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1.
Gut Microbes ; : 1-18, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138622

RESUMO

Little is known about the regulatory effect of microbiota on the proliferation and regeneration of ISCs. Here, we found that L. reuteri stimulated the proliferation of intestinal epithelia by increasing the expression of R-spondins and thus activating the Wnt/ß-catenin pathway. The proliferation-stimulating effect of Lactobacillus on repair is further enhanced under TNF -induced intestinal mucosal damage, and the number of Lgr5+ cells is maintained. Moreover, compared to the effects of C. rodentium on the induction of intestinal inflammation and crypt hyperplasia in mice, L. reuteri protected the intestinal mucosal barrier integrity by moderately modulating the Wnt/ß-catenin signaling pathway to avoid overactivation. L. reuteri had the ability to maintain the number of Lgr5+ cells and stimulate intestinal epithelial proliferation to repair epithelial damage and reduce proinflammatory cytokine secretion in the intestine and the LPS concentration in serum. Moreover, activation of the Wnt/ß-catenin pathway also induced differentiation toward Paneth cells and increased antimicrobial peptide expression to inhibit C. rodentium colonization. The protective effect of Lactobacillus against C. rodentium infection disappeared upon application of the Wnt antagonist Wnt-C59 in both mice and intestinal organoids. This study demonstrates that Lactobacillus is effective at maintaining intestinal epithelial regeneration and homeostasis as well as at repairing intestinal damage after pathological injury and is thus a promising alternative therapeutic method for intestinal inflammation.

2.
Res Vet Sci ; 130: 179-183, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32199176

RESUMO

S. Pullorum is a causative agent of enteric disease of poultry with serious diarrhea. However, the detailed mechanism behind its injury to intestinal mucosa barrier, especially for intestinal stem cells, is unclear. In this study, S. Pullorum were orally administrated to 3 days old chicken to investigate the pathogenesis of S. Pullorum on intestinal mucosal barrier, especially on the proliferation of epithelial cells. We found that S. Pullorum could colonize in the cecum and invade into the liver through intestinal mucosa damage, which caused obvious pathological changes in liver and intestine and even leaded to death, as well as significant reduction of body weight. We also found that S. Pullorum infection enhanced the mRNA expression of IL-1ß and IL-6 through TLR4/MyD88 pathway, which was also further verified by the increased lipopolysaccharide (LPS) levels in serum. Furthermore, S. Pullorum increased the depth of crypt and density of PCNA+ cells significantly through the over-activation of Wnt/ß-catenin signaling pathway. The expression of intestinal stem cells markers Lgr5 and Bmi1 was also increased after S. Pullorum infection to support the crypt hyperplasia. In addition, we verified that S. Pullorum infection enhanced the mRNA expression of IL-1ß, TLR4, Lgr5 and Bmi1. Our study indicated that S. Pullorum infection damaged the intestinal mucosa barrier to induce diarrhea, affected the abnormal proliferation of intestinal stem cells by over-activation of Wnt/ß-catenin pathway in chicken.

3.
Nanoscale ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191786

RESUMO

Molecular dynamics (MD) simulations were performed employing the polarized protein-specific charge (PPC) to explore the origin of the cooperativity in streptavidin-biotin systems (wild type, two single mutations and one double-mutation). The results of the experiment found that the existence of cooperativity is mainly the result of the entropic effect. In this study, the entropic contribution to the binding free energy was calculated using the recently developed interaction entropy (IE) method, and computational results are in excellent agreement with the experimental observations and are further verified by the calculation of the thermodynamic integration. Comparison of different force fields in terms of predicted binding strength ordering, cooperativity of energy and the stability of hydrogen bonding suggests that the PPC force field combined IE method is a suitable choice. In addition, the IE method enables us to obtain the residue-specific entropic contributions to the streptavidin-biotin binding affinity and identify ten hot-spot residues providing the dominant contribution to the cooperative binding. Importantly, the overall cooperativity obtained from the ten residues also comes mainly from the entropic effect in our study. The calculation of the potential of mean force shows that the unbinding of streptavidin-biotin is a multi-step process, and each step corresponds to the formation and rupture of the hydrogen bond network. And S45A mutation may increase the rigidity of the linker region, making the flap region relatively difficult to open. The present study provides significant molecular insight into the binding cooperativity of the streptavidin-biotin complex.

4.
Nutrients ; 12(3)2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32197331

RESUMO

Arthrospira platensis (spirulina) is a cyanobacterium, which contains mainly two phycobiliproteins (PBP), i.e., C-phycocyanin (C-PC) and allophycocyanin (APC). In this study, PBP were hydrolyzed using trypsin, and the composition of the hydrolysate was characterized by HPLC-ESI-MS/MS. Furthermore, the potential anti-diabetic activity was assessed by using either biochemical or cellular techniques. Findings suggest that PBP peptides inhibit DPP-IV activity in vitro with a dose-response trend and an IC50 value falling in the range between 0.5 and 1.0 mg/mL. A lower inhibition of the DPP-IV activity expressed by Caco-2 cells was observed, which was explained by a secondary metabolic degradation exerted by the same cells.

5.
Gynecol Endocrinol ; : 1-5, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32208782

RESUMO

We design this study to detect levels of Elabela (ELA) and Apelin (APLN) in women with and without gestational diabetes mellitus (GDM) in the second and third trimesters, and to identify whether there is any association between ELA, APLN, and metabolic parameters. Seventy-nine GDM and 80 control subjects in the second trimester and 87 GDM and 88 healthy subjects in the third trimester were included. In the second trimester, lower ELA levels [(14.1 versus 16.9) ng/ml, p = .025] and higher APLN levels [(1021.8 versus 923.5) pg/ml, p = .046] were observed in GDM patients compared to controls. ELA levels were positively correlated with fasting plasma glucose (FPG) (r = 0.423, p < .001) in the control group, and APLN levels were negatively correlated with triglycerides (TG) (r = -0.251, p = .025) in the control group and total cholesterol (TC) (r = -0.227, p = .044) in the GDM group. ELA appeared to be related to glucose metabolism and APLN is involved in lipid metabolism during pregnancy. The expression of ELA is significantly downregulated from the second trimester to the third trimester.

6.
BMC Psychiatry ; 20(1): 43, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013935

RESUMO

BACKGROUND: Traumatized earthquake survivors may develop poor memory function. Resting-state functional magnetic resonance imaging (rs-fMRI) and machine learning techniques may one day aid the clinical assessment of individual psychiatric patients. This study aims to use machine learning with Rs-fMRI from the perspectives of neurophysiology and neuroimaging to explore the association between it and the individual memory function of trauma survivors. METHODS: Rs-fMRI data was acquired for eighty-nine survivors (male (33%), average age (SD):45.18(6.31) years) of Wenchuan earthquakes in 2008 each of whom was screened by experienced psychiatrists based on the clinician-administered post-traumatic stress disorder (PTSD) scale (CAPS), and their memory function scores were determined by the Wechsler Memory Scale-IV (WMS-IV). We explored which memory function scores were significantly associated with CAPS scores. Using simple multiple kernel learning (MKL), Rs-fMRI was used to predict the memory function scores that were associated with CAPS scores. A support vector machine (SVM) was also used to make classifications in trauma survivors with or without PTSD. RESULTS: Spatial addition (SA), which is defined by spatial working memory function, was negatively correlated with the total CAPS score (r = - 0.22, P = 0.04). The use of simple MKL allowed quantitative association of SA scores with statistically significant accuracy (correlation = 0.28, P = 0.03; mean squared error = 8.36; P = 0.04). The left middle frontal gyrus and the left precuneus contributed the largest proportion to the simple MKL association frame. The SVM could not make a quantitative classification of diagnosis with statistically significant accuracy. LIMITATIONS: The use of the cross-sectional study design after exposure to an earthquake and the leave-one-out cross-validation (LOOCV) increases the risk of overfitting. CONCLUSION: Spontaneous brain activity of the left middle frontal gyrus and the left precuneus acquired by rs-fMRI may be a brain mechanism of visual working memory that is related to PTSD symptoms. Machine learning may be a useful tool in the identification of brain mechanisms of memory impairment in trauma survivors.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32052123

RESUMO

Neuroimaging findings suggest that the amygdala plays a primary role in both the psychopathology of posttraumatic stress disorder (PTSD) and poor sleep quality, which are common in trauma survivors. However, the neural mechanisms of these two problems in trauma survivors associated with amygdala remain unclear. In the current study, we aimed to explore the role of functional connectivity of amygdala subregions in both PTSD symptoms and poor sleep quality. A total of 94 trauma-exposed subjects were scanned on a 3T MR system using resting-state functional magnetic resonance imaging. Both Pittsburgh Sleep Quality Index and Clinician-Administered PTSD Scale scores were negatively correlated with the resting-state functional connectivity between the left basolateral amygdala-left medial prefrontal cortex and the right basolateral amygdala-right medial prefrontal cortex. Our findings suggest a shared amygdala subregional neural circuitry underlying the neuropathological mechanisms of PTSD symptoms and poor sleep quality in trauma survivors.

8.
J Pineal Res ; 68(3): e12635, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32012354

RESUMO

Embryo culture conditions are crucial as they can affect embryo quality and even offspring. Oviductal extracellular vesicles (EVs) long been considered a major factor influencing interactions between the oviduct and embryos, and thus its absence is associated with inferior embryonic development in in vitro culture. Herein, we demonstrated that melatonin is present in oviduct fluids and oviduct fluid-derived EVs. Addition of either EVs (1.87 × 1011 particles/mL) or melatonin (340 ng/mL) led to a significant downregulation of reactive oxygen species (ROS) and 5-methylcytosine (5-mC), as well as an increase in the blastocyst rate of embryos, which was inhibited by the addition of luzindole-a melatonin receptor agonist. A combination of EVs (1.87 × 1010 particles/mL) and melatonin (at 34.3 pg/mL) led to the same results as well as a significant decrease in the apoptosis index and increase in the inner cell mass (ICM)/trophectoderm (TE) index. These results suggest that an EV-melatonin treatment benefits embryonic development. Our findings provide insights into the role of EVs and melatonin during cell communication and provide new evidence of the communication between embryos and maternal oviduct.

9.
BMC Public Health ; 20(1): 230, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059652

RESUMO

BACKGROUND: The Chinese government is piloting canteen services for older adults, but few studies have explored the influence of canteen services on the health of these older adults. This study aimed to investigate the impact of canteen services on older adults' general mental health, nutritional status, satisfaction with life, and social capital in rural areas. METHODS: This study used a cross-sectional design. We selected 14 villages in Jinhua City, Zhejiang Province, China, including seven villages with canteen services and seven villages without canteen services. Participants were 284 senior older adults (aged 75~98), including 140 residing in villages with canteen services (Canteen Group [CG]) and 144 residing in villages without canteen services (Non-Canteen Group [NCG]). We also divided the CG into two sub-groups according to the funding sources (one receiving government support only, the other receiving government support plus enterprise donations). We used a self-designed questionnaire, including sociodemographics, diet-related items (e.g., satisfaction with the meals, diet expenditure, self-evaluation of meal nutrition), and the four scales including the Chinese version of the 12-item General Health Questionnaire (GHQ-12), the Chinese version of the Mini Nutritional Assessment Short-Form (MNA-SF), the Satisfaction with Life Scale (SWLS), and the Social Capital Questionnaire (SCQ). RESULTS: The overall mental health, satisfaction with life, and social capital of the CG were better than the NCG (P <  0.05). The nutritional status of these two groups did not show a significant difference. Participants in the CG with financial support from local government and donations from an enterprise with a better dietary diversity exhibited a better nutritional status (P <  0.05); the average satisfaction with diet and self-evaluation of food nutrition of the CG were higher than the NCG (P < 0.05); the ratio of having a diet on time in the CG was higher than that of the NCG (P < 0.05). CONCLUSION: The free canteen services provided by the government can improve older adults' satisfaction with life and diet, and mental health status and also enrich their social capital, but this still needs to be future evidenced. More financial support for canteen services is an essential component in promoting successful aging in China.

10.
J Agric Food Chem ; 68(4): 961-974, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31910000

RESUMO

Manipulating light transmission by shading is the most effective method of improving the nutritional value and sensory qualities of tea. In this study, the metabolic profiling of two tea cultivars ("Yulv" and "Maotouzhong") in response to different shading periods during the summer season was performed using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS) and gas chromatography-mass spectrometry (GC-MS). The metabolic pathway analyses showed that the glycolytic pathway and the tricarboxylic acid cycle (TCA cycle) in the leaves and shoots of "Maotouzhong" were significantly inhibited by long-term shading. The nitrogen metabolism in the leaves of the two cultivars was promoted by short-term shading, while it was inhibited by long-term shading. However, the nitrogen metabolism in the shoots of the two cultivars was always inhibited by shading, whether for short or long-term periods. In addition, the intensity of the flavonoid metabolism in both tea cultivars could be reduced by shading. These results revealed that shading could regulate the carbon and nitrogen metabolism and short-term shading could improve the tea quality to some extent.


Assuntos
Camellia sinensis/metabolismo , Camellia sinensis/efeitos da radiação , Carbono/metabolismo , Nitrogênio/metabolismo , Folhas de Planta/química , Camellia sinensis/química , Cromatografia Líquida , Produção Agrícola , Flavonoides/química , Flavonoides/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Luz , Metabolômica , Folhas de Planta/metabolismo , Folhas de Planta/efeitos da radiação , Espectrometria de Massas em Tandem
11.
Reprod Toxicol ; 93: 54-60, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926278

RESUMO

Cadmium is involved in female gonadal toxicity. Although many studies concur in suggesting a significant influence on female reproduction, the mechanisms of action are still needed to study. This study was designed to examine the characteristics of 0, 5, 10, and 20 µM cadmium toxicity in granulosa cells culture for 12 h, and the subsequent effect of cadmium exposure on AMH production and formation. Here we demonstrate that the viability of granulosa cells cadmium exposed was decreased, and the apoptosis was increased. Intriguingly, After exposure to cadmium the SCF was decreased and the AMH was increased in granulosa cells. This study may demonstrate that AMH signaling is involved in Cd action through SCF activation. The signaling pathways may play a role in the reproductive effects caused by environmental and occupational exposures to Cd. These results further confirm the functional significance of AMH signaling in mediating the intraovarian actions of Cd.

12.
Curr Neuropharmacol ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31903882

RESUMO

Aneurysmal subarachnoid hemorrhage (aSAH) is a subtype of hemorrhagic stroke with significant morbidity and mortality. Aneurysmal bleeding causes elevated intracranial pressure, decreased cerebral blood flow, global cerebral ischemia, brain edema, blood component extravasation, and accumulation of breakdown products. These post-SAH injuries can disrupt the integrity and function of blood-brain barrier (BBB), and brain tissues are directly exposed to the neurotoxic blood contents and immune cells, which leads to secondary brain injuries including inflammation and oxidative stress, and other cascades. Though the exact mechanisms are not fully clarified, multiple interconnected and/or independent signaling pathways have been reported to be involved in BBB disruption after SAH. In addition, alleviation of BBB disruption via various pathways or chemicals has a neuroprotective effect in SAH. Hence, BBB permeability plays an important role in the pathological course and outcomes of SAH. This review discusses the recent understandings of the underlying mechanisms and potential therapeutic targets in BBB disruption after SAH, emphasizing the dysfunction of tight junctions and endothelial cells in the development of BBB disruption. The emerging molecular targets, including toll-like receptor 4, netrin-1, lipocalin-2, tropomyosin-related kinase receptor B, and receptor tyrosine kinase ErbB4, are also summarized in detail. Finally, we discuss the emerging treatments for BBB disruption after SAH and put forward our perspectives on future research.

13.
Cells ; 9(2)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31973233

RESUMO

Glioblastoma (GBM) is a treatment-refractory central nervous system (CNS) tumour, and better therapies to treat this aggressive disease are urgently needed. Primary GBM models that represent the true disease state are essential to better understand disease biology and for accurate preclinical therapy assessment. We have previously presented a comprehensive transcriptome characterisation of a panel (n = 12) of primary GBM models (Q-Cell). We have now generated a systematic, quantitative, and deep proteome abundance atlas of the Q-Cell models grown in 3D culture, representing 6167 human proteins. A recent study has highlighted the degree of functional heterogeneity that coexists within individual GBM tumours, describing four cellular states (MES-like, NPC-like, OPC-like and AC-like). We performed comparative proteomic analysis, confirming a good representation of each of the four cell-states across the 13 models examined. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified upregulation of a number of GBM-associated cancer pathway proteins. Bioinformatics analysis, using the OncoKB database, identified a number of functional actionable targets that were either uniquely or ubiquitously expressed across the panel. This study provides an in-depth proteomic analysis of the GBM Q-Cell resource, which should prove a valuable functional dataset for future biological and preclinical investigations.

14.
Food Chem Toxicol ; 135: 110897, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31654709

RESUMO

The mechanisms of prenatal cadmium (Cd) exposure cause adverse effect transmission to future generations that remain unclear. In this study, pregnant SD rats were orally dosed with Cd (0, 0.5, 2.0, and 8.0 mg/kg/day) from gestation day 1 until birth. F1 female rats were mated with untreated males for F2 generation. In both generations, after prenatal Cd exposure, histopathological examinations showed testicular development disorder. A significant decrease in serum testosterone (T) was observed in the F1 rats, but a significant increase in serum T was observed in the F2 rats. Moreover, both the F1 and F2 rats had different patterns of mRNA and protein expression for testicular steroidogenic factor 1 (SF-1) and steroidogenic enzymes at postnatal days (PNDs) 21 and 56. We also found that rno-miR-328a-5 and rno-miR-10b-5p significantly changed and TargetScan software showed that both of these microRNAs targeted SF-1 and steroidogenic acute regulatory (StAR), respectively. Overall, the results indicate that prenatal Cd exposure causes male reproductive problems in a multigenerational manner. In addition, SF-1 signaling was disrupted and the expressions of microRNAs were affected, which may be an important target for Cd-induced reproductive toxicity in offspring.


Assuntos
Cádmio/toxicidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator Esteroidogênico 1/metabolismo , Testosterona/metabolismo , Animais , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Luteinizante/metabolismo , Masculino , Exposição Materna/efeitos adversos , MicroRNAs/metabolismo , Gravidez , Progesterona/metabolismo , Ratos Sprague-Dawley , Testículo/patologia
15.
Gut ; 69(3): 540-550, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31562239

RESUMO

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose at resectable stage. Recent studies have suggested that extracellular vesicles (EVs) contain long RNAs. The aim of this study was to develop a diagnostic (d-)signature for the detection of PDAC based on EV long RNA (exLR) profiling. DESIGN: We conducted a case-control study with 501 participants, including 284 patients with PDAC, 100 patients with chronic pancreatitis (CP) and 117 healthy subjects. The exLR profile of plasma samples was analysed by exLR sequencing. The d-signature was identified using a support vector machine algorithm and a training cohort (n=188) and was validated using an internal validation cohort (n=135) and an external validation cohort (n=178). RESULTS: We developed a d-signature that comprised eight exLRs, including FGA, KRT19, HIST1H2BK, ITIH2, MARCH2, CLDN1, MAL2 and TIMP1, for PDAC detection. The d-signature showed high accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.960, 0.950 and 0.936 in the training, internal validation and external validation cohort, respectively. The d-signature was able to identify resectable stage I/II cancer with an AUC of 0.949 in the combined three cohorts. In addition, the d-signature showed superior performance to carbohydrate antigen 19-9 in distinguishing PDAC from CP (AUC 0.931 vs 0.873, p=0.028). CONCLUSION: This study is the first to characterise the plasma exLR profile in PDAC and to report an exLR signature for the detection of pancreatic cancer. This signature may improve the prognosis of patients who would have otherwise missed the curative treatment window.

16.
Toxicol Lett ; 319: 175-186, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31733319

RESUMO

Information on the effects of gibberellic acid (gibberellin A3, GA3) on ovarian follicle development is limited. In our present study, 21-day-old female Wistar rats were exposed to GA3 by gavage (25, 50, and 100 mg/kg body weight, once per day) for eight weeks to evaluate the influence of GA3 on ovarian follicle development. After treatment, significant (P < 0.05) increases (to 40.17 % and 44.5 %, respectively) in atretic follicle proportions and significant decreases (to 19.49 % and 17.86 %, respectively) in corpus luteum proportions were observed in the 50 and 100 mg/kg treatment groups compared to the control group. Significant (P < 0.05) increases (to 31.3 % and 42.0 %, respectively) in follicle apoptosis were observed in the 50 and 100 mg/kg treatment groups by transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays. Significantly increased expression of caspase-3, caspase-8, caspase-9 and Fas was observed by real-time PCR and Western blotting. Bisulfite sequencing PCR (BSP) revealed obviously decreased total methylation percentages of the caspase-3 promoter region in the two treatment groups. Real-time quantitative PCR also showed significantly decreased mRNA expression of DNA methyltransferase (Dnmt) 3a and Dnmt3b. Further in vitro studies showed that a DNA methylation inhibitor could enhance the GA3-induced increase in the mRNA expression of caspase-3. Overall, our present study indicates that GA3 administration from weaning until sexual maturity can affect ovarian follicle development by inducing apoptosis and suggests that signaling through the Fas-mediated apoptotic pathway may be an important underlying mechanism of this apoptosis. In addition, GA3-induced aberrant DNA methylation patterns might be partly responsible for upregulation of caspase-3 gene expression.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Proteína de Domínio de Morte Associada a Fas/biossíntese , Giberelinas/toxicidade , Células da Granulosa/efeitos dos fármacos , Ovário/citologia , Transdução de Sinais/efeitos dos fármacos , Animais , DNA (Citosina-5-)-Metiltransferases/biossíntese , DNA (Citosina-5-)-Metiltransferases/genética , Proteína de Domínio de Morte Associada a Fas/efeitos dos fármacos , Feminino , Folículo Ovariano/efeitos dos fármacos , Ovário/efeitos dos fármacos , Regiões Promotoras Genéticas/efeitos dos fármacos , Ratos , Ratos Wistar , Superovulação/efeitos dos fármacos
17.
Hepatology ; 71(1): 259-274, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31173389

RESUMO

Hepatocellular carcinoma (HCC) is a highly lethal cancer and its underlying etiology remains understudied. The immense diversity and complexity of the cancer transcriptome hold the potential to yield tumor-specific transcripts (TSTs). Here, we showed that hundreds of TSTs are frequently expressed in HCC by an assembling spliced junction analysis of RNA sequencing raw data from approximately 1,000 normal and HCC tissues. Many of the TSTs were found to be unannotated and noncoding RNAs. We observed that intergenic TSTs are generated from transcription initiation sites frequently harboring long terminal repeat (LTR) elements. The strong presence of TSTs indicates significantly poor prognoses in HCC. Functional screening revealed a noncoding TST (termed TST1), which acted as a regulator of HCC cell proliferation and tumorigenesis. TST1 is generated from an LTR12C promoter regulated by DNA methylation and retinoic-acid-related drugs. Additionally, we observed that TSTs may be detected in the blood extracellular vesicles of patients with HCC. Conclusion: Our findings suggest an abundance of TSTs in HCC and their potential in clinical settings. The identification and characterization of TSTs may help toward the development of strategies for cancer diagnosis and treatment.

18.
Addict Behav ; 101: 105976, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31101387

RESUMO

PURPOSE: The current study attempts to clarify the mediating role of cognitive function on the relationship between environmental pressure (pressure caused by negative parenting styles and dysfunctional school environments) and Internet Use Disorder (IUD); this study explores the effects of sex and left-behind children (LBC). METHODS: A cross-sectional sample of adolescents aged 12-15 years was recruited in 2018. A total of 3048 junior high school adolescents in rural areas of the Sichuan province in western China completed a series of psychological inventories, including the Adolescent Pathological Internet Use Scale (APIUS), the Junior High School Students' Perceived School Climate Inventory (PSCI-M), the Egna Minnen av. Barndoms Uppfostran (EMBU), and the Mental Health Screening Inventory for Children and Adolescents (MHS-C), for an analysis of IUD, school climate, parenting styles and cognition, respectively. RESULTS: Among the participants, 18.5% (N = 565) exhibited significant symptoms of IUD. The correlation analysis showed that IUD was positively correlated with parents' punishment, rejection and over-interference and academic pressure, whereas IUD was negatively associated with good teacher-student relationships, good schoolmate relationships and cognitive function scores. Structural equation modelling (SEM) showed that cognitive function partially contributed to the association between family and school pressures and IUD. DISCUSSION: Cognitive function is one of the mediating pathways through which environmental pressures may predict IUD among junior high school students. Interventions may target the mediating pathway of cognitive function to alleviate the negative impact of environmental pressure on IUD.

19.
Hepatology ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31815296

RESUMO

Alternative splicing (AS) is a key step that increases the diversity and complexity of the cancer transcriptome. Recent evidence has highlighted that AS has an increasingly crucial role in cancer. Nonetheless, the mechanism underlying AS and its dysregulation in hepatocellular carcinoma (HCC) remain elusive. Here, we report that the expression of RNA-binding protein p54nrb /non-POU domain-containing octamer-binding protein (NONO) is frequently increased in HCC patients and is associated with poor outcomes. Knockdown of NONO significantly abolished liver cancer cell proliferation, migration, and tumor formation. RNA-sequencing revealed that NONO regulates MYC box-dependent interacting protein 1 (or bridging integrator 1) (BIN1) (also known as amphiphysin 2 or SH3P9) exon 12a splicing. In the normal liver, BIN1 generates a short isoform (BIN1-S) that acts as a tumor suppressor by inhibiting the binding of c-Myc to target gene promoters. In HCC, NONO is highly up-regulated and produces a long isoform (BIN1-L, which contains exon 12a) instead of BIN1-S. High levels of BIN1-L promote carcinogenesis by binding with the protein polo-like kinase 1 to enhance its stability through the prevention of ubiquitin/proteasome-dependent cullin 3 degradation. Further analysis revealed that NONO promotes BIN1 exon 12a inclusion through interaction with DExH-box helicase 9 (DHX9) and splicing factor, proline- and glutamine-rich (SFPQ). Notably, frequent coexpression of DHX9-NONO-SFPQ is observed in HCC patients. Taken together, our findings identify the DHX9-NONO-SFPQ complex as a key regulator manipulating the oncogenic splicing switch of BIN1 and as a candidate therapeutic target in liver cancer.

20.
Microb Cell Fact ; 18(1): 218, 2019 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-31884968

RESUMO

Following publication of the original article [1], the authors have noted that the standard curve in Additional file 1: Figure S7 is incorrect.

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