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1.
Nucleic Acids Res ; 52(W1): W398-W406, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38587201

RESUMEN

We introduce MetaboAnalyst version 6.0 as a unified platform for processing, analyzing, and interpreting data from targeted as well as untargeted metabolomics studies using liquid chromatography - mass spectrometry (LC-MS). The two main objectives in developing version 6.0 are to support tandem MS (MS2) data processing and annotation, as well as to support the analysis of data from exposomics studies and related experiments. Key features of MetaboAnalyst 6.0 include: (i) a significantly enhanced Spectra Processing module with support for MS2 data and the asari algorithm; (ii) a MS2 Peak Annotation module based on comprehensive MS2 reference databases with fragment-level annotation; (iii) a new Statistical Analysis module dedicated for handling complex study design with multiple factors or phenotypic descriptors; (iv) a Causal Analysis module for estimating metabolite - phenotype causal relations based on two-sample Mendelian randomization, and (v) a Dose-Response Analysis module for benchmark dose calculations. In addition, we have also improved MetaboAnalyst's visualization functions, updated its compound database and metabolite sets, and significantly expanded its pathway analysis support to around 130 species. MetaboAnalyst 6.0 is freely available at https://www.metaboanalyst.ca.


Asunto(s)
Algoritmos , Metabolómica , Programas Informáticos , Espectrometría de Masas en Tándem , Metabolómica/métodos , Cromatografía Liquida , Humanos , Bases de Datos Factuales
2.
PLoS Comput Biol ; 20(6): e1011912, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38843301

RESUMEN

To standardize metabolomics data analysis and facilitate future computational developments, it is essential to have a set of well-defined templates for common data structures. Here we describe a collection of data structures involved in metabolomics data processing and illustrate how they are utilized in a full-featured Python-centric pipeline. We demonstrate the performance of the pipeline, and the details in annotation and quality control using large-scale LC-MS metabolomics and lipidomics data and LC-MS/MS data. Multiple previously published datasets are also reanalyzed to showcase its utility in biological data analysis. This pipeline allows users to streamline data processing, quality control, annotation, and standardization in an efficient and transparent manner. This work fills a major gap in the Python ecosystem for computational metabolomics.


Asunto(s)
Metabolómica , Programas Informáticos , Metabolómica/métodos , Metabolómica/estadística & datos numéricos , Biología Computacional/métodos , Lipidómica/métodos , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Lenguajes de Programación , Humanos
3.
Eur Spine J ; 33(8): 3242-3260, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38955868

RESUMEN

OBJECTIVE: This study aimed to develop and validate a predictive model for osteoporotic vertebral fractures (OVFs) risk by integrating demographic, bone mineral density (BMD), CT imaging, and deep learning radiomics features from CT images. METHODS: A total of 169 osteoporosis-diagnosed patients from three hospitals were randomly split into OVFs (n = 77) and Non-OVFs (n = 92) groups for training (n = 135) and test (n = 34). Demographic data, BMD, and CT imaging details were collected. Deep transfer learning (DTL) using ResNet-50 and radiomics features were fused, with the best model chosen via logistic regression. Cox proportional hazards models identified clinical factors. Three models were constructed: clinical, radiomics-DTL, and fusion (clinical-radiomics-DTL). Performance was assessed using AUC, C-index, Kaplan-Meier, and calibration curves. The best model was depicted as a nomogram, and clinical utility was evaluated using decision curve analysis (DCA). RESULTS: BMD, CT values of paravertebral muscles (PVM), and paravertebral muscles' cross-sectional area (CSA) significantly differed between OVFs and Non-OVFs groups (P < 0.05). No significant differences were found between training and test cohort. Multivariate Cox models identified BMD, CT values of PVM, and CSAPS reduction as independent OVFs risk factors (P < 0.05). The fusion model exhibited the highest predictive performance (C-index: 0.839 in training, 0.795 in test). DCA confirmed the nomogram's utility in OVFs risk prediction. CONCLUSION: This study presents a robust predictive model for OVFs risk, integrating BMD, CT data, and radiomics-DTL features, offering high sensitivity and specificity. The model's visualizations can inform OVFs prevention and treatment strategies.


Asunto(s)
Densidad Ósea , Osteoporosis , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Tomografía Computarizada por Rayos X , Humanos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/epidemiología , Femenino , Masculino , Anciano , Fracturas Osteoporóticas/diagnóstico por imagen , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , Osteoporosis/complicaciones , Densidad Ósea/fisiología , Medición de Riesgo/métodos , Factores de Riesgo , Anciano de 80 o más Años , Aprendizaje Profundo
4.
Medicine (Baltimore) ; 103(18): e38010, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38701318

RESUMEN

Accumulating evidences have indicated that lipid-lowering drugs have effect for the treatment of cancers. However, causal associations between lipid-lowering drugs and the risk of cancers are still unclear. In our study, we utilized single nucleotide polymorphisms of proprotein convertase subtilis kexin 9 (PCSK9) inhibitors and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors and performed a drug target Mendelian randomization to explore the causal association between lipid-lowering drugs and the risk of cancers. Five regression methods were carried out, including inverse variance weighted (IVW) method, MR Egger, weighted median, simple mode and weighted mode methods, of which IVW method was considered as the main analysis. Our outcome dataset contained the risk of breast cancer (BC), colorectal cancer, endometrial cancer, gastric cancer (GC), hepatocellular carcinoma (HCC), lung cancer, esophageal cancer, prostate cancer (PC), and skin cancer (SC). Our results demonstrated that PCSK9 inhibitors were significant associated with a decreased effect of GC [IVW: OR = 0.482, 95% CI: 0.264-0.879, P = .017]. Besides, genetic inhibitions of HMGCR were significant correlated with an increased effect of BC [IVW: OR = 1.421, 95% CI: 1.056-1.911, P = .020], PC [IVW: OR = 1.617, 95% CI: 1.234-2.120, P = .0005] and SC [IVW: OR = 1.266, 95% CI: 1.022-1.569, P = .031]. For GC [IVW: OR = 0.559, 95% CI: 0.382-0.820, P = .0029] and HCC [IVW: OR = 0.241, 95% CI: 0.085-0.686, P = .0077], HMGCR inhibitors had a protective risk. Our method suggested that PCSK9 inhibitors were significant associated with a protective effect of GC. Genetic inhibitions of HMGCR were significant correlated with an increased effect of BC, PC and SC. Meanwhile, HMGCR inhibitors had a protective risk of GC and HCC. Subsequent studies still needed to assess potential effects between lipid-lowering drugs and the risk of cancers with clinical trials.


Asunto(s)
Hidroximetilglutaril-CoA Reductasas , Análisis de la Aleatorización Mendeliana , Neoplasias , Polimorfismo de Nucleótido Simple , Proproteína Convertasa 9 , Humanos , Neoplasias/genética , Neoplasias/epidemiología , Hidroximetilglutaril-CoA Reductasas/genética , Femenino , Inhibidores de PCSK9 , Hipolipemiantes/uso terapéutico , Masculino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico
5.
Medicine (Baltimore) ; 103(17): e37735, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669367

RESUMEN

Growing evidences of recent studies have shown that gut microbrome are causally related to digestive system diseases (DSDs). However, causal relationships between the gut microbiota and the risk of DSDs still remain unclear. We utilized identified gut microbiota based on class, family, genus, order and phylum information and digestive system diseases genome-wide association study (GWAS) dataset for two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used to evaluate causal relationships between gut microbiota and 7 DSDs, including chronic gastritis, colorectal cancer, Crohn's disease, gastric cancer, gastric ulcer, irritable bowel syndrome and esophageal cancer. Finally, we verified the robustness of MR results based on heterogeneity and pleiotropy analysis. We discovered 15 causal associations with genetic liabilities in the gut microbiota and DSDs, such as genus Victivallis, genus RuminococcaceaeUCG005, genus Ruminococcusgauvreauiigroup, genus Oxalobacter and so on. Our MR analysis revealed that the gut microbiota is causally associated with DSDs. Further researches of the gut microbiota and the pathogenesis of DSDs are still significant and provide new methods for the prevention and treatment of DSDs.


Asunto(s)
Enfermedades del Sistema Digestivo , Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Microbioma Gastrointestinal/genética , Enfermedades del Sistema Digestivo/microbiología , Enfermedades del Sistema Digestivo/genética
6.
Nat Commun ; 15(1): 3675, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693118

RESUMEN

The wide applications of liquid chromatography - mass spectrometry (LC-MS) in untargeted metabolomics demand an easy-to-use, comprehensive computational workflow to support efficient and reproducible data analysis. However, current tools were primarily developed to perform specific tasks in LC-MS based metabolomics data analysis. Here we introduce MetaboAnalystR 4.0 as a streamlined pipeline covering raw spectra processing, compound identification, statistical analysis, and functional interpretation. The key features of MetaboAnalystR 4.0 includes an auto-optimized feature detection and quantification algorithm for LC-MS1 spectra processing, efficient MS2 spectra deconvolution and compound identification for data-dependent or data-independent acquisition, and more accurate functional interpretation through integrated spectral annotation. Comprehensive validation studies using LC-MS1 and MS2 spectra obtained from standards mixtures, dilution series and clinical metabolomics samples have shown its excellent performance across a wide range of common tasks such as peak picking, spectral deconvolution, and compound identification with good computing efficiency. Together with its existing statistical analysis utilities, MetaboAnalystR 4.0 represents a significant step toward a unified, end-to-end workflow for LC-MS based global metabolomics in the open-source R environment.


Asunto(s)
Espectrometría de Masas , Metabolómica , Flujo de Trabajo , Algoritmos , Cromatografía Liquida/métodos , Cromatografía Líquida con Espectrometría de Masas , Espectrometría de Masas/métodos , Metabolómica/métodos , Programas Informáticos
7.
bioRxiv ; 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38405981

RESUMEN

To standardize metabolomics data analysis and facilitate future computational developments, it is essential is have a set of well-defined templates for common data structures. Here we describe a collection of data structures involved in metabolomics data processing and illustrate how they are utilized in a full-featured Python-centric pipeline. We demonstrate the performance of the pipeline, and the details in annotation and quality control using large-scale LC-MS metabolomics and lipidomics data and LC-MS/MS data. Multiple previously published datasets are also reanalyzed to showcase its utility in biological data analysis. This pipeline allows users to streamline data processing, quality control, annotation, and standardization in an efficient and transparent manner. This work fills a major gap in the Python ecosystem for computational metabolomics.

8.
Environ Toxicol Chem ; 43(4): 772-783, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38116984

RESUMEN

Understanding species differences in sensitivity to toxicants is a critical issue in ecotoxicology. We recently established that double-crested cormorant (DCCO) embryos are more sensitive than Japanese quail (JQ) to the developmental effects of ethinylestradiol (EE2). We explored how this difference in sensitivity between species is reflected at a transcriptomic level. The EE2 was dissolved in dimethyl sulfoxide and injected into the air cell of eggs prior to incubation at nominal concentrations of 0, 3.33, and 33.3 µg/g egg weight. At midincubation (JQ 9 days; DCCO 16 days), livers were collected from five embryos/treatment group for RNA sequencing. Data were processed and analyzed using EcoOmicsAnalyst and ExpressAnalyst. The EE2 exposure dysregulated 238 and 1,987 genes in JQ and DCCO, respectively, with 78 genes in common between the two species. These included classic biomarkers of estrogen exposure such as vitellogenin and apovitellenin. We also report DCCO-specific dysregulation of Phase I/II enzyme-coding genes and species-specific transcriptional ontogeny of vitellogenin-2. Twelve Kyoto Encyclopedia of Genes and Genomes pathways and two EcoToxModules were dysregulated in common in both species including the peroxisome proliferator-activated receptor (PPAR) signaling pathway and fatty acid metabolism. Similar to previously reported differences at the organismal level, DCCO were more responsive to EE2 exposure than JQ at the gene expression level. Our description of differences in transcriptional responses to EE2 in early life stage birds may contribute to a better understanding of the molecular basis for species differences. Environ Toxicol Chem 2024;43:772-783. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Asunto(s)
Coturnix , Etinilestradiol , Animales , Etinilestradiol/toxicidad , Coturnix/genética , Vitelogeninas , Perfilación de la Expresión Génica , Hígado
9.
Sci Total Environ ; 929: 171926, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38547991

RESUMEN

Carbon emissions caused by economic growth are the main cause of global warming, but controlling economic growth to reduce carbon emissions does not meet China's conditions. Therefore, how to synergize economic growth and carbon emission reduction is not only a sustainable development issue for China, but also significant for mitigating global warming. The territorial spatial functional pattern (TSFP) is the spatial carrier for coordinating economic development and carbon emissions, but how to establish the TSFP of synergizing economic growth and carbon emission reduction remains unresolved. We propose a decision framework for optimizing TSFP coupled with the multi-objective fuzzy linear programming and the patch-generating land use simulation model, to provide a new path to synergize economic growth and carbon emission reduction in China. To confirm the reliability, we took Qionglai City as the demonstration. The results found a significant spatiotemporal coupling between TSFP and the synergistic states between economic growth and carbon emission reduction (q ≥ 0.8220), which resolves the theoretical uncertainty about synergizing economic growth and carbon emission reduction through the path of TSFP optimization. The urban space of Qionglai City in 2025 and 2030 obtained by the decision framework was 6497.57 hm2 and 6628.72 hm2 respectively, distributed in the central and eastern regions; the rural space was 60,132.92 hm2 and 56,084.97 hm2, concentrated in the east, with a few located in the west; and the ecological space was 71,072.52 hm2 and 74,998.31 hm2, mainly located in the western and southeastern areas. Compared with the TSFP in 2020, the carbon emission intensity of the TSFP obtained by the decision framework was reduced by 0.7 and 4.7 tons/million yuan, respectively, and realized the synergy between economic growth and carbon emission reduction (decoupling index was 0.25 and 0.21). Further confirming that TSFP optimization is an effective way to synergize economic growth and carbon emission reduction, which can provide policy implications for coordinating economic growth and carbon emissions for China and even similar developing countries.

10.
Nat Protoc ; 19(5): 1467-1497, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38355833

RESUMEN

The growing number of multi-omics studies demands clear conceptual workflows coupled with easy-to-use software tools to facilitate data analysis and interpretation. This protocol covers three key components involved in multi-omics analysis, including single-omics data analysis, knowledge-driven integration using biological networks and data-driven integration through joint dimensionality reduction. Using the dataset from a recent multi-omics study of human pancreatic islet tissue and plasma samples, the first section introduces how to perform transcriptomics/proteomics data analysis using ExpressAnalyst and lipidomics data analysis using MetaboAnalyst. On the basis of significant features detected in these workflows, the second section demonstrates how to perform knowledge-driven integration using OmicsNet. The last section illustrates how to perform data-driven integration from the normalized omics data and metadata using OmicsAnalyst. The complete protocol can be executed in ~2 h. Compared with other available options for multi-omics integration, the Analyst software suite described in this protocol enables researchers to perform a wide range of omics data analysis tasks via a user-friendly web interface.


Asunto(s)
Internet , Metabolómica , Proteómica , Programas Informáticos , Humanos , Metabolómica/métodos , Proteómica/métodos , Islotes Pancreáticos/metabolismo , Biología Computacional/métodos , Lipidómica/métodos , Genómica/métodos , Multiómica
11.
Brain Imaging Behav ; 18(3): 622-629, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38332385

RESUMEN

This study aimed to identify damaged segments of brain white matter fiber tracts in patients with systemic lupus erythematosus (SLE) using diffusion tensor imaging (DTI)-based automated fiber quantification (AFQ), and analyze their relationship with cognitive impairment. Clinical and imaging data for 39 female patients with SLE and for 44 female healthy controls (HCs) were collected. AFQ was used to track whole-brain white matter tracts in each participant, and each tract was segmented into 100 equally spaced nodes. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated at each node. Correlations were also explored between DTI metrics in the damaged segments of white matter fiber tracts and neuropsychological test scores of patients with SLE. Compared with HCs, SLE patients exhibited significantly lower FA values, and significantly higher MD, AD, RD values in many white matter tracts (all P < 0.05, false discovery rate-corrected). FA values in nodes 97-100 of the left inferior fronto-occipital fasciculus (IFOF) positively correlated with the mini-mental state examination score. AFQ enables precise and accurate identification of damage to white matter fiber tracts in brains of patients with SLE. FA values in the left IFOF correlate with cognitive impairment in SLE.


Asunto(s)
Encéfalo , Imagen de Difusión Tensora , Lupus Eritematoso Sistémico , Sustancia Blanca , Humanos , Femenino , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Imagen de Difusión Tensora/métodos , Lupus Eritematoso Sistémico/diagnóstico por imagen , Lupus Eritematoso Sistémico/patología , Lupus Eritematoso Sistémico/complicaciones , Adulto , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Pruebas Neuropsicológicas , Anisotropía , Persona de Mediana Edad , Procesamiento de Imagen Asistido por Computador/métodos
12.
Front Endocrinol (Lausanne) ; 15: 1370838, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38606087

RESUMEN

Purpose: To develop and validate a deep learning radiomics (DLR) model that uses X-ray images to predict the classification of osteoporotic vertebral fractures (OVFs). Material and methods: The study encompassed a cohort of 942 patients, involving examinations of 1076 vertebrae through X-ray, CT, and MRI across three distinct hospitals. The OVFs were categorized as class 0, 1, or 2 based on the Assessment System of Thoracolumbar Osteoporotic Fracture. The dataset was divided randomly into four distinct subsets: a training set comprising 712 samples, an internal validation set with 178 samples, an external validation set containing 111 samples, and a prospective validation set consisting of 75 samples. The ResNet-50 architectural model was used to implement deep transfer learning (DTL), undergoing -pre-training separately on the RadImageNet and ImageNet datasets. Features from DTL and radiomics were extracted and integrated using X-ray images. The optimal fusion feature model was identified through least absolute shrinkage and selection operator logistic regression. Evaluation of the predictive capabilities for OVFs classification involved eight machine learning models, assessed through receiver operating characteristic curves employing the "One-vs-Rest" strategy. The Delong test was applied to compare the predictive performance of the superior RadImageNet model against the ImageNet model. Results: Following pre-training separately on RadImageNet and ImageNet datasets, feature selection and fusion yielded 17 and 12 fusion features, respectively. Logistic regression emerged as the optimal machine learning algorithm for both DLR models. Across the training set, internal validation set, external validation set, and prospective validation set, the macro-average Area Under the Curve (AUC) based on the RadImageNet dataset surpassed those based on the ImageNet dataset, with statistically significant differences observed (P<0.05). Utilizing the binary "One-vs-Rest" strategy, the model based on the RadImageNet dataset demonstrated superior efficacy in predicting Class 0, achieving an AUC of 0.969 and accuracy of 0.863. Predicting Class 1 yielded an AUC of 0.945 and accuracy of 0.875, while for Class 2, the AUC and accuracy were 0.809 and 0.692, respectively. Conclusion: The DLR model, based on the RadImageNet dataset, outperformed the ImageNet model in predicting the classification of OVFs, with generalizability confirmed in the prospective validation set.


Asunto(s)
Aprendizaje Profundo , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Humanos , Fracturas Osteoporóticas/diagnóstico por imagen , Radiómica , Distribución Aleatoria , Fracturas de la Columna Vertebral/diagnóstico por imagen , Columna Vertebral , Rayos X
13.
Environ Toxicol Chem ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39073395

RESUMEN

Efforts to use transcriptomics for toxicity testing have classically relied on the assumption that chemicals consistently produce characteristic transcriptomic signatures that are reflective of their mechanism of action. However, the degree to which transcriptomic responses are conserved across different test methodologies has seldom been explored. With increasing regulatory demand for New Approach Methods (NAMs) that use alternatives to animal models and high-content approaches such as transcriptomics, this type of comparative analysis is needed. We examined whether common genes are dysregulated in Japanese quail (Coturnix japonica) liver following sublethal exposure to the flame retardant hexabromocyclododecane (HBCD), when life stage and test methodologies differ. The four exposure scenarios included one NAM: Study 1-early-life stage (ELS) exposure via a single egg injection, and three more traditional approaches; Study 2-adult exposure using a single oral gavage; Study 3-ELS exposure via maternal deposition after adults were exposed through their diet for 7 weeks; and Study 4-ELS exposure via maternal deposition and re-exposure of nestlings through their diet for 17 weeks. The total number of differentially expressed genes (DEGs) detected in each study was variable (Study 1, 550; Study 2, 192; Study 3, 1; Study 4, 3) with only 19 DEGs shared between Studies 1 and 2. Factors contributing to this lack of concordance are discussed and include differences in dose, but also quail strain, exposure route, sampling time, and HBCD stereoisomer composition. The results provide a detailed overview of the transcriptomic responses to HBCD at different life stages and routes of exposure in a model avian species and highlight certain challenges and limits of comparing transcriptomics across different test methodologies. Environ Toxicol Chem 2024;00:1-11. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

14.
Pharmaceuticals (Basel) ; 17(7)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39065685

RESUMEN

Chemotherapy-induced peripheral neuropathy (CIPN) remains a clinical challenge for up to 80% of breast cancer survivors. In an open-label study, participants underwent three interventions: standard care (duloxetine) for 1 month (Phase 1), oral cannabidiol (CBD) for 2 months (Phase 2), and CBD plus multi-modal exercise (MME) for another 2 months (Phase 3). Clinical outcomes and gut microbiota composition were assessed at baseline and after each phase. We present the case of a 52-year-old female with a history of triple-negative breast cancer in remission for over five years presenting with CIPN. She showed decreased monocyte counts, c-reactive protein, and systemic inflammatory index after each phase. Duloxetine provided moderate benefits and intolerable side effects (hyperhidrosis). She experienced the best improvement and least side effects with the combined (CBD plus MME) phase. Noteworthy were clinically meaningful improvements in CIPN symptoms, quality of life (QoL), and perceived physical function, as well as improvements in pain, mobility, hand/finger dexterity, and upper and lower body strength. CBD and MME altered gut microbiota, showing enrichment of genera that produce short-chain fatty acids. CBD and MME may improve CIPN symptoms, QoL, and physical function through anti-inflammatory and neuroprotective effects in cancer survivors suffering from long-standing CIPN.

15.
Cell Metab ; 36(7): 1619-1633.e5, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38959864

RESUMEN

Population-level variation and mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized. We defined prototypical insulin secretion responses to three macronutrients in islets from 140 cadaveric donors, including those with type 2 diabetes. The majority of donors' islets exhibited the highest insulin response to glucose, moderate response to amino acid, and minimal response to fatty acid. However, 9% of donors' islets had amino acid responses, and 8% had fatty acid responses that were larger than their glucose-stimulated insulin responses. We leveraged this heterogeneity and used multi-omics to identify molecular correlates of nutrient responsiveness, as well as proteins and mRNAs altered in type 2 diabetes. We also examined nutrient-stimulated insulin release from stem cell-derived islets and observed responsiveness to fat but not carbohydrate or protein-potentially a hallmark of immaturity. Understanding the diversity of insulin responses to carbohydrate, protein, and fat lays the groundwork for personalized nutrition.


Asunto(s)
Diabetes Mellitus Tipo 2 , Secreción de Insulina , Insulina , Islotes Pancreáticos , Proteómica , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Femenino , Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Persona de Mediana Edad , Nutrientes/metabolismo , Adulto , Glucosa/metabolismo , Anciano , Ácidos Grasos/metabolismo
16.
medRxiv ; 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38496562

RESUMEN

Population level variation and molecular mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized despite ramifications for personalized nutrition. Here, we define prototypical insulin secretion dynamics in response to the three macronutrients in islets from 140 cadaveric donors, including those diagnosed with type 2 diabetes. While islets from the majority of donors exhibited the expected relative response magnitudes, with glucose being highest, amino acid moderate, and fatty acid small, 9% of islets stimulated with amino acid and 8% of islets stimulated with fatty acids had larger responses compared with high glucose. We leveraged this insulin response heterogeneity and used transcriptomics and proteomics to identify molecular correlates of specific nutrient responsiveness, as well as those proteins and mRNAs altered in type 2 diabetes. We also examine nutrient-responsiveness in stem cell-derived islet clusters and observe that they have dysregulated fuel sensitivity, which is a hallmark of functionally immature cells. Our study now represents the first comparison of dynamic responses to nutrients and multi-omics analysis in human insulin secreting cells. Responses of different people's islets to carbohydrate, protein, and fat lay the groundwork for personalized nutrition. ONE-SENTENCE SUMMARY: Deep phenotyping and multi-omics reveal individualized nutrient-specific insulin secretion propensity.

17.
bioRxiv ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38948734

RESUMEN

Comprehensive molecular and cellular phenotyping of human islets can enable deep mechanistic insights for diabetes research. We established the Human Islet Data Analysis and Sharing (HI-DAS) consortium to advance goals in accessibility, usability, and integration of data from human islets isolated from donors with and without diabetes at the Alberta Diabetes Institute (ADI) IsletCore. Here we introduce HumanIslets.com, an open resource for the research community. This platform, which presently includes data on 547 human islet donors, allows users to access linked datasets describing molecular profiles, islet function and donor phenotypes, and to perform various statistical and functional analyses at the donor, islet and single-cell levels. As an example of the analytic capacity of this resource we show a dissociation between cell culture effects on transcript and protein expression, and an approach to correct for exocrine contamination found in hand-picked islets. Finally, we provide an example workflow and visualization that highlights links between type 2 diabetes status, SERCA3b Ca2+-ATPase levels at the transcript and protein level, insulin secretion and islet cell phenotypes. HumanIslets.com provides a growing and adaptable set of resources and tools to support the metabolism and diabetes research community.

18.
Journal of Preventive Medicine ; (12): 325-329, 2020.
Artículo en Zh | WPRIM | ID: wpr-822752

RESUMEN

@#Severe acute respiratory syndrome coronavirus(SARS-CoV-2)is highly infectious and people are generally susceptible to it. In this article,we reviewed current research into the epidemiological characteristics of coronavirus disease 2019(COVID-19),introduced China's effective prevention and control experience,preliminarily summarized the phased Results of China's fight against the COVID-19,and reviewed the early measures taken by Singapore,Japan,Italy,Iran and South Korea. We recommended China’s prevention and control measures in response to COVID-19 to the world;appealed to pay attention to non-drug interventions,to strengthen the cooperation and sharing of COVID-19 epidemic data and research,to improve the global ability in respond to public health emergencies,and to reduce the impact of COVID-2019 on the sustainable development of economy and society.

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