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1.
Cell Mol Life Sci ; 79(3): 135, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35179655

RESUMO

Oxaliplatin is the first-line regime for advanced gastric cancer treatment, while its resistance is a major problem that leads to the failure of clinical treatments. Tumor cell heterogeneity has been considered as one of the main causes for drug resistance in cancer. In this study, the mechanism of oxaliplatin resistance was investigated through in vitro human gastric cancer organoids and gastric cancer oxaliplatin-resistant cell lines and in vivo subcutaneous tumorigenicity experiments. The in vitro and in vivo results indicated that CD133+ stem cell-like cells are the main subpopulation and PARP1 is the central gene mediating oxaliplatin resistance in gastric cancer. It was found that PARP1 can effectively repair DNA damage caused by oxaliplatin by means of mediating the opening of base excision repair pathway, leading to the occurrence of drug resistance. The CD133+ stem cells also exhibited upregulated expression of N6-methyladenosine (m6A) mRNA and its writer METTL3 as showed by immunoprecipitation followed by sequencing and transcriptome analysis. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA. The CD133+ tumor stem cells can regulate the stability and expression of m6A to PARP1 through METTL3, and thus exerting the PARP1-mediated DNA damage repair ability. Therefore, our study demonstrated that m6A Methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Metiltransferases/metabolismo , Células-Tronco Neoplásicas/patologia , Oxaliplatina/farmacologia , Poli(ADP-Ribose) Polimerase-1/genética , Estabilidade de RNA , Neoplasias Gástricas/tratamento farmacológico , Antígeno AC133 , Animais , Antineoplásicos/farmacologia , Apoptose , Proliferação de Células , Criança , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Metiltransferases/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/química , Poli(ADP-Ribose) Polimerase-1/metabolismo , Prognóstico , RNA Mensageiro , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Endocr J ; 69(5): 529-537, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34937832

RESUMO

We aimed to explore the role of microRNA 195 (miR-195) in diabetic retinopathy (DR). From January 2019 to July 2020, 50 patients with DR undergoing vitrectomy and 40 patients with idiopathic macular holes undergoing vitrectomy were selected as the observation group (OG) and control group (CG), respectively. The mRNA and protein expression levels of miR-195, SIRT1, BAX, and BCL-2 were detected in the retinal tissues obtained from the two groups during surgery. In addition, human retinal endothelial cells and human dermal microvascular endothelial cells were cultured in a high-glucose environment to detect the targeted relationship between miR-195 and SIRT1; determine the mRNA and protein expression levels of SIRT1, BAX, and BCL-2 after miR-195 knockdown; and assess the levels of cell proliferation and apoptosis. In OG, the mRNA and protein expression levels of miR-195 and BAX were high, whereas those of BCL-2 and SIRT1 were low. Moreover, we detected a targeted relationship between miR-195 and SIRT1. Conversely, miR-195 knockdown led to the downregulation of the mRNA and protein expression levels of BAX and the upregulation of the mRNA and protein expression levels of SIRT1 and BCL-2 as well as improvement in cell growth and a decrease in the apoptosis rate. miR-195 is overexpressed in DR, and its targeted relationship with SIRT1 inhibits the growth of cells in the retina and accelerates apoptosis.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , MicroRNAs , Apoptose/genética , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Células Endoteliais/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína X Associada a bcl-2/genética
3.
Phys Chem Chem Phys ; 23(39): 22629-22639, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34596188

RESUMO

In this study, the liquid-liquid equilibrium of DMSO-C8H10 aromatic isomer-n-decane systems was measured at 30 °C under atmospheric pressure at first, followed by Othmer-Tobias equation data reliability verification and NRTL/UNIQUAC activity coefficient model correlation. Moreover, intermolecular interaction energies and molecular polarity indexes (MPI) were calculated to interpret the extraction results. Finally, a set of wave function analyses was accomplished to elaborate the physical nature of the interaction in the DMSO extraction process. These investigations show that: (1) intermolecular interaction energy and the MPI results corroborate the aromatic and alkane extraction distribution coefficients well. (2) The interactions between aromatics and DMSO are weak hydrogen bonding and van der Waals (vdW) interactions. The attractive part mainly involves dispersion (49.57-53.30%) and electrostatic (35.49-37.83%) effects. (3) The interactions between aromatics and n-decane are vdW interactions, dominated by attractive dispersion (70.41-70.93%) and repulsive exchange effects.

4.
Opt Express ; 22(23): 29111-6, 2014 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-25402149

RESUMO

We report herein an efficient eye-safe Raman laser, which is based upon Nd:YVO4₋YVO4 and in-band pumped by a wavelength-locked laser diode array at 878.6 nm. By virtue of mitigated thermal load and improved pump absorption, a maximum average output power of 5.2 W at 1525 nm is obtained under the incident pump power of 30.6 W with the pulse repetition frequency of 140 kHz, corresponding to an optical efficiency of 17.0%.


Assuntos
Segurança de Equipamentos , Olho/efeitos da radiação , Lasers Semicondutores , Lasers de Estado Sólido , Desenho de Equipamento , Humanos
5.
Appl Opt ; 53(29): 6778-81, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25322382

RESUMO

A multisegmented Nd:YVO4 laser operating at 1342 nm that is in-band pumped by a wavelength-locked 878.6 nm laser diode is reported here. We achieve an output power of 12.45 W at 1342 nm for an absorbed pump power of 35.6 W, corresponding to an optical-to-optical efficiency of 34.9% and a slope efficiency of 36.1%. To the best of our knowledge, it is the highest optical-to-optical efficiency of Nd:YVO4 lasers operating at 1342 nm with an output power more than 10 W.


Assuntos
Raios Infravermelhos , Lasers de Estado Sólido , Semicondutores , Transferência de Energia , Desenho de Equipamento , Análise de Falha de Equipamento
6.
Pharm Biol ; 52(10): 1341-4, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25046547

RESUMO

CONTEXT: Proton pump inhibitor (PPI) increases the risk of decrease in bone mineral density (BMD). However, whether calcitrol improves this situation is unknown. OBJECTIVE: The current study investigates the effects of calcitriol on BMD in patients with esomeprazole therapy. MATERIALS AND METHODS: Three hundred and eighty-six participants with gastrointestinal ulcerations were enrolled and randomly assigned into controlled and supplemented groups. Participants in the controlled group were prescribed esomeprazole (20 mg/qd), while the supplemented group was prescribed esomeprazole (20 mg/qd) and calcitriol (2.5 µg/qd). BMD, serum levels of calcium, carboxy-terminal collagen crosslinks (CTX), and alkaline-phosphatase (ALP) were assessed. RESULTS: (1) No significant between-group difference of age, gender, smoking, previous glucocorticoid use and hemoglobin level was found; (2) after 10.6 ± 0.8 d of PPI therapy, BMD T score in the controlled group was slightly increased compared with initial (-1.25 ± 0.08 versus -1.28 ± 0.06, p = 0.084), while there was no change in the supplemented group (-1.25 ± 0.05 versus -1.26 ± 0.03, p = 0.308); (3) during study termination, calcium level in the supplemented group was slightly higher than the controlled group (2.05 ± 0.03 mmol/L versus 2.01 ± 0.05 mmol/L, p = 0.073), while no significant differences of CTX (366.57 ± 43.71 pg/mL versus 373.15 ± 50.23 pg/mL, p = 0.036) and ALP were found among these two groups (50.47 ± 9.32 U/L versus 52.23 ± 10.45 U/L, p = 0.075). CONCLUSION: Patients with gastrointestinal ulcerations with esomeprazole therapy, calcitriol supplement showed no efficacy on BMD changes.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Calcitriol/administração & dosagem , Esomeprazol/administração & dosagem , Úlcera Péptica/tratamento farmacológico , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/diagnóstico , Resultado do Tratamento
7.
J Med Case Rep ; 18(1): 123, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38515205

RESUMO

BACKGROUND: Giant cell tumor of soft tissue is a low malignant uncommon neoplasm, with histologic features and immunophenotype similar to its bone counterpart. Primary giant cell tumor of soft tissue in the thyroid gland is considered an exceedingly rare entity. CASE PRESENTATION: We describe a case of primary thyroid giant cell tumor of soft tissue in a 69-year-old Chinese female patient. Neck ultrasonography showed a 19 mm × 12 mm × 5 mm nodule with heterogeneous echo and clear boundary located within the left thyroid. Histopathological examination revealed that the neoplasm was composed of two morphological components, mononuclear cells admixed with multinucleated osteoclast-like giant cells. Immunohistochemically, the tumor cells were positive for CD68 and vimentin, but were negative for epithelial membrane antigen, cytokeratin, and additional muscle markers. She underwent left unilateral thyroidectomy, and total thyroidectomy was performed for local recurrence 3 months later. The patient remained well without recurrence or metastasis following up for 12 months. CONCLUSION: The significance of this case lies in its rarity, the challenge of preoperative clinical diagnosis, and the differential diagnosis with other malignancies.


Assuntos
Tumores de Células Gigantes , Glândula Tireoide , Feminino , Humanos , Idoso , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Tumores de Células Gigantes/diagnóstico , Pescoço/patologia , Tireoidectomia , Diagnóstico Diferencial
8.
Phys Chem Chem Phys ; 15(27): 11394-401, 2013 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-23740151

RESUMO

Improving the Li storage properties of a Si negative electrode is of great significance for Li-ion batteries. A major challenge is to fabricate Si-based active materials with good electronic conduction and structural integrity in the process of discharging and charging. In this study, novel Si nanoparticles-graphene composites have been synthesized by hybrid electrostatic assembly between positively charged aminopropyltriethoxysilane modified Si nanoparticles and negatively charged graphene oxide, followed by thermal reduction. Commercially available Si nanoparticles are well embedded and uniformly dispersed into the graphene sheets, and the typically wrinkled graphene sheets form a network and cover the highly dispersed Si nanoparticles well. No any obvious aggregation of the Si nanoparticles can be found and many nanospaces exist around the Si nanoparticles, which provide buffering spaces needed for volume changes of Si nanoparticles during insertion/extraction of Li. High capacity and long cycle life (822 mA h g(-1) after 100 cycles at a current density of 0.1 A g(-1)) have been realized in the novel Si nanoparticles-graphene composites for Li-ion batteries. The excellent electrochemical performance is ascribed to the uniform distribution of Si nanoparticles and graphene, which effectively prevents aggregation and pulverization of Si nanoparticles, keeps the overall electrode highly conductive, and maintains the stability of the structure.


Assuntos
Fontes de Energia Elétrica , Grafite/química , Lítio/química , Nanopartículas/química , Silício/química , Eletrodos , Tamanho da Partícula , Propriedades de Superfície
9.
Zhonghua Bing Li Xue Za Zhi ; 42(1): 10-4, 2013 Jan.
Artigo em Zh | MEDLINE | ID: mdl-23611266

RESUMO

OBJECTIVE: To study the possible clonal origin of neuroendocrine cells in colorectal adenocarcinoma. METHODS: Twenty-six microsatellite loci were screened using laser capture microdissection, DNA extraction and whole genome amplification. Microsatellite instability (MSI) and loss of heterozygosity (LOH) in adenocarcinoma cells and neuroendocrine cells amongst 30 cases of colorectal carcinoma with neuroendocrine differentiation were detected using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)-silver staining. The mutation status of p53 was evaluated by PCR-sequencing. The clonal origin of neuroendocrine cells in colorectal adenocarcinoma was determined. RESULTS: Amongst the 30 cases studied, the prevalence of MSI was 16.9% while that of LOH was 8.5%. The rate showed no statistically significant difference between adenocarcinoma cells and neuroendocrine cells. In 6 cases, the microsatellite alteration was entirely consistent. In 23 cases, the rate of microsatellite alteration consistency was greater than that of inconsistency. In 1 case, the consistency and inconsistency rates were identical. There was statistically significant difference between consistency and inconsistency of microsatellite alteration. The prevalence of p53 mutation was 16.7% which was the same for both adenocarcinoma cells and neuroendocrine cells. CONCLUSIONS: Adenocarcinoma cells and neuroendocrine cells in colorectal adenocarcinoma with neuroendocrine differentiation have similar biologic changes. It is likely that they are of identical origin.


Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Perda de Heterozigosidade , Instabilidade de Microssatélites , Proteína Supressora de Tumor p53/genética , Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , Humanos , Microdissecção e Captura a Laser , Células Neuroendócrinas/patologia
10.
Brain Res Bull ; 203: 110758, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37704055

RESUMO

This study aims to explore a method based on brain networks for implicit attention by using wavelet coherence as feature to identify individual targets in the visual field, find the optimal classification rhythm and time window, and investigate the relationship between the optimal rhythm and N2pc event-related potential. The study uses a weighted minimum norm estimate to locate the sources of the scalp EEG and reconstructs the source time series. The functional connectivity between brain areas during the visual search process is evaluated using wavelet coherence analysis, and a lateral difference network is constructed based on the difference in coherence values between the left and right visual fields. A support vector machine classifier is trained based on the wavelet coherence network features to identify the target in the left or right visual field. We also extract N2pc from the source activity data of the parieto-occipital brain region and record the time period in which N2pc occurred. The study finds that the best classification performance is achieved in the theta rhythm from 200 to 400 ms and achieved an average classification accuracy of 87% (chance level: 51.07%) in a serial search task. And this time window corresponds to the time period when N2pc appeared. The results show that the use of wavelet coherence analysis to evaluate the functional connectivity between brain areas during the visual search process provides a new approach for analyzing brain activity. The study's findings regarding the relationship between the N2pc and theta rhythm and the effectiveness of using wavelet coherence network features based on the theta rhythm for visual search classification contribute to the understanding of the neural mechanisms underlying visual search.


Assuntos
Eletroencefalografia , Potenciais Evocados , Eletroencefalografia/métodos , Encéfalo , Atenção , Ritmo Teta
11.
Front Pediatr ; 11: 1181462, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37528876

RESUMO

We report a case of a 10-year-old male patient with pulmonary artery aneurysm (PAA) caused by infective endarteritis of the pulmonary artery attributed to patent ductus arteriosus. He was found to have patent ductus arteriosus at the age of 2, but he was not treated because of the absence of symptoms and normal physical development. He sought medical attention for fever and cough in August 2022. Echocardiography showed pulmonary artery aneurysm, intrapulmonary artery bulge, patent ductus arteriosus, and pericardial effusion. Contrast-enhanced CT showed pulmonary artery aneurysm, patent ductus arteriosus, and a slight compression of the left main bronchus. Surgery was performed to reconstruct the main pulmonary trunk and repair the ductus arteriosus in November 2022. The surgical outcomes were satisfactory.

12.
Opt Express ; 20(25): 27953-8, 2012 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-23262741

RESUMO

We report herein the enhancement in both power and efficiency performance of a continuous-wave intra-cavity singly resonant optical parametric oscillator (ICSRO) by introducing finite resonant wave output coupling. While coupling out the resonant wave to useful output, the output coupling increases the SRO threshold properly thus suppresses the back-conversion under high pump power. Therefore, the down-conversion efficiency is maintained under high pump without having to raise the threshold by defocusing. With a T = 9.6% signal wave output coupler used, the SRO threshold is 2.46 W and the down-conversion efficiency is 72.9% under the maximum pump power of 21.4 W. 1.43 W idler power at 3.66 µm and 5.03 W signal power at 1.5 µm are obtained, corresponding to a total extraction efficiency of 30.2%. The resonant wave out coupling significantly levels up the upper limit for the power range where the ICSRO exhibits high efficiency, without impeding its advantage of low threshold.


Assuntos
Modelos Teóricos , Óptica e Fotônica/instrumentação , Óptica e Fotônica/métodos , Oscilometria/instrumentação , Oscilometria/métodos , Desenho de Equipamento , Lasers de Estado Sólido , Neodímio/química , Nióbio/química , Óxidos/química
13.
Artigo em Inglês | MEDLINE | ID: mdl-34639508

RESUMO

The Smog Free Tower (SFT) in the city of Xi'an, China, is the world's first outdoor architecture that uses solar energy and filtration technology to purify polluted air. It provides a unique opportunity to explore residents' willingness to pay for air quality and their related behaviors. Drawing on data collected after the establishment of the SFT, this paper reveals the characteristics of changes in people's willingness to pay for clean air. We found that, prior to the release of an assessment report on the SFT, housing prices had an inverted U-shaped relationship with the distance to the SFT, which indicated people tended to purchase houses a certain distance away from the SFT. The threshold value of distance was inversely related to the greening ratio of the residential area. However, after the publication of the experimental report on the SFT, housing prices decreased as the distance to the SFT increased, indicating the closer the house was to the SFT, the more likely people were to buy it. These changes confirmed that people are willing to pay for clean air. The convenience of transportation had a significant moderating effect on the willingness to pay for clean air, however. In other words, people may buy houses with lower air quality if they have better transportation accessibility. The findings of this paper may have practical implications for environmental governance, urban planning, residential satisfaction, and real estate market regulation.


Assuntos
Poluição do Ar , Smog , Poluição do Ar/prevenção & controle , China , Conservação dos Recursos Naturais , Política Ambiental , Habitação , Humanos
14.
Mitochondrial DNA B Resour ; 6(6): 1729-1731, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34104753

RESUMO

Pluchea pteropoda Hemsl is a mangrove associate plant of Asteraceae with medicinal properties such as anti-inflammation and fever-relieving. Here, our study presented the complete chloroplast (cp) genome of Pluchea pteropoda Hemsl. The cp genome of P. pteropoda was 152,300 bp in length, including a large single copy (LSC) region of 84,127 bp, a small single copy (SSC) region of 18,093 bp and a pair of inverted repeats (IR) regions of 25,040 bp. A total of 111 unique genes were found, comprising 79 protein-coding genes, 28 tRNA genes, and 4 rRNA genes. The GC content of the cp genome was 37.5%. Phylogenetic analysis suggested that P. pteropoda nested in Pluchea clade, which was closely related to Ageratina adenophora and Senecio scandens. The work provides beneficial data for following researches on the genetic variation, species delimitation, phylogeny and classification of Pluchea genus.

15.
Toxins (Basel) ; 13(4)2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807312

RESUMO

Ochratoxin A (OTA) usually contaminates agricultural products such as grapes, oatmeal, coffee and spices. Light was reported as an effective strategy to control spoilage fungi and mycotoxins. This research investigated the effects of light with different wavelengths on the growth and the production of OTA in Aspergillus ochraceus and Aspergillus carbonarius. The results showed that the growth of both fungi were extremely inhibited by UV-B. Short-wavelength (blue, violet) significantly inhibited the production of OTA in both fungi, while the inhibitory effect of white was only demonstrated on A. ochraceus. These results were supported by the expression profiles of OTA biosynthetic genes of A. ochraceus and A. carbonarius. To clarify, the decrease in OTA production is induced by inhibition or degradation; therefore, the degradation of OTA under different wavelengths of light was tested. Under UV-B, the degradation rate of 10 µg/mL OTA standard pure-solution samples could reach 96.50% in 15 days, and the degradation effect of blue light was relatively weak. Furthermore, infection experiments of pears showed that the pathogenicity of both fungi was significantly decreased under UV-B radiation. Thus, these results suggested that light could be used as a potential target for strategies in the prevention and control of ochratoxigenic fungi.


Assuntos
Aspergillus ochraceus/efeitos da radiação , Aspergillus/efeitos dos fármacos , Frutas/microbiologia , Ocratoxinas/biossíntese , Pyrus/microbiologia , Raios Ultravioleta , Aspergillus/genética , Aspergillus/crescimento & desenvolvimento , Aspergillus/metabolismo , Aspergillus ochraceus/genética , Aspergillus ochraceus/crescimento & desenvolvimento , Aspergillus ochraceus/metabolismo , Microbiologia de Alimentos , Regulação Fúngica da Expressão Gênica , Fatores de Tempo
16.
J Exp Clin Cancer Res ; 40(1): 260, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34412665

RESUMO

BACKGROUND: Oxaliplatin is one of the most commonly used chemotherapeutic agent for the treatment of various cancers, including gastric cancer. It has, however, a narrow therapeutic index due to its toxicity and the occurrence of drug resistance. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect and reduce the toxicity of oxaliplatin. In our previous study, we demonstrated that ethaselen (BBSKE), an inhibitor of thioredoxin reductase, effectively inhibited the growth of gastric cancer cells and promoted apoptosis in vitro. In the present study, we investigated whether BBSKE can potentiate the anti-tumor effect of oxaliplatin in gastric cancer in vivo and vitro. METHODS: Cellular apoptosis and ROS levels were analyzed by flow cytometry. Thioredoxin reductase 1 (TrxR1) activity in gastric cancer cells, organoid and tumor tissues was determined by using the endpoint insulin reduction assay. Western blot was used to analyze the expressions of the indicated proteins. Nude mice xenograft models were used to test the effects of BBSKE and oxaliplatin combinations on gastric cancer cell growth in vivo. In addition, we also used the combined treatment of BBSKE and oxaliplatin in three cases of gastric cancer Patient-Derived organoid (GC-PDO) to detect the anti-tumor effect. RESULTS: We found that BBSKE significantly enhanced oxaliplatin-induced growth inhibition in gastric cancer cells by inhibiting TrxR1 activity. Because of the inhibition of TrxR1 activity, BBSKE synergized with oxaliplatin to enhance the production of ROS and activate p38 and JNK signaling pathways which eventually induced apoptosis of gastric cancer cells. In vivo, we also found that BBSKE synergized with oxaliplatin to suppress the gastric cancer tumor growth in xenograft nude mice model, accompanied by the reduced TrxR1 activity. Remarkably, we found that BBSKE attenuated body weight loss evoked by oxaliplatin treatment. We also used three cases of GC-PDO and found that the combined treatment of BBSKE and oxaliplatin dramatically inhibited the growth and viability of GC-PDO with increased ROS level, decreased TrxR1 activity and enhanced apoptosis. CONCLUSIONS: This study elucidates the underlying mechanisms of synergistic effect of BBSKE and oxaliplatin, and suggests that the combined treatment has potential value in gastric cancer therapy.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Organosselênicos/farmacologia , Oxaliplatina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/metabolismo , Tiorredoxina Redutase 1/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Sinergismo Farmacológico , Ativação Enzimática , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Nus , Organoides , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Int J Biol Sci ; 17(11): 2811-2825, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34345209

RESUMO

Chemotherapy plays an irreplaceable role in the treatment of GC, but currently available chemotherapeutic drugs are not ideal. The application of medicinal plants is an important direction for new drug discovery. Through drug screening of GC organoids, we determined that ailanthone has an anticancer effect on GC cells in vitro and in vivo. We also found that AIL can induce DNA damage and apoptosis in GC cells. Further transcriptome sequencing of PDX tissue indicated that AIL inhibited the expression of XRCC1, which plays an important role in DNA damage repair, and the results were also confirmed by western blotting. In addition, we found that AIL inhibited the expression of P23 and that inhibition of P23 decreased the expression of XRCC1, indicating that AIL can regulate XRCC1 via P23. The results of coimmunoprecipitation showed that AIL can inhibit the binding of P23 and XRCC1 to HSP90. These findings indicate that AIL can induce DNA damage and apoptosis in GC cells. Meanwhile, AIL can decrease XRCC1 activity by downregulating P23 expression to inhibit DNA damage repair. The present study sheds light on the potential application of new drugs isolated from natural medicinal plants for GC therapy.


Assuntos
Apoptose/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Piridinolcarbamato/metabolismo , Quassinas/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Ailanthus/química , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Regulação para Baixo , Descoberta de Drogas , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Gástricas/metabolismo , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Toxins (Basel) ; 12(11)2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33152993

RESUMO

Carbon is one of the most important nutrients for the development and secondary metabolism in fungi. CreA is the major transcriptional factor mediating carbon catabolite repression, which is employed in the utilization of carbon sources. Aspergillus ochraceus contaminates various food and feed containing different carbon sources by producing ochratoxin A (OTA). However, little is known about the function of AoCreA in regulating the morphology and OTA production of A. ochraceus. To give an insight into the mechanism of the carbon sources regulating development of A. ochraceus and OTA production, we have identified AoCreA in A. ochraceus. The homologous recombination strategy was used to generate the AoCreA deletion mutant (ΔAoCreA). We have investigated the morphology and OTA production of the wild type (WT) and ΔAoCreA of A. ochraceus with media containing different carbon sources (glucose, fructose, maltose, D-xylose, D-mannose, acetate, D-galactose, D-mannitol and lactose). ΔAoCreA showed a significant growth and conidiation defect on all media as compared with WT. Glucose and maltose were the most inducing media for OTA production by A. ochraceus, followed by sucrose and the nutrient-rich Yeast Extract Sucrose (YES) and Potato Dextrose Agar (PDA). The deletion of AoCreA led to a drastic reduction of OTA production on all kinds of media except PDA, which was supported by the expression profile of OTA biosynthetic genes. Furthermore, infection studies of ΔAoCreA on oats and pears showed the involvement of AoCreA in the pathogenicity of A. ochraceus. Thus, these results suggest that AoCreA regulates morphological development and OTA biosynthesis in response to carbon sources in A. ochraceus.


Assuntos
Aspergillus ochraceus/metabolismo , Repressão Catabólica , Proteínas Fúngicas/metabolismo , Ocratoxinas/biossíntese , Proteínas Repressoras/metabolismo , Aspergillus ochraceus/genética , Aspergillus ochraceus/crescimento & desenvolvimento , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Mutação , Filogenia , Proteínas Repressoras/genética
19.
J Cancer ; 11(10): 3013-3019, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32226516

RESUMO

Gastric cancer (GC) is the third leading cause of cancer deaths worldwide. Conventional chemotherapy has been proven useful to only a portion of the patients. Previous developed targeted drugs are more effective and tolerable than conventional drugs. Thus the development of novel drugs targeting markers is an urgent task and the main direction for future research. Ethaselen, an inhibitor of thioredoxin reductase (TrxR), has been considered an important anticancer target drug. Previous studies show that it is effective on treating many kinds of cancers. In this paper, we examined that ethaselen effectively inhibited the growth of gastric cancer cells and promoted apoptosis. Organoids were cultured from patient-derived cells in a three-dimension form which are widely used in cancer research to help us understand cancer cells behavior at the sub-organ level and develop novel drugs. We established a drug testing and screening system using GC-derived organoids by recapitulating tumor microenvironment. We confirmed that the TrxR-targeting ethaselen could be a novel and effective drug for gastric cancer treatment.

20.
Artif Cells Nanomed Biotechnol ; 47(1): 3904-3912, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31566021

RESUMO

This study aimed to investigate the effect of Junduqing extractive on proliferation, apoptosis, migration and invasion of nasopharyngeal carcinoma (NPC) cells and the involved mechanism. Junduqing extractive was prepared. CCK-8 assay found that IC50 of Junduqing extractive in HNE-1 cells was 2.99 mg/ml, so its concentration of 1.0, 2.0 and 3.0 mg/ml was selected to perform the following experiments. HNE-1, HNE-2 and HONE1 cells were then divided into four groups: (1) Control (no treatment); (2) 1.0 mg/ml (1.0 mg/ml Junduqing); (3) 2.0 mg/ml (2.0 mg/ml Junduqing) and (4) 3.0 mg/ml (3.0 mg/ml Junduqing). Cell viability, apoptosis, migration and invasion were examined by CCK-8 assay, annexin V-FITC/PI staining, scratch wound assay and transwell assay, respectively. Compared with the control group, the viability, migration rates and invasive capacity of HNE-1, HNE-2 and HONE1 cells with Junduqing treatments decreased significantly. Higher concentration of Junduqing extractive caused lower viability, smaller migration rates and weaker invasive capacity. Compared with the control group, the apoptosis of HNE-1, HNE-2 and HONE1 cells after treatment with 2.0 and 3.0 mg/ml of Junduqing extractive increased remarkably. Levels of Bcl-xL, Mcl-1, Caspase-3, Caspase-8 and Caspase-9 were examined by western blotting. Compared with the control group, the expression of Bcl-xL and Mcl-1 and the expression of Caspase-3, Caspase-8 and Caspase-9 in HNE-1, HNE-2 and HONE1 cells were significantly down-regulated and up-regulated, respectively, after treatment with Junduqing extractive. In conclusion, Junduqing extractive could inhibit the proliferation, migration and invasion, and promote the apoptosis of human NPC cells through down-regulating Mcl-1 and Bcl-xL and up-regulating Caspase-3, Caspase-8 and Caspase-9.


Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Carcinoma Nasofaríngeo/patologia , Proteína bcl-X/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Humanos , Invasividade Neoplásica , Regulação para Cima/efeitos dos fármacos
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