the factors influencing it in order to provide a reference for subsequent interventions. METHODS: A cross-sectional study was done on 246 HD patients by convenience sampling in the hemodialysis center of a 3 A hospital in Shanghai from March to September 2019. The measures include General Information Questionnaire, Benefit Finding Scale, Perceived Social Support Scale, General Self-efficacy Scale, and Simplified Coping Style scale. RESULTS: The median (interquartile range, IQR) score of BF was 66 (IQR = 19) and it was lower compared with other chronic diseases. Significant differences in BF scores were found between different age groups, HD duration categories, and understanding degrees of HD. Taking BF as the dependent variable, the results of multiple linear regression analysis showed that age, duration of HD, family support, other support, positive coping, and self-efficacy entered the regression equation to explain 43.8% of the total variation. Social support played an indirect effect in the relationship between positive coping and BF, accounting for 54.1% of the total effect. CONCLUSION: The BF of HD patients is worrisome and affected by many factors. Medical staff could pay attention to the positive psychology of HD patients, and construct individualized interventions according to the influencing factors to improve their BF level and achieve physical and mental health.
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Adaptación Psicológica , Insuficiencia Renal Crónica , Humanos , Estudios Transversales , China/epidemiología , Diálisis Renal/psicología , Insuficiencia Renal Crónica/terapiaRESUMEN
MicroRNA (miRNA), as a kind of small non-coding ribonucleic acid (RNA) that plays a crucial role in regulating transcriptional activities, is a potential biomarker for EC diagnosis. However, reliable detection of miRNA remains a huge challenge, especially for these methods that require multiple probes for signal amplifications, due to the detective deviation caused by variation of probe concentrations. Herein, we present a novel approach for miRNA-205 identification and quantification by employing simply a ternary hairpin probe (TH probe). The ternary hybridization of three sequences results in the construction of the TH probe, which combines high-efficient signal amplification and specific target recognition. A significant number of G-rich sequences have been produced as a result of the enzymes assisted signal amplification process. The G-rich sequences can fold into G-quadruplexes, which can then be detected in a label-free manner by a common fluorescent dye (thioflavin T). Eventually, the approach exhibits a low limit of detection of 278 aM with a wide detection range of 7 orders of magnitude. In summary, the proposed approach possesses a great potential for both clinical diagnosis of EC and fundamental biomedical researches.
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Técnicas Biosensibles , Neoplasias Endometriales , G-Cuádruplex , MicroARNs , Humanos , Femenino , MicroARNs/genética , MicroARNs/análisis , Hibridación de Ácido Nucleico/métodos , Colorantes Fluorescentes , Técnicas de Amplificación de Ácido Nucleico/métodos , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Límite de Detección , Técnicas Biosensibles/métodosRESUMEN
OBJECTIVE: This study aimed to establish a practical protocol for early noninvasive prenatal testing (NIPT) for fetuses at risk of Peutz-Jeghers syndrome or familial adenomatous polyposis, two classical types of hereditary colorectal cancer syndromes, for risk evaluation and whole-life monitoring. METHOD: Target enrichment was performed using hybridization probes coordinating the serine-threonine kinase 11 gene region and APC gene region, with 1458 highly heterozygous Single Nucleotide Polymorphisms included. Semitarget amplification random sequencing was used for large fragment deletion detection. For relative haplotype dosage (RHDO) analysis, haplotype construction was performed by segmented haplotype estimation and imputation tool software, the circular binary segmentation algorithm was used for recombination event calculation, and Bayes factor was used for the determination of whether the fetus was affected. RESULTS: Haplotypes were successfully constructed in the nine recruited families with different pedigree characteristics, and the results for the RHDO analysis were consistent with the amniocentesis sampling detection results. The cell-free fetal DNA fraction can be detected as low as 2% in maternal plasma. CONCLUSION: This is the first NIPT assay on hereditary colorectal cancer syndromes based upon RHDO analysis.
Asunto(s)
Ácidos Nucleicos Libres de Células , Neoplasias Colorrectales , Pruebas Prenatales no Invasivas , Teorema de Bayes , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Femenino , Humanos , Embarazo , Diagnóstico Prenatal/métodos , SíndromeRESUMEN
BACKGROUND: The de Winter ECG pattern was described by upsloping ST-segment depression in leads V1-V6, tall and symmetrical T waves in precordial leads. The ECG pattern is regarded to be associated with occlusion of the left anterior descending (LAD) artery. METHODS: One patient with de Winter ECG pattern was included. The 12-lead ECG of patients with chest pain showed upsloping ST-segment depression up to 3 mm at the J point in leads V2-V6; tall symmetrical T waves in leads V2-V4; 1mm J point elevation in lead aVR; ST-segment depression 1mm in I, aVL leads and inverted T waves in the inferior leads. The ECG was showed the de Winter pattern. RESULTS: The ECG was showed the de Winter pattern. CAG was performed, which showed the normal left main; 60%-80% LAD stenosis; 50%-60% ostial right coronary artery(RCA) stenosis; and 90% stenosis of the vessel at middle segment. Both proximal and middle RCA vascular lesions were dilated and successfully inserted with drug-eluting stents, respectively. CONCLUSION: Our case the ECG was showed horizontal ST depression with tall T waves in leads V2-V4 (maximal ST depression in lead V4) while only ST depression in leads V5-V6, which may result from multivessel disease.
Asunto(s)
Vasos Coronarios , Electrocardiografía , Humanos , Constricción Patológica , Dolor en el PechoRESUMEN
BACKGROUND: A growing number of studies have reported that sperm DNA fragmentation (SDF) is associated with male infertility. However, no studies have compared genome-wide DNA methylation profiles and sncRNA signatures between sperm with high and low sperm DNA fragmentation indices (DFIs). METHODS: Whole-genome bisulfite sequencing (WGBS) was performed on sperm samples from a weak group (DFI ≥ 30%, n = 6) and normal group (DFI ≤ 15%, n = 7). Small noncoding RNA (sncRNA) deep sequencing was conducted for sperm samples from the weak (DFI ≥ 30%, n = 13) and normal (DFI ≤ 15%, n = 17) groups. RESULTS: A total of 4939 differentially methylated regions (DMRs) were identified in the weak group sperm samples relative to normal group sperm samples, with 2072 (41.95%) of them located in promoter regions. The percentages of hypermethylated DMRs were higher than those of hypomethylated DMRs in all seven examined gene annotation groups. Hypermethylated DMRs were significantly enriched in terms associated with neurons and microtubules. Compared with the normal group, the global DNA methylation level of the weak group sperm showed a downward trend, with lower correlation for methylation in the weak group sperm; therefore, the chromosomes of high-DFI sperm may be loose. On average, 40.5% of sncRNAs were annotated as rsRNAs, 19.3% as tsRNAs, 10.4% as yRNAs, and 7.1% as miRNAs. A total of 27 miRNAs, 151 tsRNAs, and 70 rsRNAs were differentially expressed between the two groups of sperm samples. Finally, 7 sncRNAs were identified as candidate sperm quality biomarkers, and the target genes of the differentially expressed miRNAs are involved in nervous system development. CONCLUSION: Our findings suggest that genome-wide DNA methylation profiles and sncRNA signatures are significantly altered in high-DFI sperm. Our study provides potential biomarkers for sperm quality.
Asunto(s)
MicroARNs , ARN Pequeño no Traducido , Humanos , Masculino , Fragmentación del ADN , Metilación de ADN/genética , ARN Pequeño no Traducido/genética , Semen , Espermatozoides/metabolismo , MicroARNs/metabolismoRESUMEN
AIMS: This study aimed to investigate the dynamic pattern of serum hepatitis B virus (HBV) RNA in chronic hepatitis B (CHB) patients on long-term nucleos(t)ide analogue (NA) therapy and evaluate predictor value of end-of-treatment (EOT) serum HBV RNA status on drug-withdrawal durability. METHODS: We carried out a real-life cohort study of 326 CHB patients on NA treatment between February 12, 2016 and February 21, 2018. Thirty of these patients discontinued NA treatment after enrollment, and were included in 2-year off-therapy follow-up. Serum HBV RNA levels were determined using the RNA simultaneous amplification testing method. RESULTS: Both serum HBV RNA and DNA levels declined significantly in long-term antiviral progress. When the treatment duration was longer than 3 years, the undetectable rates of HBV RNA and DNA were 55.10% and 97.0%, respectively. The serum HBV RNA-negative rate was 39.5%. The cumulative 2-year off-therapy viral and clinical relapse rate was 40.56%; 95% confidence interval (95% CI), 21.51-59.61 and 31.31%; 95% CI, 11.32-51.29 in all patients, respectively. Patients with EOT hepatitis B surface antigen (HBsAg)≤1000 IU/mL plus HBV RNA negativity had a relatively lower cumulative 2-year off-therapy viral relapse rate (23.01%; 95% CI, 0.17-45.99). EOT HBsAg≤1000 IU/mL plus HBV RNA negativity showed obvious superiority for the EOT HBsAg≤1000 IU/mL single in drug withdrawal durability prediction, with better specificity (18.18% vs. 72.73%, P=0.03), and the positive predictive value and negative predictive value were 76.92% and 47.06%, respectively. CONCLUSIONS: In the long-term antiviral process, both serum HBV RNA and DNA levels declined significantly. EOT serum HBV RNA negativity was not an independent drug withdrawal marker, but can complement the HBsAg titer to monitor drug withdrawal in CHB patients on long-term NA therapy.
Asunto(s)
Hepatitis B Crónica , Preparaciones Farmacéuticas , Antivirales/uso terapéutico , Estudios de Cohortes , ADN Viral , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Humanos , ARN/uso terapéuticoRESUMEN
The aim of this study was to investigate the combined effect of n-3 fatty acids (EPA and DHA, at an EPA:DHA ratio of 150:500) and phytosterol esters (PS) on non-alcoholic fatty liver disease (NAFLD) patients. We conducted a randomised, double-blind, placebo-controlled trial. Ninety-six NAFLD subjects were randomly assigned to the following groups: the PS group (receiving 3·3 g/d PS); the FO group (receiving 450 mg EPA + 1500 mg DHA/d); the PS + FO combination group (receiving 3·3 g/d PS and 450 mg EPA + 1500 mg DHA/d) and the PO group (a placebo group). The baseline clinical characteristics of the four groups were similar. The primary outcome was liver:spleen attenuation ratio (L:S ratio). The percentage increase in liver-spleen attenuation (≤1) in the PS + FO group was 36 % (P = 0·083), higher than those in the other three groups (PS group, 11 %, P = 0·519; FO group, 18 %, P = 0·071; PO group, 15 %, P = 0·436). Compared with baseline, transforming growth factor-ß (TGF-ß) was significantly decreased in the three study groups at the end of the trial (PS, P = 0·000; FO, P = 0·002; PS + FO, P = 0·001) and TNF-α was significantly decreased in the FO group (P = 0·036), PS + FO group (P = 0·005) and PO group (P = 0·032) at the end of the intervention. Notably, TGF-ß was reduced significantly more in the PS + FO group than in the PO group (P = 0·032). The TAG and total cholesterol levels of the PS + FO group were reduced by 11·57 and 9·55 %, respectively. In conclusion, co-supplementation of PS and EPA + DHA could increase the effectiveness of treatment for hepatic steatosis.
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Suplementos Dietéticos , Ésteres/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Enfermedad del Hígado Graso no Alcohólico/terapia , Fitosteroles/administración & dosificación , Adulto , Método Doble Ciego , Femenino , Humanos , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Bazo/metabolismo , Resultado del TratamientoRESUMEN
Mycoplasma pneumoniae (MP) can infect both the upper and lower respiratory tracts. Polydatin (PD), a traditional Chinese medicine, is known to have anti-inflammation and antifibrosis properties. However, the protective effects of PD against MP pneumonia (MPP) remain unclear. So, the aim of this study was to describe the therapeutic effects and underlying mechanisms of PD against MPP. BALB/c mice were assigned to three groups: a normal control group, MP infection group, or PD-treated MP infection group. BEAS-2B cells transfected with or without NACHT domain-, leucine-rich repeat-, and pyd-containing protein 3 (NLRP3) were used to confirm the protective mechanisms of PD. Immunohistochemical analysis, Western blot analysis, enzyme-linked immunosorbent assay, and flow cytometry were used in this study. The results showed that PD treatment suppressed MP-induced lung injury in mice by suppressing the expression of inflammatory factors and inhibiting the development of pulmonary fibrosis. Meanwhile, PD treatment inhibited activation of the NLRP3 inflammasome and nuclear factor κB (NF-κB) pathway. Overexpression of NLRP3 reversed the protective effect of PD against MP-induced injury of BEAS-2B cells. Taken together, these results indicate that PD treatment suppressed the inflammatory response and the development of pulmonary fibrosis by inhibiting the NLRP3 inflammasome and NF-κB pathway after MP infection.
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Glucósidos/farmacología , Inflamasomas/efectos de los fármacos , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Neumonía por Mycoplasma/prevención & control , Neumonía/prevención & control , Fibrosis Pulmonar/prevención & control , Estilbenos/farmacología , Animales , Línea Celular , Medicamentos Herbarios Chinos/farmacología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Humanos , Inflamasomas/metabolismo , Pulmón/citología , Ratones Endogámicos BALB C , Neumonía/metabolismo , Neumonía/microbiología , Neumonía por Mycoplasma/metabolismo , Neumonía por Mycoplasma/microbiología , Sustancias Protectoras/farmacología , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/microbiología , Transducción de Señal/efectos de los fármacosRESUMEN
The mechanism of hepatocellular carcinoma (HCC) metastasis remains poorly understood. Tropomodulin 3 (TMOD3) is a member of the pointed end capping protein family that contributes to invasion and metastasis in several types of malignancies. It has been found to be crucial for the membranous skeleton and embryonic development, although, its role in HCC progression remains largely unclear. We observed increased levels of Tmod3 in HCCs, especially in extrahepatic metastasis. High Tmod3 expression correlated with aggressive carcinoma and poor patient with HCC survival. Loss-of-function studies conducted by us determined Tmod3 as an oncogene that promoted HCC growth and metastasis. Mechanistically, Tmod3 increases transcription of matrix metalloproteinase-2, -7, and -9 which required PI3K-AKT. Interaction between Tmod3 and epidermal growth factor receptor (EGFR) that supports the activation of EGFR phosphorylation, is essential for signaling activation of PI3K-AKT viral oncogene homolog. These findings reveal that Tmod3 enhances aggressive behavior of HCC both in vitro and in vivo by interacting with EFGR and by activating the PI3K-AKT signaling pathway.
Asunto(s)
Carcinoma Hepatocelular/genética , Proliferación Celular/genética , Neoplasias Hepáticas/genética , Tropomodulina/genética , Animales , Carcinoma Hepatocelular/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Transición Epitelial-Mesenquimal/genética , Receptores ErbB/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Xenoinjertos , Humanos , Neoplasias Hepáticas/patología , Masculino , Ratones , Persona de Mediana Edad , Metástasis de la Neoplasia , Proteína Oncogénica v-akt/genética , Fosfatidilinositol 3-Quinasas/genética , Transducción de Señal/genéticaRESUMEN
BACKGROUND: As an alternative biomarker of intrahepatic covalently closed circular DNA (cccDNA) transcriptional activity, hepatitis B virus (HBV) RNA may evolve during long-lasting virus-host interactions during chronic hepatitis B viral infection. The distribution pattern of serum HBV RNA levels in the natural course of chronic HBV infection remains unclear. The aim of this study was to evaluate the levels of HBV RNA during the natural course of CHB and the role in distinguishing the natural history of HBV infection. METHODS: A total of 291 treatment-naïve chronic HBV carriers were enrolled. Based on the clinical, biochemical, serological, and histological data as well as HBV DNA levels, patients were classified into the following four categories: the immune-tolerant phase (IT,n = 35), HBeAg-positive immune-active phase (EPIA,n = 121), inactive chronic hepatitis B(ICH,n = 77) and HBeAg-negative immune reactive hepatitis (ENH,n = 58) [corrected]. The parameters and distribution patterns of serum HBV RNA were evaluated in relation to viral replication status, immune phase, disease category and Child-Pugh class. The relationships between serum HBV RNA and other serum hepatitis B viral markers were also analyzed. RESULTS: Serum HBV RNA levels were significantly lower in the HBeAg-negative patients compared to those in the HBeAg-positive patients, with the lowest levels seen in inactive carriers. In HBeAg-negative patients, serum HBV RNA levels increased if there is reactivation to active hepatitis and showed obvious superiority for the combination of serum HBV DNA (cutoff>3.39 Log copies/mL) and HBsAg (cutoff>2.74 Log IU/mL) in discriminating between 'HBeAg-negative immune reactive' phase and inactive chronic hepatitis B phases of HBeAg-negative chronic HBV infection. Serum HBV RNA levels were positively correlated with serum HBV DNA and HBsAg levels in all chronic HBV-infected patients. A stratified analysis revealed that a correlation between serum HBV RNA and HBV DNA or HBsAg was present in HBeAg-positive patients; however, in HBeAg-negative patients, serum HBV RNA was positively correlated with HBV DNA only. CONCLUSION: During the natural course of chronic HBV infection, serum HBV RNA levels vary. Serum HBV RNA can act as a biomarker to predict the natural history of disease in chronic hepatitis B patients. In treatment-naïve HBeAg-negative chronic HBV-infected individuals, serum HBV RNA shows superiority in differentiating the 'HBeAg-negative reactive' phase.
Asunto(s)
Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , ARN Viral/sangre , Adulto , Biomarcadores/sangre , Femenino , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/clasificación , Hepatitis B Crónica/inmunología , Humanos , Masculino , Persona de Mediana Edad , Activación ViralRESUMEN
Following publication of the original article [1].
RESUMEN
Neurosurgery navigation system, which is expensive and complicated to operate, has a low penetration rate, and is only found in some large medical institutions. In order to meet the needs of other small and medium-sized medical institutions for neurosurgical navigation systems, the scalp localization system of neurosurgery based on augmented reality (AR) theory was developed. AR technology is used to fuse virtual world images with real images. The system integrates computed tomography (CT) or magnetic resonance imaging (MRI) with the patient's head in real life to achieve the scalp positioning. This article focuses on the key points of Digital Imaging and Communications in Medicine (DICOM) standard, three-dimensional (3D) reconstruction, and AR image layer fusion in medical image visualization. This research shows that the system is suitable for a variety of mobile phones, can achieve two-dimensional (2D) image display, 3D rendering and clinical scalp positioning application, which has a certain significance for the auxiliary neurosurgical head surface positioning.
Asunto(s)
Imagenología Tridimensional , Neurocirugia/métodos , Cuero Cabelludo , Humanos , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos XRESUMEN
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and represents a highly malignant tumor with a poor prognosis. Therapeutic modalities for HCC are limited and generally ineffective. UBE2Q1 is a putative E2 ubiquitin conjugating enzyme, and has been shown to be overexpressed in various types of cancers including HCC. How UBE2Q1 contributes to hepatocarcinogenesis remains unknown. Here, we show that UBE2Q1 is up-regulated in HCC cell lines and in a subset of human HCC tissues. Up-regulation of UBE2Q1 in primary HCC tumors was significantly correlated with shorter overall survival and disease-free survival. Mechanistically, we showed that the frequent up-regulation of UBE2Q1 in HCCs was attributed to the recurrent UBE2Q1 gene copy gain at chromosome 1q21. Functionally, we showed that knockdown of UBE2Q1 reduced HCC cell proliferation, promoted apoptosis via induction of GADD45α, and suppressed orthotopic tumorigenicity both in vitro and in vivo. Inactivation of UBE2Q1 also impeded HCC cell migration and invasion in vitro through regulating EMT process, and suppressed HCC metastasis in vivo. Interestingly, our data revealed a role of UBE2Q1 in the regulation of ß-catenin-EGFR-PI3K-Akt-mTOR signaling pathway. Our findings indicate that UBE2Q1 is a candidate oncogene involved in HCC development and progression and therefore a potential therapeutic target in applicable HCC patients.
Asunto(s)
Carcinoma Hepatocelular/genética , Dosificación de Gen/genética , Neoplasias Hepáticas/genética , Transducción de Señal/genética , Enzimas Ubiquitina-Conjugadoras/genética , Regulación hacia Arriba/genética , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Receptores ErbB/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Serina-Treonina Quinasas TOR/genética , beta Catenina/genéticaRESUMEN
Celastrol is well known for its anti-cancer effects, yet its specific mechanisms against colon cancer are still not fully elucidated. In this study, cytotoxic effect of celastrol against HCT116 colon cancer cells was investigated based on cell viability assay and flow cytometry assay, and the possible mechanism was explored using a strategy combining metabolic profiling and targeted metabolite analysis based on ultra performance liquid chromatography (UPLC)/MS. Celastrol was found to inhibit the growth of colon cancer cells and induce apoptosis. Metabolomics analysis revealed characteristic changes in metabolic profiles of the colon cancer cells, revealing altered levels of amino acids, carnitine, and lipid markers. Most interestingly, with the assistance of targeted metabolite analysis, tryptophan (Trp) level was significantly increased whereas kynurenine (Kyn) level was decreased in colon cancer cells after celastrol treatment, together with markedly declined Kyn/Trp ratios. Western blot analysis revealed that expression of indoleamine 2,3-dioxygenase (IDO), the enzyme catalyzing Trp to generate Kyn, was dramatically inhibited in colon cancer cells after celastrol treatment, with a dose-dependent manner. These results suggest that suppression of IDO expression and tryptophan catabolism may be part of the mechanisms of celastrol in its cytotoxic effect against HCT116 colon cancer cells. This study provided scientific basis for further development of celastrol on treating colon cancer.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias del Colon/metabolismo , Triterpenos/farmacología , Supervivencia Celular/efectos de los fármacos , Células HCT116 , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Quinurenina/metabolismo , Metabolómica , Triterpenos Pentacíclicos , Triptófano/metabolismoRESUMEN
Gastric carcinoma is one of the most common malignancies worldwide and the second most frequent cause of cancer-related death in China. Protein regulator of cytokinesis 1 (PRC1) is involved in cytokinesis and plays key roles in microtubule organization in eukaryotes. This study was aimed to analyse the expression and to investigate the functional role of PRC1 in gastric tumorigenesis. The expression of PRC1 was evaluated by qRT-PCR, Western blot and immunohistochemistry. The biological function of PRC1 was determined by CCK-8 proliferation assays, monolayer colony formation, xenografted nude mice and cell invasion assays by shRNA-mediated knockdown in AGS and HGC27 cells. The regulation of PRC1 expression by piperlongumine was also investigated using dual-luciferase reporter assay and ChIP-qPCR analysis. PRC1 was up-regulated in primary gastric cancers. Overexpression of PRC1 in gastric cancers was associated with poor disease-specific survival and overall survival. PRC1 knockdown in AGS and HGC27 cell lines suppressed proliferation, reduced monolayer colony formation, inhibited cell invasion and migration ability and induced cell-cycle arrest and apoptosis. Inhibition of PRC1 also suppressed tumour growth in vivo. We finally confirmed that PRC1 is a novel downstream target of piperlongumine in gastric cancer. Our findings supported the oncogenic role of PRC1 in gastric carcinogenesis. PRC1 might serve as a prognostic biomarker and potential therapeutic target for gastric carcinoma.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma/genética , Proteínas de Ciclo Celular/genética , Neoplasias Gástricas/genética , Carcinogénesis/genética , Carcinoma/tratamiento farmacológico , Carcinoma/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dioxolanos/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Grainyhead-like 2 is a human homolog of Drosophila grainyhead. It inhibits epithelial-to-mesenchymal transition that is necessary for cell migration, and it is involved in neural tube closure, epithelial morphogenesis, and barrier formation during embryogenesis by regulation of the expression of cell junction proteins such as E-cadherin and vimentin. Cancer shares many common characters with development such as epithelial-to-mesenchymal transition. In addition to its important role in development, grainyhead-like 2 is implicated in carcinogenesis as well. However, the reports on grainyhead-like 2 in various cancers are controversial. Grainyhead-like 2 can act as either a tumor suppressor or an oncogene with the mechanisms not well elucidated. In this review, we summarized recent progress on grainyhead-like 2 in development and cancer in order to get an insight into the regulation network of grainyhead-like 2 and understand the roles of grainyhead-like 2 in various cancers.
Asunto(s)
Carcinogénesis/genética , Proteínas de Unión al ADN/genética , Transición Epitelial-Mesenquimal/genética , Neoplasias/genética , Factores de Transcripción/genética , Regulación Neoplásica de la Expresión Génica , HumanosRESUMEN
Certain viruses use microRNAs to regulate the expression of their own genes, host genes, or both. A number of microRNAs expressed by herpes simplex virus type 2 have been confirmed by previous studies. However, whether these microRNAs play a role in the metastasis of lung cancers and how these viral microRNAs precisely regulated the tumor biological process in lung cancer bone metastasis remain obscure. We recently identified the high expression of an acutely and latently expressed viral microRNA, Hsv2-miR-H9-5p, encoded by herpes simplex virus type 2 latency-associated transcript through microarray and quantitative polymerase chain reaction analyses which compared the expression of microRNAs in bone metastasis from lung cancer with primary lung cancers. We now reported that Hsv2-miR-H9-5p was highly expressed in bone metastasis and closely associated with pathological and metastatic processes of lung cancers. The functions of Hsv2-miR-H9-5p were determined by overexpression which results in an increase in survival, migration, and invasion of lung cancer cells in vitro. We determined that Hsv2-miR-H9-5p directly targeted SOCS2 mechanistically by dual-luciferase reporter assay. Then, we investigated the functions of SOCS2 in the progress of lung cancers. Reduction of SOCS2 dosage by hsv2-miR-H9-5p induced increased migration and invasion of lung cancer cells. Overexpression of SOCS2 inverted these phenotypes generated by hsv2-miR-H9-5p, indicating the potential roles of SOCS2 in Hsv2-miR-H9-5p-driven metastasis in lung cancers. The results highlighted that Hsv2-miR-H9-5p regulated and contributed to bone metastasis of lung cancers. We proposed that Hsv2-miR-H9-5p could be used as a potential target in lung cancer therapy.