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1.
Sci Total Environ ; 857(Pt 2): 159532, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36257435

RESUMO

Co-coagulation flotation (CCF) is a novel flotation technology that renders more efficient algal removal compared to traditional mechanical coagulation flotation (MCF) due to a short residence time (< 30 s) and fast rising behavior of algal flocs (> 250 m·h-1). This study compared the algal removal performance using continuous CCF and MCF using water samples taken from Lake Dianchi with severe Microcystis aeruginosa blooms. Removal efficiency, dosage of coagulant/flocculant, rising velocity and structural characteristics of the resulting flocs in the two processes were systematically compared. The results show that CCF could save >50 % polyaluminum chloride (PAC) and polyacrylamide (PAM) compared with MCF when the removal efficiency was both over 95 %. The average rising velocity of flocs in CCF could reach 254.3 m·h-1, much higher than that in MCF (154.5 m·h-1). In the respective optimal coagulation conditions, the flocs formed in CCF (G = 164.8 s-1) were larger (1843 ± 128 µm) and more spherical with a higher fractal dimension (Df = 1.85 ± 0.01) than those generated in MCF (G = 34.1 s-1). The Stokes's Law was found to correctly predict the rising velocity of spherical flocs with large fractal dimensions (Df > 1.7). In contrast, the Haarhoff and Edzwald's extended equation was more suitable for calculating the rising velocity of irregular flocs with small fractal dimension. This study provides new insights into the mechanisms of the enhanced algal removal by CCF and lays foundation for developing cost-efficient algal mitigation processes.


Assuntos
Microcystis , Purificação da Água , Floculação , Purificação da Água/métodos
2.
Food Chem ; 398: 133913, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35964560

RESUMO

This experiment investigated the underlying mechanism of ultrasonic-assisted stewing to enhance the aroma intensity of chicken broth by measuring fat content, oil droplet sizes, zeta potential, viscosity, surface protein loading, lipid oxidation, and aroma compound concentrations. As the thermo-ultrasound time increased, the fat content increased from 0.3 % to 1.2 %, resulting in a milky white appearance. After 1 h of thermo-ultrasound, the broth had the smallest particle size and the highest surface protein load, viscosity, and emulsion stability, as well as the highest total amount of aroma-active compounds of 314.70 ng/mg. With the further extension of thermo-ultrasound time, lipid oxidation increased, but the stability of chicken broth decreased, lowering the content of aroma-active compounds. These outcomes suggested that thermo-ultrasound could enhance the aroma intensity of chicken broth by increasing the fat content and the emulsion stability of the broth.


Assuntos
Galinhas , Odorantes , Animais , Emulsões/química , Lipídeos , Proteínas de Membrana , Odorantes/análise , Ultrassom
3.
Phytomedicine ; 108: 154514, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36334390

RESUMO

BACKGROUND: A wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly resulted in a steep increase in the infected population and an overloaded healthcare system. Effective medications for Omicron are currently limited. The previous observational study supports the efficacy and safety of Reyanning (RYN) mixture in the treatment of coronavirus disease 2019 (COVID-19). PURPOSE: To evaluate the efficacy of RYN in asymptomatic and mildly infected patients with SARS-CoV-2 infection. STUDY DESIGN AND METHODS: This study was a prospective, open-label, randomized controlled trial. We consecutively recruited 2830 patients from Shanghai New International Expo Center mobile cabin hospital and randomized them in a 1:1 ratio to receive RYN plus standard care or receive standard care alone. The primary outcomes were the negative conversion of nucleic acid. Secondary outcomes included the hospital duration, new-onset symptoms, proportion of disease progression, and the viral load measured by the cycle threshold (Ct) value. RESULTS: A total of 1393 patients in the intervention group and 1407 patients in the control group completed the study. The negative conversion time of nucleic acid was significantly shortened in the intervention group (median: 6 d vs. 7 d, Hazard ratio: 0.768, 95CI %: 0.713-0.828, p < 0.0001). The negative conversion rate of nucleic acid was significantly higher in the intervention group (Day 3: 32.4% vs. 18.3%; Day7: 65.3% vs. 55.2%, p < 0.001). The hospitalization duration was significantly shortened in the intervention group (median: 8 d vs. 9 d, Hazard ratio: 0.759, 95% CI: 0.704-0.818, p < 0.0001). The proportion of new-onset fever (2.4% vs. 4.1%, p = 0.012), coughing (12.2% vs. 14.8%, p = 0.046), and expectoration (6.0% vs. 8.0%, p = 0.032) in the intervention group was significantly lower. RYN treatment increased Ct values and reduced the viral load. No disease progression and serious adverse events were reported during the study. CONCLUSION: RYN is a safe and effective treatment that can accelerate virus clearance and promote disease recovery in asymptomatic and mild Omicron infections.

4.
Front Public Health ; 10: 974848, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339206

RESUMO

Background: The coronavirus disease (COVID-19) pandemic, which has been ongoing for more than 2 years, has become one of the largest public health issues. Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is one of the most important interventions to mitigate the COVID-19 pandemic. Our objective is to investigate the relationship between vaccination status and time to seroconversion. Methods: We conducted a cross-sectional observational study during the SARS-CoV-2 B.1.617.2 outbreak in Jiangsu, China. Participants who infected with the B.1.617.2 variant were enrolled. Cognitive performance, quality of life, emotional state, chest computed tomography (CT) score and seroconversion time were evaluated for each participant. Statistical analyses were performed using one-way ANOVA, univariate and multivariate regression analyses, Pearson correlation, and mediation analysis. Results: A total of 91 patients were included in the analysis, of whom 37.3, 25.3, and 37.3% were unvaccinated, partially vaccinated, and fully vaccinated, respectively. Quality of life was impaired in 30.7% of patients, especially for mental component summary (MCS) score. Vaccination status, subjective cognitive decline, and depression were risk factors for quality-of-life impairment. The chest CT score mediated the relationship of vaccination status with the MCS score, and the MCS score mediated the relationship of the chest CT score with time to seroconversion. Conclusion: Full immunization course with an inactivated vaccine effectively lowered the chest CT score and improved quality of life in hospitalized patients. Vaccination status could influence time to seroconversion by affecting CT score and MCS score indirectly. Our study emphasizes the importance of continuous efforts in encouraging a full vaccination course.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Pandemias , Vacinas contra COVID-19 , Soroconversão , COVID-19/prevenção & controle , Saúde Mental , Estudos Transversais , Qualidade de Vida , Tomografia Computadorizada por Raios X , Vacinação
5.
Front Cell Infect Microbiol ; 12: 1002140, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339330

RESUMO

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare congenital immune deficiency characterized by susceptibility to weakly virulent mycobacteria. Loss-of-function (LOF) mutation of signal transducer and activator of transcription 1 (STAT1) is one of the common genetic causes of MSMD. In this study, we identified a patient who presented with multiple lymph node enlargements and multiple osteolytic disruptions. Mycobacterium gordonae infection was confirmed by metagenomic next-generation sequencing. Whole-exome sequencing identified a novel paternal heterozygous mutation in exon 22 of STAT1 (NM_007315.4, c.1892T>C, p.Val631Ala). This variant was confirmed pathogenic by multiple software predictions. Based on functional assays, STAT1 expression in STAT1V631A cells was not different from STAT1WT cells. But STAT1V631A mutation caused much lower activation of STAT1 when stimulated by interferon-γ (IFN-γ). Fluorescence localization analysis revealed that both STAT1V631A and STAT1WT proteins were located in the cytoplasm, and only a few STAT1V631A proteins were translocated to the nucleus in response to IFN-γ. These results suggest that STAT1V631A leads to LOF in IFN-γ-mediated mycobacterial immunity, resulting in MSMD. Treatment with antibiotics has achieved ideal disease control for this patient, and no adverse events occurred during follow-up. The STAT1 LOF deficiency is a genetic cause of MSMD, which should be considered in patients with mycobacterial disease, especially those with bone involvement.


Assuntos
Infecções por Mycobacterium , Mycobacterium , Humanos , Predisposição Genética para Doença , Infecções por Mycobacterium/genética , Mutação , Interferon gama/metabolismo , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo
6.
Artigo em Inglês | MEDLINE | ID: mdl-36344453

RESUMO

Despite the advances in the area of catalytic alkene hydrosilylation, the enantioselective hydrosilylation of alkenes bearing a heteroatom substituent is scarce. Here we report a rhodium-catalyzed hydrosilylation of ß,ß-disubstituted enamides to directly afford valuable α-aminosilanes in a highly regio-, diastereo-, and enantioselective manner. Stereodivergent synthesis could be achieved by regulating substrate geometry and ligand configuration to generate all the possible stereoisomers in high enantio-purity.

7.
Sci Rep ; 12(1): 19333, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369435

RESUMO

Lysophosphatidylcholine (LPC) was previously found to show neuroprotective effect on nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) induced signalings. Also, numerous studies reported the emerging roles of long noncoding RNAs (LncRNAs) involved in neurodegenerative disease. However, the biological mechanism of LPC and expression profile of lncRNAs has not been reported. Here, lncRNAs in PC12 cells under LPC and NGF treatment were analyzed using high throughput sequencing technology for the first time. We identified 564 annotated and 1077 novel lncRNAs in PC12 cells. Among them, 121 lncRNAs were differentially expressed in the PC12 cells under LPC stimulation. KEGG analysis showed that differentially expressed mRNAs co-expressed with lncRNAs mainly enriched in ribosome, oxidative phosphorylation, Parkinson's disease, Huntington's disease and Alzheimer's disease etc. LncRNA-mRNA network analysis showed that lncRNA ENSRNOT00000082515 had interactions with 626 different mRNAs suggesting that lncRNA ENSRNOT00000082515 probably play vital role. Finally, sequencing data were validated by qRT-PCR for ENSRNOT00000084874, ENSRNOT00000082515, LNC_001033 forward Fgf18, Vcam1, and Pck2.


Assuntos
Doenças Neurodegenerativas , RNA Longo não Codificante , Ratos , Animais , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Lisofosfatidilcolinas/farmacologia , Fator de Crescimento Neural/genética , Perfilação da Expressão Gênica , Células PC12 , Redes Reguladoras de Genes
8.
Comput Struct Biotechnol J ; 20: 5859-5869, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36382196

RESUMO

Alternative polyadenylation (APA) is an important post-transcription regulatory mechanism widely occurring in eukaryotes and has been associated with special traits/diseases by several studies. However, the dynamic roles and patterns of APA in cell differentiation remain largely unknown. Here, we systematically characterized the APA profiles during the differentiation of induced pluripotent stem cells (iPSCs) to cardiomyocytes by the previously published RNA-seq data across 16 time points. We identified 950 differential APA events and found five dynamic APA patterns with fuzzy c-means clustering analysis. Among them, 3'UTR progressive lengthening is the main APA pattern over time, the genes of which are enriched in cell cycle and mRNA metabolic process pathways. By constructing the linear mixed-effects model, we also indicated that TIA1 plays an important role in regulating APA events with this pattern, including genes essential to cardiac function. Additionally, APA and polyA machinery activity with another pattern can immediately respond to developmental signal-mediated stimuli at the early differentiation stage and result in a sharp shortening of the 3'UTR. Finally, a miRNA-APA network is constructed and several hub miRNAs potentially regulating cardiomyocyte differentiation are detected. Our results show the complex APA mechanisms during the differentiation of iPSCs into cardiomyocytes and provide further insights for the understanding of APA regulation and cell differentiation.

9.
Small ; : e2204864, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36394082

RESUMO

Electrochemical activation strategy is very effective to improve the intrinsic catalytic activity of metal phosphate toward the sluggish oxygen evolution reaction (OER) for water electrolysis. However, it is still challenging to operando trace the activated reconstruction and corresponding electrocatalytic dynamic mechanisms. Herein, a constant voltage activation strategy is adopted to in situ activate Ni2 P4 O12 , in which the break of NiONi bond and dissolution of PO4 3- groups could optimize the lattice oxygen, thus reconstructing an irreversible amorphous Ni(OH)2 layer with a thickness of 1.5-3.5 nm on the surface of Ni2 P4 O12 . The heterostructure electrocatalyst can afford an excellent OER activity in alkaline media with an overpotential of 216.5 mV at 27.0 mA cm-2 . Operando X-ray absorption fine structure spectroscopy analysis and density functional theory simulations indicate that the heterostructure follows a nonconcerted proton-electron transfer mechanism for OER. This activation strategy demonstrates universality and can be used to the surface reconstruction of other metal phosphates.

10.
Cell Rep ; 41(6): 111606, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36351407

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and CD4+ T cells are known to promote SLE development. Here, we explore heterogeneities in the CD4+ T cell regulome and their associations with SLE pathogenesis by performing assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and single-cell transcriptome sequencing (single-cell RNA sequencing [scRNA-seq]) of peripheral CD4+ T cells from 72 SLE patients and 30 healthy controls. Chromatin accessibility signatures of CD4+ T cells are correlated with disease severity. Further, we generate 34,176 single-cell transcriptomes of healthy and SLE CD4+ T cells and reveal transcriptional dysfunction of regulatory T (Treg) cells, identifying two Treg subpopulations, among which the CCR7lowCD74hi Treg subgroup features type I interferon-induced functional exhaustion in SLE patients. These transcriptome-level findings for SLE Tregs are mirrored in trends from the ATAC-seq data. Our study establishes a rich empirical foundation for understanding SLE and uncovers previously unknown contributions of Treg with exhaustion-like properties to SLE pathogenesis.


Assuntos
Lúpus Eritematoso Sistêmico , Linfócitos T Reguladores , Humanos , Linfócitos T CD4-Positivos/patologia , Cromatina/metabolismo , Subpopulações de Linfócitos T/metabolismo , Perfilação da Expressão Gênica
11.
Front Public Health ; 10: 1015811, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353283

RESUMO

Objective: To evaluate determinants of prolonged viral RNA shedding in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. Materials and methods: Hospitalized patients tested SARS-CoV-2 positive by nasopharyngeal real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were included in the single-center, retrospective study. Patients were divided into 2 groups according to the timing of viral clearance (≤ 8 days, "early clearance" and ≥15 days, "late clearance"). Results: 4,084 patients were included in the study (1,023 late clearance, 3,061 early clearance), with median age of 50 years and a higher proportion (61.4%) of male. Univariate analyses showed that comorbidities (including hypertension, diabetes, and coronary heart disease), receiving vaccine, the number of vaccinations, cycle threshold (Ct) open reading frame 1ab (ORF 1ab), and nucleocapsid protein (N) gene values on admission were associated with late viral clearance. In the multivariable analysis, the number of vaccinations (P = 0.010) and Ct ORF 1ab gene (P < 0.001) values on admission were significantly associated with late viral clearance. Generalized Estimating Equations (GEE) analysis showed that the Ct value of ORF 1ab gene and N gene remained unchanged within 3 days, and showed progressively higher values with increasing days during late viral RNA clearance. Conclusion: The number of vaccinations and Ct values of ORF 1ab gene were independently associated with a prolonged SARS-CoV-2 RNA shedding.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , Eliminação de Partículas Virais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Viral/análise , Estudos Retrospectivos , COVID-19/epidemiologia , China/epidemiologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-36357335

RESUMO

The inflammatory microenvironment involves changes in pH and protein phosphorylation has closely related to the occurrence and development of atherosclerosis (AS). Herein, we constructed a dual-detection fluorescence nanosensor PCN-NP-HPZ based on post modification of MOFs, which realized the simultaneous detection and imaging of pH and phosphorylation through the pH sensitive group piperazine and the Zr(IV) node of MOFs. The sensors were used to track changes in blood pH and phosphate levels at different time stages during atherosclerotic plaque formation. Two-photon fluorescence imaging was also performed in vascular endothelium. Blood tests combined with two-photon fluorescence images indicated that in the early stage of AS, blood and tissue pH levels were lower than that of the normal mice, while phosphate and tissue phosphorylation levels were higher than that of the normal mice. The present study provides a new analysis method for the assessment of early atherosclerotic disease.

13.
Front Pharmacol ; 13: 1065438, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386143

RESUMO

Chemodynamic therapy (CDT), a newly developed approach for cancer treatment, can convert hydrogen peroxide (H2O2) into toxic hydroxyl radicals (•OH) by using Fenton/Fenton-like reaction to kill tumor cells. However, due to the complexity of the intracellular environment of tumor cells, the therapeutic efficacy of CDT was severely restricted. Recently, combination therapy strategies have become popular approaches for tumor treatment, and there are numerous studies have demonstrated that the CDT-based combination strategies can significantly improve the anti-tumor efficiency of CDT. In this review, we outline some of the recent progress in cancer chemodynamic therapy from 2020, and discuss the progress in the design of nanosystems for CDT synergistic combination therapies.

14.
Front Oncol ; 12: 911160, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387112

RESUMO

This research found that the clinical outcomes (PFS, ORR, OS) of the non-platinum-based doublet regimen (docetaxel capecitabine combination) were similar to those of the platinum-based (oxaliplatin capecitabine combination) when used as first line therapy for MGC patients. Background: Docetaxel, platinum and fluorouracil are the three most important drugs in the treatment of MGC. This study was to compare clinical outcomes of the docetaxel capecitabine combination and the oxaliplatin capecitabine combination as first-line therapy in MGC patients. Methods: In this phase II trial, MGC patients were randomly assigned and treated with either TX (capecitabine 1000 mg/m2/twice daily/1-14 days and docetaxel 60/75 mg/m2 on the 1st day) (because of toxicity, the dose of docetaxel was reduced to 60 mg/m2) or XELOX (capecitabine the same dose with TX and oxaliplatin 130 mg/m2 on the 1st day) as first-line therapy. After progression, patients were crossover to the other group as second-line treatment. Results: Total 134 MGC patients were randomized (69 in TX, 65 in XELOX). There was no significant difference between the PFS of the two groups (TX vs XELOX, 4.6 months vs 5.1 months, p=0.359), and the SFS (9.3 months vs 7.5 months, p=0.705), OS (13.1 months vs 9.6 months, p=0.261), and ORR (46.4% vs 46.2%) were also similar. Among patients with ascites, the TX group had significantly longer PFS and OS than the XELOX group. A total of 85 patients (48 in TX, 37 in XELOX) received second-line treatment, with overall survival of second-line chemotherapy (OS2) of 8.0 m and 5.3 m (p=0.046), respectively. Grade 3 to 4 treatment-related adverse events of first line treatment occurred more in TX group than that in XELOX group(60.6% vs 55.4%). Conclusion: TX regimen is an alternative choice of first-line treatment for MGC patients. We still need to explore the large number of cohort to confirm this results.

15.
Inorg Chem ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36395345

RESUMO

Exploration of high-order multiphoton-excited fluorescent (H-MPEF) material for bioimaging with deeper tissue penetration and higher spatial resolution has attracted great interest but remains a challenge. Herein, a H-MPEF-responsive metal-organic framework-based material, ZLPH, was rationally fabricated by the pore confinement of a two-photon active unit (ZL) using the "ship-in-bottle" strategy. It demonstrated that the judicious selection effectively avoided the annoying weakened/quenched H-MPEF behavior due to the instability of ZL in the molecular state. Moreover, the obtained material, ZLPH, exhibited bright four-photon-excited fluorescence (4PEF) under the excitation of a 1550 nm femtosecond laser. In view of deep-tissue biological applications, it is envisioned that this work provides a promising platform for bright H-MPEF imaging.

16.
Asia Pac J Oncol Nurs ; 9(12): 100152, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36389624

RESUMO

Objective: The aim of this paper is to systematically evaluate the effects of virtual reality (VR) on pain, anxiety, and fear symptoms of pediatric patients with cancer. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, CINAHL, and four Chinese medical databases were searched from January 1, 1975, to February 22, 2022. Randomized controlled trials on the effects of VR technology on pediatric cancer patients were searched. Two researchers independently screened literatures, extracted data, and evaluated literature quality according to inclusion and exclusion criteria, and meta-analysis was performed by RevMan 5.3. Results: A total of 379 children with cancer were included in six randomized controlled trials. Overall, there were significant differences in favor of VR in pain (MD â€‹= â€‹-4.82, 95% CI [-7.74, -1.89], P<0.01; I 2 ​= â€‹95%, P<0.01), anxiety (SMD â€‹= â€‹-1.47, 95% CI â€‹[​-2.46, -0.48], P<0.01; I 2  â€‹= â€‹92%, P<0.01), and fear (MD â€‹= â€‹-1.25, 95% CI [-1.78,0.72], P<0.01; I 2  â€‹= â€‹0%, P â€‹= â€‹0.69). Conclusions: VR is beneficial to improve the pain, anxiety, and fear mood of pediatric cancer patients. Larger sample sizes and more rigorous studies are needed.

17.
Chem Sci ; 13(42): 12511-12518, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36349272

RESUMO

Clear elucidation of the changes in Alzheimer's disease (AD)-related methylglyoxal (MGO) levels in vivo is significant yet highly challenging. Fluorescence imaging in the second near-infrared region (NIR-II, 1000-1700 nm) has gained increasing attention as an observation method in living organisms, but an MGO-activatable fluorescent probe that emits in this region for in vivo brain imaging is lacking because of the existence of the blood-brain barrier (BBB). Herein, a biocompatible Fe3O4 nanoparticle (IONP)-conjugated MGO-activatable NIR-II fluorescent probe (MAM) modified with the peptide T7 (HAIYPRH) (named TM-IONP) is reported for the in situ detection of MGO in a transgenic AD mouse model. In this system, the T7 peptide enhances BBB crossing and brain accumulation by specifically targeting transferrin receptors on the BBB. Due to the MAM probe, TM-IONPs emit fluorescence in the NIR-II region and display high selectivity with an MGO detection limit of 72 nM and a 10-fold increase in the fluorescence signal. After intravenous administration, the TM-IONPs are easily delivered to the brain and pass through the BBB without intervention, and as a result, the brains of AD mice can be noninvasively imaged for the first time by the in situ detection of MGO with a 24.2-fold enhancement in NIR-II fluorescence intensity compared with wild-type mice. Thus, this MGO-activated NIR-II-emitting nanoprobe is potentially useful for early AD diagnosis in clinic.

18.
Future Med Chem ; 14(22): 1649-1662, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36317642

RESUMO

Aim: Several VEGFR-2 inhibitors with the structure of [3,4-d]pyrimidine and based on sorafenib were designed and synthesized. Materials & methods: Cytotoxic activity was evaluated by MTT, wound healing and clone formation assays. Cell cycle and apoptosis were analyzed by flow cytometry. Molecular simulation and western blot were also applied. Results: Among them, II-1 significantly inhibited tumor cellular activity (IC50 = 5.90 ± 0.05 µM on HepG2 cells) compared with sorafenib (IC50 = 9.05 ± 0.54 µM on HepG2 cells). Molecular docking demonstrated that II-1 and sorafenib have the same hydrogen binding. Finally, the protein expression of phosphorylated VEGFR-2 was substantially reduced after II-1 treatment. Conclusion: Compound II-1 can inhibit VEFGR-2 activation and is an effective antitumor agent in liver cancer cells.


Assuntos
Antineoplásicos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Simulação de Acoplamento Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Proteínas Quinases/química , Desenho de Fármacos , Relação Estrutura-Atividade , Sorafenibe/farmacologia , Estrutura Molecular , Relação Dose-Resposta a Droga , Proliferação de Células , Pirimidinas/química , Antineoplásicos/química
19.
Anal Chim Acta ; 1235: 340540, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36368817

RESUMO

Accurate detection of butyrylcholinesterase (BChE) activity is imperative to understand its biological function and diagnose related disease. Far-red (FR)/Near-Infrared (NIR) fluorescent probe with large Stokes shift for BChE detection is extremely important. In this study, we reported a new "off-on" FR/NIR fluorescent probe (DX-2) with large Stokes shift (110 nm). DX-2 was constructed through cyclopropionate to pull-push the optical tuable hydroxyl group of chloro-substituted dicyanoisophorone fluorophore. DX-2 (λex/λem = 555/665 nm) featured high sensitivity (LOD∼0.08 U/mL) and selectivity, good pH practicability, low toxicity and good cell membrane permeability with a bright emission triggered by BChE. Furthermore, DX-2 exhibited good optical performance to image BChE activity in living cells. More importantly, the FR/NIR probe DX-2 was successfully applied to real-time monitor BChE in live tumor-bearing mouse model. These studies suggest that probe DX-2 has potential applicable value for detecting BChE in living biological systems and diagnosing BChE-related diseases.


Assuntos
Butirilcolinesterase , Corantes Fluorescentes , Camundongos , Animais , Butirilcolinesterase/metabolismo , Corantes Fluorescentes/toxicidade , Microscopia de Fluorescência , Modelos Animais de Doenças
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