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1.
Nutr Res ; 109: 58-70, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36587538

RESUMO

Intake biomarkers of cranberry juice in women can assess consumption in clinical trials. Discriminant biomarkers in urine may explain urinary tract infection (UTI) preventive activities. We hypothesized that validated and annotated discriminant metabolites in human urine could be used as intake biomarkers in building predictive multivariate models to classify cranberry consumers. Urine samples were collected from 16 healthy women aged 18 to 29 years at baseline and after 3- and 21-day consumption of cranberry or placebo juice in a double-blind, crossover study. Urine metabolomes were analyzed using ultra high-performance liquid chromatography coupled with Orbitrap mass spectrometry. Paired and unpaired multivariate analyses were used to annotate or identify discriminant metabolic features after cranberry consumption. Twenty-six discriminant metabolic features (paired analysis) and 27 (unpaired analysis) after cranberry consumption in an open-label intervention were rediscovered in the blinded study. These metabolites included exogenous (quinic acid) and endogenous ones (hippuric acid). The paired analysis showed better model fitting with partial least-square discriminant analysis models built on all metabolites than the unpaired analysis. Predictive models built on shared metabolites by the unpaired analysis were able to classify cranberry juice consumers with 84.4% to 100% correction rates, overall better than the paired analysis (50%-100%). The double-blind study validated discriminant metabolites from a previous open-label study. These urinary metabolites may be associated with the ability of cranberries to prevent UTIs and serve as potential cranberry intake biomarkers. It reveals the importance of selecting the right predictive models to classify cranberry consumers with higher than 95% correction rates.


Assuntos
Infecções Urinárias , Vaccinium macrocarpon , Humanos , Feminino , Vaccinium macrocarpon/química , Estudos Cross-Over , Infecções Urinárias/prevenção & controle , Infecções Urinárias/tratamento farmacológico , Metaboloma , Extratos Vegetais , Biomarcadores/urina
2.
Chemosphere ; 314: 137747, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36608880

RESUMO

Nitrogenous flame retardants (NFRs) have aroused worldwide public concern as their nephrotoxic effect. However, knowledge regarding the pathogenesis mechanism of their exposure to induce kidney injury remains largely unknown. In this study, eight NFRs, four oxidative stress biomarkers (OSBs), and one kidney injury biomarker, namely neutrophil gelatinase-associated lipocalin (NGAL), were measured in urine specimens collected from residents living around e-waste disassembly and reference areas, representing two exposure scenarios. Significant higher concentrations of Σ8NFR (median: 70.6 vs. 33.8 µg/g Cre) and five biomarkers (124 vs. 97.4 µg/g Cre) were found in urines of populations living in e-waste site compared to those in the reference site (p < 0.05). Primary NFRs exhibited significant positive associations with OSBs and NGAL regardless of the population examined, implying that chronic NFRs exposure could induce oxidative stress and kidney damage. By using structure equation model, we found that oxidative stress, particularly DNA and RNA oxidation mediated 16.1% of the total effect of NFRs on NGAL in e-waste related people, but not on the general population. Overall, this study suggests long-term chronic exposure to NFRs can induce oxidative stress and renal injury in humans but the pathogenesis mode may be scenario-specific.


Assuntos
Resíduo Eletrônico , Retardadores de Chama , Humanos , Retardadores de Chama/toxicidade , Lipocalina-2 , Resíduo Eletrônico/efeitos adversos , Resíduo Eletrônico/análise , China , Estresse Oxidativo , Biomarcadores/urina , Rim
3.
Se Pu ; 41(1): 47-57, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36633076

RESUMO

Premature ovarian failure (POF) is a prevalent gynecological disease. In traditional Chinese medicine, it is believed that POF is directly related to abnormal function of the liver and kidneys. As such, regulation of the liver metabolism through the use of medicinal and edible substances is important for the treatment of POF. Pine pollen, a traditional Chinese medicinal and edible pollen variety, contains various active substances, such as sex hormones and phytohormones, which have been used to inhibit inflammation, regulate the immune system, and protect reproductive tissues. Using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS), this study examined the influence of pine pollen on the liver metabolome of cyclophosphamide-induced POF model Sprague Dawley (SD) rats. The variations in the metabolites present in the liver tissue of control SD rats, model SD rats, and SD rats treated with various doses of pine pollen or estrogen were analyzed using principal component analysis (PCA) in combination with orthogonal partial least squares discriminant analysis (OPLS-DA) and other multivariate statistical methods to reveal the mechanism of pine pollen intervention in the livers of POF SD rats. An animal model experiment was conducted using six groups of ten-week-old rats. Cyclophosphamide was administered intraperitoneally to the model group and four intervention groups at a dosage of 60 mg/kg for 1 d followed by a dosage of 10 mg/kg for 14 d. Within the following four weeks, each of the four intervention groups received the intragastric administration of 0.1, 0.5, or 1.5 g/kg bodyweight (BW) of pine pollen, or 0.075 g/kg BW of conjugated estrogens (positive control). Equal quantities of normal saline were administered to the control and cyclophosphamide-treated model groups. Subsequently, the rat livers were subject to pseudotargeted metabolomics, and a total of 687 liver metabolites were discovered using both positive and negative ions. The metabolites differing in content were screened using the t-test (p<0.05) and the fold change (FC>2 or <0.5) in univariate analysis, and the variable importance in projection (VIP>1) in multivariate analysis. It was found that in comparison with the control group, the contents of 32 metabolites significantly increased, while those of 28 metabolites significantly decreased in the model group. The majority of these metabolites were involved α-linolenic acid metabolism, vitamin B6 metabolism, and purine metabolism, along with the lysine degradation and glycolysis/gluconeogenesis metabolic pathways. Compared with the cyclophosphamide-induced model group, the estrogen group exhibited increased levels of 47 metabolites and decreased levels of 29 metabolites, wherein 34 metabolites were restored to the levels found in the control group. These metabolites mainly involved the vitamin B6, lysine, glycolysis/gluconeogenesis, arginine and proline, and cysteine and methionine metabolic pathways. In the low/medium/high-dose pine pollen groups, the contents of 34/32/34 metabolites increased, the contents of 30/37/24 metabolites decreased, and the contents of 47/38/34 metabolites were restored to the levels found in the control group, respectively. These metabolites were mainly involved in vitamin B6 metabolism, purine metabolism, and the glycolysis/gluconeogenesis metabolic pathway. These results therefore indicate that the restoring effect of pine pollen is equivalent or superior to that of conjugated estrogen. Additionally, based on the known metabolic pathways, it appears that when estrogen interferes with the liver metabolism, the key metabolic pathways that become affected are the arginine and proline metabolism and cysteine and methionine metabolism pathways. In contrast, pine pollen intervention affected existing metabolic pathways that were known to be disordered by cyclophosphamide. The use of pine pollen may therefore restore the levels of many metabolites. It should be noted that 23 overlaps exist between the estrogen-restored metabolites and the pine pollen-restored metabolites, including a variety of acylcarnitines, such as ACar 10∶0. As a result, pine pollen extract may be able to normalize the liver metabolic abnormalities induced by POF. This study therefore establishes a theoretical reference for the development of functional applications for pine pollen and for the treatment of POF.


Assuntos
Medicamentos de Ervas Chinesas , Insuficiência Ovariana Primária , Humanos , Feminino , Ratos , Animais , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Insuficiência Ovariana Primária/tratamento farmacológico , Cisteína , Lisina , Medicamentos de Ervas Chinesas/química , Metabolômica , Cromatografia Líquida de Alta Pressão , Fígado/metabolismo , Estrogênios , Ciclofosfamida , Purinas , Biomarcadores/urina
4.
Environ Res ; 216(Pt 2): 114638, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306878

RESUMO

Starting in 2002, regulations and legislative amendments in Germany focused on the non-smoker protection with several measures to reduce exposure to secondhand tobacco smoke (SHS). The present work aimed to evaluate the relationship between polycyclic aromatic hydrocarbons (PAHs) and SHS exposure and to determine to which extent enforced non-smoking regulations and smoking bans affected the exposure of the non-smoking population in Germany since their implementation in the early 2000s until today. For this purpose, cotinine and selected monohydroxylated PAHs (OH-PAHs) were analyzed by means of (UP)LC-MS/MS in 510 24-h-urine samples of the Environmental Specimen Bank collected over a time span of 24 years from 1995 to 2019. Median urinary cotinine levels were found to steadily and significantly decline by 82% from 1995 to 2019. A significant decrease of urinary 3-hydroxybenzo[a]pyrene (19%), 1-OH-pyrene (39%), 1-naphthol (66%), 1- (17%), 2- (25%), and 3-OH-phenanthrene (22%) was also observed throughout the same time span. The decline in urinary levels of cotinine and several OH-PAHs can most likely be attributed to smoking bans and regulations limiting SHS and PAH exposure. This study therefore emphasizes the relevance of human biomonitoring to investigate the exposure of humans to chemicals of concern, assess the effectiveness of regulatory measures, and help policies to enforce provisions to protect public health.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluição por Fumaça de Tabaco , Humanos , Hidrocarbonetos Policíclicos Aromáticos/urina , Cotinina/urina , Poluição por Fumaça de Tabaco/análise , Cromatografia Líquida , Monitoramento Ambiental , Espectrometria de Massas em Tandem , Pirenos , Alemanha , Biomarcadores/urina
5.
Am J Physiol Gastrointest Liver Physiol ; 324(2): G142-G154, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36513601

RESUMO

Excess alcohol intake causes millions of deaths annually worldwide. Asymptomatic early-stage, alcohol-associated liver disease (ALD) is easily overlooked, and ALD is usually only diagnosed in more advanced stages. We explored the possibility of using polar urine metabolites as biomarkers of ALD for early-stage diagnosis and functional assessment of disease severity by quantifying the abundance of polar metabolites in the urine samples of healthy controls (n = 18), patients with mild or moderate liver injury (n = 21), and patients with severe alcohol-associated hepatitis (n = 25). The polar metabolites in human urine were first analyzed by untargeted metabolomics, showing that 209 urine metabolites are significantly changed in patients, and 17 of these are highly correlated with patients' model for end-stage liver disease (MELD) score. Pathway enrichment analysis reveals that the caffeine metabolic pathway is the most affected in ALD. We then developed a targeted metabolomics method and measured the concentration of caffeine and its metabolites in urine using internal and external standard calibration, respectively. The described method can quantify caffeine and its 14 metabolites in 35 min. The results of targeted metabolomics analysis agree with the results of untargeted metabolomics, showing that 13 caffeine metabolites are significantly decreased in patients. In particular, the concentrations of 1-methylxanthine, paraxanthine, and 5-acetylamino-6-amino-3-methyluracil are markedly decreased with increased disease severity. We suggest that these three metabolites could serve as functional biomarkers for differentiating early-stage ALD from more advanced liver injury.NEW & NOTEWORTHY Our study using both untargeted and targeted metabolomics reveals the caffeine metabolic pathway is dysregulated in ALD. Three caffeine metabolites, 1-methylxanthine, paraxanthine, and 5-acetylamino-6-amino-3-methyluracil, can differentiate the severity of early-stage ALD.


Assuntos
Doença Hepática Terminal , Hepatopatias Alcoólicas , Humanos , Cafeína/metabolismo , Índice de Gravidade de Doença , Hepatopatias Alcoólicas/urina , Metabolômica/métodos , Biomarcadores/urina
6.
J Am Chem Soc ; 145(2): 919-928, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36524698

RESUMO

Urinary monitoring of diseases has gained considerable attention due to its simple and non-invasive sampling. However, urinalysis remains limited by the dearth of reliable urinary biomarkers and the intrinsically enormous heterogeneity of urine samples. Herein, we report, to our knowledge, the first renal-clearable Raman probe encoded by an internal standard (IS)-conjugated reporter that acts as a quantifiable urinary biomarker for reliable monitoring of cancer development, simultaneously eliminating the impact of sample heterogeneity. Upon delivery of the probes into tumor microenvironments, the endogenously overexpressed ß-glucuronidase (GUSB) can cleave the target-responsive residues of the probes to produce IS-retained gold nanoclusters, which were excreted into host urine and analyzed by Au growth-based surface-enhanced Raman spectroscopy. As a result, the in vivo GUSB activity was transformed into in vitro quantitative urinary signals. Based on this IS-encoded synthetic biomarker, both the cancer progression and therapy efficacy were quantitatively monitored, potentiating clinical implications.


Assuntos
Nanopartículas Metálicas , Neoplasias , Humanos , Biomarcadores/urina , Neoplasias/diagnóstico , Rim , Análise Espectral Raman/métodos , Ouro/química , Nanopartículas Metálicas/química , Microambiente Tumoral
7.
Environ Res ; 218: 115039, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36513126

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental endocrine disruptors with known carcinogenic, reproductive, and developmental toxicity. Important knowledge gaps remain regarding the relationship between PAH exposure and unexplained recurrent spontaneous abortion (URSA). In the present study, twelve monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were measured in the urine of 413 URSA cases and 434 controls. The main OH-PAHs measured in this study were monohydroxy metabolites of naphthalene, followed by fluorene and phenanthrene. After the creatinine correction, the median concentration of urinary OH-PAHs in the control group (17.4 µg/g Creatinine) was higher than that in the case group (14.2 µg/g Creatinine). There was no positive relationship between PAH exposure and URSA using binary logistic regression analysis. Among 847 Chinese women of childbearing age, residential environment, type of drinking water, and education level were the influencing factors of PAH exposure. The health risk assessment showed that over 98% of women had a carcinogenic risk with carcinogenic risk values above the acceptable level (10-6). Although this large-scale case-control study did not observe an association between PAH exposure and URSA, more attention should be paid to the high carcinogenic risk due to PAH exposure in women of reproductive age.


Assuntos
Aborto Espontâneo , Hidrocarbonetos Policíclicos Aromáticos , Gravidez , Humanos , Feminino , Hidrocarbonetos Policíclicos Aromáticos/urina , Creatinina , Estudos de Casos e Controles , Carcinógenos , Medição de Risco , Biomarcadores/urina
8.
Sci Total Environ ; 858(Pt 3): 159994, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36368381

RESUMO

Phthalates and other plasticisers are extensively used in medical devices (MD) from which they can leach out and lead to potential multiple problems for the patients. This exposure is a major issue because it is associated with reproductive and neurodevelopment disorders. The Neonatal Intensive Care Units (NICU) population is at high risk due to the daily intensive medical interventions, the reduced ability of newborns to remove these contaminants and their higher sensitivity to endocrine disruptors. We conducted a multicentric biomonitoring study to assess and compare the urinary levels of DEHP (di-(2-ethylhexyl)phthalate), DEHTP (di-(2-ethylhexyl)terephthalate) and TEHTM (tri-(2-ethylhexyl)trimellitate) metabolites as biomarkers of this exposure during and after the newborns' stay in NICU. Daily urinary samples were collected in NICU and at discharge from the hospital for each patient. MD sources and exposure factors were also investigated. 508 urinary samples from 97 patients enrolled in centres 1 and 2 (C1/C2) were collected. The exposure of newborns to DEHP was greater than that of DEHTP and TEHTM, with a median concentration of DEHP metabolites (C1:195.63 ng/mL;C2:450.87 ng/mL) respectively 5 to 10 times higher and 57 to 228 times higher than the median concentrations of DEHTP and TEHTM metabolites. The urinary concentrations of DEHP and TEHTM metabolites were significantly lower at discharge than in NICU, with a 18-and 35-fold decrease for DEHP and a 4 and 8-fold decrease for TEHTM, respectively for C1 and C2, but were similar for DEHTP metabolites. MD used for respiratory assistance, infusion therapy,enteral nutrition and transfusion were the main sources of exposure. Smaller gestational age and body weight significantly increased the newborns' exposure. The elevated levels of DEHP metabolites in NICU patients are still alarming. Additional efforts are necessary to promote its substitution in MD by possibly safer alternatives such as TEHTM and DEHTP, particularly when used for the care of newborns.


Assuntos
Disruptores Endócrinos , Unidades de Terapia Intensiva Neonatal , Ácidos Ftálicos , Plastificantes , Humanos , Recém-Nascido , Ácidos Ftálicos/análise , Plastificantes/análise , Exposição Ambiental , Disruptores Endócrinos/análise , Biomarcadores/urina , Dietilexilftalato/urina
9.
Pediatr Nephrol ; 37(4): 881-890, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34545446

RESUMO

BACKGROUND: AKI is an important complication post cardiac surgery in children. An early diagnosis can help in mitigating complications and allow for prognostication. Urinary albumin:creatinine ratio (ACR) as a biomarker can provide a cheaper and more accessible AKI risk assessment and prediction. There is a paucity of paediatric literature regarding its utility. METHODS: This was a prospective observational study, enrolling all children aged 1 month to 18 years, who underwent cardiac surgery, with use of cardiopulmonary bypass. Cohort was divided into groups < 2 years and ≥ 2 years for analyses to account for differences in physiological albumin excretion with age. RESULTS: Of 143 children enrolled in the study, 36 developed AKI. In both age groups, the post-operative ACR was higher than pre-operative ACR among patients with and without AKI. In the group aged ≥ 2 years, the highest first post-operative ACR tertile (> 75.8 mg/g) predicted post-operative AKI after adjusting for clinical variables (adjusted RR, 11.71; 1.85-16.59). In the group aged < 2 years, the highest first post-operative ACR tertile (> 141.3 mg/g) predicted post-operative AKI in unadjusted analysis but not after adjusting for clinical variables (RR, 2.78; 0.70-6.65). For AKI risk prediction, AUC (95% CI) was highest after combining clinical model and pre-operative ACR for groups aged < 2 years [0.805 (0.713-0.896)] and ≥ 2 years [0.872 (0.772-0.973)]. CONCLUSIONS: This study provides evidence for use of albuminuria as a feasible biomarker in AKI prediction in children post cardiac surgery, especially when added to a clinical model. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Albuminas , Albuminúria/complicações , Albuminúria/etiologia , Biomarcadores/urina , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/urina
10.
J Pediatr ; 241: 133-140.e3, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34547334

RESUMO

OBJECTIVE: To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: We performed a multicenter prospective observational study of 64 neonates. Urine specimens were obtained at 12, 24, 48, and 72 hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin-18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor-binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO (Kidney Disease: Improving Global Outcomes) AKI criteria. RESULTS: AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use compared with those without AKI (median [IQR], 2 [0-5] days vs 0 [0-2] days; P = .026). Mortality was greater in neonates with AKI (25% vs 2%; P = .012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs yielded only a fair prediction. KIM-1 had the best predictive performance across time points, with an AUC (SE) of 0.79 (0.11) at 48 hours of life. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48 hours of life. CONCLUSIONS: Urine NGAL, KIM-1, and IL-18 levels were elevated in neonates with HIE receiving therapeutic hypothermia who developed AKI. However, wide variability and unclear cutoff levels make their clinical utility unclear.


Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/urina , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/terapia , Biomarcadores/urina , Cistatina C/urina , Feminino , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Recém-Nascido , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Interleucina-18/urina , Lipocalina-2/urina , Masculino , Estudos Prospectivos , Inibidor Tecidual de Metaloproteinase-2/urina , Vasoconstritores/administração & dosagem
11.
Anal Chem ; 94(50): 17477-17484, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36480771

RESUMO

To diagnose renal function using a biochip capable of detecting SERS and to assess Raman measurements taken from a bilateral renal ischemia model and the feasibility of early diagnosis was done. After generating a bilateral renal ischemia rat model, blood and urine were collected. After confirming the presence of renal injury and function, liquid drops were placed onto a Raman chip whose surface had been enhanced with Au-ZnO nanorods. SERS biomarkers that diffused into the nanogaps were selectively amplified. Raman signals varied based on the severity of the renal function, and these differences were confirmed statistically. These results confirm that renal ischemia leads to renal dysfunction and that surface-enhanced Raman spectroscopy and a machine learning algorithm can be used to track signals in the urine from the release of SERS biomarkers.


Assuntos
Nefropatias , Insuficiência Renal , Ratos , Animais , Análise Espectral Raman/métodos , Ouro/química , Biomarcadores/urina , Algoritmos
12.
Arch Ital Urol Androl ; 94(4): 443-446, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36576463

RESUMO

OBJECTIVE: To evaluate the role of urinary Monocyte Chemotactic Protein-1 (MCP1) and urinary epidermal growth factor (EGF) in diagnosing of upper urinary tract obstruction (UUTO). PATIENT AND METHODS: Over a period of 6 months (January 2022 to June 2022) this prospective case control comparative study was conducted on 120 participants, 60 of them with UUTO and 60 healthy controls. A morning urine sample of all participants was tested for EGF and MCP-1. after taking a detailed history taking and laboratory and radiological evaluation. RESULTS: Urinary MCP-1(uMCP-1) was significantly (p-value = 0.000) increased in UUTO group showing a mean ± SD of 518.10 ± 51.19 ng/L compared to a mean ± SD of 143.32 ± 58.03 ng/L in the controls, whereas a significantly (p-value = 0.000) decrease of urinary EGF (uEGF) was observed in patients with UUTO compared to control group. A significant difference of uEGF level and uEGF/uMCP1 ratio was observed between mild compared to moderate/severe UUTO. CONCLUSIONS: Utilization of the urinary biomarker MCP1, EGF and uEGF/uMCP1 ratio in patients with UUTO can adequately be used as a simple, efficacious and noninvasive way in diagnosis of UUTO.


Assuntos
Fator de Crescimento Epidérmico , Nefropatias , Humanos , Fator de Crescimento Epidérmico/metabolismo , Quimiocina CCL2/urina , Rim , Biomarcadores/urina
13.
Physiol Rep ; 10(24): e15533, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36541220

RESUMO

Hypoxic ischemic encephalopathy (HIE) is associated with acute kidney injury (AKI) in neonates with birth asphyxia. This study aimed to utilize urinary biomarkers to characterize AKI in an established neonatal rat model of HIE. Day 7 Sprague-Dawley rat pups underwent HIE using the Rice-Vannucci model (unilateral carotid ligation followed by 120 mins of 8% oxygen). Controls included no surgery and sham surgery. Weights and urine for biomarkers (NGAL, osteopontin, KIM-1, albumin) were collected the day prior, daily for 3 days post-intervention, and at sacrifice day 14. Kidneys and brains were processed for histology. HIE pups displayed histological evidence of kidney injury including damage to the proximal tubules, consistent with resolving acute tubular necrosis, and had significantly elevated urinary levels of NGAL and albumin compared to sham or controls 1-day post-insult that elevated for 3 days. KIM-1 significantly increased for 2 days post-HIE. HIE did not significantly alter osteopontin levels. Seven days post-start of experiment, controls were 81.2% above starting weight compared to 52.1% in HIE pups. NGAL and albumin levels inversely correlated with body weight following HIE injury. The AKI produced by the Rice-Vannucci HIE model is detectable by urinary biomarkers, which can be used for future studies of treatments to reduce kidney injury.


Assuntos
Injúria Renal Aguda , Hipóxia-Isquemia Encefálica , Animais , Ratos , Injúria Renal Aguda/complicações , Biomarcadores/urina , Hipóxia-Isquemia Encefálica/complicações , Lipocalina-2 , Osteopontina , Ratos Sprague-Dawley
14.
Biomolecules ; 12(12)2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36551217

RESUMO

The aim of this study was to demonstrate that pseudocholinesterase (CHE) serum level is a useful diagnostic biomarker for untreated Wilson's disease (WD). Between 2013 and 2019, about 75 patients were referred to the outpatient department of the University of Düsseldorf with suspected Wilson's disease. In 31 patients with suspected Wilson's disease (WD-SUS-group), WD was excluded by means of investigations other than analysis of blood and urine. A total of 27 parameters of blood and urine in these 31 patients were compared to those of 20 de novo patients with manifest WD (WD-DEF-group), which parameter showed the highest significance level of difference between the WD-DEF-group and the WD-SUS-group. Thereafter, receiver operating characteristics (ROC-curves) were analyzed to evaluate which parameter showed the largest area under the curve (AUC) to detect WD. Finally, a logistic regression analysis was performed to analyze which combination of parameters allowed the best classification of the 51 patients either into the WD-DEF-group or into the WD-SUS-group. CHE showed the highest significance level for a difference between the WD-DEF- and WD-SUS-group, had the highest AUC, and, in combination with ceruloplasmin, allowed 100% correct classification. Without CHE, no other combination of parameters reached this level of correct classification. After the initiation of treatment, which regularly results in an improvement in CHE, the high diagnostic accuracy of this biomarker was lost. Cholinesterase turns out to be an excellent biomarker for differentiation between untreated de novo patients with manifest WD and heterozygotic gene carriers.


Assuntos
Butirilcolinesterase , Degeneração Hepatolenticular , Humanos , Biomarcadores/sangue , Biomarcadores/urina , Butirilcolinesterase/sangue , Butirilcolinesterase/urina , Ceruloplasmina/análise , Ceruloplasmina/urina , Degeneração Hepatolenticular/diagnóstico , Curva ROC
15.
Front Immunol ; 13: 1044743, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569940

RESUMO

Introduction: The gold standard for diagnosis of active lupus nephritis (ALN), a kidney biopsy, is invasive with attendant morbidity and cannot be serially repeated. Urinary ALCAM (uALCAM) has shown high diagnostic accuracy for renal pathology activity in ALN patients. Methods: Lateral flow assays (LFA) for assaying uALCAM were engineered using persistent luminescent nanoparticles, read by a smartphone. The stability and reproducibility of the assembled LFA strips and freeze-dried conjugated nanoparticles were verified, as was analyte specificity. Results: The LFA tests for both un-normalized uALCAM (AUC=0.93) and urine normalizer (HVEM)-normalized uALCAM (AUC=0.91) exhibited excellent accuracies in distinguishing ALN from healthy controls. The accuracies for distinguishing ALN from all other lupus patients were 0.86 and 0.74, respectively. Conclusion: Periodic monitoring of uALCAM using this easy-to-use LFA test by the patient at home could potentially accelerate early detection of renal involvement or disease flares in lupus patients, and hence reduce morbidity and mortality.


Assuntos
Nefrite Lúpica , Humanos , Nefrite Lúpica/patologia , Molécula de Adesão de Leucócito Ativado , Reprodutibilidade dos Testes , Rim/patologia , Biomarcadores/urina
16.
Biosensors (Basel) ; 12(12)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36551084

RESUMO

Creatinine is one of the most common and specific biomarkers for renal diseases, usually found in the serum and urine of humans. Its level is extremely important and critical to know, not only in the case of renal diseases, but also for various other pathological conditions. Hence, detecting creatinine in clinically relevant ranges in a simplistic and personalized manner is interesting and important. In this direction, an optical sensing device has been developed for the simple, point-of-care detection of creatinine. The developed biosensor was able to detect creatinine quantitatively based on optical signals measured through a change in color. The sensor has been integrated with a smartphone to develop a palm-sized device for creatinine analysis in personalized settings. The sensor has been developed following facile chemical modification steps to anchor the creatinine-selective antibody to generate a sensing probe. The fabricated sensor has been thoroughly characterized by FTIR, AFM, and controlled optical analyses. The quantitative analysis is mediated through the reaction between picric acid and creatinine which was detected by the antibody-functionalized sensor probe. The differences in color intensity and creatinine concentrations show an excellent dose-dependent correlation in two different dynamic ranges from 5 to 20 µM and 35 to 400 µM, with a detection limit of 15.37 (±0.79) nM. Several interfering molecules, such as albumin, glucose, ascorbic acid, citric acid, glycine, uric acid, Na+, K+, and Cl-, were tested using the biosensor, in which no cross-reactivity was observed. The utility of the developed system to quantify creatinine in spiked serum samples was validated and the obtained percentage recoveries were found within the range of 89.71-97.30%. The fabricated biosensor was found to be highly reproducible and stable, and it retains its original signal for up to 28 days.


Assuntos
Técnicas Biossensoriais , Humanos , Creatinina/urina , Colorimetria , Biomarcadores/urina , Anticorpos , Rim
17.
Molecules ; 27(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36558031

RESUMO

Plant polyphenols have various health effects. Genistein, which is abundant in soybeans, and epigallocatechin-3-gallate, which is abundant in green tea, are major flavonoids, a subclass group of polyphenols. Several epidemiological studies have shown that these flavonoids have beneficial effects against cancer and cardiovascular diseases. However, other studies did not show such effects. Several confounding factors, including recall bias, are related to these inconsistent findings, and the determination of metabolites in the urine may be useful in reducing the number of confounding factors. Equipment, which can be used by research participants to collect samples from a portion of voided urine within 24 h without the help of medical workers, has been developed for epidemiological investigations. Previous studies, in which flavonoid metabolites in these urine samples were measured, revealed that soy intake was correlated with a reduced risk of certain types of cancer and cardiovascular diseases worldwide. Although soybeans and green tea consumption may have protective effects against cancer and cardiovascular diseases, further clinical studies that consider different confounding factors are required to provide evidence for the actual impact of dietary flavonoids on human diseases, including cancer and cardiovascular diseases. One possible mechanism involved is discussed in relation to the downregulation of reactive oxygen species and the upregulation of 5'-adenosine monophosphate-activated protein kinase elicited by these flavonoids.


Assuntos
Doenças Cardiovasculares , Catequina , Neoplasias , Humanos , Catequina/farmacologia , Chá , Doenças Cardiovasculares/prevenção & controle , Neoplasias/prevenção & controle , Flavonoides/farmacologia , Polifenóis/farmacologia , Biomarcadores/urina , Genisteína , Soja
18.
Kidney Int ; 102(6): 1219-1221, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36411018

RESUMO

Noninvasive methods for obtaining intrarenal information are required to understand the mechanism of acute kidney injury (AKI). Klocke et al. explored the feasibility of using urinary single-cell RNA sequencing in assessing human AKI. Urine samples from patients with AKI included tubular epithelial cells with injury-related dedifferentiation and adaptive phenotypes, which could reflect kidney tissue damage. Thus, urinary single-cell RNA sequencing would provide new insights into human AKI, leading to the identification of novel biomarkers and therapeutic targets.


Assuntos
Injúria Renal Aguda , Transcriptoma , Humanos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/genética , Injúria Renal Aguda/urina , Rim , Biomarcadores/urina
19.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 40(10): 727-732, 2022 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-36348551

RESUMO

Objective: To learn the investigate of polycyclic aromatic hydrocarbons (PAHs) and to explore the association between PAHs exposure and oxidative stress' neurotransmitter levels in coal miners. Methods: A cross-sectional survey was conducted in 652 coal miners (239 in the underground first line group, 280 in the underground auxiliary group and 133 in the surface group) from April to June 2017. The levels of urinary monohydroxy PAHs metabolites (OH-PAHs) , oxidative stress and neurotransmitters in blood were determined. A linear regression model was used to evaluate the correlation between OH-PAHs and oxidative stress' neurotransmitter levels. The mediating role of oxidative stress between urinary OH-PAHs and neurotransmitters change was assessed by mediation analysis. Results: The levels of 2-hydroxynaphthalene (2-NAP) 、2-hydroxy uorene (2-FLU) 、1-hydroxypyrene (1-OHP) in urine OH-PAHs of coal miners in different workplaces were significantly different (H=33.64, 9.63, 26.82, P<0.01, =0.008, <0.01) . The levels of neurotransmitters [5-hydroxytryptamine (5-HT) , norepinephrine (NE) , epinephrine (E) , dopamine (DA) , acetylcholine (Ach) , acetylcholinesterase (AChE) ] and oxidative stress [malondialdehyde (MDA) (F=36.81, 15.58, 79.16, 179.58, 33.48, 67.63, 4.96, P<0.01) ] in the blood of three groups of coal miners were significantly different. After controlling the potential confounding factors, NE content was negatively correlated with 2-FLU level, and AChE activity was also negatively correlated with 1-OHP level (ß=-134.99, 95% CI: -250.74~-19.23, P=0.02; ß=-0.80, 95%CI: -1.54~-0.05, P=0.036) . Positive correlation was found between Ach content and 9-hydroxyphenanthrene (9-PHE) level, AChE activity was also positively correlated with 2-NAP level and 9-PHE level (ß=0.96, 95%CI: 0.26~1.64, P=0.007; ß=1.78, 95%CI: 0.75~2.82, P=0.001; ß=0.77, 95%CI: 0.07~1.47, P=0.031) . In addition, superoxide dismutase activity was correlated with 1-OHP level and AChE activity (ß=0.32, 95%CI: 0.02~0.62, P=0.034; ß=-0.23, 95%CI: -0.43~-0.02, P=0.032) . Mediation analysis indicated that 1-OHP level may directly affect AChE activity (P<0.05) . Conclusion: The level of PAHs in underground coal miners is relatively higher, and may lead to changes of neurotransmitter levels. The mediating effect of oxidative stress has not been observed.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/análise , Estudos Transversais , Acetilcolinesterase , Biomarcadores/urina , Estresse Oxidativo , Neurotransmissores , Carvão Mineral
20.
BMC Pediatr ; 22(1): 643, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344956

RESUMO

INTRODUCTION: Infection is one of the most frequent causes of morbidity and mortality in diabetic patients. Some microorganisms become more virulent in a high glucose concentration. Diabetics are more likely to have asymptomatic and symptomatic bacteriuria. NGAL is secreted in high concentrations into the blood and urine within two hours of AKI. OBJECTIVES: The aim of the study is early detection of UTI in type1diabetic children through screening of their urine samples, and measurement of NGAL urinary levels in cases with asymptomatic bacteriuria for early detection of AKI to prevent serious complications. PATIENTS AND METHODS: One thousand twenty-two known diabetic children on regular follow up in endocrine outpatient clinic at Minia Children University hospital were screened for UTI. From them only 52 diabetic children were diagnosed as asymptomatic bacteriuria (group I), 52 diabetic children with normal urine analysis (group II) and 52 apparently healthy children, age and sex matched, served as controls (group III). CBC, Renal function test, HbA1c, hs- CRP, Albumin/creatinine ratio, urine examination, urine culture, GFR and urinary NGAL were done to all children. RESULTS: Thirty-seven females (71.2%) had asymptomatic bacteriuria, Hs CRP and urinary NGAL were significantly higher, while GFR was significantly lower in diabetic children with bacteriuria than the other two groups. For diabetic children with bacteriuria, (AUC) for NGAL was 1 with optimal cutoff value of > 44.1 (Sensitivity 100% and Specificity 100%) while AUC for hsCRP was 0.887 with optimal cutoff value of > 1 (Sensitivity 82.69% and Specificity 90.38%). CONCLUSION: Routine urine analysis should be done for all diabetic children even if they are asymptomatic. NGAL and hsCRP are non-invasive methods that could detect early renal injury in these patients thus, early, and proper management of UTI should be started to prevent renal injury.


Assuntos
Injúria Renal Aguda , Bacteriúria , Diabetes Mellitus Tipo 1 , Criança , Feminino , Humanos , Bacteriúria/complicações , Bacteriúria/diagnóstico , Lipocalina-2 , Diabetes Mellitus Tipo 1/complicações , Proteína C-Reativa , Injúria Renal Aguda/diagnóstico , Rim/fisiologia , Biomarcadores/urina
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