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1.
Chem Biodivers ; 21(5): e202400648, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38545941

RESUMEN

Taxodin A (1), a unique C30 terpenoid featuring an unprecedented skeleton composed of an abietane-type diterpene and a menthane-type monoterpene, was obtained from the leaves and branches of Taxodium mucronatum. The structure and absolute configuration of compound 1 was unequivocally established by the combination of extensive spectroscopic analyses and X-ray single-crystal diffraction analysis. Compound 1 exhibited potent cytotoxic activities against A549, SMMC-7721, MDA-MB-231, and SW480 cell lines with IC50 values of 15.35±0.73, 8.49±0.35, 17.53±0.79, 18.93±0.60 µM, respectively.


Asunto(s)
Antineoplásicos Fitogénicos , Ensayos de Selección de Medicamentos Antitumorales , Taxodium , Humanos , Taxodium/química , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Terpenos/química , Terpenos/farmacología , Terpenos/aislamiento & purificación , Conformación Molecular , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Hojas de la Planta/química , Relación Estructura-Actividad , Estructura Molecular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Modelos Moleculares
2.
Behav Res Methods ; 56(1): 379-405, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36650402

RESUMEN

What Works Clearinghouse (WWC, 2022) recommends a design-comparable effect size (D-CES; i.e., gAB) to gauge an intervention in single-case experimental design (SCED) studies, or to synthesize findings in meta-analysis. So far, no research has examined gAB's performance under non-normal distributions. This study expanded Pustejovsky et al. (2014) to investigate the impact of data distributions, number of cases (m), number of measurements (N), within-case reliability or intra-class correlation (ρ), ratio of variance components (λ), and autocorrelation (ϕ) on gAB in multiple-baseline (MB) design. The performance of gAB was assessed by relative bias (RB), relative bias of variance (RBV), MSE, and coverage rate of 95% CIs (CR). Findings revealed that gAB was unbiased even under non-normal distributions. gAB's variance was generally overestimated, and its 95% CI was over-covered, especially when distributions were normal or nearly normal combined with small m and N. Large imprecision of gAB occurred when m was small and ρ was large. According to the ANOVA results, data distributions contributed to approximately 49% of variance in RB and 25% of variance in both RBV and CR. m and ρ each contributed to 34% of variance in MSE. We recommend gAB for MB studies and meta-analysis with N ≥ 16 and when either (1) data distributions are normal or nearly normal, m = 6, and ρ = 0.6 or 0.8, or (2) data distributions are mildly or moderately non-normal, m ≥ 4, and ρ = 0.2, 0.4, or 0.6. The paper concludes with a discussion of gAB's applicability and design-comparability, and sound reporting practices of ES indices.


Asunto(s)
Proyectos de Investigación , Humanos , Reproducibilidad de los Resultados , Sesgo
3.
Psychooncology ; 30(6): 853-862, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33523559

RESUMEN

OBJECTIVE: This study explored the multiple mediating effects of cancer threat appraisal, functional status, and symptom distress on the association between mindfulness and depression in colorectal cancer (CRC) patients at the transition stage after completing cancer treatments. METHODS: A total of 90 CRC survivors who received cancer treatments within 3 months participated in this cross-sectional study. The functional status and symptom distress (EORTC-C30 and EORTC CR29), dispositional mindfulness (Five Facet Mindfulness Questionnaire), cancer threat appraisal ( Constructed Meaning Scale), and depressive symptoms (Beck Depression Inventory-II scale) were collected. The mediation and moderation analyses were conducted using the PROCESS macros for SPSS. RESULTS: Survivors' dispositional mindfulness (γ = -0.49, p < 0.001) and cancer threat appraisal (γ = -0.59, p < 0.001) were significantly associated with depressive symptoms. Simple mediation analysis indicated that cancer threat appraisal mediated the relationship between dispositional mindfulness and depression (ß = -0.02, 95% CI = -0.04 to -0.001). The multiple mediated analysis identified the path between dispositional mindfulness and depression via cancer threat appraisal and colorectal symptom distress (ß = -0.01, 95% CI = -0.03 to -0.01). In the mediated moderation model, the path between dispositional mindfulness and depression via colorectal function was moderated by cancer threat appraisal (ß = -0.02, 95% CI = -0.05 to -0.004). CONCLUSIONS: The two cognitive mechanisms of reducing CRC survivors' depression are as follows: (1) dispositional mindfulness reducing the appraisal of cancer as a threat and increasing positive perceptions of CRC symptoms and (2) the cancer threat appraisal buffered the impacts of CRC's mindfulness and colorectal function on depressive symptoms. Developing mindfulness with cognitive training is recommended for improving depressive symptoms among CRC patients in the transition period.


Asunto(s)
Neoplasias Colorrectales , Atención Plena , Neoplasias Colorrectales/terapia , Estudios Transversales , Depresión/epidemiología , Humanos , Calidad de Vida , Sobrevivientes
4.
Analyst ; 146(22): 6935-6943, 2021 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-34647547

RESUMEN

A common strategy to improve the sensitivity of a biosensor for the detection of a low abundance analyte is to preconcentrate the analyte molecules before detection. A dual-functional gold-iron oxide core-satellite hybrid nanoparticle structure is proposed in this work to overcome the drawbacks of traditional sample pretreatment methods and the methods using non-magnetic nanomaterials for sample pretreatment. The new dual-functional hybrid nanoparticle structure can simultaneously serve as a signal reporter of a biorecognition event and a preconcentrator of a target at an extremely low concentration in a nanoplasmonic biosensor. By utilizing a fiber optic nanogold-linked sorbent assay in the fiber optic particle plasmon resonance (FOPPR) biosensor and an arbitrary DNA sequence as a target, we have demonstrated that the use of the new hybrid nanoparticle structure with magnetic preconcentration improves the limit of detection (LOD) for the DNA by 18 times as compared to the same method without magnetic preconcentration, so that the LOD for detecting the DNA can be as low as 2.6 fM. The new hybrid nanoparticle structure is easy to prepare and its use in the high-sensitivity and low-cost FOPPR biosensor provides vast opportunities in point-of-care applications.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Compuestos Férricos , Oro , Límite de Detección , Resonancia por Plasmón de Superficie
5.
J Biochem Mol Toxicol ; 35(5): e22737, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33751715

RESUMEN

Homocysteine (Hcy) is a sulfur-containing amino acid that originated in methionine metabolism and the elevated level of Hcy in plasma is considered to be an independent risk factor for cardiovascular diseases (CVD). Endothelial dysfunction plays a major role in the development of CVD, while the potential mechanism of Hcy-induced endothelial dysfunction is still unclear. Here, in Hcy-treated endothelial cells, we observed the destruction of mitochondrial morphology and the decline of mitochondrial membrane potential. Meanwhile, the level of ATP was reduced and the reactive oxygen species was increased. The expressions of dynamin-related protein 1 (Drp1) and phosphate-Drp1 (Ser616) were upregulated, whereas the expression of mitofusin 2 was inhibited by Hcy treatment. These findings suggested that Hcy not only triggered mitochondrial dysfunction but also incurred an imbalance of mitochondrial dynamics in endothelial cells. The expression of mitochondrial calcium uniporter (MCU) was activated by Hcy, contributing to calcium transferring into mitochondria. Interestingly, the formation of mitochondria-associated membranes (MAMs) was increased in endothelial cells after Hcy administration. The inositol 1,4,5-triphosphate receptor (IP3R)-glucose-regulated protein 75 (Grp75)-voltage-dependent anion channel (VDAC) complex, which was enriched in MAMs, was also increased. The accumulation of mitochondrial calcium could be blocked by inhibiting with the IP3R inhibitor Xestospongin C (XeC) in Hcy-treated cells. Then, we confirmed that the mitochondrial dysfunction and the increased mitochondrial fission induced by Hcy could be attenuated after Hcy and XeC co-treatment. In conclusion, Hcy-induced mitochondrial dysfunction and dynamics disorder in endothelial cells were mainly related to the increase of calcium as a result of the upregulated expressions of the MCU and the IP3R-Grp75-VDAC complex in MAMs.


Asunto(s)
Calcio/metabolismo , Homocisteína/farmacología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Homocisteína/efectos adversos , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Mitocondrias/patología
6.
Sensors (Basel) ; 20(2)2020 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-31936424

RESUMEN

A silk fibroin composite film that can simultaneously scavenge and probe H2O2 in situ was developed for possibly examining local concentrations of H2O2 for biomedical applications. A multi-functional composite film (GDES) that consists of graphene oxide (G), a photothermally responsive element that was blended with polydopamine (PDA, D)/horseradish peroxidase (HRP, E) (or DE complex), and then GDE microaggregates were coated with silk fibroin (SF, S), a tyrosine-containing protein. At 37 °C, the H2O2-scavenging ability of a GDES film in solution at approximately 7.5 × 10-3 µmol H2O2/mg film was the highest compared with those of S and GS films. The intensities of UV-excitable blue fluorescence of a GDES film linearly increased with increasing H2O2 concentrations from 4.0 µM to 80 µM at 37 °C. Interestingly, after a GDES film scavenged H2O2, the UV-excitable blue fluorescent film could be qualitatively monitored by eye, making the film an eye-probe H2O2 sensor. A GDES film enabled to heat H2O2-containing samples to 37 °C or higher by the absorption of near-IR irradiation at 808 nm. The good biocompatibility of a GDES film was examined according to the requirements of ISO-10993-5. Accordingly, a GDES film was developed herein to scavenge and eye-probe H2O2 in situ and so it has potential for biomedical applications.

7.
Behav Res Methods ; 52(1): 131-150, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-30805863

RESUMEN

Single-case experimental design (SCED) research plays an important role in establishing and confirming evidence-based practices. Due to multiple measures of a target behavior in such studies, missing information is common in their data. The expectation-maximization (EM) algorithm has been successfully applied to deal with missing data in between-subjects designs, but only in a handful of SCED studies. The present study extends the findings from Smith, Borckardt, and Nash (2012) and Velicer and Colby (2005b, Study 2) by systematically examining the performance of EM in a baseline-intervention (or AB) design under various missing rates, autocorrelations, intervention phase lengths, and magnitudes of effects, as well as two fitted models. Three indicators of an intervention effect (baseline slope, level shift, and slope change) were estimated. The estimates' relative bias, root-mean squared error, and relative bias of the estimated standard error were used to assess EM's performance. The findings revealed that autocorrelation impacted the estimates' qualities most profoundly. Autocorrelation interacted with missing rate in impacting the relative bias of the estimates, impacted the root-mean squared error nonlinearly, and interacted with the fitted model in impacting the relative bias of the estimated standard errors. A simpler model without autocorrelation can be used to estimate baseline slope and slope change in time-series data. EM is recommended as a principled method to handle missing data in SCED studies. Two decision trees are presented to assist researchers and practitioners in applying EM. Emerging research directions are identified for treating missing data in SCED studies.


Asunto(s)
Algoritmos , Sesgo , Exactitud de los Datos , Proyectos de Investigación
8.
Langmuir ; 35(44): 14203-14212, 2019 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-31596591

RESUMEN

A facile aerosol-based synthetic approach is demonstrated for the fabrication of silver-manganese oxide (Ag-MnOx) and cetyltrimethylammonium bromide (CTAB)-templated silver-manganese oxide (c-Ag-MnOx) hybrid nanostructures as the positive electrode materials of supercapacitors. Through gas-phase evaporation-induced self-assembly, silver nanoparticles are homogeneously decorated in the hybrid nanostructure to create a conductive path at the interface of the cluster of MnOx crystallites. The utilization of the capacitance of MnOx increases by the addition of Ag nanoparticles (>2 times for Ag-MnOx and ∼1.7 times for c-Ag-MnOx). An optimal specific capacitance is achieved when the concentration of the silver precursor (CAg) is 0.5 wt %, 118 F g-1 for Ag-MnOx, and 154 F g-1 for c-Ag-MnOx at a specific current of 1 A g-1. The enhanced supercapacitive performance by the addition of CTAB at low CAg is attributed to the increased surface area (>19.4%) for electrochemical reactions. The prototype method with mechanistic understanding demonstrated in this study shows promise for the fabrication of a variety of MnOx-based hybrid nanostructures for supercapacitor applications.

9.
Palliat Support Care ; 17(1): 95-106, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-29911519

RESUMEN

OBJECTIVE: The aims of this systematic review were to examine the effects of the overall and the different types of the interventions on the do-not-resuscitate (DNR) designation and the time between DNR and death among cancer patients. METHOD: Data were searched from the databases of PubMed, CINAHL, EMbase, Medline, and Cochrane Library through 2 November 2017. Studies were eligible for inclusion if they were (1) randomized control trails, quasi-experimental study, and retrospective observational studies and (2) used outcome indicators of DNR designation rates. The Effective Public Health Practice Project tool was used to assess the overall quality of the included studies. RESULT: The 14 studies with a total of 7,180 participants were included in this review. There were 78.6% (11 of 14) studies that indicated that the interventions could improve the DNR designation rates. Three types of DNR interventions were identified in this review: palliative care unit service, palliative consultation services, and patient-physician communication program. The significant increases of the time between DNR designation and death only occurred in a patient-physician communication program. SIGNIFICANCE OF RESULTS: The palliative care unit service provided a continuing care model to reduce unnecessary utilization of healthcare service. The palliative consultation service is a new care model to meet the needs of cancer patients in non-palliative care unit. The share decision-making communication program and physician's compassion attitudes facilitate to make DNR decision early. The individualized DNR program needs to be developed according to the needs of cancer patients.


Asunto(s)
Neoplasias/terapia , Órdenes de Resucitación , Toma de Decisiones , Humanos , Relaciones Médico-Paciente , Factores de Tiempo
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(6): 573-579, 2019 Jun.
Artículo en Zh | MEDLINE | ID: mdl-31208512

RESUMEN

OBJECTIVE: To study the clinical value of serum neuroglobin in evaluating hypoglycemic brain injury in neonates. METHODS: A total of 100 neonates with hypoglycemia were enrolled as subjects. According to amplitude-integrated EEG (aEEG) findings and/or clinical manifestations, they were divided into symptomatic hypoglycemic brain injury group (n=22), asymptomatic hypoglycemic brain injury group (n=37) and hypoglycemic non-brain injury group (n=41). The three groups were compared in terms of blood glucose, duration of hypoglycemia, levels of neuroglobin and neuron-specific enolase (NSE), and modified aEEG score. The correlation of neuroglobin with NSE and modified aEEG score was analyzed. The receiver operating characteristic (ROC) curve was plotted. RESULTS: Compared with the asymptomatic hypoglycemic brain injury and hypoglycemic non-brain injury groups, the symptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia (P<0.05). Compared with the hypoglycemic non-brain injury group, the asymptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia (P<0.05). Neuroglobin was positively correlated with NSE and duration of hypoglycemia (r=0.922 and 0.929 respectively; P<0.05) and negatively correlated with blood glucose and modified aEEG score (r=-0.849 and -0.968 respectively; P<0.05). The areas under the ROC curve of neuroglobin, NSE and modified aEEG score were 0.894, 0.890 and 0.941 respectively, and neuroglobin had a sensitivity of 80.8% and a specificity of 95.8% at the optimal cut-off value of 108 mg/L. CONCLUSIONS: Like NSE and modified aEEG score, serum neuroglobin can also be used as a specific indicator for the assessment of brain injury in neonates with hypoglycemia and has a certain value in clinical practice.


Asunto(s)
Lesiones Encefálicas , Neuroglobina/sangre , Electroencefalografía , Humanos , Hipoglucemiantes , Recién Nacido , Fosfopiruvato Hidratasa
11.
Langmuir ; 34(17): 5030-5039, 2018 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-29606007

RESUMEN

A gas-phase-controlled synthetic approach is demonstrated to fabricate Ag-ZnO hybrid nanostructure as a high-performance catalyst for photodegradation of water pollutants. The degradation of rhodamine B (RhB) was used as representative, which were tested and evaluated with respect to the environmental pH and the presence of dodecyl sulfate corona on the surface of the catalyst. The results show that a raspberry-structure Ag-ZnO hybrid nanoparticle cluster was successfully synthesized via gas-phase evaporation-induced self-assembly. The photodegradation activity increased significantly (20×) by using the Ag-ZnO hybrid nanoparticle cluster as a catalyst. A surge of catalytic turnover frequency of ZnO nanoparticle cluster (>20×) was observed through the hybridization with silver nanoparticles. The dodecyl sulfate corona increased the photocatalytic activity of the Ag-ZnO hybrid nanoparticle cluster, especially at the acidic and neutral pH environments (maximum 6×), and the enhancement in catalytic activity was attributed to the improved colloidal stability of ZnO-based nanoparticle cluster under the interaction with RhB. Our work provides a generic route of facile synthesis of the Ag-ZnO hybrid nanoparticle cluster with a mechanistic understanding of the interface reaction for enhancing photocatalysis toward the degradation of water pollutants.

12.
Sleep Breath ; 21(2): 487-495, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28210922

RESUMEN

STUDY OBJECTIVES: The aim of this study is to investigate changes in regional cerebral blood flow (rCBF) in awake people with untreated severe obstructive sleep apnoea (OSAs) compared with good sleepers (GSs). DESIGN: Arterial spin labelling perfusion imaging was used to quantify cerebral perfusion based on resting-state functional magnetic resonance imaging (MRI). SETTING: Lying supine in a 3.0-T magnetic resonance imaging scanner in the night was done. PARTICIPANTS: Included in this study were 30 subjects with OSA (males; mean age 38.4 years, range 25-55) and 30 controls (males; mean age: 38.3 years, range 26-52) matched for age and years of education. RESULTS: Compared with GSs, participants with severe OSA had reduced rCBF in the left cerebellum posterior lobe, left temporal lobe, right medial frontal gyrus, and bilateral parahippocampal gyrus and increased rCBF in the bilateral superior frontal gyrus. The lower mean CBF in the right parahippocampal gyrus exhibited a significant positive correlation with arousal index (r = 0.365, P = 0.047). The increased mean CBF in the left superior frontal gyrus exhibited a significant positive correlation with the longest apnoea time (r = 0.422, P = 0.020), and the increased mean CBF in the right superior frontal gyrus exhibited a significant positive correlation with the longest apnoea time (r = 0.447, P = 0.013). CONCLUSIONS: Our results show that the altered rCBF pattern in the left cerebellum posterior lobe, left temporal lobe, left medial frontal gyrus, bilateral parahippocampal gyrus and superior frontal gyrus in patients have with severe OSA. The arterial spin labelling perfusion imaging method is a useful non-invasive imaging tool for detection of early changes in the regional cerebral blood flow in patients with OSA.


Asunto(s)
Encéfalo/irrigación sanguínea , Espectroscopía de Resonancia por Spin del Electrón , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/fisiopatología , Marcadores de Spin , Adulto , Dominancia Cerebral/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Flujo Sanguíneo Regional/fisiología
13.
Behav Res Methods ; 47(1): 107-26, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24793819

RESUMEN

Confidence interval (CI) estimation for an effect size (ES) provides a range of possible population ESs supported by data. In this article, we investigated the noncentral t method, Bonett's method, and the bias-corrected and accelerated (BCa) bootstrap method for constructing CIs when a standardized linear contrast of means is defined as an ES. The noncentral t method assumes normality and equal variances, Bonett's method assumes only normality, and the BCa bootstrap method makes no assumptions. We simulated data for three and four groups from a variety of populations (one normal and five nonnormals) with varied variance ratios (1, 2.25, 4, 8), population ESs (0, 0.2, 0.5, 0.8), and sample size patterns (one equal and two unequal). Results showed that the noncentral method performed the best among the three methods under the joint condition of ES = 0 and equal variances. Performance of the noncentral method was comparable to that of the other two methods under (1) equal sample size, unequal weight for each group, and the last group sampled from a leptokurtic distribution, or (2) equal sample size and equal weight for all groups, when all are sampled from a normal population, or only the last group sampled from a nonnormal distribution. In the remaining conditions, Bonett's and the BCa bootstrap methods performed better than the noncentral method. The BCa bootstrap method is the method of choice when the sample size per group is 30 or more. Findings from this study have implications for simultaneous comparisons of means and of ranked means in between- and within-subjects designs.


Asunto(s)
Intervalos de Confianza , Modelos Estadísticos , Tamaño de la Muestra , Humanos , Probabilidad , Sensibilidad y Especificidad
14.
Molecules ; 19(2): 1603-7, 2014 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-24473216

RESUMEN

A new dicoumarinyl ether, 3-hydroxy-6-methoxy-7,7'-dicoumarinyl ether (1), was isolated from the roots of Stellera chamaejasme L, together with the known compound umbelliferone (2). Their structures were determined on the basis of spectroscopic techniques, including IR, NMR, and HR-ESI-MS.


Asunto(s)
Éteres/química , Estructura Molecular , Extractos Vegetales/química , Umbeliferonas/química , Éteres/farmacología , Espectroscopía de Resonancia Magnética , Raíces de Plantas/química , Thymelaeaceae/química
15.
Nanotechnology ; 24(43): 435201, 2013 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-24084604

RESUMEN

Single-walled carbon nanotube (SWCNT) transparent conducting films (TCFs) were fabricated for the electrodes of organic light-emitting diodes (OLEDs); three types of film were studied. The as-prepared SWCNT TCFs displayed a relatively low sheet resistance of 82.6 Ω/sq at 80.7 T% with a relatively large surface roughness of 30 nm. The TCFs were top-coated with poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) to obtain PEDOT:PSS-coated TCFs. The PEDOT:PSS cover improved the conductivity and decreased the surface roughness to 12 nm at the cost of film transmittance. The SWCNT TCFs mixed with PEDOT:PSS (PM-TCFs) exhibited a high conductivity (70.6 Ω/sq at 81 T%) and a low surface roughness (3 nm) and were thus selected as the best TCFs for OLEDs. Blue flexible OLEDs with 4,4'-bis(2,2'-diphenylvinyl)-1,1'-biphenyl (Dpvbi) as the emitting layer were fabricated on TCFs with the same structures to evaluate the performances of the different types of SWCNT films for use in OLEDs. Of these three types of OLEDs, the PM-TCF devices exhibited the optimal performance with a maximum luminance of 2587 cd m(-2) and a current efficiency of 5.44 cd A(-1). This result was explored using field-emission scanning electron microscopy and atomic force microscopy to further study the mechanisms that are involved in applying SWCNT TCFs to OLEDs.

16.
Cell Genom ; 2(2): 100096, 2022 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36778661

RESUMEN

Organoid evolution models complemented with integrated single-cell sequencing technology provide a powerful platform to characterize intra-tumor heterogeneity (ITH) and tumor evolution. Here, we conduct a parallel evolution experiment to mimic the tumor evolution process by evolving a colon cancer organoid model over 100 generations, spanning 6 months in time. We use single-cell whole-genome sequencing (WGS) in combination with viral lineage tracing at 12 time points to simultaneously monitor clone size, CNV states, SNV states, and viral lineage barcodes for 1,641 single cells. We integrate these measurements to construct clonal evolution trees with high resolution. We characterize the order of events in which chromosomal aberrations occur and identify aberrations that recur multiple times within the same tumor sub-population. We observe recurrent sequential loss of chromosome 4 after loss of chromosome 18 in four unique tumor clones. SNVs and CNVs identified in our organoid experiments are also frequently reported in colorectal carcinoma samples, and out of 334 patients with chromosome 18 loss in a Memorial Sloan Kettering colorectal cancer cohort, 99 (29.6%) also harbor chromosome 4 loss. Our study reconstructs tumor evolution in a colon cancer organoid model at high resolution, demonstrating an approach to identify potentially clinically relevant genomic aberrations in tumor evolution.

17.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 2): o358, 2011 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-21523037

RESUMEN

The title compound, C(20)H(20)N(2)O(4), crystallizes with four independent mol-ecules in the asymmetric unit. In the mol-ecules, the dihedral angles between the benzene rings and indole mean planes are 24.5 (1), 22.5 (1), 8.8 (1) and 13.9 (1)°. In the crystal, inter-molecular N-H⋯O hydrogen bonds are present between the imino groups and the adjacent carbonyl groups. π-π stacking is also observed with a centroid-centroid distance between nearly parallel pyrrole rings of 3.745 (3) Å.

18.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 6): o1538-9, 2011 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-21754898

RESUMEN

In the title compound, C(31)H(34)N(2)O(7), the fused tetra-hydro-furan and six-membered rings each display an envelope conformation. The dihedral angles between the benzene ring of the benzo[d][1,3]dioxole and the other two benzene rings are 89.68 (3) and 63.38 (2)°. In the crystal, weak inter-molecular C-H⋯O hydrogen bonds link the mol-ecules.

19.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 6): o1491, 2011 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-21754859

RESUMEN

In the title compound, C(29)H(28)ClNO(7), the tetra-hydro-furan ring and the six-membered ring fused to it both display envelope conformations. The dihedral angles between the plane of the benzene ring of the benzo[d][1,3]dioxole system and the planes of the other two benzene rings are 80.59 (3) and 63.60 (2)°.

20.
J Tissue Eng Regen Med ; 15(7): 648-659, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33982442

RESUMEN

Meniscus regeneration could be enhanced by targeting meniscus cells and mesenchymal stromal cells (MSCs) with the right growth factors. Combining these growth factors with the Collagen Meniscus Implant (CMI®) could accelerate cell ingrowth and tissue formation in the implant and thereby improve clinical outcomes. Using a transwell migration assay and a micro-wound assay, the effect of insulin-like growth factor-1, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF-ß1), fibroblast growth factor, and platelet lysate (PL) on migration and proliferation of meniscus cells and MSCs was assessed. The formation of extracellular matrix under influence of the above-mentioned growth factors was assessed after 28 days of culture of both MSCs and meniscus cells. As a proof of concept, the CMI® was functionalized with a VEGF binding peptide and coated with platelet-rich plasma (PRP) for clinical application. Our results demonstrate that PDGF, TGF-ß1, and PL stimulate migration, proliferation, and/or extracellular matrix production of meniscus cells and MSCs. Additionally, the CMI® was successfully functionalized with a VEGF binding peptide and PRP which increased migration of meniscus cell and MSC into the implant. This study demonstrates proof of concept of functionalizing the CMI® with growth factor binding peptides. A CMI® functionalized with the right growth factors holds great potential for meniscus replacement after partial meniscectomy.


Asunto(s)
Plaquetas/química , Implantes Experimentales , Péptidos y Proteínas de Señalización Intercelular/farmacología , Menisco/fisiología , Células Madre Mesenquimatosas/citología , Regeneración/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Colágeno/farmacología , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/metabolismo , Humanos , Proteínas Inmovilizadas/farmacología , Factor de Crecimiento Derivado de Plaquetas/farmacología , Factor A de Crecimiento Endotelial Vascular/farmacología
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