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1.
Food Chem ; 400: 133998, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36055141

RESUMEN

Colostrum is essential for immune system development and has a protective role for infants in early life. However, the lipid compositions of human and ewe colostra have not been characterized. We hypothesized that lipidomics can be used to compare lipids in two mammalian colostra. Herein, 1004 lipids assigned to 26 subclasses were identified in both human and ewe colostra using a quantitative lipidomics approach. In total, 173 significantly different lipids (SDLs) were investigated (variable importance in projection > 1.1, fold change (FC) ≥ 2 or ≤0.5, and P < 0.0001). Four potential lipid biomarkers, namely, DG (19:0/18:0), TG (10:0/15:0/16:0), FFA (22:0), and TG (18:1/24:1/18:2), were selected from the 173 SDLs based on FC values. These different lipids were involved in 44 metabolic pathways, of which sphingolipid metabolism and glycerophospholipid metabolism were the major pathways. Our results improve the understanding of the differences between human and ewe colostra lipids.


Asunto(s)
Calostro , Lipidómica , Animales , Biomarcadores/metabolismo , Calostro/metabolismo , Femenino , Glicerofosfolípidos/metabolismo , Humanos , Metabolismo de los Lípidos , Lípidos , Mamíferos , Embarazo , Ovinos , Esfingolípidos
2.
Food Chem ; 400: 134038, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36067688

RESUMEN

Gellan gum (GG) is an anionic polysaccharide used as an additive in the food industry. However, the effect of GG on gut microbiota regulation and nonalcoholic fatty liver disease (NAFLD) has not yet been investigated. In vitro fermentation experiments have demonstrated that GG promoted the growth of probiotic strains such as Lactiplantibacillus rhamnosus and Bifidobacterium bifidum, producing metabolites beneficial to gut health. In mice, GG reduced hepatic triglyceride content, serum biomarkers, and body fat mass and weight gain induced by a high fat diet. Additionally, GG regulated the gut microbiota including Desulfovibrionales, Deferribacterales, Bacteroidales, and Lactobacillales at the order level and also promoted short-chain fatty acid production. Moreover, GG improved the expression of proteins related to hepatic inflammation and lipid metabolism. Taken together, GG ameliorated NAFLD, possibly by acting on the gut-liver axis via improving the gut health, indicating its potential as a food supplement and/or prebiotic against NAFLD.


Asunto(s)
Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Animales , Biomarcadores/metabolismo , Dieta Alta en Grasa/efectos adversos , Ácidos Grasos Volátiles/metabolismo , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/genética , Polisacáridos Bacterianos/farmacología , Triglicéridos/metabolismo
3.
Bioanalysis ; 14(14): 985-1004, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36066044

RESUMEN

Background: Industry-standard guidance on method development and validation of hybrid LC-MS/MS assays for protein biomarkers, particularly on evaluation of parallelism, is lacking. Methods: Using a protein endogenous to humans and mice as a model analyte, a quantitative hybrid LC-MS/MS workflow was developed using a surrogate matrix approach with a recombinant form of the protein as the calibrant. Results: The developed workflow identified a surrogate matrix, established parallelism between the surrogate and authentic matrices and assessed parallelism between the recombinant and authentic forms of the protein. The final method was qualified using precision and accuracy with recovery assessments. Conclusion: The established workflow can be used in future bioanalytical studies to develop effective hybrid LC-MS/MS methods for endogenous protein biomarkers.


Asunto(s)
Proteínas , Espectrometría de Masas en Tándem , Animales , Biomarcadores/metabolismo , Cromatografía Liquida/métodos , Humanos , Ratones , Espectrometría de Masas en Tándem/métodos , Flujo de Trabajo
4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 2920-2923, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36085927

RESUMEN

Single-cell RNA sequencing is a powerful method that helps delineate the regulatory mechanisms shaping the diverse cellular populations. Heterogeneous cell populations consist of individual cells, and the expression of distinct sets of genes can differentiate one sub-population of cells from another, as they are responsible for the emergence of distinct cellular phenotypes. Of particular importance are cells at transition states that bridge these different cellular phenotypes. In this study, we develop a method to identify the cells at transition states bridging different cellular phenotypes. Our approach is based on persistent homology, which enabled us to identify the group of cells located on the boundaries between different sub-populations of cells. We applied this method to study the reprogramming of human fibroblasts toward induced pluripotent stem cells using single-cell time-course data. Even though only the data that is representative of the early stages of the reprogramming process are analyzed, we are able to uncover transient cells bridging different cell sub-populations. The most prominent group of transient cells are found to be enriched for NANOG, which is a known stem cell transcription factor that takes part in the maintenance of pluripotency and other stem cell marker genes. Overall, our method can identify cells in transient states bridging major cellular phenotypes, even though they are only a small fraction of the overall cell population. We also discuss how this approach can link the topology of the surface of cellular transcripts and bring order to the transition between cellular states and how it automatically uncovers the underlying time process.


Asunto(s)
Reprogramación Celular , Células Madre Pluripotentes Inducidas , Biomarcadores/metabolismo , Fibroblastos/metabolismo , Humanos
5.
Br J Hosp Med (Lond) ; 83(8): 1-11, 2022 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-36066298

RESUMEN

The current diagnosis of acute kidney injury relies on the measurement of serum creatinine levels and urine output. However, both measures are subject to considerable limitations; for example, change in serum creatinine levels ideally requires a knowledge of baseline function that is often not available. Furthermore, creatinine levels are influenced by many factors including diet, drug therapy, muscle mass, gender and ethnicity, which may lead to underestimation of the extent of renal dysfunction. Similarly, urine output lacks both specificity and sensitivity as a marker of acute kidney injury given that oliguria may be an appropriate physiological response to a multitude of stressors and that output may be maintained until significant renal damage has already occurred. Given the well-documented consequences of acute kidney injury and the considerable burden associated with its development, much attention has focused on early identification of patients at high risk to try and improve outcomes. Many studies have focused on the identification of candidate molecules that may enable the early detection of individuals at risk of developing acute kidney injury, including constitutive proteins associated with kidney damage, as well as molecules upregulated in response to injury, non-renal products that may be filtered, reabsorbed or secreted by the kidney, and markers of renal stress. Such biomarkers may also aid stratification for adverse events, such as the need for kidney replacement therapy or progression to chronic kidney disease and end-stage kidney disease. This article discusses some of these novel biomarkers and assesses the role they may have in the understanding, management, diagnosis and prognostication of acute kidney injury.


Asunto(s)
Lesión Renal Aguda , Lesión Renal Aguda/diagnóstico , Biomarcadores/metabolismo , Creatinina/metabolismo , Humanos , Riñón , Terapia de Reemplazo Renal
6.
Cell Commun Signal ; 20(1): 145, 2022 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-36123730

RESUMEN

BACKGROUND: Exosomes are progressively known as significant mediators of cell-to-cell communication. They convey active biomolecules to target cells and have vital functions in several physiological and pathological processes, and show substantial promise as novel treatment strategies for diseases. METHODS: In this review study, we studied numerous articles over the past two decades published on application of exosomes in different diseases as well as on perspective and challenges in this field. RESULTS: The main clinical application of exosomes are using them as a biomarker, cell-free therapeutic agents, drug delivery carriers, basic analysis for exosome kinetics, and cancer vaccine. Different exosomes from human or plant sources are utilized in various clinical trials. Most researchers used exosomes from the circulatory system for biomarker experiments. Mesenchymal stem cells (MSCs) and dendritic cells (DCs) are two widely held cell sources for exosome use. MSCs-derived exosomes are commonly used for inflammation treatment and drug delivery, while DCs-exosomes are used to induce inflammation response in cancer patients. However, the clinical application of exosomes faces various questions and challenges. In addition, translation of exosome-based clinical trials is required to conform to specific good manufacturing practices (GMP). In this review, we summarize exosomes in the clinical trials according to the type of application and disease. We also address the main questions and challenges regarding exosome kinetics and clinical applications. CONCLUSIONS: Exosomes are promising platforms for treatment of many diseases in clinical trials. This exciting field is developing hastily, understanding of the underlying mechanisms that direct the various observed roles of exosomes remains far from complete and needs further multidisciplinary research in working with these small vesicles. Video Abstract.


Asunto(s)
Vacunas contra el Cáncer , Exosomas , Biomarcadores/metabolismo , Vacunas contra el Cáncer/metabolismo , Sistemas de Liberación de Medicamentos , Exosomas/metabolismo , Humanos , Inflamación/metabolismo
7.
Cell Death Dis ; 13(9): 805, 2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-36127346

RESUMEN

F-box only protein 22 (FBXO22) is a key subunit of the Skp1-Cullin 1-F-box protein (SCF) E3 ubiquitin ligase complex. Little is known regarding its biological function and underlying molecular mechanisms in regulating cervical cancer (CC) progression. In this study, we aim to explore the role and mechanism of FBXO22 in CC progression. The correlation between FBXO22 and clinicopathological characteristics of CC was analyzed by tissue microarray. MTT, colony formation, flow cytometry, Western blotting, qRT-PCR, protein half-life, co-immunoprecipitation, ubiquitination, and xenograft experiments were performed to assess the functions of FBXO22 and potential molecular mechanisms of FBXO22-mediated malignant progression in CC. The expression of FBXO22 protein in CC tissues was higher than that in adjacent non-tumor cervical tissues. Notably, high expression of FBXO22 was significantly associated with high histology grades, positive lymph node metastasis, and poor outcomes in CC patients. Functionally, ectopic expression of FBXO22 promoted cell viability in vitro and induced tumor growth in vivo, while knockdown of FBXO22 exhibited opposite effects. In addition, overexpression of FBXO22 promoted G1/S phase progression and inhibited apoptosis in CC cells. Mechanistically, FBXO22 physically interacted with the cyclin-dependent kinase inhibitor p57Kip2 and subsequently mediated its ubiquitination and proteasomal degradation leading to tumor progression. FBXO22 protein level was found negatively associated with p57Kip2 protein levels in patient CC samples. FBXO22 promotes CC progression partly through regulating the ubiquitination and proteasomal degradation of p57Kip2. Our study indicates that FBXO22 might be a novel prognostic biomarker and therapeutic target for CC.


Asunto(s)
Proteínas F-Box , Neoplasias del Cuello Uterino , Biomarcadores/metabolismo , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/genética , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Femenino , Humanos , Receptores Citoplasmáticos y Nucleares/metabolismo , Ubiquitinación , Neoplasias del Cuello Uterino/genética
8.
Sci Rep ; 12(1): 15686, 2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-36127415

RESUMEN

Extracellular vesicles (EVs) are phospholipid bilayer vesicles released from cells, containing natural cargos. Microgreens of Raphanus sativus L. var. caudatus Alef were used in this study as the source of EVs. EVs were isolated by differential centrifugation. The physical properties were determined by dynamic light scattering (DLS) and electron microscopy. The biological and chemical composition were studied by Fourier-transform infrared (FTIR) microspectroscopy and high-performance liquid chromatography analysis, respectively. EVs had a median size of 227.17 and 234.90 ± 23.30 nm determined by electron microscopy and DLS, respectively with a polydispersity index of 0.293 ± 0.019. Electron microscopy indicated the intact morphology and confirmed the size. The FTIR spectra revealed that EVs are composed of proteins as the most abundant macromolecules. Using a curve-fitting analysis, ß-pleated sheets were the predominant secondary structure. Notably, the micromolecular biomarkers were not detected. EVs exerted anti-cancer activity on HCT116 colon cancer over Vero normal cells with an IC50 of 448.98 µg/ml and a selectivity index of > 2.23. To conclude, EVs could be successfully prepared with a simple and effective isolation method to contain nano-sized macromolecules possessing anti-cancer activity.


Asunto(s)
Vesículas Extracelulares , Raphanus , Biomarcadores/metabolismo , Núcleo Caudado/metabolismo , Proliferación Celular , Vesículas Extracelulares/metabolismo , Células HCT116 , Humanos , Sustancias Macromoleculares/metabolismo , Fosfolípidos/metabolismo , Raphanus/metabolismo
9.
PLoS One ; 17(9): e0274623, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36129929

RESUMEN

Three-dimensional (3D) cell culture technologies, which more closely mimic the complex microenvironment of tissue, are being increasingly evaluated as a tool for the preclinical screening of clinically promising new molecules, and studying of tissue metabolism. Studies of metabolites released into the extracellular space (secretome) allow understanding the metabolic dynamics of tissues and changes caused by therapeutic interventions. Although quite advanced in the field of proteomics, studies on the secretome of low molecular weight metabolites (< 1500 Da) are still very scarce. We present an untargeted metabolomic protocol based on the hybrid technique of liquid chromatography coupled with high-resolution mass spectrometry for the analysis of low-molecular-weight metabolites released into the culture medium by 3D cultures and co-culture (secretome model). For that we analyzed HT-29 human colon carcinoma cells and 3T3-L1 preadipocytes in 3D-monoculture and 3D-co-culture. The putative identification of the metabolites indicated a sort of metabolites, among them arachidonic acid, glyceric acid, docosapentaenoic acid and beta-Alanine which are related to cancer and obesity. This protocol represents a possibility to list metabolites released in the extracellular environment in a comprehensive and untargeted manner, opening the way for the generation of metabolic hypotheses that will certainly contribute to the understanding of tissue metabolism, tissue-tissue interactions, and metabolic responses to the most varied interventions. Moreover, it brings the potential to determine novel pathways and accurately identify biomarkers in cancer and other diseases. The metabolites indicated in our study have a close relationship with the tumor microenvironment in accordance with the literature review.


Asunto(s)
Neoplasias del Colon , Secretoma , Ácido Araquidónico , Biomarcadores/metabolismo , Cromatografía Liquida/métodos , Técnicas de Cocultivo , Humanos , Espectrometría de Masas/métodos , Metabolómica/métodos , Microambiente Tumoral , beta-Alanina/metabolismo
10.
Nat Commun ; 13(1): 5538, 2022 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-36130949

RESUMEN

Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived cell-free fetal DNA (cffDNA) significantly overlapped with DMRs from infant brain. The DMRs were enriched for neurodevelopmental functions, methylation-sensitive developmental transcription factor motifs, and human NDD DMRs identified from brain and placenta. Brain and cffDNA methylation levels from a large region overlapping mir-663 correlated with maternal obesity, metabolic and immune markers, and infant behavior. A DUX4 hippocampal co-methylation network correlated with maternal obesity, infant behavior, infant hippocampal lipidomic and metabolomic profiles, and maternal blood measurements of DUX4 cffDNA methylation, cytokines, and metabolites. We conclude that in this model, maternal obesity was associated with changes in the infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic factors.


Asunto(s)
Ácidos Nucleicos Libres de Células , Obesidad Materna , Animales , Biomarcadores/metabolismo , Encéfalo/metabolismo , Ácidos Nucleicos Libres de Células/metabolismo , Citocinas/metabolismo , ADN/metabolismo , Metilación de ADN , Epigénesis Genética , Femenino , Humanos , Lactante , Macaca mulatta/genética , Embarazo , Factores de Transcripción/metabolismo
11.
Oxid Med Cell Longev ; 2022: 2852251, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36132225

RESUMEN

Doxorubicin (DOX) is a class of effective chemotherapeutic agents widely used in clinical practice. However, its use has been limited by cardiotoxicity. The mechanism of DOX-induced cardiotoxicity (DIC) is complex, involving oxidative stress, Ca2+ overload, inflammation, pyroptosis, ferroptosis, apoptosis, senescence, etc. Exosomes (EXOs), as extracellular vesicles (EVs), play an important role in the material exchange and signal transmission between cells by carrying components such as proteins and RNAs. More recently, there has been a growing number of publications focusing on the protective effect of EXOs on DIC. Here, this review summarized the main mechanisms of DIC, discussed the mechanism of EXOs in the treatment of DIC, and further explored the value of EXOs as diagnostic biomarkers and therapeutic strategies for DIC.


Asunto(s)
Cardiotoxicidad , Exosomas , Apoptosis , Biomarcadores/metabolismo , Cardiotoxicidad/tratamiento farmacológico , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Dacarbazina/metabolismo , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Doxorrubicina/efectos adversos , Exosomas/metabolismo , Humanos , Miocitos Cardíacos/metabolismo , Estrés Oxidativo
12.
Oxid Med Cell Longev ; 2022: 5815843, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36132228

RESUMEN

Stroke is a neurological disease that causes significant disability and death worldwide. Ischemic stroke accounts for 75% of all strokes. The pathophysiological processes underlying ischemic stroke include oxidative stress, the toxicity of excitatory amino acids, ion disorder, enhanced apoptosis, and inflammation. Noncoding RNAs (ncRNAs) may have a vital role in regulating the pathophysiological processes of ischemic stroke, as confirmed by the altered expression of ncRNAs in blood samples from acute ischemic stroke patients, animal models, and oxygen-glucose-deprived (OGD) cell models. Due to specific changes in expression, ncRNAs can potentially be biomarkers for the diagnosis, treatment, and prognosis of ischemic stroke. As an important brain cell component, glial cells mediate the occurrence and progression of oxidative stress after ischemic stroke, and ncRNAs are an irreplaceable part of this mechanism. This review highlights the impact of ncRNAs in the oxidative stress process of ischemic stroke. It focuses on specific ncRNAs that underlie the pathophysiology of ischemic stroke and have potential as diagnostic biomarkers and therapeutic targets.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Biomarcadores/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Glucosa , Accidente Cerebrovascular Isquémico/genética , Estrés Oxidativo/genética , Oxígeno , ARN no Traducido/genética , ARN no Traducido/metabolismo , Accidente Cerebrovascular/metabolismo
13.
Biogerontology ; 23(5): 641-652, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36048311

RESUMEN

In the present study, attempts have been made to evaluate the potential role of 3 Bromopyruvate (3-BP) a glycolytic inhibitor and a caloric restriction mimetic (CRM), to exert neuroprotection in rats during aging through modulation of autophagy. Young male rats (4 months), and naturally aged (22 months) male rats were supplemented with 3-BP (30 mg/kg b.w., orally) for 28 days. Our results demonstrate a significant increase in the antioxidant biomarkers (ferric reducing antioxidant potential level, total thiol, superoxide dismutase, and catalase activities) and a decrease in the level of pro-oxidant biomarkers such as protein carbonyl after 3-BP supplementation in brain tissues. A significant increase in reactive oxygen species (ROS) was observed due to the mitohormetic effect of 3-BP supplementation in the treated rats. Furthermore, the 3-BP treatment also enhanced the activities of electron transport chain complexes I and IV in aged brain mitochondria thus proving its antioxidant potential at the level of mitochondria. Gene expression analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to assess the expression of autophagy, neuroprotective and aging marker genes. RT-PCR data revealed that 3-BP up-regulated the expression of autophagy markers genes (Beclin-1 and LC3 ß), sirtuin-1, and neuronal marker gene (NSE), respectively in the aging brain. The results suggest that 3-BP induces a mitohormetic effect through the elevation of ROS which reinforces defensive mechanism(s) targeted at regulating autophagy. These findings suggest that consistently low-dose 3-BP may be beneficial for neuroprotection during aging and age-related disorders.


Asunto(s)
Restricción Calórica , Neuroprotección , Envejecimiento/metabolismo , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Autofagia , Biomarcadores/metabolismo , Masculino , Estrés Oxidativo , Piruvatos , Ratas , Especies Reactivas de Oxígeno/metabolismo
14.
Oxid Med Cell Longev ; 2022: 7657876, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36071866

RESUMEN

The present review gathers together the most important information about variability in clusterin molecular structure, its profile, and the degree of glycosylation occurring in human tissues and body fluids in the context of the utility of these characteristics as potential diagnostic biomarkers of selected pathophysiological conditions. The carbohydrate part of clusterin plays a crucial role in many biological processes such as endocytosis and apoptosis. Many pathologies associated with neurodegeneration, carcinogenesis, metabolic diseases, and civilizational diseases (e.g., cardiovascular incidents and male infertility) have been described as causes of homeostasis disturbance, in which the glycan part of clusterin plays a very important role. The results of the discussed studies suggest that glycoproteomic analysis of clusterin may help differentiate the severity of hippocampal atrophy, detect the causes of infertility with an immune background, and monitor the development of cancer. Understanding the mechanism of clusterin (CLU) action and its binding epitopes may enable to indicate new therapeutic goals. The carbohydrate part of clusterin is considered necessary to maintain its proper molecular conformation, structural stability, and proper systemic and/or local biological activity. Taking into account the wide spectrum of CLU action and its participation in many processes in the human body, further studies on clusterin glycosylation variability are needed to better understand the molecular mechanisms of many pathophysiological conditions. They can also provide the opportunity to find new biomarkers and enrich the panel of diagnostic parameters for diseases that still pose a challenge for modern medicine.


Asunto(s)
Clusterina , Enfermedad , Glicosilación , Biomarcadores/metabolismo , Clusterina/metabolismo , Humanos , Polisacáridos
15.
Front Immunol ; 13: 983255, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36091042

RESUMEN

Background: During liver injury, liver sinusoidal endothelial cells (LSECs) dysfunction and capillarization promote liver fibrosis. We have previously reported that the LSEC vascular cell adhesion molecule 1 (VCAM1) plays a key role in liver inflammation in nonalcoholic steatohepatitis (NASH) and we now aim to uncover its role in LSEC capillarization and liver fibrosis. Methods: Wild-type C57BL/6J mice were fed either chow or high fat, fructose and cholesterol diet to induce NASH and treated with either anti-VCAM1 neutralizing antibody or control isotype antibody. Inducible endothelial cell-specific Vcam1 deleted mice (Vcam1Δend ) and control mice (Vcam1fl/fl ) were fed choline-deficient high-fat diet (CD-HFD) to induce NASH or injected with carbon tetrachloride to induce liver fibrosis. LSECs isolated from Vcam1fl/fl or Vcam1Δend and hepatic stellate cells (HSCs) isolated from wild-type mice were cocultured in a 3-D system or a µ-Slide 2 well co-culture system. Results: Immunostaining for Lyve1 (marker of differentiated LSECs) was reduced in Vcam1fl/fl mice and restored in Vcam1Δend mice in both NASH and liver fibrosis models. Co-immunostaining showed increased α-smooth muscle actin in the livers of Vcam1fl/fl mice in areas lacking Lyve1. Furthermore, scanning electron microscopy showed reduced LSEC fenestrae in the Vcam1fl/fl mice but not Vcam1Δend mice in both injury models, suggesting that VCAM1 promotes LSEC capillarization during liver injury. HSCs profibrogenic markers were reduced when cocultured with LSECs from CD-HFD fed Vcam1Δend mice compared to Vcam1fl/fl mice. Furthermore, recombinant VCAM1 activated the Yes-associated protein 1 pathway and induced a fibrogenic phenotype in HSCs in vitro, supporting the profibrogenic role of LSEC VCAM1. Conclusion: VCAM1 is not just a scaffold for leukocyte adhesion during liver injury, but also a modulator of LSEC capillarization and liver fibrosis.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Animales , Biomarcadores/metabolismo , Células Endoteliales/metabolismo , Cirrosis Hepática/patología , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/patología , Molécula 1 de Adhesión Celular Vascular/metabolismo
16.
Front Endocrinol (Lausanne) ; 13: 970489, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36072925

RESUMEN

Glycosylation is one of the most important post-translational modifications (PTMs) in a protein, and is the most abundant and diverse biopolymer in nature. Glycans are involved in multiple biological processes of cancer initiation and progression, including cell-cell interactions, cell-extracellular matrix interactions, tumor invasion and metastasis, tumor angiogenesis, and immune regulation. As an important biomarker, tumor-associated glycosylation changes have been extensively studied. This article reviews recent advances in glycosylation-based biomarker research, which is useful for cancer diagnosis and prognostic assessment. Truncated O-glycans, sialylation, fucosylation, and complex branched structures have been found to be the most common structural patterns in malignant tumors. In recent years, immunochemical methods, lectin recognition-based methods, mass spectrometry (MS)-related methods, and fluorescence imaging-based in situ methods have greatly promoted the discovery and application potentials of glycomic and glycoprotein biomarkers in various cancers. In particular, MS-based proteomics has significantly facilitated the comprehensive research of extracellular glycoproteins, increasing our understanding of their critical roles in regulating cellular activities. Predictive, preventive and personalized medicine (PPPM; 3P medicine) is an effective approach of early prediction, prevention and personalized treatment for different patients, and it is known as the new direction of medical development in the 21st century and represents the ultimate goal and highest stage of medical development. Glycosylation has been revealed to have new diagnostic, prognostic, and even therapeutic potentials. The purpose of glycosylation analysis and utilization of biology is to make a fundamental change in health care and medical practice, so as to lead medical research and practice into a new era of 3P medicine.


Asunto(s)
Glicómica , Neoplasias , Biomarcadores/metabolismo , Glicoproteínas/metabolismo , Glicosilación , Humanos , Neoplasias/diagnóstico , Neoplasias/metabolismo , Neoplasias/terapia , Polisacáridos
17.
Dis Markers ; 2022: 4000424, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36072900

RESUMEN

Background: Polycystic ovary syndrome (PCOS) is a complex class of endocrine disorders with insulin resistance, compensatory hyperinsulinemia, and obesity. However, the pathogenesis and therapies of PCOS have not been fully elucidated. Exosomal miRNAs have the potential to serve as biomarkers and therapies for a wide range of medical conditions. Method: We collected follicular fluid from 5 PCOS patients and 5 healthy people. High-throughput sequencing technology to identify differentially expressed miRNAs and untargeted metabolome identify differential metabolites in follicular fluid exosomal. RT-qPCR and AUC analysis were performed. Result: miRNA high-throughput sequencing identified 124 differential miRNAs. RT-qPCR analysis confirmed the sequencing results. These differential miRNA target genes are mainly involved in metabolic pathways. Metabolomics studies identified 31 differential metabolites. miRNA and lncRNA coexpression networks in metabolic pathways rigorously screened 28 differentially expressed miRNAs. This network would identify miRNA signatures associated with metabolic processes in PCOS. Meanwhile, the area under curve of receiver operating characteristic revealed that hsa-miR-196a-3p, hsa-miR-143-5p, hsa-miR-106a-3p, hsa-miR-34a-5p, and hsa-miR-20a-5p were potential biomarkers for the diagnosis of PCOS. Conclusion: Collectively, these results demonstrate the potential pathogenesis of PCOS, and follicular fluid exosomal miRNAs may be efficient targets for the diagnosis and treatment of PCOS in long-term clinical studies.


Asunto(s)
MicroARNs , Síndrome del Ovario Poliquístico , Biomarcadores/metabolismo , Femenino , Líquido Folicular/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Síndrome del Ovario Poliquístico/genética , Transcriptoma
18.
Oxid Med Cell Longev ; 2022: 9614819, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36046686

RESUMEN

Protein disulfide isomerase A3 (PDIA3) is a kind of thiol oxidoreductase with a wide range of functions, and its expression is elevated in a variety of tumors, which is closely related to the invasion and metastasis of tumor cells, and has a significant impact on the immunogenicity of tumor cells. Although more and more studies have shown that PDIA3 plays an important role in the occurrence and development of many tumors, there is no systematic pan-cancer study on PDIA3. Therefore, in this study, the differential expression of PDIA3 in 33 kinds of tumors was analyzed to explore its ability to regulate tumor immunity as a biomarker and evaluate its role in different cancer onset stages or clinical prognosis. In this paper, by analyzing the multilevel data including 33 kinds of cancers in the databases of Cancer Genome Atlas (TCGA), UCSC Xena, Cancer Cell Encyclopedia (CCLE), Genotypic Tissue Expression (GTEx), Human Protein Atlas (HPA), cBioPortal, and GDC; the differential expression level of PDIA3 in different types of malignant tumors and its relationship with prognosis and the potential correlation between PDIA3 expression and microsatellite instability (MSI), tumor mutation load (TMB), mismatch repair gene (MMR), DNA methylation level, and immune infiltration level were analyzed with bioinformatics. The results showed that PDIA3 was highly expressed in 19 types of cancers, but downregulated only in THCA. Next, PDIA3 in different tumors was positively or negatively correlated with patient outcome, Kaplan-Meier survival analysis showed that PDIA3 plays an important role in the prognosis of patients with KIRP, KICH, and CESC and may be used as a prognostic biomarker, and the methylation level of PDIA3 promoter region was closely related to patient outcome in eight tumors. The expression level of PDIA3 was correlated with TMB in 13 tumors and MSI in 9 tumors. Among them, the expression level of PDIA3 in THYM has the strongest correlation with TMB, and the expression level of PDIA3 in READ has the strongest correlation with MSI. In addition, the expression of PDIA3 in eight kinds of tumors, including BRCA, HNSC, THYM, LGG, LUAD, LUSC, PRAD, and THCA, had the highest correlation with the infiltration degree of immune cells, and the expression of PDIA3 had the highest correlation with the infiltration degree of 11 kinds of immune cells, including regulatory T cell and macrophages. And LGG is the tumor most likely to be affected by the tumor microenvironment to affect its development and prognosis. To sum up, this study suggests that PDIA3 plays an important role in the occurrence and development of KIRP, KICH, and CESC and in the immunotherapeutic response of THYM, READ, and LGG and can be used as a prognostic biomarker for these tumors.


Asunto(s)
Neoplasias , Proteína Disulfuro Isomerasas , Biomarcadores/metabolismo , Metilación de ADN/genética , Humanos , Factores Inmunológicos , Inmunoterapia , Neoplasias/genética , Neoplasias/terapia , Proteína Disulfuro Isomerasas/genética , Proteína Disulfuro Isomerasas/metabolismo , Microambiente Tumoral
19.
Oxid Med Cell Longev ; 2022: 2633123, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36062187

RESUMEN

Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases with high morbidity and mortality. Numerous studies have indicated that S100A12 may has an essential role in the occurrence and development of AMI, and in-depth studies are currently lacking. The purpose of this study is to investigate the effect of S100A12 on inflammation and oxidative stress and to determine its clinical applicability in AMI. Here, AMI datasets used to explore the expression pattern of S100A12 in AMI were derived from the Gene Expression Omnibus (GEO) database. The pooled standard average deviation (SMD) was calculated to further determine S100A12 expression. The overlapping differentially expressed genes (DEGs) contained in all included datasets were recognized by the GEO2R tool. Then, functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were carried out to determine the molecular function of overlapping DEGs. Gene set enrichment analysis (GSEA) was conducted to determine unrevealed mechanisms of S100A12. Summary receiver operating characteristic (SROC) curve analysis and receiver operating characteristic (ROC) curve analysis were carried out to identify the diagnostic capabilities of S100A12. Moreover, we screened miRNAs targeting S100A12 using three online databases (miRWalk, TargetScan, and miRDB). In addition, by comprehensively using enzyme-linked immunosorbent assay (ELISA), real-time quantitative PCR (RT-qPCR), Western blotting (WB) methods, etc., we used the AC16 cells to validate the expression and underlying mechanism of S100A12. In our study, five datasets related to AMI, GSE24519, GSE60993, GSE66360, GSE97320, and GSE48060 were included; 412 overlapping DEGs were identified. Protein-protein interaction (PPI) network and functional analyses showed that S100A12 was a pivotal gene related to inflammation and oxidative stress. Then, S100A12 overexpression was identified based on the included datasets. The pooled standard average deviation (SMD) also showed that S100A12 was upregulated in AMI (SMD = 1.36, 95% CI: 0.70-2.03, p = 0.024). The SROC curve analysis result suggested that S100A12 had remarkable diagnostic ability in AMI (AUC = 0.90, 95% CI: 0.87-0.92). And nine miRNAs targeting S100A12 were also identified. Additionally, the overexpression of S100A12 was further confirmed that it maybe promote inflammation and oxidative stress in AMI through comprehensive in vitro experiments. In summary, our study suggests that overexpressed S100A12 may be a latent diagnostic biomarker and therapeutic target of AMI that induces excessive inflammation and oxidative stress. Nine miRNAs targeting S100A12 may play a crucial role in AMI, but further studies are still needed. Our work provides a positive inspiration for the in-depth study of S100A12 in AMI.


Asunto(s)
Infarto del Miocardio , Proteína S100A12 , Biomarcadores/metabolismo , Humanos , Inflamación/genética , MicroARNs/metabolismo , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Estrés Oxidativo/genética , Proteína S100A12/genética
20.
J Transl Med ; 20(1): 399, 2022 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-36064568

RESUMEN

BACKGROUND: Peripheral biomarkers are increasingly vital non-invasive methods for monitoring coronary artery disease (CAD) progression. Their superiority in early detection, prognosis evaluation and classified diagnosis is becoming irreplaceable. Nevertheless, they are still less explored. This study aimed to determine and validate the diagnostic and therapeutic values of differentially expressed immune-related genes (DE-IRGs) in CAD. METHODS: We downloaded clinical information and RNA sequence data from the GEO database. We used R software, GO, KEGG and Cytoscape to analyze and visualize the data. A LASSO method was conducted to identify key genes for diagnostic model construction. The ssGSEA analysis was used to investigate the differential immune cell infiltration. Besides, we constructed CAD mouse model (low-density lipoprotein receptor deficient mice with high fat diet) to discover the correlation between the screened genes and severe CAD progress. We further uncovered the role of IL13RA1 might play in atherosclerosis. RESULTS: A total of 762 differential genes were identified between the peripheral blood of 218 controls and 199 CAD patients, which were significantly associated with infection, immune response and neural activity. 58 DE-IRGs were obtained by overlapping the differentially expressed genes(DEGs) and immune-related genes downloaded from ImmpDb database. Through LASSO regression, CCR9, CER1, CSF2, IL13RA1, INSL5, MBL2, MMP9, MSR1, NTS, TNFRSF19, CXCL2, HTR3C, IL1A, and NR4A2 were distinguished as peripheral biomarkers of CAD with eligible diagnostic capabilities in the training set (AUC = 0.968) and test set (AUC = 0.859). The ssGSEA analysis showed that the peripheral immune cells had characteristic distribution in CAD and also close relationship with specific DE-IRGs. RT-qPCR test showed that CCR9, CSF2, IL13RA1, and NTS had a significant correlation with LDLR-/- mice. IL13RA1 knocked down in RAW264.7 cell lines decreased SCARB1 and ox-LDL-stimulated CD36 mRNA expression, TGF-ß, VEGF-C and α-SMA protein levels and increased the production of IL-6, with downregulation of JAK1/STAT3 signal pathway. CONCLUSIONS: We constructed a diagnostic model of advanced-stage CAD based on the screened 14 DE-IRGs. We verified 4 genes of them to have a strong correlation with CAD, and IL13RA1 might participate in the inflammation, fibrosis, and cholesterol efflux process of atherosclerosis by regulating JAK1/STAT3 pathway.


Asunto(s)
Aterosclerosis , Enfermedad de la Arteria Coronaria , Animales , Aterosclerosis/genética , Biomarcadores/metabolismo , Enfermedad de la Arteria Coronaria/genética , Perfilación de la Expresión Génica , Ratones , Transducción de Señal/genética
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