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1.
Molecules ; 26(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34443627

RESUMO

The importance of yeast old yellow enzymes is increasingly recognized for direct asymmetric reduction of (E/Z)-citral to (R)-citronellal. As one of the most performing old yellow enzymes, the enzyme OYE3 from Saccharomyces cerevisiae S288C exhibited complementary enantioselectivity for the reduction of (E)-citral and (Z)-citral, resulting in lower e.e. value of (R)-citronellal in the reduction of (E/Z)-citral. To develop a novel approach for the direct synthesis of enantio-pure (R)-citronellal from the reduction of (E/Z)-citral, the enzyme OYE3 was firstly modified by semi-rational design to improve its (R)-enantioselectivity. The OYE3 variants W116A and S296F showed strict (R)-enantioselectivity in the reduction of (E)-citral, and significantly reversed the (S)-enantioselectivity in the reduction of (Z)-citral. Next, the double substitution of OYE3 led to the unique variant S296F/W116G, which exhibited strict (R)-enantioselectivity in the reduction of (E)-citral and (E/Z)-citral, but was not active on (Z)-citral. Relying on its capability discriminating (E)-citral and (Z)-citral, a new cascade reaction catalyzed by the OYE3 variant S296F/W116G and glucose dehydrogenase was developed, providing the enantio-pure (R)-citronellal and the retained (Z)-citral after complete reduction of (E)-citral.


Assuntos
Monoterpenos Acíclicos/metabolismo , NADPH Desidrogenase/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Aldeídos/metabolismo , Catálise , Glucose 1-Desidrogenase/metabolismo
2.
Aging (Albany NY) ; 13(14): 18498-18514, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34292880

RESUMO

Breast cancer (BC) is a common malignant tumor in females. The challenge in treating BC is overcoming chemoresistance. Exosome-mediated transfer of miRNAs is a molecule-shuttle in intercellular communication. Thus, we aimed to investigate whether exosomal miRNA-205 could affect chemoresistance and tumorigenesis in recipient tumor cells and to elucidate the underlying mechanism in vivo and in vitro. Microarray and qRT-PCR assays demonstrated that miRNA-205 was upregulated in tamoxifen resistance MCF-7/TAMR-1 (M/T) cells and M/T cell-derived exosomes (M/T-Exo). The M/T-Exo was internalized by human BC cells (BCCs), causing increased expression of miRNA-205 in BCCs. Coculturing with M/T-Exo promoted tamoxifen resistance, proliferation, migration, and invasion while suppressed apoptosis in recipient BCCs, which were associated with activating the caspase pathway and phosphorylating Akt. Luciferase reporter assays showed that miRNA-205 directly targeted E2F Transcription Factor 1 (E2F1) in BCCs. Furthermore, knockdown of miRNA-205 or overexpression of E2F1 reversed the roles of M/T-Exo in BCCs. In vivo experiments showed that the intratumoral injection of M/T-Exo caused greater tamoxifen resistance and larger tumor size relative to mice treated with miRNA-205-knockdown or E2F1-overexpressing BCCs. Together, the results suggest that exosomal miRNA-205 may promote tamoxifen resistance and tumorigenesis in BC through targeting E2F1 in vivo and in vitro.

3.
ACS Appl Mater Interfaces ; 13(11): 12824-12835, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33689289

RESUMO

Pancreatic tumor is extremely lethal because its cancerous structures are sheltered by dense stromal barriers that hinder the infiltration of therapeutics. To facilitate the infiltration of therapeutics through the stromal barrier, remodeling the stroma with an adjuvant prior to or together with gemcitabine-the current chemotherapeutic standard for pancreatic cancer-is a widely studied strategy; nevertheless, the intrinsic nonuniformity in distribution (spatial and/or temporal) of the adjuvant and gemcitabine has raised the increased risk of tumor metastasis as a major concern. In this work, we propose long-circulating, pH-sensitive nanoparticles composed solely of cellular membrane-disruptive molecules as a new approach for treating pancreatic cancer. Using a micelle of a polymeric mimetic of host defense peptides as the model for such nanoparticles, we showed that this nanoparticle exhibited acid-activated cytotoxicity indiscriminately to both cancerous and fibroblast cells, and the underlying activity mode was acid-activatable disruption of cellular membrane integrity. As a result, our acid-activatable nanoparticle effectively permeabilized the stromal barrier and eradicated the otherwise sheltered pancreatic cancer cells, as demonstrated with a three-dimensional spheroid in which a shell of fibroblast NIH-3T3 cells was cultured over a core of pancreatic BxPC-3 cells. When administered intravenously into mouse models bearing xenograft pancreatic BxPC-3 tumors, our acid-activatable nanoparticle efficiently inhibited tumor growth without causing noticeable off-target adverse effects or promoting tumor metastasis. Notably, this nanoparticle permeabilized the otherwise dense pancreatic tumor tissue while significantly suppressing the expression of extracellular matrix components and activated cancer-associated fibroblasts. Although the feasibility of our approach was demonstrated with a micelle of a polymeric molecule, we trust that future research efforts in this pathway may eventually offer translational formulations for improving the therapeutic efficacy of pancreatic cancer.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Preparações de Ação Retardada/química , Desoxicitidina/análogos & derivados , Nanopartículas/química , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Antimetabólitos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células NIH 3T3
4.
Bull Cancer ; 108(4): 385-398, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33685627

RESUMO

Numerous epigenetic alterations are observed in cancer cells, and dysregulation of mono-ubiquitination of histone H2B (H2Bub1) has often been linked to tumorigenesis. H2Bub1 is a dynamic post-translational histone modification associated with transcriptional elongation and DNA damage response. Histone H2B monoubiquitination occurs in the site of lysine 120, written predominantly by E3 ubiquitin ligases RNF20/RNF40 and deubiquitinated by ubiquitin specific peptidase 22 (USP22). RNF20/40 is often altered in the primary tumors including colorectal cancer, breast cancer, ovarian cancer, prostate cancer, and lung cancer, and the loss of H2Bub1 is usually associated with poor prognosis in tumor patients. The purpose of this review is to summarize the current knowledge of H2Bub1 in transcription, DNA damage response and primary tumors. This review also provides novel options for exploiting the potential therapeutic target H2Bub1 in personalized cancer therapy.


Assuntos
Regulação Neoplásica da Expressão Gênica , Histonas/fisiologia , Proteínas de Neoplasias/fisiologia , Neoplasias/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Ubiquitinadas/fisiologia , Carcinoma/etiologia , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/terapia , Dano ao DNA , Reparo do DNA , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Progressão da Doença , Humanos , Proteínas de Neoplasias/genética , Neoplasias/etiologia , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisão , Elongação da Transcrição Genética , Ubiquitina Tiolesterase/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
5.
J Steroid Biochem Mol Biol ; 209: 105853, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33617965

RESUMO

Inhibition of Poly(ADP-ribose) polymerase (PARP) is effective for breast cancer susceptibility genes 1 (BRCA1)-deficient breast cancers. Although hormones play critical roles on the occurrence as well as being used in conventional therapies of breast cancer, their impacts on PARP-targeted therapy have been poorly addressed. Here, we showed that addition of estrogen could enhance the cytotoxicity of PARP inhibitors on estrogen receptor (ER)-positive breast cancer cells, causing significant suppression of cell growth. Further analysis revealed that the impact was due to estrogen's stimulating the production of nitric oxide (NO), which could be abrogated when blocking NO formation. Moreover, the effect of estrogen can be resembled by two exogenous nitric oxide donors (SNAP and GSNO). Using ER-negative cell line MDA-MB231, estrogen could not enhance the cell killing of PARP inhibitors any more, but addition of NO donors re-established the enhancing effects. The increased NO level led to accumulation of DNA double strand breaks (DSBs) based on the formation of H2AX foci. Consistent with earlier studies, we demonstrated that NO suppressed the expression of BRCA1, a key player involved in DSB recombination repair. Taken together, these data reveal an important role of estrogen on the treatment of PARP inhibitors, which may affect its clinical treatment and should be considered in precision therapies for ER-positive and negative cancers.


Assuntos
Apoptose , Neoplasias da Mama/tratamento farmacológico , Sinergismo Farmacológico , Estrogênios/farmacologia , Óxido Nítrico/metabolismo , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular , Proliferação de Células , Feminino , Humanos , Células Tumorais Cultivadas
6.
Cancer Manag Res ; 12: 10163-10172, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116871

RESUMO

Background: Clinical tolerance to trastuzumab greatly affects the therapeutic effect in breast cancer (BC). Long-chain non-coding RNA (lncRNA) plays an important role in the development of trastuzumab resistance, in which SNHG7 can promote the epithelial mesenchymal transformation (EMT) of breast cancer cells into, while EMT is related to trastuzumab resistance of breast cancer cells. Objective: To investigate whether lncRNA-SNHG7 can enhance chemotherapy resistance and cell viability of BC cells by regulating miR-186. Methods: SK-BR-3 and SNHG7 of HER2+BC cells were induced to enhance the resistance of BC cells to trastuzumab by regulating miR-186, and to regulate the expression levels of SNHG7 and miR-186. The sensitivity of drug-resistant cells to trastuzumab and the changes of cell proliferation, migration, apoptosis, and EMT were measured and verified by tumorigenesis in vivo. The effects of miR-186 on SNHG7 were investigated through rescue experiments; the regulatory relationship between the expression of SNHG7 and miR-186 was verified by the double luciferase reporter (DLR) and the mechanism of SNHG7 was explored. Results: Down-regulation of SNHG7 or up-regulation of miR-186 could increase the sensitivity of BC cells to trastuzumab, inhibit the proliferation, migration and EMT, and promote apoptosis. Compared with the down-regulation of SNHG7 or miR-186 alone, simultaneous down-regulation of SNHG7 and miR-186 on drug-resistant cells brought notably lower sensitivity to trastuzumab and apoptosis rate, and higher proliferation and apoptosis ability. The DLR showed that miR-186 could specifically inhibit the expression of SNHG7. The results of tumorigenesis in vivo revealed that down-regulation of SNHG7 or up-regulation of miR-186 could improve the therapeutic effect of trastuzumab and reduce the tumor volume, and miR-186 could also antagonize the effect of SNHG7. Conclusion: Down-regulation of SNHG7-targeted miR-186 can reverse trastuzumab resistance of BC cells, inhibit the proliferation, migration, and EMT levels of BC cells, and promote apoptosis.

7.
Acta Biochim Biophys Sin (Shanghai) ; 52(9): 927-934, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32510153

RESUMO

Chronic hypoxia is a common inducer of end-stage cardiovascular disease. In cells under hypoxia, the hypoxia-inducible factor-1 (HIF-1) plays a vital role in regulating downstream target genes. However, the mechanism of hypoxia in cardiomyocytes is still unclear. In this study, we aimed to identify novel downstream epigenetic targets of HIF-1α in cardiomyocytes under hypoxia. H9c2 cells were exposed to hypoxia condition, and quantitative real-time PCR analysis was performed to evaluate the expression of miR-20b-5p. The results indicated that the expression of miR-20b-5p was down-regulated in H9c2 cells under low oxygen condition. Meanwhile, HIF-1α overexpression further down-regulated the miR-20b-5p expression in H9c2 cells transfected with HIF-1α plasmids. In addition, Annexin-V-FITC/PI flow cytometry analysis suggested that overexpression of miR-20b-5p attenuated cell apoptosis under hypoxia condition in H9c2 cells. Western blot analysis showed that the hypoxia apparently increased Bax and cleaved-caspase-3, but decreased Bcl-2 expression in H9c2 cells, indicating that hypoxia-induced NF-κB signaling pathway activation is mediated by miR-20b-5p. Hypoxia-induced H9c2 cell apoptosis was reduced after HIF-1α knockdown as shown by the flow cytometry analysis. In conclusion, we identified that miR-20b-5p plays an important role in mediating cardiomyocytes apoptosis under hypoxia, which is mediated by the HIF-1/NF-κB signaling pathway.


Assuntos
Apoptose , Regulação da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Idoso , Animais , Hipóxia Celular , Linhagem Celular , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/patologia , NF-kappa B/genética , Ratos
8.
Cell Biol Int ; 44(10): 2002-2010, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32544280

RESUMO

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. The aim of this study is to identify the diagnostic and poor prognostic signatures in TNBC by exploring the aberrant DNA methylation and gene expression. Differential expression and methylation analysis of the TNBC and paracancer samples from The Cancer Genome Atlas were performed. Gene set enrichment and protein-protein interaction (PPI) network analysis was used to explore the mechanisms of TNBC. Methylation-gene expression correlation analysis was performed, and multivariate Cox analysis and receiver operating characteristics analysis were used to further screen the hub genes for TNBC. We identified 1,525 differentially expressed genes and 150 differentially methylated genes between TNBC and paracancer samples. About 96.64% of the methylation sites were located on the CpG island. A total of 17 Gene Ontology biological process terms and 18 signal pathways were significantly enriched. GNG4, GNG11, PENK, MAOA, and AOX1 were identified as the core genes of the PPI network. Methylation-expression correlations revealed that ABCC9 (cg06951626), NKAPL (cg18675097, cg01031101, and cg17384889), and TMEM132C (cg03530754) showed promise as diagnostic and prognostic markers in TNBC. ABCC9 (cg06951626), NKAPL (cg18675097, cg01031101, and cg17384889), and TMEM132C (cg03530754) were potential diagnostic and prognostic markers in TNBC.

9.
Bioresour Technol ; 312: 123555, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32447123

RESUMO

In-situ detection on primary volatiles and stable radicals is of great importance for better understanding of lignin pyrolysis mechanisms and utilization. In this study, a novel in-situ pyrolysis time-of-flight mass spectrometry with double ionization sources was taken to in-situ detect primary volatiles and gas products, and the evolution of stable radicals in lignin pyrolysis residues was explored by EPR spectroscopy. The results show that the cleavage of ß-O-4 linkage is mainly responsible for lignin depolymerization at 100-300 °C, releasing the G-type compounds. And these G-type compounds can further undergo O-CH3, Car-OCH3 and Car-OH bonds cleavage to form biphenolic hydroxyl compounds, phenols and aromatic hydrocarbons. According to the EPR analysis, the radical concentration increased from 1017 to 1019 spins/g with the temperature, and stable free-radical species are mainly composed of the o-methoxy and hydroxyl substituted phenoxy radicals and carbon-centered aromatic radicals, which can well interpret the demethylation, demethoxylation and dehydroxylation mechanisms.


Assuntos
Lignina , Pirólise , Espectroscopia de Ressonância de Spin Eletrônica , Temperatura Alta , Espectrometria de Massas
10.
Aging (Albany NY) ; 12(9): 8289-8300, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396524

RESUMO

OBJECTIVE: Nano micelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. This study aimed to investigated the anti-tumor effect of doxorubicin (Dox)-loaded Pluronic P123 (P123) and PEG2000-DSPE mixed NMs in drug-resistant breast cancer cells. RESULTS: The expression of P-gp and MDR1 gene was highly expressed in MCF-7R but not MCF-7 cells. The cellular uptake of P123-PEG2000-DSPE (Dox) was higher than that of free Dox and PEG2000-DSPE (Dox) in MCF-7R cells. Furthermore, compared with free Dox, both PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) significantly diminished cell viability, and promoted cell apoptosis in MCF-7R cells. In addition, the P123-modified NMs obviously inhibited the expression of P-gp and MDR1. CONCLUSIONS: P123-PEG2000-DSPE (Dox) had a superior anti-tumor activity than PEG2000-DSPE (Dox) in MCF-7R cells through P-gp-mediated drug excretion and drug resistance mechanisms. METHODS: The PEG2000-DSPE NMs (PEG2000-DSPE), P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE), Dox-loaded PEG2000-DSPE NMs (PEG2000-DSPE (Dox)), and Dox-loaded Pluronic P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE (Dox)) were prepared, and then the morphologies and the size distribution of PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Poloxaleno/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Micelas
11.
ACS Omega ; 5(15): 8483-8495, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32337409

RESUMO

Exploring deep and ultradeep wells has rapidly become more significant to meet the global demand for oil and gas. The study of rheological and filtration-loss properties is essential to designing drilling muds and determining their performance under operational conditions. Rheological and filtration-loss properties of drilling muds were found to have a negative impact when exposed to elevated temperatures in the wells. In this study, an amphoteric polymer (abbreviated to PEX) was synthesized and characterized using a combination of analyses: FTIR, SEM, 13CNMR, and TGA. The synthesized PEX was used as an additive in water-based drilling muds to improve rheological properties and reduce fluid loss at elevated temperatures (180-220 °C). The experimental results demonstrated that inclusion of an optimal concentration of PEX (0.3 wt %) into the drilling mud formulation increased the rheological properties by 62.3% and decreased the filtration loss by 63.5% at an aging temperature of 180 °C. Moreover, PEX was found to perform superbly compared to polyanionic cellulose (PAC-LV) and polyacrylamide (PAM), the widely used drilling mud additives. PEX not only improved the rheological properties and reduced the filtration loss behavior but also bolstered the thermostability of the drilling mud formulation. It was concluded that the rigidity and amphoteric nature of PEX accounted for the exceptional performance and temperature resistance for PEX-drilling mud formulations. Succinctly, PEX exhibits admirable properties in smart drilling mud formulations for drilling operations under high-temperature geothermal conditions. Moreover, in terms of rheological models, the Herschel-Bulkley model adequately described the rheological properties of all the studied drilling mud formulations.

12.
World J Stem Cells ; 12(1): 87-99, 2020 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-32110277

RESUMO

BACKGROUND: Breast cancer is a common malignant tumor that seriously threatens women's health. Breast cancer stem cell (CSC)-like cell population may be the main factor for breast cancer metastasis. Therefore, targeted therapy for CSCs has great potential significance. Hypoxia-inducible factor is a transcription factor widely expressed in tumors. Studies have shown that down-regulation of the hypoxia signaling pathway inhibits tumor stem cell self-renewal and increases the sensitivity of stem cells to radiotherapy and chemotherapy mediated by hypoxia-inducible factor-2α (HIF-2α). However, the specific mechanism remains unclear and further research is necessary. AIM: To investigate the effect of HIF-2α down-regulation on stem cell markers, microsphere formation, and apoptosis in breast cancer cell line MDA-MB-231 under hypoxia and its possible mechanism. METHODS: Immunohistochemistry was used to detect the expression of HIF-2α and CD44 in triple-negative breast cancer (TNBC) and non-TNBC tissues. Double-labeling immunofluorescence was applied to detect the co-expression of HIF-2α and CD44 in MDA-MB-231 cells and MCF-7 cells. HIF-2α was silenced by RNA interference, and the expression of CD44 and transfection efficiency were detected by real-time fluorescent quantitative PCR. Further, flow cytometry, TdT-mediated X-dUTP nick end labeling, and mammosphere formation assays were used to evaluate the effect of HIF-2α on CSCs and apoptosis. The possible mechanisms were analyzed by Western blot. RESULTS: The results of immunohistochemistry showed that HIF-2α was highly expressed in both TNBC and non-TNBC, while the expression of CD44 in different molecular types of breast cancer cells was different. In in vitro experiments, it was found that HIF-2α and CD44 were expressed almost in the same cell. Compared with hypoxia + negative-sequence control, HIF-2α small interfering ribonucleic acid transfection can lower the expression of HIF-2α and CD44 mRNA(P < 0.05), increase the percentage of apoptotic cells (P < 0.05), and resulted in a reduction of CD44+/CD24- population (P < 0.05) and mammosphere formation (P < 0.05) in hypoxic MDA-MB-231 cells. Western blot analysis revealed that phosphorylated protein-serine-threonine kinase (p-AKT) and phosphorylated mammalian target of rapamycin (p-mTOR) levels in MDA-MB-231 decreased significantly after HIF-2α silencing (P < 0.05). CONCLUSION: Down-regulation of HIF-2α expression can inhibit the stemness of human breast cancer MDA-MB-231 cells and promote apoptosis, and its mechanism may be related to the CD44/phosphoinosmde-3-kinase/AKT/mTOR signaling pathway.

13.
Oncol Lett ; 18(6): 5821-5830, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788055

RESUMO

Breast cancer has been the leading cause of cancer-associated mortality in women worldwide. Perturbation of oncogene and tumor suppressor gene expression is generally considered as the fundamental cause of cancer initiation and progression. In the present study, three gene expression datasets containing information of breast cancer and adjacent normal tissues that were detected using traditional gene microarrays were downloaded and batch effects were removed with R programming software. The differentially expressed genes between breast cancer and normal tissue groups were closely associated with cancer development pathways. Interestingly, five pathways, including 'extracellular matrix-receptor interaction', 'peroxisome proliferator-activated receptors signaling pathway', 'propanoate metabolism', 'pyruvate metabolism' and 'regulation of lipolysis in adipocytes', were thoroughly connected by 10 genes. Patients with upregulation of six of these hub genes (acetyl-CoA carboxylase ß, acyl-CoA dehydrogenase medium chain, adiponectin, C1Q and collagen domain containing, acyl-CoA synthetase short chain family member 2, phosphoenolpyruvate carboxykinase 1 and perilipin 1) exhibited improved breast cancer prognosis. Additionally, breast cancer-specific network analysis identified several gene-gene interaction modules. These gene clusters had strong interactions according to the scoring in the whole network, which may be important to the development of breast cancer. In conclusion, the present study may improve the understanding of the mechanisms of breast cancer and provide several valuable prognosis and treatment signatures.

14.
Bioresour Technol ; 290: 121739, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302467

RESUMO

To explore fast pyrolysis behaviors of cedar biomass, the infrared heating technique with quick heating rate was taken in a fixed-bed reactor. The effects of heating rates (5-30 °C/s) and pyrolysis temperatures (400-600 °C) on pyrolysis products distribution and compositions were discussed, and the reaction mechanism was proposed. The results show that high heating rate can significantly suppress secondary reaction of primary volatiles. GC/FID and GC/MS analyses indicate that higher heating rate is favorable to the generation of glucose derivatives such as acids and furans. However, higher temperature can obviously promote further conversion of guaiacyl-contained structure following demethylation, demethoxylation and H/CH3 assisted demethoxylation routes, which were proposed to interpret the formation of biphenolic hydroxyl and monophenolic hydroxyl compounds such as phenol, 2-methyl-phenol and 2,4-dimethyl-phenol, respectively. Moreover, the demethylation route exhibits obvious conversion advantage at higher temperature due to lower energy barrier.


Assuntos
Temperatura Alta , Pirólise , Biomassa , Calefação , Temperatura
15.
World J Gastrointest Oncol ; 11(12): 1206-1217, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31908725

RESUMO

BACKGROUND: Accurate assessment of the prognosis after colorectal cancer surgery is of great significance in patients with colorectal cancer. However, there is no systematic analysis of factors affecting the prognosis of colorectal cancer currently. AIM: To systematically analyze the influence of clinical data and serological and histological indicators on the prognosis of patients with colorectal cancer, and to explore the indicators that can accurately assess the prognosis of patients with colorectal cancer. METHODS: A total of 374 patients with colorectal cancer were enrolled. The clinical data, tumor-node-metastasis (TNM) stage, and Dukes stage were recorded. All patients received examinations including carcinoembryonic antigen (CEA), carbohydrate antigen 199, C-reactive protein, albumin, D-dimer, and fibrinogen as well as routine blood tests one week before surgery. The tumor location, size, depth of invasion, lymph node metastasis, and distant metastasis were recorded during surgery. The pathological tissue typing and expression of proliferating cell nuclear antigen (PCNA) and p53 were observed. All patients were followed for 3 years, and patients with endpoint events were defined as a poor prognosis group, and the remaining patients were defined as a good prognosis group. The differences in clinical data, serology, and histology were analyzed between the two groups. Multivariate COX regression was used to analyze the independent influencing factors for the prognosis of colorectal cancer. The receiver operating characteristic curve was used to evaluate the predictive value of each of the independent influencing factors and their combination for the prognosis of colorectal cancer. RESULTS: The follow-up outcomes showed that 81 patients were in the good prognosis group and 274 patients in the poor prognosis group. The TNM stage, PCNA, Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), C-reactive protein/albumin ratio (CAR), D-dimer, and CEA were independent influencing factors for the prognosis of colorectal cancer (P = 0.000). NLR had the highest predictive power for colorectal cancer prognosis [area under the receiver operating characteristic curve (AUC) = 0.925], followed by D-dimer (AUC = 0.879) and GPS (AUC = 0.872). The accuracy of the combination of all indicators in predicting the prognosis of colorectal cancer was the highest (AUC = 0.973), which was significantly higher than that of any of the indicators alone (P < 0.05). The sensitivity and specificity of the combination were 92.59% and 90.51%, respectively. CONCLUSION: The independent influence factors for the prognosis of colorectal cancer include TNM stage, PCNA, GPS, NLR, CAR, D-dimer, and CEA. The combined assessment of the independent factors is the most accurate predictor of the prognosis after colorectal cancer surgery.

16.
Int J Nanomedicine ; 13: 3897-3906, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30013343

RESUMO

Introduction: The objective of this study is to stimulate wound healing using bioinspired hydrogels with basic fibroblast growth factor (bFGF). Materials and methods: Inspired by the crosslinking mechanism in algae-based adhesives, hydrogels were fabricated with gum arabic, pectin, and Ca2+. The physical properties of the bioinspired hydrogels were characterized, and the in vitro release of bFGF was investigated. Then, the in vitro scratch assay for wound healing and in vivo wound healing experiment in a full-thickness excision wound model were performed for the bioinspired hydrogels with bFGF. Finally, histological examinations and organ toxicity tests were conducted to investigate the wound healing applications of the bioinspired hydrogels with bFGF. Results: The in vitro and in vivo results showed that the bioinspired hydrogels with bFGF could significantly enhance cell proliferation, wound re-epithelialization, collagen deposition, and contraction without any noticeable toxicity and inflammation compared with the hydrogels without bFGF and commercial wound healing products. Conclusion: These results suggest the potential application of bioinspired hydrogels with bFGF for wound healing.


Assuntos
Materiais Biomiméticos/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Adesivos , Animais , Materiais Biomiméticos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Preparações de Ação Retardada , Derme/citologia , Fibroblastos/citologia , Hidrogéis/química , Camundongos Endogâmicos BALB C , Cicatrização/fisiologia
17.
Mol Med Rep ; 18(1): 877-881, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29845260

RESUMO

The present report aimed to evaluate the results of screen mutations of the fibrillin (FBN) 1 gene and analyze the symptoms in one Chinese patient clinically diagnosed with Marfan syndrome (MFS). Clinical data were collected and FBN1 gene sequencing was performed. Genomic DNA was extracted from the blood sample of the patient. All 65 exons were screened using a polymerase chain reaction assay. The diagnosis of MFS was confirmed via identification of symptoms presenting in the skeletal system (arachnodactyly, walker wrist and thumb signs) and the ocular system (ectopia lentis), in addition to a positive family history. The patient's cardiovascular manifestations (dilatation of the four cardiac chambers, severe mitral valve regurgitation and a large saccular aneurysm of the non­coronary sinus of Valsalva) were atypical to those that most frequently occur in cases of MFS. Following gene sequencing, two novel heterozygous mutations of the FBN­1 gene were identified: c.3442C>G in exon 27, proline replaced with alanine (p. Pro1148Ala) and c.6388G>A in exon 52, glutamic acid replaced with lysine (p. Glu2130Lys). The clinical symptoms and family history were important in the diagnosis of MFS, however the atypical signs that presented in the cardiovascular system may be associated with the disease, and may be noted for further cases in the future. Gene sequencing further verified the correct diagnosis of MFS.


Assuntos
Éxons , Fibrilina-1/genética , Síndrome de Marfan/genética , Síndrome de Marfan/patologia , Mutação de Sentido Incorreto , Adulto , Substituição de Aminoácidos , Grupo com Ancestrais do Continente Asiático , Humanos , Masculino
18.
Medicine (Baltimore) ; 97(13): e0238, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29595676

RESUMO

The effects of revascularization by percutaneous coronary intervention (PCI) on cardiac function and clinical outcomes in patients with confirmed coronary artery disease (CAD) and heart failure (HF), on the basis of the optimal medical treatment recommended by current guidelines, remain to be determined.A cohort study was performed to evaluate the efficacy of PCI on the basis of optimal medical treatment in patients with CAD and HF. Patients who received PCI were subsequently grouped according to partial and complete revascularization (CR) depending on the PCI outcome. The primary outcome was defined as a composite outcome of major adverse cardiovascular events (MACEs). Changes in left ventricular ejection fraction (LVEF) also were compared.A total of 69 patients (12 who received medical treatment and 57 who received PCI) were included. Patients in the PCI group showed significantly improved LVEF (P < .001), but patients in the medical treatment group did not (P > .05) after 3 months of follow-up. MACEs occurred in 50% patients in the medical treatment group and 19.3% patients of the PCI group, with this difference almost reaching statistical significance (P = .06). Compared with patients who received medical therapy only, patients who received PCI experienced better survival (P = .02). Moreover, survival seemed to be better in patients who achieved CR with PCI of the coronary arteries than in those who had partial revascularization of the coronary arteries (P = .06).PCI may be effective for improving survival in patients with CAD and HF.


Assuntos
Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/cirurgia , Intervenção Coronária Percutânea/métodos , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/mortalidade , Estudos Prospectivos , Índice de Gravidade de Doença , Volume Sistólico
19.
J Ethnopharmacol ; 214: 29-36, 2018 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-29233733

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Dioscin, a spirostane glycoside, the rhizoma of Dioscorea septemloba (Diocoreacea) is used for diuresis, rheumatism, and joints pain. Given the poor solubility and stability of Dioscin, we proposed a hypothesis that Dioscin's metabolite(s) are the active substance(s) in vivo to contribute to the reducing effects on serum uric acid levels. AIM OF THE STUDY: The aim of this study is to identify the active metabolite(s) of Dioscin in vivo and to explore the mechanism of its antihyperuricemic activity. MATERIALS AND METHODS: After oral administration of Dioscin in potassium oxonate (PO) induced hyperuricemia rats and adenine-PO induced hyperuricemia mice models, serum uric acid and creatinine levels, clearance of uric acid and creatinine, fractional excretion of uric acid, and renal pathological lesions were determined were used to evaluate the antihyperuricemic effects. Renal glucose transporter-9 (GLUT-9) and organic anion transporter-1 (OAT-1) expressions were analyzed by western blotting method. Renal uric acid excretion was evaluated using stably urate transporter-1 (URAT-1) transfected human epithelial kidney cell line. Intestinal uric acid excretion was evaluated by measuring the transcellular transport of uric acid in HCT116 cells. RESULTS: In hyperuricemia rats, both 25 and 50mg/kg of oral Dioscin decreased serum uric acid levels over 4h. In the hyperuricemia mice, two weeks treatment of Dioscin significantly decreased serum uric acid and creatinine levels, increased clearance of uric acid and creatinine, increased fractional excretion of uric acid, and reduced renal pathological lesions caused by hyperuricemia. In addition, renal GLUT -9 was significantly down-regulated and OAT-1 was up-regulated in Dioscin treated hyperuricemia mice. Dioscin's metabolite Tigogenin significantly inhibited uric acid re-absorption via URAT1 from 10 to 100µM. Diosgenin and Tigogenin increased uric acid excretion via ATP binding cassette subfamily G member 2 (ABCG2). CONCLUSION: Decreasing effect of Dioscin on serum uric acid level and enhancing effect on urate excretion were confirmed in hyperuricemia animal models. Tigogenin, a metabolite of Dioscin, was identified as an active substance with antihyperuricemic activity in vivo, through inhibition of URAT1 and promotion of ABCG2.


Assuntos
Dioscorea , Diosgenina/análogos & derivados , Hiperuricemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Eliminação Renal/efeitos dos fármacos , Espirostanos/farmacologia , Ácido Úrico/sangue , Uricosúricos/farmacologia , Adenina , Animais , Biomarcadores/sangue , Creatinina/sangue , Dioscorea/química , Diosgenina/isolamento & purificação , Diosgenina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Células HCT116 , Humanos , Hiperuricemia/sangue , Hiperuricemia/induzido quimicamente , Eliminação Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Masculino , Camundongos , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Ácido Oxônico , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Ratos Sprague-Dawley , Espirostanos/isolamento & purificação , Fatores de Tempo , Uricosúricos/isolamento & purificação
20.
Heart Lung Circ ; 26(1): 49-57, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27451349

RESUMO

BACKGROUND: Platelet aggregation may predict the bleeding outcomes after percutaneous coronary intervention (PCI). METHODS: Consecutive patients with non-high risk acute coronary syndrome and indication for PCI were enrolled. Maximum adenosine diphosphate-induced platelet aggregation (ADP-PGmax) was assessed by light transmission aggregometry. Study endpoints were the incidence of haemorrhage, categorised by Thrombolysis in Myocardial Infarction criteria, and significant entry-site complications during hospitalisation and six-month follow-up period. Platelet aggregation test was organised at 24h after PCI and 1 month after discharge respectively. The optimal platelet aggregation was detected defining enhanced clopidogrel response, and associations of measurements with endpoints were assessed. RESULTS: A total of 278 patients were included in analyses. Study endpoints were observed in 24 (8.6%) patients [major bleeding, n=4 (1.4%); minor bleeding, n=11 (4.0%); significant entry-site complication, n=9 (3.2%)]. In multivariate analysis, follow-up ADP-PGmax[odds ratio (OR)=0.96;95% confidence interval (CI),0.93-0.99;p=0.008) and renal insufficiency (OR=3.29; 95%CI, 1.23-8.85; p=0.018) were predictors of bleeding events. The optimal cutoff value for follow-up ADP-PGmax was 24.5% (area under the curve=0.72; 95% CI, 0.59-0.85; p<0.001). Bleeding occurred in 26.2% (16/61) of patients with enhanced clopidogrel response and 3.7% (8/217) of other patients (OR=9.26; p<0.001). CONCLUSION: Enhanced clopidogrel responsiveness was associated with an increased risk of bleeding and entry-site complication. Platelet function testing at an appropriate time after clopidogrel administration helps to identify patients at high risk of bleeding.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/terapia , Difosfato de Adenosina/farmacologia , Hemorragia/sangue , Intervenção Coronária Percutânea/efeitos adversos , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/análogos & derivados , Idoso , Clopidogrel , Feminino , Seguimentos , Hemorragia/diagnóstico , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Ticlopidina/administração & dosagem
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