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1.
Heart Surg Forum ; 24(2): E320-E326, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798048

RESUMO

OBJECTIVES: Cardiac postoperative cognitive dysfunction (c-POCD) is a common complication. This article established a nomogram by analyzing preoperative and intraoperative data to help identify high-risk patients and take effective management for prevention of c-POCD in early stage. MEASUREMENTS AND MAIN RESULTS: A total of 265 patients were enrolled in this study, 27 of whom were diagnosed as cardiac postoperative cognitive dysfunction (c-POCD). Patients were divided into a control group and c-POCD group. Univariate analysis suggested that gender, smoking, drinking history, hypertension, white blood cell (WBC) count, aspartate aminotransferase (AST), high-sensitivity troponin (hs-CRP), arrhythmia, left atrial diameter (LAD), cardiopulmonary bypass (CPB) time, and the ascending aortic block (AAB) time were correlated with postoperative cognitive dysfunction after cardiac surgery. Multivariate regression analysis indicated that CPB time (P = 0.0015, OR (95% CI) = 6.696 (2.068-21.675), hypertension (P = 0.0098, OR (95%CI) = 3.776 (1.377-10.356), WBC count (P = 0.0227, OR (95%CI ) = 3.358 (1.184-9.522), AST (P = 0.0128, OR (95%CI) = 3.966 (1.340-11.735), and arrhythmia (P = 0.0017, OR (95%CI) = 5.164 (1.855-14.371) were the independent risk factors of cognitive dysfunction after cardiac surgery and used to establish a nomogram for clinical use. The initial C-index of the nomogram was 0.8182 and good calibration. Corrected C-index value of 0.793 was reached after internal validation. The area under ROC curve of this model was 0.8188 (95%CI: 0.7185-0.9190). The positive odds ratio (PLR) was 1.21 (95%CI: 1.1-1.3), and the negative odds ratio (NLR) was 0.18 (95%CI: 0.03-1.3). CONCLUSION: This nomogram incorporating the CPB time, hypertension, WBC count, AST, and arrhythmia to predict the risk of c-POCD. The internal validation shows a good forecasting effect.

2.
Biochem Biophys Res Commun ; 548: 60-66, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33631675

RESUMO

Repeated and long-term oxaliplatin therapy leads to drug resistance and severe adverse events, which limit its clinical use. These difficulties highlight the importance of identifying potent and specific drug combinations to enhance the antitumor effects of oxaliplatin. The farnesoid X receptor (FXR) deficiency in colorectal cancer (CRC) suggests that restoring FXR function might be a promising strategy for CRC treatment. A drug combination study showed that the GW4064 acted synergistically with oxaliplatin in colon cancer cells. The combination of oxaliplatin plus GW4064 inhibited cell growth and colony formation, induced apoptosis and pyroptosis in vitro, and slowed tumor growth in vivo. Mechanistically, GW4064 enhanced the chemosensitivity of cells to oxaliplatin by inducing BAX/caspase-3/GSDME-mediated pyroptosis. Furthermore, the combination of oxaliplatin and GW4064 synergistically inhibited STAT3 signaling by restoring SHP expression. Our study revealed that GW4064 could enhance the antitumor effects of oxaliplatin against CRC, which provides a novel therapeutic strategy based on a combinational approach for CRC treatment.

3.
Chemosphere ; 274: 129728, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33540304

RESUMO

Mercury, especially in the form of methylmercury (MeHg), is a global pollutant, and aquatic products are considered the main sources of Hg exposure to humans. The Bohai and Yellow seas are two important epicontinental seas for marine fisheries and aquaculture in China. A decreasing trend of the THg in the Yellow River Estuary toward the outer edge was reported according to 83 surface sediments (27.3 ± 15.0 ng g-1) and 3 sediment cores from the Bohai Sea and Yellow Sea. The relatively higher THg levels in the central Yellow Sea can be primarily attributed to higher organic carbon levels and finer-grained sediment sizes and partly to the particulates from the riverine input of the Yellow River driven by the currents. An increasing trend in THg levels since industrialization in north China around the Bohai and Yellow seas, and a decreasing trend of Yellow River THg input in recent years were recorded by sediment cores. The spatial distribution pattern of surface sediments MeHg (161 ± 130 pg g-1) was different from that of THg. A higher MeHg content and MeHg/THg ratio were found in the Bohai and Yellow seas compared to the East China Sea, and extremely high MeHg levels (714 pg g-1) were found in the Yellow Sea Cold Water Mass (YSCWM) area, which is considered an important region for fishery and marine breeding, suggesting that more attention should be paid to the potential ecological and human health risks in the region due to mercury exposure.

4.
Org Lett ; 23(3): 1081-1085, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33439657

RESUMO

The construction of functional N-containing active biomolecules and bidentate nitrogen ligands by electroreductive pyridylation of N-heteroaromatics is an eye-catching task and challenge. A simple and practical electroreductive-induced C3 pyridylation of quinoxalin-2(1H)-ones with readily available cyanopyridines is reported. More than 36 examples are supplied, and the reaction performed in >95% yield. The present protocol provides a convenient, efficient, and gram-scale synthesis strategy for a series of new types of potential bidentate nitrogen ligands.

5.
Int J Med Sci ; 18(2): 546-554, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390824

RESUMO

Long non-coding RNA musculin antisense RNA 1 (lncRNA MSC-AS1) has been recognized as an oncogene in pancreatic cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, and renal cell carcinoma. However, the functional significance of MSC-AS1 and its underlying mechanism in gastric cancer (GC) progression remain unclear. In this study, we demonstrated that the expression of MSC-AS1 in GC tissues was significantly higher than that in non-tumor tissues. Moreover, the elevated level of MSC-AS1 was detected in GC cells (MKN-45, AGS, SGC-7901, and MGC-803) compared to normal GES-1 gastric mucosal cells. The cancer genome atlas (TCGA) data further indicated that the high level of MSC-AS1 was closely correlated with advanced tumor stage and poor prognosis of GC. Next, we revealed that MSC-AS1 knockdown inhibited the proliferation, glucose consumption, lactate production, and pyruvate production of MGC-803 cells. Conversely, MSC-AS1 overexpression enhanced the proliferation and glycolysis of AGC cells. Mechanistically, modulating MSC-AS1 level affected the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), but did not impact the levels of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2) in GC cells. Based on this, we reversed the MSC-AS1 knockdown-induced the inhibition of cell proliferation and glycolysis by restoring PFKFB3 expression in MGC-803 cells. In conclusion, MSC-AS1 facilitated the proliferation and glycolysis of GC cells by maintaining PFKFB3 expression.

7.
Heart Surg Forum ; 23(6): E743-E745, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33234217

RESUMO

Acute mitral valve injury following percutaneous left atrial appendage (LAA) occlusion is a rare, but potentially life-threatening complication. This report presents a case of severe mitral valve injury following left atrial appendage occlusion (LAAO) that required mitral valve replacement. The LAAO device successfully was removed, and the LAA was closed with a double-running polypropylene suture. In addition, the mitral valve was replaced with an artificial valve. The patient had an uneventful clinical evolution and was discharged 10 days after emergency surgery.

8.
Surg Endosc ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33237468

RESUMO

BACKGROUND: Robotic colorectal cancer surgery is widely accepted and applied. However, there is still no objective and comprehensive assessment on the data of nationwide multicenter series. METHOD: A total of 28 medical centers in Mainland China participated in this nationwide retrospective observational study. From the first case performed in each center to the last until December 2017, patients with robotic resection for primary tumor and pathologically confirmed colorectal adenocarcinoma were consecutively enrolled. Clinical, pathological and follow-up data were collected and analyzed. RESULTS: A total of 5389 eligible patients were finally enrolled in this study, composing 72.2% of the total robotic colorectal surgery volume of Mainland China in the same period. For resections of one bowel segment of primary tumor, the postoperative mortality rate was 0.08% (4/5063 cases), and the postoperative complication rate (Clavien-Dindo grade II or higher) was 8.6% (434/5063 cases). For multiple resections, the postoperative mortality rate was 0.6% (2/326 cases), and the postoperative complication rate was 16.3% (53/326 cases). Out of 2956 patients receiving sphincter-preserving surgery in only primary resection, 130 (4.4%) patients had anastomotic leakage. Traditional low anterior resection (tumor at middle rectum) (OR 2.384, P < 0.001), traditional low anterior resection (tumor at low rectum) (OR 1.968, P = 0.017) and intersphincteric resection (OR 5.468, P = 0.006) were significant independent risk factors for anastomotic leakage. Female gender (OR 0.557, P = 0.005), age ≥ 60 years (OR 0.684, P = 0.040), and preventive stoma (OR 0.496, P = 0.043) were significant independent protective factors. Body mass index, preoperative chemotherapy/radiotherapy, tumor size, and TNM stage did not independently affect the occurrence of anastomotic leakage. CONCLUSION: Robotic colorectal cancer surgery was safe and reliable and might have advantages in patients at high risk of anastomotic leakage.

9.
Br J Cancer ; 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33239678

RESUMO

BACKGROUND: Emerging evidence suggests the involvement of caudal-related homoeobox transcription factor 2 (CDX2) in tumorigenesis of various cancers. Although CDX2 functions in cancer invasion and metastasis, fewer studies focus on the role of CDX2 during the induction of epithelial-mesenchymal transition (EMT) in colorectal cancer (CRC). METHODS: Immunohistochemical analysis of CDX2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of CDX2 in the invasion and metastasis of CRC. RESULTS: CDX2 was downregulated in CRC tissues and reduced CDX2 correlated with poor prognosis. Knockdown of CDX2 promoted colon cancer cell invasion in vitro and facilitated liver metastasis in vivo with inducing EMT phenotypes. Further investigation indicated that CDX2 retarded Akt and GSK-3ß phosphorylation, and thereby diminished Snail expression, ß-catenin stabilisation and nuclear translocation. The depletion of ß-catenin neutralised the regulation of Slug and ZEB1 by CDX2 knockdown. Mechanistically, CDX2 antagonised PI3K/Akt activity in CRC by modulating PTEN expression. CDX2 directly bound to the promoter of PTEN and transactivated its expression. CONCLUSIONS: Our study first uncovered that CDX2 inhibits EMT and metastasis of CRC by regulation of Snail expression and ß-catenin stabilisation via transactivation of PTEN expression.

10.
J Cell Mol Med ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33164339

RESUMO

Farnesoid X receptor (FXR, encoded by NR1H4), a bile acid-activated nuclear receptor, is widely implicated in human tumorigenesis. The FXR agonist obeticholic acid (OCA) has preliminarily displayed tumour suppressor potential. However, the anticancer effects of this agent on colorectal cancer (CRC) remain unclear. In this study, the treatment of colon cancer cells with OCA inhibited cell proliferation and invasion in vitro, retarded tumour growth in vivo and prevented the G0 /G1 to S phase transition. Moreover, the expression of active caspase-3, p21 and E-cadherin was up-regulated and the expression of cyclin D1, c-Myc, vimentin, N-cadherin and MMP9 was down-regulated in OCA-treated colon cancer cells. Mechanistic studies indicated that OCA treatment suppressed the activity of JAK2/STAT3 pathway by up-regulating SOCS3 expression. Colivelin, an agonist of JAK2/STAT3 pathway, antagonized the tumour-suppressive effect of OCA on colon cancer cells. Dual-luciferase reporter and quantitative chromatin immunoprecipitation (qChIP) assays further confirmed that OCA promoted SOCS3 transcription by enhancing the binding of FXR to the FXRE/IR9 of the SOCS3 promoter. In conclusion, our study demonstrates that targeting FXR and improving its function might be a promising strategy for CRC treatment.

11.
Org Lett ; 22(22): 8824-8828, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-33147042

RESUMO

Electrochemical-induced transfer hydrogenation (TH) of N-heteroaromatic to construct biologically active functional molecule is an appealing and yet challenging task. We report herein the first selective transfer hydrogenation of imidazopyridine derivatives with secondary amines as the hydrogen donors under electrochemical conditions. The successful conversion of cathode transfer hydrogenation depends on the solvation effect. Importantly, such electrochemical-induced transfer hydrogenation can be easily amplified with excellent efficiency.

13.
Cancer Gene Ther ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33046820

RESUMO

The tumor-suppressive role of Farnesoid X receptor (FXR) in colorectal tumorigenesis supports restoring FXR expression as a novel therapeutic strategy. However, the complicated signaling network and tumor heterogeneity hinder the effectiveness of FXR agonists in the clinical setting. These difficulties highlight the importance of identifying drug combinations with potency and specificity to enhance the antitumor effects of FXR agonists. In this study, we found that the ß-catenin level affected the antitumor effects of the FXR agonist OCA on colon cancer cells. Mechanistic studies identified a novel FXR/ß-catenin complex in colon cancer cells. Furthermore, the depletion of ß-catenin expedited FXR nuclear localization and enhanced its occupancy of the SHP promoter and thereby sensitized colon cancer cells to OCA. Furthermore, we utilized a drug combination study and identified that the antiparasitic drug nitazoxanide (NTZ) abrogated ß-catenin expression and acted synergistically with OCA in colon cancer cells. The combination of OCA plus NTZ exerts synergistic tumor inhibition in CRC both in vitro and in vivo by cooperatively upregulating SHP expression. In conclusion, our study offers useful evidence for the clinical use of FXR agonists combined with ß-catenin inhibitors in combating CRC.

14.
Oxid Med Cell Longev ; 2020: 7075836, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922653

RESUMO

Objective: The present study is aimed at investigating the anti-inflammatory, antioxidative, and antiapoptotic effects of methane on lipopolysaccharide- (LPS-) induced acute orchitis and its potential mechanisms. Methods: Adult male rats were intraperitoneally (i.p.) injected with methane-rich saline (MS, 20 mL/kg) following LPS (5 mg/kg, i.p.). The survival rate was assessed every 12 h until 72 h after LPS induction, and surviving rats were sacrificed for further detection. The wet/dry (W/D) ratio was determined, and testicular damage was histologically assessed. Inflammatory cytokines in the testes and serum, including interleukin-1ß (IL-1ß), IL-6, IL-10, and tumor necrosis factor-α (TNF-α), were measured using ELISA and RT-qPCR. Oxidative stress was evaluated by the level of superoxide dismutase (SOD) and malondialdehyde (MDA). Testicular apoptosis was detected via TUNEL staining. The expression of prokineticin 2 (PK2)/prokineticin receptor 1 (PKR1) was also analyzed using RT-qPCR, western blotting, and immunohistochemistry. Results: It was found that methane significantly prolonged rat survival, decreased the W/D ratio, alleviated LPS-induced histological changes, and reduced apoptotic cells in the testes. Additionally, methane suppressed and promoted the production of pro- and anti-inflammatory cytokines, respectively. Furthermore, methane significantly increased SOD levels, decreased MDA levels, and decreased testicular expression of PK2 and PKR1. Therefore, methane exerts therapeutic effects on acute orchitis and might be a new and convenient strategy for the treatment of inflammation-related testicular diseases.

15.
Cell Death Dis ; 11(8): 640, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807788

RESUMO

Farnesoid X receptor (FXR, encoded by NR1H4), a critical regulator of bile acid homeostasis, is widely implicated in human tumorigenesis. However, the functional role of FXR in colorectal cancer (CRC) and the precise molecular mechanism remain unclear. In this study, we demonstrated that FXR expression was downregulated in colon cancer tissues and decreased expression of FXR predicted a poor prognosis. Knockdown of FXR promoted colon cancer cell growth and invasion in vitro, and facilitated xenograft tumor formation and distant metastasis in vivo, whereas ectopic expression of FXR had the reserved change. Mechanistic studies indicated that FXR exerted its tumor suppressor functions by antagonizing Wnt/ß-catenin signaling. Furthermore, we identified an FXR/ß-catenin interaction in colon cancer cells. The FXR/ß-catenin interaction impaired ß-catenin/TCF4 complex formation. In addition, our study suggested a reciprocal relationship between FXR and ß-catenin, since loss of ß-catenin increased the transcriptional activation of SHP by FXR. Altogether, these data indicated that FXR functions a tumor-suppressor role in CRC by antagonizing Wnt/ß-catenin signaling.

16.
J Zhejiang Univ Sci B ; 21(8): 593-602, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32748575

RESUMO

Methane is the simplest hydrocarbon, consisting of one carbon atom and four hydrogen atoms. It is abundant in marsh gas, livestock rumination, and combustible ice. Little is known about the use of methane in human disease treatment. Current research indicates that methane is useful for treating several diseases including ischemia and reperfusion injury, and inflammatory diseases. The mechanisms underlying the protective effects of methane appear primarily to involve anti-oxidation, anti-inflammation, and anti-apoptosis. In this review, we describe the beneficial effects of methane on different diseases, summarize possible mechanisms by which methane may act in these conditions, and discuss the purpose of methane production in hypoxic conditions. Then we propose several promising directions for the future research.

17.
J Zhejiang Univ Sci B ; 21(8): 646-656, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32748580

RESUMO

This study aimed to establish an animal model of decompression-induced lung injury (DILI) secondary to repetitive diving in mice and explore the role of macrophages in DILI and the protective effects of high-concentration hydrogen (HCH) on DILI. Mice were divided into three groups: control group, DILI group, and HCH group. Mice were exposed to hyperbaric air at 600 kPa for 60 min once daily for consecutive 3 d and then experienced decompression. In HCH group, mice were administered with HCH (66.7% hydrogen and 33.3% oxygen) for 60 min after each hyperbaric exposure. Pulmonary function tests were done 6 h after decompression; the blood was harvested for cell counting; the lung tissues were harvested for the detection of inflammatory cytokines, hematoxylin and eosin (HE) staining, and immunohistochemistry; western blotting and polymerase chain reaction (PCR) were done for the detection of markers for M1 and M2 macrophages. Our results showed that bubbles formed after decompression and repeated hyperbaric exposures significantly reduced the total lung volume and functional residual volume. Moreover, repetitive diving dramatically increased proinflammatory factors and increased the markers of both M1 and M2 macrophages. HCH inhalation improved lung function to a certain extent, and significantly reduced the pro-inflammatory factors. These effects were related to the reduction of M1 macrophages as well as the increase in M2 macrophages. This study indicates that repetitive diving damages lung function and activates lung macrophages, resulting in lung inflammation. HCH inhalation after each diving may be a promising strategy for the prevention of DILI.

18.
Sci Total Environ ; 738: 139836, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32526422

RESUMO

Strengthening the research of riverine mercury (Hg) export is of great significance for understanding the regional and global Hg cycle, especially for the data lacking trans-Himalayan rivers. In this study, three systematic sampling campaigns were conducted in the Koshi River Basin (KRB) during the post-monsoon, pre-monsoon and monsoon seasons. Hg speciation and distribution of river water were analyzed among the different seasons for a total of 88 water samples. The total Hg (THg) concentration of surface water in the KRB ranged from 0.64 to 32.96 ng·L-1 with an average of 5.83 ± 6.19 ng·L-1 and decreased in the order of post-monsoon (8.79 ± 7.32 ng·L-1) > monsoon (6.68 ± 6.12 ng·L-1) > pre-monsoon (2.18 ± 1.29 ng·L-1). Particulate Hg (PHg) accounted for 63% of THg on average and had a positive correlation with THg among all the three sampling seasons, indicating that the differences in PHg concentration were likely one of the main factors leading to the seasonal and spatial variations in THg in the KRB surface water. The annual Hg exports and fluxes were estimated to be 339.04 kg and 3.88 µg·m-2·yr-1, respectively. Furthermore, Hg export from the KRB had significant seasonal variation and decreased in the order of monsoon (259.47 kg) > post-monsoon (61.18 kg) > winter (9.31 kg) > pre-monsoon (9.08 kg), and this pattern was mainly related to seasonal changes in river runoff. The annual Hg export is projected to increase in the future, especially in the post-monsoon season. Therefore, more attention should be paid to river runoff observations and riverine Hg research for water resources management in the Himalaya.

19.
Scand J Gastroenterol ; 55(6): 694-700, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32459113

RESUMO

Introduction: An increasing number of newly diagnosed resectable gastric cancer (GC) patients are over 85 years of age. However, studies on surgical treatment in these patients are limited. This study aimed to explore the prognosis of a large sample of the oldest old GC patients receiving surgery.Methods: A total of 2914 oldest old patients with stage I-III GC were included in the linked Surveillance, Epidemiology, and End Results (SEER) database from 2006 to 2015. Based on their treatment, we assigned these patients to the surgery and no surgery groups. We used propensity score matching (1:1) to balance the baseline characteristics. The Kaplan-Meier method was used for the survival analysis. Multivariate Cox regression analysis was used to analyse the independent risk factors.Results: After propensity score matching, the median overall survival (OS) times in the surgery and no surgery groups were 24.0 (95% CI: 20.3-27.7) and 4.0 (95% CI: 3.5-4.5) months, respectively (p < .01). Age, sex, stage, histological type, and treatment with surgery and chemotherapy were independent risk factors for OS in the oldest old patients with GC. In total, 19% of the oldest old patients with GC died from causes unrelated to cancer.Conclusions: The current large-scale study demonstrated that the oldest old patients with stage I-III GC could benefit from elective surgery.

20.
Oncol Rep ; 43(4): 1103-1112, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32323782

RESUMO

The present study aimed to investigate the role of matrix metalloproteinase­1 (MMP­1) in the development of colorectal cancer and reveal the mechanism underlying this progression. Bioinformatics methods and a public dataset were first used to analyze MMP­1 gene expression in a public dataset. MMP­1 expression in colorectal cancer patients was assessed by immunohistochemistry; its association with clinicopathological parameters and its significance for prognosis were analyzed. Then proliferation, scratch and Transwell assays and a xenograft model were used to assess the change in malignant behavior in cells transfected with an MMP­1 shRNA. Changes involved in epithelial­mesenchymal transition (EMT) and the Akt signaling pathway were detected by western blotting. According to the results, MMP­1 expression was higher in colorectal cancer tissues than it was in matched adjacent noncancerous tissues, and its high expression was significantly related to lymphatic metastasis as well as TNM stage (P<0.05). Downregulation of MMP­1 expression inhibited the progression of colorectal cancer in vitro and in vivo. Furthermore, after the cells were stably transfected with MMP­1 shRNA, the expression of N­cadherin, vimentin and Twist1 decreased while that of E­cadherin increased. The expression of p­Akt and c­Myc also decreased. In conclusion, MMP­1 may promote malignant behavior in colorectal cancer via EMT and the Akt signaling pathway.

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