Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 849
Filtrar
1.
Radiology ; : 191086, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793849

RESUMO

Background American College of Radiology contrast agent-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) was developed to improve the accuracy of hepatocellular carcinoma (HCC) diagnosis at contrast agent-enhanced US. However, to the knowledge of the authors, the diagnostic accuracy of the system in characterization of liver nodules 20 mm or smaller has not been fully evaluated. Purpose To evaluate the diagnostic accuracy of CEUS LI-RADS in diagnosing HCC in liver nodules 20 mm or smaller in patients at risk for HCC. Materials and Methods Between January 2015 and February 2018, consecutive patients at risk for HCC presenting with untreated liver nodules 20 mm or less were enrolled in this retrospective double-reader study. Each nodule was categorized according to the CEUS LI-RADS and World Federation for Ultrasound in Medicine and Biology (WFUMB)-European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) criteria. Diagnostic performance of CEUS LI-RADS and WFUMB-EFSUMB characterization was evaluated by using tissue histologic analysis, multiphase contrast-enhanced CT and MRI, and imaging follow-up as reference standard and compared by using McNemar test. Results The study included 175 nodules (mean diameter, 16.1 mm ± 3.4) in 172 patients (mean age, 51.8 years ± 10.6; 136 men). The sensitivity of CEUS LR-5 versus WFUMB-EFSUMB criteria in diagnosing HCC was 73.3% (95% confidence interval [CI]: 63.8%, 81.5%) versus 88.6% (95% CI: 80.9%, 94%), respectively (P < .001). The specificity of CEUS LR-5 versus WFUMB-EFSUMB criteria was 97.1% (95% CI: 90.1%, 99.7%) versus 87.1% (95% CI: 77%, 94%), respectively (P = .02). No malignant lesions were found in CEUS LR-1 and LR-2 categories. Only two nodules (of 41; 5%, both HCC) were malignant in CEUS LR-3 category. The incidences of HCC in CEUS LR-4, LR-5, and LR-M were 48% (11 of 23), 98% (77 of 79), and 75% (15 of 20), respectively. Two of 175 (1.1%) histologic analysis-confirmed intrahepatic cholangiocarcinomas were categorized as CEUS LR-M by CEUS LI-RADS and misdiagnosed as HCC by WFUMB-EFSUMB criteria. Conclusion The contrast-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) algorithm was an effective tool for characterization of small (≤20 mm) liver nodules in patients at risk for hepatocellular carcinoma (HCC). Compared with World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology criteria, CEUS LR-5 demonstrated higher specificity for diagnosing small HCCs with lower sensitivity. Published under a CC BY 4.0 license. See also the editorial by Crocetti in this issue.

2.
Blood Adv ; 3(22): 3818-3828, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31770438

RESUMO

We previously reported the discovery of a novel lipid deacetylase in platelets, arylacetamide deacetylase-like 1 (AADACL1/NCEH1), and that its inhibition impairs agonist-induced platelet aggregation, Rap1 GTP loading, protein kinase C (PKC) activation, and ex vivo thrombus growth. However, precise mechanisms by which AADACL1 impacts platelet signaling and function in vivo are currently unknown. Here, we demonstrate that AADACL1 regulates the accumulation of ether lipids that impact PKC signaling networks crucial for platelet activation in vitro and in vivo. Human platelets treated with the AADACL1 inhibitor JW480 or the AADACL1 substrate 1-O-hexadecyl-2-acetyl-sn-glycerol (HAG) exhibited decreased platelet aggregation, granule secretion, Ca2+ flux, and PKC phosphorylation. Decreased aggregation and secretion were rescued by exogenous adenosine 5'-diphosphate, indicating that AADACL1 likely functions to induce dense granule secretion. Experiments with P2Y12-/- and CalDAG GEFI-/- mice revealed that the P2Y12 pathway is the predominate target of HAG-mediated inhibition of platelet aggregation. HAG itself displayed weak agonist properties and likely mediates its inhibitory effects via conversion to a phosphorylated metabolite, HAGP, which directly interacted with the C1a domains of 2 distinct PKC isoforms and blocked PKC kinase activity in vitro. Finally, AADACL1 inhibition in rats reduced platelet aggregation, protected against FeCl3-induced arterial thrombosis, and delayed tail bleeding time. In summary, our data support a model whereby AADACL1 inhibition shifts the platelet ether lipidome to an inhibitory axis of HAGP accumulation that impairs PKC activation, granule secretion, and recruitment of platelets to sites of vascular damage.

3.
Life Sci ; 239: 116928, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682848

RESUMO

AIM: The dysfunction of human pulmonary arterial smooth muscle cells (HPASMCs) has been suggested to participate in the pathophysiology of pulmonary arterial hypertension (PAH). This study determined miR-19a expression in hypoxia-induced HPASMCs and explored the mechanistic actions of miR-19a in hypoxia-induced HPASMC proliferation and migration. METHODS: QRT-PCR and western blot assays respectively determined the mRNA and protein expression of miR-19a, phosphatase and tensin homolog (PTEN) and hypoxia-inducible factor-1 alpha (HIF-1α). In vitro functional assays determined HPASMC proliferation and migration, respectively. Luciferase reporter assay determined interaction between miR-19a and PTEN. The knockdown effects of miR-19a on PAH were confirmed in in vivo mice model. RESULTS: Hypoxia treatment time-dependently up-regulated miR-19a expression and enhanced cell proliferation in HPASMCs. MiR-19a overexpression increased cell proliferation and migration of HPASMCs, while repression of miR-19a reduced cell proliferative and migratory potentials of hypoxia-treated HPASMCs. Bioinformatics analysis and luciferase reporter assay showed that PTEN 3' untranslated region was targeted by miR-19a, and miR-19a repressed the mRNA and protein expression of PTEN in HPASMCs. Further rescue studies revealed that miR-19a regulated proliferative and migratory potentials of hypoxia-treated HPASMCs via suppressing PTEN expression. In addition, HIF-1α was identified as one of the mediators for the hypoxia-induced aberrant expression levels of miR-19a and PTEN. MiR-19a overexpression enhanced PI3K/AKT signaling, which was attenuated by enforced expression of PTEN in HPASMCs. More importantly, knockdown of miR-19 attenuated the chronic hypoxia-induced PAH in in vivo mice model. CONCLUSION: This study presented a novel mechanistic action of miR-19a-mediated cell proliferation and migration of HPASMCs.

4.
BMC Med Genet ; 20(1): 173, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706281

RESUMO

BACKGROUND: Familial hypercholesterolemia (FH), an autosomal dominant genetic disorder, is underdiagnosed and undertreated. The majority of FH cases are caused by low density lipoprotein receptor (LDL-R) gene mutations. The C308Y mutation in LDL-R results in approximately 70% loss of LDL-R activity, leading to the elevation of low density lipoprotein-cholesterol (LDL-C) and an increased risk of premature coronary heart disease (CHD). The aim of this study was to identify FH cases by cascade screening in family members and relatives of a 37-year old male with premature CHD and hypercholesterolemia. METHODS: Clinical exam, blood lipid profiling and genomic DNA sequencing of all exons of LDL-R were performed for the proband and his 14 family members and relatives. FH diagnosis was carried out using the Dutch Lipid Clinic Network (DLCN) criteria. RESULTS: Lipid profiling showed that 9 individuals, including the proband, had hypercholesterolemia. All these 9 subjects had a G > A substitution at nucleotide 986 in exon 7 resulting in the C308Y mutation as determined by DNA sequencing, and all those carrying the mutation were diagnosed as having definite FH under the DLCN criteria. However, most (7/9) did not have suggestive clinical manifestations of CHD. CONCLUSIONS: The C308Y mutation was discovered in multiple family members and relatives for the first time in mainland China. Cascade screening is key for the confirmatory diagnosis of FH. Our hypothesis that the C308Y is a common variant in the population of Southern China origin warrants further validation by screening for the C308Y mutation in a large population.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31727519

RESUMO

In recent years, spectral quantitative analysis for blood components has been a research hotspot in biomedical engineering. But researches have been limited to the application of high-sensitivity spectroscopy instruments and the complexity of blood components-the overlapping of absorption curves for many components is severe. This has led to the difficulty in achieving satisfactory results when using spectroscopy to quantify components in blood. In order to enhance the model robustness and improve the model performance, this paper proposed a sample set partitioning strategy based on multi-component spatial distance (SSP-MCSD). Different from the other sample set partitioning strategies, which only consider the uniformity of the concentration distribution of the target component, this strategy also concerns to the concentration distribution of non-target components. The concentration of the target component and non-target components are used to construct a multi-dimensional space, and the Euclidean Distance of sample points in this space is used as the criterion to partition the sample set. At the same time, the spectra collected in multi-modes are fused for increasing the amount of information. So as to enhance the model robustness and to improve the analysis accuracy of the target components. In order to verify the effectiveness of this strategy, the serum of 101 volunteers was analyzed. Taking total protein in serum as the non-target component, the regression model for bilirubin concentration was established by transmission spectra, fluorescence spectra, and the joint spectra after fusion of the above two spectra, respectively. The experimental results showed that the prediction accuracy of the model established by SSP-MCSD combined with multi-mode spectral fusion is obviously higher than that of other methods. It can effectively improve the analysis accuracy of blood components.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31696588

RESUMO

A microfluidic assembly method based on microfluidic chip and capillary device was developed for deftly manipulating microfluid that can be employed to create multi-compartmental particles. he ingenious microfluidic chip design endows the particles with regulable internal structure. The high degree of control afforded by the capillary device achieves the ideal particle geometry. By adjusting the microstructure of the chip, the diameter of the capillary, the gap length between the two microfluidic components and the flow rates, the size of the particles and the number or the ratio of different regions within the particle could be widely variable on demand. As convincing proof, we have found some complicated particles that even contains twenty sub-compartments, which has never been reported earlier. Additionally, the potential application of the anisotropic particles is explored for integrating magnetic-actuator unit, fluorescent-identifier unit and the cell-laden unit into a particle. We believe that this method will open new avenues for the design and application of multi-compartmental particles.

7.
Appl Opt ; 58(28): 7836-7843, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674467

RESUMO

The extraction of effective information in visible-near-infrared (VIS-NIR) spectroscopy is crucial and difficult for spectral analysis. In this research, an algorithm of wavelet feature extraction based on the Gaussian kernel function (GKF-WTEF) was developed to suppress the influence of external interference on VIS-NIR spectroscopy and improve the accuracy of quantitative analysis. This algorithm takes the root-mean-square error of the prediction set (RMSEP) of the model, which is established by partial least-squares regression, as the optimization criteria. First, the optimal type of wavelet function, the decomposition level, and the Gauss kernel function central frequency band are determined according to the RMSEP. Second, the Gauss kernel function bandwidth is determined by Newton's method. Then, the Hadamard product of the Gaussian kernel function and the wavelet coefficient is obtained. Finally, the wavelet coefficients after the Hadamard product can be reconstructed to obtain the spectral data after feature extraction. In order to verify the effectiveness of this algorithm, the difference in the optical parameters of the polyvinyl chloride material container was used as an external interference source. And the spectrum of Intra-lipid and India-ink mixed solution with different concentrations was collected therein. The volume fraction of India-ink in complex mixed solution was quantitatively analyzed by using the RMSEP and the average relative error of the prediction set as the evaluation criteria. The research results demonstrated that the Gaussian-wavelet transform feature extraction algorithm is an effective pretreatment method, it can satisfactorily suppress the influence of external interference on the spectrum, and it can improve the analytical accuracy of VIS-NIR spectroscopy.

8.
PLoS Negl Trop Dis ; 13(11): e0007829, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31765414

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus is an emerging infectious disease that was first identified in the rural areas of China in 2011. Severe cases often result in death due to multiple organ failure. To date, there are still numerous problems remain unresolved in SFTS, including unclear pathogenesis, lack of specific treatment, and no effective vaccines available. AIM: To analyze the clinical information of patients with early-stage SFTS and to establish a nomogram for the mortality risk. METHODS: Between April 2011 and December 2018, data on consecutive patients who were diagnosed with SFTS were prospectively collected from five medical centers distributed in central and northeastern China. Multivariable Cox analyses were used to identify the factors independently associated with mortality. A nomogram for mortality was established using those factors. RESULTS: During the study period, 429 consecutive patients were diagnosed with SFTS at the early stage of the disease (within 7 days of fever), among whom 69 (16.1%) died within 28 days. The multivariable Cox proportional hazard regression analysis showed that low lymphocyte percentage, early-stage encephalopathy, and elevated concentration of serum LDH and BUN were independent risk factors for fatal outcomes. Received-operating characteristic curves for 7-, 14-, and 28-days survival had AUCs of 0.944 (95% CI: 0.920-0.968), 0.924 (95% CI: 0.896-0.953), and 0.924 (95% CI: 0.895-0.952), respectively. Among low-risk patients, 6 patients died (2.2%). Among moderate-risk patients, 25 patients died (24.0%, hazard ratio (HR) = 11.957). Among high-risk patients, the mortality rate was 69.1% (HR = 57.768). CONCLUSION: We established a simple and practical clinical scoring system, through which we can identify critically ill patients and provide intensive medical intervention for patients as soon as possible to reduce mortality.

9.
Waste Manag Res ; : 734242X19886912, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769349

RESUMO

Based on the IPAT model, this study selects the two-order lag period that is then applied to the dynamic model created to explore the impact of China's urbanization on the quantity of municipal solid waste (MSW) produced. The study uses panel data collected from 27 provinces, autonomous regions, and municipalities in China that report directly to the central government. Results show that nationwide urbanization and urban per capita disposable income are positively correlated with the quantity of MSW produced. However, specifically, urbanization in the eastern and midwestern areas of China is insignificantly correlated with the quantity of MSW produced. It is, therefore, recommended that citizens should make sensible and environmental consumption decisions based on per capita disposable income. It is also suggested that quality development and Stead's urbanization plan should become national policy, and that MSW categorization and a recycling policy should be implemented to treat MSW effectively.

10.
Small ; : e1903402, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769602

RESUMO

Cellular membranes are composed of a variety of lipids in different amounts and proportions, and alterations of them are usually closely related to various diseases. To reveal the intercellular heterogeneity of the lipid variation, an integrated microfluidic system is designed, which consists of droplet-based inkjet printing, dielectrophoretic electrodes, and de-emulsification interface to achieve on-line single-cell encapsulation, manipulation, and mass spectrometry (MS) detection. This integrated system effectively improves the single-cell encapsulation rate, and meanwhile reduces the matrix interference and continuous oil phase interference to the MS detection. Using this system, the heterogeneities between the normal and cancer cells are compared, and the heterogeneity of the same cells before and after the drug treatment changed obviously, indicating that this system can be used as a promising tool for studying the link between the alterations of lipid homeostasis and various diseases.

11.
Curr Med Chem ; 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584362

RESUMO

The next-generation immunotherapy can only be effective if researchers have an in-depth understanding of the function and regulation of Treg cells in antitumor immunity combined with the discovery of new immunity targets. This can enhance clinical efficacy of future and novel therapies and reduces any adverse reactions arising from the latter. This review discusses tumor treatment strategies using regulatory T (Treg) cell therapy in a tumor microenvironment (TME). It also discusses factors affecting TME instability as well as relevant treatments to prevent future immune disorders. It is prognosticated that PD-1 inhibitors are risky and their adverse effects should be taken into account when they are administered to treat acute myeloid leukemia (AML), lung adenocarcinoma, and prostate adenocarcinoma. In contrast, Treg molecular markers FoxP3 and CD25 analyzed here have stronger expression in almost all kinds of cancers compared with normal people. However, CD25 inhibitors are more effective compared to FoxP3 inhibitors, especially in combination with TGF-ß blockade, in predicting patient survival. According to the data obtained from the Cancer Genome Atlas, we then concentrate on AML immunotherapy and discuss different therapeutic strategies including anti-CD25/IL-2, anti-CTLA-4, anti-IDO, antityrosine kinase receptor, and anti-PI3K therapies and highlight the recent advances and clinical achievements in AML immunotherapy. In order to prognosticate the risk and adverse effects of key target inhibitors (namely against CTLA-4, FoxP3, CD25, and PD-1), we finally analyzed and compared the Cancer Genome Atlas derived from ten common cancers. This review shows that Treg cells are strongly increased in AML and the comparative review of key markers shows that Tregbased immunotherapy is not effective for all kinds of cancer. Therefore, blocking CD25(+)FoxP3(+) Treg cells is suggested in AML more than other kinds of cancer; meanwhile, Treg markers studied in other cancers have also great lessons for AML immunotherapy.

12.
Phys Rev Lett ; 123(10): 101601, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31573320

RESUMO

We present O(10^{15}) string compactifications with the exact chiral spectrum of the standard model of particle physics. This ensemble of globally consistent F-theory compactifications automatically realizes gauge coupling unification. Utilizing the power of algebraic geometry, all global consistency conditions can be reduced to a single criterion on the base of the underlying elliptically fibered Calabi-Yau fourfolds. For toric bases, this criterion only depends on an associated polytope and is satisfied for at least O(10^{15}) bases, each of which defines a distinct compactification.

13.
Br J Radiol ; 92(1104): 20190526, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31595778

RESUMO

OBJECTIVE: Unsuspected pulmonary embolism (UPE) has been increasingly diagnosed as an incidental finding on CT scans for routine staging in cancer patients. Previous studies suggest that obesity is an independent risk factor for venous thromboembolism in patients with malignant tumors. In this study, we aimed to investigate the association between abdominal adipose tissue, especially visceral adipose tissue (VAT) and the occurrence of UPE in hospitalized patients with gastrointestinal cancer. METHODS: Routine contrast-enhanced chest and abdominal CT scans of 1974 patients were retrospectively assessed for the presence of UPE, of which 58 patients were identified with UPE and 108 non-UPE patients were selected as the non-UPE control group based on several matching criteria. Abdominal adipose tissue was measured by volumes of VAT and subcutaneous adipose tissue (SAT) at the navel level. RESULTS: VAT, SAT, indwelling venous catheters, surgery, chemotherapy, and bed rest or immobilization were associated with the occurrence of UPE. Higher VAT volumes were associated with increased risk of UPE (odds ratio: 1.96; 95% confidence interval: 1.25, 3.06; p = 0.003) adjusting body mass index (BMI), bed rest or immobilization, surgery, chemotherapy and smoking, while SAT was not associated with UPE adjusting the same confounders (p = 0.117). No statistical association was found between BMI and UPE (p = 0.102). CONCLUSION: Higher VAT rather than SAT is associated with an increased risk of unsuspected pulmonary embolism on routine CT scans in hospitalized gastrointestinal cancer patients. ADVANCES IN KNOWLEDGE: Our findings indicate that VAT is a stronger risk factor for unsuspected pulmonary embolism than BMI and SAT in hospitalized patients with gastrointestinal cancer.


Assuntos
Embolia Gordurosa/etiologia , Gordura Intra-Abdominal/diagnóstico por imagem , Embolia Pulmonar/etiologia , Gordura Subcutânea Abdominal/diagnóstico por imagem , Idoso , Repouso em Cama/efeitos adversos , Índice de Massa Corporal , Estudos de Casos e Controles , Cateteres de Demora/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Embolia Gordurosa/diagnóstico por imagem , Feminino , Neoplasias Gastrointestinais , Humanos , Imobilização/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Embolia Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco
14.
Cell Cycle ; 18(21): 2939-2953, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31522588

RESUMO

Background: Hepatocellular carcinoma (HCC) afflicts more than half a million people each year worldwide. It was reported that circ_0015756 was up-regulated in HCC, but the mechanism did not extensively studied. Methods: we collected 24 paired cancerous and noncancerous liver tissues surgically resected from HCC patients. HCC cell proliferation, invasion, migration and apoptosis in vitro were evaluated using MTT assay, Transwell assay, scratch test and Annexin-V/PI staining respectively. Interactions between circ_0015756 and miR-7, miR-7 and FAK were further validated by the luciferase reporter assay. Tumor xenografts of HCC cells with circ_0015756 knockdown were established in nude mice. Results: The expression level of circ_0015756 was increased and the expression level of miR-7 was diminished in cancerous liver tissues relative to noncancerous liver tissues. Circ_0015756 knockdown was shown to increase the expression of miR-7, reduce the proliferation, invasion, migration and resistance to apoptosis, and down-regulate the expression of FAK in HCC. We found miR-7 impaired expression of FAK to inhibit HCC cells, suggesting that miR-7 is responsible for the dysfunction of FAK. Importantly, we showed circ_0015756 could up-regulate FAK via targeting miR-7. These in vitro findings were reproduced in vivo that circ_0015756 knockdown decreased HCC xenograft growth. Conclusion: Our present study reveals a model of HCC development that is composed of circ_0015756, miR-7 and FAK. Modulation of their levels exhibits a promise in the treatment of HCC. Abbreviations: HCC: hepatocellular carcinoma; circRNAs: circular RNAs; miRNA/miR: microRNA; miR-7: microRNA-7; FAK: focal adhesion kinase; KLF-4: kruppel like factor 4; DKK1: dickkopf WNT signaling pathway inhibitor 1; ccRCC: clear cell renal cell carcinoma; PI3K: phosphoinositide 3-kinase; Ct: comparative threshold cycle; RPMI: Roswell Park Memorial Institute; FBS: fetal bovine serum; RT: reverse transcription; qPCR: quantitative polymerase chain reaction; RIPA: radioimmunoprecipitation assay; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; PVDF: polyvinylidene difluoride; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; DMSO: dimethyl sulfoxide; DMEM: Dulbecco's modified Eagle's medium; PI: propidium iodide; SPF: specific pathogen-free; SD: standard deviation; p-Akt: phosphorylated-Akt; shRNAs: small hairpin RNAs; 3'UTR: 3'-untranslated regions.

15.
Phys Rev Lett ; 123(6): 067601, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31491163

RESUMO

Within Landau theory, magnetism and polarity are homotopic, displaying a one-to-one correspondence between most physical characteristics. However, despite widely reported noncollinear magnetism, spontaneous noncollinear electric dipole order as a ground state is rare. Here, a dioxydihalides family is predicted to display noncollinear ferrielectricity, induced by competing ferroelectric and antiferroelectric soft modes. This intrinsic of dipoles generates unique physical properties, such as Z_{2}×Z_{2} topological domains, atomic-scale dipole vortices, and negative piezoelectricity.

16.
Org Lett ; 21(18): 7424-7429, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31487185

RESUMO

A strategically novel Pd-catalyzed nucleophilic addition induced allylic alkylation reaction (NAAA) of allenoates has been successfully accomplished. By judiciously integrating ZnCl2-promoted Michael addition with Pd-catalyzed allylic alkylation, allenoates readily undergo allyl-sunfonylation at the internal double bond, thus providing a straightforward avenue for the rapid assembly of a host of structurally diversified α-allyl-ß-sufonylbut-3-enoate derivatives. The success of this transformation profits from a delicate control of the reaction kinetic of each elementary step, thanks to the synergistic interaction of Pd/Zn bimetallic system, thus suppressing either direct allylic sulfonylation or premature quenching of therein in situ generated ester enolate intermediate. Furthermore, by expanding the scope of workable Michael acceptor beyond those previously required doubly activated ones, such as methylenemalononitrile, the present work substantially enriches the repertoire of NAAA reactions.

17.
Biomed Res Int ; 2019: 9454913, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534969

RESUMO

Aim: To investigate the effect of crocin on the learning and memory acquisition of AD rats and its underlying mechanisms. Methods: A total of 48 healthy male SD rats were randomly divided into control group, AD model group, resveratrol group, and crocin group, with 12 rats per group. AD model was established by injecting Aß 25-35 to the lateral ventricle of rats, and thereafter the rats were administrated with resveratrol (40 mg/kg), crocin (40 mg/kg), or PBS daily for 14 days. Y-maze test and sucrose preference test were used to detect the learning and memory acquisition of rats. Neuronal apoptosis was detected by TUNEL staining and Western blot for apoptosis-related proteins Bax, Bcl-2, and Caspase-3. Immunofluorescence staining and Western blot tests were used to detect the expression of glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) in hippocampal CA1 region (Hippo) and prefrontal cortical neurons (PFC). Results: The learning and memory abilities of AD rats were significantly decreased, which was significantly rescued by resveratrol and crocin. The apoptotic cell number of Hippo and PFC neurons in AD model group was significantly higher than that in control group (P<0.01), while resveratrol and crocin significantly decreased the apoptotic cell number in AD group (P<0.01). Compared with the control group, the expression of Bcl2 in PFC and hippo of AD model group was significantly decreased (P<0.01), while those of Bax, Caspase3, GRP78, and CHOP were significantly increased (P<0.01). Resveratrol and crocin could significantly reverse the expression of these proteins in AD rats (P<0.05). Conclusion: Crocin can improve the learning and memory ability of AD rats possibly by reducing endoplasmic reticulum stress and neuronal apoptosis.

18.
Dig Dis Sci ; 2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31377883

RESUMO

BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the highly selective autoimmune injury of small intrahepatic bile ducts. Studies reported that the cholangiocytes from PBC patients expressed significantly higher levels of both receptor activator of nuclear factor-kappa B (RANK) and its ligand RANKL. However, the accurate role of RANK/RANKL axis in PBC remains unclear. METHODS: Forty patients with PBC were enrolled according to the inclusion criteria. The biochemical parameters (alkaline phosphatase, ALP; gamma-glutamyltransferase, GGT; alanine aminotransferase, ALT; aspartate transaminase, AST; total bilirubin, TB) were collected at baseline and followed-up after 6 months of treatment with ursodeoxycholic acid (UDCA, 15 mg/kg d). Stages of PBC were diagnosed based on liver biopsy histopathology according to Nakanuma's criteria. RANK expression in hepatic tissues was detected by immunohistochemistry. The cellular immunofluorescence method was used to locate the distribution of RANK in the human intrahepatic biliary epithelial cells (HIBECs) cultured in vitro. HIBECs were treated with RANKL at a concentration of 100 ng/ml or transfected with RANK-overexpressing lentivirus (LV-RANK). CCK-8 assay and cell cycle assay were used to detect the cell proliferation. Real-time PCR was used to detect the expression of IL-6, E-cadherin, VCAM, ICAM-1, TNF-α, and CD80. RESULTS: RANK expression in liver biopsies from early PBC patients (stage I + stage II) was significantly lower than that from advanced PBC patients (stage III + stage IV) (1.7 ± 0.63 vs. 2.3 ± 0.45 scores, P < 0.05). High-RANK patients seemed to have better response to UDCA than low-RANK patients (88.9% vs. 40.9%, P < 0.05). The baseline biochemical parameters between the two groups were comparable. The decline percentages of ALP and GGT after UDCA treatment were more obvious in high-RANK patients than those in low-RANK patients (53.90% ± 9.82% vs. 23.93% ± 6.24%, P < 0.05; 74.11% ± 7.18% vs. 48.00% ± 8.17%, P < 0.05, respectively). HIBECs proliferation was significantly inhibited after treatment of RANKL or transfection with LV-RANK. Increased expression of IL-6 and E-cadherin was observed in HIBECs treated with RANKL or LV-RANK. CONCLUSION: The overall hepatic RANK expression was associated with disease severity and biochemical response in PBC patients. Activation of RANK/RANKL signaling pathway inhibited cholangiocytes proliferation in vitro. Our study suggested that RANK/RANKL pathway might be a potential target of immunotherapy of PBC based on its involvement in the occurrence and development of the disease.

19.
Anal Chem ; 91(19): 12283-12289, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31456388

RESUMO

Three-dimensional (3D) hydrogel microspheres have aroused increasing attention as an in vitro cell culture model. Yet the preservation of cells' original biological properties has been overlooked during model construction. Here we present an integrated microfluidic device to accomplish the overall process including cell-laden microsphere generation, online extraction, and dynamic-culture. The method extends the noninvasive and nonsuppression capabilities of the droplet preparation system and provides a constant microenvironment, which reduces intracellular oxidative stress damage and the accumulation of mitochondria. Compared to the conventional preparation method, the coculture model of tumor-endothelial construction on an integrated platform displays high-level angiogenic protein expression. We believe that this versatile and biocompatible platform will provide a more reliable analysis tool for tissue engineering and cancer therapy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA