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Non-pharmaceutical interventions (NPIs) implemented to control SARS-CoV-2 have significantly influenced the activity of respiratory pathogens. This study investigated epidemiological changes among hospitalized patients with respiratory syncytial virus (RSV) before (2017-2019) and during (2020-2022) the COVID-19 pandemic in Hangzhou, China. We also examined viral load distribution across demographic and temporal variables. Nasopharyngeal swabs were collected and RSV loads were quantified using reverse transcriptase polymerase chain reaction (RT-qPCR). RSV epidemic characteristics, seasonal dynamics, and viral load distributions were compared between pre- and pandemic years. General linear models were employed to assess associations between viral loads and age. Among 19 742 cases, 1576 and 2092 tested positive during the pre- and pandemic years, respectively. From February to July 2020, the implementation of NPIs led to the cessation of RSV circulation. However, after these measures were relaxed, RSV cases resurged over two consecutive seasons during the pandemic, notably affecting older children compared to those in the pre-pandemic years (1.00 years, IQR: 0.50-2.00 vs. 0.58 years, IQR: 0.27-1.00, p < 0.001). Specifically, in 2021-2022, an off-season resurgence of RSV began earlier (mid-June), lasted longer (40 weeks), and involved more positive cases (1238 cases) than both 2020-2021 and pre-pandemic years. Viral load distribution demonstrated a clear age-related relationship in both pre- and pandemic years, with younger children consistently showing higher viral loads, independently of gender and season (all p-values for trends <0.001). These findings highlight the impact of NPIs on RSV epidemiology and underscore the need to prioritize RSV infection prevention in younger children from the perspective of viral load.
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COVID-19 , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , SARS-CoV-2 , Estaciones del Año , Carga Viral , Humanos , China/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , COVID-19/epidemiología , COVID-19/virología , Lactante , Preescolar , Masculino , Femenino , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Niño , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Hospitalización/estadística & datos numéricos , Recién Nacido , Niño Hospitalizado/estadística & datos numéricos , Adolescente , Nasofaringe/virologíaRESUMEN
Genetic risk for schizophrenia is thought to trigger variation in clinical features of schizophrenia, but biological processes associated with neuronal activity in brain regions remain elusive. In this study, gene expression features were mapped to various sub-regions of the brain by integrating low-frequency amplitude features and gene expression data from the schizophrenia brain and using gene co-expression network analysis of the Allen Transcriptome Atlas of the human brain from six donors to identify genetic features of brain regions and important associations with neuronal features. The results indicate that changes in the dynamic amplitude of low-frequency fluctuation (dALFF) are mainly associated with transcriptome signature factors such as cortical layer synthesis, immune response, and expanded membrane transport. Further modular disease enrichment analysis revealed that the same set of signature genes associated with dALFF levels was enriched for multiple neurological biological processes. Finally, genetic profiling of individual modules identified multiple core genes closely related to schizophrenia, also potentially associated with neuronal activity. Thus, this paper explores genetic features of brain regions in the schizophrenia closely related to low-frequency amplitude ratio levels based on imaging genetics, which suggests structural endophenotypes associated with schizophrenia.
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Esquizofrenia , Humanos , Esquizofrenia/genética , Esquizofrenia/metabolismo , Encéfalo/metabolismo , Transcriptoma , Perfilación de la Expresión Génica , Neuronas/metabolismo , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: The MC-80 (Mindray, Shenzhen, China), a newly available artificial intelligence (AI)-based digital morphology analyzer, is the focus of this study. We aim to compare the leukocyte differential performance of the Mindray MC-80 with that of the Sysmex DI-60 and the gold standard, manual microscopy. METHODS: A total of 100 abnormal peripheral blood (PB) smears were compared across the MC-80, DI-60, and manual microscopy. Sensitivity, specificity, predictive value, and efficiency were calculated according to the Clinical and Laboratory Standards Institute (CLSI) EP12-A2 guidelines. Comparisons were made using Bland-Altman analysis and Passing-Bablok regression analysis. Additionally, within-run imprecision was evaluated using five samples, each with varying percentages of mature leukocytes and blasts, in accordance with CLSI EP05-A3 guidelines. RESULTS: The within-run coefficient of variation (%CV) of the MC-80 for most cell classes in the five samples was lower than that of the DI-60. Sensitivities for the MC-80 ranged from 98.2% for nucleated red blood cells (NRBC) to 28.6% for reactive lymphocytes. The DI-60's sensitivities varied between 100% for basophils and reactive lymphocytes, and 11.1% for metamyelocytes. Both analyzers demonstrated high specificity, negative predictive value, and efficiency, with over 90% for most cell classes. However, the DI-60 showed relatively lower specificity for lymphocytes (73.2%) and lower efficiency for blasts and lymphocytes (80.1% and 78.6%, respectively) compared with the MC-80. Bland-Altman analysis indicated that the absolute mean differences (%) ranged from 0.01 to 4.57 in MC-80 versus manual differential and 0.01 to 3.39 in DI-60 versus manual differential. After verification by technicians, both analyzers exhibited a very high correlation (r = 0.90-1.00) with the manual differential results in neutrophils, lymphocytes, and blasts. CONCLUSIONS: The Mindray MC-80 demonstrated good performance for leukocyte differential in PB smears, notably exhibiting higher sensitivity for blasts identification than the DI-60.
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Leucocitos , Humanos , Leucocitos/patología , Leucocitos/citología , Sensibilidad y Especificidad , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/patología , Recuento de Leucocitos/instrumentación , Recuento de Leucocitos/métodos , Recuento de Leucocitos/normas , Femenino , Automatización de Laboratorios , Masculino , Reproducibilidad de los Resultados , Inteligencia ArtificialRESUMEN
PURPOSE: Immunoglobulin A (IgA) nephropathy (IgAN) is a common chronic glomerulonephritis and the main cause of end-stage renal diseases. Recent evidence suggests that mannan binding lectin associated serine proteases 2 (MASP2) is related to IgAN; therefore, we investigated the expression and significance of MASP2 in serum and urinary extracellular vesicles (UEVs) in patients with IgAN. METHODS: Thirty-eight patients with IgAN and 17 healthy controls were enrolled in this study. UEVs were extracted by ultracentrifugation. The separation by ultra-high-speed centrifuge was verified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Candidate internal references (TSG101, CD9, flotillin, ß-actin and GAPDH) were identified by western blotting in the control group, and the expression of MASP2 in the UEVs was compared. The levels of MASP2 in the serum and UEVs in the IgAN and control groups were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: TEM and NTA results demonstrated that UEVs were successfully extracted. Western blotting results confirmed that TSG101 was suitable as an internal reference for this study. Compared with the control group, the IgAN group showed positive expression of MASP2. MASP2 levels in the UEVs, determined by ELISA, showed significant differences between IgAN and control groups, which were significantly positively correlated with the level of urinary microalbumin. CONCLUSIONS: The level of MASP2 in UEVs was related to IgAN and shows promise as a biomarker for evaluating the severity of renal injury and prognosis of IgAN, thereby helping to elucidate the role of MASP2 in the mannan-binding lectin pathway.
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Vesículas Extracelulares , Glomerulonefritis por IGA , Lectina de Unión a Manosa , Actinas , Biomarcadores , Vesículas Extracelulares/metabolismo , Glomerulonefritis por IGA/metabolismo , Humanos , Inmunoglobulina A/metabolismo , Serina Proteasas Asociadas a la Proteína de Unión a la Manosa , Serina ProteasasRESUMEN
Solasonine, a steroidal glycoalkaloid isolated from the herbal plant Solanum nigrum Linn., has shown active against multiple human cancers; however, there is little knowledge on the activity of solasonine against gastric cancer until now. This study aimed to examine the effect of solasonine on the biological behaviours of human gastric cancer SGC-7901 cells. The results showed that solasonine suppressed SGC-7901 cell proliferation in a dose-dependent manner. Solasonine treatment mainly induced the cell cycle arrest at G2 phase in SGC-7901 cells. Treatment with solasonine resulted in significant down-regulation of Bcl-2 and Caspase-3 protein expression and reduced Bax and Bcl-xL protein expression in SGC-7901 cells. Solasonine shows a comparable inhibitory effect on the proliferation of human gastric cancer SGC-7901 cells with cisplatin, and solasonine induces of SGC-7901 cell apoptosis through triggering the endoplasmic reticulum stress pathway and the mitochondrial pathway. Our data indicate that solasonine may be a promising agent for the treatment of gastric cancer.
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Neoplasias Gástricas , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Humanos , Mitocondrias/metabolismo , Alcaloides Solanáceos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismoRESUMEN
Renal injury in lupus nephritis (LN) does not manifest as one uniform entity. The clinical presentation, management, and prognosis of membranous LN (MLN) differ from that of the proliferative LN (PLN). Differentiating the molecular mechanisms involved in MLN and PLN and discovering the reliable biomarkers for early diagnosis and target therapy are important. We compared the kidney protein expression patterns of 11 pure MLN and 12 pure PLN patients on formalin-fixed paraffin-embedded (FFPE) kidney tissues using label-free liquid chromatography-mass spectrometry (LC-MS) for quantitative proteomics analysis. FunRich software was used to identify proteins in differentially expressed pathways. Quantitative comparisons of differentially expressed proteins in each patient were further analyzed based on protein intensity levels determined by LC-MS. The protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was established through Search Tool for the Retrieval of Interacting Genes database (STRING) website, visualized by Cytoscape. A total of 5112 proteins were identified. In total, 12 significantly upregulated (fold change ≥2, p < 0.05) proteins were identified in the MLN group and 220 proteins (fold change ≥2, p < 0.05) were upregulated in the PLN group. Further analysis showed that the most significant upregulated pathway involved in MLN was histone deacetylase (HDAC) class I pathway, and the three most significant upregulated pathways in PLN were interferon signaling, interferon gamma signaling, and the immune system. Next, we selected sirtuin-2 (SIRT2) in MLN, and vascular cell adhesion protein 1 (VCAM1) and Bcl-xl in PLN for further mass spectrometry (MS) intensity and PPI analysis. SIRT2 expression was significantly increased in the MLN group compared with the PLN group, and VCAM1, Bcl-xl expression was significantly increased in the PLN group compared with the MLN group, based on MS intensity. These results may help to improve our understanding of the underlying molecular mechanisms of MLN and PLN and provide potential targets for the diagnosis and treatment of different subclasses of LN.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Riñón , Lupus Eritematoso Sistémico/metabolismo , Nefritis Lúpica/metabolismo , ProteómicaRESUMEN
Listeria monocytogenes, a food-borne Gram-positive pathogen, often causes diseases such as gastroenteritis, bacterial sepsis, and meningitis. Newly discovered extracellular electron transfer (EET) from L. monocytogenes plays critical roles in the generation of redox molecules as electron carriers in bacteria. A Mg2+-dependent protein flavin mononucleotide (FMN) transferase (FmnB; UniProt: LMRG_02181) in EET is responsible for the transfer of electrons from intracellular to extracellular by hydrolyzing cofactor flavin adenine dinucleotide (FAD) and transferring FMN. FmnB homologs have been investigated in Gram-negative bacteria but have been less well studied in Gram-positive bacteria. In particular, the catalytic and inhibitory mechanisms of FmnB homologs remain elusive. Here, we report a series of crystal structures of apo-FmnB and FmnB complexed with substrate FAD, three inhibitors AMP, ADP, and ATP, revealing the unusual catalytic triad center (Asp301-Ser257-His273) of FmnB. The three inhibitors indeed inhibited the activity of FmnB in varying degrees by occupying the binding site of the FAD substrate. The key residue Arg262 of FmnB was profoundly affected by ADP but not AMP or ATP. Overall, our studies not only provide insights into the promiscuous ligand recognition behavior of FmnB but also shed light on its catalytic and inhibitory mechanisms.
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C3 glomerulopathy (C3G) is a rare renal disease characterized by predominant glomerular C3 staining. Complement alternative pathway dysregulation due to inherited complement defects is associated with C3G. To identify novel C3G-related genes, we screened 86 genes in the complement, coagulation and endothelial systems in 35 C3G patients by targeted genomic enrichment and massively parallel sequencing. Surprisingly, the most frequently mutated gene was VWF. Patients with VWF variants had significantly higher proteinuria levels, higher crescent formation and lower factor H (FH) levels. We further selected two VWF variants to transiently express the von Willebrand factor (vWF) protein, we found that vWF expression from the c.1519A > G variant was significantly reduced. In vitro results further indicated that vWF could regulate complement activation, as it could bind to FH and C3b, act as a cofactor for factor I-mediated cleavage of C3b. Thus, we speculated that vWF might be involved in the pathogenesis of C3G.
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Complemento C3/metabolismo , Glomerulonefritis Membranoproliferativa/genética , Glomerulonefritis/genética , Factor de von Willebrand/genética , Adolescente , Adulto , Estudios de Casos y Controles , China , Estudios de Cohortes , Complemento C3b/metabolismo , Factor H de Complemento/metabolismo , Vía Alternativa del Complemento , Femenino , Variación Genética , Glomerulonefritis/inmunología , Glomerulonefritis/patología , Glomerulonefritis Membranoproliferativa/inmunología , Glomerulonefritis Membranoproliferativa/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Técnicas In Vitro , Glomérulos Renales/inmunología , Glomérulos Renales/patología , Masculino , Persona de Mediana Edad , Modelos Inmunológicos , Simulación de Dinámica Molecular , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Análisis de Secuencia de ADN , Adulto Joven , Factor de von Willebrand/química , Factor de von Willebrand/metabolismoRESUMEN
The UbiA superfamily of intramembrane prenyltransferases catalyzes an isoprenyl transfer reaction in the biosynthesis of lipophilic compounds involved in cellular physiological processes. Digeranylgeranylglyceryl phosphate (DGGGP) synthase (DGGGPase) generates unique membrane core lipids for the formation of the ether bond between the glycerol moiety and the alkyl chains in archaea and has been confirmed to be a member of the UbiA superfamily. Here, the crystal structure is reported to exhibit nine transmembrane helices along with a large lateral opening covered by a cytosolic cap domain and a unique substrate-binding central cavity. Notably, the lipid-bound states of this enzyme demonstrate that the putative substrate-binding pocket is occupied by the lipidic molecules used for crystallization, indicating the binding mode of hydrophobic substrates. Collectively, these structural and functional studies provide not only an understanding of lipid biosynthesis by substrate-specific lipid-modifying enzymes but also insights into the mechanisms of lipid membrane remodeling and adaptation.
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Proteínas Arqueales/metabolismo , Glicerofosfatos/biosíntesis , Methanocaldococcus/enzimología , Archaea/enzimología , Proteínas Arqueales/biosíntesis , Proteínas Arqueales/genética , Glicerofosfatos/metabolismo , Lípidos de la Membrana , Methanocaldococcus/metabolismo , Estructura Secundaria de ProteínaRESUMEN
BACKGROUND: Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM), and the most frequent cause of end-stage renal disease (ESRD) in many countries. Urinary extracellular vesicles (UEVs) are considered a rich non-invasive source of markers for renal diseases. In this study, UEV enrichment and analysis in diabetic nephropathy (DN) was performed in a community epidemiological survey supported through the ISN CKHDP program. MATERIALS AND METHODS: Patients were divided into five groups according to severity of kidney damage. A hydrostatic dialysis method was used for UEV enrichment followed by quantitation using Coomassie protein assays and subsequent adjustment using urinary creatinine levels. UEVs were then characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting of tumor susceptibility gene product TSG101. Two-dimensional DIGE (2D-DIGE) was used to analyze differential protein expression in the UEVs. Mass spectrometry (MS) was conducted and MASCOT search engine was used to identify potential biomarkers. RESULTS: Bradford protein assay showed that protein concentration of UEVs in diabetics with kidney injury increased significantly as compared to normal controls. UEVs present a round, cup-shaped, membrane-encapsulated structure under TEM, and the main peak of UEVs show 55 - 110 nm nanoparticles with NTA. MS and MASCOT identified 22 differential proteins, and MASP2, CALB1, S100A8, and S100A9 were selected as potential biomarkers of early DN based on bioinformatic analysis. DISCUSSION: Our results show UEV proteome changes in different stages of DN. The results of this study show four unique proteins that undergo changes in early DN. These promising discoveries may prompt a new field of research focused on improving the diagnosis of DN.
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Nefropatías Diabéticas/diagnóstico , Vesículas Extracelulares/química , Estado Prediabético/diagnóstico , Biomarcadores/orina , Calgranulina A/análisis , Proteínas de Unión al ADN/orina , Nefropatías Diabéticas/orina , Complejos de Clasificación Endosomal Requeridos para el Transporte/orina , Humanos , Serina Proteasas Asociadas a la Proteína de Unión a la Manosa/orina , Estado Prediabético/orina , Proteómica , Factores de Transcripción/orinaRESUMEN
OBJECTIVE: To investigate which plasma lipid parameters are useful for detecting chronic kidney disease (CKD) in a Chinese population without known CKD or renal impairment. METHODS: This was a prospective study. In southern Chinese cities from 2012 to 2013, a total of 1037 subjects aged ≥ 18 years old received a survey. Logistic regression and multiple linear regression analyses were performed. The lipid parameters studied included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (nHDL-C), TG/HDL-C ratio, TC/HDL-C ratio and nHDL-C/HDL-C ratio. RESULTS: After adjusting for confounding factors, the fourth percentile of logTG/HDL-C was observed to be an independent risk factor for CKD (OR = 2.453, P < 0.001), and the highest quantile of the logTG/HDL-C ratio was associated with a higher prevalence of CKD (P < 0.05). This risk was reduced when the model was adjusted with Insulin resistance (IR) (OR = 2.034, P < 0.05). In the group of women, glucose metabolism disorders, high uric acid, and obesity, this risk was increased. Multiple regression models showed that log TG and nonHDL-C/HDL-C were negatively correlated with eGFR (P < 0.05), while log TG and TC were positively correlated with logACR (P < 0.05). The area under the curve (ROC) of lgTG/HDL was 0.623 (p < 0.001). CONCLUSION: The serum logTG/HDL-C ratio is the only suitable predictor of CKD, and IR may be the mechanism. This risk needs to be controlled in a specific population. Log TG and nonHDL-C/HDL-C were negatively correlated with eGFR, while log TG and TC were positively correlated with logACR.
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PURPOSE: To investigate the correlation between visceral obesity and pathogenesis of chronic kidney disease (CKD) among non-diabetic individuals, and to evaluate the potential of visceral adiposity index (VAI) as a predictor of CKD. PATIENTS AND METHODS: From December 2017 to March 2018, 1877 non-diabetic participants (male n=699, female n=1208) in southern China were recruited for a cross-sectional survey. Males and females were divided into four groups according to gender-specific quartiles of VAI scores. A logistic regression model was established to analyze the correlation between visceral adiposity index and CKD. RESULTS: Visceral adiposity index was positively correlated with CKD and was negatively associated with estimated glomerular filtration rate (eGFR). Using group one as the control, odds ratios (ORs) were calculated to determine the risk of developing CKD as VAI increased (male: group four 2.73 [P<0.005]; female: Group three 1.76 [P<0.05], Group four 2.88 [P<0.005]). When related factors such as history of hypertension, smoking, alcohol use, and physical inactivity were normalized in the logistic model before calculation, ORs became 2.73 (male: P<0.05), and 2.18 (female: P<0.05), respectively. The results differed after normalizing further for systolic blood pressure (SBP), diastolic blood pressure (DBP), hypersensitive c-reactive protein (hsCRP), interleukin-6 (IL-6), homocysteine (Hcy), superoxide dismutase (SOD), and retinol-binding protein (RBP). There were no significant differences in ORs among the female groups. CONCLUSION: Visceral adiposity index was significantly associated with CKD in non-diabetic individuals. It may be a good predictor of the pathogenesis of CKD and was dependent on hsCRP, IL-6, Hcy, SOD, RBP, and blood pressure levels in females and males with VAI scores of 1.41 and higher. Visceral adiposity index may be used to predict CKD in males with VAI less than 0.983.
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PURPOSE: Metabolic syndrome (MetS), which is a global public health problem, is a state of chronic low-grade inflammation. This study looked at the changes in hematological parameters and the predictive value of the lymphocyte to high-density lipoprotein cholesterol (HDL-C) ratio (LHR) as a new index in subjects with and without MetS in coastal cities in southern China. PATIENTS AND METHODS: In this cross-sectional study, there were 852 participants (n = 598 with MetS and n = 254 without MetS). MetS was defined in accordance with the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATP III) criteria. RESULTS: MetS was positively correlated with white blood cell count, total lymphocyte count, neutrophil count, red blood cell count, hematocrit, hemoglobin, and high-sensitivity C-reactive protein levels (p<0.05). In addition, there was a positive correlation between LHR and the number of metabolic risk factors for MetS. In a logistic regression analysis, LHR (odds ratio: 4.117; 95% CI: 2.766-6.309; p<0.001) was an independent predictor of MetS. When a receiver operating characteristic (ROC) curve analysis was used to assess the value of LHR for predicting MetS, the area under the curve yielded a cut-off value of 1.657, with a sensitivity of 65% and a specificity of 64% (p<0.0001). CONCLUSION: In summary, MetS can involve changes in blood parameters, and LHR may be a useful marker of inflammation to assess the presence and severity of MetS.
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BACKGROUND: Urinary extracellular vesicles (UEVs) carry rich markers of their parent cells, so they can serve as possible biomarkers of kidney diseases. METHODS: In this study, we isolated urinary extracellular vesicles from five individuals using a simple, clinically applicable method called hydrostatic filtration dialysis (HFD) and compared it to the gold-standard ultracentrifuga-tion (UC) with transmission electron microscopy (TEM). We also employed a proteomic approach using pooled human urine samples from the same five individuals to profile the protein composition of UEVs to evaluate the effectiveness of these two methods. RESULTS: Notably, using TEM, we found that all isolations contained 0 - 400 nm vesicles with the traditionally reported morphology, although the TEM results showed that the UEVs isolated from HFD compared to those from UC are larger and more extensive. We obtained a total of 2,564 UEV proteins in the two methods. We showed a large overlap (2,185 > 85%) between the proteins identified by both isolation methods. The result also showed that the obtained proteins in extracellular vesicles, which are isolated with these methods, are consistent with the results in currently available databases. However, in the associated gene ontologies, the enriched proteins found by the two methods showed some differences. CONCLUSIONS: The HFD method is clinically feasible and allows large-scale protein profiling of UEV biomarkers. The results of this study also provide valuable UEV protein data from the methodological comparison, which might be valuable to other researchers.
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Vesículas Extracelulares/metabolismo , Perfilación de la Expresión Génica , Enfermedades Renales/orina , Proteómica/métodos , Ultracentrifugación/métodos , Urinálisis/normas , Adulto , Biomarcadores/metabolismo , Femenino , Humanos , Masculino , Microscopía Electrónica de Transmisión , Diálisis Renal , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem , Urinálisis/métodos , Adulto JovenRESUMEN
[This corrects the article DOI: 10.1186/s13039-014-0078-3.].
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Autoimmune diseases are characterized by pathogenic immune responses to self-antigens. In systemic lupus erythematosus (SLE), many self-antigens are found in apoptotic cells (ACs), and defects in removal of ACs from the body are linked to a risk for developing SLE. This includes pathological memory that gives rise to disease flares. In this study, we investigated how memory to AC-derived self-antigens develops and the contribution of self-memory to the development of lupus-related pathology. Multiple injections of ACs without adjuvant into wild-type mice induce a transient primary autoimmune response without apparent anti-nuclear Ab reactivity or kidney pathology. Interestingly, as the transient Ab response reached baseline, a single boost injection fully recalled the immune response to ACs, and this memory response was furthermore transferable into naive mice. Additionally, the memory response contains elements of pathogenicity, accompanied by selective memory to selective Ags. Thus, we provide evidence for a selective self-memory that underlies progression of the response to self-antigens with implications for SLE development therapy.
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Apoptosis/inmunología , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Memoria Inmunológica/inmunología , Lupus Eritematoso Sistémico/inmunología , Animales , Lupus Eritematoso Sistémico/terapia , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND/PURPOSE: This study investigated the correlation between antibiotic consumption and the incidence of health care-associated infections (HCAIs) caused by imipenem-resistant Acinetobacter baumannii (IRAB) at a hospital in Taiwan from 2005 to 2010. METHODS: Data on annual consumption (defined daily dose per 1000 patient-days) of extended-spectrum cephalosporins, ß-lactam-ß-lactamase inhibitor combinations, carbapenems, aminoglycosides, and fluoroquinolones from 2005 to 2010 were analyzed. Yearly aggregated data on the number of nonduplicate clinical IRAB isolates causing HCAI were collected. The incidence rates of HCAI caused by IRAB were defined as the number of patients infected with IRAB per 1000 inpatient-days. RESULTS: The trend of total consumption (defined daily dose per 1000 patient-days) of extended-spectrum cephalosporins, carbapenems, and fluoroquinolones was significantly increased, but the use of aminoglycosides decreased during 2005 to 2010. During the same period, the incidence of HCAI caused by IRAB gradually increased. The consumptions of carbapenems and fluoroquinolones were positively correlated with the incidence of HCAI caused by IRAB. There was no significant association between the use of extended-spectrum cephalosporins, ß-lactam-ß-lactamase inhibitor combinations, and aminoglycosides and the incidence of HCAI caused by IRAB. CONCLUSION: The increasing use of carbapenems and fluoroquinolones was associated with the increasing incidence of HCAI caused by IRAB.
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Infecciones por Acinetobacter/epidemiología , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/uso terapéutico , Carbapenémicos/uso terapéutico , Infección Hospitalaria/epidemiología , Utilización de Medicamentos , Resistencia betalactámica , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/aislamiento & purificación , Infección Hospitalaria/microbiología , Fluoroquinolonas/uso terapéutico , Hospitales , Humanos , Incidencia , Taiwán/epidemiologíaRESUMEN
OBJECTIVE: To employ single nucleotide polymorphisms (SNP) microarray to detect copy number variations (CNVs) for the diagnosis of disease and molecular classification. METHODS: For a patient with split-hand/split-foot malformation, genome-wide copy number variants SNP microarray was applied. Tiny copy number variations were verified by real-time fluorescent quantitative PCR. RESULTS: The results of SNP microarray has revealed that the patient has carried a 0.39 Mb duplication in 10q24.31-24.32 (102 955 122-103 348 688), which has encompassed genes including LBX1, BTRC and POLL. By real-time fluorescent quantitative PCR, duplicate area encompassing the pathogenic genes have been verified. The results for LBX1, BTRC, POLL genes were all consistent with the SNP microarray test. Moreover, a duplication was detected in exon 9 of FBXW4 gene which is in nearby. CONCLUSION: SNP chips can efficiently identify tiny CNVs (< 1.0 Mb). In combination with real-time fluorescence quantitative PCR, this may provide valuable information for prenatal diagnosis.
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Variaciones en el Número de Copia de ADN , Deformidades Congénitas de las Extremidades/genética , Adulto , Pueblo Asiatico/genética , China , Duplicación Cromosómica , ADN Polimerasa beta/genética , Proteínas de Homeodominio/genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Factores de Transcripción/genética , Proteínas con Repetición de beta-Transducina/genéticaRESUMEN
BACKGROUND: Terminal deletion of 6q27 produces a rare syndrome associated with unexplained mental retardation, hypotonia, epilepsy, and multiple malformations. Structural brain malformations are consistently observed, including agenesis of the corpus callosum, hydrocephalus, periventricular nodular heterotopia, polymicrogyria, and cerebellar malformations. Here we report a fetal risk assessment of a 27-year-old woman with mental retardation, hypotonia and dysmorphic features at 17 weeks of pregnancy. RESULTS: Cytogenetic analyses revealed an addition at chromosome 6qter in the mother. Haploinsufficiency of 6q27 to 6qter (1.3 Mb) and trisomy of the entire short arm of chromosome 18 (15.2 Mb) were found using a single nucleotide polymorphism based array. Results were confirmed by molecular cytogenetics and multiplex ligation-dependent probe amplification. The karyotype of the mother was 46,XX dic(6;18)(6pter â 6q27::18p10 â 18pter).arr [hg19]6q27(169,591,548-170,898,549) × 1,18p11.3p10(12,842-15,375,878) × 3.ish dic(6;18)(q27;p10)(RP11-614P3-,RP11-1035E2+,D18Z1+). Deletion of 6q27 was associated with the structural brain malformations, whereas trisomy of 18p had minor clinical effects. The unbalanced rearrangement of chromosome 6 and chromosome 18 was de novo and was not inherited by the developing fetus. CONCLUSIONS: A rare rearrangement between 6q27 and 18p was identified, which led to a de novo 1.3 Mb deletion of 6q27 and a 15.2 Mb duplication of 18p in an adult with mental retardation, hypotonia, epilepsy, and multiple malformations.