RESUMO
Mass spectrometry imaging (MSI) is a powerful tool that can be used to simultaneously investigate the spatial distribution of different molecules in samples. However, it is difficult to comprehensively analyze complex biological systems with only a single analytical technique due to different analytical properties and application limitations. Therefore, many analytical methods have been combined to extend data interpretation, evaluate data credibility, and facilitate data mining to explore important temporal and spatial relationships in biological systems. Image registration is an initial and critical step for multimodal imaging data fusion. However, the image registration of multimodal images is not a simple task. The property difference between each data modality may include spatial resolution, image characteristics, or both. The image registrations between MSI and different imaging techniques are often achieved indirectly through histology. Many methods exist for image registration between MSI data and histological images. However, most of them are manual or semiautomatic and have their prerequisites. Here, we built MSI Registrar (MSIr), a web service for automatic registration between MSI and histology. It can help to reduce subjectivity and processing time efficiently. MSIr provides an interface for manually selecting region of interests from histological images; the user selects regions of interest to extract the corresponding spectrum indices in MSI data. In the performance evaluation, MSIr can quickly map MSI data to histological images and help pinpoint molecular components at specific locations in tissues. Most registrations were adequate and were without excessive shifts. MSIr is freely available at https://msir.cmdm.tw and https://github.com/CMDM-Lab/MSIr.
Assuntos
Diagnóstico por Imagem , Técnicas Histológicas , Espectrometria de Massas/métodos , Mineração de DadosRESUMO
Optimal selenium (Se) status is necessary for overall health. That status can be affected by food intake pattern, age, sex, and health status. At nutritional levels of intake, Se functions metabolically as an essential constituent of some two dozen selenoproteins, most, if not all, of which have redox functions. Insufficient dietary intake of Se reduces, to varying degrees, the expression of these selenoproteins. Recent clinical and animal studies have indicated that both insufficient and excessive Se intakes may increase risk of type 2 diabetes mellitus (T2D), perhaps by way of selenoprotein actions. In this review, we discuss the current evidence linking Se status and T2D risk, and the roles of 14 selenoproteins and other proteins involved in selenoprotein biosynthesis. Understanding such results can inform the setting of safe and adequate Se intakes.
Assuntos
Diabetes Mellitus Tipo 2 , Selênio , Animais , Selenoproteínas/metabolismo , Oxirredução , Estado NutricionalRESUMO
BACKGROUND: Although dietary selenium (Se) deficiency or excess induces type 2 diabetes-like symptoms in mice, suboptimal body Se status usually causes no symptoms but may promote age-related decline in overall health. OBJECTIVES: We sought to determine the dietary Se requirement for protection against type 2 diabetes-like symptoms in mice. METHODS: Thirty mature (aged 4 mo) male C57BL/6J mice were fed a Se-deficient torula yeast AIN-93M diet supplemented with Na2SeO4 in graded concentrations totaling 0.01 (basal), 0.04, 0.07, 0.10, and 0.13 (control) mg Se/kg for 4 mo (n = 6) until they were middle-aged (8 mo). Droplets of whole blood were used to determine glucose tolerance and insulin sensitivity in the mice from ages 5 to 8 mo. Postmortem serum, liver, and skeletal muscle were collected to assay for selenoprotein expression and markers of glucose metabolism. Data were analyzed by 1-way ANCOVA with or without random effects for time-repeated measurements using live mice or postmortem samples, respectively. RESULTS: Compared with control, the consumption of basal diet increased (P < 0.05) fasting serum insulin (95% CI: 52%, 182%) and leptin (95% CI: 103%, 118%) concentrations in middle-aged mice. Dietary Se insufficiency decreased (P < 0.05) 1) glucose tolerance (13-79%) and insulin sensitivity (15-65%) at ≤0.10 mg Se/kg; 2) baseline thymoma viral proto-oncogene phosphorylation on S473 (27-54%) and T308 (22-46%) at ≤0.10 and ≤0.07 mg Se/kg, respectively, in the muscle but not the liver; and 3) serum glutathione peroxidase 3 (51-83%), liver and muscle glutathione peroxidase 1 (32-84%), serum and liver selenoprotein P (28-42%), and liver and muscle selenoprotein H (39-48%) and selenoprotein W (16-73%) protein concentrations at ≤0.04, ≤0.10, ≤0.07, and ≤0.10 mg Se/kg, respectively. CONCLUSIONS: Mice fed diets containing ≤0.10 mg Se/kg display impaired glucose tolerance and insulin sensitivity, suggesting increased susceptibility to type 2 diabetes by suboptimal Se status at levels ≤23% of nutritional needs.
Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Resistência à Insulina , Selênio , Animais , Diabetes Mellitus Tipo 2/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Paper spray ionization has been used as a fast sampling/ionization method for the direct mass spectrometric analysis of biological samples at ambient conditions. Here, we demonstrated that by utilizing paper spray ionization-mass spectrometry (PSI-MS) coupled with field asymmetric waveform ion mobility spectrometry (FAIMS), predictive metabolic and lipidomic profiles of routine breast core needle biopsies could be obtained effectively. By the combination of machine learning algorithms and pathological examination reports, we developed a classification model, which has an overall accuracy of 87.5% for an instantaneous differentiation between cancerous and noncancerous breast tissues utilizing metabolic and lipidomic profiles. Our results suggested that paper spray ionization-ion mobility spectrometry-mass spectrometry (PSI-IMS-MS) is a powerful approach for rapid breast cancer diagnosis based on altered metabolic and lipidomic profiles.
Assuntos
Neoplasias da Mama/diagnóstico , Aprendizado de Máquina , Papel , Algoritmos , Feminino , Humanos , Espectrometria de Mobilidade Iônica , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
PURPOSE: To evaluate the clinical features and surgical outcomes of rhegmatogenous retinal detachment in pediatric patients and to identify the independent effect of each etiology on the outcome. METHODS: A review of patients younger than 18 years who underwent vitreoretinal surgery was conducted at Chang Gung Memorial Hospital, Taoyuan, between 2008 and 2013. Patients were classified according to etiology. Multivariate logistic regression analysis was performed to evaluate the association between outcomes and each etiologic factor. RESULTS: A total of 86 cases (mean age: 12.9 ± 4.8 years; 76.7% male) were included. The mean follow-up was 46.3 ± 23.9 months. In 90.7% of patients, at least one etiology could be identified, including myopia (55.8%), congenital or developmental disease (39.5%), trauma (27.9%), and previous intraocular surgery (17.4%). Among the risk factors examined in this study, congenital or developmental disease had the worst functional outcomes (P = 0.006). Myopia was a good prognostic factor for a better retinal reattachment rate (P = 0.030). Myopic rhegmatogenous retinal detachment had the lowest probability of surgical failure (8.08%), and idiopathic rhegmatogenous retinal detachment had the lowest likelihood of postoperative visual decline (4.65%). CONCLUSION: Myopia and congenital or developmental disease are the leading etiologies of pediatric rhegmatogenous retinal detachment. Different etiologies are associated with distinctive outcomes, and congenital and developmental diseases are independent prognostic factors of a poor response.
Assuntos
Traumatismos Oculares/complicações , Miopia/complicações , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Descolamento Retiniano/etiologia , Acuidade Visual , Cirurgia Vitreorretiniana/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prognóstico , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
Blood testing for endogenous small metabolites to determine physiological and biochemical states is routine for laboratory analysis. Here we demonstrate that by combining the commercial direct analysis in real time (DART) ion source with an ion trap mass spectrometer, native cholesterol in its free alcohol form is readily detected from a few hundred nanoliters of human serum loaded onto chromatography paper. Deuterium-labeled cholesterol was used as the internal standard to obtain the absolute quantity of the endogenous cholesterol. The amount of the cholesterol measured by this paper-loaded DART mass spectrometry (pDART-MS) is statistically comparable with that obtained by using commercially available fluorometric-enzymatic assay and liquid chromatography/mass spectrometry. Furthermore, sera from 21 participants at three different time points in an ultramarathon were collected to obtain their cholesterol levels. The test requires only very minimal sample preparation, and the concentrations of cholesterol in each sample were acquired within a minute.
Assuntos
Colesterol/sangue , Papel , Colesterol/química , Cromatografia Líquida , Humanos , Espectrometria de Massas , Fatores de TempoRESUMO
OBJECTIVES: To evaluate respiratory outcomes in preterm infants with retinopathy of prematurity (ROP) following intravitreal bevacizumab injection (IVB). METHODS: This single-centre study enroled preterm infants with a gestational age (GA) < 34 weeks or a birth weight (BW) < 1500 g with bilateral type 1 ROP who received a single IVB, and a treatment-free control group matched by GA, postmenstrual age, and respiratory status at the time of the IVB. The primary outcome was serial respiratory changes in mean airway pressure (MAP), fraction of inspired oxygen (FiO2), and respiratory severity score (RSS, MAP x FiO2) during the 28-day post-IVB/matching period and overall respiratory improvement at day 28 and at discharge. The duration of supplemental oxygen therapy following IVB/matching was documented. RESULTS: A total of 5578 infants were included. Seventy-eight infants were enroled in the IVB group, and another 78 infants were matched as the control group. Both groups had downward trends in the MAP, FiO2, and RSS over the study period (all P < 0.001), but there were no between-group differences in these measures. The percentage of overall respiratory improvement was similar between the IVB and control groups, so was the duration of invasive and in-hospital oxygen ventilation. A lower percentage of oxygen dependence at discharge in the IVB group (P = 0.03) remained significant after adjusting for GA and BW. CONCLUSIONS: This is a matched case study to evaluate respiratory outcomes in preterm infants following IVB for ROP. We found that the IVBs did not compromise respiratory outcomes in preterm infants during the 28-day post-IVB period and at discharge.
Assuntos
Recém-Nascido Prematuro , Retinopatia da Prematuridade , Lactente , Recém-Nascido , Humanos , Bevacizumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Retinopatia da Prematuridade/tratamento farmacológico , Idade Gestacional , Peso ao Nascer , Injeções Intravítreas , Estudos Retrospectivos , OxigênioRESUMO
Mass spectrometry imaging (MSI) using the ambient ionization technique enables a direct chemical investigation of biological samples with minimal sample pretreatment. However, detailed morphological information of the sample is often lost due to its limited spatial resolution. In this study, predictive high-resolution molecular imaging was produced by the fusion of ambient ionization MSI with optical microscopy of routine hematoxylin and eosin (H&E) staining. Specifically, desorption electrospray ionization (DESI) and nanospray desorption electrospray ionization (nanoDESI) mass spectrometry were employed to visualize lipid and protein species on mice tissue sections. The resulting molecular distributions obtained by ambient ionization MSI-microscopy fusion were verified with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MSI and immunohistochemistry (IHC) staining. Label-free molecular imaging with 5-µm spatial resolution can be acquired using DESI and nanoDESI, whereas the typical spatial resolution of ambient ionization MSI was â¼100⯵m. In this regard, sharpened molecular histology of tissue sections was achieved, providing complementary references to the pathology. Such a multi-modal integration enables the discovery of potential tumor biomarkers. After image fusion, more than a dozen potential biomarkers on a metastatic mouse lung tissue section and Luminal B breast tumor tissue section were identified.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/diagnóstico por imagem , Lipídeos/análise , Neoplasias Pulmonares/diagnóstico por imagem , Proteínas de Neoplasias/análise , Imagem Óptica , Animais , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos ICR , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Cholesterol is an important lipid molecule in cell membranes and lipoproteins. Cholesterol is also a precursors of steroid hormones, bile acids, and vitamin D. Abnormal levels of cholesterol or its precursors have been observed in various human diseases, such as heart diseases, stroke, type II diabetes, brain diseases and many others. Therefore, accurate quantification of cholesterol is important for individuals who are at increased risk for these diseases. Multiple analytical methods have been developed for analysis of cholesterol, including classical chemical methods, enzymatic assays, gas chromatography (GC), liquid chromatography (LC), and mass spectrometry (MS). Strategy known as ambient ionization mass spectrometry (AIMS), operating at atmospheric pressure, with only minimal sample pretreatments for real time, in situ, and rapid interrogation of the sample has also been employed for quantification of cholesterol. In this review, we summarize the most prevalent methods for cholesterol quantification in biological samples and foods. Nevertheless, we highlight several new technologies, such as AIMS, used as alternative methods to measure cholesterol that are potentially next-generation platforms. Representative examples of molecular imaging of cholesterol in tissue sections are also included in this review article.
Assuntos
Colesterol/análise , Cromatografia Gasosa , Cromatografia Líquida , Ensaios Enzimáticos , Humanos , Espectrometria de Massas , Estrutura MolecularRESUMO
The integration of quadruple therapy in a 13-year-old boy with stage 3B Coats' disease achieved retinal reattachment and visual improvement. Scleral buckling might play a role in retinal detachment in Coats' disease, although it has previously been considered insignificant. Instead of performing vitrectomy and internal drainage with a drainage hole in the retina, less-invasive procedures that do not require retinotomy appear to be beneficial in cases of advanced Coats' disease. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:865-868.].
Assuntos
Bevacizumab/administração & dosagem , Drenagem/métodos , Fotocoagulação a Laser/métodos , Retina/patologia , Descolamento Retiniano/terapia , Telangiectasia Retiniana/complicações , Recurvamento da Esclera/métodos , Adolescente , Inibidores da Angiogênese/administração & dosagem , Humanos , Injeções Intravítreas , Masculino , Retina/cirurgia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Telangiectasia Retiniana/diagnóstico , Telangiectasia Retiniana/tratamento farmacológico , Esclera , Índice de Gravidade de Doença , Líquido Sub-Retiniano , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade VisualRESUMO
OBJECTIVE: The purpose of this study was to prospectively investigate the degree of pain experienced by the patients receiving transrectal ultrasonography (TRUS) of the prostate by applying a visual analog scale. We also identified the clinical parameters influencing pain during the TRUS examination. MATERIALS AND METHODS: Records were obtained from a prospective database for male patients who received TRUS of prostate in the outpatient department of Chang Gung Memorial Hospital, Taiwan, from January 2014 to June 2014. The patients underwent a detailed physical examination and medical history review. Immediately after the TRUS examination, the patients completed questionnaires based on a ten-point visual analog pain scale. The variables of interest were age, body mass index, prostate volume, prostate sagittal length, prostate-specific antigen, previous TRUS experience, external hemorrhoids, anal surgical history, prostate calcification, and image artifact caused by stool in the rectum. All variables were correlated to the visual analog scale by applying multivariate regression analysis. RESULTS: By using linear regression analysis, we identified the independent factors that affected the pain score during the TRUS examination. The patients who received the examination for the first time or had longer prostate sagittal lengths, external hemorrhoids, anal surgical history, or stool stored in the rectum experienced more pain during the TRUS examination. Furthermore, the pain was reduced when we provided the patients with a detailed explanation before the procedure and allowed them to observe the real-time images during the examination. CONCLUSION: Although a TRUS examination is uncomfortable for patients, after having identified the factors affecting pain, physicians can assist patients in reducing pain during the procedure, thus providing higher quality examinations.