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1.
Sensors (Basel) ; 24(4)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38400472

RESUMO

Because of its uneven and large slope, unstructured pavement presents a great challenge to obtaining the adhesion coefficient of pavement. An estimation method of the peak adhesion coefficient of unstructured pavement on the basis of the extended Kalman filter is proposed in this paper. The identification accuracy of road adhesion coefficients under unstructured pavement is improved by introducing the equivalent suspension model to optimize the calculation of vertical wheel load and modifying vehicle acceleration combined with vehicle posture data. Finally, the multi-condition simulation experiments with Carsim are conducted, the estimation accuracy of the adhesion coefficient is at least improved by 3.6%, and then the precision and effectiveness of the designed algorithm in the article are verified.

2.
Int J Mol Sci ; 25(2)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38256044

RESUMO

Tyrosinase is vital in fruit and vegetable browning and melanin synthesis, crucial for food preservation and pharmaceuticals. We investigated 6'-O-caffeoylarbutin's inhibition, safety, and preservation on tyrosinase. Using HPLC, we analyzed its effect on mushroom tyrosinase and confirmed reversible competitive inhibition. UV_vis and fluorescence spectroscopy revealed a stable complex formation with specific binding, causing enzyme conformational changes. Molecular docking and simulations highlighted strong binding, enabled by hydrogen bonds and hydrophobic interactions. Cellular tests showed growth reduction of A375 cells with mild HaCaT cell toxicity, indicating favorable safety. Animal experiments demonstrated slight toxicity within safe doses. Preservation trials on apple juice showcased 6'-O-caffeoylarbutin's potential in reducing browning. In essence, this study reveals intricate mechanisms and applications of 6'-O-caffeoylarbutin as an effective tyrosinase inhibitor, emphasizing its importance in food preservation and pharmaceuticals. Our research enhances understanding in this field, laying a solid foundation for future exploration.


Assuntos
Arbutina/análogos & derivados , Ácidos Cafeicos , Monofenol Mono-Oxigenase , Chá , Animais , Simulação de Acoplamento Molecular , Preparações Farmacêuticas
3.
Chem Biodivers ; 20(5): e202201099, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37096966

RESUMO

Subcritical water extraction was used to extract bioactive phenolic compounds from Vaccinium dunalianum Wight leaves. The optimal extraction conditions were determined as an extraction temperature of 150 °C, an extraction time of 40 min, and a liquid-solid ratio of 35 : 1 mL/g. The total phenolic content reached 21.35 mg gallic acid /g, which was 16 % higher than that by hot water extraction. The subcritical water extraction extract exhibited strong scavenging activity of DPPH free radical and ABTS+ free radical, as well as significant tyrosinase inhibitory activity. The study suggests that subcritical water extraction can alter the composition of the extracts, leading to the production of various phenolic compounds, effective antioxidants, and tyrosinase inhibitors from Vaccinium dulciana Wight leaves. These findings confirm the potential of Vaccinium dunalianum Wight as a natural antioxidant molecule source for the medicine and food industries, and for the therapy of skin pigmentation disorders.


Assuntos
Antioxidantes , Vaccinium , Antioxidantes/química , Água/química , Monofenol Mono-Oxigenase , Vaccinium/química , Extratos Vegetais/química , Fenóis/química , Folhas de Planta/química
4.
Mol Biol Evol ; 38(4): 1595-1607, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33331879

RESUMO

Sturgeons and paddlefishes (Acipenseriformes) occupy the basal position of ray-finned fishes, although they have cartilaginous skeletons as in Chondrichthyes. This evolutionary status and their morphological specializations make them a research focus, but their complex genomes (polyploidy and the presence of microchromosomes) bring obstacles and challenges to molecular studies. Here, we generated the first high-quality genome assembly of the American paddlefish (Polyodon spathula) at a chromosome level. Comparative genomic analyses revealed a recent species-specific whole-genome duplication event, and extensive chromosomal changes, including head-to-head fusions of pairs of intact, large ancestral chromosomes within the paddlefish. We also provide an overview of the paddlefish SCPP (secretory calcium-binding phosphoprotein) repertoire that is responsible for tissue mineralization, demonstrating that the earliest flourishing of SCPP members occurred at least before the split between Acipenseriformes and teleosts. In summary, this genome assembly provides a genetic resource for understanding chromosomal evolution in polyploid nonteleost fishes and bone mineralization in early vertebrates.


Assuntos
Evolução Biológica , Calcificação Fisiológica/genética , Cromossomos , Peixes/genética , Genoma , Animais , Proteínas de Ligação ao Cálcio/genética , Genes Homeobox , Fosfoproteínas/genética
5.
Breast Cancer Res Treat ; 182(1): 35-46, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32424721

RESUMO

PURPOSE: Oxidative stress-responsive kinase 1 (OSR1) plays a crucial role in regulating diverse cellular pathophysiologic functions, including ion homeostasis, development, differentiation, angiogenesis, invasive migration, and metastasis. Regardless, the clinical significance of OSR1 in breast cancer is scarce. The current study was conducted to evaluate the effect of OSR1 on the prognosis of patients with breast cancer with a long-term follow-up. METHODS: OSR1 expression in formalin-fixed and paraffin-embedded tissue specimens was analyzed. These specimens were collected from 551 evaluable breast cancer cases by immunohistochemistry (IHC). OSR1 expression was dichotomized based on the H-score in IHC. The effects of OSR1 levels on the clinicopathological attributes and survival prediction in patients with breast cancer were explored. RESULTS: Among 551 specimens, 183 (33.2%) exhibited high expression of OSR1 in tumor cells. High OSR1 levels were markedly correlated with histologic grade (P = 0.035), ER (P < 0.001) and PgR (P = 0.043) expression, lymph node involvement (P < 0.001), TNM stage (P < 0.001), and axillary surgery procedures (P = 0.003). Univariate analysis results indicate that patients with high OSR1 expression had significantly poor overall survival (P < 0.001), distant disease-free survival (P < 0.001), and breast cancer-specific survival (P < 0.001). Multivariable Cox regression analyses suggest that OSR1 expression was an independent predictive marker of poor prognosis and lymph node metastasis (HR 3.224, 95% CI 1.182-8.702, P = 0.023) in patients with breast cancer. CONCLUSIONS: Our findings indicate that OSR1 is a significantly independent prognosis index for patients with breast cancer with respect to distant disease-free survival, overall survival, and breast cancer-specific survival. High OSR1 expression caused an increase in deaths specifically attributed to breast cancer and was related to increased lymph node metastasis. However, the precise cellular mechanisms for OSR1 in breast cancer require further research.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Proteínas Serina-Treonina Quinases/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/terapia , Terapia Combinada , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida
6.
Tumour Biol ; 37(2): 1871-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26323259

RESUMO

Notch receptors are frequently deregulated in several human malignancies including human breast cancer. Activation of Notch has been reported to cause mammary carcinomas in mice. However, the prognostic value of individual Notch receptors in breast cancer (BC) patients remains elusive. In the current study, we investigated the prognostic value of Notch receptors in human BC patients. More specifically, we investigated the prognostic value of four Notch receptors in breast cancer patients through "the Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information are from a total of 3554 breast cancer patients. Our results showed that Notch1 messenger RNA (mRNA) high expression was correlated to worsen overall survival (OS) in PgR-negative BC patients. Notch2, Notch3, and Notch4 mRNA high expressions were found to be correlated to better OS for all breast cancer patients. Notch2 was also found to be correlated to better OS in lymph node-negative breast cancer patients and HER2-positive breast cancer patients. These results will be useful for better understanding of the heterogeneity and complexity in the molecular biology of breast cancer and for developing tools to more accurately predict their prognosis and design their customized treatment strategies.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptores Notch/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Prognóstico , RNA Mensageiro/genética , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética
7.
Nanotechnology ; 27(8): 085402, 2016 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-26808457

RESUMO

Reaction beyond intercalation and the utilization of metal ions beyond lithium-ions are two promising approaches for developing the next generation of high capacity and low cost energy storage materials. Here, we use graphene supported Co3O4 nanocubes and study their reaction with lithium, magnesium and aluminum using in situ transmission electron microscopy. On lithiation, the Co3O4 nanocubes decompose to Co metal nanoparticles (2 to 3 nm) and embed in as-formed Li2O matrix; conversely, the CoO nanoparticles form on the Co site accompanying the decomposition of Li2O in the delithiation process. The lithiation process is dominated by surface diffusion of Li(+), and graphene sheets enhance the Li(+) diffusion. However, upon charge with magnesium, the Mg(2+) diffusion is sluggish, and there is no sign of conversion reaction between Mg and Co3O4 at room temperature. Instead, a thin film consisting of metal Mg nanoparticles is formed on the surface of graphene due to a process similar to metal plating. The Al(3+) diffusion is even more sluggish and no reaction between Al and Co3O4 is observed. These findings provide insights to tackle the reaction mechanism of multivalent ions with electrode materials.

8.
Nature ; 464(7285): 59-65, 2010 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-20203603

RESUMO

To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, approximately 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.


Assuntos
Trato Gastrointestinal/microbiologia , Genômica , Metagenoma/genética , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Estudos de Coortes , Mapeamento de Sequências Contíguas , Dinamarca , Fezes/microbiologia , Genes Bacterianos/genética , Genes Essenciais/genética , Genoma Bacteriano/genética , Saúde , Humanos , Doenças Inflamatórias Intestinais/genética , Obesidade/genética , Fases de Leitura Aberta/genética , Sobrepeso/genética , Análise de Sequência de DNA , Espanha
9.
Liver Transpl ; 21(3): 339-43, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25408472

RESUMO

Transabdominal intrapericardial control of the suprahepatic inferior vena cava (SIVC) is a rather uncommon procedure occasionally required in conjunction with complicated liver transplantation (LT) and hepatobiliary surgery. Experience with this technique is limited. Here we report 6 cases of LT in which transabdominal intrapericardial control of the SIVC was necessary. After institutional review board approval was obtained, a single-center, retrospective review was conducted from January 1991 to December 2013 to identify adult cases (age > 18 years) of LT in which transabdominal intrapericardial isolation of the SIVC was necessary. Among 4102 adult LT cases in the study period, 6 such cases were identified. To gain access to the pericardial space, a 6- to 9-cm vertical incision was made above the SIVC. After reperfusion, the diaphragmatic incision was partially closed and selectively drained. Pericardial tamponade developed in 1 patient, and it necessitated emergent reoperation and widespread drainage. In conclusion, transabdominal intrapericardial isolation of the SIVC is easily achieved without the need for a separate thoracic incision. However, to be effective, the pericardial incision should be only partially closed, and the pericardial sac should be drained liberally. Such patients should be carefully monitored for signs and symptoms of pericardial tamponade, the development of which should prompt an immediate return to the operating room for emergent decompression and widespread drainage.


Assuntos
Tamponamento Cardíaco/etiologia , Transplante de Fígado/efeitos adversos , Veia Cava Inferior/cirurgia , Adulto , Idoso , Tamponamento Cardíaco/diagnóstico , Tamponamento Cardíaco/cirurgia , Descompressão Cirúrgica/métodos , Drenagem , Feminino , Humanos , Transplante de Fígado/métodos , Los Angeles , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
10.
Tumour Biol ; 36(2): 959-66, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25315189

RESUMO

The high-mobility group nucleosome-binding domain 5 (HMGN5) is a member of the high-mobility group proteins family. Previous study found that HMGN5 is required for tumorigenesis in vitro, and aberrations in the expression of HMGN5 were found in human osteosarcoma, prostate cancer, and squamous cell carcinoma. Nevertheless, the role of HMGN5 in breast cancer remains unclear. This study aimed to investigate the expression and clinical significance of HMGN5 in human breast cancer, confirm the oncogenic role of HMGN5, and explore the mechanism by which HMGN5 contributes to invasion and metastasis. HMGN5 expression was detected in breast cancer tissues and corresponding adjacent non-cancerous tissues from 43 patients by immunohistochemistry, and the clinicopathologic characteristics of all patients were also analyzed. Next, knockdown of HMGN5 protein in MDA-MB-231 cells was performed through a small interfering RNA (siRNA) technique, and cell viability, apoptosis, and invasion were detected by cell vitality test, flow cytometry, and transwell assay, respectively. Immunohistostaining showed that HMGN5 were highly expressed in the nucleus in all breast cancer tissues as compared with the adjacent non-cancerous tissues (ANCT;(73.5 ± 11 vs. 31.0 ± 5 %, P < 0.01). HMGN5 expression level was associated with the poorly differentiated tumor cells, lymph node involvement tumor, and T4 staging tumor. Knockdown of HMGN5 inhibited cell growth, suppressed invasion, and increased cell apoptosis in human breast cancer MDA-MB-231 cells. Western blot analysis demonstrated that the expressions of PCNA, connective tissue growth factor (CTGF), and MMP-9 were decreased in human breast MDA-MB-231 cells depleted of HMGN5. In addition, the apoptotic markers (cleaved PARP and cleaved caspase-3) were significantly increased by HMGN5 knockdown, but microtubule-associated protein 1 light chain 3-II/I (LC3-II/I) did not alter. HMGN5 plays an oncogenic role in human breast cancer by inhibiting cell proliferation and invasion, and activating apoptosis, which could be exploited as a target for therapy in human breast cancer.


Assuntos
Neoplasias da Mama/genética , Proliferação de Células/genética , Proteínas HMGN/biossíntese , Invasividade Neoplásica/genética , Transativadores/biossíntese , Apoptose/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Proteínas HMGN/genética , Humanos , Pessoa de Meia-Idade , Transativadores/genética
11.
Tumour Biol ; 36(4): 2257-61, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25787748

RESUMO

Serum levels of carbohydrate antigen 19-9 (CA 19-9) were shown to be associated with poorer prognosis in several cancers, but the prognostic role of CA 19-9 levels in patients with hepatocellular carcinoma was unclear. A retrospective cohort of 97 patients with resectable hepatocellular carcinoma was performed to assess the prognostic role of CA 19-9 levels on overall survival in hepatocellular carcinoma. Both Kaplan-Meier product-limit method and multivariate analysis were performed to determine the prognostic role of CA 19-9 levels. The results indicated that among those 97 patients, 24 (24.7%) had elevated preoperative CA 19-9 levels (≥37 U/mL). Elevated serum CA 19-9 levels did not correlate with patient age, gender, tumor size, tumor stage, diabetes, and hepatitis B virus (HBV) infection. Kaplan-Meier product-limit method showed that patients with elevated CA 19-9 levels had poorer survival than those with normal CA 19-9 levels (log-rank test P < 0.001). Multivariate analysis showed that elevated CA 19-9 level was a significantly independent predictor of poorer overall survival (hazard ratio [HR] = 2.56; 95% confidence interval [95% CI] 1.41-4.64, P = 0.002). In addition, tumor stages and multiple tumors were also independent predictors of poorer overall survival in hepatocellular carcinoma (P < 0.01). In conclusion, serum CA 19-9 levels have an independent prognostic role in patients with resectable hepatocellular carcinoma. Elevated CA 19-9 level is significantly associated with poorer overall survival in hepatocellular carcinoma.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Adulto , Idoso , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
12.
J Med Genet ; 51(5): 319-26, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24665059

RESUMO

BACKGROUND: Elucidating the genetic basis underlying hepatic gene expression variability is of importance to understand the aetiology of the disease and variation in drug metabolism. To date, no genome-wide expression quantitative trait loci (eQTLs) analysis has been conducted in the Han Chinese population, the largest ethnic group in the world. METHODS: We performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue samples (n=64). The data were then compared with published eQTL data from a Caucasian population. We then performed correlations between these eQTLs with important pharmacogenes, and genome-wide association study (GWAS) identified single nucleotide polymorphisms (SNPs), in particular those identified in the Asian population. RESULTS: Our analyses identified 1669 significant eQTLs (false discovery rate (FDR) < 0.05). We found that 41% of Asian eQTLs were also eQTLs in Caucasians at the genome-wide significance level (p=10⁻8). Both cis- and trans-eQTLs in the Asian population were also more likely to be eQTLs in Caucasians (p<10⁻4). Enrichment analyses revealed that trait-associated GWAS-SNPs were enriched within the eQTLs identified in our data, so were the GWAS-SNPs specifically identified in Asian populations in a separate analysis (p<0.001 for both). We also found that hepatic expression of very important pharmacogenetic (VIP) genes (n=44) and a manually curated list of major genes involved in pharmacokinetics (n=341) were both more likely to be controlled by eQTLs (p<0.002 for both). CONCLUSIONS: Our study provided, for the first time, a comprehensive hepatic eQTL analysis in a non-European population, further generating valuable data for characterising the genetic basis of human diseases and pharmacogenetic traits.


Assuntos
Povo Asiático/genética , Fígado/fisiologia , Locos de Características Quantitativas , Adulto , Perfilação da Expressão Gênica , Genética Populacional , Estudo de Associação Genômica Ampla , Humanos , Masculino , Farmacogenética , Polimorfismo de Nucleotídeo Único , População Branca/genética
13.
Tumour Biol ; 35(3): 1757-62, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24385382

RESUMO

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene are considered to have some influence on both folate metabolism and cancer risk. Previous studies on the associations of MTHFR genetic polymorphisms with hepatocellular carcinoma (HCC) risk in Chinese population reported inconsistent results. We performed this meta-analysis to comprehensively assess the associations. Finally, 12 individual case-control studies were included into the meta-analysis. There were seven studies (6,384 subjects) on the MTHFR C677T polymorphism and five studies (4,502 subjects) on the MTHFR A1298C polymorphism. Overall, MTHFR C677T polymorphism was significantly associated with susceptibility to HCC in Chinese population (T versus C, odds ratio (OR) = 1.09, 95 % confidence interval (95% CI) 1.01-1.17; TT versus CC, OR = 1.17, 95% CI 1.00-1.38; TT/CT versus CC, OR = 1.12, 95% CI 1.00-1.26). MTHFR A1298C polymorphism was conversely associated with HCC risk in Chinese population (CC versus AA, OR = 0.65, 95% CI 0.46-0.91; CC versus AA/AC, OR = 0.64, 95% CI 0.46-0.90). The sensitivity analysis confirmed the reliability and stability of the meta-analysis. Thus, the findings from our meta-analysis support the associations of MTHFR C677T and A1298C polymorphisms with HCC risk in Chinese population.


Assuntos
Povo Asiático/genética , Carcinoma Hepatocelular/genética , Predisposição Genética para Doença/genética , Neoplasias Hepáticas/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Humanos , Fatores de Risco
14.
Zhonghua Gan Zang Bing Za Zhi ; 22(7): 529-35, 2014 Jul.
Artigo em Zh | MEDLINE | ID: mdl-25203806

RESUMO

OBJECTIVE: Endogenous hydrophobic bile acids may be a pathogenetic factor of biliary complications after orthotopic liver transplantation (OLT).This study was designed to investigate the effects of hydrophilic ursodeoxycholic acid (UDCA), when administered early after OLT, on serum liver tests and on the incidence of biliary complications. METHODS: A total of 112 adult patients undergoing OLT were randomly assigned to one of two groups for receipt of UDCA (13 to 15 mg/kg/d for 4 weeks, n=56) or a placebo (n=56). All patients underwent serum liver testing and measurement of serum bile acids during the 4 weeks following OLT.Patients with T-tube underwent measurement of biliary bile acids during the 4 weeks following OLT.Biliary complications, as well as patient and graft survival rates, were analyzed during the follow-up period (mean of 65.6 months). RESULTS: At post-OLT days 7, 21 and 28, the UDCA-treated patients showed significantly lower levels of alanine aminotransferase, aspartate aminotransferase and gamma glutamyl transpeptidase (all P less than 0.05).In addition, the UDCA-treated patients showed significantly lower incidence of biliary sludge and casts within the first year post-OLT (3.6% vs.14.3%; x2=3.953, P=0.047). However, there were no significant differences for the incidence of other biliary complications at post-OLT years 1, 3 and 5.The graft and patient survival rates were also similar between the two groups. CONCLUSION: UDCA, when administered early after OLT, improves results from serum liver tests and decreases the incidence of biliary sludge and casts within the first postoperative year.


Assuntos
Doenças Biliares/tratamento farmacológico , Doenças Biliares/fisiopatologia , Fígado/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Ácido Ursodesoxicólico/uso terapêutico , Alanina Transaminase , Aspartato Aminotransferases , Bile , Ácidos e Sais Biliares , Humanos , Cirrose Hepática Biliar , Testes de Função Hepática , Transplante de Fígado , gama-Glutamiltransferase
15.
J Cancer ; 15(4): 981-989, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38230217

RESUMO

Flap endonuclease 1 (FEN1) is a structure-specific nuclease that is involved in the occurrence and development of various types of tumors. Previous studies have shown that FEN1 plays an important role in the development of hepatocellular carcinoma, however, the molecular mechanisms remain fully elucidated, especially its effect on the cell cycle of hepatocellular carcinoma has not been investigated. In this study, via bioinformatics prediction and clinical specimen verification, we confirmed that FEN1 was highly expressed in HCC and correlated with poor prognosis. The knockdown or overexpression of FEN1 could inhibit or promote the proliferation and invasion of HCC cells. Importantly, cell cycle and functional experiments showed that FEN1 could promote cell proliferation by inducing cell cycle transition from G2 to M phase. Further studies indicated that FEN1 regulated the G2/M transition by modulating cell division cycle 25C (Cdc25C), cyclin-dependent kinase 1 (CDK1) and Cyclin B1 expressions. To sum up, our research suggested that FEN1 could promote the proliferation, migration and invasion of HCC cells via activating cell cycle progression from G2 to M phase, indicating that FEN1 may be a potential target for the treatment of HCC.

16.
J Gastroenterol ; 59(7): 531-542, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38819499

RESUMO

BACKGROUND: Microbiota may be associated with esophageal squamous cell carcinoma (ESCC) development. However, it is not known the predictive value of microbial biomarkers combining epidemiological factors for the early detection of ESCC and precancerous lesions. METHODS: A total of 449 specimens (esophageal swabs and saliva) were collected from 349 participants with different esophageal statuses in China to explore and validate ESCC-associated microbial biomarkers from genes level to species level by 16S rRNA sequencing, metagenomic sequencing and real-time quantitative polymerase chain reaction. RESULTS: A bacterial biomarker panel including Actinomyces graevenitzii (A.g_1, A.g_2, A.g_3, A.g_4), Fusobacteria nucleatum (F.n_1, F.n_2, F.n_3), Haemophilus haemolyticus (H.h_1), Porphyromonas gingivalis (P.g_1, P.g_2, P.g_3) and Streptococcus australis (S.a_1) was explored by metagenomic sequencing to early detect the participants in Need group (low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and ESCC) vs participants without these lesions as the Noneed group. Significant quantitative differences existed for each microbial target in which the detection efficiency rate was higher in saliva than esophageal swab. In saliva, the area under the curve (AUC) based on the microbial biomarkers (A.g_4 ∩ P.g_3 ∩ H.h_1 ∩ S.a_1 ∩ F.n_2) was 0.722 (95% CI 0.621-0.823) in the exploration cohort. Combining epidemiological factors (age, smoking, drinking, intake of high-temperature food and toothache), the AUC improved to 0.869 (95% CI 0.802-0.937) in the exploration cohort, which was validated with AUC of 0.757 (95% CI 0.663-0.852) in the validation cohort. CONCLUSIONS: It is feasible to combine microbial biomarkers in saliva and epidemiological factors to early detect ESCC and precancerous lesions in China.


Assuntos
Detecção Precoce de Câncer , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Lesões Pré-Cancerosas , Humanos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/microbiologia , China/epidemiologia , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/epidemiologia , Carcinoma de Células Escamosas do Esôfago/microbiologia , Detecção Precoce de Câncer/métodos , Idoso , Saliva/microbiologia , RNA Ribossômico 16S/genética , Microbiota , Biomarcadores Tumorais , Adulto , Metagenômica/métodos , Valor Preditivo dos Testes
17.
RSC Adv ; 14(9): 6085-6095, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38370459

RESUMO

Tyrosinase is a widely distributed copper-containing enzyme found in various organisms, playing a crucial role in the process of melanin production. Inhibiting its activity can reduce skin pigmentation. Hydroquinone is an efficient inhibitor of tyrosinase, but its safety has been a subject of debate. In this research, a scaffold hybridization strategy was employed to synthesize a series of hydroquinone-benzoyl ester analogs (3a-3g). The synthesized compounds were evaluated for their inhibitory activity against mushroom tyrosinase (mTyr). The results revealed that these hydroquinone-benzoyl ester analogs exhibited inhibitory activity against mTyr, with compounds 3a-3e displaying higher activity, with compound 3b demonstrating the highest potency (IC50 = 0.18 ± 0.06 µM). Kinetic studies demonstrated that the inhibition of mTyr by compounds 3a-3e was reversible, although their inhibition mechanisms varied. Compounds 3a and 3c exhibited non-competitive inhibition, while 3b displayed mixed inhibition, and 3d and 3e showed competitive inhibition. UV spectroscopy analysis indicated that none of these compounds chelated with copper ions in the active center of the enzyme. Molecular docking simulations and molecular dynamics studies revealed that compounds 3a-3e could access the active pocket of mTyr and interact with amino acid residues in the active site. These interactions influenced the conformational flexibility of the receptor protein, subsequently affecting substrate-enzyme binding and reducing enzyme catalytic activity, in line with experimental findings. Furthermore, in vitro melanoma cytotoxicity assay of compound 3b demonstrated its higher toxicity to A375 cells, while displaying low toxicity to HaCaT cells, with a dose-dependent effect. These results provide a theoretical foundation and practical basis for the development of novel tyrosinase inhibitors.

18.
Hum Cell ; 36(2): 712-724, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36520346

RESUMO

RNA modification serves as a kind of posttranscriptional modification. Besides N6-methyladenosine (m6A), 5-methylcytosine(m5C) is also an important RNA modification. Long non-coding RNAs (lncRNAs) play an important role in tumor progression. Thus, we performed bioinformatic analysis to establish a m5C-related lncRNA signature(m5ClncSig) for hepatocellular carcinoma (HCC). The RNA sequencing data and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Pearson correlation coefficient analysis was applied to conduct m5C-related genes and m5C-related lncRNAs co-expressing network. Univariate Cox regression was used to screen the m5C-related lncRNAs with prognosis value. LASSO regression was applied to establish m5ClncSig. Functional analysis including KEGG and GO were performed. The relation between m5ClncSig and immunity was assessed by CIBERSORT and ESTIMATE. RP11-498C9.15 was selected for in vitro validation. A m5ClncSig was established containing 8 lncRNAs with significantly prognosis value. According to risk score calculated by m5ClncSig, high-risk group had worse clinical outcomes than low-risk group. The risk score was validated as an independent prognosis factor. Moreover, the abundances of 11 types of immune cells were significantly different between high-risk group and low-risk group while 8 immune-related genes expressed differently between these two groups. RP11-498C9.15 was validated as a risk factor in HCC progression.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Fatores de Risco
19.
J Cancer Res Ther ; 19(1): 78-85, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37006046

RESUMO

Purpose: To compare the survival prognosis of percutaneous transhepatic biliary stenting (PTBS) in the treatment of malignant obstructive jaundice (MOJ) at different horizontal sites. Methods: A total of 120 patients with MOJ who underwent biliary stenting were retrospectively included and analyzed and divided into the high-position group (36 patients), middle-position group (43 patients), and low-position group (41 patients) according to biliary obstruction plane by biliary anatomy. Kaplan-Meier curves were used to test for differences in the overall survival (OS), risk assessment of death and potential risk factors for 1-year survival were analyzed using multifactorial Cox regression. Results: The median survival of the high-, middle-, low-position groups were 16, 8.6, and 5.6 months, with a statistically significant difference (P = 0.017). The 1-year survival rate was 67.6%, 41.9%, and 41.5% in the high-, middle-, low-position groups (P < 0.05), and the 1-year risk of death was 2.35 and 2.93 times higher in the medium- and low-position groups, respectively. The incidences of the main complications were 25%, 48.8%, and 65.9% in the high-, middle-, and low-position groups, respectively, (P = 0.002). While the differences in median stent patency were not statistically significant (P > 0.05) in the groups, alanine transaminase, aspartate transaminase, and total bilirubin levels decreased gradually in each group at 1 month and 3 months after interventional therapy (P < 0.001), while there was no significant difference in the decrease between the groups. Conclusions: Different levels of biliary obstruction in patients with MOJ affect survival, especially at 1 year, where high obstruction treated with PTBS has a low incidence of complications and a low risk of death.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar , Colestase , Icterícia Obstrutiva , Humanos , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/cirurgia , Prognóstico , Estudos Retrospectivos , Colestase/cirurgia , Colestase/complicações , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Stents/efeitos adversos , Resultado do Tratamento
20.
Biotechnol Genet Eng Rev ; : 1-23, 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37078456

RESUMO

Lectin-likeoxidized low-density lipoprotein receptor (LOX-1) has been identified to beinvolved in the development of atherosclerosis. There is an increasing experimental evidence which indicated that LOX-1 was implicated in cancer tumorigenesis. However, the expression and the prognostic value of LOX-1 in multiple cancers still require the further analysis. Pubmed, Embase and the Cochrane Library were used for the literature review collection with the confined date up to 31 December 2021. Ten studies including 1982 patients were performed in meta-analysis according to the inclusion and exclusion criteria. Oncomine, Gene Expression Profiling Interactive Analysis(GEPIA), Kaplan-Meier plotter and Tumor Immune Estimation Resource (TIMER) were utilized to analyze the differential expression and the prognostic value of LOX-1 in different cancers. Records from Gene Expression Omnibus (GEO) database were applied for the verification test. The meta-pooled result demonstrated that elevated LOX-1 predicted a poor survival in some cancers (HR = 1.95, 95%CI 1.46-2.44, P < 0.001). In this sense, further analysis using databases found the expression of LOX-1 was higher in breast cancer, colorectal cancer, gastric cancer and pancreatic cancer while the lower expression in lung squamous cell carcinoma was observed. Moreover, the expression of LOX-1 was related to the tumor stages of colorectal cancer, gastric cancer and pancreatic cancer. The survival analysis revealed that LOX-1 was a potential prognostic factor for the patients with colorectal cancer, gastric cancer, pancreatic cancer and lung squamous cell carcinoma. Consequently, this study may provide a novel insight for the expression and the prognostic value of LOX-1 in specific cancers.

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