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INTRODUCTION: We analyzed the effect of dexmedetomidine (DEX) as a local anesthetic adjuvant on postoperative delirium (POD) in elderly patients undergoing elective hip surgery. METHODS: In this study, 120 patients undergoing hip surgery were enrolled and randomly assigned to two groups: fascia iliaca compartment block with DEX + ropivacaine (the Y group, n = 60) and fascia iliaca compartment block with ropivacaine (the R group, n = 60). The primary outcomes: presence of delirium during the postanesthesia care unit (PACU) period and on the first day (D1), the second day (D2), and the third day (D3) after surgery. The secondary outcomes: preoperative and postoperative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), occurrence of insomnia on the preoperative day, day of operation, D1 and D2; HR values of patients in both groups before iliac fascia block (T1), 30 min after iliac fascia block (T2), at surgical incision (T3), 20 min after incision (T4), when they were transferred out of the operating room (T5) and after leaving the recovery room (T6) at each time point; VAS for T1, PACU, D1, D2; the number of patients requiring remedial analgesics within 24 h after blockade and related complications between the two groups. RESULTS: A total of 97 patients were included in the final analysis, with 11 and 12 patients withdrawing from the R and Y groups, respectively. The overall incidence of POD and its incidence in the PACU and ward were all lesser in the Y group than in the R group (p < 0.05). Additionally, fewer cases required remedial analgesia during the PACU period, and more vasoactive drugs were used for maintaining circulatory system stability in the Y group as compared to the R group (p < 0.05). At the same time, the incidence of intraoperative and postoperative bradycardia in the Y group was higher than that in the R group, accompanied by lower postoperative CRP and ESR (all p < 0.05). CONCLUSION: Ultrasound-guided high fascia iliaca compartment block with a combination of ropivacaine and DEX can reduce the incidence of POD, the use of intraoperative opioids and postoperative remedial analgesics, and postoperative inflammation in elderly patients who have undergone hip surgery, indicating that this method could be beneficial in the prevention and treatment of POD.
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Anestésicos Locales , Dexmedetomidina , Procedimientos Quirúrgicos Electivos , Bloqueo Nervioso , Ropivacaína , Humanos , Dexmedetomidina/administración & dosificación , Masculino , Anciano , Femenino , Anestésicos Locales/administración & dosificación , Bloqueo Nervioso/métodos , Ropivacaína/administración & dosificación , Procedimientos Quirúrgicos Electivos/efectos adversos , Procedimientos Quirúrgicos Electivos/métodos , Fascia , Anciano de 80 o más Años , Delirio del Despertar/prevención & control , Delirio del Despertar/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Cadera/cirugía , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodosRESUMEN
DNA G-quadruplex(G4) is a guanine-rich single-stranded DNA sequence that spontaneously folds into a spherical four-stranded DNA secondary structure in oncogene promoter sequences and telomeres. G4s are highly associated with the occurrence and development of cancer and have emerged as promising anticancer targets. Natural products have long been important sources of anticancer drug development. In recent years, significant progress has been made in the discovery of natural drugs targeting DNA G4s, with many DNA G4s have been confirmed as promising targets of natural products, including MYC-G4, KRAS-G4, PDGFR-ß-G4, BCL-2-G4, VEGF-G4, and telomeric G4. This review summarizes the research progress in discovering natural small molecules that target DNA G4s and their binding mechanisms. It also discusses the opportunities of and challenges in developing drugs targeting DNA G4s. This review will serve as a valuable reference for the research on natural products, particularly in the development of novel antitumor medications.
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Productos Biológicos , G-Cuádruplex , G-Cuádruplex/efectos de los fármacos , Productos Biológicos/química , Productos Biológicos/farmacología , Humanos , Animales , ADN/química , ADN/genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Antineoplásicos/química , Antineoplásicos/farmacologíaRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cancer worldwide. miRNA has been linked to cancer processes. We want to figure out what the underlying mechanism and functions of miR-3682-3p are in HCC. METHODS: Thirty pairs of tumor tissues and adjacent tissues were obtained from HCC patients. mRNA and protein expressions were detected by quantitative real-time PCR and Western blot, respectively. The migration and invasion were measured using transwell or wound-healing assays. Dual luciferase and ChIP assays were utilized to detect gene interactions. RESULTS: miR-3682-3p was highly expressed in HCC tissues and cell lines. Silencing of miR-3682-3p inhibited cell migration and invasion, increased E-cadherin expression, and decreased N-cadherin, vimentin, and snail expressions, as well as the SOX2, OCT4, and Bmi1 expression, thereby restraining EMT and stemness of HCC in vitro. miR-3682-3p was positively activated by c-Myc and could directly target PTEN to activate PI3K/AKT/ß-catenin pathway. In addition, inhibition of PTEN weakened the anti-migration and anti-stemness effects of miR-3682-3p downregulation in HCC cells. CONCLUSION: miR-3682-3p promoted HCC migration and stemness through PTEN/PI3K/AKT/ß-catenin signaling, implying that miR-3682-3p might be a promising target for HCC clinical treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/patología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias Hepáticas/patología , beta Catenina/genética , beta Catenina/metabolismo , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismoRESUMEN
OBJECTIVE: To evaluate the effect of the individualized positive end-expiratory pressure (PEEP) lung protection ventilation strategy by combining driving pressure (ΔP) and pulmonary ultrasound (LUS)-based titration on lung function and postoperative cognitive function in patients with chronic obstructive pulmonary disease (COPD) during laparoscopic surgery. METHODS: A total of 108 patients with COPD undergoing laparoscopic gastrointestinal surgery under general anesthesia were included in this study. They were randomly divided into three groups (n = 36): traditional volume ventilation group (Group C), fixed PEEP 5 cmH2O group (Group P), and ΔP combined with LUS-based PEEP titration in the resuscitation room group (Group T). All three groups were given volume ventilation mode, I:E = 1:2; In group C, VT was 10 mL/kg and PEEP was 0 cmH2O; In groups P and T, VT was 6 mL/kg and PEEP was 5 cmH2O; After mechanical ventilation for 15 min in Group T, ΔP in combination with LUS was used to titrate PEEP. The oxygenation index (PaO2/FiO2), airway platform pressure (Pplat), dynamic lung compliance (Cdyn), Montreal Cognitive Assessment (MoCA), and venous interleukin-6(IL-6) were recorded at the corresponding time points, and the final PEEP value in Group T was recorded. RESULTS: The final PEEP value of Group T was (6.4 ± 1.2) cmH2O; Compared with groups C and P: PaO2/FiO2 and Cdyn in Group T were significantly increased (P < 0.05) and value of IL-6 was significantly decreased (P < 0.05) at the corresponding time points. Compared with group C, the MoCA score on day 7 after surgery in Group T was significantly higher (P < 0.05). CONCLUSION: Compared with the traditional ventilation strategy, the individualized ΔP combined with LUS-based PEEP titration in patients with COPD during the perioperative period of laparoscopic surgery can play a better role in lung protection and can improve postoperative cognitive function.
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Interleucina-6 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Cognición , Ultrasonografía , Pulmón/diagnóstico por imagenRESUMEN
Colorectal cancer (CRC) has been the third leading cause of cancer-associated deaths. LncRNA SNHG16 is reported to be involved in metastasis of CRC cells. However, the mechanism by which SNHG16 regulates CRC progression is poorly understood. The proliferation of CRC cells was examined by MTT. Wound healing and transwell assay were used to measure migration and invasion ability. RT-qPCR and western blot were used to examine gene expression. Immunofluorescence was conducted to evaluate the EMT of CRC cells. Luciferase reporter assay were used to confirm direct interaction between miR-124-3p and SNHG16 or MCP-1. The interaction between miR-124-3p and SNHG16 was detected by RIP and RNA pull down assay. H&E staining was used to test the histomorphological changes of hepatic metastatic nodules. Finally, xenograft tumor experiment was utilized to determine tumor growth in vivo. SNHG16 and miR-124-3p were dysregulated in human colorectal tumors or cells. Knockdown of SNHG16 led to attenuate cell proliferation, migration, invasion, and EMT of CRC cells. And xenograft tumor experiment showed that SNHG16 might influence tumor growth. In contrast, miR-124-3p exerted the antitumor effects. Knockdown of miR-124-3p can reverse the effect of sh-SNHG16 on CRC cells. miR-124-3p could directly bind to SNHG16 or MCP-1. More importantly, MCP-1 acts as a critical effector mediating the role of SNHG16/ miR-124-3p in CRC cells. In summary, our data suggest that SNHG16 plays a contributory role in proliferation, migration, and EMT of CRC cells via miR-124-3p/MCP-1 axis, which offers a rationale for targeting SNHG16 and developing therapeutic drugs to treat CRC.
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Neoplasias Colorrectales , MicroARNs , ARN Largo no Codificante , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
OBJECTIVE: To evaluate the effects of doxofylline on inflammatory responses and oxidative stress during mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD). METHODS: Eight-week-old male Sprague Dawley rats were selected, and the COPD rat model was constructed. The rats were randomly divided into a model group (group M), a model + normal saline group (group N), a doxofylline group (group D), and a control group fed with conventional chow and given normal oxygen supply (group C) (n = 12 in each group). Tracheal intubation and mechanical ventilation were conducted in the rats in each group after anesthesia. A real-time intravenous infusion with 50 mg/kg of doxofylline was conducted in group D, and there was no drug intervention in groups C, N and M. Pathological manifestations of the pulmonary tissues were observed and compared among the groups. And some indicators were evaluated. RESULTS: (1) The pulmonary tissues of the rats in groups M, N, and D exhibited typical pathological histological changes of COPD. (2) Groups M, N, and D showed increased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue and BALF, and decreased PaO2 and IL-10 and SOD levels, compared with group C. (3). Group D showed decreased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue, and increased PaO2 and IL-10 and SOD levels, compared with group N or M. CONCLUSION: Doxofylline was shown to improve ventilation and air exchange during mechanical ventilation in rats with COPD, reduce the inflammatory response and oxidative stress, and mitigate the degree of pulmonary tissue injury.
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Inflamación/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Teofilina/análogos & derivados , Animales , Modelos Animales de Enfermedad , Inflamación/metabolismo , Interleucina-10/metabolismo , Masculino , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Respiración Artificial/métodos , Teofilina/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Cercospora leaf blight (CLB), primarily caused by Cercospora cf. flagellaris, is one of the most important diseases of soybean (Glycine max) in Louisiana. The pathogen produces cercosporin, a nonspecific toxin and an important virulence factor. There are no commercial cultivars with CLB resistance, and the pathogen has developed substantial resistance to the frequently used fungicides. Consequently, alternative methods are needed to manage CLB. One possibility is the RNA interference-based topical application of double-stranded (ds)RNA. The present study addressed the two most critical steps for this novel approach to be practical: inexpensively producing large quantities of dsRNA and identifying the right target genes for silencing. A screening method was developed to compare the effectiveness of Escherichia coli-produced dsRNAs targeting five fungal genes involved in cercosporin production for silencing in liquid culture. As much as 151.6 mg of dsRNA-containing total nucleic acids (TNAs) was produced from 1 liter of E. coli Luria broth culture using the L4440 vector. All tested dsRNAs reduced cercosporin production. However, significant target gene suppression was only detected in the cultures treated with dsRNAs from Avr4 and CTB8. The most potent dsRNA was from Avr4, which reduced 50% of cercosporin production at an estimated TNA concentration of 10.4 µg/ml (half maximal effective concentration [EC50]), and the least potent dsRNA was from HN-2, with an estimated EC50 of 46.7 µg/ml TNA. The present study paves the road for managing CLB under field conditions using dsRNA. Additionally, this approach could be adapted to identify the best dsRNAs to manage other fungal diseases.
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Ascomicetos , Ascomicetos/genética , Cercospora , Escherichia coli/genética , Perileno/análogos & derivados , Enfermedades de las Plantas , ARN Bicatenario/genéticaRESUMEN
BACKGROUND: Alternate-day fasting (ADF) is a novel diet therapy that may achieve reduction in body weight and improvement of dyslipidaemia, but the impact of this diet on patients with non-alcoholic fatty liver disease (NAFLD) remains unknown. The aim of this study was to evaluate the effects of ADF on the body weight and lipid profile of individuals with NAFLD. METHODS: NAFLD patients (n = 271) were randomised to the ADF group, time-restricted feeding (TRF) group, or the control group and subjected to the respective diet for 12 weeks. Anthropometric measurements (body weight, fat mass/fat-free mass) were performed, and plasma lipids were analysed enzymatically. RESULTS: Within 4 weeks, the body weight decreased significantly (P < 0.001) in the ADF group by 4.56 ± 0.41 kg (6.1 ± 0.5%) and the TRF group by 3.62 ± 0.65 kg (4.83 ± 0.9%) compared to the control group, and it decreased even more after 12 weeks in both groups (ADF: - 4.04 ± 0.54 kg, 5.4 ± 0.7%; TRF: - 3.25 ± 0.67 kg, 4.3 ± 0.9%). Fat mass was significantly reduced by ADF (- 3.49 ± 0.37 kg; 11 ± 1.2%) and TRF (- 2.91 ± 0.41 kg; 9.6 ± 1.3%), with ADF leading to a further reduction in fat mass after 12 weeks (- 3.48 ± 0.38 kg; 11 ± 1.2%). Total cholesterol was significantly decreased at both time points in the ADF group (- 0.91 ± 0.07 mmol/L; 18.5 ± 1.5%) compared to the control and TRF groups. Both ADF (- 0.64 ± 0.06 mmol/L; 25 ± 1.9%) and TRF (0.58 ± 0.07 mmol/L; 20 ± 1.7%) achieved a significant reduction in serum triglycerides (P < 0.001) after 12 weeks. Changes in fat free mass, HDL, LDL, fasting insulin, glucose, liver stiffness, and systolic or diastolic blood pressure did not differ between the groups. CONCLUSIONS: ADF appears to be an effective diet therapy for individuals with NAFLD that can achieve weight loss and improvement of dyslipidaemia within a relatively short period of time (4 to 12 weeks). Potential preventive effects of ADF on cardiovascular disease need to be confirmed by future investigations. TRIAL REGISTRATION: ChiCTR1900024411, this trial was retrospectively registered on July 10, 2019.
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Dislipidemias/dietoterapia , Ayuno , Conducta Alimentaria , Enfermedad del Hígado Graso no Alcohólico/dietoterapia , Pérdida de Peso , Adiposidad/fisiología , Adulto , Composición Corporal , Peso Corporal , Colesterol/sangre , Dislipidemias/sangre , Ingestión de Energía , Ayuno/sangre , Femenino , Humanos , Hambre , Masculino , Enfermedades Metabólicas/etiología , Enfermedad del Hígado Graso no Alcohólico/sangre , Evaluación de Resultado en la Atención de Salud , Factores de Riesgo , Factores de Tiempo , Triglicéridos/sangreRESUMEN
Aflatoxins, highly toxic and carcinogenic to humans, are synthesized via multiple intermediates by a complex pathway in several Aspergilli, including Aspergillus flavus. Few analytical methods are available for monitoring the changes in metabolite profiles of the aflatoxin biosynthesis pathway under different growth and environmental conditions. In the present study, we developed by a D-optimal mixture design a solvent system, methanol/dichloromethane/ethyl acetate/formic acid (0.36/0.31/0.32/0.01), that was suitable for extracting the pathway metabolites. The matrix effect from dilution of cell extracts was negligible. To facilitate the identification of these metabolites, we constructed a fragmentation ion library. We further employed liquid chromatography coupled with high-resolution mass spectroscopy (UHPLC-HRMS) for simultaneous quantification of the metabolites. The limit of detection (LOD) and limit of quantitation (LOQ) were 0.002-0.016 and 0.008-0.05 µg/kg, respectively. The spiked recovery rates ranged from 81.3 to 100.3% with intraday and interday precision less than 7.6%. Using the method developed to investigate the time-course aflatoxin biosynthesis, we found that precursors, including several possible toxins (with a carcinogenic group similar to aflatoxin B1), occurred together with aflatoxin, and that production increased rapidly at the early growth stage, peaked on day four, and then decreased substantially. The maximum production of aflatoxin B1 and aflatoxin B2 occurred 1 day later. Moreover, the dominant branch pathway was the one for aflatoxin B1 formation. We revealed that the antiaflatoxigenicity mechanism of Leclercia adecarboxylata WT16 was associated with a factor upstream of the aflatoxin biosynthesis pathway. The design strategies can be applied to characterize or detect other secondary metabolites to provide a snapshot of the dynamic changes during their biosynthesis.
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Aflatoxinas/biosíntesis , Aspergillus flavus/metabolismo , Espectrometría de Masas , Aflatoxinas/química , Aflatoxinas/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Contaminación de Alimentos , Solventes/químicaRESUMEN
MAIN CONCLUSION: Expressing an RNAi construct in maize kernels that targets the gene for alpha-amylase in Aspergillus flavus resulted in suppression of alpha-amylase (amy1) gene expression and decreased fungal growth during in situ infection resulting in decreased aflatoxin production. Aspergillus flavus is a saprophytic fungus and pathogen to several important food and feed crops, including maize. Once the fungus colonizes lipid-rich seed tissues, it has the potential to produce toxic secondary metabolites, the most dangerous of which is aflatoxin. The pre-harvest control of A. flavus contamination and aflatoxin production is an area of intense research, which includes breeding strategies, biological control, and the use of genetically-modified crops. Host-induced gene silencing, whereby the host crop produces siRNA molecules targeting crucial genes in the invading fungus and targeting the gene for degradation, has shown to be promising in its ability to inhibit fungal growth and decrease aflatoxin contamination. Here, we demonstrate that maize inbred B104 expressing an RNAi construct targeting the A. flavus alpha-amylase gene amy1 effectively reduces amy1 gene expression resulting in decreased fungal colonization and aflatoxin accumulation in kernels. This work contributes to the development of a promising technology for reducing the negative economic and health impacts of A. flavus growth and aflatoxin contamination in food and feed crops.
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Aflatoxinas/metabolismo , Aspergillus flavus/enzimología , Enfermedades de las Plantas/microbiología , Zea mays/microbiología , alfa-Amilasas/genética , Aspergillus flavus/genética , Aspergillus flavus/crecimiento & desarrollo , Aspergillus flavus/fisiología , Productos Agrícolas , Proteínas Fúngicas/genética , Silenciador del Gen , Interacciones Huésped-Patógeno , Plantas Modificadas Genéticamente , Interferencia de ARN , Semillas/microbiologíaRESUMEN
Aflatoxin contamination in peanuts poses major challenges for vulnerable populations of sub-Saharan Africa and South Asia. Developing peanut varieties to combat preharvest Aspergillus flavus infection and resulting aflatoxin contamination has thus far remained a major challenge, confounded by highly complex peanut-Aspergilli pathosystem. Our study reports achieving a high level of resistance in peanut by overexpressing (OE) antifungal plant defensins MsDef1 and MtDef4.2, and through host-induced gene silencing (HIGS) of aflM and aflP genes from the aflatoxin biosynthetic pathway. While the former improves genetic resistance to A. flavus infection, the latter inhibits aflatoxin production in the event of infection providing durable resistance against different Aspergillus flavus morphotypes and negligible aflatoxin content in several peanut events/lines well. A strong positive correlation was observed between aflatoxin accumulation and decline in transcription of the aflatoxin biosynthetic pathway genes in both OE-Def and HIGS lines. Transcriptomic signatures in the resistant lines revealed key mechanisms such as regulation of aflatoxin synthesis, its packaging and export control, besides the role of reactive oxygen species-scavenging enzymes that render enhanced protection in the OE and HIGS lines. This is the first study to demonstrate highly effective biotechnological strategies for successfully generating peanuts that are near-immune to aflatoxin contamination, offering a panacea for serious food safety, health and trade issues in the semi-arid regions.
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Aflatoxinas/metabolismo , Arachis/microbiología , Aspergillus/química , Defensinas/metabolismo , Contaminación de Alimentos/prevención & control , Aspergillus flavus/química , Biotecnología , Defensinas/genética , Inocuidad de los Alimentos , Silenciador del Gen , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , TranscriptomaRESUMEN
Glycogen storage disease type I and glycogenic hepatopathy are the most common type of primary and secondary hepatic glycogenosis, with presenting common radiological features of hepatomegaly, hepatic signal, or density change. Beyond that, glycogen storage disease type I shows hepatocellular adenomas or fatty liver, while glycogenic hepatopathy does not.
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Enfermedad del Almacenamiento de Glucógeno Tipo I/diagnóstico por imagen , Glucógeno/metabolismo , Hepatopatías/diagnóstico por imagen , Hígado/diagnóstico por imagen , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Diagnóstico Diferencial , Enfermedad del Almacenamiento de Glucógeno Tipo I/metabolismo , Humanos , Hígado/metabolismo , Hepatopatías/metabolismo , Valor Predictivo de las PruebasRESUMEN
BACKGROUND AND AIMS: To explore the relationship between habitual tea consumption and arterial stiffness. METHODS: This is a cross-sectional, epidemiological survey of 6589 male and female residents aged 40-75 in Wuyishan, Fujian Province, China. Tea consumption and other lifestyle characteristics were obtained by structured questionnaires. Pulse wave velocity (PWV) and ankle-brachial pressure index (ABI) were measured using an automated analyzer. RESULTS: Among the 5006 analyzed subjects, 1564 adults (31.2%) consumed tea once or more per week for at least one year. The levels of brachial-ankle pulse wave velocity (ba-PWV) were lowest among subjects who consumed tea habitually for more than 10 years compared with the other 3 subgroups (nonhabitual, 1 to 5 years, and 6 to 10 years habitual tea drinkers), and the levels of ba-PWV were lower with subjects who consumed 10-20 and >20 g/d tea habitually compared to nonhabitual tea drinkers. As the duration and the daily amount of habitual tea consumption increased the average ba-PWV decreased. Multiple logistic regression models revealed that habitual tea consumption was a positive predictor for ba-PWV (odds ratio [OR] = 0.63, 95% confidence interval [CI], 0.57-0.70). CONCLUSIONS: Habitual tea consumption may have a protective effect against arterial stiffness, especially for subjects who have habitually consumed tea for more than 6 years and >10 g daily.
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Té , Rigidez Vascular/fisiología , Adulto , Anciano , Índice Tobillo Braquial , China , Estudios Transversales , Femenino , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Análisis de la Onda del Pulso , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To explore whether fractional anisotropy (FA) value could be taken as a quantitative indicator for tracing and reexamining amyotrophic lateral sclerosis (ALS), and to analyze the correlation between FA value and integrative medical treatment. METHODS: Totally 18 ALS patients were recruited in this study. All patients received diffusion tensor imaging (DTI) using 3. OT (Propeller HD) MRI twice. Six regions of interest (ROI) were selected to measure FA values. Survival analyses were performed in 11 cases of end point events. RESULTS: (1) Three ROI (cerebral peduncle, posterior limb of internal capsule, and corona radiata) all indicated that FA value was the highest in patients with mild health status scale of amyotrophic lateral sclerosis (ALS/HSS). (2) There was statistical difference in the means of FA values in cerebral peduncle, posterior limb of internal capsule, and corona radiata of 18 cases between initial examination and reexamination (P < 0.01). (3) Kaplan-Meier survival curve showed the survival rate of ALS patients decreased as time went by, with the median survival time of 48 months. CONCLUSIONS: FA value was inversely proportional to the severity of ALS, the more severe, the lower FA values. FA value was an objective indicator for assessing the severity of ALS. ALS is an incurable disease till now. Integrative medical treatment might become one direction for ALS patients.
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Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/terapia , Imagen de Difusión Tensora , Anisotropía , Humanos , Medicina IntegrativaRESUMEN
We aimed to determine the prognostic values of 39 circulating cytokines in Chinese patients with metastatic colorectal cancer (CRC) and to develop a novel cytokine-based prognostic classifier (CBPC) for prognostic prediction. A total of 176 patients were divided into two cohorts based on the date of first-line chemotherapy. The first 99 cases were assigned to the training cohort, and the remaining 77 cases were assigned to the validation cohort. Thirty-nine cytokines were simultaneously analyzed in the patient serum samples using multiplex bead-based Luminex technology. We used support vector machine-based methods and Cox proportional hazards models to develop a CBPC from the training cohort, which we then validated using the second patient cohort. Univariate analysis showed that FGF-2, TGFα, Flt-3L, GM-CSF, INFα2, GRO, IL-10, MCP-3, MDC, sIL-2Rα, IL-2, IL-7, IL-8, MCP-1, MIP-1ß, TNFα and VEGF were significant risk factors affecting the overall survival (OS) of both the training cohort and the validation cohort. We developed a CBPC to predict the OS of metastatic CRC patients using these 17 cytokines (sensitivity, 0.835; specificity, 0.800). In the validation cohort, the CBPC was found to have significant power in predicting the OS of metastatic CRC patients. Our study showed that there were significant associations between cytokine expression and prognosis of the patients with metastatic CRC. The CBPC that we developed includes multiple circulating cytokines and may serve as a novel screening tool for identifying metastatic CRC patients with a high risk of short OS. These high-risk individuals may also be suitable for cytokine-targeted therapies.
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Neoplasias Colorrectales/mortalidad , Citocinas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Increasing evidence suggests that transforming growth factor-beta 1 (TGF-ß1) triggers epithelial to mesenchymal transition (EMT) and facilitates breast cancer stem cell differentiation. Gelsolin (GSN) is a ubiquitous actin filament-severing protein. However, the relationship between the expression level of GSN and the TGF-ß signaling for EMT progression in breast cancer cells is not clear. RESULTS: TGF-ß1 acted on MDA-MB231 breast cancer cells by decreasing cell proliferation, changing cell morphology to a fibroblast-like shape, increasing expressions for CD44 and GSN, and increasing EMT expression and cell migration/invasion. Study with GSN overexpression (GSN op) in both MDA-MB231 and MCF-7 cells demonstrated that increased GSN expression resulted in alterations of cell proliferation and cell cycle progression, modification of the actin filament assembly associated with altering cell surface elasticity and cell detachment in these breast cancer cells. In addition, increased cell migration was found in GSN op MDA-MB231 cells. Studies with GSN op and silencing by small interfering RNA verified that GSN could modulate the expression of vimentin. Sorted by flow cytometry, TGF-ß1 increased subpopulation of CD44+/CD22- cells increasing their expressions for GSN, Nanog, Sox2, Oct4, N-cadherin, and vimentin but decreasing the E-cadherin expression. Methylation specific PCR analysis revealed that TGF-ß1 decreased 50 % methylation but increased 3-fold unmethylation on the GSN promoter in CD44+/CD22- cells. Two DNA methyltransferases, DNMT1 and DNMT3B were also inhibited by TGF-ß1. CONCLUSIONS: TGF-ß1 induced epigenetic modification of GSN could alter the EMT process in breast cancer cells.
Asunto(s)
Neoplasias de la Mama/metabolismo , Transición Epitelial-Mesenquimal , Gelsolina/metabolismo , Proteínas de Neoplasias/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Ciclo Celular , Epigénesis Genética , Femenino , Gelsolina/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Proteínas de Neoplasias/genética , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
Plant ß-1,3-glucanases are members of the pathogenesis-related protein 2 (PR-2) family, which is one of the 17 PR protein families and plays important roles in biotic and abiotic stress responses. One of the differentially expressed proteins (spot 842) identified in a recent proteomic comparison between five pairs of closely related maize (Zea mays L.) lines differing in aflatoxin resistance was further investigated in the present study. Here, the corresponding cDNA was cloned from maize and designated as ZmGns. ZmGns encodes a protein of 338 amino acids containing a potential signal peptide. The expression of ZmGns was detectible in all tissues studied with the highest level in silks. ZmGns was significantly induced by biotic stresses including three bacteria and the fungus Aspergillus flavus. ZmGns was also induced by most abiotic stresses tested and growth hormones including salicylic acid. In vivo, ZmGns showed a significant inhibitory activity against the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and fungal pathogen Botrytis cinerea when it overexpressed in Arabidopsis. Its high level of expression in the silk tissue and its induced expression by phytohormone treatment, as well as by bacterial and fungal infections, suggest it plays a complex role in maize growth, development, and defense.
Asunto(s)
Antiinfecciosos/farmacología , Endo-1,3(4)-beta-Glucanasa/genética , Estrés Fisiológico/efectos de los fármacos , Zea mays/enzimología , Secuencia de Aminoácidos , Antifúngicos/farmacología , Arabidopsis/genética , Arabidopsis/microbiología , Aspergillus/efectos de los fármacos , Botrytis/efectos de los fármacos , Clonación Molecular , Endo-1,3(4)-beta-Glucanasa/química , Endo-1,3(4)-beta-Glucanasa/metabolismo , Escherichia coli/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Genes de Plantas , Concentración de Iones de Hidrógeno , Datos de Secuencia Molecular , Especificidad de Órganos/efectos de los fármacos , Especificidad de Órganos/genética , Filogenia , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Reguladores del Crecimiento de las Plantas/farmacología , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/enzimología , Hojas de la Planta/genética , Plantas Modificadas Genéticamente , Proteínas Recombinantes/metabolismo , Ácido Salicílico/farmacología , Alineación de Secuencia , Análisis de Secuencia de ADN , Especificidad por Sustrato/efectos de los fármacos , Temperatura , Zea mays/efectos de los fármacos , Zea mays/genética , Zea mays/microbiologíaRESUMEN
A novel palladium-catalyzed norbornene-mediated three-component reaction for the construction of ortho-alkenyl aromatic tertiary amines has been achieved, which represents a useful extension of the Catellani-type tandem ortho-selective CH amination transformations.
RESUMEN
BACKGROUND: The reported prevalence of unruptured cerebral aneurysms (UCAs) varies widely. OBJECTIVE: To measure the prevalence of UCAs by using 3-dimensional time-of-flight magnetic resonance angiography in adults aged 35 to 75 years. DESIGN: Cross-sectional study done between June 2007 and June 2011. SETTING: Two communities chosen at random from 2 districts (1 urban and 1 suburban) in Shanghai, China. PARTICIPANTS: 4813 adults aged 35 to 75 years. MEASUREMENTS: Three-dimensional time-of-flight magnetic resonance angiography, interpreted by 3 observers blinded to the participants' information, was used to identify the location and size of UCAs and to estimate the overall, age-specific, and sex-specific prevalence. RESULTS: 369 UCAs were found in 336 participants (130 men and 206 women); 4477 participants had no evidence of UCAs. The prevalence was 7.0% overall (95% CI, 6.3% to 7.7%), with 5.5% for men (CI, 4.6% to 6.4%) and 8.4% for women (CI, 7.3% to 9.5%). The overall prevalence of UCAs was higher in women than in men (P < 0.001) and peaked at ages 55 to 64 years in men and women. The UCAs were mostly located in the internal carotid artery (81%), and 90.2% had a maximum diameter less than 5 mm. Mean diameter was larger in women than in men (3.7 mm vs. 3.2 mm; P < 0.009). LIMITATION: Participants were from 2 communities selected from 2 districts in Shanghai, and adults older than 75 years were not studied. CONCLUSION: The overall prevalence of UCAs was 7.0% in Chinese adults aged 35 to 75 years, and most lesions had a diameter less than 5 mm. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.