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Water freezing is a crucial physical phenomenon. The process of ice formation, and the estimation of the ice nucleation rate also have important applications. However, until now, the experimental phenomenon of rapid freezing of water in nanoseconds has not been fully explained theoretically, and the physics underlying the experimental phenomenon has still not been revealed. In this work, combining classical nucleation theory with Mie theory, a kinetic model is developed that reproduces for the first time the experimental phenomenon of decreasing transmissivity. The process of ice formation (nucleation, growth and engulfment) has been revealed. In the process of theoretical derivation, the Zel'dovich-Frenkel (ZF) equation is developed, indicating a limit to the phase transition driving force |Δµ|/(kBT) ≤ 1. By analyzing the experimental and simulation results, it is suggested that the change in the transparency of the sample may be caused by the ice/vacuum interface scattering. In addition, during the rapid phase transition, it was found that the phase transition continues to occur even after phase fraction normalization. Finally, the approximate formula between the nucleation rate and sample transparency is given. This formula can predict the change of sample transparency during phase transition and provides a way to measure the nucleation rate. The results presented here give an insight into the phase transition kinetics, and the methodology may also work for the phase transitions of other materials.
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Nuclease-resistant assay probes are of significant importance for biochemical analysis and disease diagnosis. In this contribution, a reconfigurable lipidic moiety-attached DNA nanoparticle (LDN) is constructed from a cholesterol-conjugated multifunctional hairpin-type DNA probe (Chol-DP) by hydrophobicity-mediated self-assembly. The LDN holds high serum stability and displays a low false-positive signal even in a complex biological milieu. The hydrophobic cholesterol moiety enables the hydrophobicity-mediated assembly, while hydrophilic DNA sequence serves as a recognition element and a polymerization template. The initiator-activated strand displacement amplification (SDA) reaction can convert the hairpin-shaped probe into rigid double-stranded DNA (dsDNA), causing the conformational rearrangement-based LDN swelling that can be used to reliably and fluorescently signal the cancer-related p53 gene. The size increase and structural reconfiguration are confirmed by dynamic light scattering (DLS) analysis and confocal microscopy imaging, respectively. Target p53 is specifically detected down to 10 pM. The whole assay process involved only several simple mixing steps. Recovery test and blind test further confirm the feasibility of the use of the LDN for the detection of target DNA in a complex biological milieu, indicating a promising nanotool for biomedical applications.
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Técnicas Biossensoriais , Nanopartículas , Neoplasias , Sequência de Bases , Técnicas Biossensoriais/métodos , DNA/genética , Sondas de DNA/química , Sondas de DNA/genética , Humanos , Neoplasias/genética , Técnicas de Amplificação de Ácido Nucleico/métodosRESUMO
BACKGROUND: Soil quality assessment is a critical strategy for determining optimum fertilization in intensive pomelo production. In this study, we evaluated the soil quality status and mapped the spatial distribution of 347 soil samples collected from pomelo orchards in Pinghe County, southern China. We analyzed nine chemical parameters and an altitude indicator. RESULTS: The mean soil quality index (SQI) was 0.355 in the total data set (TDS) and 0.292 in the minimum data set (MDS). Available Ca (Avail-Ca), pH value, organic matter and altitude were selected as indicators of soil quality in the MDS. The SQI in mature orchards (>10 years) was higher than that in young orchards (<10 years), while no differences between soil types and altitude gradients were identified. We detected a significant positive correlation between the SQI based on TDS (SQITDS ) and the SQI based on MDS (SQIMDS ), and the spatial distribution of soil properties and SQITDS showed a uniform pattern, except for Avail-N, Avail-B and SQIMDS . Overall, unfavorable soil quality indicators, including rich in Avail-P, deficient in Avail-Ca, -Mg and -B, soil acidification and high altitude, were considered to be limiting factors for pomelo production. CONCLUSION: The soil chemical quality in pomelo orchards is generally low, indicating that integrated management by controlling acidification, reducing planting altitude, regulating fertilization and monitoring soil properties is required for sustainable pomelo production. © 2021 Society of Chemical Industry.
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Frutas , Solo , China , Solo/químicaRESUMO
OBJECTIVE: To study the molecular mechanism of extracts from Euodia rutaecarpa on hepatotoxicity in mice. METHOD: Totally 30 KM mice were divided into 3 groups and orally administrated extracts from E. rutaecarpa for consecutively 15 days. The expressions of Erkl/2, CDK8, CK1e, Stat3 and Src were detected by Western blotting method. RESULT: The extracts from E. rutaecarpa could up-regulated Erkl/2, CDK8 and CK1e expressions (P <0.01) and down-regulate Stat3 and Src (P <0.01). CONCLUSION: The molecular mechanism of E. rutaecarpa on hepatotoxicity may be correlated with Erkl/2, CDK8, CKle, Stat3 and Src signal molecules.
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Medicamentos de Ervas Chinesas/toxicidade , Evodia/química , Frutas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Regulação para Baixo , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Plantas Medicinais , Organismos Livres de Patógenos Específicos , Triglicerídeos/sangue , Regulação para CimaRESUMO
BACKGROUND: A meta-analysis was performed in this study to evaluate the association between serum uric acid and the risk of colorectal cancer (CRC). METHODS: Relevant observational studies observing the relationship between uric acid and the incidence of CRC were obtained by the search of electronic databases, including Medline, Embase, Cochrane Library and Web of Science . A randomized-effects model was selected to pool the data by incorporating the influence of potential heterogeneity. RESULTS: Eight observational studies involving 1,226,379 adults were included. During a mean follow-up duration of 12.8 years, CRC was developed in 12349 (1.0%) participants. Pooled results showed that compared to those with the lowest category of serum uric acid at baseline, participants with the highest category of serum uric acid had an increased incidence of CRC during follow-up [risk ratio (RR), 1.28; 95% confidence interval (CI), 1.17-1.42; P < 0.001; I2 = 0%]. Sensitivity analysis limited to prospective cohort studies retrieved similar results (RR, 1.32; 95% CI, 1.19-1.47; P < 0.001; I2 = 0%). Subgroup analyses showed consistent results in men and women, in estimates of the incidence of colon cancer and rectal cancer and in studies with different follow-up durations and quality scores ( P for subgroup differences all > 0.05). CONCLUSION: Although the cutoff for defining a high uric acid varied among the included studies, results of the meta-analysis suggest that a high serum uric acid may be associated with an increased risk of CRC in an adult population.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Masculino , Adulto , Humanos , Feminino , Ácido Úrico , Estudos Prospectivos , Incidência , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologiaRESUMO
Helicobacter pylori (H. pylori) is a major factor in peptic ulcer disease and gastric cancer, and its infection rate is rising globally. The efficacy of traditional antibiotic treatment is less effective, mainly due to bacterial biofilms and the formation of antibiotic resistance. In addition, H. pylori colonizes the gastrointestinal epithelium covered by mucus layers, the drug must penetrate the double barrier of mucus layer and biofilm to reach the infection site and kill H. pylori. The ethanol injection method was used to synthesize nanoliposomes (EPI/R-AgNPs@RHL/PC) with a mixed lipid layer containing rhamnolipids (RHL) and phosphatidylcholine (PC) as a carrier, loaded with the urease inhibitor epiberberine (EPI) and the antimicrobial agent rubropunctatin silver nanoparticles (R-AgNPs). EPI/R-AgNPs@RHL/PC had the appropriate size, negative charge, and acid sensitivity to penetrate mucin-rich mucus layers and achieve acid-responsive drug release. In vitro experiments demonstrated that EPI/R-AgNPs@RHL/PC exhibited good antibacterial activity, effectively inhibited urease activity, removed the mature H. pylori biofilm, and inhibited biofilm regeneration. In vivo antibacterial tests showed that EPI/R-AgNPs@RHL/PC exhibited excellent activity in eradicating H. pylori and protecting the mucosa compared to the traditional clinical triple therapy, providing a new idea for the treatment of H. pylori infection.
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Infecções por Helicobacter , Helicobacter pylori , Nanopartículas Metálicas , Humanos , Prata/farmacologia , Urease/farmacologia , Urease/uso terapêutico , Antibacterianos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologiaRESUMO
Clarifying current situation of farmers' fertilization and yield in citrus producing areas and the effects of different fertilization measures can provide a scientific basis for improving the yield and quality of citrus in China. We retrieved 92 literatures on citrus fertilization from the CNKI and Web of Science to examine the impacts of nitrogen (N), phosphorus (P or P2O5), and potassium (K or K2O) fertilizer dosage and partial productivity under farmers' conventional fertilization and experts' optimized fertilization, as well as the effects of optimized fertilization measures on citrus yield and quality by using meta-analysis approach. The average conventional application rates of N, P2O5, and K2O were 507.3, 262.2, and 369.3 kg·hm-2 in citrus production in China. Compared with conventional fertilization, optimized fertilization resulted in a reduction of N and P2O5 by 14.7% and 8.3%, an increase in K2O application by 6.6%, which promoted partial productivity of N, P2O5, and K2O fertilizers by 7.8%, 18.4%, and 14.7%, correspondingly. The optimized fertilization resulted in 11.9% and 2.8% increase in fruit yield and single fruit weight, while improved vitamin C content (Vc, 3.1%), total soluble solids (TSS, 5.9%) and total sugar content (TSC, 8.6%). Additionally, it also led to a reduction in titratable acid (TA, -3.4%) and total acid content (TAC, -3.6%), and consequently elevated the TSS/TA (14.0%) and TSC/TAC (9.5%). Among different optimized fertilization methods, the effect of optimized NPK + medium and/or micro element fertilizer on citrus yield and fruit quality was the best, especially NPK decrement ≤25% between optimized NPK measures. The effect of conventional NPK + organic fertilizer was higher than conventional NPK + medium and/or micro element fertilizer. However, different citrus varieties, including mandarins, pomelos, and oranges, showed different responses to optimized fertilization. Optimized fertilization management could synergistically improve citrus yield, fertilizer use efficiency, and fruit quality. Therefore, the strategy of integrated nutrient management1 with reducing NPK fertilizer, balancing medium and/or micro nutrient fertilizer and improving soil fertility by organic fertilizer should be adopted according to local conditions in citrus producing areas of China.
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Citrus , Fertilizantes , Frutas , Nitrogênio , Fósforo , Fertilizantes/análise , Citrus/crescimento & desenvolvimento , China , Fósforo/análise , Nitrogênio/análise , Frutas/crescimento & desenvolvimento , Frutas/química , Nutrientes/análise , Agricultura/métodos , Potássio/análise , Biomassa , Produção Agrícola/métodosRESUMO
Introduction: The bibliometric analysis aims to identify research trends in estrogen receptor (ERs) and progesterone receptor (PRs) in prostate cancer (PCa), and also discuss the hotspots and directions of this field. Methods: 835 publications were sourced from the Web of Science database (WOS) from 2003 to 2022. Citespace, VOSviewer, and Bibliometrix were used for the bibliometric analysis. Results: The number of published publications increased in early years, but declined in the last 5 years. The United States was the leading country in citations, publications, and top institutions. Prostate and Karolinska Institutet were the most publications of journal and institution, respectively. Jan-Ake Gustafsson was the most influential author based on the number of citations/publications. The most cited paper was "Estrogen receptors and human disease" by Deroo BJ, published in the Journal of Clinical Investigation. The most frequently used keywords were PCa (n = 499), gene-expression (n = 291), androgen receptor (AR) (n = 263), and ER (n = 341), while ERb (n = 219) and ERa (n = 215) further emphasized the importance of ER. Conclusions: This study provides useful guidance that ERa antagonists, ERb agonists, and the combination of estrogen with androgen deprivation therapy (ADT) will potentially serve as a new treatment strategy for PCa. Another interesting topic is relationships between PCa and the function and mechanism of action of PRs subtypes. The outcome will assist scholars in gaining a comprehensive understanding of the current status and trends in the field, and provide inspiration for future research.
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AIMS: Machine learning-based identification of key variables and prediction of postoperative delirium in patients with extensive burns. METHODS: Five hundred and eighteen patients with extensive burns who underwent surgery were included and randomly divided into a training set, a validation set, and a testing set. Multifactorial logistic regression analysis was used to screen for significant variables. Nine prediction models were constructed in the training and validation sets (80% of dataset). The testing set (20% of dataset) was used to further evaluate the model. The area under the receiver operating curve (AUROC) was used to compare model performance. SHapley Additive exPlanations (SHAP) was used to interpret the best one and to externally validate it in another large tertiary hospital. RESULTS: Seven variables were used in the development of nine prediction models: physical restraint, diabetes, sex, preoperative hemoglobin, acute physiological and chronic health assessment, time in the Burn Intensive Care Unit and total body surface area. Random Forest (RF) outperformed the other eight models in terms of predictive performance (ROC:84.00%) When external validation was performed, RF performed well (accuracy: 77.12%, sensitivity: 67.74% and specificity: 80.46%). CONCLUSION: The first machine learning-based delirium prediction model for patients with extensive burns was successfully developed and validated. High-risk patients for delirium can be effectively identified and targeted interventions can be made to reduce the incidence of delirium.
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Delírio , Unidades de Terapia Intensiva , Humanos , Aprendizado de Máquina , Algoritmo Florestas Aleatórias , Delírio/diagnóstico , Delírio/etiologiaRESUMO
OBJECTIVES: Burn patients are reportedly prone to complications, such as skeletal muscle wasting, anemia, and slow wound healing, during treatment, due to disease and metabolic depletion, which affect prognosis. Nutritional support is essential in treating burns and can significantly improve patient survival and reduce complications such as infection. This study aimed to perform a bibliometric analysis of the existing literature on nutritional support for burns and to explore possible future research trends. METHODS: The literature related to nutritional support for burns from 1983 to 2022 was searched on Web of Science. The included literature was used for bibliometric analysis using VOSviewer and CiteSpace software. RESULTS: There were 260 publications on nutritional support for burns. The United States contributes significantly to research in this area. The United States has the highest number of publications (n = 119) and citations (n = 4424). Nutrition support was the keyword with strongest burst intensity. A diet of ≥ 60% carbohydrates and 12% to 15% fat is suitable for burn patients, but the optimal ratios have not been fully determined. CONCLUSIONS: An optimal nutritional support program is essential for treating burn patients. Individualized nutritional support programs are the trend in this field. At present, more rigorous multicenter prospective studies with large samples are needed to explore the optimal ratios for specific dietary programs, especially macronutrients, to achieve satisfactory nutritional support and improve patient prognosis.
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Queimaduras , Apoio Nutricional , Humanos , Estudos Prospectivos , Bibliometria , Queimaduras/complicações , Queimaduras/terapia , Atrofia MuscularRESUMO
Introduction: Citrus fruit is considered a superfood due to its multiple nutritional functions and health benefits. Quantitative analysis of the numerous quality characteristics of citrus fruit is required to promote its sustainable production and industrial utilization. However, little information is available on the comprehensive quality assessment of various fruit quality indicators in different citrus cultivars. Methods: A total of nine different fresh citrus fruits containing seeds were collected as the experimental materials. The objectives of this study were: (i) to determine the morphological and juice properties of citrus fruits, (ii) to measure the mineral elements in the peel, pulp, and seeds, and (iii) to evaluate the fruit quality index (FQI) using the integrated quality index (IQI) and the Nemoro quality index (NQI) methods. Results: There were significant differences in fruit quality characteristics, including morphological, mineral, and juice quality, among the investigated citrus cultivars. The proportion of pulp biomass was the highest, followed by that of peel and seeds. N and Cu had the highest and lowest concentrations, respectively, among the measured elements across all citrus fruits, and the amounts of N, P, Mg, Cu, and Zn in seeds, K and Al in pulp, and Ca, Fe, and Mn in peel were the highest, dramatically affecting the accumulation of minerals in the whole fruit and their distribution in various fruit parts. Additionally, Ningmeng fruits had the highest vitamin C and titratable acidity (TA) but the lowest total soluble solids (TSS) and total phenolic (TP) contents, resulting in the lowest TSS/TA and pH values. In contrast, Jinju fruits had the highest TSS and TP contents. Based on the mineral element and juice quality parameters, principal component analysis showed that the citrus fruits were well separated into four groups, and the dendrogram also showed four clusters with different distances. The FQI range based on the IQI method (FQIIQI) and NQI method (FQINQI) was 0.382-0.590 and 0.106-0.245, respectively, and a positive relationship between FQIIQI and FQINQI was observed. Conclusion: Our results highlight the great differences in mineral and juice characteristics among fruit parts, which mediated fruit quality. The strategy of fruit quality assessment using the FQI can be expanded for targeted utilization in the citrus industry.
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In order to solve the problems of rubropunctatin insoluble in water and its low bioavailability, and explore the synthesis method of green silver nanoparticles, rubropunctatin was used as reducing agent and blocking agent, rubropunctatin-functionalized silver nanoparticles (R-AgNPs) were successfully synthesized. The distinctive absorption peak at 410 nm confirmed the formation of R-AgNPs. Zeta potential measurement showed excellent stability of R-AgNPs with negative values of -29.81 ± 0.37 mV. The results of TEM and XRD showed that the prepared R-AgNPs were round, well dispersed and crystallized with average particle size of 13.54 ± 0.42 nm. FT-IR and XPS studies show that functional groups are involved in R-AgNPs synthesis. The antibacterial activity of R-AgNPs was compared with commercial silver nanoparticles (AgNPs) by microdilution method. The results showed that R-AgNPs (MIC 7.81 µg/mL) has stronger antibacterial activity than commercial AgNPs. The bacteria morphology was observed by the live and dead (SYTO 9/PI) staining assay and SEM showed that the antibacterial effect of R-AgNPs was caused by the destruction of the bacterial cell membrane. Cytotoxicity of rubropunctatin-functionalized silver nanoparticles and commercial silver nanoparticles on mouse fibroblast 3T3 cells was assessed by CCK-8 assay. The results showed that the toxicity of rubropunctatin-functionalized silver nanoparticles to 3T3 cells was lower than that of commercial silver nanoparticles. In summary, synthesis of silver nanoparticles using rubropunctatin is a green synthesis method, and R-AgNPs is a potential antibacterial agent.
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Background: Sepsis is one of the most common complications in burn patients and causes high morbidity, especially in those with severe burns. Nevertheless, there are no formal criteria for diagnosing and treating burn sepsis. Therefore, this bibliometric analysis is applied to reveal research trends in this field and predicts its possible hot spots. Methods: We screened relevant literature on burn sepsis that met the inclusion criteria of the Web of Sciences (WOS) database and analyzed publication trends and research hot spots in related fields using VOSviewer software. Results: From 1981 to 2022, we screened 2,486 documents that met the requirements and analyzed them bibliometrically. The American scholar Herndon DN had a much higher h-index [47] than other authors. Most published, cited, and h-indexed publications are from the USA (Np: 1193, Nc: 42154, H: 98). The second most publishing country is China, but the second most cited and h-indexed country is Germany. Burns also outperforms other journals in this field (Np: 376, Nc: 8019, H: 46). "Biomarkers" is a newly emerging keyword (cluster "clinical research," APY was 2018.16), and clinically relevant research in burn sepsis maybe a future research trend. Conclusions: Sepsis in burn patients has unique pathophysiological characteristics and the general diagnostic criteria for sepsis lack specificity. Consequently, we must establish a database and construct an intelligent predictive model to help achieve a more individualized and precise early diagnosis and treatment of burn sepsis. This may also be an important development direction for future research in this field.
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Delirium, an acute brain dysfunction, is a common and serious complication in burn patients. The occurrence of delirium increases the difficulty of patient treatment, is associated with various adverse outcomes, and increases the burden on the patient's family. Many scholars have studied the factors that cause delirium, but the causes, pathogenesis, and treatment of delirium in burn patients have not been fully revealed. There is no effective pharmacological treatment for delirium, but active preventive measures can effectively reduce the incidence of delirium in burn patients. Therefore, it is necessary to study the relevant factors affecting the occurrence of delirium in burn patients. This study was conducted on December 20, 2021 by searching the PubMed database for a narrative review of published studies. The search strategy included keywords related to "burns," "delirium," and "risk factors." We reviewed the characteristics of delirium occurrence in burn patients and various delirium assessment tools, and summarized the risk factors for the development of delirium in burn patients in terms of personal, clinical, and environmental factors, and we found that although many risk factors act on the development of delirium in burn patients, some of them, such as clinical and environmental factors, are modifiable, suggesting that we can estimate the exposure of burn patients to risk factors by assessing their likelihood of delirium occurring and to make targeted interventions that provide a theoretical basis for the prevention and treatment of burn delirium.
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α(1)-Adrenergic receptor (α(1)-AR) is a crucial mediator of cardiac hypertrophy. Although numerous intracellular pathways have been implicated in α(1)-AR-induced hypertrophy, its precise mechanism remains elusive. We aimed to determine whether α(1)-AR induces cardiac hypertrophy through a novel signaling pathway-α(1)-AR/epidermal growth factor receptor (EGFR)/signal transducer and activator of transcription 3 (STAT3). The activation of STAT3 by α(1)-AR was first demonstrated by tyrosine phosphorylation, nuclear translocation, DNA binding, and transcriptional activity in neonatal Sprague-Dawley rat cardiomyocytes. Activated STAT3 showed an essential role in α(1)-AR-induced cardiomyocyte hypertrophic growth, as assessed by treatment with STAT3 inhibitory peptide and lentivirus-STAT3 small interfering RNA. The results were further confirmed by in vivo experiments involving intraperitoneal injection of the STAT3 inhibitor WP1066 significantly inhibiting phenylephrine-infusion-induced heart hypertrophy in male C57BL/6 mice. Furthermore, the α(1)-AR-activated STAT3 was associated with transactivation of EGFR because inhibition of EGFR with the selective inhibitor AG1478 prevented α(1)-AR-induced STAT3 tyrosine phosphorylation and its transcriptional activity, as well as cardiac hypertrophy. In summary, these results suggest that α(1)-AR induces the activation of STAT3, mainly through transactivation of EGFR, which plays an important role in α(1)-AR-induced cardiac hypertrophy.
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Cardiomegalia/metabolismo , Receptores ErbB/metabolismo , Miocárdio/metabolismo , Receptor Cross-Talk , Receptores Adrenérgicos alfa 1/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas ADAM/metabolismo , Transporte Ativo do Núcleo Celular , Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Animais , Animais Recém-Nascidos , Cardiomegalia/induzido quimicamente , Cardiomegalia/genética , Cardiomegalia/patologia , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Receptores ErbB/antagonistas & inibidores , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Fenilefrina , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa 1/efeitos dos fármacos , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Transdução de Sinais , Fatores de Tempo , TirosinaRESUMO
Increased intraocular pressure is the main cause of glaucoma development. However, the systemic information of genes related to ocular hypertension has not yet been clarified. In the present study, oligomicroarray determined the profile of gene expression in the retina after ocular hypertension. A rat ocular hypertension model was constructed through photocoagulation by diode lasers. On postoperative days 7, 35, 60, 90, 180 and 360, the intraocular pressure and the gene expression profile were determined using an ophthalmotonometer and an Oligochip containing 35,000 oligonucleotides, respectively. Oligochip reliability was verified by real-time PCR, and the Oligochip data were analyzed through functional distribution analysis. In our study, we found that the intraocular pressure was significantly increased in a time-dependent manner but returned to the normal level on postoperative day 360. We also found that 1,692 genes were differentially expressed, including 719 upregulated and 973 downregulated genes. The χ² value of gene clusters related to transport function is significantly higher than that of other gene clusters as determined through function distribution analysis, suggesting that this group of genes plays an important role in the repair process of the optical nerve. In conclusion, the gene expression pattern at different time points of ocular hypertension was determined, which may contribute to clarify the molecular mechanism of glaucoma and to establish better therapeutic strategies to treat glaucoma.
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Modelos Animais de Doenças , Perfilação da Expressão Gênica , Hipertensão Ocular/genética , Análise de Sequência com Séries de Oligonucleotídeos , Retina/metabolismo , Animais , Pressão Intraocular , Microscopia Confocal , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tonometria OcularRESUMO
BACKGROUND INFORMATION: APN (adiponectin), an adipocyte-derived cytokine highly presented in serum, which exerts antidiabetic, anti-atherosclerotic and cardioprotective actions, also enhances CFB (cardiac fibroblast) proliferation and protects against cardiac fibrosis. STAT3 (signal transducer and activator of transcription 3), a major mediator in the gp130/JAK2 (Janus kinase 2)/STATs signalling pathway, plays a critical role in cardioprotective events. Almost two-thirds of total myocardial cells are CFBs; however, whether APN regulates STAT3 signalling pathway has not been clarified yet in CFBs. In the present study, we investigated the effect of recombinant globular APN on the STAT3 activity in adult mouse CFBs and explored the possible signalling transduction mechanism. RESULTS: In cultured CFBs, APN (10 microg/ml) can significantly induce delayed STAT3 Tyr(705) phosphorylation time-dependently, up to 60 min, and mediate STAT3 translocation from cytoplasm to nucleus. Transfection of siRNA (small interfering RNA) specific for AdipoR1 (APN receptor 1), but not AdipoR2, obviously inhibited APN-induced STAT3 Tyr(705) phosphorylation, indicating that AdipoR1, not AdipoR2, is required for STAT3 phosphorylation. Both inhibition of gp130 by anti-gp130 neutralizing antibody and JAK2 by AG490 (a specific inhibitor for JAK2) can inhibit APN-induced STAT3 phosphorylation and STAT3 transcription activity detected using 2 x pAPRE-Luc (APRE reporter) assay. Furthermore, we found that the IL (interleukin)-6 level in culture medium was significantly increased after stimulation with APN and the IL-6 mRNA level was also markedly increased in CFBs, which can be reversed by siRNA for AdipoR1, but not for AdipoR2, and that anti-IL-6 neutralizing antibody can significantly inhibit APN-induced STAT3 Tyr(705) phosphorylation. CONCLUSIONS: APN induces IL-6 production mediated by AdipoR1, not AdipoR2, in adult mouse CFBs, which leads to the stimulation of the gp130/JAK signalling pathway, and as a result causes STAT3 activation.
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Adiponectina/metabolismo , Interleucina-6/imunologia , Miócitos Cardíacos/metabolismo , Receptores de Adiponectina/metabolismo , Fator de Transcrição STAT3/metabolismo , Adiponectina/imunologia , Animais , Células Cultivadas , Receptor gp130 de Citocina/metabolismo , Janus Quinase 2/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Miócitos Cardíacos/imunologia , Fosforilação , Transdução de SinaisRESUMO
OBJECTIVE: To investigate whether adiponectin plays a role in the protection of myocardium in the rat myocardial ischemia preconditioning (IPC) model. METHOD: Infarct size was measured by Masson's Trichrome staining, the expression of protein and mRNA of adiponectin at 0, 6, 12 and 24 h after IPC was examined by immunohistochemistry and quantitative real time RT-PCR, plasma levels of adiponectin at above mentioned four time points after IPC were detected by ELISA in IPC and MI rats. RESULT: Infarct size was smaller in IPC than in MI rats (20% ± 2% vs. 31% ± 3%, P < 0.05). The expression of adiponectin mRNA at 6 h and 12 h after IPC was 2.2 and 2.1 times higher than in Sham rats at respective time points (P < 0.05). Immunohistochemistry staining evidenced increased adiponectin expression in the ischemic area and weak expression of adiponectin in non-ischemic area (P < 0.05). Compared to the sham group, the plasma level of adiponectin increased significantly at 0, 6 and 12 h after IPC (0 h: 7.40 ± 0.47 vs. 10.90 ± 1.74; 6 h: 8.18 ± 1.41 vs. 10.98 ± 1.74; 12 h: 6.97 ± 1.02 vs. 9.31 ± 0.96, P < 0.05). CONCLUSION: IPC reduced infarction size, upregulated the myocardial expression of adiponectin at mRNA and protein levels, and increased plasma adiponectin concentration, suggesting that the adiponectin may play a critical role in the protective effect of IPC.
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Precondicionamento Isquêmico Miocárdico , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Adiponectina/metabolismo , Animais , Masculino , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/prevenção & controle , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: to observe the effect of ischemia preconditioning (IPC) on the expression of pro-angiogenic VEGF, PDGF and anti-angiogenic ADAMTS-1, and arteriogenesis. METHODS: rat heart IPC model was made by 4 circles of occluding the LAD for 6 min followed by 6 min of reperfusion. The expression of VEGF, PDGF-B and ADAMTS-1 in the ischemic area was examined with immunohistochemistry at 6, 12 and 24 h after IPC. IPC plus myocardial infarction model was induced by LAD ligation 24 h after IPC, 14 days later, the anti-SM-α-actin antibody was used to detect the mature neovascularization in the border of the infracted area. RESULTS: VEGF, PDGF-B and ADAMTS-1 were significantly upregulated in the ischemic area in IPC group compared with the control group (P < 0.05). Density of mature arteries was also significantly increased in IPC plus MI group than that in MI group (P < 0.05). CONCLUSION: IPC promoted the formation of mature new arteries which may be modulated by upregulating VEGF, PDGF-B, and ADAMTS-1 expressions.
Assuntos
Artérias/metabolismo , Precondicionamento Isquêmico , Neovascularização Fisiológica , Proteínas Proto-Oncogênicas c-sis/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas ADAM/metabolismo , Proteína ADAMTS1 , Animais , Artérias/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
To investigate the clinicopathological characteristics and relevant prognostic factors of gastro-entero-pancreatic neuroendocrine neoplasm (GEP-NEN), to improve our understanding of GEP-NEN.This was a retrospective analysis of 155 patients (average age 53.7â±â13.6 years) pathologically diagnosed with GEP-NEN. We analyzed the clinicopathological characteristics, treatment, and prognostic factors of GEP-NEN.The most common primary site was the pancreas (41.9%), followed by the rectum, stomach and duodenum. Most cases were nonfunctional GEP-NENs (149/155) with nonspecific symptoms. TNM stage and histological grade were determined by the latest criteria. Surgical resection was the mainstay of treatment in 150 patients, and 22 patients received chemotherapy under different circumstances. A total of 130 patients were followed up for a median of 44 months, and 1-year and 3-year survival rates were 82.3% and 72.3%, respectively. According to univariate and multivariate analysis, incidental diagnosis, maximum tumor diameter, tumor stage, lymph node and distant metastasis, TNM stage, and histological grade were significantly correlated with overall survival, but histological grade was the only factor confirmed as an independent prognostic factor for long-term survival of GEP-NEN.GEP-NEN, with an increasing trend in incidence, occurred most frequently in the pancreas. Nonfunctional tumors with nonspecific symptoms comprised the majority of cases. The main treatment was surgical resection. Histological grade was confirmed as the only independent prognostic factor.