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1.
Am J Surg Pathol ; 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32149737

RESUMO

The aim of this study was to investigate predictors of lymph node metastasis (LNM) in early gastric signet-ring cell carcinoma (SRCC) and determine clinicopathologic and prognostic differences of different histologic subtypes. We retrospectively analyzed 13,661 gastric cancer patients; 231 were eligible for inclusion. Data for clinical, endoscopic, and histopathologic characteristics and prognoses were collected. Patients were followed up regarding postresection survival; overall and disease-specific survival rates were estimated by the Kaplan-Meier method with a log-rank test, and prognostic factors were evaluated by Cox regression. LNM incidence in early SRCC was 16.0% (37/231) overall: 6.9% (8/116) and 25.2% (29/115) in patients with pure and mixed SRCC, respectively. Univariate and multivariate analyses revealed SM2 invasion (odds ratio [OR]=5.070, P=0.003), lymphovascular invasion (LVI) (OR=14.876, P<0.001), pathologic pattern of mixed SRCC (OR=3.226, P=0.026), ulcer presence (OR=3.340, P=0.019) and lesion size over 20 mm (OR=2.823, P=0.015) as independent risk factors for LNM. Compared with pure SRCC, the mixed subtype was associated with older age, larger lesion size, higher LVI frequency, more frequent perineural invasion, and most importantly, higher LNM incidence. Patients with pure SRCC showed significantly longer overall survival (P=0.004) and disease-specific survival (P=0.002) than mixed SRCC patients. Pathologic subtype (hazard ratio [HR]=3.682; P=0.047), age (HR=5.246; P=0.001), SM1 invasion (HR=6.192; P=0.023), SM2 invasion (HR=7.529; P=0.021) and LNM (HR=5.352; P<0.001) were independent prognostic factors. Independent risk factors for LNM in early gastric SRCC were SM2 invasion, LVI, pathologic pattern, ulcer presence and lesion size over 20 mm. Early SRCC should be further classified by the purity of the SRC component.

2.
Cancer Biomark ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32116236

RESUMO

BACKGROUND: Gastric cancer is one of the leading causes of death worldwide. MicroRNA-30a (miR-30a) has been demonstrated to be involved in several types of cancer development. OBJECTIVE: We aimed to identify he molecular mechanism of miR-30a in gastric cancer. METHODS: We investigated the expression of miR-30a in gastric cancer tissues by qRT-PCR. The role of miR-30a on the metastasis and proliferation of gastric cancer was evaluated by cell migration assay, CCK-8 assay and tumor peritoneal dissemination model. The target of miR-30a in gastric cancer was identified. RESULTS: We discovered that miR-30a was significantly downregulated in gastric cancer tissues compared with adjacent nonmalignant tissues. The expression of miR-30a was inversely correlated with progression of gastric cancer. Gain- and loss-of function revealed that miR-30a acted as a potent tumor suppressor in gastric cancer. Re-expressed miR-30a inhibited gastric cancer cells migration, knock down miR-30a have the opposite effects. Furthermore, overexpression of miR-30a suppressed tumor peritoneal dissemination in vivo. We identified that fibroblast activation protein α (FAPα) was a direct target of miR-30a. The relative expression of FAPα was significantly higher in gastric cancer tissues compared with adjacent nonmalignant tissues. Inhibition of FAPα could recapitulate the effects of miR-30a, and overexpression of FAPα could abrogate the effect of miR-30a. CONCLUSION: MiR-30a inhibited gastric cancer metastasis by targeting FAPα, suggesting that miR-30a may function as a novel tumor suppressor in gastric cancer.

3.
Vaccine ; 38(14): 2978-2983, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32113807

RESUMO

Botulinum neurotoxins (BoNTs) are highly toxic proteins that mediate their effects by binding to neuronal receptors and block the neutralizing ability of therapeutic antibodies. Vaccination is currently the most effective strategy to prevent botulism. In this study, a series of recombinant functional domain antigens of BoNT/A were prepared and identified, and their immunoprotective efficacies were explored and compared. Our results showed that all antigens produced strong humoral immune responses, although their protective effects against the toxin were different. Only the Hc and HN-L antigens produced strong protective effects and afforded complete immunoprotection. In addition, the combined vaccine groups showed that there was no synergistic effect on immune responses after antigen combination, suggesting that the integrity of the toxin antigen or domain is crucial to the immune effects. Studies of the dose-dependent immunoprotective effects further confirmed that the Hc domain antigen afforded more effective protective potency than the HN-L antigen, equivalent to the immune effect of the full-length toxin (Hc + HN-L combination group). Overall, our results demonstrated that the Hc domain elicited a strong protective immune response and also provided basic data and theoretical support for the development of Hc-based BoNT/A subunit vaccine. Therefore, the receptor binding domain Hc is implicated as a promising target antigen of the BoNT/A recombinant subunit vaccine as an alternative to the toxoid vaccine.

4.
Cancer Cell ; 37(3): 403-419.e6, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32183952

RESUMO

Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To identify molecular subtypes of NKTCL based on genomic structural alterations and EBV sequences, we performed multi-omics study on 128 biopsy samples of newly diagnosed NKTCL and defined three prominent subtypes, which differ significantly in cell of origin, EBV gene expression, transcriptional signatures, and responses to asparaginase-based regimens and targeted therapy. Our findings thus identify molecular networks of EBV-associated pathogenesis and suggest potential clinical strategies on NKTCL.

5.
BMC Surg ; 20(1): 50, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183778

RESUMO

BACKGROUND: Many options exist for the management of cholelithiasis and secondary choledocholithiasis. Among them, laparoscopic common bile duct exploration (LCBDE) with choledocotomy followed by laparoscopic cholecystectomy has gained popularity. However, efforts should be made to ensure minimally invasive or noninvasive management of the common bile duct (CBD). The purpose of this study was to explore the clinical experience of non-invasive surgical modality, i.e., laparoscopic transcystic dilation of the cystic duct confluence in CBD exploration (LTD-CBDE), including feasibility, safety, adverse events, and incidence. METHODS: In this retrospective analysis, 68 patients were offered the LTD-CBDE technique from December 2015 to April 2018 based on patient's own intention. During the surgery, the cystic duct confluence was dilated with separation forceps and/or a columnar dilation balloon. Subsequently, CBD exploration and stone extraction were performed with a choledochoscope. The entrance of the CBD was covered with a cystic duct stump wall and was subjected to primary closure at the end of surgery. RESULTS: Forty-nine females and 19 males with cholelithiasis and secondary choledocholithiasis were included. The mean age was 53 years old (18 to 72 year). Of these patients, 62 (91.2%) were successfully treated with the LTD-CBDE technique, and bile leakage was observed in 3 patients (4.4%). The mean operation time was 106 min, and the mean hospital stay was 5.9 days. Among the other 6 patients, 3 were converted to open cholecystectomy due to severe fibrosis, unclear anatomical structure at Calot's triangle (n = 2) or Mirizze syndrome (n = 1); LCBDE was performed in 3 patients due to cystic duct atresia (n = 2) and low level of flow from the gallbladder duct into the CBD (n = 1). These patients had a smooth postoperative course. In total, 43/68 of the patients presented no radiological evidence of retained CBD stones at the postoperative follow-up (40 patients treated with LTD-CBDE) 1 year later. CONCLUSIONS: The current work suggests that LTD-CBDE for the management of cholelithiasis and secondary choledocholithiasis is a feasible, safe and effective technique with a low complication rate. LTD-CBDE offers another alternative for surgeons to treat patients in similar scenarios. However, additional randomized, controlled studies are needed to demonstrate its efficacy, safety, and impact on CBD stenosis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32207017

RESUMO

N-doped biochar as adsorption material for heavy metal removal has attracted increasing concern in environmental application due to its unique features. Here, N-doped biochar was prepared by hydrothermal carbonization of Camellia sinensis branch waste using KOH/NH4Cl at 120-280 °C for 2 h under 0.4-6.5 MPa, followed by structural analysis. The results showed that the highest N content determined by elemental analysis could reach up to 6.18% in biochar, and the major N species were involved in graphitic N, pyrrolic N, and pyridinic N. Interestingly, these N-doped biochar exhibited the effective adsorption ability of Cu2+, Pb2+, Zn2+, and Cr6+. The batch adsorption behavior had a better adjustment to the pseudo-second-order kinetic and the Langmuir adsorption isotherm models. In brief, the present results are attributed to develop low-cost adsorbent for removing heavy metal ions.

7.
J Mol Neurosci ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125624

RESUMO

Whether blood amyloid-ß (Aß) could be a peripheral biomarker of Alzheimer's disease (AD) remains in dispute. In the present study, we conducted a meta-analysis with 19 citations searched from Embase, PubMed, and the Cochrane Library database. Weighted mean difference (WMD) with 95% confidence intervals (CIs) was used to estimate the effect size. We firstly analyzed the plasma Aß40, Aß42, and Aß42/Aß40 ratio in AD and control group subjects. However, only a lower level of plasma Aß42 was figured out in AD group subjects with weak statistical significance (WMD 1.82; 95% CI 0.59, 3.06; P = 0.004; I2 = 84%). We considered that the medical histories of control subjects could influence the biomarker ability of plasma Aß. Therefore, subgroup analyses were then carried out based on a new recruiting criterion for control subjects, defining as no afflictions of any Aß-related diseases. Surprisingly, AD group subjects showed a significant decrease in plasma Aß42/Aß40 ratio with low heterogeneity among studies (WMD 0.02; 95% CI 0.02, 0.02; P < 0.00001; I2 = 0%). Moreover, not only the Aß42/Aß40 ratio but also Aß42 and Aß40 were indifferent between AD and pseudo-control subjects which might be afflicted with Aß-related diseases. This meta-analysis demonstrated that medical histories of control subjects were interference factors impeding plasma Aß to be a biomarker of AD.

8.
J Ethnopharmacol ; 253: 112679, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32101773

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gardenia Fructus (GF), a traditional Chinese medicine for clearing heat and purging fire, has been reported to use to treat thrombotic related diseases, but the antithrombotic components are not clear. AIM OF THE STUDY: To develop efficient research methods for discovering some representative antithrombotic compounds of GF. MATERIALS AND METHODS: AB line zebrafish induced by arachidonic acid (AA) was used as a fast and trace-sample-required valuation model for antithrombptic effect of GF samples. Among nine samples of GF from different production areas, two samples with the largest difference in bioactivity were selected for downstream analysis. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF/MS) was applied to detect compounds in the GF samples. And herbal metabolomics and grey correlation analysis (GCA) were used to identify crucial compounds with potential antithrombotic activity. Then the bioactivity of those important compounds was verified on the zebrafish model. Network pharmacology was used to explore the protein targets and signaling pathways of these compounds. RESULTS: Among the GF samples, S1 (Huoshan City, Anhui Province), and S6 (Jichun City, Hubei Province), significantly differed in thrombus inhibiting bioactivity. HPLC-Q-TOF/MS identified a total of 614 compounds in each GF sample. 19 compounds were selected as important potential variables from metabolomics data by orthogonal partial least squares discriminant analysis (OPLS-DA). And 10 compounds among them were further found to be positively correlated with the antithrombotic bioactivity of GF by GCA. Finally, 3 compounds in them, geniposide, citric acid, and quinic acid, were confirmed as representative antithrombotic chemical markers of GF. Using network pharmacology analysis, some key protein targets, such as proto-oncogene tyrosine-protein kinase Src (SRC) and cyclin-dependent kinase 2 (CDK2), and some signaling pathways were found to supply powerful evidence about antithrombotic mechanisms of three compounds and GF. CONCLUSIONS: This research have succeeded to discover and identify three representative antithrombotic compounds of GF using an efficient integrated research strategy we established, an Omics Discriminant-Grey Correlation-Biological Activity strategy. The antithrombotic chemical makers we found could also contribute to provided more accurate index components for comprehensive quality control of GF.

9.
J Affect Disord ; 267: 123-130, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32063563

RESUMO

OBJECTIVES: This is a meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of adjunctive folate for three major mental disorders (schizophrenia, bipolar disorder, and major depressive disorder (MDD)). METHODS: Review Manager Program Version 5.3 was used to analyze data. RESULTS: Fourteen studies with 16 RCTs (n = 1,520) on folate for schizophrenia (4 RCTs, n = 210), mood disorders (i.e., unipolar and bipolar depression) (1 RCT, n = 60), bipolar disorder (2 RCTs, n = 189) and MDD (9 RCTs, n = 1,061) were analyzed separately by diagnosis. For schizophrenia, adjunctive folate was not superior to placebo in terms of total psychopathology (standardized mean difference (SMD) = -0.14, 95% confidential interval (CI): -0.67, 0.39; I2 = 30%, P = 0.60), and positive (SMD = 0.09, 95% CI: -0.44, 0.62; I2 = not applicable, P = 0.74), negative (SMD = -0.39, 95% CI:-0.84, 0.05; I2 = 50%, P = 0.08), and general symptom scores (SMD = -0.33, 95%CI:-0.87, 0.20; I2 = not applicable, P = 0.22). For bipolar and unipolar depression, adjunctive folate was significantly superior to placebo in improving depressive symptoms. For bipolar disorder, adjunctive folate was effective in treating the acute phase of mania in bipolar disorder, but not in the acute phase of depression. For MDD, adjunctive folate was significantly superior to placebo in improving depressive symptoms (SMD = -0.38, 95%CI: -0.66, -0.09; I2 = 71%, P = 0.01), which was confirmed in 5 of the 10 subgroups. Discontinuation due to any reason and adverse drug reactions were similar between folate and placebo in each diagnostic category. CONCLUSION: This systematic review found adjunctive folate appeared to be effective and safe for MDD and bipolar manic episode, but it was not effective in treating schizophrenia.

10.
J Transl Med ; 18(1): 40, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000807

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms. METHODS: GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein-protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan-Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. RESULTS: In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes. CONCLUSION: CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC.

11.
Int J Infect Dis ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32109625

RESUMO

OBJECTIVES: To characterize the pharmacokinetics (PK) of intravenous voriconazole (VRC) in critically ill patients with liver dysfunction. METHODS: Patients with liver dysfunction in the intensive care unit (ICU) were prospectively included. The Child-Pugh (C-P) score was used to categorize the degree of liver dysfunction. The initial intravenous VRC dosing regimen comprised of a loading dose of 300 mg q12 h for the first 24 h followed by 200 mg q12 h. The first PK curves (PK curve 1) were drawn within one dosing interval of the first dose from 17 patients, and the second PK curves (PK curve 2) were drawn within one dosing interval after a minimum of seven doses from 12 patients. PK parameters were estimated by noncompartmental analysis. RESULTS: There were good correlations between area under the curve (AUC0-12) of PK curve 2 and the corresponding trough concentration (C0) and peak concentration (Cmax) ( r2 = 0.951 and 0.963, respectively; both P < 0.001). The median half-life (t1/2) and clearance (CL) of patients in C-P classes A (n = 3), B (n = 5), and C (n = 4) of PK curve 2 were 24.4 h and 3.31 l/h, 29.1 h and 2.54 l/h, and 60.7 h and 2.04 l/h, respectively. The CL (median) of PK curve 2 were all lower than those of PK curve 1 in different C-P classes. Apparent steady-state volume of distribution (Vss) of PK curve 1 was positively correlated with actual body weight ( r2 = 0.450, P = 0.004). The first C0 of 17 patients determined on day 5 (median) was 5.27 ± 2.61 µg/ml, and 29.4% of C0 exceeded the upper limit of the therapeutic window (2-6 µg/ml). CONCLUSIONS: The CL of VRC was decreased with the increased severity of liver dysfunction according to C-P classification, along with the increased t1/2, which resulted in high plasma exposure of VRC. Adjusted dosing regimens of intravenous VRC should be established based on C-P classes for these ICU patients and plasma concentrations should be closely monitored to avoid serious adverse events. This clinical study is registered on Chinese Clinical Trial Registry (http://www.chictr.org.cn; Registration number: ChiCTR1800019472).

12.
Biosci Rep ; 40(2)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32003781

RESUMO

OBJECTIVE: To study the effect of puerarin on electrophysiology using a hypertrophic cardiomyocyte (HC) model. MATERIALS AND METHODS: Human urine epithelial cells were used to generate the HC model (hiPSC-CM). Cardiomyocyte hypertrophy was induced by applying 10 nM endothelin-1 (ET-1). Effects of puerarin pre-treatment (PPr) and post-treatment (PPo) on action potential, sodium current (INa) activation and inactivation, and recovery following INa inactivation were tested using patch clamp electrophysiology. RESULTS: Depolarization to repolarization 50% time (APD50) and repolarization 30% time (APD30) were significantly prolonged in the PPo and PPr groups compared with the controls. However, there were no significant differences in the action potential depolarization amplitude (APA) or the maximum depolarization velocity (Vmax) in phase 0. The PPr group had a slightly shortened APD90, and an extended APD50 and APD30, but did not exhibit any significant changes in stage A of APA and Vmax. The PPo group did not exhibit any significant changes in INa, while 12 h of PPr improved INa. However, puerarin did not significantly affect the activation, inactivation, or recovery of the sodium channel. CONCLUSIONS: Cardiomyocyte hypertrophy significantly decreased the Vmax of the action potential and the peak density of INa. PPr inhibited the decrease in Vmax and increased the peak density of INa. Thus, puerarin could be used to stabilize the electrophysiological properties of hypertrophic cardiomyocytes and reduce arrhythmias.

13.
J Clin Neurosci ; 72: 63-67, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31956088

RESUMO

BACKGROUND: Knowledge of prognostic factors related to the survival of Motor Neuron Diseases (MND) remains scarce in Southeast Asia. PURPOSE: To determine potential prognostic factors for survival, need for feeding and ventilation support in MND patients in a multi-racial Asian population. METHODS: One hundred and four MND patients from the Singapore General Hospital (SGH) between January 2004 and December 2017 were reviewed. All relevant clinical data, demographic information were collected. Kaplan-Meier and Cox regression model were performed to identify potential prognostic factors for crucial outcomes (survival, need for feeding support and ventilation support). RESULTS: Mean age of onset was 59.54 ± 10.91 years, Mean age of onset in Malays was significantly younger than that of other ethnic groups (Malay: 54.18 ± 12.95 years; Non-Malay: 60.39 ± 10.38 years, p = 0.035). Fifty six of the male and 33of the female were diagnosed with ALS (90.3% vs. 78.6% p = 0.048). Mean overall survival duration from symptom onset was significantly longer in female than male patients (female: 39.2 ± 29.04 months; male: 29.4 ± 24.06 months, P = 0.03). In the multivariable Cox regression model, bulbar onset (aHR = 5.28, p = 0.035) correlated with poor survival outcome while longer duration from onset to second symptom (aHR = 0.96, P = 0.037) indicated better survival. CONCLUSIONS: Bulbar onset was a significant risk predictor for survival. Slower disease progression correlated with better outcomes. Age of onset may differ among ethnic groups. Male patients are more likely to develop Amyotrophic Lateral Sclerosis (ALS) and have shorter survival duration.

14.
Phys Med ; 69: 184-191, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31918371

RESUMO

PURPOSE: We introduced and evaluated an end-to-end organs-at-risk (OARs) segmentation model that can provide accurate and consistent OARs segmentation results in much less time. METHODS: We collected 105 patients' Computed Tomography (CT) scans that diagnosed locally advanced cervical cancer and treated with radiotherapy in one hospital. Seven organs, including the bladder, bone marrow, left femoral head, right femoral head, rectum, small intestine and spinal cord were defined as OARs. The annotated contours of the OARs previously delineated manually by the patient's radiotherapy oncologist and confirmed by the professional committee consisted of eight experienced oncologists before the radiotherapy were used as the ground truth masks. A multi-class segmentation model based on U-Net was designed to fulfil the OARs segmentation task. The Dice Similarity Coefficient (DSC) and 95th Hausdorff Distance (HD) are used as quantitative evaluation metrics to evaluate the proposed method. RESULTS: The mean DSC values of the proposed method are 0.924, 0.854, 0.906, 0.900, 0.791, 0.833 and 0.827 for the bladder, bone marrow, femoral head left, femoral head right, rectum, small intestine, and spinal cord, respectively. The mean HD values are 5.098, 1.993, 1.390, 1.435, 5.949, 5.281 and 3.269 for the above OARs respectively. CONCLUSIONS: Our proposed method can help reduce the inter-observer and intra-observer variability of manual OARs delineation and lessen oncologists' efforts. The experimental results demonstrate that our model outperforms the benchmark U-Net model and the oncologists' evaluations show that the segmentation results are highly acceptable to be used in radiation therapy planning.

15.
Genomics ; 112(3): 2318-2326, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31923617

RESUMO

The tea leaf is economically important, while reproductive growth reduce tea output. However, little is known about flowering mechanisms in tea plants. Here, we determined the approximate times of floral induction, floral transition and floral organ differentiation by morphological observation. We identified 401 and 356 flowering-related genes from the genomes of Camellia sinensis var. sinensis and Camellia sinensis var. assamica, respectively. Then, we compared the expression profiles of flowering-related genes in floriferous and oliganthous cultivars, the result showed that PRR7, GI, GID1B and GID1C expression is correlated with the floral induction; LFY, PNF and PNY expression was correlated with floral bud formation. Transcriptome analysis also showed that GI, PRR7 and GID1 were correlated with stress-induced flowering. Thus, we proposed putative mechanisms of flowering in tea plants. This study provides new insights into flowering and a theoretical basis for balancing vegetative and reproductive growth in tea plants and other economical plants.

16.
Mol Ther ; 28(3): 914-928, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-31951832

RESUMO

Increasing studies indicated that circular RNAs (circRNAs) play important roles in cancer progression. However, the roles of circRNAs in colorectal cancer (CRC) remain largely unknown. In this study, we determined the circRNA expression profile by next-generation RNA sequencing from eight CRC and paired non-cancerous matched tissues. circCAMSAP1 (originating from exon 2 to exon 3 of the CAMSAP1 gene, hsa_circ_0001900) was significantly upregulated in CRC tissues. Increased circCAMSAP1 expression was significantly correlated with advanced tumor/node/metastasis (TNM) stage and shortened overall survival. An elevation of circCAMSAP1 expression was detected via droplet digital PCR in the serum of CRC patients prior to surgery. Functionally, circCAMSAP1 promoted the malignant behavior of CRC. Mechanism study of upstream biogenesis of circCAMSAP1 indicated that circCAMSAP1 cyclization in CRC was mediated by splicing factor epithelial-splicing regulatory protein 1. Moreover, circCAMSAP1 acted as a sponge for miR-328-5p and abrogated its suppression on transcription factor E2F1. Taken together, our data indicated an essential role of the circCAMSAP1/miR-328-5p/E2F1 axis in the progression of CRC, which implied that circCAMSAP1 could serve as a diagnostic and prognostic biomarker as well as a potential therapeutic target for CRC.

17.
Nat Prod Res ; : 1-6, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31928368

RESUMO

One new flavanonol 4 H-​1-​benzopyran-​4-​one,2-​(4-​hydroxyphenyl)​-​3,​7-​dihydroxy-​5-​methoxy-​8-​[5-​methyl-​2-​(1-​methylethenyl)​-​4-​hexenyl]​(21), and twenty-six known compounds 1-20, 22-27 were isolated from the dried root of Sophora flavescens (S. flavescens) in this chemical study. Their structures were elucidated according to the spectroscopic and spectrometric methods. All the isolated compounds were evaluated for their cytotoxicity against lung cancer A549 cells and colon cancer HCT116 cells. Among them, compound 21 showed relatively predominant cell proliferation inhibition effect on the two tumor cell lines. Moreover, it induced cells apoptosis as evidenced by the Annexin V/PI double staining assay as well as the increased cleaved-PARP expression. The aforementioned data indicated that the flavonoids of S. flavescens have potential anti-cancer effect.

18.
Zygote ; : 1-10, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31933449

RESUMO

Studies have indicated that psychological stress impairs human fertility and that various stressors can induce apoptosis of testicular cells. However, the mechanisms by which psychological stress on males reduces semen quality and stressors induce apoptosis in testicular cells are largely unclear. Using a psychological (restraint) stress mouse model, we tested whether male psychological stress triggers apoptosis of spermatozoa and spermatogenic cells through activating tumour necrosis factor (TNF)-α signalling. Wild-type or TNF-α-/- male mice were restrained for 48 h before examination for apoptosis and expression of TNF-α and TNF receptor 1 (TNFR1) in spermatozoa, epididymis, seminiferous tubules and spermatogenic cells. The results showed that male restraint significantly decreased fertilization rate and mitochondrial membrane potential, while increasing levels of malondialdehyde, active caspase-3, TNF-α and TNFR1 in spermatozoa. Male restraint also increased apoptosis and expression of TNF-α and TNFR1 in caudae epididymides, seminiferous tubules and spermatogenic cells. Sperm quality was also significantly impaired when spermatozoa were recovered 35 days after male restraint. The restraint-induced damage to spermatozoa, epididymis and seminiferous tubules was significantly ameliorated in TNF-α-/- mice. Furthermore, incubation with soluble TNF-α significantly reduced sperm motility and fertilizing potential. Taken together, the results demonstrated that male psychological stress induces apoptosis in spermatozoa and spermatogenic cells through activating the TNF-α system and that the stress-induced apoptosis in spermatogenic cells can be translated into impaired quality in future spermatozoa.

19.
Spine (Phila Pa 1976) ; 45(4): 275-283, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31999653

RESUMO

STUDY DESIGN: A bibliometric analysis. OBJECTIVE: To identify and analyze the 100 top-cited articles on spinal deformity. SUMMARY OF BACKGROUND DATA: The nature of spinal deformity leads to the complexity of its treatment. There is a scarcity of guidelines for the treatment of spinal deformity despite of the growing literature. So it is crucial to discern researches with higher impact and quality. METHODS: A keyword search using the Thomson Reuters Web of Science was conducted to select articles relevant to spinal deformity. The 100 top-cited articles were identified based on titles and abstracts, and then analyzed. RESULTS: The citation count for the final 100 articles ranged from 154 to 775, with an average of 243.0 citations. Most studies were published in the journal Spine (49/100). The most productive publication time was from 2000 to 2009. The natural history of scoliosis was the most frequent topic (10 articles), followed by pedicle screw instrumentation (8), outcome of nonoperative treatment for adolescent idiopathic scoliosis (AIS) (8), health-related quality of life (7), relationship between sagittal parameters and clinical symptoms (7), and complications of surgical treatment (7). Despite AIS was the most common deformity, the top two most frequently cited articles were all about adult spinal deformity, both describing the correlation between sagittal parameters and symptoms. CONCLUSION: The current study attempted to develop a resource with detailed information on 100 top-cited articles on spinal deformity. It demonstrated the essential advances in spinal deformity. Although the most common spinal deformity is AIS, the adult spinal deformity is of greater impact. These insights into priorities and trends of the researches could help future academic pursuits. LEVEL OF EVIDENCE: 5.

20.
J Immunol Methods ; 477: 112701, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31705859

RESUMO

INTRODUCTION: ndirect immunofluorescence assay (IFA) using HEp-2 as substrate plays a consolidate role for the detection and measurement of ANA, which is currently considered as the reference method for detection. Manual operation is still very common in China, therefore, the need of standardization and automation for ANA-IFA detecting has been highlighted. OBJECTIVE: The current multi-center study is aimed to evaluate if HELIOS (AESKU Diagnostics, Wendelsheim, Germany) contributes to comparability of ANA screening results among different labs,and establish application specification of HELIOS for standardization of ANA detection. METHODS: ANA detection by manual IFA method and HELIOS on 230 clinical serum samples in eight laboratories. The performance to discriminate positive/negative screening results, endpoint titer estimation and pattern recognition were evaluated in HELIOS and manual visual. RESULTS: The positive coincident rate for ANA detection by manual IFA ranges from 87.7% to 97.8%, the negative coincidence rate ranges from 68.8% to 100%, the correctly estimated titer evaluation were 80 to 171 cases, the correct pattern in 146 to 161 cases, respectively. The positive coincident rate of HELIOS for ANA detection ranges from 91.2% to 97.7%, the negative coincidence rate ranges from 96.5% to 100%, the correctly estimated titer evaluation were 145 to 157 cases, the correct pattern in 123 to 140 cases, respectively. CONCLUSION: HELIOS could provide accurate diagnostic results, this include not only positive/negative results, but also endpoint titer, common patterns. The application of this system can help to promote standardization of ANA detection.

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