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1.
J Cell Mol Med ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052561

RESUMO

Cisplatin is the major chemotherapeutic drug in gastric cancer, particularly in treating advanced gastric cancer. Tumour cells often develop resistance to chemotherapeutic drugs, which seriously affects the efficacy of chemotherapy. GPR30 is a novel oestrogen receptor that is involved in the invasion, metastasis and drug resistance of many tumours. Targeting GPR30 has been shown to increase the drug sensitivity of breast cancer cells. However, few studies have investigated the role of GPR30 in gastric cancer. Epithelial-mesenchymal transition (EMT) has been shown to be associated with the development of chemotherapeutic drug resistance. In this study, we demonstrated that GPR30 is involved in cisplatin resistance by promoting EMT in gastric cancer. GPR30 knockdown resulted in increased sensitivity of different gastric cancer (GC) cells to cisplatin and alterations in the epithelial/mesenchymal markers. Furthermore, G15 significantly enhanced the cisplatin sensitivity of GC cells while G1 inhibited this phenomenon. In addition, EMT occurred when AGS and BGC-823 were treated with cisplatin. Down-regulation of GPR30 with G15 inhibited this transformation, while G1 promoted it. Taken together, these results revealed the role of GPR30 in the formation of cisplatin resistance, suggesting that targeting GPR30 signalling may be a potential strategy for improving the efficacy of chemotherapy in gastric cancer.

2.
Gene ; 726: 144169, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669642

RESUMO

BACKGROUND (OBJECTIVE): In the development of tumor therapy, the role of long non-coding RNA actin filagenin 1 antisense RNA 1 (1ncRNA AFAP1-AS1) is quite significant, but the actual role of AFAP1-AS1 in the treatment of prostate cancer has not been determined. In view of this, the author took AFAP1-AS1 as the research object to design an experimental study, and conducted an in-depth exploration of the pathogenesis of prostate cancer. METHODS: RT-qPCR was used to detect the expression of AFAP1-AS1 and miR-512-3p in prostate cancer tissues and cell lines. Perforation, flow cytometry and CCK-8 were used to detect the effects of cell proliferation, migration and invasion of mir-512-3p and a AFAP1-AS1. And the luciferase reporter gene was used to detect the downstream target gene of AFAP1-AS1, and the expression of CDK4, CDK6 and CCND1 protein was detected by Western blot. RESULTS: AFAP1-AS1 is highly expressed in prostate cancer tissues and cell lines. The expression level of AFAP1-AS1 is correlated with histological grade and distant metastasis. The overall level of patients with high expression of AFAP1-AS1 is low, and their survival rate is relatively low. Silencing AFAP1-AS1 can significantly increase the proliferation and migration of prostate cancer cells. AFAP1-AS1 silencing induces cell cycle arrest at G0/G1 phase. The downstream target of AFAP1-AS1 was mir-512-3p. The role of AFAP1-AS1 in the progression of prostate cancer cells was mediated by mir-512-3p. CONCLUSION: AFAP1-AS1 regulates miR-512-3p, so as to realize the regulation effect on the proliferation, invasion and migration of prostate cancer cells, and thereby promote the occurrence and development of prostate cancer, so as to provide the corresponding program for the treatment of prostate cancer. Abberivation: ADPC, androgen-dependent prostate cancer; CRPC, castrated prostate cancer; RNA1 AFAP1-Asl, Actin fiber-associated protein 1-anti-RNA1; miRNAs, MicroRNAs.


Assuntos
Proliferação de Células/genética , MicroRNAs/genética , Invasividade Neoplásica/genética , Neoplasias da Próstata/genética , RNA Longo não Codificante/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Fase G1/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Fase de Repouso do Ciclo Celular/genética , Taxa de Sobrevida
3.
J Cell Mol Med ; 24(2): 1360-1369, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31883303

RESUMO

Gastric cancer (GC) is a common malignancy with low 5-year overall survival (OS). Recently, immune therapy has been used to treat cancer. B7H5 and CD28H are novel immune checkpoint molecules. However, the prognostic value of B7H5/CD28H expression in patients with GC remains unclear. In this study, seventy-one patients diagnosed with GC were included in this study. Patients' GC tissues and matched adjacent tissue constructed a tissue microarray. The expression levels of B7H5 and CD28H were examined using immunohistochemistry. Correlations between the expression of B7H5 and CD28H and the clinical data were evaluated. We found that the expression of B7H5 and CD28H (both P = .001) were higher in GC tumour tissues than in adjacent noncancerous tissues. B7H5/CD28H expression acted as an independent predictive factor in the OS of patients with GC. High expression of B7H5 and CD28H predicted poor outcome. Patients in the B7H5+CD28H+ group had a lower 5-year OS compared with patients in the B7H5-CD28- group (4.5% vs 55.6%, P = .001). A significant difference was found in the 5-year OS between patients in the B7H5+CD28H- and B7H5+CD28H+ groups (33.5% vs 4.5%, P = .006). However, there was no correlation between B7H5 and CD28H expression (P = .844). Therefore, B7H5 and CD28H expression are up-regulated in GC and are independent prognostic factors for overall survival in patients with GC. Although there was no correlation between B7H5 and CD28H expression, high expression of B7H5 and CD28H predicts poor prognosis, especially when both are highly expressed.

4.
Environ Res ; 180: 108862, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31706597

RESUMO

In this study, the effects of electro-dewatering technology applied to high-salt industrial sludge dewatering performance were investigated, in terms of ions migrations and distributions by model simulation and layered tests. The simulation results of Na+ and K+ migrations were consistent with layered experiments during electro-dewatering, where Na+ ions migrated faster than K+ ions. More than 80% Na+ ions were removed by electromigration, which would be useful in subsequent sludge utilization. The mass specific energy consumption was reduced from 350.08 to 295.88 kWh per ton sludge by means of piecewise voltage electro-dewatering method. This study provided insights into the soluble ions migration and distribution mechanism in electro-dewatering process, and a method to improve commercial application performance of high-salt industrial sludge electro-dewatering.

5.
Opt Express ; 27(22): 31629-31643, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31684393

RESUMO

Neutral atoms have been observed to survive intense laser pulses in high Rydberg states with surprisingly large probability. Only with this Rydberg-state excitation (RSE) included is the picture of intense-laser-atom interaction complete. Various mechanisms have been proposed to explain the underlying physics. However, neither one can explain all the features observed in experiments and in time-dependent Schrödinger equation (TDSE) simulations. Here we propose a fully quantum-mechanical model based on the strong-field approximation (SFA). It well reproduces the intensity dependence of RSE obtained by the TDSE, which exhibits a series of modulated peaks. They are due to recapture of the liberated electron and the fact that the pertinent probability strongly depends on the position and the parity of the Rydberg state. We also present measurements of RSE in xenon at 800 nm, which display the peak structure consistent with the calculations.

6.
J Transl Med ; 17(1): 378, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730006

RESUMO

BACKGROUND: Atherosclerosis preferentially develops in regions of disturbed flow (DF). Emerging evidence indicates that yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway, sense different blood flow patterns and regulate atherosclerotic lesions. We previously found that methotrexate (MTX) reduces in-stent neoatherosclerosis, decreases the plaque burden, and has an effect on local fluid shear stress. Here, we investigated the atheroprotective effect of MTX under DF and the mechanisms underlying these properties. METHODS: Human umbilical vein endothelial cells (HUVECs) were subjected to biomechanical stretch using a parallel-plate flow system and treated with or without MTX at therapeutically relevant concentrations. Additionally, an extravascular device was used to induce DF in the left common carotid artery of C57BL/6 mice, followed by treatment with MTX or 0.9% saline. The artery was then assessed histopathologically after 4 weeks on a Western diet. RESULTS: We observed that MTX significantly inhibited DF-induced endothelial YAP/TAZ activation. Furthermore, it markedly decreased pro-inflammatory factor secretion and monocyte adhesion in HUVECs but had no effect on apoptosis. Mechanistically, AMPKa1 depletion attenuated these effects of MTX. Accordingly, MTX decreased DF-induced plaque formation, which was accompanied by YAP/TAZ downregulation in vivo. CONCLUSIONS: Taken together, we conclude that MTX exerts protective effects via the AMP-dependent kinase (AMPK)-YAP/TAZ pathway. These results provide a basis for the prevention and treatment of atherosclerosis via the inhibition of YAP/TAZ.

7.
J Environ Manage ; 250: 109473, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31505382

RESUMO

In the field of environmental wastewater treatment, it is a very meaningful topic to recover phosphate from swine wastewater in the form of struvite precipitation. The solution pH is one of the important influencing factors in the process of struvite precipitation. In this paper, an attempt was made to recover the phosphate from swine wastewater by adding plant ash. Experimental results have revealed that aeration can be replaced by optimal plant ash adding mode to increase the phosphate recovery efficiency. With the dosages of plant ash and magnesium metal were respectively 11.66 and 3.33 g/L the phosphate recovery efficiency reached 97.69% in 60 min. The efficiency was still above 95% after repeatedly using magnesium pellet for 3 times. The economic evaluation further revealed that the recovery cost of the proposed method was 0.62 $/kg PO4-P.


Assuntos
Fosfatos , Águas Residuárias , Animais , Precipitação Química , Concentração de Íons de Hidrogênio , Gado , Compostos de Magnésio , Fósforo , Estruvita , Suínos , Eliminação de Resíduos Líquidos
8.
J Phys Chem A ; 123(39): 8365-8369, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31525035

RESUMO

Benzene cation is a prototypical complex system that exhibits ultrafast conical intersections of different electronic states located close to the Franck-Condon region, yet little information is available about the dynamics of the cationic excited states. Here we utilize femtosecond time-resolved strong field ionization-photo fragmentation (SFI-PF) method to prepare and probe the electronic states of benzene cations. The transient of both the parent ion and the daughter ions are obtained, which present distinct behaviors at different pulse energies of the SFI laser. The results provide the first experimental evidence of B2E2g-X2E1g ultrafast relaxation of benzene cation, which occurs in about 250-270 fs. Our study should pave the way to revealing the ultrafast photochemistry of complex molecular cations.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31354847

RESUMO

Oligosaccharide esters, which are among the main active components of Polygalae Radix (PR), demonstrate significant pharmacological activities in the human nervous system. In our previous research, some other constituents in PR were able to improve the bioavailability of oligosaccharide esters such as sibiricose A5 (SA5), sibiricose A6 (SA6), and 3,6'-disinapoyl sucrose (DISS), but the related components and their underlying mechanisms remain unknown. The present study aimed to investigate the intestinal absorptive profile of SA5, SA6, and DISS and the absorptive behavior influenced by the coadministration of polygalaxanthone III and total saponins of PR (TS) using an in vitro everted rat gut sac model, along with the possible mechanisms that may influence absorption. The results showed that TS could significantly enhance the absorption of SA5, SA6, and DISS monomers. Verapamil, a P-glycoprotein inhibitor, was able to elevate the absorption of SA5 and SA6, and an absorption experiment using Rho123 led us to conclude that TS influenced the absorption of SA5 and SA6 in a manner similar to that of a P-glycoprotein inhibitor. Sodium caprate, a paracellular absorption enhancer, was found to increase the absorption of SA5, SA6, and DISS. Results showed that the absorption mechanisms of SA5 and SA6 may combine active transport with paracellular passive penetration, while DISS's absorption was dominated by paracellular passive penetration. However, the relationship between polygala saponins and the absorption of SA5, SA6, and DISS by paracellular passive penetration remain to be examined. This is the direction of our future research.

10.
Cancer Manag Res ; 11: 4905-4915, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213909

RESUMO

Background and aim: Paclitaxel (PTX) plus 5-fluorouracil (5-Fu) has become the standard chemotherapy for advanced gastric cancer (GC). Apatinib, a small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, improves outcomes in GC patients as a third-line treatment. However, its impact on the chemosensitivity of GC remains to be determined. Hence, we aimed to assess the efficacy and safety of apatinib combined with chemotherapy in vivo and in vitro. Methods: The MGC803 cell viability was determined by Cell Counting Kit-8 assay, and the interactions between apatinib and conventional cytotoxic agents revealed by combination index values were calculated using Calcusyn 2.0 software. We also used a zebrafish embryo xenograft model to validate the synergistic interactions. Furthermore, 4 patients with late-stage GC were enrolled to explore the efficacy and safety of PTX/Tegafur Gimeracil Oteracil Potassium (S1) (PS) chemotherapy plus apatinib in conversion surgery. Results: Apatinib showed synergistic interactions with both PTX and 5-Fu in vivo. The zebrafish embryo xenograft model also demonstrated that apatinib significantly enhanced the antitumor activity of PTX and 5-Fu. Apatinib plus PS chemotherapy was well tolerated before surgery. Objective response to preoperative SPA treatment was achieved in all 4 patients. No postoperative bleeding events or wound-healing complications were observed. No postperative morbidity occurred and no morbidity was encountered. Pathological examination showed that all patients had grade Ib pathological response. Conclusion: The experimental data suggested that apatinib improves the efficacy of PTX and 5-Fu both in vitro and in vivo. Clinical evidence showed that a combination of PS chemotherapy with apatinib may be an efficient and acceptable safety treatment for late-stage GC, especially in conversion surgery.

11.
Sci Rep ; 9(1): 8893, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222075

RESUMO

Struvite precipitation electrolyzers are interesting environmental electrochemical reactors with potential applications for efficient phosphate recovery from wastewater, such as swine wastewater. In this paper, effects of phosphate concentration and pH on the struvite precipitation reaction rate were investigated. When phosphate concentration decreased from 100 to 20 mg/L, the precipitation reaction rate decreased from 396.65 mg/L·h to 70.46 mg/L·h, indicating that the reaction rate of struvite crystallization can be controlled by adjusting pH according to the change of phosphate concentration. Numerical simulation of different currents and flow rates on pH in the electrolyzer was developed and validated, and pH in the electrolyzer was dynamically measured along the distribution point of the flow field. We aimed to test the treatment effect of the electrolyzer on actual swine wastewater. When the flow rate was 20 L/h and constant voltage was 4 V, the electrolyzer was run continuously for 5 hours with the volume of 50 L. The phosphate recovery efficiency reached 99.51%, and the time-space yield of the struvite precipitation electrolyzer was 0.0219 kg/m2·h. The harvested struvite particles were identified by XRD and SEM-EDS, which presented orthorhombic structure and high purity. Economic analysis demonstrated that the proposed electrolyzer was cost-effective and technologically convenient.

12.
J Psychiatr Res ; 114: 55-66, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31039481

RESUMO

Chronic stress-induced anxiety disorder is a highly-prevalent, modern social disease in which oxidative stress plays an important role. It is necessary to determine the underlying mechanisms governing this disorder to establish an effective treatment target for anxiety disorders. In this study, we examined the behavioral changes in mice subjected to chronic mild stress (CMS). We found that CMS exposure leads to anxiety-like phenotypes and increased levels of oxidative stress in the ventral hippocampus of mice. Furthermore, CMS increased the excitatory synaptic transmission of pyramidal cells in the ventral CA1 (vCA1). Administration of 4-hydroxy-3-methoxy-acetophenone (apocynin), an inhibitor of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, clearly ameliorated the changes induced by CMS exposure. In addition, our results of behavioral tests and analyses of reactive oxygen species (ROS) using NOX2-deficient mice indicate that CMS-induced enhanced oxidative stress level is primarily caused by the increased expression of NOX2. NOX2-derived oxidative stress can serve as a target for anxiety therapy led by chronic stress.

13.
Environ Monit Assess ; 191(3): 151, 2019 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-30739246

RESUMO

The effect of spring snowmelt infiltration in a seasonal soil frost area on groundwater recharge was evaluated by systematically monitoring meteorological factors, soil temperature and humidity, groundwater table and temperature, electrical conductivity, and the value of δ18O in a small field site over a 2-year period. The variation of soil temperature and humidity, groundwater table during the freezing period, and the snowmelt period respectively, as well as their correspondence to the relevant environmental factors, and the influencing factors of the permeability of frozen layer were analyzed. The results showed that the evaluation of precipitation infiltration in seasonal soil frost areas should be divided into three stages: a non-freezing period, a freezing period, and a snowmelt period. Snow is the main form of precipitation during the freezing period, and groundwater cannot be recharged. During the snowmelt period of spring, the snow cover that accumulated during the freezing period infiltrates together with rainfall and has a significant effect on groundwater recharge. The general precipitation infiltration process occurs after the frozen soil thaws completely. These research results can improve the accuracy of groundwater recharge calculations for snowmelt infiltration in the seasonal soil frost area of Northeast China and provide a scientific basis for the evaluation and management of regional water resources.


Assuntos
Monitoramento Ambiental/métodos , Água Subterrânea/análise , Estações do Ano , Neve/química , Solo/química , Recursos Hídricos , China , Água Subterrânea/química
14.
Front Psychol ; 10: 64, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30766497

RESUMO

Background: Depression is a common mental disorder worldwide. Psychological treatments and antidepressant medication are the usual treatments for depression. However, a large proportion of patients with depression do not respond to the treatments. In 2005, Vagus nerve stimulation was approved for the adjunctive long-term treatment of chronic or recurrent depression in adult patients experiencing a major depressive episode who had failed to respond to four or more adequate antidepressant treatments. However, the efficacy of VNS for treating depression remains unclear. Accordingly, we performed a systematic review to evaluate the efficacy and safety of VNS. Methods: We conducted a systematic review in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Systematic search was performed in the database of Pubmed, Embase, CENTRAL, and Web of science for identifying the suitable trials. Suicidal rate was considered as the primary outcome in this review. Result: Only two randomized sham controlled add-on studies including 255 cases (134 with VNS treatment and 121 control cases) were included in this review. None of the studies reported suicidal rate. We performed a qualitative analysis and it is suggested that there was no significant statistic difference between VNS and sham VNS on the score of 24-item Hamilton Rating Scale for Depression (HAMD24) (MD: -2.40, 95% CI: -7.90 to 3.10). Similar findings were also reported on improvement percentage of HAMD24 (MD: 1.00, 95%CI: -6.06 to 8.06), Montgomery-Asberg Depression Rating Scale (MADRS) (MD: 4.70, 95%CI: -2.98 to 12.38) and 30 item Inventory of Depressive Symptomalogy-Self-Report (IDS-SR30) (MD: 4.9, 95%CI: -1.89 to 11.69). However, a marginal difference of Beck Depression Inventory self-rating score was detected between the real and sham treatment (MD: 7.80, 95% CI: 0.34 to 15.26). Aminor effect of IDS-SR30was also found in real VNS group (RR: 2.33, 95% CI: 1.07 to 5.10). Conclusion: The efficacy and safety of VNS for depression is still unclear. Further randomized controlled trials are needed to confirm the efficacy and safety of VNS.

15.
Neurosci Bull ; 35(4): 637-648, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30790216

RESUMO

Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems. The immunopotentiator thymosin alpha-1 (Tα1) has recently been reported to have anti-inflammatory and neuroprotective functions in rodents. However, how Tα1 affects inflammatory pain remains unclear. In the present study, intraperitoneal injection of Tα1 attenuated complete Freund's adjuvant (CFA)-induced pain hypersensitivity, and decreased the up-regulation of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in inflamed skin and the spinal cord. We found that CFA-induced peripheral inflammation evoked strong microglial activation, but the effect was reversed by Tα1. Notably, Tα1 reversed the CFA-induced up-regulation of vesicular glutamate transporter (VGLUT) and down-regulated the vesicular γ-aminobutyric acid transporter (VGAT) in the spinal cord. Taken together, these results suggest that Tα1 plays a therapeutic role in inflammatory pain and in the modulation of microglia-induced pro-inflammatory cytokine production in addition to mediation of VGLUT and VGAT expression in the spinal cord.

16.
Sci Rep ; 9(1): 447, 2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30679589

RESUMO

Gastric cancer (GC) ranks as the third leading cause of cancer-related mortality worldwide, and approximately 42% of all cases diagnosed each year worldwide are diagnosed in China. A large number of clinical applications have revealed that Trametes robiniophila Μurr. (Huaier) exhibits an anti-tumour effect. However, loss of the bioactive components of Huaier during the extraction procedure with water is unavoidable, and the underlying mechanism of the anti-cancer effect of Huaier remains poorly understood. In this study, we investigated the anti-cancer effect of Huaier n-butanol extract, which contained 51.4% total flavonoids, on HGC27, MGC803, and AGS human GC cell lines in vitro. At a low concentration, Huaier n-butanol extract inhibited the growth of these GC cell types, induced cell cycle arrest and reduced cell metastasis. Moreover, Huaier n-butanol extract suppressed the c-Myc-Bmi1 signalling pathway, and overexpression of Bmi1 reversed the effects of Huaier n-butanol extract on GC cells. Thus, our findings indicate that Huaier n-butanol extract suppresses the proliferation and metastasis of GC cells via a c-Myc-Bmi1-mediated approach, providing a new perspective for our understanding of the anti-tumour effects of Huaier. These results suggest that Huaier n-butanol extract could be an attractive therapeutic adjuvant for the treatment of human GC.

17.
Ann Diagn Pathol ; 38: 1-5, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30380400

RESUMO

Fat mass and obesity associated (FTO) is a protein-coding gene, also known as the obesity gene. It has been reported previously to be associated with a variety of malignant cancers, such as breast, thyroid and acute myeloid leukemia. The aim of the present study was to investigate the FTO mRNA expression in human clear cell renal cell carcinoma and its clinical value. FTO mRNA expression and its prognostic value were investigated by bioinformatic analysis of the data from The Cancer Genome Atlas (TCGA, https://cancergenome.nih.gov/). The Kaplan-Meier analysis showed that FTO mRNA expression in the lower quartile is significantly associated with poor survival in clear cell renal cell carcinoma patients (P < 0.0001). This study indicated that higher FTO mRNA expression may have a protective role and it may be a vital molecular marker in the prognosis of clear cell renal cell carcinoma patients.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/biossíntese , Biomarcadores Tumorais/análise , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Adulto , Idoso , Dioxigenase FTO Dependente de alfa-Cetoglutarato/análise , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Mineração de Dados , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Prognóstico , RNA Mensageiro/análise , Transcriptoma
18.
Phys Chem Chem Phys ; 20(41): 26117-26125, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30306996

RESUMO

The mechanical stability of porous zeolitic materials has long been an important issue due to their advanced applications in many fields. Here, we choose to study the pressure induced structural modifications on the AlPO4-5 (AFI) framework. We find that the Raman characteristics of the confined iodine molecules in the AFI channels, with a low filling density, show discontinuities at around 3 and 10 GPa, which can be attributed to the implications of framework changes. Subsequent theoretical simulations on the AFI framework demonstrate that both a tilting mechanism along the c axis and a rotating mechanism in the ab plane of the tetrahedrons contribute to the structural deformation, and the AFI framework is collapsible at 4 and 10 GPa, which confirms those values found in the Raman studies. In this nanoconfinement system of I@AFI, the host and guest depend on and interact with each other mutually. No supporting effect on the AFI framework is found for the confined individual iodine molecules with such a low filling density, but they can be regarded as molecular probes to reflect the structural collapse of AFI. Thus, we provide a novel way to detect the structural deformation of porous materials under high pressure.

19.
Toxicol Appl Pharmacol ; 358: 1-9, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30196066

RESUMO

Non-small cell lung cancer (NSCLC) has a high mortality rate worldwide. Various treatments strategies have been used against NSCLC including individualized chemotherapies, but innate or acquired cancer cell drug resistance remains a major obstacle. Recent studies revealed that the Kelch-like ECH associated protein 1/Nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) pathway is intimately involved in cancer progression and chemoresistance. Thus, antagonizing Nrf2 would seem to be a viable strategy in cancer therapy. In the present study a traditional Chinese medicine, triptolide, was identified that markedly inhibited expression and transcriptional activity of Nrf2 in various cancer cells, including NSCLC and liver cancer cells. Consequently, triptolide made cancer cells more chemosensitivity toward antitumor drugs both in vitro and in a xenograft tumor model system using lung carcinoma cells. These results suggest that triptolide blocks chemoresistance in cancer cells by targeting the Nrf2 pathway. Triptolide should be further investigated in clinical cancer trials.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Elementos de Resposta Antioxidante/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Diterpenos/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fenantrenos/administração & dosagem , Células A549 , Animais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Elementos de Resposta Antioxidante/fisiologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/fisiologia , Compostos de Epóxi/administração & dosagem , Células Hep G2 , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
20.
Cancer Manag Res ; 10: 3125-3139, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214305

RESUMO

Background: Many studies have evaluated the relationship between alkaline phosphatase (ALP) and the prognosis for prostate cancer (PCa). But they have not reached a widespread consensus yet. Therefore, we completed a meta-analysis to ascertain the significance of ALP and the prognosis for PCa. Methods: A literature search was performed in the PubMed, Embase, and Web of Science databases. HRs concerning overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS) were extracted to evaluate the impacts of ALP on the prognosis for PCa. Subgroup analyses were conducted on different study types, regions, sample sizes, and cutoff values. Sensitivity analysis was performed by removing one study in sequence. Results: A total of 63 studies from 54 articles with 16,135 patients were included in this meta-analysis. The pooled results indicated that high baseline ALP was associated with obviously poor OS (HR=1.74, 95% CI: 1.47-2.06) and PFS (HR=1.60, 95% CI: 1.13-2.26) in patients with PCa. The pooled HR for bone-specific ALP and OS was 1.76 (95% CI: 1.45-2.15). However, no association between ALP and CSS (HR=1.002, 95% CI: 0.998-1.005) was found for PCa. The results of subgroup analyses were all in accordance with the main findings. Sensitivity analysis suggested that no single study could affect the stability of the results. Conclusion: High serum ALP is significantly associated with poor OS and PFS except for CSS in PCa. ALP is an efficient and convenient biomarker for PCa prognosis.

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