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1.
Ann Surg Oncol ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33783640

RESUMO

OBJECTIVE: The aim of this study was to create a risk-scoring model to preoperatively predict the incidence of lymph node metastasis (LNM) in early gastric cancer (EGC) patients to guide treatment. METHODS: To construct the risk-scoring model, we retrospectively analyzed a primary cohort of 548 EGC patients. Univariate analysis and logistic regression were performed. A risk-scoring model for predicting LNM in EGC patients was developed based on preoperative factors, and another cohort of 73 patients was then analyzed to validate the model. RESULTS: In the primary cohort, LNM was pathologically confirmed in 72 (13.1%) patients. In the multivariate analysis, the presence of ulceration and tumor size on gastroscopy, undifferentiated histological type, and presence of enlarged lymph nodes on computed tomography or endoscopic ultrasonography were independent risk factors for LNM. A 17-point risk-scoring model was developed to predict LNM risk. The cut-off score of the model was 8, and the area under the receiver operating characteristic curve (AUC) of the model was 0.835 [95% confidence interval (CI) 0.784-0.886]. In the validation cohort, the AUC of the model was 0.829 (95% CI 0.699-0.959). CONCLUSIONS: We developed and validated an effective 17-point risk-scoring model that could preoperatively predict LNM for EGC patients.

2.
Surgery ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33745733

RESUMO

BACKGROUND: Ischemia/reperfusion of the intestine often leads to distant organ injury, but the mechanism of intestinal ischemia/reperfusion-induced renal dysfunction is still not clear. The present study aimed to investigate the mechanisms of acute renal damage after intestinal ischemia/reperfusion challenge and explore the role of released high-mobility group box-1 in this process. METHODS: Intestinal ischemia/reperfusion was induced in male Sprague-Dawley rats by clamping the superior mesenteric artery for 1.5 hours. At different reperfusion time points, anti-high-mobility group box-1 neutralizing antibodies or ethyl pyruvate were administered to neutralize or inhibit circulating high-mobility group box-1, respectively. RESULTS: Significant kidney injury was observed after 6 hours of intestinal reperfusion, as indicated by increased serum levels of urea nitrogen and creatinine, increased expression of neutrophil gelatinase-associated lipocalin, interleukin-6, and MIP-2, and enhanced cell apoptosis, as indicated by cleaved caspase 3 levels in renal tissues. The levels of phosphorylated eIF2ɑ, activating transcription factor 4, and C/EBP-homologous protein (CHOP) were markedly elevated, indicating the activation of endoplasmic reticulum stress in the impaired kidney. High-mobility group box-1 translocated to cytoplasm in the intestine and serum concentrations of high-mobility group box-1 increased notably during the reperfusion phase. Both anti-high-mobility group box-1 antibodies and ethyl pyruvate treatment significantly reduced serum high-mobility group box-1 concentrations, attenuated endoplasmic reticulum stress in renal tissue and inhibited the development of renal damage. Moreover, the elevated expression of receptor for advanced glycation end products in the kidneys after intestinal ischemia/reperfusion was abrogated after high-mobility group box-1 inhibition. CONCLUSION: These results suggested that high-mobility group box-1 signaling regulated endoplasmic reticulum stress and promoted intestinal ischemia/reperfusion-induced acute kidney injury. High-mobility group box-1 neutralization/inhibition might serve as a pharmacological intervention strategy for these pathophysiological processes.

3.
Mult Scler Relat Disord ; 50: 102856, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33662858

RESUMO

BACKGROUND: The COVID-19 pandemic has raised concerns for increased risk of infection in patients with multiple sclerosis (MS) and disrupted their routine MS care. The aim of this study is to characterize the extent of MS patients' perceptions of risk and adherence to care during the pandemic. METHODS: A survey was emailed to patients from a large MS center in New York City during the local peak of the pandemic to assess perceptions of infection risk and adherence to MS care including appointments, laboratory studies, MRIs, and taking disease-modifying therapies (DMT). RESULTS: 529 patients from the MS center responded to the survey during two weeks in April 2020. Patients collectively showed concern about becoming infected with COVID-19 (88%) and perceived a higher infection risk due of having MS (70%) and taking DMTs (68%). Patients frequently postponed appointments (41%), laboratory studies (46%), and MRIs (41%). Noncompliance with DMTs was less common (13%). Decisions to alter usual recommendations for care were made by the patient more often than by the provider regarding adherence to appointments (68%), laboratory studies (70%), MRI (67%), and DMT (65%). Degree of concern for infection was associated with adherence to appointments (p=0.020) and laboratory studies (p=0.016) but not with adherence to MRI and DMTs. Thirty-five patients reported being tested for COVID-19, of whom fourteen reported a positive test. CONCLUSION: Patients with MS were highly concerned about becoming infected during the local peak of the COVID-19 pandemic. Behaviors that deviated from originally recommended MS care were common and often self-initiated, but patients were overall compliant with continuing DMTs.

4.
BMC Cancer ; 21(1): 216, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653317

RESUMO

BACKGROUND: HIPEC is an emerging procedure to treat peritoneal metastasis of gastric cancer. Data about HIPEC in locally advanced gastric cancer is scarce. The purpose of this trial is to evaluate the safety and toxicity of prophylactic HIPEC with cisplatin for patients with locally advanced gastric cancer. METHODS: From March 2015 to November 2016, a prospective, randomized phase II trial was conducted. After radical gastrectomy, patients in the experimental group underwent HIPEC with cisplatin followed by adjuvant chemotherapy with SOX regime. Patients in the other group were treated with SOX regime alone. Postoperative complications and patient survival were compared. RESULTS: In total, 50 patients were eligible for analyses. No significant difference was found in the incidence of postoperative complications including anastomotic/intestinal leakage, liver dysfunction, bone marrow suppression, wound infection and ileus (P > 0.05). Mean duration of hospitalization after radical gastrectomy was 11.7 days. 12.2 days in experimental group and 10.8 days in control group respectively (P = 0.255). The percentage of patients with elevated tumor markers was 12.1% in experimental group, which was significantly lower than 41.2% in control group (P = 0.02). 3-year RFS of patients who treated with or without prophylactic HIPEC were 84.8 and 88.2% respectively (P = 0.986). In the multivariate analysis, pathological T stage was the only independent risk factor for the RFS of patients (P = 0.012, HR =15.071). CONCLUSION: Additional intraoperative HIPEC with cisplatin did not increase postoperative complications for locally advanced gastric cancer after curative surgery. Prophylactic HIPEC with cisplatin was safe and tolerable, while it did not reduce the risk of peritoneal recurrence in this trial, supporting further studies to validate the efficacy of it. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000038331. Registered 18 September 2020 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=59692 .

6.
Molecules ; 26(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33672038

RESUMO

Our previous study found that desmethylxanthohumol (1) inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol (2) and its dimer analogue rottlerone (3) exhibited more potent α-glucosidase inhibitory activity than 1. The aim of this study was to synthesize a series of rottlerone analogues and evaluate their α-glucosidase and DPP-4 dual inhibitory activity. The results showed that compounds 4d and 5d irreversibly and potently inhibited α-glucosidase (IC50 = 0.22 and 0.12 µM) and moderately inhibited DPP-4 (IC50 = 23.59 and 26.19 µM), respectively. In addition, compounds 4d and 5d significantly promoted glucose consumption, with the activity of 5d at 0.2 µM being comparable to that of metformin at a concentration of 1 mM.


Assuntos
Inibidores da Dipeptidil Peptidase IV/farmacologia , Flavonoides/síntese química , Flavonoides/farmacologia , Glucose/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Propiofenonas/síntese química , Propiofenonas/farmacologia , Dipeptidil Peptidase 4/metabolismo , Flavonoides/química , Células Hep G2 , Humanos , Cinética , Propiofenonas/química , alfa-Glucosidases/metabolismo
7.
J Exp Clin Cancer Res ; 40(1): 76, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33618745

RESUMO

BACKGROUND: Accumulating evidence has revealed that circular RNAs (circRNAs), as novel noncoding RNAs, play critical roles in carcinogenesis and tumor progression. However, the functions and molecular mechanisms of circRNAs in clear cell renal cell carcinoma (ccRCC) are largely unknown. METHODS: The expression and functions of circAGAP1 were identified in clinical samples, ccRCC cells and in vivo animal models. The molecular mechanism of circAGAP1 was investigated by fluorescence in situ hybridization, RNA immunoprecipitation and luciferase assays. RESULTS: circAGAP1 (circ0058792) expression was significantly upregulated in ccRCC tissues compared to adjacent nontumor tissues. Moreover, the expression of circAGAP1 was closely related to the tumor size, nuclear grade and clinical stage of ccRCC in patients. Mechanistic studies demonstrated that cytoplasmic circAGAP1 targeted miR-15-5p in an RNA-induced silencing complex. Additionally, miR-15-5p expression was downregulated in ccRCC. Luciferase reporter assays showed that E2F transcription factor 3 (E2F3) was a target of miR-15-5p, and upregulated E2F3 expression was positively correlated with circAGAP1 in ccRCC. Furthermore, the tumor-promoting functions of circAGAP1 could be alleviated by miR-15-5p mimics in vitro and in vivo. CONCLUSION: Our results clarify that circAGAP1 exerts its oncogenic functions as a competitive endogenous RNA (ceRNA) by sponging miR-15-5p, which promotes E2F3 expression. Targeting circAGAP1 might be a new attractive therapeutic strategy in ccRCC.

8.
J Bioeth Inq ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33449316

RESUMO

There are differences in caregivers' literacy and health literacy levels that may affect their ability to consent to children participating in clinical research trials. This study aimed to explore the effectiveness, and caregivers' understandings, of the process of informed consent that accompanied their child's participation in a dental randomized control trial (RCT). Telephone interviews were conducted with a convenience sample of ten caregivers who each had a child participating in the RCT. Pre-tested closed and open-ended questions were used, and the findings were produced from an inductive analysis of the latter and a descriptive analysis of the former. Participants had limited understanding of the purpose of the RCT and rated the readability of the consent form more highly than they rated their understanding of the research. All felt that informed consent was vital, but some caregivers had not read the consent documents. Some caregivers enrolled their child in the RCT because they trusted the researchers, and the majority wanted to improve dental care for children. The informed consent process was not always effective despite high readability of the informed consent documents. Researchers must consider the health literacy of the study group, and actively engaging with caregivers to achieve meaningful informed consent may be challenging. Future research could explore participants' perspectives of informed consent in populations with low health literacy and assess whether an underlying expectation not to comprehend health-related information may be a barrier to informed consent.

9.
J Proteome Res ; 20(1): 1005-1014, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347754

RESUMO

Large-scale population screenings are not feasible by applying laborious oral glucose tolerance tests, but using fasting blood glucose (FPG) and glycated hemoglobin (HbA1c), a considerable number of diagnoses are missed. A novel marker is urgently needed to improve the diagnostic accuracy of broad-scale diabetes screening in easy-to-collect blood samples. In this study, by applying a novel knowledge-based, multistage discovery and validation strategy, we scaled down from 108 diabetes-associated metabolites to a diagnostic metabolite triplet (Met-T), namely hexose, 2-hydroxybutyric/2-hydroxyisobutyric acid, and phenylalanine. Met-T showed in two independent cohorts, each comprising healthy controls, prediabetic, and diabetic individuals, distinctly higher diagnostic sensitivities for diabetes screening than FPG alone (>79.6 vs <68%). Missed diagnoses decreased from >32% using fasting plasma glucose down to <20.4%. Combining Met-T and fasting plasma glucose further improved the diagnostic accuracy. Additionally, a positive association of Met-T with future diabetes risk was found (odds ratio: 1.41; p = 1.03 × 10-6). The results reveal that missed prediabetes and diabetes diagnoses can be markedly reduced by applying Met-T alone or in combination with FPG and it opens perspectives for higher diagnostic accuracy in broad-scale diabetes-screening approaches using easy to collect sample materials.

10.
Org Lett ; 23(2): 279-284, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33352055

RESUMO

An efficient divergent approach of Pd-catalyzed C-H oxygenation of polyaromatic rings is described. Reversible directing groups enable regiospecific peri- and ortho-oxygenation to readily access a wide array of polyaromatic phenols without pre- and postmanipulation of directing groups. The systematic mechanistic investigation, including deuterium-labeling experiments, palladacycle trapping, and DFT calculations, reveals that the tunable ligand-assisted C-H bond cleavage played a crucial role during the reaction process.

11.
Light Sci Appl ; 9(1): 191, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33298827

RESUMO

Magnetic resonances not only play crucial roles in artificial magnetic materials but also offer a promising way for light control and interaction with matter. Recently, magnetic resonance effects have attracted special attention in plasmonic systems for overcoming magnetic response saturation at high frequencies and realizing high-performance optical functionalities. As novel states of matter, topological insulators (TIs) present topologically protected conducting surfaces and insulating bulks in a broad optical range, providing new building blocks for plasmonics. However, until now, high-frequency (e.g. visible range) magnetic resonances and related applications have not been demonstrated in TI systems. Herein, we report for the first time, to our knowledge, a kind of visible range magnetic plasmon resonances (MPRs) in TI structures composed of nanofabricated Sb2Te3 nanogrooves. The experimental results show that the MPR response can be tailored by adjusting the nanogroove height, width, and pitch, which agrees well with the simulations and theoretical calculations. Moreover, we innovatively integrated monolayer MoS2 onto a TI nanostructure and observed strongly reinforced light-MoS2 interactions induced by a significant MPR-induced electric field enhancement, remarkable compared with TI-based electric plasmon resonances (EPRs). The MoS2 photoluminescence can be flexibly tuned by controlling the incident light polarization. These results enrich TI optical physics and applications in highly efficient optical functionalities as well as artificial magnetic materials at high frequencies.

12.
J Hazard Mater ; : 124601, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33250312

RESUMO

The past several decades have witnessed tremendous research to discover ways for controlling heavy metal pollution, but most of the strategies do not involve reuse of the captured heavy metals. Herein, we propose a graphene oxide -based strategy for the effective removal of Cu2+ ions from water, coupled with their reuse as an antibacterial agent. Using GO nanosheets as an adsorbent and nanosupport, the Cu2+ ions were effectively extracted from water (>99.9%) and reduced in situ to copper nanoparticles (Cu NPs) containing both crystalline Cu and Cu2O. The as-captured Cu NPs showed efficient in vitro antibacterial ability against Escherichia coli, reducing the bacteria from 109 to 101 CFU mL-1 by using 1 mg mL-1 Cu NPs/GO NSs for 1 h. The minimum inhibitory concentration determined to be only 16 µg mL-1. For practical applications, Cu recovered from wastewater could reduce bacteria by 8 log CFU in 1 h. The recovered Cu was still able to reduce the bacteria by 7 log CFU after 2 months of storage in an argon atmosphere. This strategy of extracting heavy metals and subsequently reutilizing to kill bacteria will be of great significance for environmental remediation and public healthcare.

13.
J Med Chem ; 63(22): 14067-14086, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33191745

RESUMO

Mithramycin A (MTM) inhibits the oncogenic transcription factor EWS-FLI1 in Ewing sarcoma, but poor pharmacokinetics (PK) and toxicity limit its clinical use. To address this limitation, we report an efficient MTM 2'-oxime (MTMox) conjugation strategy for rapid MTM diversification. Comparative cytotoxicity assays of 41 MTMox analogues using E-twenty-six (ETS) fusion-dependent and ETS fusion-independent cancer cell lines revealed improved ETS fusion-independent/dependent selectivity indices for select 2'-conjugated analogues as compared to MTM. Luciferase-based reporter assays demonstrated target engagement at low nM concentrations, and molecular assays revealed that analogues inhibit the transcriptional activity of EWS-FLI1. These in vitro screens identified MTMox32E (a Phe-Trp dipeptide-based 2'-conjugate) for in vivo testing. Relative to MTM, MTMox32E displayed an 11-fold increase in plasma exposure and improved efficacy in an Ewing sarcoma xenograft. Importantly, these studies are the first to point to simple C3 aliphatic side-chain modification of MTM as an effective strategy to improve PK.

14.
J Cancer ; 11(24): 7146-7156, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193877

RESUMO

Background: Circular RNAs (circRNAs), a novel class of endogenous noncoding RNAs, are involved in a variety of diseases, including several types of cancers. We hypothesized that circRNAs are involved in the tumorigenesis and development of clear cell renal cell carcinoma (ccRCC). Methods: To verify our hypothesis, we explored the circRNA expression profiles in 4 pairs of ccRCC tissues and their adjacent non-carcinoma tissues via microarray analysis. Selected circRNAs were further validated by qPCR. Moreover, hsa_circ_0005875 was selected for further study and the potential clinical values of hsa_circ_0005875 were investigated in 60 pairs of ccRCC tissues and adjacent normal controls. In addition, the role of hsa_circ_0005875 in ccRCC progression were performed using colony formation assay, Transwell assay and Martrigel-Transwell assay respectively. Finally, interactions between the circRNAs and miRNAs were predicted using Arraystar's miRNA target prediction software. Luciferase reporter assays were performed to evaluate the interaction between hsa_circ_0005875 and hsa_miR-145-5p. Results: The microarray data showed 1988 circRNAs were significantly dysregulated circRNAs, including 1033 upregulated and 955 downregulated ones in the ccRCC tissues. Hsa_circ_0005875 was confirmed to be significantly upregulated in the ccRCC tumor tissues and renal carcinoma cells. Further analysis revealed that hsa_circ_0005875 expression was associated with tumor size, pathological TNM stage, histological differentiation, and lymphatic metastasis. Functional experiments demonstrated that overexpression of hsa_circ_0005875 increased proliferation, migration and invasion abilities. Moreover, bioinformatics analysis and luciferase reporter assays suggest that hsa_circ_0005875 may serve as a ceRNA (competing endogenous RNA) of miR-145-5p to relieve the repressive effect of miR-145-5p on target ZEB2. Conclusions: These data indicate that hsa_circ_0005875 might play a role in promoting tumor growth and metastasis and be a potential biomarker of ccRCC.

15.
Eur J Med Chem ; 207: 112784, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33007722

RESUMO

Exosomes are cystic vesicles secreted by living cells with a phospholipid bilayer membrane. Importantly, these vesicles could serve to carry lipids, proteins, genetic materials, and transmit biological information in vivo. The cell-specific proteins and genetic materials in exosomes are capable of reflecting their cell origin and physiological status. Based on the different tissues and cells (macrophage, dendritic cells, tumor cells, mesenchymal stem cells, various body fluids, and so on), exosomes exhibit different characteristics and functions. Furthermore, owing to their high delivery efficiency, biocompatibility, and multifunctional properties, exosomes are expected to become a new means of drug delivery, disease diagnosis, immunotherapy, and precise treatment. At the same time, in order to supplement or enhance the therapeutic applicability of exosomes, chemical or biological modifications can be used to broaden, change or improve their therapeutic capabilities. This review focuses on three aspects: the characteristics and original functions of exosomes secreted by different cells, the modification and transformation of exosomes, and the application of exosomes in different diseases.

16.
J Hazard Mater ; : 124063, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33092878

RESUMO

Phytoremediation offers a great potential for affordable remediation of heavy metal (HM)-polluted soil and water. Screening and identifying candidate genes related to HM uptake and transport is prerequisite for improvement of phytoremediation by genetic engineering. Using the cadmium (Cd)-hypersensitive Populus euphratica, an annexin encoding gene facilitating Cd enrichment was identified in this study. With a 12 h exposure to CdCl2 (50-100 µM), P. euphratica cells down-regulated transcripts of annexin1 (PeANN1). PeANN1 was homologue to Arabidopsis annexin1 (AtANN1) and localized mainly to the plasma membrane (PM) and cytosol. Compared with wild type and Atann1 mutant, PeANN1 overexpression in Arabidopsis resulted in a more pronounced decline in survival rate and root length after a long-term Cd stress (10 d, 50 µM), due to a higher cadmium accumulation in roots. PeANN1-transgenic roots exhibited enhanced influx conductance of Cd2+ under cadmium shock (30 min, 50 µM) and short-term stress (12 h, 50 µM). Noteworthy, the PeANN1-facilitated Cd2+ influx was significantly inhibited by a calcium-permeable channel (CaPC) inhibitor (GdCl3) but was promoted by 1 mM H2O2, indicating that Cd2+ entered root cells via radical-activated CaPCs in the PM. Therefore, PeANN1 can serve as a candidate gene for improvement of phytoremediation by genetic engineering.

17.
Cell Death Dis ; 11(9): 770, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943612

RESUMO

Gypenosides, extracts of Gynostemma yixingense, have been traditionally prescribed to improve metabolic syndrome in Asian folk and local traditional medicine hospitals. However, the mechanism of its action remains unclarified. In this work, our results indicated that chronic administration of 2α-OH-protopanoxadiol (GP2), a metabolite of gypenosides in vivo, protected mice from high-fat diet-induced obesity and improved glucose tolerance by improving intestinal L-cell function. Mechanistically, GP2 treatment inhibited the enzymatic activity of bile salt hydrolase and modulated the proportions of the gut microbiota, which led to an increase in the accumulation of tauro-ß-muricholic acid (TßMCA) in the intestine. TßMCA induced GLP-1 production and secretion by reducing the transcriptional activity of nuclear receptor farnesoid X receptor (FXR). Transplantation of GP2-remodelled fecal microbiota into antibiotic-treated mice also increased the intestinal TßMCA content and improved intestinal L-cell function. These findings demonstrate that GP2 ameliorates metabolic syndrome at least partly through the intestinal FXR/GLP-1 axis via gut microbiota remodelling and also suggest that GP2 may serve as a promising oral therapeutic agent for metabolic syndrome.

18.
Cancer Cell Int ; 20: 453, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32944001

RESUMO

Background: It has been well documented that long non-coding RNAs (lncRNAs) regulate numerous characteristics of cancer, including proliferation, migration, metastasis, apoptosis, and even metabolism. LncRNA BCYRN1 (BCYRN1) is a newly identified brain cytoplasmic lncRNA with 200 nucleotides that was discovered to be highly expressed in tumour tissues, including those of hepatocellular carcinoma, gastric cancer and lung cancer. However, the roles of BCYRN1 in colorectal cancer (CRC) remain obscure. This study was designed to reveal the role of BCYRN1 in the occurrence and progression of CRC. Methods: RT-PCR was used to detect the expression level of BCYRN1 in tumour tissues and CRC cell lines. BCYRN1 was knocked down in CRC cells, and cell proliferation changes were evaluated by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and Ki-67 and proliferating cell nuclear antigen (PCNA) expression assays. Cell migration and invasion changes were evaluated by wound healing, Transwell and invasion-related protein expression assays. Flow cytometry analysis was used to assess whether BCYRN1 regulates the apoptosis of CRC cells. The dual luciferase reporter gene detects the competitive binding of BCYRN1 to miR-204-3p. In vivo experiments were performed to evaluate the effect of BCYRN1 on tumour development. TargetScan analysis and dual luciferase reporter gene assays were applied to detect the target gene of miR-204-3p. Rescue experiments verified that BCYRN1 affects CRC by regulating the effect of miR-204-3p on KRAS. Results: We found that compared with normal tissues and human intestinal epithelial cells (HIECs), CRC tumour tissues and cell lines had significantly increased BCYRN1 levels. We further determined that knockdown of BCYRN1 inhibited the proliferation, migration, and invasion and promoted the apoptosis of CRC cells. In addition, bioinformatics analysis and dual luciferase reporter assay showed that BCYRN1 served as a competitive endogenous RNA (ceRNA) to regulate the development of CRC through competitively binding to miR-204-3p. Further studies proved that overexpression of miR-204-3p reversed the effects of BCYRN1 on CRC. Next, TargetScan analysis and dual luciferase reporter assay indicated that KRAS is a target gene of miR-204-3p and is negatively regulated by miR-204-3p. A series of rescue experiments showed that BCYRN1 affected the occurrence and development of CRC by regulating the effects of miR-204-3p on KRAS. In addition, tumorigenesis experiments in a CRC mouse model confirmed that BCYRN1 downregulation effectively inhibited tumour growth. Conclusions: Our findings suggest that BCYRN1 plays a carcinogenic role in CRC by regulating the miR-204-3p/KRAS axis.

19.
Org Biomol Chem ; 18(37): 7414-7424, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32936186

RESUMO

The dirhodium tetraacetate-catalyzed iminoiodane-mediated reaction of 1,3-dimethyl-5-vinyluracil with phenyl sulfamate provided a high yield of 5-(1-acetyl-2-phenylsulfamoyl)ethyluracil via regioselective nucleophilic ring opening by acetate anion of the transiently formed 5-(1,2)-N-phenylsulfonylaziridine intermediate. This 1,2-oxyamidation reaction was found to be general for a variety of aryl- and alkylsulfamates as well as for various 1,3-dialkyl-5-vinyluracil derivatives. Addition of an alcohol to the reaction mixture allowed formation of the corresponding 1-alkoxy products. A selection of the substituted uracil derivatives prepared by this procedure was evaluated for cytotoxic activities in HCT-116 and HepG2 cancer cell lines and showed either no or modest activities. Further evaluation for α-glucosidase inhibition revealed that compounds 15ca and 15da were more active than acarbose, the reference inhibitor. This methodology thus allows efficient preparation of highly functionalized uracil derivatives thereby providing a synthetic route to novel compounds with potentially useful biological activities.

20.
Nano Lett ; 20(11): 7811-7818, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-32833464

RESUMO

Owing to its good air stability and high refractive index, two-dimensional (2D) noble metal dichalcogenide shows intriguing potential for versatile flat optics applications. However, light field manipulation at the atomic scale is conventionally considered unattainable because the small thickness and intrinsic losses of 2D materials completely suppress both resonances and phase accumulation effects. Here, we demonstrate that losses of structured atomically thick PtSe2 films integrated on top of a uniform substrate can be utilized to create the spots of critical coupling, enabling singular phase behaviors with a remarkable π phase jump. This finding enables the experimental demonstration of atomically thick binary meta-optics that allows an angle-robust and high unit thickness diffraction efficiency of 0.96%/nm in visible frequencies (given its thickness of merely 4.3 nm). Our results unlock the potential of a new class of 2D flat optics for light field manipulation at an atomic thickness.

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