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Great advances have been made in mass spectrometric data interpretation for intact glycopeptide analysis. However, accurate identification of intact glycopeptides and modified saccharide units at the site-specific level and with fast speed remains challenging. Here, we present a glycan-first glycopeptide search engine, pGlyco3, to comprehensively analyze intact N- and O-glycopeptides, including glycopeptides with modified saccharide units. A glycan ion-indexing algorithm developed for glycan-first search makes pGlyco3 5-40 times faster than other glycoproteomic search engines without decreasing accuracy or sensitivity. By combining electron-based dissociation spectra, pGlyco3 integrates a dynamic programming-based algorithm termed pGlycoSite for site-specific glycan localization. Our evaluation shows that the site-specific glycan localization probabilities estimated by pGlycoSite are suitable to localize site-specific glycans. With pGlyco3, we confidently identified N-glycopeptides and O-mannose glycopeptides that were extensively modified by ammonia adducts in yeast samples. The freely available pGlyco3 is an accurate and flexible tool that can be used to identify glycopeptides and modified saccharide units.
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Biologia Computacional/métodos , Glicopeptídeos/química , Proteoma , Proteômica/métodos , Algoritmos , Animais , Vaga-Lumes , Glicosilação , Células HEK293 , Humanos , Manose/química , Polissacarídeos/química , Probabilidade , Reprodutibilidade dos Testes , Saccharomyces cerevisiae , Schizosaccharomyces , SoftwareRESUMO
The global concern over arsenic contamination in water due to its natural occurrence and human activities has led to the development of innovative solutions for its detection and remediation. Microbial metabolism and mobilization play crucial roles in the global cycle of arsenic. Many microbial arsenic-resistance systems, especially the ars operons, prevalent in bacterial plasmids and genomes, play vital roles in arsenic resistance and are utilized as templates for designing synthetic bacteria. This review novelty focuses on the use of these tailored bacteria, engineered with ars operons, for arsenic biosensing and bioremediation. We discuss the advantages and disadvantages of using synthetic bacteria in arsenic pollution treatment. We highlight the importance of genetic circuit design, reporter development, and chassis cell optimization to improve biosensors' performance. Bacterial arsenic resistances involving several processes, such as uptake, transformation, and methylation, engineered in customized bacteria have been summarized for arsenic bioaccumulation, detoxification, and biosorption. In this review, we present recent insights on the use of synthetic bacteria designed with ars operons for developing tailored bacteria for controlling arsenic pollution, offering a promising avenue for future research and application in environmental protection.
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Arsênio , Bactérias , Biodegradação Ambiental , Técnicas Biossensoriais , Óperon , Técnicas Biossensoriais/métodos , Arsênio/metabolismo , Bactérias/genética , Bactérias/metabolismo , Biologia Sintética/métodos , Engenharia GenéticaRESUMO
Mass spectrometry-based glycome analysis is a viable strategy for the compositional and functional exploration of glycosylation. However, the lack of generic tools for high-throughput and reliable glycan spectral interpretation largely hampers the broad usability of glycomic research. Here, we developed a generic and reliable glycomic tool, GlycoNote, for comprehensive and precise glycome analysis. GlycoNote supports interpretation of tandem-mass spectrometry glycomic data from any sample source, uses a novel target-decoy method with iterative decoy searching for highly reliable result output, and embeds an open-search component analysis mode for heterogeneity analysis of monosaccharides and modifications. We tested GlycoNote on several different large-scale glycomic datasets, including human milk oligosaccharides, N- and O-glycome from human cell lines, plant polysaccharides, and atypical glycans from Caenorhabditis elegans, demonstrating its high capacity for glycome analysis. An application of GlycoNote to the analysis of labeled and derived glycans further demonstrates its broad usability in glycomic studies. By enabling generic characterization of various glycan types and elucidation of component heterogeneity in glycomic samples, the freely available GlycoNote is a promising tool for facilitating glycomics in glycobiology research.
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Glicômica , Polissacarídeos/química , Glicômica/métodos , Humanos , Espectrometria de Massas em TandemRESUMO
BACKGROUNDS: Beta-2-microglobulin (ß2-MG) levels vary in many infectious and autoimmune diseases. We investigated plasma and cerebrospinal fluid (CSF) ß2-MG levels in patients with Guillain-Barré syndrome (GBS) and their correlations with clinical parameters. METHODS: CSF samples from 50 patients with GBS including 19 acute inflammatory demyelinating polyneuropathy (AIDP), 6 acute motor axonal neuropathy (AMAN), 10 acute motor-sensory axonal neuropathy (AMSAN), 7 Miller-Fisher syndrome (MFS), and 8 unclassified patients were collected. Moreover, 23 CSF samples from patients with non-inflammatory neurological disorders (NIND) as controls were collected. Plasma samples from 42 enrolled patients and 29 healthy individuals were also collected. The ß2-MG levels were measured by immunoturbidimetry on automatic biochemical analyser. Besides, clinical data were extracted from electronic patient documentation system. RESULTS: CSF levels of ß2-MG, lactate dehydrogenase (LDH), and lactate were significantly increased in patients with GBS (p = 0.004, p = 0.041, p = 0.040, respectively), particularly in patients with AIDP (p < 0.001, p = 0.001, p = 0.015, respectively), whereas no statistically significant difference was found in plasma levels of ß2-MG. Furthermore, CSF levels of ß2-MG were positively correlated with Hughes functional score (r = 0.493, p = 0.032), LDH (r = 0.796, p < 0.001), and lactate (r = 0.481, p = 0.037) but not with protein (r = - 0.090, p = 0.713) in AIDP patients. CONCLUSIONS: CSF ß2-MG levels may help identify AIDP and indicate clinical severity. CSF LDH and lactate levels correlate with CSF ß2-MG levels; interaction among these biomarkers would need further investigation.
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Síndrome de Guillain-Barré , Síndrome de Miller Fisher , Humanos , Microglobulina beta-2RESUMO
Introduction: Glycomics, which aims to define the glycome of a biological system to better assess the biological attributes of the glycans, has attracted increasing interest. However, the complexity and diversity of glycans present challenging barriers to glycome definition. Technological advances are major drivers in glycomics.Areas covered: This review summarizes the main methods and emphasizes the most recent advances in mass spectrometry-based methods regarding glycomics following the general workflow in glycomic analysis.Expert opinion: Recent mass spectrometry-based technological advances have significantly lowered the barriers in glycomics. The field of glycomics is moving toward both generic and precise analysis.
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Glicômica/métodos , Espectrometria de Massas/métodos , Animais , Humanos , Polissacarídeos/químicaRESUMO
Efficient detection of aberrant glycoproteins in serum is particularly important for biomarker discovery. However, direct quantitation of glycoproteins in serum remains technically challenging because of the extraordinary complexity of the serum proteome. In the current work, we proposed a straightforward and highly efficient strategy by using the nonglycopeptides releasing from the specifically enriched glycoproteins for targeted glycoprotein quantification. With this so-called nonglycopeptide-based mass spectrometry (NGP-MS) strategy, a powerful and nondiscriminatory pipeline for hepatocellular carcinoma (HCC) glycoprotein biomarker discovery, verification, and validation has been developed. First, a data set of 234 NGPs was strictly established for multiple-reaction monitoring (MRM) quantification in serum. Second, the NGPs enriched from 20 HCC serum mixtures and 20 normal serum mixtures were labeled with mTRAQ reagents (Δ0 and Δ8, respectively) to find the differentially expressed glycoproteins in HCC. A total of 97 glycoprotein candidates were preliminarily screened and submitted for absolute quantitation with NGP-based stable-isotope-labeled (SID)-MRM in the individual samples of 38 HCC serum and 24 normal controls. Finally, 21 glycoproteins were absolutely quantified with high quality. The diagnostic sensitivity results showed that three glycoproteins, ß-2-glycoprotein 1 (APOH), α-1-acid glycoprotein 2 (ORM2), and complement C3 (C3), could be used for the discrimination between HCC patients and healthy people. A novel glycoprotein biomarker panel [APOH, ORM2, C3, and α-fetoprotein (AFP)] has proven to outperform AFP, the known HCC serum biomarker, alone, in this study. We believe that this strategy and the panel of glycoproteins might hold great clinical value for HCC detection in the future.
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Carcinoma Hepatocelular/sangue , Glicoproteínas/sangue , Neoplasias Hepáticas/sangue , Espectrometria de Massas/métodos , Biomarcadores/sangue , Humanos , alfa-Fetoproteínas/metabolismoRESUMO
The endo-galacturonase A gene (pgaA) was cloned using the cDNAs synthesized from total RNA of Aspergillus niger JL-15 by reverse transcription as template. The open reading frame (ORF) of pgaA was 1113bp, encoding a peptide of 370 amino acids with the predicted molecular mass of 38.8kDa. The pgaA was successfully expressed in Pichia pastoris GS115 under the control of AOX1 promoter. After induction by methanol for 96h, the activity of the recombinant endo-galacturonase A (rePgaA) in culture supernatant was 2091.0U/mg. SDS-PAGE analysis showed that the molecular mass of rePgaA was about 40.0kDa. Enzymatic properties assays showed that the optimum temperature and pH for rePgaA were 50°C and pH 5.0, respectively. The Michaelis-Menten constant (Km) and maximal velocity (Vmax) of rePgaA for citrus pectin were 3.20mgml(-1) and 40.97µmolmin(-1)ml(-1), respectively. The rePgaA mediated a rapid decrease in viscosity of pectin solution with release of small amount of reducing sugar. High performance liquid chromatography (HPLC) analysis revealed that digalacturonate (G2) and trigalalcturonate (G3) were the main hydrolysis products released from pectin by rePgaA. The rePgaA showed very low activity on G2 and G3, which suggested it was a typical endo-acting enzyme.
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Aspergillus niger/enzimologia , Pichia/genética , Poligalacturonase/genética , Poligalacturonase/isolamento & purificação , Sequência de Aminoácidos , Aspergillus niger/genética , Clonagem Molecular , Expressão Gênica , Ácidos Hexurônicos/química , Ácidos Hexurônicos/isolamento & purificação , Poligalacturonase/biossíntese , TemperaturaRESUMO
Arsenic contamination in environmental water sources poses a significant threat to human health, necessitating the development of sensitive and accessible detection methods. This study presents a multidimensional optimization of a bacterial biosensor for the susceptible and deoxyviolacein (DV)-based visual detection of arsenic. The research involved screening six different arsenic resistance (ars) operons and optimizing the genetic circuit to minimize background noise. Introducing an arsenic-specific transport channel enhanced the sensor's sensitivity to 1 nM with a quantitative range from 0.036 to 1.171 µM. The pigment-based biosensor offers a simple colorimetric approach for arsenic detection without complex instrumentation. The preferred biosensor demonstrated characteristics of anti-chelating agent interference, consistently quantified As(III) concentrations ranging from 0.036 to 1.171 µM covering the World Health Organization (WHO) drinking water limit. Innovatively, it effectively detects arsenic in seawater within a linear regression range of 0.071 to 1.125 µM. The biosensor's selectivity for arsenic was confirmed, with minimal cross-response to group 15 metals. Our naked-eye biosensor offers a novel approach for the rapid, on-site detection of arsenic in various water sources. Its simplicity, cost-effectiveness, and versatility make it a valuable tool for environmental monitoring and public health initiatives.
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Arsênio , Técnicas Biossensoriais , Poluentes Químicos da Água , Arsênio/análise , Técnicas Biossensoriais/métodos , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Colorimetria/métodos , Água do Mar/análise , Água do Mar/químicaRESUMO
The xylan binding domain (XBD) and linker sequences (LS) from thermostable and thermophilic Thermomonospora fusca xylanase A (TfxA) was fused to the carboxyl-terminus of a family 11 hybrid xylanase ATx. The constructed chimera (ATxX) was successfully expressed in Pichia pastoris, partially purified to homogeneity, and then characterized in detail. After 96-h 0.25% methanol induction, the xylanase and cellulose activity of ATxX from pPATxX1 transformant culture medium supernatant were 452.1 U/mg and 19.3 U/mg, respectively. SDS-PAGE analysis revealed that the molecular mass of ATxX was about 33.01 kDa. 3.7% ATxX was bound after incubation with 1% microcrystal cellulose at 25 °C for 3 h, while the ATx did not show cellulose binding-hydrolyzing ability. These results suggested that ATx obtained cellulose binding and hydrolyzing ability by fusing with XBD and LS. Enzymatic studies showed that the temperature and pH optimum of the ATxX xylanase activity were 60 °C and pH 5.0, respectively, which were the same as that of ATx. The temperature and pH optimum of the ATxX cellulase activity were 60 °C and pH 6.0, respectively. The major hydrolytic products released by ATxX from birchwood xylan were xylotriose and xylohexaose. Xylooligosaccharides from xylobiose to xylohexaose could be hydrolyzed by ATxX. Mode of action analysis showed that the chimeric ATxX was an endo-acting enzyme. The XBD and LS plays an important role in the binding and hydrolyzing of xylanase to insoluble substrates.
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Actinomycetales/enzimologia , Endo-1,4-beta-Xilanases/genética , Endo-1,4-beta-Xilanases/isolamento & purificação , Proteínas Recombinantes de Fusão/isolamento & purificação , Celulose/química , Endo-1,4-beta-Xilanases/biossíntese , Endo-1,4-beta-Xilanases/química , Concentração de Íons de Hidrogênio , Pichia , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Xilanos/química , Xilanos/metabolismoRESUMO
With the rapid development of synthetic biology, various whole-cell biosensors have been designed as valuable biological devices for the selective and sensitive detection of toxic heavy metals in environmental water. However, most proposed biosensors are based on fluorescent and bioluminescent signals invisible to the naked eye. The development of visible pigment-based biosensors can address this issue. The pbr operon from Klebsiella pneumoniae is selectively induced by bioavailable Pb(II). In the present study, the proviolacein biosynthetic gene cluster was transcriptionally fused to the pbr Pb(II) responsive element and introduced into Escherichia coli. The resultant biosensor responded to Pb(II) in a time- and dose-dependent manner. After a 5-h incubation with Pb(II), the brown pigment was produced, which could be extracted into n-butanol. Extra hydrogen peroxide treatment during n-butanol extract resulted in the generation of a stable green pigment. An increased brown signal was observed upon exposure to lead concentrations above 2.93 nM, and a linear regression was fitted from 2.93 to 3,000 nM. Extra oxidation significantly decreased the difference between parallel groups. The green signal responded to as low as 0.183 nM Pb(II), and a non-linear regression was fitted in a wide concentration range from 0.183 to 3,000 nM. The specific response toward Pb(II) was not interfered with by various metals except for Cd(II) and Hg(II). The PV-based biosensor was validated in monitoring bioaccessible Pb(II) spiked into environmental water. The complex matrices did not influence the regression relationship between spiked Pb(II) and the dual-color signals. Direct reading with the naked eye and colorimetric quantification enable the PV-based biosensor to be a dual-color and low-cost bioindicator for pollutant heavy metal.
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BACKGROUND: Low-molecular citrus pectin (LCP) is a pectin polysaccharide with low molec-ular weight, low degree of crux, and no branching. It is obtained by degrading natural citrus pectin (CP) through physical, chemical and enzymatic methods. LCP has received considerable attention in recent years due to its potential applications in the medical and biological fields. METHODS: In our previous study, LCP was prepared from CP by using recombinant Bacillus subtilis pectate lyase B. Monosaccharide comparative analysis revealed that the galacturonic acid content of LCP was higher than that of CP. The cell viability effect of LCP was elucidated by using HepG2 cells and the Cell Counting Kit-8 (CCK-8) assay. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, Annexin V-FITC/PI staining, and flow cytometer propidium iodide stain-ing were performed to detect the effects of LCP on apoptosis and cell cycle arrest in HepG2 cells. Mi-tochondrial membrane potential (MMP) was observed through 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine assay. RESULTS & DISCUSSION: The Mw of the prepared LCP was 7.6 kDa, which was significantly lower than that of CP (140 kDa). Cell viability decreased with the increase in the concentration of LCP. The half-inhibitory concentration of 1.46 ± 0.02 mg/mL was determined. Treatment with 1.6 mg/mL LCP in-duced the apoptosis of HepG2 cells with the inhibition rate of 83.10% ± 4.72%, and the cell cycle was arrested in the S phase. Furthermore, the MMP of HepG2 cells decreased with the increase in LCP concentration. CONCLUSION: The enzymatically prepared LCP could inhibit the proliferation of HepG2 cells. This study provided a partial experimental basis and reference for LCP to become a potential functional food for anti-liver cancer.
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Neoplasias Hepáticas , Apoptose , Proliferação de Células , Sobrevivência Celular , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Pectinas/farmacologiaRESUMO
Objective: The aim of this study was to develop and validate a nomogram to predict the overall survival of incidental gallbladder cancer. Methods: A total of 383 eligible patients with incidental gallbladder cancer diagnosed in Shanghai Eastern Hepatobiliary Surgery Hospital from 2011 to 2021 were retrospectively included. They were randomly divided into a training cohort (70%) and a validation cohort (30%). Univariate and multivariate analyses and the Akaike information criterion were used to identify variables independently associated with overall survival. A Cox proportional hazards model was used to construct the nomogram. The C-index, area under time-dependent receiver operating characteristic curves and calibration curves were used to evaluate the discrimination and calibration of the nomogram. Results: T stage, N metastasis, peritoneal metastasis, reresection and histology were independent prognostic factors for overall survival. Based on these predictors, a nomogram was successfully established. The C-index of the nomogram in the training cohort and validation cohort was 0.76 and 0.814, respectively. The AUCs of the nomogram in the training cohort were 0.8, 0.819 and 0.815 for predicting OS at 1, 3 and 5 years, respectively, while the AUCs of the nomogram in the validation cohort were 0.846, 0.845 and 0.902 for predicting OS at 1, 3 and 5 years, respectively. Compared with the 8th AJCC staging system, the AUCs of the nomogram in the present study showed a better discriminative ability. Calibration curves for the training and validation cohorts showed excellent agreement between the predicted and observed outcomes at 1, 3 and 5 years. Conclusions: The nomogram in this study showed excellent discrimination and calibration in predicting overall survival in patients with incidental gallbladder cancer. It is useful for physicians to obtain accurate long-term survival information and to help them make optimal treatment and follow-up decisions.
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OBJECTIVE: This study aims to explore the serum levels of IL-27 and the percentages of IL-27-producing cells in MG patients with positive acetylcholine receptor antibody (AChR-MG). METHODS: A total of 17 AChR-MG patients and 22 sex- and age- matched healthy controls (HCs) were recruited. Serum IL-27 levels were determined by enzyme linked immunosorbent assay. The percentages of IL-27+ cells, IL-27-producing T (CD3+IL-27+) cells, and IL-27-producing B (CD19+IL-27+) cells were measured by flow cytometry. RESULTS: Serum IL-27 levels in AChR-MG were significantly higher than those in HCs (13.44 ± 0.89 vs 7.14 ± 0.75 pg/mL, P < 0.0001), and were decreased after intravenous immunoglobulin (IVIG) treatment (P = 0.004). Moreover, the frequencies of IL-27+ lymphocytes were significantly elevated in AChR-MG patients than those in HCs (P = 0.011), and were decreased after IVIG treatment (P = 0.014). Furthermore, the frequencies of IL-27-producing T cells (P = 0.017) and IL-27-producing B cells (P = 0.015) were significantly elevated in AChR-MG patients as compared to those in HCs. Meanwhile, we observed positive correlations between the frequencies of IL-27+ lymphocytes and MG-ADL score (P = 0.030, r = 0.527). By contrast, no significant correlation was found between IL and 27 serum levels and MG-ADL score (P = 0.099, r = -0.414). CONCLUSION: IL-27 may play an important role in the pathological process in AChR-MG patients, and the frequencies of IL-27-producing (CD3+IL-27+) T cells may be a potential biomarker for predicting the severity of AChR-MG.
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Autoanticorpos/sangue , Interleucinas/sangue , Miastenia Gravis/sangue , Miastenia Gravis/diagnóstico , Receptores Colinérgicos/sangue , Adulto , Idoso , Linfócitos B/imunologia , Linfócitos B/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Citometria de Fluxo/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Cerebrospinal fluid (CSF) ß2-microglobulin (ß2-MG) levels elevated in patients with multiple sclerosis (MS). We examined the levels of ß2-MG in serum and cerebrospinal fluid (CSF) from 46 patients with neuromyelitis optica spectrum disorders (NMOSD), in serum from 21 healthy controls (HC), in CSF from 25 disease controls with non-inflammatory neurological diseases (NIND) with normal CSF results. CSF ß2-MG levels were significantly higher in patients with NMOSD than controls and with weak association with the number of white blood cells, protein and lactate levels in CSF. CSF ß2-MG is thus one more, non-specific indicator of inflammation in NMOSD.
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Esclerose Múltipla , Neuromielite Óptica , Aquaporina 4 , Humanos , Inflamação , Contagem de LeucócitosRESUMO
BACKGROUND: Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS), and whether herpes simplex virus (HSV) infection is associated with the development of MS remains controversial. We aimed to investigate potential associations between MS or clinically isolated syndrome (CIS) and the prevalence of IgG and DNA for HSV in the clinical samples. METHODS: A systematic search of English databases (PubMed, Embase and Cochrane Library) was performed. The prevalence of IgG against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) and DNA for HSV-1 or HSV-2 in clinical samples were pooled and compared between patients with MS/CIS and controls using Stata 12.0. RESULTS: A total of 1756 patients with MS/CIS and 6429 controls from eight studies were included. The pooled results showed a significantly statistical difference in the seroprevalence of IgG against HSV-2 (OR 1.764, 95% CI [1.410 to 2.206], P = 0.000) between patients with MS/CIS and controls. However, no significantly statistical difference was shown in the seroprevalence of IgG against HSV-1 (OR 1.166, 95% CI [0.737 to 1.845], P = 0.512) between patients with MS/CIS and controls. Similarly, there was no significantly statistical difference in the prevalence of HSV-1 DNA (OR 0.957, 95% CI [0.310 to 2.949], P = 0.938) and HSV-2 DNA in cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) (OR 0.506, 95% CI [0.022 to 11.416], P = 0.668) between patients with MS/CIS and controls. Subgroup analysis suggested that mean age at sampling might be a source of heterogeneity, and the seroprevalence of IgG against HSV-1 was significantly increased in the pediatric patients with MS/CIS (OR 1.488, 95% CI [1.130 to 1.959], P = 0.005), compared with the controls. CONCLUSIONS: The study demonstrated that prior HSV-1 infection might relate to the onset of pediatric MS/CIS and might not play a role in the development of adult MS. Furthermore, prior HSV-2 infection might have a correlation with MS/CIS. The mechanism remains to be further studied.
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Herpes Simples , Esclerose Múltipla , Adulto , Anticorpos Antivirais , Criança , Herpes Simples/complicações , Herpes Simples/epidemiologia , Humanos , Imunoglobulina G , Leucócitos Mononucleares , Esclerose Múltipla/complicações , Esclerose Múltipla/epidemiologia , Estudos SoroepidemiológicosRESUMO
BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) may be similar to each other in clinical features. The differential diagnosis between them remains challenging in clinical practice. This retrospective study is aimed to describe the difference of cerebrospinal fluid (CSF) lactate level between aquaporin-4 antibody (AQP4-Ab) positive NMOSD and MS, to discuss the possible explanation upon immunopathogenesis and the significance in differential diagnosis. METHOD: We retrospectively analysed cerebral biochemical results from 60 AQP4-Ab positive NMOSD and 55 MS Asian patients. To assess the diagnostic ability of cerebrospinal fluid lactate for distinguishing AQP4-Ab positive NMOSD from MS using receiver operating characteristic (ROC) curve analysis. RESULTS: The cerebrospinal fluid lactate level is significantly higher in AQP4-Ab positive NMOSD than in MS based on multiple linear regression (P<0.0001). The differential diagnostic efficacy of cerebrospinal fluid lactate distinguishing AQP4-Ab positive NMOSD from MS reached an area under ROC curve (AUC) of 0.8842 (95% CI 0.82-0.95, P<0.0001), using 1.50 as the diagnostic critical point of the cerebrospinal fluid lactate level, the sensitivity was 88.3%, the specificity was 78.2%. CONCLUSION: The cerebrospinal fluid lactate level differs between AQP4-Ab positive NMOSD and MS, which also contributes in differential diagnosis. The distinct patterns of cerebral biochemical results may cast a light on the immunopathogenesis of AQP4-Ab positive NMOSD.
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Neuromielite Óptica , Aquaporina 4 , Autoanticorpos , Diagnóstico Diferencial , Humanos , Lactatos , Neuromielite Óptica/diagnóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: Infectious encephalitis (IE) and autoimmune encephalitis (AE) are symptomatically similar in clinic, however essentially different in pathogenesis. Therefore, the objective of this study was to identify specific features to distinguish the two types of encephalitis for early effective diagnosis and treatments through a comparative analysis. METHODS: Fifty-nine IE patients and 36 AE patients were enrolled. The patients with IE were divided into viral encephalitis (VE) and bacterial encephalitis (BE) according to the pathogens in cerebrospinal fluid (CSF). Patients with AE were categorized by with or without neural autoantibodies (NAAb). We further divided patients with NAAb into those with neural cell-surface antibodies (NSAbs) or intracellular antibodies (Abs). Clinical features, laboratory data, and imaging findings were compared between AE, IE, and subgroups. RESULTS: Memory deficits, involuntary movement, and seizures were relatively more commonly presenting symptoms in AE patients (p < 0.05). The positive rate of Pandy test was higher in IE patients (p = 0.007). Decreased leukocyte, erythrocyte, and platelet counts in blood were found in IE patients (p < 0.05). Lower serum calcium level was found in VE compared to BE (p = 0.027). Meanwhile, higher serum calcium level was found in patients with NSAbs compared with intracellular Abs (p = 0.034). However, higher levels of LDH in CSF were found in patients with intracellular Abs (p = 0.009). In magnetic resonance imaging, hippocampus lesions were more commonly present in patients with AE (p = 0.042). Compared with AE patients, more IE patients displayed the background electroencephalogram rhythm of slow-frequency delta (p = 0.013). CONCLUSION: Involuntary movement and memory deficits were more specifically present in AE patients. CSF Pandy, blood routine test and hippocampus lesions detections were potential markers for distinguishing AE and IE. Further, CSF LDH, and serum calcium levels were potentially useful to distinguish subgroups of encephalitis.
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Uric acid (UA) is a natural scavenger for peroxynitrite and can reflect antioxidant activity and oxidative stress in several neurological disorders. Changes in serum and cerebrospinal fluid (CSF) levels of UA have been reported in patients with multiple sclerosis and neuromyelitis optica spectrum disorders. The levels of UA in CSF are relatively poorly understood in patients with Guillain-Barré syndrome (GBS). It remains unclear whether UA can play an antioxidant role and reflect oxidative stress in GBS. The purpose of this study is to investigate CSF and serum UA levels in patients with GBS and their relationship with clinical characteristics. The CSF and serum UA levels were detected in 43 patients with GBS, including 14 acute inflammatory demyelinating polyneuropathy (AIDP), 6 acute motor axonal neuropathy (AMAN), 13 with acute motor and sensory axonal neuropathy (AMSAN), 7 Miller Fisher syndrome (MFS), and 3 unclassified, and 25 patients with non-inflammatory neurological disorders (NIND) as controls. Moreover, serum UA levels were also detected in 30 healthy controls. The levels of UA were measured using uricase-based methods with an automatic biochemical analyzer. CSF UA levels were significantly increased in patients with GBS (p = 0.011), particularly in patients with AIDP (p = 0.004) when compared with NIND. Among patients with GBS, CSF UA levels were higher in those with demyelination (p = 0.022), although the difference was not significant after multiple testing correction. CSF UA levels in GBS were positively correlated with serum UA levels (r = 0.455, p = 0.022) and CSF lactate (r = 0.499, p = 0.011). However, no significant correlations were found between CSF UA levels and GBS disability scores. There were no significant differences in serum UA levels among GBS, NIND, and healthy controls. These results suggest that CSF UA may be related to the pathogenesis of demyelination in patients with GBS and may be partially determined by serum UA and the impaired blood-nerve barrier.
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AIMS: Neuromyelitis optica spectrum disorders (NMOSD) are aquaporin-4 antibody-mediated diseases of the central nervous system. Endothelin-1 (ET-1) is an inflammatory cytokine released by vascular endothelial cells and activated astrocytes. Previous studies have reported the aberrant expressions of cytokines/chemokines in patients diagnosed with NMOSD. However, the serum levels of ET-1 in NMOSD patients remain unknown. The purpose of this study was to measure the serum levels of ET-1 and other immune-related cytokines/chemokines in patients with NMOSD, and to investigate the correlation between serum ET-1 levels and clinical characteristics of NMOSD. METHODS: Thirty-eight patients with NMOSD and twenty-eight healthy controls (HCs) were recruited in this study. The serum concentrations of ET-1 and other cytokines/chemokines were measured, and their correlations to the clinical features of patients with NMOSD were analyzed. RESULTS: The serum levels of ET-1 in patients with NMOSD were significantly higher than those in HCs (Pâ¯=⯠0.0001). The serum concentrations of ET-1 were positively correlated with the Expanded Disability Status Scale score (râ¯=â¯0.428, Pâ¯=â¯0.0183). High-dose intravenous methylprednisolone treatment significantly reduced the levels of ET-1 and interleukin (IL)-6 in blood, but significantly increased the serum concentrations of IL-10 in NMOSD patients. No correlations were found between serum ET-1 levels and the concentrations of other cytokines/chemokines in these patients. CONCLUSION: ET-1 and IL-6 might exert pro-inflammatory effects in the pathogenesis of NMOSD, whereas IL-10 played an anti-inflammatory role in this process. ET-1 might be a potential biomarker for predicting the severity of NMOSD. However, the serum levels of ET-1 were not correlated with the changes of other cytokines/chemokines in patients with NMOSD. The involvement of ET-1 in the development of NMOSD needs to be further studied.
Assuntos
Biomarcadores , Endotelina-1/sangue , Neuromielite Óptica/sangue , Neuromielite Óptica/diagnóstico , Citocinas/sangue , Citocinas/metabolismo , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Humanos , MicroRNAs/genética , Monócitos/imunologia , Monócitos/metabolismo , Neuromielite Óptica/etiologia , Prognóstico , Índice de Gravidade de Doença , Transdução de SinaisRESUMO
BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is a severe immune-mediated inflammatory central nervous system (CNS) syndrome. YKL-40, as a new inflammatory marker, has been studied in many autoimmunity and CNS diseases. Our aim of this study was to investigate cerebrospinal fluid (CSF) and serum YKL-40 levels in patients with NMOSD and their association with disease severity. METHODS: We measured CSF and serum YKL-40 levels in 29 patients with NMOSD and 21 age- and sex-matched controls. We analyzed the associations between CSF YKL-40 levels and the clinical variables of NMOSD. RESULTS: Compared to controls, patients with NMOSD had significantly higher CSF YKL-40 levels. Moreover, CSF YKL-40 levels were positively correlated with the Expanded Disability Status Scale scores. CONCLUSIONS: YKL-40 could be a NMOSD severity biomarker and a potential target for NMOSD treatment.