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1.
Anal Chem ; 96(12): 4925-4932, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38471137

RESUMO

Sepsis is a dysregulated inflammatory response leading to multiple organ failure. Current methods of sepsis detection are time-consuming, involving nonspecific clinical signs, biomarkers, and blood cultures. Hence, efficient and rapid sepsis detection platforms are of utmost need for immediate antibiotic treatment. In the current study, a noninvasive rapid monitoring electrochemical sensing (ECS) platform was developed for the detection and classification of plasma samples of patients with liver cirrhosis by measuring the current peak shifts using the cyclic voltammetry (CV) technique. A total of 61 hospitalized cirrhotic patients with confirmed (culture-positive) or suspected (culture-negative) sepsis were enrolled. The presence of bacteria in the plasma was observed by growth kinetics, and for rapidness, the samples were co-encapsulated in microscaffolds with carbon nanodots that were sensitive enough to detect redox changes occurring due to the change in the pH of the surrounding medium, causing shifts in current peaks in the voltammograms within 2 h. The percentage area under the curve for confirmed infections was 94 and that with suspected cases was 87 in comparison to 69 and 71 with PCT, respectively. Furthermore, the charge was measured for class identification. The charge for LPS-absent bacteria ranged from -400 to -600 µC, whereas the charge for LPS-containing bacteria class ranged from -290 to -300 µC. Thus, the developed cost-effective system was sensitive enough to detect and identify bacterial sepsis.


Assuntos
Calcitonina , Sepse , Humanos , Peptídeo Relacionado com Gene de Calcitonina/uso terapêutico , Lipopolissacarídeos , Precursores de Proteínas , Sepse/diagnóstico , Biomarcadores , Bactérias , Cirrose Hepática/diagnóstico
2.
BMJ Open ; 14(3): e076483, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485478

RESUMO

OBJECTIVES: The objective of this study was to evaluate the early predictors of bacterial pneumonia infection in children with congenital heart disease (CHD) after cardiopulmonary bypass (CPB). DESIGN: Retrospective study. SETTING: A freestanding tertiary paediatric hospital in China. PARTICIPANTS: Patients admitted to the hospital due to CHD who underwent open-heart surgery. OUTCOME MEASURES: We retrospectively reviewed and analysed data from 1622 patients with CHD after CPB from June 2018 to December 2020 at the Children's Hospital of Nanjing Medical University. Enrolled patients were assigned to an infection group or a non-infection group according to the presence of postoperative bacterial pneumonia infection, and the differences in clinical indicators were compared. Potential predictors were analysed by multivariate logistic regression analysis and area under the curve (AUC) analysis. RESULTS: Among the 376 patients (23.2%) in the infection group, the three most common bacteria were Streptococcus pneumoniae in 67 patients (17.8%), Escherichia coli in 63 patients (16.8%) and Haemophilus influenzae in 53 patients (14.1%). The infection group exhibited a lower weight (8.0 (6.0-11.5) kg vs 11.0 (7.5-14.5) kg, p<0.001). In the infection group, procalcitonin (PCT) (ng/mL: 4.72 (1.38-9.52) vs 1.28 (0.47-3.74), p<0.001) and C reactive protein (CRP) (mg/L: 21.0 (12.1-32.0) vs 17.0 (10.0-27.0), p<0.001) levels were significantly greater than those in the non-infection group. Binary logistic regression analysis revealed that weight, PCT and CRP were independent risk factors for pulmonary bacterial infection after CPB. The AUCs of weight, PCT, CRP and PCT+CRP for predicting pulmonary bacterial infection after CPB were 0.632 (95% CI 0.600 to 0.664), 0.697 (95% CI 0.667 to 0.727), 0.586 (95% CI 0.554 to 0.618) and 0.694 (95% CI 0.664 to 0.724), respectively, and the cut-off values were ≤10.25 kg, ≥4.25 ng/mL, ≥6.50 mg/L and ≥0.20, respectively. The sensitivities were 69.7%, 54.0%, 93.9% and 70.2%, and the specificities were 53.5%, 77.7%, 19.4% and 59.1%, respectively. CONCLUSIONS: In our study, weight, PCT and CRP were found to be independent predictors of pulmonary bacterial infection after CPB. Moreover, PCT was the most specific predictor, and CRP was the most sensitive independent predictor that might be beneficial for the early diagnosis of pulmonary bacterial infection after CPB in patients with CHD.


Assuntos
Cardiopatias Congênitas , Pneumonia Bacteriana , Humanos , Criança , Estudos Retrospectivos , Ponte Cardiopulmonar/efeitos adversos , Calcitonina , Peptídeo Relacionado com Gene de Calcitonina , Precursores de Proteínas , Pró-Calcitonina , Proteína C-Reativa/análise , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/etiologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/cirurgia , Centros de Atenção Terciária , Biomarcadores
3.
BMJ Paediatr Open ; 8(1)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499348

RESUMO

INTRODUCTION: The management of fever without source in children ≤36 months old remains a diagnostic challenge as the underlying aetiologies can vary from self-limiting viral infections to serious bacterial infections (SBIs). Biomarkers such as C reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) have varying thresholds in the prediction of SBIs due to differences in SBI definitions, SBI prevalence, patient characteristics and timing of presentation. This protocol describes a systematic review and meta-analysis that aims to determine the thresholds at which CRP, PCT and IL-6 can perform optimally in distinguishing the presence of SBIs in children ≤36 months old, as well as to determine their performances in early detection of bacterial infections within 48 hours of fever onset. METHODS AND ANALYSIS: We will systematically search electronic databases including MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane CENTRAL, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and Science Citation Index from 1 July 2023 to 31 July 2023. We will include studies that report the diagnostic accuracy of CRP, PCT and IL-6 in detecting SBIs in children aged ≤36 months presenting with fever without apparent source. Randomised controlled trials (RCTs) and non-randomised studies including non-RCTs and controlled before-and-after studies will be included. A meta-analysis will be performed and diagnostic performances of these biomarkers will be reported. ETHICS AND DISSEMINATION: The results of this study will provide guidance on clinical decision-making in young children presenting with fever without source. Ethics approval will not be required for this study. The authors aim to publish the findings in a peer-reviewed journal as well as present at international conferences. PROSPERO REGISTRATION NUMBER: CRD42023439093.


Assuntos
Infecções Bacterianas , Proteína C-Reativa , Criança , Humanos , Pré-Escolar , Proteína C-Reativa/análise , Interleucina-6 , Pró-Calcitonina , Calcitonina , Peptídeo Relacionado com Gene de Calcitonina , Precursores de Proteínas , Infecções Bacterianas/diagnóstico , Febre/etiologia , Febre/microbiologia , Biomarcadores , Metanálise como Assunto , Revisões Sistemáticas como Assunto
4.
Nutrients ; 16(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474812

RESUMO

Celiac disease (CeD) is an autoimmune condition triggered by gluten in genetically predisposed individuals, affecting all ages. Intestinal permeability (IP) is crucial in the pathogenesis of CeD and it is primarily governed by tight junctions (TJs) that uphold the intestinal barrier's integrity. The protein zonulin plays a critical role in modulating the permeability of TJs having emerged as a potential non-invasive biomarker to study IP. The importance of this study lies in providing evidence for the usefulness of a non-invasive tool in the study of IP both at baseline and in the follow-up of paediatric patients with CeD. In this single-centre prospective observational study, we explored the correlation between faecal zonulin levels and others faecal and serum biomarkers for monitoring IP in CeD within the paediatric population. We also aimed to establish reference values for faecal zonulin in the paediatric population. We found that faecal zonulin and calprotectin values are higher at the onset of CeD compared with the control population. Specifically, the zonulin levels were 347.5 ng/mL as opposed to 177.7 ng/mL in the control population (p = 0.001), while calprotectin levels were 29.8 µg/g stool compared to 13.9 µg/g stool (p = 0.029). As the duration without gluten consumption increased, a significant reduction in faecal zonulin levels was observed in patients with CeD (348.5 ng/mL vs. 157.1 ng/mL; p = 0.002), along with a decrease in the prevalence of patients with vitamin D insufficiency (88.9% vs. 77.8%). We conclude that faecal zonulin concentrations were higher in the patients with active CeD compared with healthy individuals or those following a gluten-free diet (GFD). The significant decrease in their values over the duration of the GFD suggests the potential use of zonulin as an additional tool in monitoring adherence to a GFD.


Assuntos
Doença Celíaca , Haptoglobinas , Precursores de Proteínas , Humanos , Criança , Dieta Livre de Glúten , Glutens , Biomarcadores , Complexo Antígeno L1 Leucocitário
5.
Front Endocrinol (Lausanne) ; 15: 1329363, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405153

RESUMO

Introduction: Zonulin recently emerged as a valuable biological marker to assess the integrity of the intestinal mucosal barrier. Nevertheless, data about zonulin in pediatric age are extremely scarce. Aim of this study was to investigate the relationship between serum zonulin levels, both fasting and postprandial, with body mass index (BMI) and biochemical markers of insulin resistance (IR), insulin sensitivity, b-cell function and cardio-metabolic risk in obese non-diabetic youths. Methods: One hundred and four children and adolescents with obesity (BMI ≥ 2.0 SDS) were enrolled (mean age 11.43 ± 2.66). All the patients underwent clinical and biochemical assessment, including oral glucose tolerance test (OGTT) and liver ultrasonography. Zonulin serum levels were measured at fasting state, at 60-minute and 120-minute OGTT timepoint. Results: Impaired fasting glycaemia and impaired glucose tolerance were documented in 27.9% and 11.5% of patients, respectively. IR was documented in 69.2% of cases. Liver steatosis was diagnosed in 39.4%. Zonulin serum levels significantly increased from baseline to 60-minute and 120-minute OGTT timepoint (p positive correlation between BMI SDS and serum zonulin levels at 120-minute OGTT timepoint (p highlighted a positive association of zonulin fasting levels with IR and glutamicoxalacetic transaminase levels (GOT, p zonulin levels were demonstrated for age, sex, pubertal status, glucose, lipid profile and the other obesity-related parameters. Discussion: Our results show, for the first time in a pediatric cohort, the meal-related pattern of secretion of serum zonulin, which tends to significantly increase during and at 2-hours postprandial assessment. Even if the underlying mechanisms associating intestinal permeability and obesity have not been fully elucidated yet, our data confirm a close relationship between zonulin concentration and obesity in pediatric population. IR seems to significantly influence zonulin serum levels, thus a central role of IR in this pathway is conceivable.


Assuntos
Haptoglobinas , Resistência à Insulina , Obesidade Pediátrica , Humanos , Criança , Adolescente , Obesidade Pediátrica/complicações , Precursores de Proteínas , Resistência à Insulina/fisiologia , Jejum
6.
Biomarkers ; 29(2): 55-67, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38361436

RESUMO

BACKGROUND: The conventional markers for hepatocellular carcinoma (HCC), α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), have several limitations; both have low sensitivity in patients with early-stage HCC; low sensitivity for AFP with HCC after eliminating hepatitis C virus (HCV); low specificity for DCP in patients with non-viral HCC, which is increasing worldwide; low specificity for AFP in patients with liver injury; and low specificity for DCP in patients treated with warfarin. To overcome these issues, the identification of novel biomarkers is an unmet need. OBJECTIVE: This study aimed to assess the usefulness of serum protein kinase C delta (PKCδ) for detecting these HCCs. METHODS: PKCδ levels were measured using a sandwich enzyme-linked immunosorbent assay in 363 chronic liver disease (CLD) patients with and without HCC. RESULTS: In both viral and non-viral CLD, PKCδ can detect HCCs with high sensitivity and specificity, particularly in the very early stages. Notably, the value and sensitivity of PKCδ were not modified by HCV elimination status. Liver injury and warfarin administration, which are known to cause false-positive results for conventional markers, did not modify PKCδ levels. CONCLUSIONS: PKCδ is an enhanced biomarker for the diagnosis of HCC that compensates for the drawbacks of conventional markers.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , alfa-Fetoproteínas , Biomarcadores Tumorais , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Proteína Quinase C-delta , Varfarina , Sensibilidade e Especificidade , Precursores de Proteínas , Biomarcadores , Protrombina/metabolismo
7.
Arch Med Res ; 55(2): 102966, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38330831

RESUMO

BACKGROUND AND AIM: The increasing dilemma of multidrug-resistant cancer cells in response to currently available chemotherapeutic drugs and their associated side effect(s), calls for the investigation of alternative anticancer advances and molecules. Therefore, the present study aimed to elucidate the combinatorial potential against colon cancer of human defensin 5 in combination with 5-fluorouracil (5-FU), and against 5-FU resistant colon tumor cells. METHODS: The in vivo combinatorial potential of HD-5 with 5-FU was elucidated in terms of tumor morphometrics, apoptosis assay, surface morphology histology of the colon(s), and transcriptional alterations. Changes in membrane dynamics with mucin expression were evaluated by fluorescence microscopy and histochemistry. The in vitro activity of the peptide/drug conjunction was explored by phase contrast microscopy, MTT, LDH assay, and AO/EtBr staining. Chemoresistance to 5-FU was determined by phase contrast microscopy, MTT assay, annexin V-FITC/PI flow cytometry, and MDR-1, Bak, and Bax expression. RESULTS: In vivo decreases in tumor parameters, with a marked increase in apoptosis and neutrophil infiltrations indicated restoration of normal architecture with improved mucin content in the treated colons. This happened with substantial changes in key molecular markers of the intrinsic apoptotic cascade. Membrane dynamics revealed that peptides and chemotherapeutic drugs could bind to cancerous cells by taking advantage of altered levels of membrane fluidity. CONCLUSION: Peptide treatment of drug-resistant Caco-2 cells promotes enhanced 5-FU uptake, in contrast to when cells were treated with 5-FU alone. Hence, HD-5 as an adjunct to 5-FU, exhibited strong cancer cell killing even against 5-FU-resistant tumorigenic cells.


Assuntos
Neoplasias do Colo , Fluoruracila , Precursores de Proteínas , Humanos , Fluoruracila/farmacologia , Resistência a Múltiplos Medicamentos , Células CACO-2 , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Apoptose , Peptídeos/uso terapêutico , Mucinas/uso terapêutico
8.
J Rheumatol ; 51(2): 134-138, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302186

RESUMO

OBJECTIVE: Recent advances imply that early events triggering rheumatoid arthritis (RA) occur at mucosal surfaces. We aimed to evaluate whether intestinal permeability is altered in patients at increased risk of RA, and/or predicts the development of clinical arthritis, by measuring serum zonulin family peptides (ZFP) levels, which are shown to reflect intestinal barrier integrity. METHODS: Two independent prospective observational cohorts were studied, including subjects with musculoskeletal symptoms and anticitrullinated protein antibodies (ACPA), but without clinical arthritis at baseline. In Sweden, 82 such at-risk patients were compared to 100 age-matched healthy blood donors. In the UK, 307 at-risk patients were compared to 100 ACPA-negative symptomatic controls. ZFP was measured in baseline sera by enzyme-linked immunoassays. RESULTS: In the Swedish at-risk cohort, ZFP levels were significantly increased in patients compared to controls (mean 41.4 vs 33.6 ng/mL, P < 0.001) and Cox regression analysis showed prognostic value of ZFP for arthritis development (hazard ratio [HZ] 1.04 per ng/mL ZFP increase, 95% CI 1.01-1.07, P = 0.02). Elevated ZFP levels among ACPA-positive at-risk patients compared to symptomatic ACPA-negative controls were confirmed in the UK at-risk cohort (mean 69.7 vs 36.0 ng/mL, P < 0.001), but baseline ZFP were not associated with arthritis development (HR 1.00 per ng/mL ZFP increase, 95% CI 1.00-1.01, P = 0.30). CONCLUSION: Serum ZFP levels are elevated in ACPA-positive at-risk patients when compared to both healthy blood donors and symptomatic ACPA-negative controls. Thus, gut barrier function may be of importance in RA-associated autoimmunity. A possible prognostic value of serum ZFP merits further investigation, preferably in larger prospective cohorts.


Assuntos
Artrite Reumatoide , Autoanticorpos , Haptoglobinas , Precursores de Proteínas , Humanos , Estudos Prospectivos , Peptídeos Cíclicos , Artrite Reumatoide/diagnóstico , Peptídeos
9.
BMC Pediatr ; 24(1): 140, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402172

RESUMO

BACKGROUND: Using Zonulin and Copeptin as potential obesity markers in children, hasn't yet been focused. AIM: To evaluate the association between serum levels of both Zonulin and Copeptin with the obesity markers, and to assess their role as metabolic disturbance predictors in obese children. METHODS: A case-control study comprised 111 Egyptian children (45 males and 66 females); aged 6-10 years to avoid the effect of puberty (prepubertal). They were classified according to their body mass index (BMI) percentiles into: 72 obese (BMI ≥ 95th ), and 39 control ones (BMI > 15th - <85th ), based on the Egyptian Growth Charts for children and adolescents. Anthropometric parameters and blood pressure were measured, and body composition analysis, lipid profile, Zonulin, and Copeptin levels were assessed. RESULTS: The obese group showed a significantly higher value of Copeptin and a lower value of Zonulin than the control one Also, the obese group showed significant negative correlations between Zonulin and both anthropometric obesity markers and body composition, whereas Copeptin showed significant positive ones. Moreover, significant positive correlations were found between Copeptin and both body weight and fat distribution. Insignificant correlations were observed between both serum Zonulin and Copeptin levels and blood pressure and lipid profile. CONCLUSION: Zonulin and Copeptin cannot be used as metabolic disturbance predictors, among Egyptian children, as they were insignificantly correlated with lipid profile or blood pressure.


Assuntos
Glicopeptídeos , Haptoglobinas , Obesidade Pediátrica , Precursores de Proteínas , Masculino , Feminino , Adolescente , Humanos , Criança , Estudos de Casos e Controles , Índice de Massa Corporal , Lipídeos
10.
Int J Mol Sci ; 25(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38396923

RESUMO

The epidermis serves as a protective barrier against external threats and is primarily composed of keratinocytes, which ultimately form corneocytes. Involucrin, a protein integral to the cornified envelope, plays a pivotal role in preserving the functional integrity of the skin barrier. Previous studies have shown that Akt plays an important role in keratinocyte differentiation and skin barrier development. This study investigated whether dihydromyrcenol (DHM), a plant-derived terpene, could increase involucrin production in keratinocytes and sought to elucidate the possible underlying mechanisms. To accomplish this objective, we assessed the alterations in involucrin by DHM through quantitative PCR and Western blot on the HaCaT cell line. The changes in the promoter levels were investigated using luciferase assays. Furthermore, upstream mechanisms were explored through the use of siRNA and inhibitors. To strengthen our findings, the results were subsequently validated in primary cells and 3D skin equivalents. DHM significantly increased involucrin mRNA and protein levels in a concentration-dependent manner. In addition, the Fyn-Akt signaling pathway was found to be required for DHM-induced involucrin expression, as inhibition of Fyn or Akt blocked the increase in involucrin mRNA induced by DHM. The transcription factor Sp1, which is recognized as one of the transcription factors for involucrin, was observed to be activated in response to DHM treatment. Moreover, DHM increased epidermal thickness in a 3D human skin model. These findings suggest that the modulation of involucrin expression with DHM could improve skin barrier function and highlight the importance of manipulating the Akt pathway to achieve this improvement.


Assuntos
Queratinócitos , Monoterpenos , Octanóis , Precursores de Proteínas , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Queratinócitos/metabolismo , Diferenciação Celular/genética , Transdução de Sinais , RNA Mensageiro/metabolismo
11.
Mol Med Rep ; 29(4)2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38391118

RESUMO

Prothymosin α (ProT), a highly acidic nuclear protein with multiple cellular functions, has shown potential neuroprotective properties attributed to its anti­necrotic and anti­apoptotic activities. The present study aimed to investigate the beneficial effect of ProT on neuroplasticity after ischemia­reperfusion injury and elucidate its underlying mechanism of action. Primary cortical neurons were either treated with ProT or overexpressing ProT by gene transfection and exposed to oxygen­glucose deprivation for 2 h in vitro. Immunofluorescence staining for ProT and MAP­2 was performed to quantify ProT protein expression and assess neuronal arborization. Mice treated with vehicle or ProT (100 µg/kg) and ProT overexpression in transgenic mice received middle cerebral artery occlusion for 50 min to evaluate the effect of ProT on neuroplasticity­associated protein following ischemia­reperfusion injury. The results demonstrated that in cultured neurons ProT significantly increased neurite lengths and the number of branches, accompanied by an upregulation mRNA level of brain­derived neurotrophic factor. Furthermore, ProT administration improved the protein expressions of synaptosomal­associated protein, 25 kDa and postsynaptic density protein 95 after ischemic­reperfusion injury in vivo. These findings suggested that ProT can potentially induce neuroplasticity effects following ischemia­reperfusion injury.


Assuntos
Traumatismo por Reperfusão , Timosina , Timosina/análogos & derivados , Camundongos , Animais , Camundongos Transgênicos , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Regulação para Cima , Timosina/genética , Timosina/farmacologia , Timosina/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico
12.
J Mol Biol ; 436(6): 168492, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360088

RESUMO

Many insulin gene variants alter the protein sequence and result in monogenic diabetes due to insulin insufficiency. However, the molecular mechanisms of various disease-causing mutations are unknown. Insulin is synthesized as preproinsulin containing a signal peptide (SP). SPs of secreted proteins are recognized by the signal recognition particle (SRP) or by another factor in a SRP-independent pathway. If preproinsulin uses SRP-dependent or independent pathways is still debatable. We demonstrate by the use of site-specific photocrosslinking that the SRP subunit, SRP54, interacts with the preproinsulin SP. Moreover, SRP54 depletion leads to the decrease of insulin mRNA and protein expression, supporting the involvement of the RAPP protein quality control in insulin biogenesis. RAPP regulates the quality of secretory proteins through degradation of their mRNA. We tested five disease-causing mutations in the preproinsulin SP on recognition by SRP and on their effects on mRNA and protein levels. We demonstrate that the effects of mutations are associated with their position in the SP and their severity. The data support diverse molecular mechanisms involved in the pathogenesis of these mutations. We show for the first time the involvement of the RAPP protein quality control pathway in insulin biogenesis that is implicated in the development of neonatal diabetes caused by the Leu13Arg mutation.


Assuntos
Insulina , Precursores de Proteínas , Estabilidade de RNA , Partícula de Reconhecimento de Sinal , Humanos , Recém-Nascido , Diabetes Mellitus , Insulina/genética , Insulina/metabolismo , Precursores de Proteínas/metabolismo , Sinais Direcionadores de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Partícula de Reconhecimento de Sinal/metabolismo
13.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 53(1): 131-139, 2024 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38310085

RESUMO

OBJECTIVES: To assess the value of serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) and glypican-3 (GPC-3) in the diagnosis of hepatocellular carcinoma (HCC). METHODS: Studies of AFP, PIVKA-Ⅱ, GPC-3 or in combination for the diagnosis of HCC since 2002 were searched in PubMed, Web of Science and Embase databases. The literature was screened according to the inclusion and exclusion criteria, the quality of the included articles was evaluated by QUADAS checklist, and relevant data were extracted by Meta DiSc, Review Manager 5.4 and Stata 15.1. The diagnostic values of AFP, PIVKA-Ⅱ and GPC-3 alone or in combination for HCC were assessed with receiver operating characteristic (ROC) curve. RESULTS: A total of 32 articles were included in the study. Meta-analysis showed that when a single marker was used to diagnose HCC, the area under the ROC curve (AUC) of PIVKA-Ⅱ was the highest (0.88, 95%CI: 0.85-0.91), followed by GPC-3 and AFP. The AUC of combination of serum markers was higher than that of a single marker, and the AUC of PIVKA-Ⅱ combined with GPC-3 was the highest (0.90, 95%CI: 0.87-0.92). When a single marker was used for diagnosis, the sensitivity of PIVKA-Ⅱ and GPC-3 were relatively high (0.75 and 0.76), while the specificity of PIVKA-Ⅱ (0.88) and AFP (0.87) were higher than that of GPC-3 (0.81). The sensitivity of the combination of serum markers was higher than that of a single marker, while the specificity was not significantly improved. When a single marker is used to diagnose HCC, the diagnostic odds ratio (DOR) of PIVKA-Ⅱ was the highest (22, 95%CI: 13-36), followed by GPC-3 and AFP. The DOR of the combination of two markers in the diagnosis of HCC was higher than that of a single marker, and the DOR of AFP combined with GPC-3 was the highest (25, 95%CI: 9-67). The DOR of the combination of the three markers was significantly reduced to 10 (95%CI: 7-45). CONCLUSIONS: When a single marker is used, PIVKA-Ⅱ has a higher diagnostic value for HCC. The combination of two markers can significantly improve the diagnostic sensitivity, and AFP combined with PIVKA-Ⅱ is recommended for the diagnosis of HCC. The combination of all three markers failed to further improve the diagnostic value.


Assuntos
Biomarcadores , Carcinoma Hepatocelular , Neoplasias Hepáticas , Precursores de Proteínas , Protrombina , Humanos , alfa-Fetoproteínas , Carcinoma Hepatocelular/diagnóstico , Glipicanas , Neoplasias Hepáticas/diagnóstico
14.
Clin Chim Acta ; 556: 117831, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38378104

RESUMO

BACKGROUND: Volatile organic compounds (VOCs) have been shown as promising biomarkers for hepatocellular carcinoma (HCC) diagnosis. We aimed to investigate the performance of VOCs for diagnosing early-stage HCC in patients at-risk for HCC. METHODS: VOCs were identified in exhaled breath samples collected from 87 early-stage HCC patients, 90 cirrhotic patients, and 72 HBV-infected patients using thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry. The VOC levels were compared between the three groups. An association between VOCs and HCC was determined using logistic regression analysis. Diagnostic performance of VOCs was estimated using the AUROC and compared to serum alpha-fetoprotein (AFP). RESULTS: The levels of acetone monomer, dimethyl sulfide, 1,4-pentadiene, isopropyl alcohol, and acetone dimer were significantly different between the three groups. After adjusting for liver function test and AFP, acetone dimer was significantly associated with HCC. Acetone dimer significantly outperformed AFP with 86.2 % vs. 61.2 % sensitivity, 87.6 % vs. 66.2 % specificity, 86.9 % vs. 63.5 % for accuracy, and AUROC of 0.908 vs. 0.665, p = 0.007, <0.001, <0.001, and 0.001, respectively, for differentiating between HCC and cirrhosis. CONCLUSION: Acetone showed a better performance than AFP for diagnosing early HCC in at-risk patients. Further studies to validate the utility of VOCs as an HCC surveillance tool are needed.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , alfa-Fetoproteínas/análise , Acetona/análise , Curva ROC , Precursores de Proteínas , Protrombina , Cromatografia Gasosa-Espectrometria de Massas , Cirrose Hepática , Biomarcadores Tumorais
16.
Cancer Med ; 13(3): e6825, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38361401

RESUMO

AIM: The aim of our study was to evaluate the accuracy of serum biomarkers (AFP/PIVKA-II) and their combination in HCC diagnosis among Caucasian cirrhotic patients. METHODS: Serum AFP/PIVKA-II levels were evaluated in 218 cirrhotics (163 males, 118 CTP-A, 66 ALBI-I, 111 with varices, 63 with diabetes) with (n = 90) or without (n = 128) HCC. Patients with HCC were categorized to BCLC Stage 0/A (n = 12), B (n = 21), C (n = 48), and D (n = 9). RESULTS: The two groups were comparable for all baseline parameters except for age, platelets, and diabetes presence. Median levels of AFP (239.1 vs. 4.0 ng/mL) and PIVKA-II (4082.7 vs. 45.8 mAU/mL) were both significantly higher in HCC group compared to controls (p < 0.001). AUROC and cutoff value for HCC diagnosis were 88%/12.35 ng/mL (AFP) and 84.4%/677.13 mAU/mL (PIVKA-II), whereas their combination showed better diagnostic accuracy (AUROC = 90.2%). The diagnostic accuracy of each biomarker separately was moderate or good in BCLC-0/A/B and was excellent only for BCLC-C patients (AFP: AUROC = 94.3%, cutoff = 12.35 ng/mL and PIVKA-II: 91.3%, 253.51 mAU/mL) whereas their combination presented quite acceptable results in BCLC-B (AUROC = 92.4%) and BCLC-C (AUROC = 95.7%). Excluding HCC patients with high AFP (above 400 ng/mL), the diagnostic accuracy of each biomarker separately and their combination was moderate/good in all groups, except for their combination in BCLC-C (AUROC = 90.5%). CONCLUSIONS: Each biomarker separately showed acceptable accuracy for detecting HCC in cirrhotic patients and excellent for those in BCLC-C stage. The combination of the biomarkers presented excellent results in BCLC-B/C patients. The diagnostic accuracy of PIVKA-II and the combination of the two biomarkers in patients expressing low/non-diagnostic AFP levels was good in BCLC-B and excellent in BCLC-C patients.


Assuntos
Biomarcadores , Carcinoma Hepatocelular , Diabetes Mellitus , Neoplasias Hepáticas , Precursores de Proteínas , Protrombina , Masculino , Humanos , Vitamina K , Carcinoma Hepatocelular/diagnóstico , alfa-Fetoproteínas , Neoplasias Hepáticas/diagnóstico , Proteínas Sanguíneas , Vitaminas , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico
17.
BMC Nephrol ; 25(1): 16, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200454

RESUMO

BACKGROUND: Plasma proenkephalin A (PENK-A) is a precursor of active enkephalins. Higher blood concentrations have been associated with estimated glomerular filtration rate (eGFR) decline in European populations. Due to the significant disparity in incident chronic kidney disease (CKD) between White and Black people, we evaluated the association of PENK-A with incident CKD and other kidney outcomes among a biracial cohort in the U.S. METHODS: In a nested cohort of 4,400 participants among the REasons for Geographic And Racial Differences in Stroke, we determined the association between baseline PENK-A concentration and incident CKD using the creatinine-cystatin C CKD-EPI 2021 equation without race coefficient, significant eGFR decline, and incident albuminuria between baseline and a follow-up visit 9.4 years later. We tested for race and sex interactions. We used inverse probability sampling weights to account for the sampling design. RESULTS: At baseline, mean (SD) age was 64 (8) years, 49% were women, and 52% were Black participants. 8.5% developed CKD, 21% experienced ≥ 30% decline in eGFR and 18% developed albuminuria. There was no association between PENK-A and incident CKD and no difference by race or sex. However, higher PENK-A was associated with increased odds of progressive eGFR decline (OR: 1.12; 95% CI 1.00, 1.25). Higher PENK-A concentration was strongly associated with incident albuminuria among patients without diabetes mellitus (OR: 1.29; 95% CI 1.09, 1.53). CONCLUSION: While PENK-A was not associated with incident CKD, its associations with progression of CKD and incident albuminuria, among patients without diabetes, suggest that it might be a useful tool in the evaluation of kidney disease among White and Black patients.


Assuntos
Precursores de Proteínas , Insuficiência Renal Crônica , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Albuminúria/epidemiologia , Fatores Raciais , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Encefalinas
18.
Contact Dermatitis ; 90(4): 385-393, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38205911

RESUMO

BACKGROUND: Common hyperkeratotic palmar skin lesions include chronic hand eczema (CHE), hyperkeratotic hand eczema (HHE), palmar psoriasis (PP). However, clinically differentiating these disorders is often challenging. OBJECTIVES: To compare the expressions of keratin (K) 5, K9, K14 and involucrin in palmar hyperkeratotic lesions (HHE, CHE and PP). MATERIALS AND METHODS: Immunohistochemical staining was performed on skin biopsy specimens obtained from the palms of patients clinically diagnosed with CHE, HHE and PP (n = 21, 24 and 18, respectively). RESULTS: K5 and K14 expression levels were higher in the spinous and granular layers of PP and HHE compared to CHE. Involucrin was expressed in the basal layer of PP and HHE but not in CHE. K9 expression was decreased in PP and HHE compared to CHE. CONCLUSION: Keratin and involucrin expression in the epidermis are markers of keratinocyte differentiation. Expression levels of keratin and involucrin were similar between the HHE and PP groups, suggesting that HHE shares pathogenesis with PP rather than CHE.


Assuntos
Dermatite Alérgica de Contato , Eczema , Precursores de Proteínas , Psoríase , Dermatopatias , Humanos , Queratinas/metabolismo
19.
Life Sci ; 340: 122460, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38286207

RESUMO

AIMS: Extracellular vesicles (EVs) are involved in intercellular communication and are a topic of increasing interest due to their therapeutic potential. The aim of this study was to determine whether human islet-derived EVs contain insulin, and if so, what role do they play in glucose stimulated insulin secretion. MAIN METHODS: We isolated EVs from human islets culture and plasma to probe for insulin. Plasma from hyperglycemic glucose clamp experiments were also used to isolate and measure EV insulin content in response to a secretory stimulus. We performed immunogold electron microscopy for insulin presence in EVs. Co-culture experiments of isolated EVs with fresh islets were performed to examine the effect of EV cargo on insulin receptor signaling. KEY FINDINGS: EVs isolated from culture medium contained insulin. Glucose treatment of islets increased the level of EV insulin. Hyperglycemic glucose clamp experiments in humans also lead to increased levels of insulin in plasma-derived EVs. Immunogold electron microscopy and proteinase K-digestion experiments demonstrated that insulin in EVs predominantly associated with the exterior surface of EVs while western blot analyses uncovered the presence of only preproinsulin in EVs. Membrane-bound preproinsulin in EVs was capable of activating insulin signaling pathway in an insulin receptor-dependent manner. The physiological relevance of this finding was observed in priming of human naïve islets by EVs during glucose stimulated insulin secretion. SIGNIFICANCE: Our data suggest that (1) human islets secret insulin via an alternate pathway (EV-mediated) other than conventional granule-mediated insulin secretion, and (2) EV membrane bound preproinsulin is biologically active.


Assuntos
Vesículas Extracelulares , Células Secretoras de Insulina , Ilhotas Pancreáticas , Precursores de Proteínas , Humanos , Células Secretoras de Insulina/metabolismo , Secreção de Insulina , Receptor de Insulina/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Vesículas Extracelulares/metabolismo , Ilhotas Pancreáticas/metabolismo
20.
Bratisl Lek Listy ; 125(2): 102-106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38219063

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common forms of cancer significantly affecting the mortality and morbidity rates. The increasing incidence of HCC is a great concern across the globe. The current methods of HCC screening, detection and diagnosis depend mainly on imaging techniques. However, biomarkers represent a relatively easy and noninvasive way to detect and estimate the disease prognosis. New potential biomarkers such as α-fetoprotein (AFP), des­Î³­carboxyprothrombin (DCP), α-fetoprotein L3 (AFP-L3), glypican 3 (GCP3), micro-RNA, and Golgi-protein 73 (GP73) are being used more often in the diagnosis and prognosis of HCC. The lack of prudent diagnostic measures makes early detection of HCC nearly impossible. The use of biomarkers to detect cancer has helped to screen for the disease. However, the most commonly used biomarkers for HCC have inadequate performance characteristics. Despite numerous efforts to identify molecules as potential biomarkers, there is no single ideal marker for HCC. In this paper the main biomarkers for the surveillance, diagnosis and prognosis of HCC are reviewed. The advantages and limitations of these biomarkers are summarized, and the future development directions are proposed (Tab. 1, Ref. 30). Keywords: hepatocellular carcinoma, biomarkers, AFP, DCP, diagnosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , alfa-Fetoproteínas , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Biomarcadores Tumorais , Precursores de Proteínas , Protrombina , Biomarcadores
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