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1.
New Phytol ; 226(1): 232-243, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31778576

RESUMEN

In the processes controlling ecosystem fertility, fungi are increasingly acknowledged as key drivers. However, our understanding of the rules behind fungal community assembly regarding the effect of soil fertility level remains limited. Using soil samples from typical tea plantations spanning c. 2167 km north-east to south-west across China, we investigated the assemblage complexity and assembly processes of 140 fungal communities along a soil fertility gradient. The community dissimilarities of total fungi and fungal functional guilds increased with increasing soil fertility index dissimilarity. The symbiotrophs were more sensitive to variations in soil fertility compared with pathotrophs and saprotrophs. Fungal networks were larger and showed higher connectivity as well as greater potential for inter-module connection in more fertile soils. Environmental factors had a slightly greater influence on fungal community composition than spatial factors. Species abundance fitted the Zipf-Mandelbrot distribution (niche-based mechanisms), which provided evidence for deterministic-based processes. Overall, the soil fungal communities in tea plantations responded in a deterministic manner to soil fertility, with high fertility correlated with complex fungal community assemblages. This study provides new insights that might contribute to predictions of fungal community complexity.

2.
J Geriatr Cardiol ; 16(9): 689-694, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31645854

RESUMEN

Background: Anemia is a common comorbidity of patients with Takayasu arteritis (TA). This study evaluated the prevalence, clinical characteristics, and treatment in Chinese TA patients with anemia. Methods: This retrospective study included 533 consecutive patients hospitalized for TA from January 2009 to April 2018. Anemia was diagnosed on the basis of hemoglobin level, according to World Health Organization criteria. Results: A total of 194 patients (36.4%) were diagnosed with anemia. Most had mild anemia (177, 91.2%). Female patients were predominant (92.8% of anemic patients). Normocytic anemia (62.9%) was the most common pattern. Anemic patients were more likely than non-anemic patients to have dizziness (29.4% vs. 21.2%), low body mass index (22.0 ± 3.6 vs. 22.9 ± 3.4 kg/m2), and active disease stage (64.9% vs. 50.1%); pulmonary involvement (12.4% vs. 26.8%), pulmonary hypertension (12.9% vs. 20.1%) and pulmonary hypertensive-target drugs (2.8% vs. 11.6%) were less common among anemic than non-anemic patients (all P < 0.05). Larger left ventricular end-diastolic diameter and lower left ventricular ejection fraction were observed in anemic patients. Over a median follow-up of four months, the increase of hemoglobin in anemic patients was associated with the use of iron supplementation. Conclusions: Anemia is a very common concurrent condition in TA, especially in young, female patients. Patients with anemia are more likely to be in the active disease stage. Iron supplementation helps increase hemoglobin.

3.
Cancer Sci ; 110(9): 2941-2959, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31343810

RESUMEN

A sensitive and specific diagnosis biomarker, in principle scalable to most cancer types, is needed to reduce the prevalent cancer mortality. Meanwhile, the investigation of diagnosis determinants of a biomarker will facilitate the interpretation of its screening results in clinic. Here we design a large-scale (1558 enrollments), multicenter (multiple hospitals), and cross-validation (two datasets) clinic study to validate plasma Hsp90α quantified by ELISA as a pan-cancer biomarker. ROC curve shows the optimum diagnostic cutoff is 69.19 ng/mL in discriminating various cancer patients from all controls (AUC 0.895, sensitivity 81.33% and specificity 81.65% in test cohort; AUC 0.893, sensitivity 81.72% and specificity 81.03% in validation cohort). Similar results are noted in detecting early-stage cancer patients. Plasma Hsp90α maintains also broad-spectrum for cancer subtypes, especially with 91.78% sensitivity and 91.96% specificity in patients with AFP-limited liver cancer. In addition, we demonstrate levels of plasma Hsp90α are determined by ADAM10 expression, which will affect Hsp90α content in exosomes. Furthermore, Western blotting and PRM-based quantitative proteomics identify that partial false ELISA-negative patients secret high levels of plasma Hsp90α. Mechanism analysis reveal that TGFß-PKCγ gene signature defines a distinct pool of hyperphosphorylated Hsp90α at Theronine residue. In clinic, a mechanistically relevant population of false ELISA-negative patients express also higher levels of PKCγ. In sum, plasma Hsp90α is a novel pan-cancer diagnosis biomarker, and cancer diagnosis with plasma Hsp90α is particularly effective in those patients with high expression of ADAM10, but may be insufficient to detect the patients with low ADAM10 and those with hyperphosphorylated Hsp90α.


Asunto(s)
Biomarcadores de Tumor/sangre , Proteínas HSP90 de Choque Térmico/sangre , Neoplasias/diagnóstico , Proteína ADAM10/genética , Proteína ADAM10/metabolismo , Adolescente , Adulto , Secretasas de la Proteína Precursora del Amiloide/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Niño , Preescolar , Conjuntos de Datos como Asunto , Ensayo de Inmunoadsorción Enzimática , Exosomas/metabolismo , Reacciones Falso Negativas , Femenino , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Lactante , Recién Nacido , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/patología , Fosforilación , Estudios Prospectivos , Curva ROC , Treonina/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Adulto Joven
4.
J Exp Clin Cancer Res ; 38(1): 239, 2019 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-31174569

RESUMEN

BACKGROUND: Temozolomide-perillyl alcohol conjugate (NEO212), a novel temozolomide (TMZ) analog, was previously reported to exert its anti-cancer effect in non-small cell lung cancer (NSCLC), and human nasopharyngeal carcinoma (NPC), etc.. In the current study, we intend to illuminate the potential anticancer property and the underly mechanisms of NEO212 in ovarian cancer cells. METHODS: The cytotoxicity of NEO212 was detected by MTT, colony formation analysis and xenograft model. The proteins involved in cell proliferation, DNA damage, autophagy and lysosomal function were detected by western blots; mitochondria, lysosome and autophagosome were visualized by TEM and/or immunofluorescence; Apoptosis, cell cycle analysis and mitochondrial transmembrane potential were detected by flow cytometry. TFEB translocation was detected by immunofluorescence and western blot. RESULTS: NEO212 has the potential anticancer property in ovarian cancer cells, as evidence from cell proliferation inhibition, G2/M arrest, DNA damage, xenograft, mitochondrial dysfunction and apoptosis. Importantly, we observed that although it induced significant accumulation of autophagosomes, NEO212 quenched GFP-LC3 degradation, down-regulated a series of lysosome related gene expression and blocked the autophagic flux, which significantly facilitated it induced apoptosis and was largely because it inhibited the nuclear translocation of transcription factor EB (EB). CONCLUSIONS: NEO212 inhibited TFEB translocation, and impaired the lysosomal function, implying NEO212 might avoid from autophagy mediated chemo-resistance, thus proposing NEO212 as a potential therapeutic candidate for ovarian cancer.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Dacarbazina/análogos & derivados , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neoplasias Ováricas/metabolismo , Animales , Antineoplásicos/uso terapéutico , Autofagosomas/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular , Daño del ADN/efectos de los fármacos , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Modelos Animales de Enfermedad , Femenino , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Mitocondrias/ultraestructura , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Transporte de Proteínas , Ensayos Antitumor por Modelo de Xenoinjerto
5.
J Cardiol ; 74(5): 443-450, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31235418

RESUMEN

BACKGROUND: Although current guidelines recommend the use of statins for severe atherosclerotic renal artery stenosis (ARAS), the renal protection of intensive lipid-lowering therapy in patients with ARAS who underwent stent placement remains uncertain. The aim of this study was to compare the renal-protective effect of intensive lipid lowering with that of conventional lipid lowering in patients with ARAS undergoing stent placement. METHODS: A total 150 patients with severe ARAS undergoing stent placement were randomly (1:1) assigned to receive intensive lipid lowering [target low-density lipoprotein cholesterol (LDL-C) <70mg/dL] or conventional lipid lowering (target LDL-C ≥70mg/dL, <128mg/dL). All patients received rosuvastatin. We adjusted LDL-C to the goal within two months after renal stenting and maintained stability. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) at 12 months. RESULTS: During the study period, LDL-C was lower in the patients with intensive lipid lowering than with conventional lipid lowering (at 12 months 58.0±11.6 vs 85.1±15.5mg/dL, p<0.001). At 12-month follow-up, eGFR (91.8±30.2 vs 78.5±19.5)mL/min·1.73m2, p=0.002) and the increase in eGFR compared to baseline [14.8(IQR, 4.1, 26.7) vs -0.4(IQR, -9.5, 8.0)mL/min·1.73m2, p<0.001] were higher in the patients with intensive lipid lowering than with conventional lipid lowering. Urinary albumin-creatinine ratio [42.2(IQR, 20.0, 60.9) vs 60.8(IQR, 26.8, 121.6)mg/g, p=0.032] was lower and the decrease in urinary albumin-creatinine ratio compared to baseline [27.4(IQR, 3.0, 53.8) vs -3.1(IQR, -17.3, 30.9)mg/g, p=0.001] was higher in the patients with intensive lipid lowering than with conventional lipid lowering. The restenosis rate (3.1% vs 3.4%, p=0.711) and major clinical events (6.8% vs 11.0%, p=0.37) were similar between the two groups. CONCLUSIONS: In patients with severe ARAS undergoing stent placement, intensive lipid lowering showed significant benefits in renal protection over conventional lipid-lowering therapy.

6.
J Geriatr Cardiol ; 16(4): 354-361, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31105756

RESUMEN

Objective: To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs, as monotherapy or dual combination therapy, to improve daytime and nighttime BP control. Methods: We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg; daytime mean BP < 135/85 mmHg; and nighttime mean BP < 120/70 mmHg), as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups. Results: Patients' mean age was 71 years, and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy, and renin-angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52, P = 0.05 and OR = 0.41, P = 0.007, respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45, P = 0.004). Compared with RAS/diuretic therapy, BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27, P = 0.45). Conclusions: Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP, whereas diuretic-based therapies provided lower nighttime BP, compared with other antihypertensive regimens.

7.
Appl Opt ; 58(12): 3310-3316, 2019 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-31044811

RESUMEN

Dynamic speckles, which carry information about beam parameters of a diffuse object, are produced by a moving diffuse object under illumination of a Gaussian beam. In this paper, we consider that the diffuse object moves in a plane with constant velocity and discuss the statistical properties of dynamic speckles for estimating the variation of focusing spot size. The space-time statistical properties of dynamic speckle have been revealed by analyzing the space-time cross-correlation function of speckle intensity fluctuations detected at two points in the receiving plane. We discuss the influence of the distance between two point detectors on the detection results by simulation analyses, and the theoretical analysis results are verified by experiment. This method, which applies feedback of the dynamic speckle fields for estimating the variation of focusing spot size, will help a laser focusing system optimize focusing performance.

9.
PLoS One ; 14(3): e0213012, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30830909

RESUMEN

The present study aimed to understand the effect of venous valve lesion on the valve cycle. A modified immersed finite element method was used to model the blood-tissue interactions in the pathological vein. The contact process between leaflets or between leaflet and sinus was evaluated using an adhesive contact method. The venous valve modeling was validated by comparing the results of the healthy valve with those of experiments and other simulations. Four valve lesions induced by the abnormal elasticity variation were considered for the unhealthy valve: fibrosis, atrophy, incomplete fibrosis, and incomplete atrophy. The opening orifice area was inversely proportional to the structural stiffness of the valve, while the transvalvular flow velocity was proportional to the structural stiffness of the valve. The stiffening of the fibrotic leaflet led to a decrease in the orifice area and a stronger jet. The leaflet and blood wall shear stress (WSS) in fibrosis was the highest. The softening of the atrophic leaflet resulted in overly soft behavior. The venous incompetence and reflux were observed in atrophy. Also, the atrophic leaflet in incomplete atrophy exhibited weak resistance to the hemodynamic action, and the valve was reluctant to be closed owing to the large rotation of the healthy leaflet. Low blood WSS and maximum leaflet WSS existed in all the cases. A less biologically favorable condition was found especially in the fibrotic leaflet, involving a higher mechanical cost. This study provided an insight into the venous valve lesion, which might help understand the valve mechanism of the diseased vein. These findings will be more useful when the biology is also understood. Thus, more biological studies are needed.


Asunto(s)
Hemorreología , Modelos Cardiovasculares , Válvulas Venosas/patología , Algoritmos , Simulación por Computador , Elasticidad , Fibrosis , Análisis de Elementos Finitos , Humanos , Estrés Mecánico , Válvulas Venosas/fisiopatología
10.
Int J Stroke ; 14(3): 270-281, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30058959

RESUMEN

BACKGROUND: Covert vascular disease of the brain manifests as infarcts, white matter hyperintensities, and microbleeds on MRI. Their cumulative effect is often a decline in cognition, motor impairment, and psychiatric disorders. Preventive therapies for covert brain ischemia have not been established but represent a huge unmet clinical need. AIMS: The MRI substudy examines the effects of the antithrombotic regimens in COMPASS on incident covert brain infarcts (the primary outcome), white matter hyperintensities, and cognitive and functional status in a sample of consenting COMPASS participants without contraindications to MRI. METHODS: COMPASS is a randomized superiority trial testing rivaroxaban 2.5 mg bid plus acetylsalicylic acid 100 mg and rivaroxaban 5 mg bid against acetylsalicylic acid 100 mg per day for the combined endpoint of MI, stroke, and cardiovascular death in individuals with stable coronary artery disease or peripheral artery disease. T1-weighted, T2-weighted, T2*-weighted, and FLAIR images were obtained close to randomization and near the termination of assigned antithrombotic therapy; biomarker and genetic samples at randomization and one month, and cognitive and functional assessment at randomization, after two years and at the end of study. RESULTS: Between March 2013 and May 2016, 1905 participants were recruited from 86 centers in 16 countries. Of these participants, 1760 underwent baseline MRI scans that were deemed technically adequate for interpretation. The mean age at entry of participants with interpretable MRI was 71 years and 23.5% were women. Coronary artery disease was present in 90.4% and 28.1% had peripheral artery disease. Brain infarcts were present in 34.8%, 29.3% had cerebral microbleeds, and 93.0% had white matter hyperintensities. The median Montreal Cognitive Assessment score was 26 (interquartile range 23-28). CONCLUSIONS: The COMPASS MRI substudy will examine the effect of the antithrombotic interventions on MRI-determined covert brain infarcts and cognition. Demonstration of a therapeutic effect of the antithrombotic regimens on brain infarcts would have implications for prevention of cognitive decline and provide insight into the pathogenesis of vascular cognitive decline.


Asunto(s)
Anticoagulantes/uso terapéutico , Infarto Encefálico/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Encéfalo/patología , Trastornos del Conocimiento/tratamiento farmacológico , Rivaroxabán/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Anciano , Infarto Encefálico/diagnóstico , Isquemia Encefálica/diagnóstico , Cognición , Trastornos del Conocimiento/diagnóstico , Femenino , Humanos , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/diagnóstico , Resultado del Tratamiento
11.
Eur J Prev Cardiol ; 26(7): 681-697, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30537846

RESUMEN

BACKGROUND AND DESIGN: There are limited data on the effects of blood pressure and cholesterol lowering in Asians at intermediate risk and no cardiovascular disease. We report an analysis of the effects of blood pressure and cholesterol lowering in Asians enrolled in the Heart Outcomes Prevention Evaluation 3 (HOPE 3) trial. METHODS: We randomly assigned 6241 Asians and 6464 non-Asians at intermediate risk without cardiovascular disease to candesartan 16 mg/hydrochlorothiazide 12.5 mg or placebo and rosuvastatin 10 mg or placebo. The first co-primary outcome was a composite of cardiovascular disease death, myocardial infarction and stroke. The second co-primary outcome additionally included heart failure, cardiac arrest and revascularisation. Median follow-up was 5.6 years. RESULTS: Reduction in systolic blood pressure was less among Asians (4.3 vs. 7.7 mmHg for non-Asians, P < 0.0001) mainly due to a lesser effect in Chinese (2.1 mmHg) than in other Asians (7.3 mmHg), reduction in the latter being similar to non-Asians. The effect on the composite outcomes was similar, with no significant benefits from blood pressure lowering for either Asians (Chinese or non-Chinese) or non-Asians. Rosuvastatin reduced low-density lipoprotein cholesterol to a lesser degree in Asians (0.49 mmol/L (-19.1 mg/dL) compared with non-Asians 0.95 mmol/L (-36.7 mg/dL), Pinteraction < 0.0004). Yet both groups had similar reductions in the two co-primary outcomes. There was no increase in permanent medication discontinuation due to muscle-related symptoms in either group. There was an excess in new diabetes in non-Asians (4.70% rosuvastatin, 3.52% placebo, P = 0.025) but not in Asians (3.02% rosuvastatin, 4.04% placebo, P = 0.0342), Pinteraction = 0021. CONCLUSIONS: Candesartan/hydrochlorothiazide had fewer effects in reducing blood pressure in Chinese and rosuvastatin reduced low-density lipoprotein cholesterol to a lesser extent in Asians compared with non-Asians. There was no overall reduction in clinical events with lowering blood pressure in either Asians or non-Asians, whereas there were clear and consistent benefits with lipid lowering in both. Despite extensive analyses, we have no obvious explanation for the observed findings. Future studies need to include larger numbers of individuals from different regions of the world to ensure that the results of trials are applicable globally.

12.
Materials (Basel) ; 11(12)2018 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-30545087

RESUMEN

The influence of hygrothermal aging on high-velocity impact damage of carbon fiber-reinforced polymer (CFRP) laminates is investigated. Composite laminate specimens were preconditioned in water at 70 °C. The laminates were subsequently impacted by flat-, sphere-, and cone- ended projectiles with velocities of 45, 68, and 86 m/s. The incident and residual velocities were collected during the impact test. The impact-induced damages were measured by ultrasonic C-scan, a digital microscope system, and a scanning electron microscope. The results show that the hygrothermally conditioned laminates offer a higher energy absorption during high-velocity impact. Due to the weakening of the interlaminar properties, the hygrothermally conditioned laminates are more susceptible to delamination failure, and shear-induced debonding dominates. The projected delamination area increases with the increment of impact velocity. The damaged region becomes close to a circular shape after hydrothermal conditioning, and close to a rhomboidal shape for the dry specimens.

13.
Micromachines (Basel) ; 9(9)2018 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-30424392

RESUMEN

In past decades, considerable advances have been achieved in micro and nanomotors. Particular attention has been given to self-propelled catalytic micromotors, which have been widely used in cell separation, drug delivery, microsurgery, lithography and environmental remediation. Fast moving, long life micromotors appear regularly, however it seems there are no solutions yet that thoroughly clarify the hydrodynamic behavior of catalytic micromotors moving in fluid. Dynamic behavior of this kind of micromotors is mainly determined by the driving force and drag force acting on the micromotors. Based on the hydromechanics theory, a hydrodynamic model is established to predict the drag force for a conical micromotor immersed in the flow field. By using the computational fluid dynamics software Fluent 18.0 (ANSYS), the drag force and the drag coefficient of different conical micromotors are calculated. A mathematical model was proposed to describe the relationship among Reynolds numbers Re, the ratio λ, the semi-cone angle δ and the drag coefficient Cd of the micromotors. This work provides theoretical support and reference for optimizing the design and development of conical micromotors.

14.
Am J Med Sci ; 356(4): 357-364, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30360804

RESUMEN

BACKGROUND: Takayasu arteritis (TA) can involve the aortic root or cardiac valves, resulting in hemodynamic disorders. In this study, we focused on the prevalence and clinical characteristics of TA patients with valve regurgitation. MATERIALS AND METHODS: We retrospectively assessed the clinical data in the electronic medical records of 1,069 consecutive patients with TA admitted to Fuwai Hospital from January 1992 to August 2017. We evaluated the valvular structure and function mainly by cardiac ultrasound. RESULTS: Among the 1,069 patients, 373 (34.9%) had valve regurgitation. The female to male ratio was 4.8:1. The average age at symptom onset was 28.1 ± 10.6 years. The median duration from symptom onset to first hospitalization was 65.9 months. Of patients with valve involvement, 47.4% and 40.1% had a high erythrocyte sediment rate and C-reactive protein level, respectively, at the time of echocardiography. Most patients (69.7%) had aortic regurgitation, and nearly half had moderate to severe aortic regurgitation. A total of 38.8% of patients had aortic valve damage, and 23.3% had involvement of the ascending aorta. Most other valve insufficiency was mild, including mitral regurgitation in 39.1% of patients, tricuspid regurgitation in 34.6%, and pulmonary regurgitation in 11.8%. Valve stenosis was rare. Misdiagnosis of other cardiac diseases occurred in 13 patients. CONCLUSIONS: Cardiac valve insufficiency is common in Chinese TA patients. Patients should undergo echocardiography once TA is diagnosed. In young women of reproductive age, TA should be considered when aortic regurgitation is detected.


Asunto(s)
Enfermedades de las Válvulas Cardíacas/epidemiología , Válvulas Cardíacas/fisiopatología , Arteritis de Takayasu/etiología , Adolescente , Adulto , China/epidemiología , Ecocardiografía , Femenino , Enfermedades de las Válvulas Cardíacas/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Arteritis de Takayasu/fisiopatología , Adulto Joven
15.
Materials (Basel) ; 11(10)2018 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-30274282

RESUMEN

The effects of carbon content on the mechanical properties and deformation mechanisms of boron carbides were investigated by first-principles calculations, based on the density functional theory. The B12⁻CBC (13.33 at % C) and B10 C 2 P ⁻CC (28.75 at % C) were studied and then compared with the deformation of regular B11CP⁻CBC (20.0 at % C). The results show the B10 C 2 P ⁻CC, which has the lowest carbon content, has the highest strength and hardness as well as the lowest toughness. With the increase of carbon content, the rhombohedral symmetry will be broken and the three-atoms chains will be replaced by diatomic carbon chains. These changes may have an influence on their anisotropic deformation mechanisms. For the B12⁻CBC, the destruction of icosahedra without bending three-atom chains causes structural failure for compression along the c axis; while for compression along the a axis, new B⁻B bonds are formed, causing an unrecoverable deformation; then it is gradually destroyed until full destruction. For the B10 C 2 P ⁻CC, the anisotropic deformation mechanism is not obvious. For both loading directions, the breakage of B⁻CP bonds causes the stress to drop, suggesting that the structure is beginning to be destroyed. Finally, the icosahedra are fully destroyed, resulting in structural failure.

16.
Gene ; 678: 261-269, 2018 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-30103008

RESUMEN

Colorectal cancer is a leading cause of cancer-related death. Glutaminolysis has been suggested as a therapeutic target for cancer. Costunolide is a natural sesquiterpene lactone showing potent antitumor activity. Our studies were aimed at evaluating how costunolide affected glutaminolysis leading to proliferation inhibition in human colorectal cancer cells. Costunolide suppressed viability and proliferation of HCT116 cells concentration-dependently, but did not apparently affect human intestinal epithelial cells. Costunolide at 20 µM reduced viability and proliferation of HCT116 cells time-dependently. Costunolide also repressed phosphorylation of mTOR and its downstream kinases p70S6K and 4E-BP1. Examinations of glutaminolysis metabolites showed that costunolide increased intracellular glutamine levels, but decreased intracellular levels of glutamate, α-ketoglutarate (α-KG), and ATP in HCT116 cells, suggesting costunolide blockade of glutaminolysis. Furthermore, costunolide inhibited promoter activity of glutaminase 1 (GLS1), the first rate-limiting enzyme in glutaminolysis, and reduced mRNA and protein expression of GLS1 in HCT116 cells, The GLS1 inhibitor BPTES, similar to costunolide, significantly reduced intracellular levels of α-KG and ATP and inhibited proliferation in HCT116 cells. Finally, costunolide increased phosphorylation and nuclear translocation of p53 in HCT116 cells. Both p53 inhibitor pifithrin-α and p53 siRNA significantly rescued costunolide suppression of GLS1 promoter activity and expression in HCT116 cells. These data in aggregate suggested that activation of p53 was required for costunolide inhibition of GLS1 resulting in blockade of glutaminolysis and inhibition of proliferation in colorectal cancer cells, which was a novel mechanism underlying the antitumor activity of costunolide against colorectal cancer.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias Colorrectales/metabolismo , Glutamina/química , Sesquiterpenos/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glutaminasa/metabolismo , Células HCT116 , Humanos , Fosforilación/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Factores de Tiempo
17.
J Clin Hypertens (Greenwich) ; 20(9): 1302-1309, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30027575

RESUMEN

The time trends regarding the etiology of renal artery stenosis (RAS) are changing, but few investigations have focused on these issues. This study aimed to analyze the time trends regarding the etiology of RAS in a large patient sample from the China Center for Cardiovascular Disease. Consecutive inpatients with RAS from January 1999 to December 2016 were enrolled in this study. The etiologic diagnosis of RAS was based on established criteria. We retrospectively analyzed the time trends regarding the etiology of RAS during an 18-year period. A total of 2905 patients with RAS were enrolled. There were 2393 (82.4%) patients with atherosclerosis (AS), 345 (11.9%) with Takayasu arteritis (TA), 126 (4.3%) with fibromuscular dysplasia (FMD), and 41 (1.4%) with other causes. Among all patients (n = 2905), patients aged ≤ 40 years (n = 450), patients aged >40 years (n = 2455), female patients (n = 1097), male patients (n = 1808), female patients aged >40 years (n = 808), and male patients aged >40 years (n = 1647), there were a gradual increase in the proportion of atherosclerotic RAS (P < 0.05), a gradual decrease in the proportion of RAS caused by TA (P < 0.05), and almost no change in the proportion of RAS caused by FMD during the 18-year period (P > 0.05). The data show that the primary causes of RAS are AS, TA, and FMD. The proportion of RAS caused by AS and TA gradually increased and decreased, respectively, over time, and the proportion of RAS caused by FMD showed no significant change.


Asunto(s)
Aterosclerosis/epidemiología , Displasia Fibromuscular/epidemiología , Obstrucción de la Arteria Renal/etiología , Arteritis de Takayasu/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Aterosclerosis/complicaciones , Niño , China/epidemiología , Femenino , Displasia Fibromuscular/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Arteritis de Takayasu/complicaciones , Adulto Joven
18.
Biomark Med ; 12(8): 881-890, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29939072

RESUMEN

AIM: We investigated HSP90α as screening biomarker for early colorectal cancer (CRC). METHODS & RESULTS: Seventy-seven CRC patients and 78 healthy controls were enrolled. Plasma HSP90α was significantly higher in CRC patients than in healthy controls (p < 0.05). levels were higher in late (stages III and IV) CRC than in early (stages I and II) CRC (p = 0.022). HSP90α conferred an advantage in the diagnosis of early CRC. Combination of HSP90α and carcinoembryonic antigen improved the diagnostic sensitivity (84.4%) and specificity (89.5%) for CRC (area under the curve: 0.968); for early CRC, the sensitivity was 82.5% and specificity was 89.5% (area under the curve: 0.955). CONCLUSION: HSP90 is a potential biomarker for the diagnosis of early CRC.


Asunto(s)
Biomarcadores de Tumor/sangre , Antígeno Carcinoembrionario/sangre , Neoplasias Colorrectales , Proteínas HSP90 de Choque Térmico/sangre , Adulto , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias
19.
Cancer Sci ; 109(5): 1701-1709, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29573061

RESUMEN

The present study aimed to investigate the overall changes in exosomal proteomes in metastatic and non-metastatic non-small-cell lung cancers (NSCLC) and healthy human serum samples, and evaluate the potential of serum exosomal biomarkers to predict NSCLC metastasis. Tandem mass tags combined with multidimensional liquid chromatography and mass spectrometry analysis were used for screening the proteomic profiles of serum samples. Quantitative proteome, significant pathway, and functional categories of patients with metastatic and non-metastatic NSCLC and healthy donors were investigated. In total, 552 proteins of the 628 protein groups identified were quantified. Bioinformatics analysis indicated that quantifiable proteins were mainly involved in multiple biological functions, metastasis-related pathways. Moreover, lipopolysaccharide-binding proteins (LBP) in the exosomes were found to be well distinguished between patients with metastatic and patients with non-metastatic NSCLC. Area under the curve (AUC) was 0.803 with a sensitivity of 83.1% and a specificity of 67% (P < .0001). Circulating LBP were also well distinguishable between metastatic and non-metastatic NSCLC, the AUC was 0.683 with a sensitivity of 79.5% and a specificity of 47.2% (P = .005). This novel study provided a reference proteome map for metastatic NSCLC. Patients with metastatic and non-metastatic NSCLC differed in exosome-related proteins in the serum. LBP might be promising and effective candidates of metastatic NSCLC.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/secundario , Exosomas/química , Neoplasias Pulmonares/patología , Proteómica/métodos , Proteínas de Fase Aguda , Área Bajo la Curva , Carcinoma de Pulmón de Células no Pequeñas/sangre , Proteínas Portadoras/sangre , Biología Computacional , Humanos , Neoplasias Pulmonares/sangre , Glicoproteínas de Membrana/sangre
20.
Lab Invest ; 98(7): 935-946, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29497175

RESUMEN

Genotype-directed targeted therapy has become one of the standard treatment options for non-small cell lung cancer (NSCLC). There have been numerous limitations associated with mutation analysis of tissue samples. Consequently, mutational profile analysis of circulating cell-free DNA (cfDNA) by highly sensitive droplet digital PCR (ddPCR) assay has been developed. Possibly due to differences in cfDNA concentrations, previous studies have shown numerous discrepancies in mutation detection consistency between tissue and cfDNA. In order to rigorously analyze the amount of cfDNA needed, we constructed 72 athymic nude mice xenografted with NCI-H1975 (harboring a EGFR T790M mutation) or NCI-H460 (harboring a KRAS Q61H mutation) human NSCLC. We thoroughly investigated the relationship between plasma cfDNA using Q-PCR targeting human long interspersed nuclear element-1 (LINE-1) retrotransposon and the mouse ACTB gene, and the accuracy of mutation detection by ddPCR at different times post-graft. Our results show that the concentration and fragmentation of human (tumor) derived cfDNA (hctDNA) were positively correlated with tumor weight, but not with mouse-derived cfDNA (mcfDNA). Quantification of cfDNA by Q-PCR depends on the amplified target length. Mutation copies in plasma of per milliliter were positively linked to tumor weight, hctDNA level and hctDNA/mcfDNA ratio, respectively. Furthermore, tumor weight, hctDNA level and ratio of hctDNA/mcfDNA were significantly higher in cfDNA mutation-positive mice than in negative mice. Also, our data indicate that when plasma hctDNA level and hctDNA/mcfDNA ratio reach a certain level in xenografted mice, plasma cfDNA mutation can be detected. In summary, the present study suggests that determination of ctDNA levels may be essential for reliable mutation detection by analysis of cfDNA.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , ADN Tumoral Circulante/sangre , Neoplasias Pulmonares/genética , Mutación/genética , Animales , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , ADN Tumoral Circulante/genética , Análisis Mutacional de ADN , Humanos , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Neoplasias Experimentales , Reacción en Cadena de la Polimerasa
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