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1.
Chem Commun (Camb) ; 57(33): 4027-4030, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33885672

RESUMO

The crystallization mechanism of the perovskite crystals inside the mesopores of printable mesoscopic perovskite solar cells is demonstrated by in situ grazing-incidence X-ray diffraction. Ionic liquids can universally tune the crystallization process of different perovksites in the mesopores regradless of the precursor solvents, resulting in enhanced efficiency.

2.
Bioorg Chem ; 111: 104872, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33838560

RESUMO

Triple-negative breast cancer (TNBC) has an unfavorable prognosis attribute to its low differentiation, rapid proliferation and high distant metastasis rate. PI3K/Akt/mTOR as an intracellular signaling pathway plays a key role in the cell proliferation, migration, invasion, metabolism and regeneration. In this work, we designed and synthesized a series of anilide (dicarboxylic acid) shikonin esters targeting PI3K/Akt/mTOR signaling pathway, and assessed their antitumor effects. Through three rounds of screening by computer-aided drug design method (CADD), we preliminarily obtained sixteen novel anilide (dicarboxylic acid) shikonin esters and identified them as excellent compounds. CCK-8 assay results demonstrated that compound M9 exhibited better antiproliferative activities against MDA-MB-231, A549 and HeLa cell lines than shikonin (SK), especially for MDA-MB-231 (M9: IC50 = 4.52 ± 0.28 µM; SK: IC50 = 7.62 ± 0.26 µM). Moreover, the antiproliferative activity of M9 was better than that of paclitaxel. Further pharmacological studies showed that M9 could induce apoptosis of MDA-MB-231 cells and arrest the cell cycle in G2/M phase. M9 also inhibited the migration of MDA-MB-231 cells by inhibiting Wnt/ß-catenin signaling pathway. In addition, western blot results showed that M9 could inhibit cell proliferation and migration by down-regulating PI3K/Akt/mTOR signaling pathway. Finally, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model was also constructed to provide a basis for further development of shikonin derivatives as potential antitumor drugs through structure-activity relationship analysis. To sum up, M9 could be a potential candidate for TNBC therapy.

4.
Aging (Albany NY) ; 122020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33291081

RESUMO

Genome-wide association studies have revealed that multiple single-nucleotide polymorphisms in the intergenic region between estrogen receptor 1 and coiled-coil domain containing 170 (CCDC170) are associated with breast cancer risk. We performed microarray and bioinformatics analyses to identify genes that were induced upon CCDC170 overexpression, and confirmed our findings by evaluating paraffin-embedded breast cancer tissues and conducting cellular assays. In CCDC170-overexpressing MCF7 breast cancer cells, microarray analyses revealed that inositol-requiring enzyme 1 (IRE1) was the most elevated gene in enriched pathways. In breast cancer tissues, IRE1 expression correlated positively with CCDC170 and X-box binding protein 1 expression at both the mRNA and protein levels. In a survival analysis, patients with higher CCDC170 levels exhibited better disease-free survival. Western blotting indicated that overexpressing CCDC170 in MCF7 cells increased protein levels of IRE1α, estrogen receptor α and X-box binding protein 1, while silencing CCDC170 reduced them. CCDC170 overexpression promoted apoptosis in MCF7 cells, and this effect was more obvious under endoplasmic reticulum stress. MCF7 cells overexpressing CCDC170 were more sensitive to paclitaxel. Our study showed that higher CCDC170 expression is associated with a better prognosis in breast cancer patients and that CCDC170 may promote apoptosis through the IRE1α pathway.

5.
Ann Transl Med ; 8(18): 1132, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33240981

RESUMO

Background: Spontaneous tumor rupture is a distinctive disease pattern in patients with hepatocellular carcinoma (HCC). The application of hyperthermic intraperitoneal chemotherapy (HIPEC) in spontaneously ruptured hepatocellular carcinoma (srHCC) is debatable. Our study aimed to compare the long-term outcomes of srHCC vs. nrHCC and to test the role of postoperative HIPEC in patients with srHCC after hepatectomy. Methods: From 2014 to 2018, PSM was performed to compare 57 patients who performed liver resection for srHCC and met the research criteria with 57 nrHCC patients selected from 446 consecutive patients. Then patients with srHCC were divided into two groups according to whether they underwent HIPEC after hepatectomy. Results: After 1:1 PSM, the clinical characteristics of the patients with srHCC and nrHCC were comparable. In terms of long-term outcomes, the nrHCC group had significantly longer OS (P=0.026) and DFS (P<0.001) than the srHCC group. Of the 57 srHCC patients, the HIPEC group showed added complications compared to the non-HIPEC group, including an increased length of hospital stay and higher in-hospital costs. However, there were no significant differences in the metastatic patterns of these recurrent patients, and there was no statistically significant difference in DFS (P=0.28) or OS (P=0.56) between the two groups. Conclusions: The prognosis of ruptured HCC patients were worse than those of non-ruptured HCC patients. HIPEC may not be a robust treatment for srHCC now.

6.
Front Oncol ; 10: 526602, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194585

RESUMO

Background: Models for predicting patient survival after resection of a non-metastatic adenocarcinoma of the pancreatic body and tail (APBT) are scarce. We wished to establish and validate a nomogram to predict disease-specific survival (DSS) of these patients. Methods: A total of 1,435 patients screened from the Surveillance, Epidemiology, and End Results (SEER) database were included and divided randomly into a training set (TS; n = 1,007) and internal validation set (IVS; n = 428) at a ratio of 7:3. Cox regression analyses were conducted to select independent predictors in the TS, and a nomogram was constructed. The model was subjected to the IVS and an external validation set (EVS) comprising 151 patients from two tertiary hospitals. Results: Five independent risk factors (age at the diagnosis, chemotherapy, tumor grade, T stage, and the lymph node radio) were identified and integrated into the nomogram. Calibration curves indicated that the nomogram could predict DSS at 1, 2, and 3 years accurately. The nomogram had a higher concordance index for predicting DSS compared with that using the 8th edition of the American Joint 23 Committee on Cancer (AJCC8) stage (TS: 0.681 vs. 0.606; IVS: 0.662 vs. 0.590; and EVS: 0.675 vs. 0.608). The nomogram had better discrimination ability and clinical utility than the AJCC8 stage for predicting 1-, 2-, and 3-year DSS. Conclusion: Our developed nomogram could accurately predict DSS in patients after resection of a non-metastatic APBT.

7.
J Phys Chem Lett ; 11(22): 9689-9695, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33136402

RESUMO

The all-inorganic CsPb(IxBr1-x)3 (0 ≤ x ≤ 1) perovskite solar cells (PSCs) are attractive by virtue of their high environmental and thermal stability. Nevertheless, multiple-step deposition and high annealing temperature (>250 °C) and the structural and optoelectronic properties changes upon temperature-dependent phase-transition are potential impediments for highly efficient and stable PSCs. Herein, a space-confined method to fabricate stable lower-order symmetric pure monoclinic CsPbBr3 phase at low temperature (<50 °C) is for the first time reported. It is found that the carbon-based mesoporous fully printable area can inhibit the phase transition to get a pure phase. Therefore, the device exhibits a power conversion efficiency of 7.52% with a low hysteresis index of 0.024. Moreover, the device passed the 1000 h 85 °C thermal test and the 200 cycles thermal cycling test according to IEC-61625 stability tests. These are critical progresses for achieving long-term stability and the stable pure inorganic perovskite phase of high-performance photovoltaics.

8.
iScience ; 23(11): 101684, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33196019

RESUMO

Cancer cells alter their nutrition metabolism to cope the stressful environment. One important metabolism adjustment is that cancer cells activate glutaminolysis in response to the reduced carbon from glucose entering into the TCA cycle due to inactivation of several enzymes in glycolysis. An important question is how the cancer cells coordinate the changes of glycolysis and glutaminolysis. In this report, we demonstrate that the pyruvate kinase inactive dimer PKM2 facilitates activation of glutaminolysis. Our experiments show that growth stimulations promote PKM2 dimer. The dimer PKM2 plays a role in regulation of glutaminolysis by upregulation of mitochondrial glutaminase I (GLS-1). PKM2 dimer regulates the GLS-1 expression by controlling internal ribosome entry site (IRES)-dependent c-myc translation. Growth stimulations promote PKM2 interacting with c-myc IRES-RNA, thus facilitating c-myc IRES-dependent translation. Our study reveals an important linker that coordinates the metabolism adjustment in cancer cells.

9.
Nano Lett ; 20(11): 8178-8184, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33125246

RESUMO

Stable electron transport materials (ETMs) with fewer surface defects and proper energy level alignments with halide perovskite active layers are required for efficient perovskite solar cells (PSCs) with long-term durability. Here, two-dimensional van der Waals mixed valence tin oxides Sn2O3 and Sn3O4 are controllably synthesized and applied as ETMs for planar PSCs. The synthesized Sn2O3 and Sn3O4 have size of 5-20 nm and disperse well in water as stable colloids for months. Both Sn2O3 and Sn3O4 exhibit typical n-type semiconductor energy band structures, low trap density, and suitable energy level alignments with halide perovskites. Steady-state power conversion efficiencies (PCEs) of 22.36% and 21.83% are obtained for Sn2O3-based and Sn3O4-based planar PSCs. In addition, the half cells without hole transport materials and back electrodes show good UV-stability with average PCE of 99.0% and 95.7% for Sn2O3-based and Sn3O4-based devices remaining after 1000 h of ultraviolet soaking with an intensity of 70 mW cm-2.

10.
Epigenomics ; 12(17): 1501-1513, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32901506

RESUMO

Aim: Alzheimer's disease (AD) is the most frequent cause of dementia and characterized by the accumulation of ß-amyloid peptides in plaques and vessel walls. This study proposed a hypothesis of an inhibitory role of miR-96-5p in AD via regulating Foxo1. Methods & methods: AD mouse models were established by injecting with 1% pentobarbital. Results: Knockdown of miR-96-5p in the presence of naringin was shown to reduce the expression of Foxo1 and contents of superoxide dismutase, catalase and glutathione peroxidase, yet increase lipocalin-2 expression as well as hydroxyproline and malondialdehyde contents. Also, Foxo1-mediated lipocalin-2 inhibition attenuated AD. Conclusion: Our study shows downregulating miR-96-5p limited AD progression, highlighting miR-96-5p a potential therapeutic target in treating AD.

11.
Med Sci Monit ; 26: e925289, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32863381

RESUMO

BACKGROUND Orderly G2/M transition in the cell cycle is controlled by the cyclin-dependent kinase 1/cyclin B (CDK1/CCNB) complex. We aimed to comprehensively investigate the roles of CDK1, CCNB1, and CCNB2 via multi-omics analysis and their relationships with immune infiltration in hepatocellular carcinoma (HCC). MATERIAL AND METHODS The transcriptional data and the epigenetic and genetic alterations of CDK1, CCNB1, and CCNB2, as well as their impacts on prognosis in HCC patients, were identified using multiple databases. The correlations between expression of these genes and immune infiltration in HCC were then explored using the TIMER database. RESULTS Overall, mRNA expression of CDK1, CCNB1, and CCNB2 was up-regulated in various tumor tissues including HCC. Higher expression of these genes was associated with poorer prognosis in HCC patients. Lower promoter methylation of these genes might cause higher expression levels in tumor tissues of HCC. Genetic alterations and several methylated-CpG sites in these genes were significantly associated with survival. Notably, expression levels of CDK1, CCNB1, and CCNB2 were positively correlated with infiltrating levels of CD4⁺ T cells, CD8⁺ T cells, neutrophils, macrophages, and dendritic cells in HCC. In addition, significant correlations between the expression of these genes and various immune markers in HCC, such as PD-1, PDL-1, and CTLA-4, were also observed. CONCLUSIONS CDK1, CCNB1, and CCNB2 are potential prognostic biomarkers and associated with immune cell infiltration in HCC. The genes may be utilized to predict the reaction of immunotherapy. Combining inhibitors of these genes with immunotherapy may improve the survival time of HCC patients.

12.
G3 (Bethesda) ; 10(10): 3505-3514, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32769136

RESUMO

To generate the full-length transcriptome of Xinjiang green and purple turnips, Brassica rapa var. Rapa, using single-molecule real-time (SMRT) sequencing. The samples of two varieties of Brassica rapa var. Rapa at five developmental stages were collected and combined to perform SMRT sequencing. Meanwhile, next generation sequencing was performed to correct SMRT sequencing data. A series of analyses were performed to investigate the transcript structure. Finally, the obtained transcripts were mapped to the genome of Brassica rapa ssp. pekinesis Chiifu to identify potential novel transcripts. For green turnip (F01), a total of 19.54 Gb clean data were obtained from 8 cells. The number of reads of insert (ROI) and full-length non-chimeric (FLNC) reads were 510,137 and 267,666. In addition, 82,640 consensus isoforms were obtained in the isoform sequences clustering, of which 69,480 were high-quality, and 13,160 low-quality sequences were corrected using Illumina RNA seq data. For purple turnip (F02), there were 20.41 Gb clean data, 552,829 ROIs, and 274,915 FLNC sequences. A total of 93,775 consensus isoforms were obtained, of which 78,798 were high-quality, and the 14,977 low-quality sequences were corrected. Following the removal of redundant sequences, there were 46,516 and 49,429 non-redundant transcripts for F01 and F02, respectively; 7,774 and 9,385 alternative splicing events were predicted for F01 and F02; 63,890 simple sequence repeats, 59,460 complete coding sequences, and 535 long-non coding RNAs were predicted. Moreover, 5,194 and 5,369 novel transcripts were identified by mapping to Brassica rapa ssp. pekinesis Chiifu. The obtained transcriptome data may improve turnip genome annotation and facilitate further study of the Brassica rapa var. Rapa genome and transcriptome.

13.
Huan Jing Ke Xue ; 41(6): 2762-2770, 2020 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608792

RESUMO

An anoxic membrane bioreactor-microalgae membrane reactor coupling system (anoxic MBR-MMR) was used to deal with mariculture wastewater. Pre-anoxic MBR was used for the degradation of organic matter, NO3--N and NO2--N, and the released NH4+-N entered MMR for microalgae growth and was removed. Meanwhile, the treatment efficiency and the microalgae recovery were studied, and the membrane fouling behavior was investigated. After running for 91 days, the removal rates of the system toward NO3--N and NH4+-N were stable at above 90.0% and 88.0%, respectively. Furthermore, the average removal rates of PO43--P and TOC were 49.4% and 84.7%, respectively. Under the condition that the microalgae were harvested continuously, the biomass can be stably operated at an average concentration of 9×107 cells·mL-1 and good removal efficiency and resource utilization could be achieved. Through infrared spectrum and three-dimensional fluorescence spectrum analysis, the main substances causing membrane fouling in MMR were tryptophan proteins and humic acids. The membrane fouling in MMR was lighter than that in anoxic MBR.

14.
Sensors (Basel) ; 20(13)2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32610586

RESUMO

Recent years have witnessed the development of the applications of machine learning technologies to well logging-based lithology identification. Most of the existing work assumes that the well loggings gathered from different wells share the same probability distribution; however, the variations in sedimentary environment and well-logging technique might cause the data drift problem; i.e., data of different wells have different probability distributions. Therefore, the model trained on old wells does not perform well in predicting the lithologies in newly-coming wells, which motivates us to propose a transfer learning method named the data drift joint adaptation extreme learning machine (DDJA-ELM) to increase the accuracy of the old model applying to new wells. In such a method, three key points, i.e., the project mean maximum mean discrepancy, joint distribution domain adaptation, and manifold regularization, are incorporated into extreme learning machine. As found experimentally in multiple wells in Jiyang Depression, Bohai Bay Basin, DDJA-ELM could significantly increase the accuracy of an old model when identifying the lithologies in new wells.

15.
Chem Sci ; 11(2): 474-481, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-32190267

RESUMO

Printable mesoscopic perovskite solar cells are usually fabricated by drop-casting perovskite precursor solution on a screen-printed mesoporous TiO2/ZrO2/carbon triple-layer followed by thermal annealing. They have attracted much attention due to their simple fabrication process and remarkable stability. However, challenges lie in how to achieve complete pore fillings of perovskites in the meso-pores and to obtain high-quality perovskite crystals. Here, we report an in situ crystal transfer (ICT) process based on gas-solid interaction to deposit perovskite CH3NH3PbI3 absorber in the scaffold. CH3NH3PbI3 single crystals are first transformed into a liquid phase via exposure to methylamine gas flow. After complete infiltration into the nano-structured scaffolds, the liquid phase is converted back to the solid phase with reduction of methylamine gas partial pressure, maintaining the high-quality of CH3NH3PbI3 single crystals. Compared with the conventional drop-casting method, the ICT method effectively leads to interconnected morphology and prolongs the charge-carrier lifetime (from ∼37.52 ns to ∼110.85 ns) of the perovskite absorber in the scaffold. As a result, the devices can deliver a power conversion efficiency of 15.89%, which is attributed to the suppressed charge recombination and correspondingly enhanced open-circuit voltage of 0.98 V.

16.
Chin Med ; 15: 23, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32175001

RESUMO

Background: Tamoxifen (TAM) is a cell type-specific anti-estrogen and is applied to improve the survival of patients with estrogen receptor positive (ER +) breast cancer. However, long-term TAM use can induce serious drug resistance, leading to breast cancer recurrence and death in patients. Further, it is almost useless among patients with estrogen receptor negative (ER -) breast cancer. Shikonin (SK) is a natural product broadly explored in cancer therapy. Some studies have demonstrated the combined treatment of SK and clinical anticancer drugs including TAM on various tumors. However, the combined effect of SK and 4-hydroxytamoxifen (4-OHT) on ER- breast cancer is not known. The current study aimed to assess the combination effects of SK and 4-OHT on human breast cancer cells, MCF-7 (ER +) and MDA-MB-435S (ER -), in vitro and in vivo and to investigate the underlying mechanisms. Methods: CCK-8 assays and flow cytometry were conducted to determine the cell viability and apoptotic profiles of human breast cancer cell lines (MCF-7 and MDA-MB-435S) treated with SK, 4-OHT, and the combination. ROS and JC-1 assays were used to determine ROS level and mitochondrial membrane potential. Western blot analysis was performed to investigate proteins that are associated with apoptosis. Haematoxylin & Eosin (HE) staining was used to detect the tumor and kidney morphology of mice. TUNEL and immunohistochemical staining were performed to detect Ki67 expression level and cell apoptotic profile in tumor tissues. Results: SK and 4-OHT synergistically inhibited MCF-7 and MDA-MB-435S cell proliferation and promoted apoptosis by reducing mitochondrial membrane potential and increasing the intracellular ROS level. The combination of SK and 4-OHT activated the mitochondrial-dependent apoptosis and the death receptor pathways, significantly regulating the PI3K/AKT/Caspase 9 signaling pathway. Compared with SK and 4-OHT alone, the combination of SK and 4-OHT could better inhibit tumor growth in mice. Conclusion: The combination of SK and 4-OHT shows highly efficient anticancer effects on breast cancer therapy. SK may be a promising candidate as an adjuvant to 4-OHT for breast cancer treatments, especially for ER- breast cancer.

17.
Public Health Nutr ; 23(8): 1450-1459, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31928552

RESUMO

OBJECTIVE: Globally, China is among the 'saltiest' nations. In order to support current nationwide salt reduction initiatives, we investigated Chinese consumers' knowledge, beliefs and behaviours related to salt intake and salt reduction. DESIGN: A cross-sectional face-to-face survey was carried out, focusing on salt knowledge, beliefs and behaviours related to salt intake and salt reduction, perceptions of salt reduction responsibility and support for different national strategies. SETTING: The survey was carried out in China mainland. PARTICIPANTS: Consumers (n 2444) from six of seven major geographical regions in China participated in the survey. After data cleaning, a sample of 2430 was included in the final analysis. RESULTS: A majority of Chinese consumers believed that salt added during home cooking was the biggest contributor to their salt intake. Knowledge gaps existed in the awareness of salt hidden in certain foods and flavouring products. Chinese consumers in general were interested in lowering their salt intake. They were aware of salt reduction tools, but the adoption level was low. Consumers expressed strong support for promotion of salt-restriction spoons and public education, but not fiscal policies (e.g. salt-related tax or subsidies). In terms of individual differences, education status demonstrated a substantial impact on salt reduction knowledge and behaviour. CONCLUSIONS: There is still big room to 'shake' Chinese consumers' salt habit. The present study provides important evidence and consumer insights to support China's efforts to meet its salt reduction targets.


Assuntos
Comportamento Alimentar , Conhecimentos, Atitudes e Prática em Saúde , Cloreto de Sódio na Dieta/administração & dosagem , Adulto , Idoso , China , Comportamento do Consumidor , Estudos Transversais , Dieta Hipossódica , Feminino , Rotulagem de Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Cloreto de Sódio na Dieta/efeitos adversos , Inquéritos e Questionários , Adulto Jovem
18.
Angew Chem Int Ed Engl ; 59(12): 4691-4697, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-31846190

RESUMO

Formamidinium (FA) lead iodide perovskite materials feature promising photovoltaic performances and superior thermal stabilities. However, conversion of the perovskite α-FAPbI3 phase to the thermodynamically stable yet photovoltaically inactive δ-FAPbI3 phase compromises the photovoltaic performance. A strategy is presented to address this challenge by using low-dimensional hybrid perovskite materials comprising guaninium (G) organic spacer layers that act as stabilizers of the three-dimensional α-FAPbI3 phase. The underlying mode of interaction at the atomic level is unraveled by means of solid-state nuclear magnetic resonance spectroscopy, X-ray crystallography, transmission electron microscopy, molecular dynamics simulations, and DFT calculations. Low-dimensional-phase-containing hybrid FAPbI3 perovskite solar cells are obtained with improved performance and enhanced long-term stability.

19.
J Phys Chem Lett ; 10(21): 6865-6872, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31599595

RESUMO

Solution-processable organic-inorganic perovskite solar cells have attracted much attention in the past few years. Energy level alignment is of great importance for improving the performance of perovskite solar cells because it strongly influences charge separation and recombination. In this report, we introduce three amide additives, namely, formamide, acetamide, and urea, into the MAPbI3 perovskite by mixing them directly in perovskite precursor solutions. The Fermi level of MAPbI3 shifts from -4.36 eV to -4.63, -4.65, and -4.61 eV, respectively, upon addition of these additives. The charge transfer between perovskite and mp-TiO2 is found to be promoted as determined via TRPL spectra, and recombination in the perovskite is suppressed. As a result, the built-in electric field (Vbi) of the printable, hole-conductor-free mesoscopic perovskite solar cells based on these perovskites with amide additives is enhanced and a peak power conversion efficiency of 15.57% is obtained.

20.
Bioorg Med Chem ; 27(23): 115153, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31648877

RESUMO

In this study, a series of shikonin derivatives combined with benzoylacrylic had been designed and synthesized, which showed an inhibitory effect on both tubulin and the epidermal growth factor receptor (EGFR). In vitro EGFR and cell growth inhibition assay demonstrated that compound PMMB-317 exhibited the most potent anti-EGFR (IC50 = 22.7 nM) and anti-proliferation activity (IC50 = 4.37 µM) against A549 cell line, which was comparable to that of Afatinib (EGFR, IC50 = 15.4 nM; A549, IC50 = 6.32 µM). Our results on mechanism research suggested that, PMMB-317 could induce the apoptosis of A549 cells in a dose- and time-dependent manner, along with decrease in mitochondrial membrane potential (MMP), production of ROS and alterations in apoptosis-related protein levels. Also, PMMB-317 could arrest cell cycle at G2/M phase to induce cell apoptosis, and inhibit the EGFR activity through blocking the signal transduction downstream of the mitogen-activated protein MAPK pathway and the anti-apoptotic kinase AKT pathway; typically, such results were comparable to those of afatinib. In addition, PMMB-317 could suppress A549 cell migration through the Wnt/ß-catenin signaling pathway in a dose-dependent manner. Additionally, molecular docking simulation revealed that, PMMB-317 could simultaneously combine with EGFR protein (5HG8) and tubulin (1SA0) through various forces. Moreover, 3D-QSAR study was also carried out, which could optimize our compound through the structure-activity relationship analysis. Furthermore, the in vitro and in vivo results had collectively confirmed that PMMB-317 might serve as a promising lead compound to further develop the potential therapeutic anticancer agents.


Assuntos
Acrilatos/farmacologia , Antineoplásicos/farmacologia , Benzoatos/farmacologia , Naftoquinonas/farmacologia , Moduladores de Tubulina/farmacologia , Células A549 , Acrilatos/química , Acrilatos/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Benzoatos/química , Benzoatos/uso terapêutico , Desenho de Fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Camundongos Nus , Simulação de Acoplamento Molecular , Naftoquinonas/química , Naftoquinonas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/química , Moduladores de Tubulina/uso terapêutico
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