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1.
Retina ; 44(6): 1026-1033, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38767850

RESUMO

PURPOSE: To evaluate Retinol-Binding Protein 3 (RBP3) from photoreceptors in aqueous and its association with vitreous concentrations, diabetic retinopathy (DR) severity, retinal layer thickness, and clinical characteristics in people with diabetes. METHODS: RBP3 concentration was measured by custom-developed enzyme-linked immunosorbent assay in aqueous and correlated with vitreous concentrations in patients from the 50-Year Medalist study and Beetham Eye Institute at Joslin Diabetes Center. RESULTS: Aqueous RBP3 concentration (N = 131) was elevated in eyes with no to mild DR (mean ± SD 0.7 nM ± 0.2) and decreased in eyes with moderate to severe DR (0.65 nM ± 0.3) and proliferative DR (0.5 nM ± 0.2, P < 0.001) compared to eyes without diabetes. Aqueous and vitreous RBP3 concentrations correlated with each other (r = 0.34, P = 0.001) and between fellow eyes (P < 0.0001). History of retinal surgery did not affect aqueous RBP3 concentrations, but cataract surgery affected both vitreous and aqueous levels. Elevated aqueous RBP3 concentration associated with increased thickness of the outer nuclear layer (P = 0.004) and correlated with hemoglobin A1c, whereas vitreous RBP3 concentrations correlated with diabetic systemic complications. CONCLUSION: These findings suggest that aqueous RBP3 concentration may be an important endogenous clinical retinal protective factor, a biomarker for DR severity, and a promising VEGF-independent clinical intervention target in DR.


Assuntos
Humor Aquoso , Biomarcadores , Retinopatia Diabética , Ensaio de Imunoadsorção Enzimática , Corpo Vítreo , Humanos , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/metabolismo , Corpo Vítreo/metabolismo , Corpo Vítreo/patologia , Masculino , Humor Aquoso/metabolismo , Feminino , Pessoa de Meia-Idade , Biomarcadores/metabolismo , Idoso , Índice de Gravidade de Doença , Tomografia de Coerência Óptica/métodos , Retina/metabolismo , Retina/patologia , Proteínas de Ligação ao Retinol/metabolismo
2.
PLoS One ; 19(5): e0303189, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38768165

RESUMO

OBJECTIVES: To establish a rat model that accurately replicates the clinical characteristics of male infertility (MI) with Liver Depression and Kidney Deficiency (LD & KD) and investigate the pathogenesis. METHODS: After subjecting the rats to chronic restraint stress (CRS) and adenine treatment, a series of tests were conducted, including ethological assessments, evaluations of reproductive characteristics, measurements of biochemical parameters, histopathological examinations, and analyses of urinary metabolites. Additionally, bioinformatics predictions were performed for comprehensive analysis. RESULTS: Compared to the control, the model exhibited significant manifestations of MI with LD & KD, including reduced responsiveness, diminished frequency of capturing estrous female rats, and absence of mounting behavior. Additionally, the kidney coefficient increased markedly, while the coefficients of the testis and epididymis decreased significantly. Sperm counts and viabilities decreased notably, accompanied by an increase in sperm abnormalities. Dysregulation of reproductive hormone levels in the serum was observed, accompanied by an upregulation of proinflammatory cytokines expressions in the liver and kidney, as well as exacerbated oxidative stress in the penile corpus cavernosum and testis. The seminiferous tubules in the testis exhibited a loose arrangement, loss of germ cells, and infiltration of inflammatory cells. Furthermore, utilizing urinary metabolomics and bioinformatics analysis, 5 key biomarkers and 2 crucial targets most closely linked to MI were revealed. CONCLUSION: The study successfully established a clinically relevant animal model of MI with LD & KD. It elucidates the pathogenesis of the condition, identifies key biomarkers and targets, and provides a robust scientific foundation for the prediction, diagnosis, and treatment of MI with LD & KD.


Assuntos
Biomarcadores , Modelos Animais de Doenças , Infertilidade Masculina , Animais , Masculino , Ratos , Biomarcadores/metabolismo , Infertilidade Masculina/metabolismo , Infertilidade Masculina/etiologia , Testículo/metabolismo , Testículo/patologia , Rim/metabolismo , Rim/patologia , Ratos Sprague-Dawley , Fígado/metabolismo , Fígado/patologia , Estresse Oxidativo , Hepatopatias/metabolismo , Hepatopatias/patologia , Insuficiência Renal/metabolismo , Insuficiência Renal/patologia , Insuficiência Renal/etiologia
3.
Environ Monit Assess ; 196(6): 564, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773003

RESUMO

This study investigated the impact of micropollutants on fish health from Segredo hydroelectric reservoir (HRS) along the Iguaçu River, Southern Brazil, contaminated by urban, industrial, and agricultural activities. This is the first comprehensive study assessment in the river after the severe drought in the 2020s in three fish species from different trophic levels Astyanax spp. (water column depth/omnivorous), Hypostomus commersoni (demersal/herbivorous), and Pimelodus maculatus (demersal/omnivorous). Animals, water, and sediment samples were collected from three distinct sites within the reservoir: Floresta (upstream), Iratim (middle), and Station (downstream). The chemical analysis revealed elevated concentrations of metals (Al, Cu, Fe) and the metalloid As in water, or Cu, Zn, and As in sediment, surpassing Brazilian regulatory limits, while the organic pollutants as DDT, PAHs, PCBs, and PBDEs were found under the Brazilian regulatory limits. The metal bioaccumulation was higher in gills with no significant differences among sites. The species Astyanax spp. and H. commersoni displayed variations in hepatosomatic index (HSI) and P. maculatus in the condition factor index (K) between sites, while adverse effects due to micropollutants bioaccumulation were observed by biochemical, genotoxic, and histopathological biomarkers. The principal component analysis and integrated biomarker response highlighted the upstream site Floresta as particularly inhospitable for biota, with distinctions based on trophic level. Consequently, this multifaceted approach, encompassing both fish biomarkers and chemical analyses, furnishes valuable insights into the potential toxic repercussions of micropollutant exposure. These findings offer crucial data for guiding management and conservation endeavors in the Iguaçu River.


Assuntos
Monitoramento Ambiental , Rios , Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo , Brasil , Rios/química , Biomarcadores/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Metais/análise , Characidae , Bifenilos Policlorados/análise , Bifenilos Policlorados/metabolismo , Sedimentos Geológicos/química , Peixes/metabolismo
4.
Sci Adv ; 10(19): eadi9156, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38718108

RESUMO

Exosomes are secreted vesicles of ~30 to 150 nm diameter that play important roles in human health and disease. To better understand how cells release these vesicles, we examined the biogenesis of the most highly enriched human exosome marker proteins, the exosomal tetraspanins CD81, CD9, and CD63. We show here that endocytosis inhibits their vesicular secretion and, in the case of CD9 and CD81, triggers their destruction. Furthermore, we show that syntenin, a previously described exosome biogenesis factor, drives the vesicular secretion of CD63 by blocking CD63 endocytosis and that other endocytosis inhibitors also induce the plasma membrane accumulation and vesicular secretion of CD63. Finally, we show that CD63 is an expression-dependent inhibitor of endocytosis that triggers the vesicular secretion of lysosomal proteins and the clathrin adaptor AP-2 mu2. These results suggest that the vesicular secretion of exosome marker proteins in exosome-sized vesicles occurs primarily by an endocytosis-independent pathway.


Assuntos
Endocitose , Exossomos , Tetraspanina 30 , Exossomos/metabolismo , Humanos , Tetraspanina 30/metabolismo , Biomarcadores/metabolismo , Sinteninas/metabolismo , Sinteninas/genética , Tetraspanina 28/metabolismo , Membrana Celular/metabolismo , Complexo 2 de Proteínas Adaptadoras/metabolismo , Tetraspanina 29/metabolismo
5.
Sci Adv ; 10(19): eadi6770, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38718114

RESUMO

Tracking stem cell fate transition is crucial for understanding their development and optimizing biomanufacturing. Destructive single-cell methods provide a pseudotemporal landscape of stem cell differentiation but cannot monitor stem cell fate in real time. We established a metabolic optical metric using label-free fluorescence lifetime imaging microscopy (FLIM), feature extraction and machine learning-assisted analysis, for real-time cell fate tracking. From a library of 205 metabolic optical biomarker (MOB) features, we identified 56 associated with hematopoietic stem cell (HSC) differentiation. These features collectively describe HSC fate transition and detect its bifurcate lineage choice. We further derived a MOB score measuring the "metabolic stemness" of single cells and distinguishing their division patterns. This score reveals a distinct role of asymmetric division in rescuing stem cells with compromised metabolic stemness and a unique mechanism of PI3K inhibition in promoting ex vivo HSC maintenance. MOB profiling is a powerful tool for tracking stem cell fate transition and improving their biomanufacturing from a single-cell perspective.


Assuntos
Biomarcadores , Diferenciação Celular , Linhagem da Célula , Células-Tronco Hematopoéticas , Biomarcadores/metabolismo , Animais , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Camundongos , Rastreamento de Células/métodos , Análise de Célula Única/métodos , Microscopia de Fluorescência/métodos , Humanos
6.
Life Sci Alliance ; 7(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38719747

RESUMO

The differential expression of plasma membrane proteins is integrally analyzed for their diagnosis, prognosis, and therapeutic applications in diverse clinical manifestations. Necessarily, distinct membrane protein enrichment methods and mass spectrometry platforms are employed for their global and relative quantitation. First of its kind to explore, we compiled membrane-associated proteomes in human and mouse systems into a database named, Resource of Experimental Membrane-Enriched Mass spectrometry-derived Proteome (REMEMProt). It currently hosts 14,626 proteins (9,507 proteins in Homo sapiens; 5,119 proteins in Mus musculus) with information on their membrane-protein enrichment methods, experimental/physiological context of detection in cells or tissues, transmembrane domain analysis, and their current attribution as biomarkers. Based on these annotations and the transmembrane domain analysis in proteins or their binary/complex protein-protein interactors, REMEMProt facilitates the assessment of the plasma membrane localization potential of proteins through batch query. A cross-study enrichment analysis platform is enabled in REMEMProt for comparative analysis of proteomes using novel/modified membrane enrichment methods and evaluation of methods for targeted enrichment of membrane proteins. REMEMProt data are made freely accessible to explore and download at https://rememprot.ciods.in/.


Assuntos
Biomarcadores , Bases de Dados de Proteínas , Proteínas de Membrana , Proteoma , Proteômica , Humanos , Proteoma/metabolismo , Proteínas de Membrana/metabolismo , Biomarcadores/metabolismo , Animais , Camundongos , Proteômica/métodos , Membrana Celular/metabolismo , Espectrometria de Massas/métodos
7.
Acta Biochim Pol ; 71: 12433, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721304

RESUMO

The study aimed to determine the osteointegration markers after dental implantation and evaluate their predictive value. The study was performed on 60 practically healthy persons who needed teeth rehabilitation using dental implants. The conical-shaped implants (CI) and hexagonal implants (HI) were used. The content of Osteopontin (OPN), Osteocalcin (OC), Alkaline Phosphatase (ALP), Osteoprotegerin (OPG), and nitric oxide (NO) was determined in patients' gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF), collected 1, 3, and 6 months after implantation. During the 3-6 months of observation level of OPN increased in patients with CIs (<50 years > 50 years) and HIs (<50 years) (CI: <50 years F = 36.457, p < 0.001; >50 years F = 30.104, p < 0.001; HI < 50 years F = 2.246, p < 0.001), ALP increased in patients with CIs (<50 years: F = 19.58, p < 0.001; >50 years: F = 12.01; p = 0.001) and HIs (<50 years) (F = 18.51, p < 0.001), OC increased in patients <50 years (CI: F = 33.72, p < 0.001; HI: F = 55.57, p < 0.001), but in patients >50 years - on the 3 days month (CI: F = 18.82, p < 0.001; HI: F = 26.26, p < 0.001), but sharply decreased at the end of sixth month. OPG increased during 1-3 months of the observation in patients <50 years (CI: F = 4.63, p = 0.037; HI: F = 2.8927, p = 0.046), but at the end of the sixth month returned to the initial level; NO content in PISF increased in patients with CI (>50 years) during 1-6 months of the observation (F = 27.657, p < 0.001). During the post-implantation period, age-related differences in osteointegration were observed. Patients <50 years old had relatively high levels of OPN, ALP, OC, and OPG in PISF, resulting in less alveolar bone destruction around dental implants and more intensive osteointegration. These indicators may be used as biological markers for monitoring implant healing. The process of osseointegration was more intense in CIs due to their comparatively high mechanical loading.


Assuntos
Fosfatase Alcalina , Biomarcadores , Implantes Dentários , Líquido do Sulco Gengival , Osseointegração , Osteocalcina , Osteopontina , Osteoprotegerina , Humanos , Pessoa de Meia-Idade , Biomarcadores/metabolismo , Feminino , Masculino , Osteoprotegerina/metabolismo , Líquido do Sulco Gengival/metabolismo , Fosfatase Alcalina/metabolismo , Osteocalcina/metabolismo , Adulto , Osteopontina/metabolismo , Prognóstico , Óxido Nítrico/metabolismo , Implantação Dentária/métodos , Fatores de Tempo
8.
Pediatr Allergy Immunol ; 35(5): e14133, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38727629

RESUMO

Food allergy (FA) is a widespread issue, affecting as many as 10% of the population. Over the past two to three decades, the prevalence of FA has been on the rise, particularly in industrialized and westernized countries. FA is a complex, multifactorial disease mediated by type 2 immune responses and involving environmental and genetic factors. However, the precise mechanisms remain inadequately understood. Metabolomics has the potential to identify disease endotypes, which could beneficially promote personalized prevention and treatment. A metabolome approach would facilitate the identification of surrogate metabolite markers reflecting the disease activity and prognosis. Here, we present a literature overview of recent metabolomic studies conducted on children with FA.


Assuntos
Hipersensibilidade Alimentar , Metabolômica , Humanos , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/diagnóstico , Metabolômica/métodos , Criança , Biomarcadores/metabolismo , Metaboloma , Alérgenos/imunologia
9.
Front Endocrinol (Lausanne) ; 15: 1360989, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38752172

RESUMO

Purpose: This feasibility study aimed to investigate the use of exhaled breath analysis to capture and quantify relative changes of metabolites during resolution of acute diabetic ketoacidosis under insulin and rehydration therapy. Methods: Breath analysis was conducted on 30 patients of which 5 with DKA. They inflated Nalophan bags, and their metabolic content was subsequently interrogated by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS). Results: SESI-HRMS analysis showed that acetone, pyruvate, and acetoacetate, which are well known to be altered in DKA, were readily detectable in breath of participants with DKA. In addition, a total of 665 mass spectral features were found to significantly correlate with base excess and prompt metabolic trajectories toward an in-control state as they progress toward homeostasis. Conclusion: This study provides proof-of-principle for using exhaled breath analysis in a real ICU setting for DKA monitoring. This non-invasive new technology provides new insights and a more comprehensive overview of the effect of insulin and rehydration during DKA treatment.


Assuntos
Testes Respiratórios , Cetoacidose Diabética , Insulina , Humanos , Cetoacidose Diabética/metabolismo , Testes Respiratórios/métodos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Insulina/metabolismo , Estudos de Viabilidade , Hidratação/métodos , Idoso , Biomarcadores/metabolismo , Biomarcadores/análise , Espectrometria de Massas por Ionização por Electrospray/métodos
10.
Front Endocrinol (Lausanne) ; 15: 1381180, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38752179

RESUMO

Background: The prevalence of autism spectrum disorder (ASD) has significantly risen in the past three decades, prompting researchers to explore the potential contributions of environmental factors during pregnancy to ASD development. One such factor of interest is gestational hypothyroxinemia (HTX), a frequent condition in pregnancy associated with cognitive impairments in the offspring. While retrospective human studies have linked gestational HTX to autistic traits, the cellular and molecular mechanisms underlying the development of ASD-like phenotypes remain poorly understood. This study used a mouse model of gestational HTX to evaluate ASD-like phenotypes in the offspring. Methods: To induce gestational HTX, pregnant mice were treated with 2-mercapto-1-methylimidazole (MMI), a thyroid hormones synthesis inhibitor, in the tap-drinking water from embryonic days (E) 10 to E14. A separate group received MMI along with a daily subcutaneous injection of T4, while the control group received regular tap water during the entire pregnancy. Female and male offspring underwent assessments for repetitive, anxious, and social behaviors from postnatal day (P) 55 to P64. On P65, mice were euthanized for the evaluation of ASD-related inflammatory markers in blood, spleen, and specific brain regions. Additionally, the expression of glutamatergic proteins (NLGN3 and HOMER1) was analyzed in the prefrontal cortex and hippocampus. Results: The HTX-offspring exhibited anxious-like behavior, a subordinate state, and impaired social interactions. Subsequently, both female and male HTX-offspring displayed elevated proinflammatory cytokines in blood, including IL-1ß, IL-6, IL-17A, and TNF-α, while only males showed reduced levels of IL-10. The spleen of HTX-offspring of both sexes showed increased Th17/Treg ratio and M1-like macrophages. In the prefrontal cortex and hippocampus of male HTX-offspring, elevated levels of IL-17A and reduced IL-10 were observed, accompanied by increased expression of hippocampal NLGN3 and HOMER1. All these observations were compared to those observed in the Control-offspring. Notably, the supplementation with T4 during the MMI treatment prevents the development of the observed phenotypes. Correlation analysis revealed an association between maternal T4 levels and specific ASD-like outcomes. Discussion: This study validates human observations, demonstrating for the first time that gestational HTX induces ASD-like phenotypes in the offspring, highlighting the need of monitoring thyroid function during pregnancy.


Assuntos
Transtorno do Espectro Autista , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Gravidez , Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/metabolismo , Camundongos , Masculino , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fenótipo , Comportamento Animal , Hipotireoidismo/metabolismo , Tiroxina/sangue , Biomarcadores/metabolismo , Camundongos Endogâmicos C57BL , Complicações na Gravidez/metabolismo , Modelos Animais de Doenças , Inflamação/metabolismo , Comportamento Social
11.
Methods Mol Biol ; 2775: 127-137, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38758315

RESUMO

Proteomic profiling provides in-depth information about the regulation of diverse biological processes, activation of and communication across signaling networks, and alterations to protein production, modifications, and interactions. For infectious disease research, mass spectrometry-based proteomics enables detection of host defenses against infection and mechanisms used by the pathogen to evade such responses. In this chapter, we outline protein extraction from organs, tissues, and fluids collected following intranasal inoculation of a murine model with the human fungal pathogen Cryptococcus neoformans. We describe sample preparation, followed by purification, processing on the mass spectrometer, and a robust bioinformatics analysis. The information gleaned from proteomic profiling of fungal infections supports the detection of novel biomarkers for diagnostic and prognostic purposes.


Assuntos
Criptococose , Cryptococcus neoformans , Modelos Animais de Doenças , Proteômica , Animais , Cryptococcus neoformans/metabolismo , Cryptococcus neoformans/patogenicidade , Camundongos , Criptococose/microbiologia , Criptococose/metabolismo , Proteômica/métodos , Biologia Computacional/métodos , Proteoma/metabolismo , Biomarcadores/metabolismo , Espectrometria de Massas/métodos
12.
Cell Commun Signal ; 22(1): 264, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734696

RESUMO

BACKGROUND: Traditional biomarkers of chronic kidney disease (CKD) detect the disease in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein and a serine/threonine protein kinase that plays multiple roles in several pathophysiological processes during renal damage. However, the involvement of ILK as a biomarker of CKD and its associated vascular problems remains to be fully elucidated. METHODS: CKD was induced by an adenine-rich diet for 6 weeks in mice. We used an inducible ILK knockdown mice (cKD-ILK) model to decrease ILK expression. ILK content in mice's peripheral blood mononuclear cells (PBMCs) was determined and correlated with renal function parameters and with the expression of ILK and fibrosis and inflammation markers in renal and aortic tissues. Also, the expression of five miRNAs that target ILK was analyzed in whole blood of mice. RESULTS: The adenine diet increased ILK expression in PBMCs, renal cortex, and aortas, and creatinine and urea nitrogen concentrations in the plasma of WT mice, while these increases were not observed in cKD-ILK mice. Furthermore, ILK content in PBMCs directly correlated with renal function parameters and with the expression of renal and vascular ILK and fibrosis and inflammation markers. Finally, the expression of the five miRNAs increased in the whole blood of adenine-fed mice, although only four correlated with plasma urea nitrogen, and of those, three were downregulated in cKD-ILK mice. CONCLUSIONS: ILK, in circulating mononuclear cells, could be a potential biomarker of CKD and CKD-associated renal and vascular damage.


Assuntos
Biomarcadores , Rim , Leucócitos Mononucleares , Proteínas Serina-Treonina Quinases , RNA Mensageiro , Insuficiência Renal Crônica , Animais , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia , Leucócitos Mononucleares/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Biomarcadores/metabolismo , Biomarcadores/sangue , Camundongos , Rim/patologia , Rim/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/sangue , MicroRNAs/metabolismo , Modelos Animais de Doenças , Fibrose
13.
J Physiol Pharmacol ; 75(2): 123-136, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38736260

RESUMO

Myocardial infarction (MI) is a significant global health issue and the leading cause of death. Myocardial infarction (MI) is characterized by events such as damage to heart cells and stress generated by inflammation. Punicalagin (PCN), a naturally occurring bioactive compound found in pomegranates, exhibits a diverse array of pharmacological effects against many disorders. This study aimed to assess the preventive impact of PCN, with its potential anti-inflammatory and antioxidant properties, on myocardial injury caused by isoproterenol (ISO) in rats and elucidate the possible underlying mechanisms. Experimental rats were randomly categorized into four groups: control group (fed a regular diet for 15 days), PCN group (orally administered PCN at 50 mg/kg body weight (b.w.) for 15 days), ISO group (subcutaneously administered ISO (85 mg/kg b.w.) on days 14 and 15 to induce MI), and PCN+ISO group (orally preadministered PCN (50 mg/kg b.w.) for 15 days and administered ISO (85 mg/kg b.w.) on days 14 and 15). The rat cardiac tissue was then investigated for cardiac marker, oxidative stress marker, and inflammatory marker expression levels. PCN prevented ISO-induced myocardial injury, suppressing the levels of creatine kinase-myocardial band, C-reactive protein, homocysteine, cardiac troponin T, and cardiac troponin I in the rats. Moreover, PCN treatment reversed (P<0.01) the ISO-induced increase in blood pressure, attenuated lipid peroxidation markers, and depleted both enzymatic and nonenzymatic markers in the rats. Additionally, PCN inhibited (P<0.01) ISO-induced overexpression of oxidative stress markers (p-38, p-c-Jun N-terminal kinase, and p-extracellular signal-regulated kinase 1), inflammatory markers (nuclear factor-kappa B, tumor necrosis factor-alpha, and interleukin-6), and matrix metalloproteinases and decreased the levels (P<0.01) of apoptosis proteins in the rats. Nuclear factor erythroid 2-related factor 2/silent information regulator transcript-1 (Nrf2/Sirt1) is a major cellular defense protein that regulates and scavenges oxidative toxic substances through apoptosis. Therefore, overexpression of Nrf2/Sirt1 to inhibit inflammation and oxidative stress is considered a novel target for preventing MI. PCN also significantly enhanced the expression of Nrf2/Sirt1 in ISO-induced rats. Histopathological analyses of cardiac tissue revealed that PCN treatment exhibited a protective effect on the heart tissue, mitigating damage. These findings show that by activating the Nrf2/Sirt1 pathway, PCN regulates oxidative stress, inflammation, and apoptosis, hence providing protection against ISO-induced myocardial ischemia.


Assuntos
Taninos Hidrolisáveis , Inflamação , Isoproterenol , Infarto do Miocárdio , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Sirtuína 1 , Animais , Isoproterenol/toxicidade , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Masculino , Taninos Hidrolisáveis/farmacologia , Sirtuína 1/metabolismo , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Inflamação/induzido quimicamente , Ratos , Estresse Oxidativo/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ratos Wistar , Biomarcadores/metabolismo , Modelos Animais de Doenças , Antioxidantes/farmacologia , Miocárdio/metabolismo , Miocárdio/patologia
14.
J Drugs Dermatol ; 23(5): 366-375, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38709706

RESUMO

OBJECTIVE:   This study aimed to investigate the ultraviolet (UV) protection/repair benefits of a patented Amino Acid Complex (AAComplex). METHODS: I) AAComplex was incubated with dermal fibroblasts, with/without UVA, and collagen I was measured with a GlasBoxPlus device. II) A lotion, with/without AAComplex (1%) was applied topically to skin explants, following UVA irradiation, and quantified for health-related biomarkers (TNFalpha, histamine, and MMP-1). III) A broad spectrum sunscreen with SPF 46 and a skincare serum containing AAComplex (2%) were assessed using epidermal equivalents, in the presence of UV irradiation, for effects on IL-1alpha, thymine dimers, Ki-67, filaggrin and Nrf2. RESULTS: I) Collagen I synthesis in dermal fibroblasts was significantly decreased after UVA compared to without UV. The presence of AAComplex prevented this decrease. II) UVA irradiation of skin explants increased histamine, TNFα, and MMP-1. Hydrocortisone aceponate cream significantly decreases all 3 biomarkers. AAComplex contained lotion also significantly decreased all 3 biomarkers, the no AAComplex control lotion only reduced histamine. III) With the regimen of sunscreen + AAComplex contained skincare serum, the significant reduction in IL-1alpha was observed along with a complete recovery of Ki-67 and stimulation of filaggrin and Nrf2T. No thymine dimer positive cell was observed indicating the most positive skin impact from the regiment.  Conclusion: This research using different human skin models demonstrated that AAComplex can provide protection and damage repair caused by UV, at the ingredient level also when formulated in a serum or lotion formula. Skin may be best protected from UV damage when the regimen is used.   J Drugs Dermatol. 2024;23(5):366-375. doi:10.36849/JDD.7916.


Assuntos
Fibroblastos , Proteínas Filagrinas , Metaloproteinase 1 da Matriz , Fator 2 Relacionado a NF-E2 , Fator de Necrose Tumoral alfa , Raios Ultravioleta , Humanos , Raios Ultravioleta/efeitos adversos , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Fibroblastos/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Pele/efeitos da radiação , Pele/efeitos dos fármacos , Pele/metabolismo , Protetores Solares/administração & dosagem , Protetores Solares/química , Protetores Solares/farmacologia , Aminoácidos/administração & dosagem , Aminoácidos/farmacologia , Aminoácidos/química , Interleucina-1alfa/metabolismo , Histamina/sangue , Creme para a Pele/administração & dosagem , Biomarcadores/metabolismo , Colágeno Tipo I , Proteínas de Filamentos Intermediários/metabolismo , Antígeno Ki-67/metabolismo , Dímeros de Pirimidina , Células Cultivadas
15.
J Orthop Surg Res ; 19(1): 281, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711140

RESUMO

PURPOSE: This study aimed to investigate an early diagnostic method for lumbar disc degeneration (LDD) and improve its diagnostic accuracy. METHODS: Quantitative biomarkers of the lumbar body (LB) and lumbar discs (LDs) were obtained using nuclear magnetic resonance (NMR) detection technology. The diagnostic weights of each biological metabolism indicator were screened using the factor analysis method. RESULTS: Through factor analysis, common factors such as the LB fat fraction, fat content, and T2* value of LDs were identified as covariates for the diagnostic model for the evaluation of LDD. This model can optimize the accuracy and reliability of LDD diagnosis. CONCLUSION: The application of biomarker quantification methods based on NMR detection technology combined with factor analysis provides an effective means for the early diagnosis of LDD, thereby improving diagnostic accuracy and reliability.


Assuntos
Biomarcadores , Degeneração do Disco Intervertebral , Vértebras Lombares , Imageamento por Ressonância Magnética , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/metabolismo , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Biomarcadores/metabolismo , Feminino , Adulto , Pessoa de Meia-Idade , Análise Fatorial , Reprodutibilidade dos Testes , Diagnóstico Precoce
16.
Int Ophthalmol ; 44(1): 220, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713261

RESUMO

BACKGROUND: This study was conducted to compare concentrations of VEGF family growth factors, inflammation-related factors, and adhesion molecules in the aqueous humor of eyes with diabetic macular edema (DME), with and without prior vitrectomy. METHODS: A total of 31 eyes were included, 11 with DME that had undergone vitrectomy, 9 with DME but without vitrectomy, and 11 from age-related cataract patients as controls. The concentrations of cytokines including TNF-α, IL-6, IL-8, IP-10, MCP-1, IFN-γ, MIP-1 α, MIP-1 ß, PECAM-1, MIF, VCAM-1, ICAM-1, PIGF were quantified using Luminex Human Discovery Assay. Central macular thickness (CMT) values of all eyes were measured using optical coherence tomography (OCT). RESULTS: (1) Vitrectomized DME eyes exhibited significantly higher levels of IL-6 and IL-8 compared to non-vitrectomized eyes (P < 0.05). (2) In vitrectomized group, after Benjamini-Hochberg correction, there was a significant positive correlation between the levels of VEGF and PlGF (rs = 0.855, P < 0.05), as well as the levels of TNF-α and IFN-γ (rs = 0.858, P < 0.05). In non-vitrectomized group, significant positive correlations were found between VEGF and PlGF levels after correcting for multiple comparisons (rs = 0.9, P < 0.05). (3) In non-vitrectomized group, the concentrations of VEGF and PlGF in aqueous humor were significantly positively correlated with CMT values (rs = 0.95, P < 0.05; rs = 0.9, P < 0.05, respectively). CONCLUSIONS: The concentrations of IL-6 and IL-8 in the aqueous humor were significantly higher in vitrectomized DME eyes compared to nonvitrectomized DME eyes and the levels of VEGF were similar in the two groups, suggesting that inflammation after vitrectomy may be a key factor in the occurrence and development of DME.


Assuntos
Humor Aquoso , Citocinas , Retinopatia Diabética , Edema Macular , Tomografia de Coerência Óptica , Vitrectomia , Humanos , Humor Aquoso/metabolismo , Edema Macular/metabolismo , Edema Macular/etiologia , Edema Macular/diagnóstico , Masculino , Citocinas/metabolismo , Feminino , Retinopatia Diabética/metabolismo , Retinopatia Diabética/cirurgia , Retinopatia Diabética/diagnóstico , Idoso , Pessoa de Meia-Idade , Tomografia de Coerência Óptica/métodos , Biomarcadores/metabolismo
17.
Br J Surg ; 111(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38736137

RESUMO

BACKGROUND: Barrett's oesophagus surveillance places significant burden on endoscopy services yet is vital to detect early cancerous change. Oesophageal cell collection device (OCCD) testing was introduced across Scotland for Barrett's surveillance in response to the COVID-19 pandemic. This national pragmatic retrospective study presents the CytoSCOT programme results and evaluates whether OCCD testing is successfully identifying high-risk Barrett's patients requiring urgent endoscopy. METHODS: All patients undergoing OCCD testing for Barrett's surveillance across 11 Scottish health boards over a 32-month period were identified. Patients who underwent endoscopy within 12 months of OCCD test were included. Individual patient records were interrogated to record clinical information and OCCD test result to categorize patients into risk groups. Endoscopic histopathology results were analysed according to risk group and segment length. Patients were deemed high risk if the OCCD test demonstrated atypia and/or p53 positivity. RESULTS: 4204 OCCD tests were performed in 3745 patients: 608 patients underwent endoscopy within 12 months and were included in this analysis. Patients with longer Barrett's segments were significantly more likely to have an abnormal OCCD test. 50/608 patients (8.2%) had high-grade dysplasia or cancer on endoscopic biopsies: this equates to 1.3% of the total group (50/3745). 46/50 patients (92.0%) were deemed high risk, triggering urgent endoscopy: this rose to 100% with insufficient tests removed. There were no cancers diagnosed within 12 months post-OCCD in the low-risk group. CONCLUSION: OCCD testing is an effective triage tool to identify high-risk patients with Barrett's oesophagus requiring further investigation with endoscopy within the real-world setting.


Assuntos
Esôfago de Barrett , Neoplasias Esofágicas , Esofagoscopia , Humanos , Esôfago de Barrett/patologia , Esôfago de Barrett/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Esofagoscopia/métodos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , COVID-19/diagnóstico , Escócia/epidemiologia , Biomarcadores/metabolismo , Medição de Risco , Esôfago/patologia , Detecção Precoce de Câncer/métodos , Adulto
18.
PLoS One ; 19(5): e0303496, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38739622

RESUMO

INTRODUCTION: Rheumatic heart disease (RHD), degenerative aortic stenosis (AS), and congenital valve diseases are prevalent in sub-Saharan Africa. Many knowledge gaps remain in understanding disease mechanisms, stratifying phenotypes, and prognostication. Therefore, we aimed to characterise patients through clinical profiling, imaging, histology, and molecular biomarkers to improve our understanding of the pathophysiology, diagnosis, and prognosis of RHD and AS. METHODS: In this cross-sectional, case-controlled study, we plan to recruit RHD and AS patients and compare them to matched controls. Living participants will undergo clinical assessment, echocardiography, CMR and blood sampling for circulatory biomarker analyses. Tissue samples will be obtained from patients undergoing valve replacement, while healthy tissues will be obtained from cadavers. Immunohistology, proteomics, metabolomics, and transcriptome analyses will be used to analyse circulatory- and tissue-specific biomarkers. Univariate and multivariate statistical analyses will be used for hypothesis testing and identification of important biomarkers. In summary, this study aims to delineate the pathophysiology of RHD and degenerative AS using multiparametric CMR imaging. In addition to discover novel biomarkers and explore the pathomechanisms associated with RHD and AS through high-throughput profiling of the tissue and blood proteome and metabolome and provide a proof of concept of the suitability of using cadaveric tissues as controls for cardiovascular disease studies.


Assuntos
Estenose da Valva Aórtica , Biomarcadores , Cardiopatia Reumática , Humanos , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/fisiopatologia , Cardiopatia Reumática/metabolismo , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/fisiopatologia , Biomarcadores/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Masculino , Feminino , Metabolômica/métodos , Ecocardiografia/métodos , Proteômica/métodos , Imageamento por Ressonância Magnética/métodos , Multiômica
19.
PLoS One ; 19(5): e0302753, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38739634

RESUMO

Leprosy has a high rate of cripplehood and lacks available early effective diagnosis methods for prevention and treatment, thus novel effective molecule markers are urgently required. In this study, we conducted bioinformatics analysis with leprosy and normal samples acquired from the GEO database(GSE84893, GSE74481, GSE17763, GSE16844 and GSE443). Through WGCNA analysis, 85 hub genes were screened(GS > 0.7 and MM > 0.8). Through DEG analysis, 82 up-regulated and 3 down-regulated genes were screened(|Log2FC| > 3 and FDR < 0.05). Then 49 intersection genes were considered as crucial and subjected to GO annotation, KEGG pathway and PPI analysis to determine the biological significance in the pathogenesis of leprosy. Finally, we identified a gene-pathway network, suggesting ITK, CD48, IL2RG, CCR5, FGR, JAK3, STAT1, LCK, PTPRC, CXCR4 can be used as biomarkers and these genes are active in 6 immune system pathways, including Chemokine signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, T cell receptor signaling pathway, Natural killer cell mediated cytotoxicity and Leukocyte transendothelial migration. We identified 10 crucial gene markers and related important pathways that acted as essential components in the etiology of leprosy. Our study provides potential targets for diagnostic biomarkers and therapy of leprosy.


Assuntos
Biomarcadores , Redes Reguladoras de Genes , Hanseníase , Hanseníase/genética , Hanseníase/microbiologia , Humanos , Biomarcadores/metabolismo , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Mapas de Interação de Proteínas/genética , Transdução de Sinais
20.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38739758

RESUMO

The complicated process of neuronal development is initiated early in life, with the genetic mechanisms governing this process yet to be fully elucidated. Single-cell RNA sequencing (scRNA-seq) is a potent instrument for pinpointing biomarkers that exhibit differential expression across various cell types and developmental stages. By employing scRNA-seq on human embryonic stem cells, we aim to identify differentially expressed genes (DEGs) crucial for early-stage neuronal development. Our focus extends beyond simply identifying DEGs. We strive to investigate the functional roles of these genes through enrichment analysis and construct gene regulatory networks to understand their interactions. Ultimately, this comprehensive approach aspires to illuminate the molecular mechanisms and transcriptional dynamics governing early human brain development. By uncovering potential links between these DEGs and intelligence, mental disorders, and neurodevelopmental disorders, we hope to shed light on human neurological health and disease. In this study, we have used scRNA-seq to identify DEGs involved in early-stage neuronal development in hESCs. The scRNA-seq data, collected on days 26 (D26) and 54 (D54), of the in vitro differentiation of hESCs to neurons were analyzed. Our analysis identified 539 DEGs between D26 and D54. Functional enrichment of those DEG biomarkers indicated that the up-regulated DEGs participated in neurogenesis, while the down-regulated DEGs were linked to synapse regulation. The Reactome pathway analysis revealed that down-regulated DEGs were involved in the interactions between proteins located in synapse pathways. We also discovered interactions between DEGs and miRNA, transcriptional factors (TFs) and DEGs, and between TF and miRNA. Our study identified 20 significant transcription factors, shedding light on early brain development genetics. The identified DEGs and gene regulatory networks are valuable resources for future research into human brain development and neurodevelopmental disorders.


Assuntos
Biomarcadores , Encéfalo , Redes Reguladoras de Genes , Células-Tronco Embrionárias Humanas , Análise de Célula Única , Humanos , Análise de Célula Única/métodos , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Embrionárias Humanas/citologia , Encéfalo/metabolismo , Encéfalo/embriologia , Encéfalo/citologia , Biomarcadores/metabolismo , Neurônios/metabolismo , Neurônios/citologia , Diferenciação Celular/genética , RNA-Seq , Neurogênese/genética , Regulação da Expressão Gênica no Desenvolvimento , Perfilação da Expressão Gênica , Análise de Sequência de RNA/métodos , Análise da Expressão Gênica de Célula Única
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