Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 249
Filtrar
1.
Endocrine ; 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488838

RESUMO

PURPOSE: The increasing burden of noncommunicable diseases (NCDs) attributable to high body mass index (BMI) represents both a threat and an opportunity for intervention. Estimates of the global latest trend of high BMI-related NCDs and its association with socioeconomic status can facilitate strategic intervention and inform further research. METHODS: This global burden of disease study extracted global, regional, and national data on death and disability-adjusted life years (DALYs) attributable to high BMI-related NCDs from the GBD Study 2017. Secondary analyses were performed by year, age, sex, and specific causes of death and DALYs. The 2017 Socio-demographic Index (SDI) was used as an indicator of national socioeconomic status. The association between age-standardized death or DALYs rate and socioeconomic status were analyzed. RESULTS: Worldwide, 4.7 million deaths and 147.7 million DALYs of NCDs were related to high BMI in 2017, with a projection to 5.5 million deaths and 176.9 million DALYs in 2025. Globally, high BMI-related burden showed an increasing trend with males being more heavily impacted overall. The trend and magnitude of high BMI-related disease burden varied substantially in different geographical and socioeconomic regions. Specifically, the low-middle, middle, and high-middle SDI countries were associated with a higher burden. The leading three causes of DALYs attributable to high BMI in 2017 were ischemic heart diseases, stroke, and diabetes mellitus. CONCLUSIONS: High BMI-related burden of NCDs is worsening, particularly in developing countries. Our findings may enhance public awareness of interventions to reduce the diseases burden caused by high BMI.

2.
Arch Oral Biol ; 117: 104794, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32553945

RESUMO

OBJECTIVE: This study aims to investigate the expression pattern of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6) in human dental pulp tissues and cells, and roughly explore the role of NLRP6 in dental pulp immunity. METHODS: Immunohistochemistry and immunofluorescence double staining were performed to determine the expression and localization of NLRP6 in healthy and inflamed pulp tissues. The expression of NLRP6 in human dental pulp cells (HDPCs) was investigated by immunocytofluorescence. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) and western blot were used to evaluate the impact of lipopolysaccharide (LPS) stimulation on NLRP6 expression in HDPCs. Last, NLRP6 gene was silenced by lentiviral short hairpin RNA to explore the impact of NLRP6 on LPS-induced interleukin (IL)-1ß. RESULTS: NLRP6 was predominantly expressed in odontoblasts layer and blood vessels of healthy dental pulp, as well as infiltrated immune cells and fibroblasts of inflamed pulp. Further immunofluorescence double staining showed that pericytes and endothelial cells in the dental pulp blood vessels, macrophages and T cells as well as fibroblasts in the inflamed pulp expressed NLRP6. NLRP6 was also basically expressed in cultured HDPCs and upregulated by LPS stimulation. Knockdown of NLRP6 in HDPCs significantly inhibited the LPS-induced IL-1ß expression. CONCLUSIONS: Our study revealed the expression and distribution of NLRP6 in human dental pulp tissues. Furthermore, NLRP6 was also basically expressed in cultured HDPCs, which could be upregulated by LPS stimulation, indicating the involvement of NLRP6 in dental pulp immune response.

3.
Target Oncol ; 15(3): 337-345, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32495159

RESUMO

BACKGROUND: Osimertinib is a standard therapy for advanced non-small cell lung cancer (NSCLC) patients with an acquired epidermal growth factor receptor (EGFR) T790M mutation; however, the exploration of clinical characteristics that may affect prognosis and long-term survival is still lacking. OBJECTIVE: This retrospective study aimed to provide long-term survival data and explore meaningful prognostic factors in patients treated with osimertinib. PATIENTS AND METHODS: A total of 246 patients with acquired EGFR T790M mutation who were treated with osimertinib were included in this study. Progression-free survival (PFS), overall survival from osimertinib initiation (OS1), overall survival from diagnosis of advanced disease (OS), and possible prognostic clinical features were analyzed. RESULTS: The median PFS, OS1, and OS values were 12.17, 24.33, and 47.86 months, respectively. The median PFS of patients harboring EGFR exon 19 deletions/T790M (19del/T790M) and those harboring EGFR 21 L858R/T790M were 13.27 and 9.77 months (p = 0.001), respectively, while the median OS1 values were 25.03 and 18.30 months (p = 0.023), respectively; however, no significant difference was found in median OS (p = 0.060). Cox regression analysis revealed that coexisting mutation type and extrathoracic metastasis affected survival (PFS, OS1). In addition, gene biopsy specimen type (tissue or blood sample) was related to PFS (p = 0.032), which implied that liquid biopsy may be an independent poor prognostic factor. CONCLUSIONS: This is the first reported survival analysis of osimertinib-treated Chinese patients, which indicates a median OS of 47.86 months. The EGFR T790M mutation is likely to coexist with 19del and indicate longer PFS and OS1 than EGFR 21 L858R/T790M. Additionally, the extrathoracic metastasis status and biopsy specimen type might also affect the survival of patients treated with osimertinib.

4.
Acta Pharmacol Sin ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415222

RESUMO

Anlotinib, a multitarget tyrosine kinase inhibitor, is effective as a third-line treatment against non-small cell lung cancer (NSCLC). However, acquired resistance occurs during its administration. To understand the molecular mechanisms of anlotinib resistance, we characterized chromatin accessibility in both the parental and anlotinib-resistant lung cancer cell line NCI-H1975 through ATAC-seq. Compared with the parental cells, we identified 2666 genomic regions with greater accessibility in anlotinib-resistant cells, in which angiogenesis-related processes and the motifs of 21 transcription factors were enriched. Among these transcription factors, TFAP2A was upregulated. TFAP2A knockdown robustly diminished tumor-induced angiogenesis and partially rescued the anti-angiogenic activity of anlotinib. Furthermore, transcriptome analysis indicated that 2280 genes were downregulated in anlotinib-resistant cells with TFAP2A knocked down, among which the PDGFR, TGF-ß, and VEGFR signaling pathways were enriched. Meanwhile, we demonstrated that TFAP2A binds to accessible sites within BMP4 and HSPG2. Collectively, this study suggests that TFAP2A accelerates anlotinib resistance by promoting tumor-induced angiogenesis.

5.
J Diabetes Res ; 2020: 4178639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32455133

RESUMO

Objective: To identify susceptibility modules and genes for cardiovascular disease in diabetic patients using weighted gene coexpression network analysis (WGCNA). Methods: The raw data of GSE13760 were downloaded from the Gene Expression Omnibus (GEO) website. Genes with a false discovery rate < 0.05 and a log2 fold change ≥ 0.5 were included in the analysis. WGCNA was used to build a gene coexpression network, screen important modules, and filter the hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the genes in modules with clinical interest. Genes with a significance over 0.2 and a module membership over 0.8 were used as hub genes. Subsequently, we screened these hub genes in the published genome-wide SNP data of cardiovascular disease. The overlapped genes were defined as key genes. Results: Fourteen gene coexpression modules were constructed via WGCNA analysis. Module greenyellow was mostly significantly correlated with diabetes. The GO analysis showed that genes in the module greenyellow were mainly enriched in extracellular matrix organization, extracellular exosome, and calcium ion binding. The KEGG analysis showed that the genes in the module greenyellow were mainly enriched in antigen processing and presentation, phagosome. Fifteen genes were identified as hub genes. Finally, HLA-DRB1, LRP1, and MMP2 were identified as key genes. Conclusion: This was the first study that used the WGCNA method to construct a coexpression network to explore diabetes-associated susceptibility modules and genes for cardiovascular disease. Our study identified a module and several key genes that acted as essential components in the etiology of diabetes-associated cardiovascular disease, which may enhance our fundamental knowledge of the molecular mechanisms underlying this disease.

6.
Pediatr Surg Int ; 36(7): 779-788, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32424498

RESUMO

PURPOSE: Congenital pyriform sinus fistula (CPSF) often presents diagnosis and treatment challenges. This study aimed to explore the treatment principles and to evaluate the effectiveness of the hypothermia plasma cauterization with suspension laryngoscopy for CPSF. METHODS: The medical records of 56 patients with CPSF from January 2000 to December 2019 were retrospectively reviewed. RESULTS: Of the 56 cases, the lesions were predominantly located on the left side (95%), and the accuracy of the first diagnosis was 30%. Ultrasound showed an abnormal rate of 86%, while CT or MRI displayed an abnormal anatomic lesion of 92%. The 3D visual reconstruction enabled the analysis of morphological characteristics of CPSF. The positive predictive value of barium esophagography was 89%, whereas the positive rate of the internal opening in CPSF under local anesthesia laryngoscopy was 33%. Nine cases of sinus type underwent open resection, and the recurrence rate was 33%. Interestingly, ten patients with sinus type underwent hypothermia plasma cauterization with suspension laryngoscopy, leading to a success rate of 100% without apparent complications. CONCLUSIONS: Hypothermia plasma cauterization with suspension laryngoscopy alongside 3D imaging is both minimally invasive and repeatable with neglectable complications, which has the potential to serve as the first-line treatment for CPSF in the future.

7.
Chin Med J (Engl) ; 133(11): 1285-1291, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32404690

RESUMO

BACKGROUND: Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people. METHODS: A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%-95%) were determined for reference ranges in different populations. RESULTS: There was a statistically significant difference in median HE4 levels between the post-menopausal (n = 2168) and pre-menopausal groups (n = 325) (36.46 vs. 24.04 pmol/L, Z = -14.41, P < 0.001). HE4 increased significantly with age in the post-menopausal groups (H = 408.18, P < 0.001) but not in the pre-menopausal subjects (Z = -0.43, P = 0.67). The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women, 78.17 pmol/L for post-menopausal women, and 73.3 pmol/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age. CONCLUSIONS: Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.

8.
Medicine (Baltimore) ; 99(17): e19727, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332612

RESUMO

Successful treatment of esophagogastric varices (EGV) with giant portal-systemic shunt is challenging. To explore the feasibility and safety of a novel hybrid procedure involving interventional radiology and endoscopy in the same sitting.Three cases clinically diagnosed to have decompensated cirrhosis and EGV with giant gastrorenal shunt (GRS) on contrast-enhanced computed tomography (CT) were included. The hybrid procedures included: indirect portography, hepatic vein pressure gradient (HVPG) measurement, HVPG-based partial splenic embolization (PSE), retrospective GRS balloon occlusion, endoscopic histoacryl injection (EHI), balloon catheter radiography and withdrawal. All the procedures were done in the same operation room. Main outcomes measurements included operation time, complications, and re-bleeding events.Hybrid interventions were performed successfully in 3 cases with a mean operation time of 63.3 minutes without any major intra- and post-operation complications. No rebleeding occurred at 6-month follow-up.Synchronous hybrid intervention combining radiology and endoscopy is feasible and safe for patients with EGV and giant GRS, preliminary study with limited cases deserves further exploration.


Assuntos
Endoscopia Gastrointestinal/métodos , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Varizes Esofágicas e Gástricas/terapia , Derivação Portossistêmica Cirúrgica/métodos , Radiologia Intervencionista/métodos , Oclusão com Balão/efeitos adversos , Oclusão com Balão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derivação Portossistêmica Cirúrgica/normas , Estudos Retrospectivos
9.
Clin Lung Cancer ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32139332

RESUMO

BACKGROUND: Although smoking is a primary cause of lung cancer, females are overrepresented among never-smokers with the disease. The mutational landscape of adenocarcinoma in never-smoking females has been extensively profiled; however, there is little knowledge about genomic alterations in non-adenocarcinoma non-small-cell lung cancer (NA-NSCLC). In the study, we reviewed the status of oncogenic drivers of NA-NSCLC in these populations. MATERIALS AND METHODS: Comprehensive genomic profiling was performed on DNA extracted from formalin-fixed, paraffin-embedded sections of 52 NA-NSCLC tissues, including 35 squamous cell carcinomas (SQCCs), 11 adenosquamous carcinomas, 5 pulmonary sarcomatoid carcinoma, and 1 large cell carcinoma by next-generation sequencing within a panel of 68 cancer-related genes. RESULTS: Mutations of the common oncogenic drivers (EGFR, KRAS, ALK, ROS1, MET, RET, and ERBB2) occurred in 61.5% of cases. The frequency of well-established targets (EGFR and ALK), new targets without widely available therapies (MET and ERBB2), and potentially actionable targets (RET and DDR2) in SQCCs of female never-smokers was significantly higher than that in The Cancer Genome Atlas dataset. There were 31%, 82%, and 80% of cases with SQCC, adenosquamous carcinoma, and pulmonary sarcomatoid carcinoma, respectively, harboring at least one of the following targets: EGFR, ALK, ERBB2, and MET. Approximately 78% (7/9) of the patients responded to various targeted treatments. CONCLUSION: Female never-smokers with NA-NSCLC in this study had a high frequency of currently known or potentially actionable oncogenic alterations and could benefit from targeted therapy. Our study also provides evidence for the recommendation of molecular analysis in never-smoking female SQCC.

10.
J Am Chem Soc ; 142(13): 6196-6205, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32150680

RESUMO

During the past few decades, the study of the single polymer chain has attracted considerable attention with the goal of exploring the structure-property relationship of polymers. It still, however, remains challenging due to the variability and low atomic resolution of the amorphous single polymer chain. Here, we demonstrated a new strategy to visualize the single metallopolymer chain with a hexameric or trimeric supramolecule as a repeat unit, in which Ru(II) with strong coordination and Fe(II) with weak coordination were combined together in a stepwise manner. With the help of ultrahigh-vacuum, low-temperature scanning tunneling microscopy (UHV-LT-STM) and scanning tunneling spectroscopy (STS), we were able to directly visualize both Ru(II) and Fe(II), which act as staining reagents on the repeat units, thus providing detailed structural information for the single polymer chain. As such, the direct visualization of the single random polymer chain is realized to enhance the characterization of polymers at the single-molecule level.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 235-241, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027283

RESUMO

OBJECTIVE: To establish a novel flow cytometric immunobead array (FCIA) for detecting plasma von Willebrand factor antigen (vWF:Ag), and to analyze the clinical value of FCIA in predicting the prognosis of patients with ischemic stroke (IS). METHODS: Anti-human vWF monoclonal antibody SZ29 IgG was coated on microspheres overnight, the diluted plasma was added after blocking, then incubated with FITC-conjugated sheep-anti-human vWF IgG polyclonal antibody, and finally detected by flow cytometry. The plasma vWF in 21 case of von Willebrand disease (vWD) and 105 controls (CTL) were detected by FCIA and ELISA, so as to carry out methodological assessment. Plasma vWF:Ag of 61 IS patients was detected by FCIA and the data of prognosis followed-up for 2-year were collected. RESULTS: The linear fitting of FCIA was good (R2=0.99) without significant difference between FCIA and ELISA. The Bland-Altman bias was 1.12% with 95% limits of agreement that spanned from -45.06% to 47.30%, and the slope of the linear regression was 0.97 (r=0.86, P<0.01). Importantly, the FCIA method was faster than ELISA, and superior to the ELISA in the detection of low levels of vWF:Ag. The levels of vWF:Ag, vWF:GPIbR and vWF:CB in IS patients were significantly higher than those in healthy controls (Z=8.36, 8.71, 6.22, respectively, P<0.01). CONCLUSION: The FCIA for detecting plasma vWF:Ag is not only an effective supplement to ELISA, but also the efficiency is faster and more sensitive, thus improves the diagnosis of type 3 vWD. Elevated levels of vWF: Ag in IS patients indicate the poor recovery of daily activities and prognosis.


Assuntos
Doenças de von Willebrand , Animais , Anticorpos , Citometria de Fluxo , Humanos , Ovinos , Acidente Vascular Cerebral , Fator de von Willebrand
12.
J Comp Eff Res ; 9(3): 201-218, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31975614

RESUMO

Aim: To evaluate and compare the short-term outcomes of robotic surgery and laparoscopic approach in distal pancreatectomy (DP). Materials & methods: EMBASE, PubMed, the Cochrane Library, CNKI and Wan Fang database were retrieved from the inception of electronic databases to June 2019. All analyses were performed using Stata/SE 15.1 version (StataCorp). Results: Twenty-two papers were included, four of which were prospective studies and the rest were retrospective studies. There was significant difference in spleen preservation rate (odds ratio: 2.020; 95% CI: 1.085-3.758; p = 0.027), operation time (mean difference [MD]: 27.372; 95% CI: 8.236-47.210; p = 0.000), the length of hospital stay (MD: -0.911; 95% CI: -1.287 to -0.535; p = 0.000), conversion rate (rate difference: -0.090; 95% CI: -1.287 to -0.535; p = 0.000), operation cost (MD: 2816.564; 95% CI: 1782.028-3851.064; p = 0.000). However, no significant difference was detected in estimated blood loss, total complication, severe complication, lymph nodules harvest, blood transfusion rate, total pancreatic fistula, severe pancreatic fistula, R0 resection rate and mortality. Conclusion: Both robotic and laparoscopic DP are safe and feasible. Although robotic DP increases the operation cost, the spleen-preserving rate is much higher. Robotic surgery may be an alternative approach to DP.

13.
Chin J Integr Med ; 26(5): 330-338, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31919749

RESUMO

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

14.
Hepatobiliary Pancreat Dis Int ; 19(2): 122-128, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31983674

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) has shown effectiveness in terms of reducing the hospital stay and cost. However, the benefit of ERAS in patients undergoing hepatectomy for benign liver lesions is still unclear. METHODS: ERAS was implemented in our center since March 1st, 2018. From September 2016 to February 2018, 109 patients were enrolled into the control group, and from March 2018 to June 2019, 124 patients were enrolled into the ERAS group. All the indicators related to operation, liver functions, and postoperative outcomes were included in the analysis. RESULTS: The clinicopathologic baselines were similar in these two groups. A significantly higher proportion of patients underwent laparoscopic surgery in the ERAS group. On the whole, intraoperative blood loss (100.00 mL vs. 200.00 mL, P < 0.001), blood transfusion (3.23% vs. 10.09%, P = 0.033), total bilirubin (17.10 µmol/L vs. 21.00 µmol/L, P = 0.041), D-dimer (2.08 µg/mL vs. 2.57 µg/mL, P = 0.031), postoperative hospital stay (5.00 d vs. 6.00 d, P < 0.001), and postoperative morbidity (16.13% vs. 32.11%, P = 0.008) were significantly shorter or less in the ERAS group than those in the control group. After stratified by operation methods, ERAS group showed significantly shorter postoperative hospital stay in both open and laparoscopic operation (both P < 0.001). In patients underwent open surgery, ERAS group demonstrated significantly shorter operative duration (131.76 ± 8.75 min vs. 160.73 ± 7.23 min, P = 0.016), less intraoperative blood loss (200.00 mL vs. 450.00 mL, P = 0.008) and less postoperative morbidity (16.00% vs. 44.44%, P = 0.040). CONCLUSIONS: ERAS program may be safe and effective for the patients underwent hepatectomy, especially open surgery, for benign liver lesions.

15.
Clin Appl Thromb Hemost ; 26: 1076029619900552, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31964151

RESUMO

von Willebrand factor (VWF) acts as a bridge between platelets and the subendothelial matrix following vessel damage and plays a vital role in coronary artery disease (CAD). The aim of this study was to investigate the association between VWF and the severity of coronary stenosis quantified by the Gensini score in acute myocardial infarction (AMI), the most dangerous complication of CAD. Plasma VWF antigen (VWF: Ag) and VWF-collagen binding (VWF: CB) in normal controls (n = 123) and in patients with AMI (n = 205) were tested, and then the patients were divided based on Gensini scores. The levels of VWF: Ag and VWF: CB in patients with AMI were significantly higher than those in the control group (P < .001). Plasma levels of VWF: Ag and VWF: CB were positively correlated with both Gensini score and the number of affected vessels. Both VWF: Ag and VWF: CB were independent factors for coronary stenosis, adjusting confounding factors. Thus, the levels of VWF: Ag and VWF: CB were positively correlated with the severity of coronary stenosis. Screening of VWF at time of AMI may have prognostic value in terms of the severity of coronary stenosis.

16.
Front Med ; 14(1): 81-90, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31280468

RESUMO

Accumulating evidence suggests that C-type lectin-like receptor-2 (CLEC-2) plays an important role in atherothrombosis. In this case-control study, we investigated the association between CLEC-2 and incidence of coronary artery disease (CAD). A total of 216 patients, including 14 cases of stable angina pectoris (SAP, non-ACS) and 202 cases of acute coronary syndrome (ACS), and 89 non-CAD control subjects were enrolled. Plasma levels of soluble CLEC-2 (sCLEC-2) were measured using the enzyme-linked immunosorbent assay (ELISA). Compared with the control group (65.69 (55.36-143.22) pg/mL), the plasma levels of sCLEC-2 were significantly increased in patients with CAD (133.67 (88.76-220.09) pg/mL) and ACS (134.16 (88.88-225.81) pg/mL). The multivariate adjusted odds ratios (95% confidence interval) of CAD reached 2.01 (1.52-2.66) (Ptrend < 0.001) for each 1-quartile increase in sCLEC-2. Restricted cubic splines showed a positive dose-response association between sCLEC2 and CAD incidence (Plinearity < 0.001). The addition of sCLEC-2 to conventional risk factors improved the C statistic (0.821 vs. 0.761, P = 0.004) and reclassification ability (net reclassification improvement: 57.45%, P < 0.001; integrated discrimination improvement: 8.27%, P < 0.001) for CAD. In conclusion, high plasma sCLEC-2 is independently associated with CAD risk, and the prognostic value of sCLEC-2 may be evaluated in future prospective studies.

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.
J Org Chem ; 85(2): 691-701, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31790239

RESUMO

A convenient acid-mediated reaction of ß-keto sulfones with sulfoxides under metal-free conditions has been developed, thereby delivering the acid-controlled synthesis of ß-sulfenyl ketones and α,ß-disulfonyl ketones in good to excellent yields. The mechanism of the transformations has been studied carefully, which suggested the involvement of a radical process in the formation of α,ß-disulfonyl ketones.

19.
Cell Signal ; 68: 109493, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31809872

RESUMO

BACKGROUND: Myelodysplastic syndromes (MDS) represent a family of hematopoietic stem cell disorders characterized by ineffective hematopoiesis. While the functions of many microRNAs have been identified in MDS, microRNA-144 (miR-144) remains poorly understood. Thus, the aim of the present study was to determine the effects of miR-144 on cell proliferation and apoptosis in MDS cells and mechanism thereof. METHODS: MDS-related microarrays were used for screening differentially expressed genes in MDS. The relationship between miR-144 and A-kinase anchoring protein 12 (AKAP12) was determined by a dual luciferase reporter gene assay. Subsequently, gain- and loss-function approaches were used to assess the effects of miR-144 and AKAP12 on cell proliferation, cell cycle and cell apoptosis by MTT assay and flow cytometry. Following the induction of a mouse model with MDS, the tumor tissues were extract for evaluation of apoptosis and the expression of miR-144, AKAP12, and the relevant genes associated with extracellular-regulated protein kinases 1/2 (ERK1/2) signaling pathway and apoptosis. RESULTS: We observed significantly diminished expression of AKAP12 in MDS samples. miR-144 directly bound to AKAP12 3'UTR and reduced its expression in hematopoietic cells. Downregulation of miR-144 or upregulation of AKAP12 was observed to prolong cell cycle, inhibit cell proliferation, and induce apoptosis, accompanied by increased expression of AKAP12, p-ERK1/2, caspase-3, caspase-9, Bax, and p53, as well as decreased expression of Bcl-2. The transplanted tumors in mice with down-regulated miR-144 exhibited a lower mean tumor diameter and weight, and increased apoptosis index and expression of AKAP12 and ERK1/2. CONCLUSION: Taken together, these studies demonstrate the stimulative role of miR-144 in MDS progression by regulating AKAP12-dependent ERK1/2 signaling pathway.

20.
Cancer Res ; 80(5): 976-987, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31874857

RESUMO

Long terminal repeat (LTR) retrotransposons are a major class of transposable elements, accounting for 8.67% of the human genome. LTRs can serve as regulatory sequences and drive transcription of tissue or cancer-specific transcripts. However, the role of these LTR-activated transcripts, especially long non-coding RNAs (lncRNA), in cancer development remains largely unexplored. Here, we identified a novel lncRNA derived from MER52A retrotransposons (lncMER52A) that was exclusively expressed in hepatocellular carcinoma (HCC). HCC patients with higher lncMER52A had advanced TNM stage, less differentiated tumors, and shorter overall survival. LncMER52A promoted invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, lncMER52A stabilized p120-catenin and triggered the activation of Rho GTPase downstream of p120-catenin. Furthermore, we found that chromatin accessibility was crucial for the expression of lncMER52A. In addition, YY1 transcription factor bound to the cryptic MER52A LTR promoter and drove lncMER52A transcription in HCC. In conclusion, we identified an LTR-activated lncMER52A, which promoted the progression of HCC cells via stabilizing p120-catenin and activating p120-ctn/Rac1/Cdc42 axis. LncMER52A could serve as biomarker and therapeutic target for patients with HCC. SIGNIFICANCE: A novel long noncoding RNA lncMER52 modulates cell migration and invasion via posttranslational control of p120-catenin protein stability. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/5/976/F1.large.jpg.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA