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1.
BMC Cancer ; 20(1): 403, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393195

RESUMO

BACKGROUND: Recent genome-wide association studies (GWASs) have suggested several susceptibility loci of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by statistical analysis at individual single-nucleotide polymorphisms (SNPs). However, these loci only explain a small fraction of HBV-related HCC heritability. In the present study, we aimed to identify additional susceptibility loci of HBV-related HCC using advanced knowledge-based analysis. METHODS: We performed knowledge-based analysis (including gene- and gene-set-based association tests) on variant-level association p-values from two existing GWASs of HBV-related HCC. Five different types of gene-sets were collected for the association analysis. A number of SNPs within the gene prioritized by the knowledge-based association tests were selected to replicate genetic associations in an independent sample of 965 cases and 923 controls. RESULTS: The gene-based association analysis detected four genes significantly or suggestively associated with HBV-related HCC risk: SLC39A8, GOLGA8M, SMIM31, and WHAMMP2. The gene-set-based association analysis prioritized two promising gene sets for HCC, cell cycle G1/S transition and NOTCH1 intracellular domain regulates transcription. Within the gene sets, three promising candidate genes (CDC45, NCOR1 and KAT2A) were further prioritized for HCC. Among genes of liver-specific expression, multiple genes previously implicated in HCC were also highlighted. However, probably due to small sample size, none of the genes prioritized by the knowledge-based association analyses were successfully replicated by variant-level association test in the independent sample. CONCLUSIONS: This comprehensive knowledge-based association mining study suggested several promising genes and gene-sets associated with HBV-related HCC risks, which would facilitate follow-up functional studies on the pathogenic mechanism of HCC.

2.
Nat Plants ; 6(5): 466-472, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32415294

RESUMO

Doubled haploid technology using inducer lines carrying mutations in ZmPLA1/MTL/NLD and ZmDMP1-4 has revolutionized traditional maize breeding. ZmPLA1/MTL/NLD is conserved in monocots and has been used to extend the system from maize to other monocots5-7, but no functional orthologue has been identified in dicots, while ZmDMP-like genes exist in both monocots and dicots4,8,9. Here, we report that loss-of-function mutations in the Arabidopsis thaliana ZmDMP-like genes AtDMP8 and AtDMP9 induce maternal haploids, with an average haploid induction rate of 2.1 ± 1.1%. In addition, to facilitate haploid seed identification in dicots, we established an efficient FAST-Red fluorescent marker-based haploid identification system that enables the identification of haploid seeds with >90% accuracy. These results show that mutations in DMP genes also trigger haploid induction in dicots. The conserved expression patterns and amino acid sequences of ZmDMP-like genes in dicots suggest that DMP mutations could be used to develop in vivo haploid induction systems in dicots.

3.
Eur J Surg Oncol ; 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32371042

RESUMO

OBJECT: To assess the risk factors for and surgical treatment of delayed trapped temporal horn (dTTH) in patients who had undergone removal of lateral ventricular trigone meningioma. METHOD: Patients with lateral ventricular trigone meningioma treated at our institution from 2011 to 2015 were identified. Predictors for dTTH were determined using logistic regression. Literature review and pooled analysis were also conducted to evaluate the comparative effectiveness of surgical treatment for dTTH. RESULTS: A total of 110 cases were included in the analysis. Thirteen (11.8%) cases developed dTTH following surgery. Multivariable logistic regression demonstrated an association of longer operative duration with higher incidence of dTTH (OR, 1.34; 95% CI, 1.00-1.80; p = 0.049). As surgical duration prolonged from less than 3 hours to 5 hours or more, the incidence of dTTH increased in a consistent, linear fashion from 7.7% to 13.9% (p = 0.03). Six cases (46.2%, 6/13) of dTTH underwent surgical treatment for their life-threatening symptoms. Seven studies including 13 cases of dTTH in the literature were identified. Literature data, including the current series, revealed a total of 24 procedures were performed in 19 cases. Endoscopic fenestration trended toward fewer complications than shunt (7.7% vs 25.0%, p = 0.530). There were no significant differences in failure rates between the two groups (23.1% vs 25.0%, p = 1.000). CONCLUSION: Patients with prolonged operative duration may be at higher risk of dTTH. Endoscopic fenestration is considered in preference to shunt placement, since it possesses equivalent success rates with fewer complications and avoids the need for a permanent implant.

6.
Euro Surveill ; 25(15)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32317050

RESUMO

BackgroundIn December 2019, a pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and has rapidly spread around the world since then.AimThis study aims to understand the research gaps related to COVID-19 and propose recommendations for future research.MethodsWe undertook a scoping review of COVID-19, comprehensively searching databases and other sources to identify literature on COVID-19 between 1 December 2019 and 6 February 2020. We analysed the sources, publication date, type and topic of the retrieved articles/studies.ResultsWe included 249 articles in this scoping review. More than half (59.0%) were conducted in China. Guidance/guidelines and consensuses statements (n = 56; 22.5%) were the most common. Most (n = 192; 77.1%) articles were published in peer-reviewed journals, 35 (14.1%) on preprint servers and 22 (8.8%) posted online. Ten genetic studies (4.0%) focused on the origin of SARS-CoV-2 while the topics of molecular studies varied. Nine of 22 epidemiological studies focused on estimating the basic reproduction number of COVID-19 infection (R0). Of all identified guidance/guidelines (n = 35), only ten fulfilled the strict principles of evidence-based practice. The number of articles published per day increased rapidly until the end of January.ConclusionThe number of articles on COVID-19 steadily increased before 6 February 2020. However, they lack diversity and are almost non-existent in some study fields, such as clinical research. The findings suggest that evidence for the development of clinical practice guidelines and public health policies will be improved when more results from clinical research becomes available.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Liver Int ; 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32329946

RESUMO

BACKGROUND: EDP-305 is a novel and potent farnesoid X receptor (FXR) agonist, with no/minimal cross-reactivity to TGR5 or other nuclear receptors. Herein we report therapeutic efficacy of EDP-305, in direct comparison with the first-in-class FXR agonist obeticholic acid (OCA), in mouse models of liver disease. METHODS: EDP-305 (10 and 30 mg/kg/day) or OCA (30mg/kg/day) was tested in mouse models of pre-established biliary fibrosis (BALBc.Mdr2-/-, n = 9-12/group) and steatohepatitis induced by methionine/choline-deficient diet (MCD, n = 7-12/group). Effects on biliary epithelium were evaluated in vivo and in primary EpCAM + hepatic progenitor cell (HPC) cultures. RESULTS: In a BALBc.Mdr2-/- model, EDP-305 reduced serum transaminases by up to 53% and decreased portal pressure, compared to untreated controls. Periportal bridging fibrosis was suppressed by EDP-305 at both doses, with up to a 39% decrease in collagen deposition in high-dose EDP-305. In MCD-fed mice, EDP-305 treatment reduced serum ALT by 62% compared to controls, and profoundly inhibited perisinusoidal 'chicken wire' fibrosis, with over 80% reduction in collagen deposition. In both models, treatment with 30mg/kg OCA reduced serum transaminases up to 30%, but did not improve fibrosis. The limited impact on fibrosis was mediated by cholestasis-independent worsening of ductular reaction by OCA in both disease models; OCA but not EDP-305 at therapeutic doses promoted ductular proliferation in healthy mice and favoured differentiation of primary HPC towards cholangiocyte lineage in vitro. CONCLUSIONS: EDP-305 potently improved pre-established liver injury and hepatic fibrosis in murine biliary and metabolic models of liver disease, supporting the clinical evaluation of EDP-305 in fibrotic liver diseases including cholangiopathies and non-alcoholic steatohepatitis.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32205218

RESUMO

BACKGROUND & AIMS: Non-invasive and accurate methods are needed to identify patients with clinically significant portal hypertension (CSPH). We investigated the ability of deep convolutional neural network (CNN) analysis of computed tomography (CT) or magnetic resonance (MR) to identify patients with CSPH. METHODS: We collected liver and spleen image from patients who underwent contrast-enhanced CT or MR analysis within 14 days of transjugular catheterization for hepatic venous pressure gradient measurement. The CT cohort comprised participants with cirrhosis in the CHESS1701 study, performed at 4 university hospitals in China from August 2016 through September 2017. The MR cohort comprised participants with cirrhosis in the CHESS1802 study, performed at 8 university hospitals in China and 1 in Turkey from December 2018 through April 2019. Patients with CSPH were identified as those with a hepatic venous pressure gradient ≥10 mmHg. In total, we analyzed 10014 liver images and 899 spleen images collected from 679 participants who underwent CT analysis, and 45554 liver and spleen images from 271 participants who underwent MR analysis. For each cohort, participants were shuffled and then randomly and equiprobably sampled for 6 times into training, validation, and test datasets (ratio of 3:1:1). Therefore, a total of 6 deep CNN models for each cohort were developed for identification of CSPH. RESULTS: The CT-based CNN analysis identified patients with CSPH with the area under receiver operating characteristic curve (AUC) value of 0.998 in the training set (95% CI, 0.996-1.000), an AUC of 0.912 in the validation set (95% CI, 0.854-0.971), and an AUC of 0.933 (95% CI, 0.883-0.984) in the test datasets. The MR-based CNN analysis identified patients with CSPH with an AUC of 1.000 in the training set (95% CI, 0.999-1.000), and AUC of 0.924 in the validation set (95% CI, 0.833-1.000), and an AUC of 0.940 in the test dataset (95% CI, 0.880-0.999). When the model development procedures were repeated 6 times, and AUCs for all CNN analyses were 0.888 or greater, with no significant differences between rounds (P>.05). CONCLUSIONS: We developed a deep CNN to analyze CT or MR images of liver and spleen from patients with cirrhosis that identifies patients with CSPH with an AUC value of 0.9. This provides a non-invasive and rapid method for detection of CSPH (ClincialTrials.gov number, NCT03138915; NCT03766880).

13.
Cell Death Dis ; 11(2): 148, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094347

RESUMO

miRNAs reportedly participate in various biological processes, such as skeletal muscle proliferation and differentiation. However, the regulation of differentially expressed (DE) miRNAs and their function in myogenesis remain unclear. Herein, miRNA expression profiles and regulation during C2C12 differentiation were analyzed in relation to chromatin states by RNA-seq, ATAC-seq, and ChIP-seq. We identified 19 known and nine novel differentially expressed miRNAs at days 0, 1, 2, and 4. The expression of the differentially expressed miRNAs was related to the chromatin states of the 113 surrounding open chromatin regions defined by ATAC-seq peaks. Of these open chromatin regions, 44.25% were colocalized with MyoD/MyoG binding sites. The remainder of the above open chromatin regions were enriched with motifs of the myoblast-expressed AP-1 family, Ctcf, and Bach2 transcription factors (TFs). Additionally, the target genes of the above differentially expressed miRNAs were enriched primarily in muscle growth and development pathways, especially the Hippo signaling pathway. Moreover, via combining a loss-of-function assay with Q-PCR, western blotting, and immunofluorescence, we confirmed that the Hippo signaling pathway was responsible for C2C12 myoblast differentiation. Thus, our results showed that these differentially expressed miRNAs were regulated by chromatin states and affected muscle differentiation through the Hippo signaling pathway. Our findings provide new insights into the function of these differentially expressed miRNAs and the regulation of their expression during myoblast differentiation.

14.
Eur J Gastroenterol Hepatol ; 32(3): 386-388, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31490416

RESUMO

OBJECTIVES: A liver stiffness × spleen size/platelet count score (LSPS) model which can rule out high-risk varices and identify high likelihood of clinically significant portal hypertension in patients with compensated cirrhosis has been endorsed by American Association for the Study of Liver Diseases in the 2016 practice guidance on portal hypertension bleeding. This study aims to evaluate the accuracy of LSPS model assessed by ultrasound in well characterized patients with compensated advanced chronic liver disease. METHODS: Eligible patients with compensated advanced chronic liver disease were retrospectively enrolled between January 2017 and March 2018, who had undergone routine clinical and laboratory tests, liver stiffness measurement, ultrasound examination, and computed tomography scanning. Spleen sizes were evaluated by ultrasound and computed tomography reconstructed model, respectively. The correlation and agreement of spleen size and LSPS derived from ultrasound and computed tomography imaging modality were compared. RESULTS: A total of 158 patients were included and analyzed. Spleen size showed a moderate correlation (R = 0.649, P < 0.001) according to ultrasound and computed tomography imaging. Also, the correlation between the two LSPS models based on ultrasound and computed tomography was excellent (R = 0.985, P < 0.001). The Bland-Altman plots demonstrated a superior agreement of LSPS model values evaluated by ultrasound and computed tomography, respectively. CONCLUSION: This study demonstrated the accuracy of LSPS model based on ultrasound in a well characterized cohort of fully compensated patients with advanced chronic liver disease.

16.
Reprod Biol ; 19(4): 404-411, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31806577

RESUMO

In vitro fertilization (IVF) for ovine embryos is strongly associated with low pregnancy rates and negative effects on embryonic and postnatal development, but the mechanisms remain unclear. We aimed to identify genes essential for successful implantation of IVF embryos in sheep by species-specific microarray analysis. Differential gene expression analysis between caruncles and intercaruncle sites of the ovine uterus with in vivo (IVV) -produced embryos on day 10 of pregnancy found 43 differentially expressed genes (DEGs) with at least a 2-fold change, such as coiled-coil domain-containing 152 (CCDC152) and pregnancy-associated plasma protein A (PAPPA). Gene ontology analysis revealed these DEGs were related to cell proliferation, the immune system process, localization and response to stimulus. Moreover, we identified 93 DEGs in endometrial caruncles with IVV- versus in vitro (IVT)-produced embryos on days 12, 14 and 16 of pregnancy, including prostaglandin-endoperoxide synthase 2 (PTGS2) and cubilin (CUBN). GO analysis revealed that these DEGs were related to cell adhesion, cell proliferation, embryo implantation, embryonic morphogenesis, the immune system process and localization. Two DEGs (PAPPA and RSAD2) in caruncle versus intercaruncle sites at day 10 were also differentially expressed between the IVV and IVT groups at the three implantation stages. Self-organizing feature map cluster analysis of transcript profiles during embryo implantation revealed different gene expression patterns between the IVV and IVT groups. In conclusion, this study identified many genes that may be associated with mechanisms underlying IVF-induced ovine embryo implantation failure during the peri-implantation period, and such genes provide potential candidates for further study.

17.
Ann Transl Med ; 7(20): 586, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807567

RESUMO

Background: Acute variceal bleeding is one of the critical complications in patients with liver cirrhosis. Severe renal vasoconstriction in consequence of low peripheral vascular resistance triggers the reduction of glomerular filtration rate (GFR), and thus induces acute kidney injury (AKI)/hepato-renal syndrome (HRS). Terlipressin and octreotide have been used in the management of cirrhotic patients with variceal bleeding. Also, terlipressin has been recommended as the international first-line pharmacological therapy for the treatment of HRS. In addition, the use of renal functional magnetic resonance imaging (fMRI) has become increasingly prevalent in research and clinical applications. However, the renal function-protective effect of terlipressin and octreotide and the value of fMRI in monitoring renal function remains unclear in patients with cirrhosis undergoing acute variceal bleeding. Methods: This is a multicenter, randomized controlled trial (RCT). Participants will be 1:1 assigned randomly into either terlipressin or octreotide groups. Sixty participants with clinically and/or pathologically diagnosed cirrhosis and active gastroesophageal variceal bleeding (GVB) will be recruited in several sites in China. Participants will receive either the treatment of terlipressin or octreotide after assigned into each group. The primary end point for the trial is the renal function. The secondary end points are (I) renal perfusion; (II) renal blood oxygenation; (III) failure to control bleeding; (IV) intra-hospital rebleeding; (V) intra-hospital mortality; (VI) adverse events (AE); (VII) overall survival. Statistical analysis including multivariate Cox regression, Kaplan-Meier analysis with log-rank test, etc. will be conducted. Discussion: The study will provide new insight into the protection of renal function in the process of the treatment of variceal bleeding in patients with cirrhosis. Trial registration number: NCT04028323.

18.
Gastroenterol Res Pract ; 2019: 6704673, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781196

RESUMO

Background and Aims: Liver fibrosis blood tests, platelet count/spleen diameter ratio (PSR), and contrast-enhanced CT are diagnostic alternatives for gastroesophageal varices, but they have heterogeneous diagnostic performance among different study populations. Our study is aimed at evaluating their diagnostic accuracy for esophageal varices (EVs) and gastric varices (GVs) in cirrhotic patients with and without previous endoscopic variceal therapy. Methods: Patients with liver cirrhosis who underwent blood tests and contrast-enhanced CT scans as well as endoscopic surveillance should be potentially eligible. EVs needing treatment (EVNTs) and GVs needing treatment (GVNTs) were recorded according to the endoscopic results. Area under the curves (AUCs) were calculated. Results: Overall, 279 patients were included. In 175 patients without previous endoscopic variceal therapy, including primary prophylaxis population (n = 70), acute bleeding population (n = 38), and previous bleeding population (n = 67), the diagnostic accuracy of contrast-enhanced CT for EVNTs was higher (AUCs = 0.816-0.876) as compared to blood tests and PSR; by comparison, the diagnostic accuracy of contrast-enhanced CT for GVNTs was statistically significant among primary prophylaxis population (AUC = 0.731, P = 0.0316), but not acute or previous bleeding population. In 104 patients with previous endoscopic variceal therapy (i.e., secondary prophylaxis population), contrast-enhanced CT was the only statistically significant alternative for diagnosing EVNTs and GVNTs but with modest accuracy (AUCs = 0.673 and 0.661, respectively). Conclusions: Contrast-enhanced CT might be a diagnostic alternative for EVNTs in cirrhotic patients, but its diagnostic performance was slightly weakened in secondary prophylaxis population. Additionally, contrast-enhanced CT may be considered for diagnosis of GVNTs in primary prophylaxis population without previous endoscopic variceal therapy and secondary prophylaxis population.

20.
Biochem Biophys Res Commun ; 520(3): 586-593, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31623830

RESUMO

Accepted as crucial participators in human malignancies, long noncoding RNAs (lncRNAs) have been proven to exert significant function on the complicated processes of cancer progression. Although existing investigations have revealed the oncogenic role of lncRNA SOX2 overlapping transcript (SOX2-OT) in different kinds of cancers, such as osteosarcoma and cholangiocarcinoma, the potential role of it in prostate cancer (PC) is poorly understood. This study was the first attempt to decipher the underlying regulatory mechanism of SOX2-OT in PC. According to the data from this study, SOX2-OT expression was conspicuously elevated in PC tissues and cells. Silenced SOX2-OT could repress PC cell proliferation and migration. Besides, mechanism assays manifested that SOX2-OT bound with miR-369-3p and negatively correlated with miR-369-3p in PC. Additionally, miR-369-3p was confirmed to elicit suppressive impact on PC progression. What's more, cofilin 2 (CFL2) was testified to be a downstream target gene of miR-369-3p. Final rescue tests uncovered that CFL2 upregulation or miR-369-3p inhibition could largely restore SOX2-OT knockdown-mediated function on PC progression. To sum up, SOX2-OT accelerates cell proliferation and migration by targeting miR-369-3p/CFL2 axis in PC.

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