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1.
J Ethnopharmacol ; 300: 115752, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36174807

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Peganum harmala L. is a traditional medicinal plant used for centuries in folk medicine. It has a wide array of therapeutic attributes, which include hypoglycemic, sedative, anti-inflammatory, and antioxidant properties. The fruit decoction of this plant was claimed by Avicenna as traditional therapy for urolithiasis. Also, P. harmala seed showed a clinical reduction in kidney stone number and size in patients with urolithiasis. AIM OF THE STUDY: In light of the above-mentioned data, the anti-urolithiatic activities of the seed extracts and the major ß-carboline alkaloids of P. harmala were investigated. MATERIALS AND METHODS: Extraction, isolation, and characterization of the major alkaloids were performed using different chromatographic and spectral techniques. The in vivo anti-urolithiatic action was evaluated using ethylene glycol (EG)-induced urolithiasis in rats by studying their mitigating effects on the antioxidant machinery, serum toxicity markers (i.e. nitrogenous waste, such as blood urea nitrogen, uric acid, urea, and creatinine), minerals (such as Ca, Mg, P, and oxalate), kidney injury marker 1 (KIM-1), and urinary markers (i.e. urine pH and urine output). RESULTS: Two major alkaloids, harmine (P1) and harmalacidine HCl (P2), were isolated and in vivo evaluated alongside the different extracts. The results showed that P. harmala and its constituents/fractions significantly reduced oxidative stress at 50 mg/kg body weight, p.o., as demonstrated by increased levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and catalase (CAT) in kidney homogenate as compared to the EG-treated group. Likewise, the total extract, pet. ether fraction, n-butanol fraction, and P1, P2 alleviated malondialdehyde (MDA) as compared to the EG-treated group. Serum toxicity markers like blood urea nitrogen (BUN), creatinine, uric acid, urea, kidney injury molecule-1 (Kim-1), calcium, magnesium, phosphate, and oxalate levels were decreased by total extract, pet. ether fraction, n-butanol fraction, P1, and P2 as compared to the EG-treated group. Inflammatory markers like NFκ-B and TNF-α were also downregulated in the kidney homogenate of treatment groups as compared to the EG-treated group. Moreover, urine output and urine pH were significantly increased in treatment groups as compared to the EG-treated group deciphering anti-urolithiatic property of P. harmala. Histopathological assessment by different staining patterns also supported the previous findings and indicated that treatment with P. harmala caused a gradual recovery in damaged glomeruli, medulla, interstitial spaces and tubules, and brown calculi materials as compared to the EG-treated group. CONCLUSION: The current research represents scientific evidence on the use of P. harmala and its major alkaloids as an effective therapy in the prevention and management of urolithiasis.


Assuntos
Alcaloides , Cálculos Renais , Peganum , Urolitíase , 1-Butanol , Alcaloides/farmacologia , Animais , Antioxidantes , Cálcio , Oxalato de Cálcio/urina , Catalase , Creatinina , Éteres , Etilenoglicol/uso terapêutico , Etilenoglicol/toxicidade , Glutationa , Glutationa Peroxidase , Glutationa Redutase , Harmina , Hipnóticos e Sedativos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Cálculos Renais/tratamento farmacológico , Magnésio , Malondialdeído , Peganum/química , Fosfatos , Extratos Vegetais , Ratos , Fator de Necrose Tumoral alfa , Ureia , Ácido Úrico , Urolitíase/induzido quimicamente , Urolitíase/tratamento farmacológico , Urolitíase/patologia
2.
Talanta ; 251: 123816, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35963014

RESUMO

Benzodiazepines exhibit central nervous system depressive activity as well as sedative, hypnotic, and anticonvulsant properties, which enable to use them as medical treatment in anxiety, epilepsy, insomnia and alcohol withdrawal syndrome. However, from 2000s illegal benzodiazepine derivatives have started to emerge on illicit drug market as new psychoactive substances (NPSs) monitored in many countries. Analysis of both pharmaceutical drugs and NPSs from benzodiazepines group could be challenging, as usually very low concentrations need to be determined. Thus, an ultra-sensitive UHPLC-QqQ-MS/MS method was developed for simultaneous determination of 54 benzodiazepines (pharmaceutical drugs, NPS and their metabolites) and 3 z-drugs with one metabolite in biological fluid samples. The lower limit of quantification for most substances was 50 pg/mL, whereas for 17 substances as low as 10 pg/mL was achieved. Together with reduced sample volume to 100 µL it makes the developed method suitable for a sensitive multidrug toxicological analysis. Presented method was applied in routine toxicological practice as well as for the determination of benzodiazepines, z-drugs and their metabolites in 25 authentic biological fluids (blood, urine, vitreous humor and bile), both antemortem and postmortem. 19 different compounds, including benzodiazepines, their metabolites and z-drugs were determined. Antemortem blood concentrations were within 0.2-114.5 ng/mL, whereas concentrations in antemortem urine samples were 0.03-102.6 ng/mL. In postmortem specimens, concentrations ranged within 0.2-473.2 ng/mL, 0.5-94.1 ng/mL, 1.3-208.8 ng/mL and 41.5-42.0 ng/mL in blood, vitreous humor, urine and bile, respectively. The developed method is suitable for a forensic toxicology analysis, as well as clinical toxicology which is evidenced by the positive results of international proficiency tests.


Assuntos
Alcoolismo , Drogas Ilícitas , Síndrome de Abstinência a Substâncias , Anticonvulsivantes , Benzodiazepinas , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Hipnóticos e Sedativos , Drogas Ilícitas/urina , Espectrometria de Massas em Tandem/métodos
3.
Chemosphere ; 311(Pt 1): 137039, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36342026

RESUMO

Limited information is available on the links between heavy metals' exposure and coronary heart disease (CHD). We aim to establish an efficient and explainable machine learning (ML) model that associates heavy metals' exposure with CHD identification. Our datasets for investigating the associations between heavy metals and CHD were sourced from the US National Health and Nutrition Examination Survey (US NHANES, 2003-2018). Five ML models were established to identify CHD by heavy metals' exposure. Further, 11 discrimination characteristics were used to test the strength of the models. The optimally performing model was selected for identification. Finally, the SHapley Additive exPlanations (SHAP) tool was used for interpreting the features to visualize the selected model's decision-making capacity. In total, 12,554 participants were eligible for this study. The best performing random forest classifier (RF) based on 13 heavy metals to identify CHD was chosen (AUC: 0.827; 95%CI: 0.777-0.877; accuracy: 95.9%). SHAP values indicated that cesium (1.62), thallium (1.17), antimony (1.63), dimethylarsonic acid (0.91), barium (0.76), arsenous acid (0.79), total arsenic (0.01) in urine, and lead (3.58) and cadmium (4.66) in blood positively contributed to the model, while cobalt (-0.15), cadmium (-2.93), and uranium (-0.13) in urine negatively contributed to the model. The RF model was efficient, accurate, and robust in identifying an association between heavy metals' exposure and CHD among US NHANES 2003-2018 participants. Cesium, thallium, antimony, dimethylarsonic acid, barium, arsenous acid, and total arsenic in urine, and lead and cadmium in blood show positive relationships with CHD, while cobalt, cadmium, and uranium in urine show negative relationships with CHD.


Assuntos
Arsênio , Doença das Coronárias , Poluentes Ambientais , Metais Pesados , Urânio , Adulto , Humanos , Inquéritos Nutricionais , Cádmio/urina , Antimônio , Exposição Ambiental/análise , Bário , Tálio , Cobalto/urina , Césio , Doença das Coronárias/epidemiologia , Aprendizado de Máquina
4.
Sci Total Environ ; 855: 158788, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36116648

RESUMO

BACKGROUND/AIMS: Phthalates and their replacements are endocrine/metabolic disruptors that may impact gestational weight gain (GWG) - a pregnancy health indicator. We investigated overall and fetal sex-specific associations of individual and cumulative phthalate/replacement biomarkers with GWG. METHODS: Illinois women (n = 299) self-reported their weight pre-pregnancy and at their final obstetric appointment before delivery (median 38 weeks). We calculated pre-pregnancy body mass index and gestational age-specific GWG z-scores (GWGz). We quantified 19 phthalate/replacement metabolites (representing 10 parent compounds) in pools of up-to-five first-morning urine samples, collected approximately monthly between 8 and 40 weeks gestation. We used linear regression, quantile-based g-computation (QGComp), and weighted quantile sum regression (WQSR) to evaluate associations of ten biomarkers (individual metabolites or parent molar-sums) individually or as mixtures (in interquartile range intervals) with GWGz. We evaluated associations in all women and stratified by fetal sex. RESULTS: Individually, sums of metabolites of di(2-ethylhexyl) phthalate (Æ©DEHP), di(isononyl) cyclohexane-1,2-dicarboxylate (Æ©DiNCH), and di(2-ethylhexyl) terephthalate (Æ©DEHTP) had consistent inverse associations with GWGz, and some associations were fetal sex-specific. When evaluating phthalates/replacements as a mixture, QGComp identified Æ©DEHP, Æ©DEHTP, and mono-(3-carboxypropyl) phthalate, along with sum of di(isononyl) phthalate metabolites (Æ©DiNP) and monobenzyl phthalate as notable contributors to lower and higher GWGz, respectively, resulting in a marginal inverse joint association in all women (ß: -0.29; 95% CI: -0.70, 0.12). In women carrying females, Æ©DEHP contributed to the marginal inverse joint association (ß: -0.54; 95% CI: -1.09, 0.03). However, there was no overall association in women carrying males (ß: 0.00; 95% CI: -0.60, 0.59), which was explained by approximately equal negative (driven by Æ©DEHTP) and positive (driven by Æ©DiNP) partial associations. WQSR analyses consistently replicated these QGComp findings. CONCLUSIONS: Biomarkers of phthalates/replacements were fetal sex-specifically associated with GWGz. Because Æ©DEHTP contributed substantively to mixture associations, additional studies in pregnant women may be needed around this plasticizer replacement.


Assuntos
Disruptores Endócrinos , Poluentes Ambientais , Ganho de Peso na Gestação , Ácidos Ftálicos , Humanos , Masculino , Feminino , Gravidez , Exposição Ambiental/análise , Ácidos Ftálicos/urina , Plastificantes/análise , Disruptores Endócrinos/urina , Biomarcadores/urina , Poluentes Ambientais/análise
5.
Sci Total Environ ; 855: 158852, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36122707

RESUMO

BACKGROUND: Few studies have investigated the adverse effects of preconception phthalate (PAE) exposure on birth weight in couples receiving assisted reproductive technology (ART) compared to naturally conceived newborns. OBJECTIVES: We examined the association between parental preconception/prenatal urinary phthalate exposure and low birth weight (LBW) risk in couples who conceived using ART or naturally. METHODS: From the Jiangsu Birth Cohort Study (China), we recruited 544 couples who conceived after infertility treatment and 940 couples who conceived naturally and gave birth to a singleton infant between November 2014 and December 2019. Seventeen metabolites of phthalate and three metabolites of phthalate alternatives were analyzed in parental spot urine samples. Clinical data were collected from medical records. We used generalized linear models, elastic net regression, Bayesian kernel machine regression, and quantile-based g-computation to examine the individual and joint effects of parental phthalate exposure on birth weight and LBW risk ratios (RR). RESULTS: The relationship between parental phthalate exposure and birth weight was consistent between ART and natural conception. Maternal exposure to mono-ethyl phthalate and mono-carboxyisooctyl phthalate was associated with an increased risk of LBW in ART-conceived infants (RR = 1.27; 95 % confidence interval (CI): 1.03, 1.56; and RR = 1.31; 95 % CI: 1.03, 1.67, respectively). In contrast, in the spontaneously conceived infants, higher paternal prenatal concentrations of mono-benzyl phthalate and mono-carboxyisononyl phthalate were associated with a 40 % and 53 % increase in LBW risk, respectively. Exposure to PAE mixtures was associated with LBW in ART-conceived infants, with the effects primarily driven by di-ethyl phthalate, benzylbutyl phthalate, and di-isononyl phthalate metabolites. Sex-specific LBW was observed, with females appearing to be more susceptible than males. CONCLUSIONS: Maternal preconception and paternal prenatal exposure to phthalates were associated with increased risk of LBW in infants. Compared with natural conception, ART-conceived fetuses were more sensitive to PAE mixtures, which requires further attention.


Assuntos
Coorte de Nascimento , Ácidos Ftálicos , Humanos , Recém-Nascido , Gravidez , Masculino , Lactente , Feminino , Peso ao Nascer , Estudos Prospectivos , Estudos de Coortes , Teorema de Bayes , Ácidos Ftálicos/urina , Recém-Nascido de Baixo Peso , Técnicas de Reprodução Assistida
6.
Sci Total Environ ; 855: 158843, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36122716

RESUMO

Pentachlorophenol (PCP) is ubiquitous and moderately persistent in the environment, and it is an identified human carcinogen. Previous animal experiments indicate that toxic mechanisms of PCP include oxidative stress. However, no epidemiological study has reported the association between PCP exposure and oxidative stress; such association in pregnant women, a vulnerable population, is of particular interest. This study aimed to characterize PCP concentrations in 2304 urine samples from 768 pregnant women, explore its determinants, and evaluate the associations between PCP exposure and three oxidative stress biomarkers across three trimesters. The median concentrations of PCP (100% detected) in the first, second, and third trimester were 0.61, 0.59, and 0.48 ng/mL, respectively, with a significant decrease trend. The intraclass correlation coefficient of specific gravity (SG)-adjusted PCP was 0.26, indicating high variability for PCP across the three trimesters. PCP concentrations were significantly higher in older, pre-pregnancy overweight, multiparous, high-income, and employed women during pregnancy. Urinary PCP was markedly lower in samples collected during spring compared to other seasons. Linear mixed effect models for repeated measures revealed that ln-transformed SG-adjusted PCP was significantly associated with increased 8-hydroxy-2'-deoxyguanosine (8-OHdG; percent change [%Δ] caused by each interquartile range increase of PCP: 46.2, 95% confidence interval [CI]: 40.2, 52.5) and 8-hydroxyguanosine (8-OHG;%Δ [95% CI]: 44.8 [40.1, 49.8]), but the positive association with 4-hydroxy2-nonenal-mercapturic acid (HNE-MA) was not significant. PCP was also positively associated with increased 8-OHdG and 8-OHG in each trimester using general linear models, and its associations with HNE-MA were only significant at T1 (%Δ [95% CI]: 19.1 [1.05, 40.3]) and T2 (%Δ [95% CI]: 12.6 [0.32, 26.3]). Our findings provide valuable information about PCP exposure characteristics during pregnancy and the potential effects of PCP exposure on oxidative stress in pregnant women.


Assuntos
Pentaclorofenol , Humanos , Animais , Feminino , Gravidez , Idoso , Pentaclorofenol/toxicidade , Estudos Longitudinais , Gestantes , Biomarcadores/urina , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina , China
7.
Sci Total Environ ; 856(Pt 1): 159050, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36174683

RESUMO

BACKGROUND: Evidence from in vitro and rodent studies suggests that organophosphate esters (OPEs) may disrupt sex steroid hormone homeostasis, but no human studies, to date, have examined the effects of in utero exposure to OPEs on offspring reproductive development. OBJECTIVE: Anogenital distance (AGD) is a sensitive biomarker of fetal hormonal milieu and has been used to assess reproductive toxicity. We evaluated the longitudinal effects of prenatal exposure to OPEs on the AGD of offspring from birth to 4 years. METHODS: Based on Shanghai-Minhang Birth Cohort Study, pregnant women provided urine samples at a gestational age of 12-16 weeks, which were analyzed for eight OPE metabolites. AGD was measured in offspring at birth and 0.5, 1, and 4 years of age. We used generalized estimating equations (GEE) and Bayesian kernel machine regression (BKMR) models to estimate the associations of prenatal exposure to individual OPE metabolites and OPE mixtures with AGD stratified by sex. RESULTS: A total of 733 mother-infant pairs were analyzed. Prenatal exposure to diphenyl phosphate and bis-(2-ethylhexyl) phosphate was associated with decreased AGD in boys in GEE models. Bis-(1-chloro-2-propyl) phosphate (BCIPP) showed a similar but marginally significant effect. Prenatal exposure to most OPE metabolites was associated with decreased AGD in girls, with the most profound association observed for bis (2-butoxyethyl) phosphate (BBOEP) and alkyl-OPEs. The OPE mixture was also inversely associated with AGD in both sexes. The single-exposure effects of BKMR models were largely consistent with those observed in the GEE models. In addition, alkyl-OPEs, particularly BBOEP, contributed the most to the decreased AGD in girls, while BCIPP contributed the most to the decreased AGD in boys. CONCLUSIONS: This study provides the first human evidence that prenatal exposure to OPEs is associated with decreased AGD in offspring. The magnitude of these effects may vary depending on the structure of OPEs.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Masculino , Lactente , Recém-Nascido , Humanos , Feminino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estudos de Coortes , Teorema de Bayes , China , Organofosfatos/toxicidade , Organofosfatos/urina , Fosfatos
8.
Chemosphere ; 311(Pt 1): 136991, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36306967

RESUMO

Humans are simultaneously exposed to phenols and phthalates (PAEs). However, the mixture effect of phenols and PAEs on the body size of twins is lacking. From 2016 to 2018, we recruited 228 pregnant twins and collected up to three urine samples. A total of 8 PAE metabolites and 7 phenols were detected in urine by liquid chromatography-tandem mass spectrometry. Chemical individual and mixture effects were estimated. Multivariable linear regression results presented the percentage change in twins' growth differences at one month old with maternal PAE and phenol exposure. These chemicals were positively associated with weight differences during the entire trimester. Moreover, the quantile g-computed model showed that increased urinary concentrations of all chemicals by one quartile were associated with a 22.85% (95%CI: 11.21-35.72%), 22.60% (95%CI: 12.31-33.83%), and 24.05% (95%CI: 13.11-36.05%) larger weight difference within twins in each trimester, respectively. Increasing all PAE metabolites and phenols by one quantile across the entire trimester, weight differences increased by 26.61% (95% CI: 15.79%, 38.44%), and height differences increased by 15.84% (95%CI: 3.92%, 29.13%). Co-exposure to PAEs and phenols may primarily play a role in twins' growth.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Gravidez , Feminino , Humanos , Lactente , Fenóis/urina , Poluentes Ambientais/urina , Ácidos Ftálicos/urina , Tamanho Corporal
9.
J Proteomics ; 270: 104735, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36174949

RESUMO

Canine babesiosis is a tick-borne disease caused by Babesia canis, with acute kidney injury as one of the common complications. In the study 8 healthy control dogs and 22 dogs with naturally occurring babesiosis were enrolled, with the aim to analyse differences in serum and urinary proteomes between healthy dogs and dogs with different degree of renal dysfunction in babesiosis using a label-based high-throughput quantitative proteomic approach. In serum, 58 proteins were found differentially abundant between healthy controls and groups of dogs with different degrees of renal dysfunction in babesiosis, while in urine there were 259 differentially abundant proteins. In addition, altered biological pathways were detected in the diseased dogs using bioinformatics tools and validation of several candidate biomarkers was performed. SIGNIFICANCE: The main aim of this comprehensive study was to perform analyses of serum and urinary proteomes of dogs with renal dysfunction in babesiosis compared to healthy dogs using, for the first time, a high-throughput proteomic method and functional enrichment analyses. Serum and urine samples of the same dogs were investigated in order to gain a more complete picture of pathologic changes taking place in renal dysfunction in babesiosis. We highlighted two putative biomarkers validated herein which could be of importance for early diagnosis of renal dysfunction in canine babesiosis, as they are easily accessible from urine and their concentration rises before the appearance of azotaemia: urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary liver-type fatty acid-binding protein (L-FABP).


Assuntos
Babesiose , Doenças do Cão , Nefropatias , Cães , Animais , Babesiose/complicações , Babesiose/diagnóstico , Proteômica , Proteoma , Doenças do Cão/diagnóstico , Biomarcadores , Nefropatias/diagnóstico , Nefropatias/urina , Nefropatias/veterinária
10.
J Proteomics ; 270: 104737, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36174950

RESUMO

The exploration of nucleoside changes in human biofluids has profound potential for cancer diagnosis. Herein, we developed a rapid methodology to quantify 17 nucleosides by UHPLC-MS/MS. Five pairs of isomers were successfully separated within 8 min. The ME was mostly eliminated by sample dilution folds of 1000 for urine and 40 for CCS. The optimized method was firstly applied to screen potential nucleoside biomarkers in CCS by comprising bladder cancer cell lines (5637 and T24) and normal human bladder cell line SV-HUC-1 together with student's t-test and OPLS-DA. Nucleosides with significant differences in the supernatant of urine samples were also uncovered comparing BCa with the non-tumor group, as well as a comparison of BCa recurrence group with the non-recurrence group. By intersecting the differential nucleosides in CCS and urine supernatant, and then further confirmed using validation sets, the combination of m3C and m1A with AUC of 0.775 was considered as a potential biomarker for bladder cancer diagnosis. A panel of m3C, m1A, m1G, and m22G was defined as potential biomarkers for bladder cancer prognosis with an AUC of 0.819. Above all, this method provided a new perspective for diagnosis and recurrence monitoring of bladder cancer. SIGNIFICANCE: The exploration of nucleoside changes in body fluids has profound potential for the diagnosis and elucidation of the pathogenesis of cancer. In this study, we developed a rapid methodology for the simultaneous quantitative determination of 17 nucleosides in the supernatant of cells and urine samples using UHPLC-MS/MS to discover and validate bladder cancer related excreted nucleoside biomarkers. The results of this paper provide a new strategy for diagnosis and postoperative recurrence monitoring of bladder cancer and provide theoretical support for the exploration of its pathogenesis.


Assuntos
Líquidos Corporais , Neoplasias da Bexiga Urinária , Humanos , Espectrometria de Massas em Tandem/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/metabolismo , Nucleosídeos/urina , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Biomarcadores Tumorais , Líquidos Corporais/metabolismo , Técnicas de Cultura de Células
11.
Sci Total Environ ; 857(Pt 2): 159449, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36244474

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) pose significant health risks. However, no nationwide cohort has been established to consistently record biomonitoring data on PAH exposure in the Chinese population. Biomonitoring data from 56 published studies were combined in this study to develop a profile of urinary PAH metabolites among Chinese population in the 2010s. The stacked column charts described the composition profiles of hydroxylated PAHs (OH-PAHs) in general, special, and occupational populations. Hydroxynaphthalene (OH-Nap) and hydroxyfluorene (OH-Flu) accounted for more than half of the urinary OH-PAH in general and special populations. The urine of the occupational populations contained a significant amount of hydroxyphenanthrene (OH-Phe) and 1-hydroxypyrene (1-OHPyr). Furthermore, this study analyzed the distribution profiles of non-occupationally exposed populations, such as spatial distribution, age distribution, and trends over time. The population of the Southern region had higher urinary OH-PAH concentrations than the population of the Northern region. Adults (45-55 years old) had the highest level of internal PAH exposure. Between 2010 and 2018, the overall trend of urinary OH-PAHs in Chinese general populations decreased. The cumulative distribution function (CDF) revealed that 1-OHNap and 1-OHPyr were better at distinguishing internal PAH exposure among different populations. The sum of OH-Flu and OH-Phe in urine can be used to assess the impact of indoor and outdoor environments on human exposure to PAHs. Our findings suggest that more emphasis should be placed on collecting biomonitoring data for adults of all ages (particularly in the Northern region) and vulnerable populations. In conclusion, this study advocates for the establishment of a nationwide cohort study of Chinese populations as soon as possible in the future to evaluate the Chinese population's exposure to environmental contaminants.


Assuntos
Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Monitoramento Biológico , China , Biomarcadores/urina
12.
BMC Vet Res ; 18(1): 389, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333744

RESUMO

BACKGROUND: In humans, kidney injury molecule-1 (KIM-1) is a biomarker of acute kidney injury that can be quantified in urine. Preliminary investigation in cats with experimentally induced acute kidney injury showed that KIM-1 urine concentration correlated with kidney injury histopathology scores. A lateral flow assay (LFA) has recently become available for patient-side feline KIM-1 measurement. In vitro parameters of the assay have not yet been determined. The objectives of this study were to determine detection of KIM-1 in urine stored at different temperatures over time, to establish the linear range of the LFA, and to assess the intra-assay repeatability of measurements.  RESULTS: Ten urine samples with a range of KIM-1 concentrations were stored at room temperature (22o C), 4o C or -20o C, and tested with the LFA on days 0, 1, 2, 3, 7, 14, and 30. The concentration of KIM-1 in samples was not significantly different from the day 0 value, except one sample that had been stored for 30 days at room temperature yielded a significantly higher value. The assay results had a correlation coefficient of 0.922. The mean coefficient of variation for all samples was 15.7%. The slope of the curve of expected versus measured values in samples diluted two-fold nine times was 0.908, and results were linear over all dilutions. CONCLUSIONS: The LFA for feline KIM-1 yields consistent results from stored urine samples. These characteristics will allow for KIM-1 to be measured retrospectively if immediate testing is not feasible. Within assay precision was high, and linearity over 9 logs of dilution suggests suitability for a range of subclinical and clinical kidney injuries.


Assuntos
Injúria Renal Aguda , Doenças do Gato , Gatos , Animais , Humanos , Temperatura , Estudos Retrospectivos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/veterinária , Injúria Renal Aguda/urina , Rim , Biomarcadores/urina
13.
BMJ Open ; 12(11): e063930, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319056

RESUMO

INTRODUCTION: Bisphenol A (BPA) is a common environmental endocrine disruptor. BPA has been reported to be associated with female infertility, which may not only affect natural pregnancy and natural fertility but also affect the outcomes of in vitro fertilisation (IVF). BPA exposure may help to partly explain the unsatisfactory IVF outcomes, but the relationship between the concentrations of BPA in urine and IVF outcomes remains controversial. Therefore, we will perform a meta-analysis to identify and review the relationship between urinary BPA concentrations and IVF outcomes. METHODS AND ANALYSIS: A comprehensive literature search will be performed in PubMed, Web of Science and the Cochrane central register of controlled trials for relevant articles using MeSH terms and related entry terms (up to 20 April 2022). The language will be restricted to English. Articles will be screened for inclusion in or exclusion from the study independently by two reviewers after removing the duplicates. The titles and abstracts followed by full-text screening will also be conducted independently by two reviewers. In addition, the references of the included literature will also be traced to supplement our search results and to obtain all relevant literature. The Newcastle-Ottawa Scale will be used to assess the methodological quality of the included studies using a star rating system ranging from 0 to 9 stars. Heterogeneity in estimates from different articles will be quantified, and publication bias will be investigated using funnel plots. Finally, a sensitivity analysis will also be conducted to estimate whether our results could have been markedly affected by a single included study. ETHICS AND DISSEMINATION: Ethical approval is not required for this protocol, as participants are not included. Findings will be disseminated through peer-reviewed publications and conference presentations.


Assuntos
Fertilização In Vitro , Infertilidade Feminina , Gravidez , Feminino , Humanos , Compostos Benzidrílicos/urina , Fenóis/urina , Metanálise como Assunto , Revisões Sistemáticas como Assunto
14.
Nutrients ; 14(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364754

RESUMO

The goal of this work was to examine whether elevated iodine intake was associated with adverse effects on IQ among school-age children in Portugal. In a representative sample of children from the north of the country, IQ percentiles by age (assessed with Raven's Colored Progressive Matrices) were dichotomized to <50 ("below-average" IQs) and ≥50. Morning urine iodine concentrations, corrected for creatinine, were dichotomized to <250 µg/g and ≥250 µg/g, according to the European Commission/Scientific Committee on Food's tolerable upper level of daily iodine intake for young children. Data were examined with Chi-square tests, logistic regression, and GLM univariate analysis. The sample (N = 1965) was classified as generally iodine-adequate (median urinary iodine concentration = 129 µg/L; median iodine-to-creatinine ratio = 126 µg/g) according to the WHO's criteria. A greater proportion of children in the ≥250 µg/g group had below-average IQs, compared to children with less than 250 µg/g (p = 0.037), despite a sizable (though non-significant) proportion of children in the less-than-250 µg/g group also presenting below-average IQs, at the bottom of the iodine distribution (<50 µg/g). The proportion of below-average IQs increased with increasingly elevated iodine concentrations (p = 0.047). The association remained significant after the adjustment for confounders, with the elevated iodine group showing increased odds of having below-average IQs when compared with the non-elevated iodine group (OR 1.55; 95% CI 1.11-2.17; p = 0.011). Consistently, the former group presented a lower mean IQ than the latter (p = 0.006). High iodine intake was associated with lower IQs even in a population classified as iodine-adequate. These results bear on child cognition and on initiatives involving iodine supplementation.


Assuntos
Iodo , Criança , Humanos , Pré-Escolar , Creatinina/urina , Portugal , Iodo/urina , Estado Nutricional , Testes de Inteligência , Iodetos
15.
Environ Health ; 21(1): 108, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36369032

RESUMO

BACKGROUND: Exposure to endocrine disruptors, such as phthalates, may impact bone mineral density (BMD) through a variety of mechanisms. Studies of phthalate exposure and BMD in humans are scarce. OBJECTIVES: To synthesize published data on the association between phthalate metabolites and BMD in humans and to provide methodological suggestions for future research. METHODS: A single investigator searched PubMed for relevant studies, including observational studies of phthalate exposure and BMD in children and postmenopausal women. Twelve studies were screened with 5 meeting the eligibility criteria and included for review. A quality assessment form was used as a quality measure and key information was extracted from the included studies. RESULTS: In one prospective study among postmenopausal women, higher levels of monocarboxyoctyl phthalate (MCOP) and monocarboxynonyl phthalate (MCNP) were significantly associated with lower BMD among nonusers of hormone therapy (HT). In cross-sectional studies of postmenopausal women, monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono (3-carboxypropyl) phthalate (MCPP), and mono-benzyl phthalate (MBzP) were negatively associated with BMD, and MCNP was positively associated with BMD, but these results were not replicated across studies. In studies of fetal exposure to phthalates and childhood BMD, significant positive associations between MCPP and BMD in children at age 12 years were found in 1 study, while associations were null in the other study. CONCLUSIONS: Studies among postmenopausal women provide suggestive evidence of an association between urinary phthalate metabolite concentration and decreased BMD. Results from studies of childhood BMD are inconclusive given the limited data and their limitations. More research is needed to address limitations and further investigate the association between phthalate exposure and human BMD.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Criança , Feminino , Humanos , Densidade Óssea , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/urina , Estudos Transversais , Estudos Prospectivos , Ácidos Ftálicos/urina , Exposição Ambiental/efeitos adversos
16.
Crit Care ; 26(1): 349, 2022 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371256

RESUMO

BACKGROUND: Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI. METHODS: In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. RESULTS: We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1-25.9), urinary NGAL (DOR 13.8, 95% CI 10.2-18.8), and serum NGAL (DOR 12.6, 95% CI 9.3-17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively. CONCLUSIONS: Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients. Trial registration CRD42020207883 , October 06, 2020.


Assuntos
Injúria Renal Aguda , Interleucina-18 , Adulto , Humanos , Lipocalina-2/urina , Inibidor Tecidual de Metaloproteinase-2 , Creatinina , Injúria Renal Aguda/terapia , Biomarcadores , Hospitais
17.
BMC Cancer ; 22(1): 1195, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36403035

RESUMO

BACKGROUND: Early detection of bladder cancer (BCa) offers patients a favorable outcome and avoids the need for cystectomy. Development of an accurate and sensitive noninvasive BCa diagnostic test is imperative. DNA methylation is an early epigenetic event in the development of BCa. Certain specific aberrant methylations could serve as useful biomarkers. The aim of this study was to identify methylation biomarkers for early detection of BCa. METHODS: CpG methylation microarray analysis was conducted on primary tumors with varying stages (T1-T4) and paired nontumor tissues from nine BCa patients. Bisulfite-pyrosequencing was performed to confirm the methylation status of candidate genes in tissues and urine sediments (n = 51). Among them, PENK was selected as a potential candidate and validated using an independent set of 169 urine sediments (55 BCa, 25 benign urologic diseases, 8 other urologic cancers, and 81 healthy controls) with a quantitative methylation-specific real time PCR (mePENK-qMSP). All statistical analyses were performed using MedCalc software version 9.3.2.0. RESULTS: CpG methylation microarray analysis and stepwise validation by bisulfite-pyrosequencing for tissues and urine sediments supported aberrant methylation sites of the PENK gene as potential biomarkers for early detection of BCa. Clinical validation of the mePENK-qMSP test using urine sediment-DNA showed a sensitivity of 86.5% (95% CI: 71.2 - 95.5%), a specificity of 92.5% (95% CI: 85.7 - 96.7%), and an area under ROC of 0.920 (95% CI: 0.863 - 0.959) in detecting Ta high-grade and advanced tumor stages (T1-T4) of BCa patients. Sensitivities for Ta low-grade, Ta high-grade, T1 and T2-T4 were 55.6, 83.3, 88.5, and 100%, respectively. Methylation status of PENK was not correlated with sex, age or stage, while it was associated with the tumor grade of BCa. CONCLUSIONS: In this study, we analyzed the comprehensive patterns of DNA methylation identified that PENK methylation possesses a high potential as a biomarker for urine-based early detection of BCa. Validation of PENK methylation confirms that it could significantly improve the noninvasive detection of BCa.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/urina , Detecção Precoce de Câncer , DNA
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
20.
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
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