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1.
Angew Chem Int Ed Engl ; : e202204967, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35510692

RESUMO

Cu-based metal-organic frameworks have attracted much attention for electrocatalytic CO2 reduction, but they are generally instable and difficult to control the product selectivity. We report flexible Cu(I) triazolate frameworks as efficient, stable, and tunable electrocatalysts for CO2 reduction to C2 H4 /CH4 . By changing the size of ligand side groups, the C2 H4 /CH4 selectivity ratio can be gradually tuned and inversed from 11.8 : 1 to 1 : 2.6, giving C2 H4 , CH4 , and hydrocarbon selectivities up to 51 %, 56 %, and 77 %, respectively. After long-term electrocatalysis, they can retain the structures/morphologies without formation of Cu-based inorganic species. Computational simulations showed that the coordination geometry of Cu(I) changed from triangular to tetrahedral to bind the reaction intermediates, and two adjacent Cu(I) cooperated for C-C coupling to form C2 H4 . Importantly, the ligand side groups controlled the catalyst flexibility by the steric hindrance mechanism, and the C2 H4 pathway is more sensitive than the CH4 one.

2.
J Cancer ; 13(6): 1914-1922, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399712

RESUMO

Background: The purpose of our dynamic nomogram is to help clinical select hepatocellular carcinoma (HCC) patients with transarterial chemoembolization (TACE) treatment advantages. Methods: In total, 1,135 patients with HCC admitted to the Beijing Ditan Hospital of Capital Medical University were enrolled in this study. We used a 7:3 random splits between a training set (n=796) and a validation set (n=339). The dynamic nomogram was established by multiple logistic regression and evaluated by the C-indices. We generated calibration plots, decision analysis curve and a clinical impact curve to assess the clinical usefulness of the nomogram. Macrovascular invasion (MVI) incidence curves were constructed using the Kaplan-Meier method and compared by the log-rank test. Results: Multivariate logistic regression analysis identified six risk factors independently associated with MVI: BCLC staging B vs 0-A (hazard ratio (HR): 2.350, 95% confidence interval (CI): 1.222-4.531; P = 0.010) and staging C vs 0-A (HR: 3.652, 95% CI: 1.212-11.184; P = 0.022), treatment -TACE (HR: 2.693, 95%CI: 1.824-3.987; P < 0.001), tumour size ≥3cm (HR: 2.239, 95%CI: 1.452-3.459; P < 0.001), É£-GGT ≥60 (HR: 1.685, 95%CI: 1.100-2.579; P = 0.016), AFP ≥400 (HR: 2.681, 95%CI: 1.692-4.248; P < 0.001) and CRP ≥5 (HR: 3.560, 95%CI: 2.361-5.388; P < 0.001). The C-indices was 0.817 and 0.829 in the training and validation sets, respectively. The calibration curves showed good agreement between the predicted probability and the actual probability by the dynamic nomogram. Conclusions: Our study developed and validated a dynamic nomogram including BCLC staging, treatment modality, tumour size, and three laboratory parameters (É£-GGT, AFP and CRP). It has good discrimination and accuracy, and provides a simple and reliable basis for clinical decision-making.

3.
Front Psychiatry ; 13: 827480, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35449566

RESUMO

Background: Nonsuicidal self-injury (NSSI) may be a type of addiction, that is characterized by cue reactivity. We aimed to explore the behavioral performance and neural reactivity during exposure to self-injury cues in adolescents with NSSI and major depressive disorder (MDD). Methods: Eighteen MDD patients, 18 MDD patients with NSSI, and 19 healthy controls (HC) were recruited to perform a two-choice oddball paradigm. All subjects were 12-18 years old. Neutral cues and self-injury related cues separately served as deviant stimuli. Difference waves in N2 and P3 (N2d and P3d) were derived from deviant waves minus standard waves. Accuracy cost and reaction time (RT) cost were used as behavioral indexes, while the N2d and P3d were used as electrophysiological indexes; the N2d reflects early conflict detection, and the P3d reflects the process of response inhibition. Results: No significant main effects of group or cue or an effect of their interaction were observed on accuracy cost and P3d latency. For RT cost, N2d amplitude, and N2d latency, there was a significant main effect of cue. For P3d amplitude, there was a significant main effect of cue and a significant group × cue interaction. In the NSSI group, the P3d amplitude with self-injury cues was significantly larger than that with neutral cues. However, there was no such effect in the MDD and HC groups. Conclusions: Adolescents with NSSI showed altered neural reactivity during exposure to self-injury cue. Further studies with larger sample sizes are needed to confirm our results.

4.
Food Chem ; 386: 132743, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35364494

RESUMO

In this work, a sensitive and cost-effective method for the quantitative analysis of azole pesticides residues in six medicinal plants was established based on magnetic cyclodextrin crosslinked with tetrafluoroterephthalonitrile (Fe3O4@TFN-CDPs) coupled with high-performance liquid chromatography (HPLC). Through characterization analysis, the outer shell of Fe3O4@TFN-CDPs has observed coating with a network of the polymer and forming a core-shell structure. Under the optimum conditions, the limits of detection (LODs) and limits of qualification (LOQs) of target pesticides were ranged from 0.011 to 0.106 µg Kg-1 and from 0.036 to 0.354 µg Kg-1, respectively. Finally, the achieved recoveries of pesticides in six medicinal samples fluctuated from 60.1% to 102.3%. Altogether, this method based on Fe3O4@TFN-CDPs composites provided a new idea for the analysis of trace pesticides in complicated matrices.


Assuntos
Resíduos de Praguicidas , Praguicidas , Plantas Medicinais , Azóis/análise , Cromatografia Líquida de Alta Pressão , Limite de Detecção , Fenômenos Magnéticos , Resíduos de Praguicidas/análise , Praguicidas/análise , Extração em Fase Sólida , Espectrometria de Massas em Tandem
5.
Clin Breast Cancer ; 2022 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-35248490

RESUMO

BACKGROUND: Limited data are available on the prognostic role of Ki-67 changes in residual tumors after neoadjuvant chemotherapy in primary inflammatory breast cancer (IBC) patients treated with trimodality therapy. This study aims to evaluate changes in Ki-67 associated with disease-free survival (DFS) and overall survival (OS) in IBC patients without pathological complete response. PATIENTS AND METHODS: We identified a cohort of primary IBC patients with matched pre- and posttreatment samples treated with anthracycline and taxane-based regimen. All patients had a pathological evaluation, including ER, PR, HER2 status, and Ki-67 expression performed both at diagnostic core biopsy and at final surgery. Kaplan-Meier and Cox proportional hazards methods were used to assess DFS and OS rates and their relationship with clinicopathological features. RESULTS: Two hundred and ten patients with stage III IBC were included. Sixty-three percent of residual tumors showed a decrease in Ki-67 positivity by at least 1%. The decrease of Ki-67 significantly correlated with better DFS (p = .001) and OS (P = .010) compared with no decrease, particularly in the luminal B-like and HER2-positive subgroups. The multivariate analysis showed that the decrease in Ki-67 level had a significant positive predictive value on DFS (HR = 0.47, 95% CI: 0.33-0.67; P< .001) and OS (HR = 0.59, 95% CI: 0.36-0.82; P= .004) in all IBC patients. CONCLUSION: The decrease of Ki-67 expression after neoadjuvant chemotherapy has a prognostic significance in IBC patients with residual disease. Evaluation of Ki-67 changes may help to identify subgroups of patients with worse outcome to receive novel treatment in this setting.

6.
Gland Surg ; 11(2): 341-351, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35284315

RESUMO

Background: This study investigated the socioeconomic and clinical factors affecting the proportion of breast conserving surgery (BCS) in China, to improve the proportion and success rate of BCS in Chinese breast cancer patients. Methods: Six hundred and forty breast cancer patients treated with BCS were compared with 700 selected breast cancer patients (controls) treated with modified radical mastectomy (MRM) in Tianjin Medical University Cancer Institute and Hospital from January 2005 to January 2018. Patients' socioeconomic and clinical factors were collected through telephone interviews or face-to-face interviews. A total of 5,660 BCS patients were enrolled to analyze independent factors affecting initial positive margins. Chi-squared test and multiple logistic regressions were used to examine factors associated with BCS. The locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method and the survival distribution between BCS and MRM groups was compared by log-rank test. Results: Breast cancer patients who were younger, lived in urban areas, had medical insurance, and higher levels of education and Personal income were more likely to choose BCS. We also observed that patients of Han nationality were more likely to choose BCS. Univariate analysis showed that the frozen section analysis (FSA) positive margin was significantly correlated with tumor distance from the nipple, preoperative magnetic resonance imaging (MRI) examination, T stage, pathological subtype, and lymphovascular invasion (LVI). Multivariate analysis showed the distance from the nipple, T stage, pathological subtype, and LVI, and no preoperative MRI examination were independent predictors of positive resection margins. Multivariate analysis of the correlation between MRI findings and positive resection margins revealed that tumor size, non-mass enhancement (NME), and malignant enhancement surrounding the tumor were independent predictors of positive resection margins. Conclusions: In China, socioeconomic factors largely influence the choice of surgical procedures for breast cancer patients. A gradual reduction in the influence of socioeconomic factors on the proportion of BCS is recommended. Furthermore, preoperative MRI should be encouraged in patients preparing for BCS. Clinicopathological characteristics and MRI findings are significantly associated with a positive resection margin in breast cancer patients.

7.
BMC Cancer ; 22(1): 185, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35180841

RESUMO

BACKGROUND: The number of young patients with hepatocellular carcinoma (HCC) is increasing, but whether patients of different ages have a survival advantage is unclear. This study was conducted to investigate whether age differences in the Barcelona Clinic Liver Cancer (BCLC) classification system contribute to the long-term survival outcomes of patients with HCC. METHODS: A total of 1602 patients with HCC admitted to the Beijing Ditan Hospital was included in this study. Patients were divided into younger (≤45 years) and older (> 45 years) groups. Factors determining overall survival and progression-free survival were analyzed using univariate and multivariate analyses with the Kaplan-Meier method and Cox proportional hazard regression model. We calculated the cumulative incidence function using the Fine-Gray model. The effect of mortality on age was also estimated using a restricted cubic spline. RESULTS: After matching, overall survival and progression-free survival were significantly better in younger patients than in older patients with BCLC stage 0-B (p = 0.015 and p = 0.017, respectively). In BCLC stage 0-B, all-cause mortality increased with age and increased rapidly around the age of 40 years (non-linear, p < 0.05). In BCLC stages 0-B, HCC-related and non-HCC-related deaths significantly differed between younger and older individuals (p = 0.0019). CONCLUSION: In stage BCLC 0-B, age affects the long-term prognosis of patients.


Assuntos
Fatores Etários , Carcinoma Hepatocelular/mortalidade , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Medição de Risco/estatística & dados numéricos , Adulto , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
8.
Mar Drugs ; 20(2)2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35200654

RESUMO

Demethylincisterol A3 (Sdy-1), a highly degraded sterol that we previously isolated from Chinese mangrove Rhizophora mucronata endophytic Pestalotiopsis sp. HQD-6, exhibits potent antitumor activity towards a variety of cancer cells. In this study, we further verified that Sdy-1 effectively inhibited the proliferation and migration of human liver (HepG2) and cervical cancer (HeLa) cells in vitro and it can induce cell apoptosis and arrest the cell cycle in the G1-phase. Mechanistically, we demonstrated that Sdy-1 executes its function via inhibition of the Wnt/ß-catenin signaling pathway. Sdy-1 may not inhibit the Wnt signaling pathway through the cascade reaction from upstream to downstream, but directly acts on ß-catenin to reduce its transcription level, thereby reducing the level of ß-catenin protein and further reducing the expression of downstream related proteins. The possible interaction between Sdy-1 and ß-catenin protein was further confirmed by molecular docking studies. In the nude mouse xenograft model, Sdy-1 can also significantly inhibit tumor growth. These results indicated that Sdy-1 is an efficient inhibitor of the Wnt signaling pathway and is a promising antitumor candidate for therapeutic applications.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Esteróis/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Células HeLa , Células Hep G2 , Humanos , Camundongos , Camundongos Nus , Simulação de Acoplamento Molecular , Rhizophoraceae/química , Esteróis/isolamento & purificação , Via de Sinalização Wnt/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Ann Hepatol ; 27(2): 100672, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35065261

RESUMO

INTRODUCTION: Among all immune cells, natural killer (NK) cells play an important role as the first line of defense against tumor. The purpose of our study is to observe whether the NK cell counts can predict the overall survival of patients with hepatocellular carcinoma (HCC). METHODS: To develop a novel model, from January 2010 to June 2015, HCC patients enrolled in Beijing Ditan hospital were divided into training and validation cohort. Cox multiple regression analysis was used to analyze the independent risk factors for 1-year, 3-year and 5-year overall survival (OS) of patients with HCC, and the nomogram was used to establish the prediction model. In addition, the decision tree was established to verify the contribution of NK cell counts to the survival of patients with HCC. RESULTS: The model used in predicting overall survival of HCC included six variables (namely, NK cell counts, albumin (ALB) level, alpha-fetoprotein (AFP) level, portal vein tumor thrombus (PVTT), tumor number and treatment). The C-index of nomogram model in HCC patients predicting 1-year, 3-year and 5-year overall survival was 0.858, 0.788 and 0.782 respectively, which was higher than tumor-lymph node-metastasis (TNM) staging system, Okuda, model for end-stage liver disease (MELD), MELD-Na, the Chinese University Prognostic Index (CUPI) and Japan Integrated Staging (JIS) scores (p < 0.001). The decision tree showed the specific 5-year OS probability of HCC patients under different risk factors, and found that NK cell counts were the third in the column contribution. CONCLUSIONS: Our study emphasizes the utility of NK cell counts for exploring interactions between long-term survival of HCC patients and predictor variables.


Assuntos
Carcinoma Hepatocelular , Doença Hepática Terminal , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Contagem de Células , Humanos , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias , Nomogramas , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
10.
Chem Commun (Camb) ; 58(6): 771-774, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-34889324

RESUMO

A proton-transporting pathway is crucial to the conduction mechanism in fuel cells and biological systems. Here, we report a novel 5-fold interpenetrated three-dimensional (3D) hydrogen-bonded quadruplex framework, which exhibits an ultrahigh single-crystal proton conductivity of 1.2(1) × 10-2 S cm-1 at 95 °C and 98% relative humidity, benefitting from the spiral H3O+/H2O chains in 1D pore channels studded with COOH/COO- groups.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34891235

RESUMO

Deep learning has achieved unprecedented success in sleep stage classification tasks, which starts to pave the way for potential real-world applications. However, due to its enormous size, deployment of deep neural networks is hindered by high cost at various aspects, such as computation power, storage, network bandwidth, power consumption, and hardware complexity. For further practical applications (e.g., wearable sleep monitoring devices), there is a need for simple and compact models. In this paper, we propose a lightweight model, namely LightSleepNet, for rapid sleep stage classification based on spectrograms. Our model is assembled by a much fewer number of model parameters compared to existing ones. Furthermore, we convert the raw EEG data into spectrograms to speed up the training process. We evaluate the model performance on several public sleep datasets with different characteristics. Experimental results show that our lightweight model using spectrogram as input can achieve comparable overall accuracy and Cohen's kappa (SHHS100: 86.7%-81.3%, Sleep-EDF: 83.7%-77.5%, Sleep-EDF-v1: 88.3%-84.5%) compared to the state-of-the-art methods on experimental datasets.


Assuntos
Aprendizado Profundo , Eletroencefalografia , Redes Neurais de Computação , Sono , Fases do Sono
13.
J Hepatocell Carcinoma ; 8: 1253-1267, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708007

RESUMO

BACKGROUND AND AIMS: Although antiviral treatment has been shown to reduce mortality in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with high HBV-DNA levels, it is still unclear whether it is useful in reducing mortality in patients with low HBV-DNA levels. METHODS: A retrospective analysis of 756 HBV-associated HCC patients at the Beijing Ditan Hospital with HBV-DNA levels < 500 IU/mL was conducted between January 2008 and June 2017. Patients were divided into antiviral and non-antiviral groups based on whether they received nucleos(t)ide analogue (NA) treatment when they were diagnosed with HCC in our hospital for the first time. We used 1:4 frequency matching by age, gender, tumor size, Barcelona Clinic Liver Cancer (BCLC) staging, anti-tumor therapy, cirrhosis, diabetes, and hyperlipoidemia to compare the antiviral (n = 366) and non-antiviral (n = 100) groups. A Cox multivariate regression analysis was employed to evaluate the effects of NA therapy on the hazard ratio (HR), and the Kaplan-Meier survival curve was used to determine the mortality risk in patients with HCC. A Log rank test was performed to analyze the effects of NA therapy on the survival rate of patients with HCC. RESULTS: After propensity score matching, the 1-, 3-, and 5-year overall survival (OS) rates for the antiviral and non-antiviral groups were 82.5%, 68.6%, and 52.2%, and 61.0%, 51.0%, and 38.0%, respectively. The l-year progression-free survival (PFS) rates for the two groups were 68.0% and 47.0%, respectively. The OS of the antiviral group was significantly higher than that of the control group (P < 0.001, P = 0.001, and P = 0.013, respectively). The 1-year PFS for the antiviral group was also significantly better than that for the non-antiviral groups (P = 0.005). After adjusting for confounding prognostic factors in the Cox model, the HR of 5-year death after antiviral treatment was 0.721 (95% confidence interval [CI], 0.530-0.980, P = 0.037). Antiviral therapy is an independent protective factor for 5-year mortality in patients with HCC and low-level viremia. CONCLUSION: Antiviral therapy significantly reduced mortality in HCC patients with low HBV-DNA levels.

14.
J Am Chem Soc ; 143(44): 18744-18754, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34714634

RESUMO

Molecular shape is an essential parameter that regulates the self-organization and recognition process, which has not yet been well appreciated and exploited in block polymers due to the lack of precise and efficient modulation methods. This work (i) develops a robust approach to break the intrinsic symmetry of linear polymers by introducing geometric features into otherwise homogeneous chains and (ii) quantitatively highlights the critical contribution of molecular geometry/architecture to the self-assembly behaviors. Iteratively connecting homologous monomers of different side chains according to pre-designed sequences generates discrete polymers with exact chemical structure, uniform chain length, and programmable side-chain gradient along the backbone, which transcribes into diverse shapes. The precise chemistry eliminates all the defects and heterogeneities, providing a delicate platform for fundamental inquiries into the role of molecular geometry. A rich collection of unconventional complex phases, including Frank-Kasper A15 and σ phases, as well as a dodecagonal quasicrystal phase, were captured in these rigorous single-component systems. The self-assembly behaviors are strikingly sensitive to subtle variations of geometry, such that simply migrating a few methylene units among the side chains would generate substantial differences in lattice size or phase stability, or even trigger a phase transition toward distinct structures. The phenomena can be rationalized with a geometric argument that nonuniform side chain distribution leads to conformational mismatch between two immiscible blocks, resulting in varied interfacial curvatures and distinct lattice symmetries. The profound contribution demonstrates that molecular geometry is an effective and robust parameter for structural engineering.

15.
Natl Sci Rev ; 8(3): nwaa094, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34691585

RESUMO

3-Ethyl-5-trifluoromethyl-1,2,4-triazole is synthesized by a one-pot reaction. Using this asymmetric triazole ligand bearing one trifluoromethyl and one ethyl as side groups, we construct two new porous coordination polymers, MAF-9 and MAF-2F, being isostructural with the classic hydrophobic and flexible materials, FMOF-1 and MAF-2, based on symmetric triazole ligands bearing two trifluoromethyl groups or two ethyl groups, respectively. MAF-9 and MAF-2F can adsorb large amounts of organic solvents but completely exclude water, showing superhydrophobicity with water contact angles of 152o in between those of FMOF-1 and MAF-2. MAF-9 exhibits very large N2-induced breathing and colossal positive and negative thermal expansions like FMOF-1, but the lower molecular weight and smaller volume of MAF-9 give 16% and 4% higher gravimetric and volumetric N2 uptakes, respectively. In contrast, MAF-2F is quite rigid and does not show the inversed temperature-dependent N2 adsorption and large guest-induced expansion like MAF-2. Further, despite the higher molecular weight and larger volume, MAF-2F possesses 6% and 25% higher gravimetric and volumetric CO2 uptakes, respectively. These results can be explained by the different pore sizes and side group arrangements in the two classic framework prototypes, which demonstrate the delicate roles of ligand side groups in controlling porosity, surface characteristic and flexibility.

16.
Soft Matter ; 17(40): 9125-9130, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34570151

RESUMO

Utilizing combined non-covalent interactions and introducing anions as structure-directing factors to build oriented self-assembly and 2D crystalline nanosheet superstructures with precise distance control of surface charges in competitive aqueous solvents still represents a formidable challenge for supramolecular chemists. Here we report a simple, efficient, and general strategy for multiple C-H/N-H⋯anion hydrogen bond enhanced π-π interaction directed 2D oriented self-assembly in water, which is based on the head-to-tail association of perylene monoimide dimers (PMIs) by directing N-H⋯anion interactions to position the anions to the C-H of π systems (PMIs). Interesting, this behavior only occurs for size-matched anions (Cl- to NO3-; <45 Å3), while larger anions could not form 2D crystalline nanosheet superstructures. The results show that crystalline nanosheet superstructures with precise distance control of surface charges can effectively capture DNA, possibly due to their high surface charge density and the distance match between the distance of surface charges and the distance between adjacent base pairs.


Assuntos
DNA , Ânions , Pareamento de Bases , Ligação de Hidrogênio
17.
Am J Cancer Res ; 11(5): 2142-2158, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094674

RESUMO

In general, the lack of effective therapeutic targets has led to the poor prognosis of triple-negative breast cancer (TNBC). Polo-like kinase 1 (PLK1) has been studied extensively as an effective therapeutic objective for the progression of tumor. Although the fundamental strategy and function of PLK1 in TNBC are still unclear. Here, we demonstrated that PLK1 upregulation was significantly correlated with poor prognosis in breast cancer cases utilizing the TCGA database. Additionally, ectopic PLK1 expression promoted TNBC cell proliferation, VEGFA production, and endothelial cell tube formation, whereas PLK1 knockdown induced the opposite effects. Moreover, expression of PLK1 K82R, the kinase-dead mutant of PLK1, completely inhibited PLK1-mediated cell proliferation, VEGFA production, and tube formation. Gene Set Enrichment Analysis (GSEA) showed that PLK1 expression significantly correlated with mitosis and the VEGF signaling pathway. We further observed that PLK1 phosphorylated centromere protein U (CENPU) at residue T78, thereby regulating the signaling pathway of COX-2/HIF-1α/VEGFA and the metaphase-anaphase transition of mitosis. The mechanism underlying the activity of PLK1 was also determined using a TNBC xenograft mouse model. Moreover, a PLK1 inhibitor effectively inhibited TNBC progression. Taken together, our results revealed that PLK1 plays an important role in TNBC progression via its kinase activity and phosphorylation of CENPU. Thus, PLK1 is an effective therapeutic objective for TNBC.

18.
Nat Prod Res ; : 1-5, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34180322

RESUMO

Chemical investigation of endophytic fungus Aspergillus fumigatus HQD24, isolated from the flower of Rhizophora mucronata led to the isolation of eight alkaloids, including pyripyropene A (1), 1,11-dideacetyl-pyripyropene A (2), pyripyropene E (3), chaetominine (4), tryptoquivaline J (5), fumitremorgin C (6), 1-acetyl-ß-carboline (7), and nicotinic acid (8). Their structures were unambiguously elucidated on the basis of extensive spectroscopic data and comparison with the data of literature. Compound 2 was known as a synthetic product and isolated as a natural product for the first time. The immunosuppressive and cytotoxic activities of all isolated compounds were evaluated.

19.
Mol Ther Oncolytics ; 21: 329-339, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34141870

RESUMO

Acute lymphoblastic leukemia (ALL) is an aggressive hematological neoplasm resulting from immature lymphoid precursors. An antibody-drug conjugate (ADC), coupling a small molecule covalently with a targeting antibody, can specifically kill tumor cells. Death receptor 5 (DR5) is considered as a promising anti-tumor drug target. In this study, we describe the preclinical evaluation of a novel DR5-targeting ADC (Oba01) as a potential therapeutic against ALL. Oba01 utilizes anti-DR5 humanized monoclonal antibody (zaptuzumab) coupled via a cleavable linker to monomethyl auristatin E (MMAE). Oba01 can specifically bind to DR5 on the tumor cells and transfer into lysosome via DR5-mediated endocytosis. It then effectively releases the MMAE, which can bind to the tubulin and prevent its aggregation, thereby leading to a significant inhibition of proliferation and cell death in tumor cells. Additionally, Oba01 displays significant dose-dependent tumoricidal activity in cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. More importantly, toxicity analysis of Oba01 showed a favorable safety profile, and pharmacokinetic analysis illustrated an excellent stability and tolerability in rats and cynomolgus monkeys. Taken together, our data conclusively demonstrate that Oba01 is an attractive candidate for further clinical trials in DR5-positive ALL patients.

20.
Medicine (Baltimore) ; 100(20): e26046, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011118

RESUMO

ABSTRACT: Psychotropic drugs are frequently used for functional dyspepsia (FD); however, the efficacy of these drugs for treating FD remains controversial. We aimed to comprehensively compare the relative efficacies of different psychotropic drugs for FD in adults.To conduct this study, we searched the PubMed, Embase, and Cochrane Library databases on March 10, 2019, and conducted a frequentist network meta-analysis on the search results. The primary outcome was treatment efficacy estimated by the proportion of patients who achieved a certain percentage decrease in symptoms or who dropped below the threshold of the global FD symptom scores. The secondary outcome was acceptability, defined as all-cause discontinuation. Odds ratios (ORs) were reported with 95% confidence intervals (CIs).We deemed 10 trials to be eligible for analysis, and these trials included 970 participants and 10 psychotropic drugs. Flupentixol + melitracen (F + M) (OR, 10.00; 95% CI, 1.59 to 62.73), tandospirone (3.24, 1.38 to 7.60), imipramine (2.21, 1.02 to 4.79), and amitriptyline (1.71, 1.06 to 3.09) were significantly superior to placebo. According to the surface under the cumulative ranking curve, the most effective treatment was F + M (89.0%), whereas the least effective was R137696 (13.6%). In terms of acceptability, escitalopram (0.32, 0.11 to 0.92) was ranked as the worst drug (12.6%), followed by imipramine and sertraline.The present network meta-analysis suggests that F + M, tandospirone, imipramine, and amitriptyline are more effective than placebo as treatment for FD. Our results indicate that among the ten psychotropic drugs included, F + M is likely to be the most effective drug for alleviating dyspepsia symptoms.


Assuntos
Dispepsia/tratamento farmacológico , Psicotrópicos/uso terapêutico , Humanos
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