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1.
Eur J Clin Invest ; 44(10): 893-901, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25104141

RESUMO

BACKGROUND: A new 4-tired classification of left ventricular hypertrophy (LVH) based on LV concentricity and dilation has been proposed; however, the association between the new categorization of LV geometry and outcomes in patients with coronary artery disease (CAD) is still unknown. METHODS: All the 2297 patients with CAD included underwent echocardiographic examination prior to discharge. Left ventricular mass (LVM) was calculated, and left ventricular end-diastolic volume (EDV) was indexed by body surface area (BSA). Study cohort was divided into five groups according to LV geometry: (i) eccentric nondilated LVH (normal LVM/EDV((2/3)) and EDV/BSA) (n = 129); (ii) eccentric dilated LVH (normal LVM/EDV((2/3)) with increased EDV/BSA) (n = 222); (iii) concentric nondilated LVH (increased LVM/EDV((2/3)) with normal EDV/BSA) (n = 441); (iv) concentric dilated LVH (increased LVM/EDV((2/3)) and EDV/BSA) (n = 118); and (v) normal LV mass (n = 1387). RESULTS: Dilated LVH was associated with a higher event rates of all-cause death (eccentric 13·1% vs. 3·1%; concentric 13·6% vs. 8·4%) and composite events (eccentric: 17·6% vs. 5·4%; concentric: 18·6% vs. 12·7%) compared with nondilated LVH. While eccentric nondilated LVH had comparable risk for adverse outcomes compared with normal LV mass (all-cause death: relative risk (RR) 0·68, 95% confidential interval (CI) 0·25-1·85; composite events: RR 0·75, 95% CI 0·36-1·58). Cox regression analyses showed that eccentric dilated LVH had the highest propensity to all-cause death (adjusted hazard ratio [aHR] 2·752 [95% CI 1·749-4·328], P < 0·001) and composite events (aHR 2·462 [95% CI 1·688-3·592], P < 0·001). CONCLUSION: In patients with CAD, dilated LVH and nondilated LVH provide distinct prognostic information. Eccentric nondilated LVH does not predict adverse outcomes.


Assuntos
Hipertrofia Ventricular Esquerda/classificação , Distribuição por Idade , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/fisiopatologia , Ecocardiografia , Métodos Epidemiológicos , Feminino , Humanos , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Remodelação Ventricular/fisiologia
2.
Ren Fail ; 36(8): 1177-86, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24986458

RESUMO

Previous reports of percutaneous coronary intervention versus coronary artery bypass graft outcomes in coronary artery disease patients with chronic kidney disease (CKD) were inconsistent. We evaluated the optimal revascularization strategy for CKD patients. We searched Pub Med, EMBASE, and the Cochrane Central Register of Controlled Trials and scanned the references of relevant articles and reviews. All studies that compared relevant clinical outcomes between percutaneous coronary intervention and coronary artery bypass graft in CKD patients were selected. We defined short-term and long-term all-cause mortality as primary outcome, and long-term incidences of myocardial infarction and revascularization as secondary outcomes. A total of 2235 citations were retrieved, and 31 studies involving 99,054 patients, with 55,383 receiving percutaneous coronary intervention and 43,671 receiving coronary artery bypass graft, were included. In subgroup analyses of dialysis patients receiving percutaneous coronary intervention with stents versus coronary artery bypass graft, CKD patients with multivessel coronary disease, and CKD patients receiving drug-eluting stent versus coronary artery bypass graft, the pooled outcomes revealed that percutaneous coronary intervention possessed lower short-term mortality, but higher late revascularization risk. No significant differences in long-term mortality were observed between the two strategies in these subgroup analyses. In conclusion, in some specific clinical circumstances, CKD patients receiving percutaneous coronary intervention possessed lower short-term all-cause mortality, but higher long-term revascularization risk, than coronary artery bypass graft; long-term all-cause mortality was not different between the two strategies.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea , Insuficiência Renal Crônica/complicações , Humanos
3.
World J Hepatol ; 16(7): 1051-1066, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39086531

RESUMO

BACKGROUND: The modified Xiaoyao San (MXS) formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer, which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival. However, the molecular mechanisms underlying that remain unclear. AIM: To investigate the role and mechanisms of MXS in ameliorating hepatic injury, steatosis and inflammation. METHODS: A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis (NASH) model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes. Liver tissues were collected for western blotting and immunohistochemistry (IHC) assays. Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining. The serum samples were collected for biochemical assays and NMR-based metabonomics analysis. The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH. RESULTS: MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress. The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation, inflammation and hepatic fibrosis in the pathogenesis of NASH. The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis. Mechanistically, we found that MXS protected against NASH by attenuating the sex hormone-related metabolism, especially the metabolism of male hormones. CONCLUSION: MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones. Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.

4.
J Nutr Biochem ; 124: 109489, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37926400

RESUMO

Epidemiological studies suggest an association between folate deficiency (FD) and cervical squamous cell carcinoma (SCC) progression. However, the underlying mechanism is unclear. Our study showed that FD-driven downregulation of miR-375 promoted proliferation of SCC SiHa cells and progression of xenograft tumors developed from SiHa; however, the exact mechanism of this process remained unclear. The current study aimed to elucidate the underlying mechanisms by which FD promotes the progression of SiHa cells by downregulating miR-375 expression. The results showed that miR-375 acted as a suppressor of SCC and inhibited the proliferation, migration, and invasion of SiHa cells. The FZD4 gene was identified as a target gene of miR-375, which can reverse the anti-onco effect of miR-375 and promote the proliferation and migration of SiHa cells. Furthermore, the regulatory effects of miR-375 and FZD4 on SiHa cells may be achieved by activating the ß-catenin signaling pathway. Moreover, FD may regulate the expression of miR-375 by regulating its DNA methylation level in the promoter region. In conclusion, our study reveals that FD regulates the miR-375/FZD4 axis by increasing the methylation of the miR-375 promoter, thereby activating ß-catenin signaling to promote SiHa cells progression. This study may provide new insights into the role of folic acid in the prevention and treatment of SCC.


Assuntos
Carcinoma de Células Escamosas , MicroRNAs , Neoplasias do Colo do Útero , Feminino , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo do Útero/genética , Via de Sinalização Wnt , Ácido Fólico/farmacologia , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular , Receptores Frizzled/genética
5.
Hepatobiliary Surg Nutr ; 13(3): 393-411, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38911213

RESUMO

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated death. Emerging evidence suggests that autophagy plays a critical role in HCC tumorigenesis, metastasis, and prognosis. Choline is an essential nutrient related to prolonged survival and reduced risk of HCC. However, it remains unclear whether this phenomenon is mediated by autophagy. Methods: Two HCC cell lines (HUH-7 and Hep3B) were used in the present study. Cell growth was evaluated by cell counting kit 8 (CCK-8), colony formation, and in vivo mouse xenografts assays. Cell motility was calculated by wound healing and transwell assays. Autophagosomes were measured by transmission electron microscope (TEM), and autophagy flux was detected by mRFP-GFP-labeled LC3 protein. The mRNA level of genes was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels were detected by Western blotting (WB). Results: We found that choline inhibited the proliferation, migration, and invasion of HCC cells by downregulating autophagy in vitro and in vivo. Upregulated expression of the solute carrier family 5 member 7 (SLC5A7), a specific choline transporter, correlated with better HCC prognosis. We further discovered that choline could promote SLC5A7 expression, upregulate cytoplasm p53 expression to impair the AMPK/mTOR pathway, and attenuate autophagy. Finally, we found that choline acted synergistically with sorafenib to attenuate HCC development in vitro and in vivo. Conclusions: Our findings provide novel insights into choline-mediated autophagy in HCC, providing the foothold for its future application in HCC treatment.

6.
Redox Biol ; 69: 103026, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38184996

RESUMO

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 µg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1ß, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1ß. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.


Assuntos
Betaína , Disfunção Cognitiva , Animais , Ratos , Ratos Sprague-Dawley , Betaína/farmacologia , Piroptose , Interleucina-18 , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Caspase 1 , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Homocisteína , Interleucina-1beta , Inflamassomos
7.
Sheng Li Xue Bao ; 64(3): 289-95, 2012 Jun 25.
Artigo em Zh | MEDLINE | ID: mdl-22717632

RESUMO

To investigate the effect of Ca(2+)-sensing receptor (CaR) on Spermine-induced extracellular Ca(2+) influx and NO generation in human umbilical vein endothelial cells (HUVEC), the small interference RNA (siRNA) specifically targeting CaR gene was designed, synthesized and transfected into HUVEC according to the cDNA sequence of human CaR gene in GenBank. The transfection efficiency and the interference efficiency of CaR protein were determined by laser scanning confocal microscopy and Western blot, respectively. Intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured by Fura-2/AM loading. The production of NO and the activity of endothelial nitric oxide synthase (eNOS) were determined by the DAF-FM diacetate (DAF-FM DA). Western blot results demonstrated that siRNA targeting the CaR specifically decreased the expression of CaR protein in CaR siRNA group 48 h after transfection (P < 0.05). At the same time, the Spermine-induced [Ca(2+)](i), eNOS activity and NO generation were also significantly reduced (P < 0.05) in CaR siRNA group compared with those in the untransfected or negative siRNA transfected group. In conclusion, the present study suggests that the CaR plays an important role in the Spermine-evoked process of extracellular Ca(2+) influx and NO generation in HUVEC.


Assuntos
Cálcio/fisiologia , Células Endoteliais da Veia Umbilical Humana/fisiologia , Óxido Nítrico/fisiologia , RNA Interferente Pequeno , Receptores de Detecção de Cálcio/fisiologia , Células Cultivadas , Humanos , Óxido Nítrico Sintase Tipo III/fisiologia , Receptores de Detecção de Cálcio/genética , Espermina/farmacologia , Transfecção
8.
Food Chem ; 345: 128761, 2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-33310557

RESUMO

2-Acetylthiazole possesses a nutty, cereal-like and popcorn-like aroma and a low odor threshold, and this compound has been identified in some processed foods, while the formation pathway of 2-acetylthiazole has not been clearly elucidated. Here, a model reaction of d-glucose and l-cysteine was constructed to investigate the formation pathway of 2-acetylthiazole. l-Cysteine, d-glucose and the corresponding intermediates, namely, dicarbonyl compounds (DCs), were involved in the formation of 2-acetylthiazole and detected by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), high-performance ion chromatography (HPIC) and HPLC, respectively. The carbon module labeling (CAMOLA) technique revealed that the C-4 and C-5 of 2-acetylthiazole were derived from the carbons of glucose. The potential of glyoxal, which is degraded by glucose, to form 2-acetylthiazole was revealed for the first time. A novel route to form 2-acetylthiazole by the reaction of glyoxal and methylglyoxal produced by d-glucose with H2S and NH3 produced by l-cysteine was proposed.


Assuntos
Reação de Maillard , Tiazóis/síntese química , Cromatografia Líquida de Alta Pressão , Cisteína/química , Glucose/química , Glioxal/química , Odorantes/análise , Aldeído Pirúvico/química , Espectrometria de Massas em Tandem
9.
Int J Vitam Nutr Res ; 80(2): 117-30, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20803426

RESUMO

Vitamin A is largely thought to have immune potential for mammal health; however, no conclusive mechanisms exist regarding its role in the pathogen-initiated innate immune response, or in the linkage between the innate and adaptive immune system during sperm formation in the male reproductive tract. Therefore, this study was conducted to evaluate the nutritional protective effect of vitamin A supplementation on reproductive performance and immune function of the male mouse challenged with pseudorabies virus (PRV). Sperm quality, testis toll-like receptors (TLRs) mRNA expression levels, and serum concentration of cytokines and immunoglobulins at 7 or 14 days post-injection were compared between control mice and PRV-challenged mice fed the same diet supplemented with vitamin A at 0, 4000, 10,000, 25,000 and 50,000 IU/kg, respectively. PRV- and phosphate buffered saline (PBS)-injection were performed when the mice in the unsupplemented group were marginally deficient in vitamin A. Sperm quality (sperm density and deformity ratio) of PRV-injected mice was significantly harmed by PRV, but this effect was attenuated by increased vitamin A consumption. Vitamin A supplements also attenuated PRV-challenge-induced increase in testis TLR3, TLR7, and TLR9 mRNA expression and serum pro-inflammatory cytokine (gamma interferon, IFN-gamma; and interleukin 1-beta,IL-1beta) concentration, and decrease in serum anti-inflammatory cytokine (IL-10) concentration. Higher than normal vitamin A consumption was recommended to counteract the deleterious effects of viral invasion, possibly through the downregulated expression of TLRs, and thus to improve immunity and reproductivity of male mice challenged with an invading pathogen.


Assuntos
Suplementos Nutricionais , Herpesvirus Suídeo 1/efeitos dos fármacos , Inflamação/imunologia , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Vitamina A/farmacologia , Análise de Variância , Animais , Cromatografia Líquida de Alta Pressão , Citocinas/sangue , Citocinas/efeitos dos fármacos , Citocinas/imunologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Seguimentos , Herpesvirus Suídeo 1/imunologia , Imunoglobulinas/sangue , Imunoglobulinas/efeitos dos fármacos , Inflamação/sangue , Masculino , Camundongos , Reação em Cadeia da Polimerase , Pseudorraiva/sangue , Pseudorraiva/imunologia , RNA/sangue , RNA/efeitos dos fármacos , RNA/imunologia , Reprodução/efeitos dos fármacos , Reprodução/imunologia , Espermatozoides/imunologia , Testículo/imunologia , Receptores Toll-Like/sangue , Receptores Toll-Like/efeitos dos fármacos , Receptores Toll-Like/imunologia , Vitamina A/imunologia
10.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(1): 247-50, 2010 Jan.
Artigo em Zh | MEDLINE | ID: mdl-20302124

RESUMO

The present paper reports a rapid method for the determination of furfural (F) and 5-hydroxymethyl furfural (HMF) in pre-extraction liquors of lignocellulosic biomass based on UV spectroscopy. In a concentrated acetic acid medium, F and HMF have an isosbestic point at 276 nm. It was found that the acidic soluble lignin in the pre-extraction sample is the major interference species in the F and HMF spectroscopic quantification However, only acidic soluble lignins have the absorption at the wavelengths above 325 nm. Based on the absorption of the acidic soluble lignins at 325 nm, their absorptions at either F or HMF absorbed wavelengths can be determined. Thus, with a simple triple-wavelength technique, both F and HMF in the pre-extraction liquors of lignocellulosic biomass can be quantified based on the spectroscopic measurement at the isosbestic point wavelength (276 nm), maximum absorption wavelength of F (272 nm) and the acid soluble lignin absorbed wavelength (325 nm). The present method does not require the hazardous organic compounds (such as phenolic compounds etc.) acting as a color reagent in the experiment. It is not only simple and rapid, but also has a good measurement precision and accuracy, with the relative standard deviations of 3.02% and 2.72%, and recoveries of 95%-107% and 96%-101%, respectively, in the F and HMF quantification. The present method is suitable for use in the research on pre-extraction hemicellulose of the lignocellulosic biomass in bio-refinery area in order to achieve a high selective sugar conversion.


Assuntos
Biomassa , Furaldeído/análogos & derivados , Furaldeído/análise , Espectrofotometria Ultravioleta , Lignina/química
11.
3 Biotech ; 10(6): 259, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32432020

RESUMO

The domestic yak (Bos grunniens) from the Qinghai-Tibet Plateau is an important animal model in high-altitude adaptation studies. Here, we performed the genome-wide selective sweep analysis to identify the candidate copy number variation (CNV) for the high-altitude adaptation of yaks. A total of 531 autosomal CNVs were determined from 29 yak genome-wide resequencing data (15 high- and 14 low-altitude distributions) by using a CNV caller with a CNV identification interval > 5 kb, CNV silhouette score > 0.7, and minimum allele frequency > 0.05. Most high-frequency CNVs were located at the exonic (44.63%) and intergenic (46.52%) regions. In accordance with the results of the selective sweep analysis, 7 candidate CNVs were identified from the interaction of the top 20 CNVs with highest divergence from the F ST and V ST between the low (LA) and high (HA) altitudes. Five genes (i.e., GRIK4, IFNLR1, LOC102275985, GRHL3, and LOC102275713) were also annotated from the seven candidate CNVs and their upstream and downstream ranges at 300 kb. GRIK4, IFNLR1, and LOC102275985 were enriched in five known signal pathways, namely, glutamatergic synapse, JAK-STAT signaling pathway, cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and olfactory transduction. These pathways are involved in the environmental adaptability and various physiological functions of animals, especially the physiological regulation under a hypoxic environment. The results of this study advanced the understanding of CNV as an important genomic structure variant type that contributes to HA adaptation and helped further explain the molecular mechanisms underlying the altitude adaptability of yaks.

12.
3 Biotech ; 9(9): 336, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31475088

RESUMO

Litter size is considered to be the most important index for estimating domestic animal productivity. The number of indigenous goats in China with higher litter sizes than those of commercial breeds in other countries may be helpful for accelerating genetic improvements in goat breeding. We performed a genome-wide selective sweep analysis of 31 Dazu black goats with extreme standard deviation in litter size within the third fetus to identify significant genomic regions and candidate genes through different analyses. The analysis identified a total of 33,917,703 variants, including 32,262,179 SNPs and 1,655,524 indels. In addition, two novel candidate genes (LRP1B and GLRB), which are related to litter size, were obtained with π, Tajima's D, πA/πB, and F ST at the individual level with a 95% threshold for each parameter. These two genes were annotated in five GO terms (localization, binding, macromolecular complex, membrane part, and membrane) and two pathways (long-term depression and neuroactive ligand-receptor interaction pathway). Regarding the result of linkage disequilibrium (LD) analysis, in LRP1B and GRID2, the high-yield Dazu black goats exhibit significantly different LD patterns from low-yield goats. Litter size variability has low heritability and is related to multiple complex factors found in domestic animals. Obtaining a clear explanation and significant signal by genome-wide selective sweep analysis with a small sample size is difficult. However, we investigated some candidate genes, particularly LRP1B and GLRB, which may provide useful information for further research.

13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 28(6): 1368-71, 2008 Jun.
Artigo em Zh | MEDLINE | ID: mdl-18800725

RESUMO

The interaction between acetamiprid and deoxyribonucleic acid (DNA) was used to determine acetamiprid by resonance light scattering (RLS). The RLS signals of DNA were greatly enhanced by acetamiprid in the spectrum region of 300-600 nm. The spectrum peak is around 316.0 nm. The optimum conditions: pH is 1.73; the concentration of DNA is 2.0 microg x mL(-1)bration curve is 0-2. 25 pg * mLU , with the detection2limit of 0. 2 ig * mL '. The acetamiprid in river water sample was determined. The results were satisfactory, and the recovery rates were in the range of 98%-106%. The interaction mechanism of acetamiprid and DNA was discussed: the interactions between acetamiprid and nucleic acid base include electrostatic effect and Tr-r cumulate effect.


Assuntos
DNA/química , Piridinas/análise , Concentração de Íons de Hidrogênio , Luz , Neonicotinoides , Piridinas/química , Espalhamento de Radiação , Eletricidade Estática
14.
Cancer Res ; 78(13): 3532-3543, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29735544

RESUMO

A high rate of disease relapse makes epithelial ovarian cancer (EOC) the leading cause of death among all gynecologic malignancies. These relapses are often due to tumor dormancy. Here we identify the RNA polymerase II transcriptional mediator subunit 12 (MED12) as an important molecular regulator of tumor dormancy. MED12 knockout (KO) induced dormancy of EOC cells in vitro and in vivo, and microarray analysis showed that MED12 KO decreased expression of EGFR. Restoration of EGFR expression in MED12 KO cells restored proliferation. Additionally, MED12 bound to the promoter of EGFR, and correlation studies showed that MED12 expression positively correlated with EGFR expression in EOC patient samples. Clinical data demonstrated that chemotherapy-resistant patients expressed lower levels of MED12 compared with responsive patients. Overall, our data show that MED12 plays an important role in regulating dormancy of EOC through regulation of EGFR.Significance: MED12 is identified as a novel, important regulator of tumor dormancy in human ovarian cancer. Cancer Res; 78(13); 3532-43. ©2018 AACR.


Assuntos
Carcinoma Epitelial do Ovário/genética , Regulação Neoplásica da Expressão Gênica , Complexo Mediador/metabolismo , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/genética , Adulto , Idoso , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistemas CRISPR-Cas/genética , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Linhagem Celular Tumoral , Proliferação de Células/genética , Estudos de Coortes , Procedimentos Cirúrgicos de Citorredução , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Técnicas de Inativação de Genes , Humanos , Estimativa de Kaplan-Meier , Complexo Mediador/genética , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Regiões Promotoras Genéticas/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
15.
J Nutr Biochem ; 32: 163-70, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27142732

RESUMO

Prenatal intake of choline has been reported to lead to enhanced cognitive function in offspring, but little is known about the effects on spatial learning deficits. The present study examined the effects of prenatal choline supplementation on developmental low-protein exposure and its potential mechanisms. Pregnant female rats were fed either a normal or low-protein diet containing sufficient choline (1.1g/kg choline chloride) or supplemented choline (5.0g/kg choline chloride) until delivery. The Barnes maze test was performed at postnatal days 31-37. Choline and its metabolites, the synaptic structural parameters of the CA1 region in the brain of the newborn rat, were measured. The Barnes maze test demonstrated that prenatal low-protein pups had significantly greater error scale values, hole deviation scores, strategy scores and spatial search strategy and had lesser random search strategy values than normal protein pups (all P<.05). These alterations were significantly reversed by choline supplementation. Choline supplementation increased the brain levels of choline, betaine, phosphatidylethanolamine and phosphatidylcholine of newborns by 51.35% (P<.05), 33.33% (P<.001), 28.68% (P<.01) and 23.58% (P<.05), respectively, compared with the LPD group. Prenatal choline supplementation reversed the increased width of the synaptic cleft (P<.05) and decreased the curvature of the synaptic interface (P<.05) induced by a low-protein diet. Prenatal choline supplementation could attenuate the spatial learning deficits caused by prenatal protein malnutrition by increasing brain choline, betaine and phospholipids and by influencing the hippocampus structure.


Assuntos
Colina/uso terapêutico , Dieta com Restrição de Proteínas/efeitos adversos , Suplementos Nutricionais , Desenvolvimento Fetal , Deficiências da Aprendizagem/prevenção & controle , Fenômenos Fisiológicos da Nutrição Materna , Aprendizagem Espacial , Animais , Animais Recém-Nascidos , Comportamento Animal , Região CA1 Hipocampal/crescimento & desenvolvimento , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Região CA1 Hipocampal/ultraestrutura , Feminino , Deficiências da Aprendizagem/etiologia , Deficiências da Aprendizagem/patologia , Aprendizagem em Labirinto , Microscopia Eletrônica de Transmissão , Neurônios/citologia , Neurônios/metabolismo , Neurônios/patologia , Neurônios/ultraestrutura , Gravidez , Distribuição Aleatória , Ratos Sprague-Dawley , Comportamento Espacial , Sinapses/metabolismo , Sinapses/patologia , Sinapses/ultraestrutura
16.
Cancer Prev Res (Phila) ; 9(2): 180-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26407680

RESUMO

Distant metastasis is the most common cause of treatment failure and mortality in nasopharyngeal carcinoma (NPC) patients. Thus, it is important to understand the mechanism of NPC metastasis and identify reliable prognostic factors. In this study, we investigated the prognostic value of unconjugated bilirubin (UCB), which was previously considered a byproduct of heme catabolism, in NPC patients and examined the effects of UCB on NPC metastasis. The receiver operating characteristic analysis-generated UCB cutoff point for DMFS was 9.7 µmol/L. We found that higher UCB levels were significantly associated with favorable distant metastasis-free survival (DMFS, 93.3% vs. 84.2%, P < 0.001) in NPC patients and was an independent predictor for DMFS (HR, 0.416; 95% confidence interval, 0.280-0.618; P < 0.001). We next found that UCB treatment impaired the invasion capability of NPC cells and potently inhibited lung metastasis of NPC cells in nude mice. Further investigation showed that UCB inhibited reactive oxygen species production, which is involved in the repression of ERK1/2 activation and matrix metalloproteinase-2 (MMP-2) expression. Moreover, lower levels of ERK1/2 phosphorylation and MMP-2 expression were observed in the NPC lung metastases of nude mice administered UCB. Taken together, our results indicate that UCB is a significantly favorable factor for DMFS in NPC patients and may play an important role in NPC chemoprevention.


Assuntos
Antioxidantes/farmacologia , Bilirrubina/farmacologia , Biomarcadores/metabolismo , Neoplasias Nasofaríngeas/secundário , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose , Western Blotting , Carcinoma , Movimento Celular , Proliferação de Células , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Eur J Intern Med ; 29: 78-87, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26809866

RESUMO

BACKGROUND: Despite strong evidence linking decreased estimated glomerular filtration rate (eGFR) to worse cardiovascular outcome, the impact of eGFR on mortality in coronary artery disease (CAD) patients with different left ventricular ejection fraction (EF) is not well defined. METHODS: A retrospective cohort study. From Jul. 2008 to Jan. 2012, consecutive patients with CAD of West China Hospital were enrolled and were grouped into 3 eGFR categories: ≥90, 60-90, and <60mL/min/1.73m(2). Patients with EF≥50% or <50% were defined as preserved EF or reduced EF, respectively. The endpoints were all-cause mortality and cardiac mortality. RESULTS: There are 2161 patients according to the inclusion criteria and follow-up requirement. The mean follow-up time was 30.97±11.70months. Cumulative survival curves showed that in patients with reduced EF, renal insufficiency significantly increases all-cause mortality and cardiovascular mortality in a graded fashion (mortality rate, moderate or severe vs. normal: 29.3% vs. 5.4%, p<0.001; cardiac mortality rate, moderate or severe vs. normal: 18.2% vs. 4.5%, p=0.001, respectively). Cox regression analysis showed that in CAD patients with reduced EF, moderate to severe renal insufficiency increased all-cause mortality by 6.10-fold (HR 6.10, 95% CI 2.50 to 14.87) and cardiac mortality by 4.10-fold (HR 4.10, 95% CI 1.51 to 11.13). Use of beta-blockers, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and statins was associated with decreased risk of mortality, but the use was lower in renal insufficiency patients, especially in combination of reduced EF. CONCLUSION: This study has found that the effect of renal function on prognosis in patients with CAD is closely related to cardiac function. In patients with reduced EF, renal insufficiency accompanies the higher risks of all-cause mortality and cardiovascular mortality. A higher number of treatments from beta-blocker, ACEIs or ARBs, and statin therapy were associated with decreased risk of mortality, even in the combination of renal insufficiency or declining cardiac function.


Assuntos
Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Renal/complicações , Volume Sistólico/efeitos dos fármacos , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , China , Doença da Artéria Coronariana/tratamento farmacológico , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
18.
Wei Sheng Yan Jiu ; 34(4): 445-8, 2005 Jul.
Artigo em Zh | MEDLINE | ID: mdl-16229272

RESUMO

OBJECTIVE: To investigate the characteristics of calcium metabolism in relation to different levels of dietary calcium intakes in premenarche Chinese girls. METHODS: Forty-nine healthy premenarche girls of Han ethic (9 - 11.5 years) were recruited, and divided into four groups respectively, receiving four different doses of calcium intakes for 6 days, 600 mg (usual diet), 900 mg (containing 250 ml of milk), 1200 mg (containing 250ml of milk and 750 mg of calcium carbonate) and 1500mg calcium (250 ml of milk and 1500 mg of calcium carbonate) per day. A 3-day urine and stool, and a 3-d duplicated food samples were collected to assess the calcium excretion in urine and feces and input of the dietary calcium during the treatment period. RESULTS: There were no significant differences in appearance calcium absorption among the four groups (55%, 53%, 52% and 52%). Urine calcium is correlated negatively with dietary protein and dietary phosphorus. And no correlation was found between dietary protein and calcium absorption. CONCLUSION: The appearance calcium absorption was (53 +/- 0.12) % in Chinese premenarche girls with dietary calcium intakes ranged between 800 to 1600 mg/d, high dietary protein intakes increase urine calcium secrete.


Assuntos
Cálcio da Dieta/administração & dosagem , Cálcio/farmacocinética , Absorção Intestinal/fisiologia , Cálcio/administração & dosagem , Cálcio/metabolismo , Criança , China , Proteínas Alimentares/administração & dosagem , Feminino , Humanos , Pré-Menopausa
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 25(7): 1021-5, 2005 Jul.
Artigo em Zh | MEDLINE | ID: mdl-16241045

RESUMO

A new equipment of pulsed DC discharge supersonic molecular beam was set up for producing transient species. Thepulsed DC discharge can be used stably under 10 kV. In data collection using software, it can be utilized as gated integrators and averagers. Using this equipment, the processes of N2O discharge were studied. The emission spectra of N2O+ (A2sigma+ - X2IIi) were obtained. From the intensity of vibrational spectra, the vibrational populations of the N2O+ (A2sigma+ ) states were calculated. Compared with other results, A states of N2O+ depart even more from a Boltzmann distribution.


Assuntos
Técnicas Eletroquímicas/métodos , Óxido Nitroso/química , Espectrometria de Fluorescência/métodos , Algoritmos , Técnicas Eletroquímicas/instrumentação , Software , Espectrometria de Fluorescência/instrumentação
20.
Chin Med J (Engl) ; 128(9): 1137-46, 2015 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-25947393

RESUMO

BACKGROUND: No national research on maternal and fetal complications and outcomes has been carried out in the mainland of China in recent years. This study was to provide a scientific basis for better control of obstetrical and neonatal diseases and better allocation of medical resources by analyzing the epidemiological characteristics of obstetrical diseases in the mainland of China. METHODS: Hospitalized obstetrical cases from 19 tertiary and 20 secondary hospitals in 14 provinces (nationally representative) during the period January 1, 2011 to December 31, 2011 were randomly selected. The general condition, pregnancy complications, and perinatal outcomes of the patients were studied. RESULTS: The top five medical and surgical complications of pregnant women in the mainland of China were anemia (6.34%), uterine fibroids (2.69%), thyroid disease (1.11%), thrombocytopenia (0.59%), and heart disease (0.59%). The incidences of premature rupture of membranes (PROM), preterm birth, prolonged pregnancy, hypertensive disorders complicating pregnancy (HDCP), multiple pregnancy, intrahepatic cholestasis of pregnancy (ICP), placenta previa, placental abruption, postpartum hemorrhage, and amniotic fluid embolism were 15.27%, 7.04%, 6.71%, 5.35%, 1.57%, 1.22%, 1.14%, 0.54%, 3.26% and 0.06%, respectively. The incidences of anemia and prolonged pregnancy were significantly lower in tertiary than secondary hospitals (P < 0.001), whereas the incidence of uterine fibroids, thyroid diseases, thrombocytopenia, heart disease, PROM, preterm birth, HDCP, multiple pregnancy, ICP, placenta previa, and placental abruption were significantly higher in tertiary than secondary hospitals (P < 0.001). The cesarean section (CS) rate was 54.77%. The newborn sex ratio was 119:100, and 1.03% of the neonates were malformed. The percentages of low birth weight and fetal macrosomia in full-term babies were 2.10% and 7.09%, respectively. CONCLUSIONS: The incidence of some obstetrical diseases is still high in the mainland of China. The CS rate is much higher than World Health Organization recommendations, in which CS delivery by maternal request (CDMR) accounted for a large proportion. The government should propose solutions to reduce CS rate, especially the rate of CDMR. Most obstetrical complications have higher incidence in tertiary hospitals compared with secondary hospitals. It is important to manage the health of pregnant women systematically, especially those with high-risk factors.


Assuntos
Complicações na Gravidez/epidemiologia , China/epidemiologia , Feminino , Doenças dos Genitais Femininos/epidemiologia , Humanos , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Gravidez
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