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1.
Bioresour Technol ; 343: 126095, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34624470

RESUMO

Astaxanthin exhibits strong antioxidant ability, so researchers endeavor to improve astaxanthin production in Haematococcus pluvialis (H. pluvialis). Previous work revealed that low-temperature plasma (LTP) could improve the astaxanthin yield in H. pluvialis, but the mechanism is still elusive. In this work, we therefore explored the mechanism of LTP promoting algal growth astaxanthin yield, especially from the perspective of epigenetics. Through measurements of hormones and transcription genes, it was found that the levels of strigolactone and abscisic acid in H. pluvialis increased significantly after LTP treatment, accompanied by enhanced expression of astaxanthin synthesis genes. Particularly, one of the key genes, namely CRTISO, was specifically up-regulated. Further experiments via immunofluorescence and ChIP-PCR methods confirmed that histone H3 lysine 4 tri-methylation (H3K4me3) in the promoter region of CRTISO was increased. Therefore, this study demonstrates that LTP can regulate CRTISO and promote the algal growth and astaxanthin accumulation by stimulating phytohormones and regulating H3K4me3.


Assuntos
Histonas , Lisina , Metilação , Temperatura , Xantofilas
2.
Sci Total Environ ; : 151348, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34728211

RESUMO

Organophosphate esters (OPEs) are widely used flame retardants that are frequently released into the environment, causing potential harm to humans and ecosystems. Tibet is located on the Tibetan Plateau, known as the "roof of the world", but the occurrence of OPEs in Tibet remains unclear. This is the first report of the occurrence, potential sources and risks of 12 OPEs in water, soil, sediment and snow from Xainza, a typical town at high-elevation in Tibet (average elevation = 4700 m). Ten OPEs were observed, with ∑OPE concentrations of 46.45-1744.73 ng/L in surface water, 29.74-73.85 ng/g in soil, and 13.30-32.23 ng/g in sediment. Moreover, the mean ∑OPE concentration in snow was 413.90 ng/L. Tris (2-chloroethyl) phosphate (TCEP) and tris (2-chloroisopropyl) phosphate (TCPP) were the main OPEs in surface water and snow, while 2-ethylhexyl diphenyl phosphate (EHDPP) was dominant in soil and sediment. Local human activities and long-distance atmospheric transport may be the main sources of OPEs in Xainza. The assessment of ecological risk indicated that EHDPP in soil poses potential risk. The occurrence of OPEs in Xainza showed that more attention should be paid to persistent organic pollutants in high-elevation regions.

3.
Front Immunol ; 12: 764825, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733292

RESUMO

Eosinophils are a minor component of circulating granulocytes, which are classically viewed as end-stage effector cells in host defense against helminth infection and promoting allergic responses. However, a growing body of evidence has emerged showing that eosinophils are versatile leukocytes acting as an orchestrator in the resolution of inflammation. Rheumatoid arthritis (RA) is the most common chronic inflammatory disease characterized by persistent synovitis that hardly resolves spontaneously. Noteworthy, a specific population of eosinophils, that is, regulatory eosinophils (rEos), was identified in the synovium of RA patients, especially in disease remission. Mechanistically, the rEos in the synovium display a unique pro-resolving signature that is distinct from their counterpart in the lung. Herein, we summarize the latest understanding of eosinophils and their emerging role in promoting the resolution of arthritis. This knowledge is crucial to the design of new approaches to rebalancing immune homeostasis in RA, considering that current therapies are centered on inhibiting pro-inflammatory cytokines and mediators rather than fostering the resolution of inflammation.

4.
Proc Natl Acad Sci U S A ; 118(42)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34649996

RESUMO

Infusing CRISPR/donor-loaded adeno-associated viral vectors (AAV/CRISPR) could enable in vivo hepatic gene editing to remedy hemophilia B (HB) with inherited deficiency of clotting factor IX (FIX). Yet, current regimens focus on correcting HB with simple mutations in the coding region of the F9, overlooking those carrying complicated mutations involving the regulatory region. Moreover, a possible adverse effect of treatment-related inflammation remains unaddressed. Here we report that a single DNA cutting-mediated long-range replacement restored the FIX-encoding function of a mutant F9 (mF9) carrying both regulatory and coding defects in a severe mouse HB model, wherein incorporation of a synthetic Alb enhancer/promoter-mimic (P2) ensured FIX elevation to clinically meaningful levels. Through single-cell RNA sequencing (scRNA-seq) of liver tissues, we revealed that a subclinical hepatic inflammation post-AAV/CRISPR administration regulated the vulnerability of the edited mF9-harboring host cells to cytotoxic T lymphocytes (CTLs) and the P2 activity in a hepatocytic subset-dependent manner via modulating specific sets of liver-enriched transcription factors (LETFs). Collectively, our study establishes an AAV/CRISPR-mediated gene-editing protocol applicable to complicated monogenetic disorders, underscoring the potentiality of improving therapeutic benefits through managing inflammation.

5.
Cell Discov ; 7(1): 98, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34697290

RESUMO

The amino acid response (AAR) and unfolded protein response (UPR) pathways converge on eIF2α phosphorylation, which is catalyzed by Gcn2 and Perk, respectively, under different stresses. This close interconnection makes it difficult to specify different functions of AAR and UPR. Here, we generated a zebrafish model in which loss of threonyl-tRNA synthetase (Tars) induces angiogenesis dependent on Tars aminoacylation activity. Comparative transcriptome analysis of the tars-mutant and wild-type embryos with/without Gcn2- or Perk-inhibition reveals that only Gcn2-mediated AAR is activated in the tars-mutants, whereas Perk functions predominantly in normal development. Mechanistic analysis shows that, while a considerable amount of eIF2α is normally phosphorylated by Perk, the loss of Tars causes an accumulation of uncharged tRNAThr, which in turn activates Gcn2, leading to phosphorylation of an extra amount of eIF2α. The partial switchover of kinases for eIF2α largely overwhelms the functions of Perk in normal development. Interestingly, although inhibition of Gcn2 and Perk in this stress condition both can reduce the eIF2α phosphorylation levels, their functional consequences in the regulation of target genes and in the rescue of the angiogenic phenotypes are dramatically different. Indeed, genetic and pharmacological manipulations of these pathways validate that the Gcn2-mediated AAR, but not the Perk-mediated UPR, is required for tars-deficiency induced angiogenesis. Thus, the interconnected AAR and UPR pathways differentially regulate angiogenesis through selective functions and mutual competitions, reflecting the specificity and efficiency of multiple stress response pathways that evolve integrally to enable an organism to sense/respond precisely to various types of stresses.

6.
Diagnostics (Basel) ; 11(10)2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34679622

RESUMO

Chest X-rays (CXR) and computed tomography (CT) are the main medical imaging modalities used against the increased worldwide spread of the 2019 coronavirus disease (COVID-19) epidemic. Machine learning (ML) and artificial intelligence (AI) technology, based on medical imaging fully extracting and utilizing the hidden information in massive medical imaging data, have been used in COVID-19 research of disease diagnosis and classification, treatment decision-making, efficacy evaluation, and prognosis prediction. This review article describes the extensive research of medical image-based ML and AI methods in preventing and controlling COVID-19, and summarizes their characteristics, differences, and significance in terms of application direction, image collection, and algorithm improvement, from the perspective of radiologists. The limitations and challenges faced by these systems and technologies, such as generalization and robustness, are discussed to indicate future research directions.

7.
Blood ; 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34695195

RESUMO

In an effort to identify novel drugs targeting fusion-oncogene induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE) driven AML we uncovered a de-regulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein which is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem- and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO positive leukemic stem cells.

8.
Cancer Commun (Lond) ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34699692

RESUMO

BACKGROUND: Abnormal alternative splicing is frequently associated with carcinogenesis. In B-cell acute lymphoblastic leukemia (B-ALL), double homeobox 4 fused with immunoglobulin heavy chain (DUX4/IGH) can lead to the aberrant production of E-26 transformation-specific family related gene abnormal transcript (ERGalt ) and other splicing variants. However, the molecular mechanism underpinning this process remains elusive. Here, we aimed to know how DUX4/IGH triggers abnormal splicing in leukemia. METHODS: The differential intron retention analysis was conducted to identify novel DUX4/IGH-driven splicing in B-ALL patients. X-ray crystallography, small angle X-ray scattering (SAXS), and analytical ultracentrifugation were used to investigate how DUX4/IGH recognize double DUX4 responsive element (DRE)-DRE sites. The ERGalt biogenesis and B-cell differentiation assays were performed to characterize the DUX4/IGH crosslinking activity. To check whether recombination-activating gene 1/2 (RAG1/2) was required for DUX4/IGH-driven splicing, the proximity ligation assay, co-immunoprecipitation, mammalian two hybrid characterizations, in vitro RAG1/2 cleavage, and shRNA knock-down assays were performed. RESULTS: We reported previously unrecognized intron retention events in C-type lectin domain family 12, member A abnormal transcript (CLEC12Aalt ) and chromosome 6 open reading frame 89 abnormal transcript (C6orf89alt ), where also harbored repetitive DRE-DRE sites. Supportively, X-ray crystallography and SAXS characterization revealed that DUX4 homeobox domain (HD)1-HD2 might dimerize into a dumbbell-shape trans configuration to crosslink two adjacent DRE sites. Impaired DUX4/IGH-mediated crosslinking abolishes ERGalt , CLEC12Aalt , and C6orf89alt biogenesis, resulting in marked alleviation of its inhibitory effect on B-cell differentiation. Furthermore, we also observed a rare RAG1/2-mediated recombination signal sequence-like DNA edition in DUX4/IGH target genes. Supportively, shRNA knock-down of RAG1/2 in leukemic Reh cells consistently impaired the biogenesis of ERGalt , CLEC12Aalt , and C6orf89alt . CONCLUSIONS: All these results suggest that DUX4/IGH-driven DNA crosslinking is required for RAG1/2 recruitment onto the double tandem DRE-DRE sites, catalyzing V(D)J-like recombination and oncogenic splicing in acute lymphoblastic leukemia.

9.
Carbohydr Polym ; 274: 118672, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34702446

RESUMO

High friction of damaged cartilage requires long-acting lubricated additive, which can also effectively scavenge reactive oxidative species (ROS) produced by mechanically stimulated chondrocytes. In this study, xanthan gum (XG) was grafted by poly (sulfobetaine methacrylate) (PSBMA) (the [XG]/[SBMA] molar ratio is 1:5 or 1:10), forming nanoparticles and then conjugated with collagen II-binding peptide, finally obtaining CBPXGSB1/5 or CBPXGSB1/10. Therein, the CBPXGSB1/5 was chosen as optimal lubricated additive. The results show that hydrated effect of PSBMA side chains endows CBPXGSB1/5 with favorable lubrication property (COF is 0.063). Furthermore, the CBPXGSB1/5 combining lubrication property and specific binding capability together may achieve the long-acting lubrication for injured cartilage in medical field. The CBPXGSB1/5 also possesses antioxidation verified by DPPH assay and exhibits synergistically enhanced ROS (OH, O2- and H2O2) scavenging. Besides, cytotoxicity experiment demonstrates that CBPXGSB1/5 has good biocompatibility. Therefore, multifunctional CBPXGSB1/5 developed here may have promising application potential in osteoarthritis treatment.

10.
Bull Environ Contam Toxicol ; 107(6): 1149-1154, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34562128

RESUMO

Cadmium contamination of agricultural soils threatens food safety. The bioaccumulation (BAF) of Cd in potato tubers ranged from 0.69 to 1.50 and 0.39 to 0.82 in acidic yellow and alkaline calcareous soils, respectively, when 0.3 to 4.8 mg Cd kg-1 was added to the soil. The order of Cd concentration for different organs was root > stem > leaf > tuber. The BAF of Cd decreased with the increase of soil Cd concentration. The effect of pH was important for the transfer and accumulation of Cd for potato. Soil Cd concentration was correlated with the plant Cd concentration and soil pH. Cultivars Hui-2 and Xuanshu 2 accumulated less Cd in six potato cultivars. Logarithmic transformation of the data increased the R2 value from 0.725 to 0.941 in the prediction model of soil Cd concentration. The data are useful in assessing the ecological risk of Cd to potato in Karst area.


Assuntos
Poluentes do Solo , Solanum tuberosum , Agricultura , Cádmio/análise , Solo , Poluentes do Solo/análise
11.
Antibiotics (Basel) ; 10(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34572628

RESUMO

Dental fluorosis (DF) is an endemic disease caused by excessive fluoride exposure during childhood. Previous studies mainly focused on the acid resistance of fluorotic enamel and failed to reach a consensus on the topic of the caries susceptibility of DF patients. In this review, we discuss the role of DF classification in assessing this susceptibility and follow the "four factors theory" in weighing the pros and cons of DF classification in terms of host factor (dental enamel and saliva), food factor, bacteria factor, and DF treatment factor. From our analysis, we find that susceptibility is possibly determined by various factors such as the extent of structural and chemical changes in fluorotic enamel, eating habits, fluoride levels in diets and in the oral cavity, changes in quantity and quality of saliva, and/or oral hygiene. Thus, a universal conclusion regarding caries susceptibility might not exist, instead depending on each individual's situation.

12.
Huan Jing Ke Xue ; 42(10): 4789-4797, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34581121

RESUMO

Peroxymonosulfate(PMS)-based advanced oxidation processes were widely used for the degradation of organic pollutants. Electron-rich azo dye Acid Orange 7(AO7) was selected as the target organic matter in this work. The differences, influencing factors, efficiency, and mechanisms of a PMS/Co2+ homogeneous system in the degradation of organic pollutants with two different buffers of boric acid(Lewis acid) and phosphoric acid(Bronstede acid) were investigated. The k value of AO7 degradation in the PMS/Co2+ homogeneous system with phosphate buffer was greater than that with borate buffer, but the degradation percentage during the first 10 seconds of the reaction was lower in the former case. These differences were affected by buffer concentration, the PMS and Co2+ dosages, and pH. In the phosphate buffer, ·OH or SO4-· contributed to organic degradation in the PMS/Co2+ system, while in the borate buffer, the nonradical pathway(1O2) made a critical contribution to the removal of organics. This study provides a reference for the application of different types of buffers in the homogeneous catalysis of PMS.


Assuntos
Boratos , Poluentes Ambientais , Catálise , Oxirredução , Peróxidos , Fosfatos
13.
J Am Chem Soc ; 143(38): 15616-15623, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34469132

RESUMO

Synthesis and implementation of highly active, stable, and affordable electrocatalysts for the oxygen evolution reaction (OER) is a major challenge in developing energy efficient and economically viable energy conversion devices such as electrolyzers, rechargeable metal-air batteries, and regenerative fuel cells. The current benchmark electrocatalyst for OER is based on iridium oxide (IrOx) due to its superior performance and excellent stability. However, large scale applications using IrOx are impractical due to its low abundance and high cost. Herein, we report a highly active hafnium-modified iridium oxide (IrHfxOy) electrocatalyst for OER. The IrHfxOy electrocatalyst demonstrated ten times higher activity in alkaline conditions (pH = 11) and four times higher activity in acid conditions (pH = 1) than a IrOx electrocatalyst. The highest intrinsic mass activity of the IrHfxOy catalyst in acid conditions was calculated as 6950 A gIrOx-1 at an overpotential (η) of 0.3 V. Combined studies utilizing operando surface enhanced Raman spectroscopy (SERS) and DFT calculations revealed that the active sites for OER are the Ir-O species for both IrOx and IrHfxOy catalysts. The presence of Hf sites leads to more negative charge states on nearby O sites, shortening of the bond lengths of Ir-O, and lowers free energies for OER intermediates that accelerate the OER process.

14.
Biosensors (Basel) ; 11(9)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34562934

RESUMO

Cancer is still a major disease that threatens human life. Although traditional cancer treatment methods are widely used, they still have many disadvantages. Aptamers, owing to their small size, low toxicity, good specificity, and excellent biocompatibility, have been widely applied in biomedical areas. Therefore, the combination of nanomaterials with aptamers offers a new method for cancer treatment. First, we briefly introduce the situation of cancer treatment and aptamers. Then, we discuss the application of aptamers in breast cancer treatment, lung cancer treatment, and other cancer treatment methods. Finally, perspectives on challenges and future applications of aptamers in cancer therapy are discussed.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Nanoestruturas , Técnica de Seleção de Aptâmeros
15.
Technol Cancer Res Treat ; 20: 15330338211038492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34520294

RESUMO

Background: Cancer cells have properties similar to those of stem cells, including high proliferation and self-renewal ability. NANOG is the key regulatory gene that maintains the self-renewal and pluripotency characteristics of embryonic stem cells. We previously reported that knockdown of the pluripotent stem cell factor NANOG obviously reduced the proliferation and drug-resistance capabilities of esophageal squamous cell carcinoma (ESCC). In this study, we gained insights into the potential regulatory mechanism of NANOG, particularly in ESCC. Methods: NANOG was ectopically expressed in the Eca-109 cell line via pcDNA3.1 vector transfection. The mRNA expression of different genes was detected using quantitative real-time polymerase chain reaction, and protein quantification was performed by western blotting. The enzyme-linked immunosorbent assay was used to detect the expression of interleukin 6 (IL-6). The capabilities of proliferation, migration, and invasion were investigated using cell count and Transwell assays. The tumor sphere-forming assay was used to investigate the sphere formation capacity of cancer stem cells. Results: The expression of NANOG promoted the cell proliferation and sphere formation capacity of cancer stem cells in a dose-dependent manner. IL-6-mediated activation of signal transducer and activator of transcription 3 (STAT3) was closely related to the expression of NANOG in ESCC. Consistently, the target genes of STAT3, including CCL5, VEGFA, CCND1, and Bcl-xL, were upregulated upon the overexpression of NANOG. Conclusion: These results revealed that the expression of NANOG promotes cell proliferation, invasion, and stemness via IL-6/STAT3 signaling in ESCC.

16.
PLoS Genet ; 17(8): e1009693, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34351909

RESUMO

The ubiquitin-proteasome system plays important roles in various biological processes as it degrades the majority of cellular proteins. Adequate proteasomal degradation of crucial transcription regulators ensures the proper development of neutrophils. The ubiquitin E3 ligase of Growth factor independent 1 (GFI1), a key transcription repressor governing terminal granulopoiesis, remains obscure. Here we report that the deficiency of the ring finger protein Interferon regulatory factor 2 binding protein 2a (Irf2bp2a) leads to an impairment of neutrophils differentiation in zebrafish. Mechanistically, Irf2bp2a functions as a ubiquitin E3 ligase targeting Gfi1aa for proteasomal degradation. Moreover, irf2bp2a gene is repressed by Gfi1aa, thus forming a negative feedback loop between Irf2bp2a and Gfi1aa during neutrophils maturation. Different levels of GFI1 may turn it into a tumor suppressor or an oncogene in malignant myelopoiesis. Therefore, discovery of certain drug targets GFI1 for proteasomal degradation by IRF2BP2 might be an effective anti-cancer strategy.


Assuntos
Proteínas de Ligação a DNA/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/crescimento & desenvolvimento , Animais , Proteínas de Ligação a DNA/metabolismo , Retroalimentação Fisiológica , Feminino , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Células HEK293 , Células HL-60 , Humanos , Leucopoese , Masculino , Proteólise , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética
17.
Ear Nose Throat J ; : 1455613211036771, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34379550

RESUMO

BACKGROUND: Laryngocarcinoma (LC) is a common malignant tumor of the head and neck, accounting for 1% to 5% of human tumors. The primary objective of the present study was to evaluate the survival time of patients with LC at different sites. METHODS: Information concerning patients with LC was extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2016. RESULTS: In total, 16 255 patients with LC were selected from the SEER database. Among all patients, 80.2% were male; males also predominated in each tumor site subgroup. Most of the patients were aged between 60 and 69 years, had white ethnicity, were single, and had American Joint Committee on Cancer (AJCC) stage I cancer with T1, N0, and M0. The present study investigated the role of interventions in all LCs at different AJCC stages. Across the whole population, regardless of the intervention used, survival increased in patients at any cancer site. CONCLUSIONS: The study found that male sex, age ≥80 years, black ethnicity, single status, T4, N4, M1, and AJCC stage IV were associated with higher mortality rates at all sites of LC. Aggressive interventions, especially surgery and radiotherapy, may improve survival in patients with LC at different sites and with different AJCC stages.

18.
J Biomed Nanotechnol ; 17(7): 1364-1370, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446139

RESUMO

Researchers have conducted in-depth research on DNA methylation mechanism, which is related to various diseases such as deficiency of imprinted gene and occurrence of tumors. This study provides a novel rapid quantitative detection assay and real-time fluorescence recombinase-aided amplification assay (RAA) for DNA methylation. Firstly, specific sequence of methylation genes was chosen and primers and fluorogenic probe for RAA experiment were designed and synthesized. Lastly, these amplification products were proven by sequencing and analysis. Results showed that the amplification efficiency and template concentration of RAA had linear dependent (R² > 95%) when the concentration range was 4.64×108 copies/µL˜4.64×104 copies/µL. The test assay can also detect positive samples when the template concentration is below 4.64×104 copies/µL. Remarkably, the entire experiment process only takes 15-20 minutes, so it is beneficial for rapid bedside simple screening of some special DNA methylation sites, such as detection of resistance genes. In a word, this method has very great potential for diseases with DNA methylation in clinical settings, especially if methylation analysis needs to be done quickly and easily.


Assuntos
Metilação de DNA , Recombinases , Primers do DNA , Técnicas de Amplificação de Ácido Nucleico , Recombinases/genética , Recombinases/metabolismo , Sensibilidade e Especificidade
19.
J Immunol Res ; 2021: 1891519, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34423050

RESUMO

The presence of anti-citrullinated protein antibodies (ACPAs) in the serum is one of the immunological features of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide (CCP) assay has been widely used in clinic for the diagnosis of RA. However, up to 40% of RA patients are anti-CCP negative and the diagnostic sensitivity in this population needs to be improved for better clinical management. In this study, peptides with Multiple Citrulline Similar Motif (MCSM) were synthesized and a new ELISA system, which we called RA_CP, was developed to detect citrullinated antigens with MCSM present in the serum. 106 RA,48 other arthritis patients and 41 sex- and age-matched healthy controls (HCs) were included in this study. Patients with RA have a significantly higher amount of citrullinated antigens with MCSM than other arthritis patients and HCs. RA patients with positive anti-CCP are also MCSM positive, whereas 75% anti-CCP negative patients are positive for MCSM. The diagnostic sensitivity for anti-CCP and MCSM was 81.1% and 95.3%, while the specificity was 100% and 94.4%, respectively. ROC curve analyses showed that the area under the curve (AUC) values were 0.906 (95% CI: 0.860-0.951) for anti-CCP and 0.948 (95% CI: 0.912-0.985) for MCSM while the combination of MCSM and anti-CCP test has the highest AUC (0.971, 95% CI: 0.946-0.996). Our results suggest that detection of citrullinated antigens with MCSM has improved sensitivity compared with anti-CCP assay and could serve as a biomarker in diagnosis of RA patients.

20.
Int J Gen Med ; 14: 4711-4721, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456583

RESUMO

Purpose: We sought to explore the prognostic value of blood urea nitrogen (BUN) to serum albumin ratio (BAR) and further develop a prediction model for critical illness in COVID-19 patients. Patients and Methods: This was a retrospective, multicenter, observational study on adult hospitalized COVID-19 patients from three provinces in China between January 14 and March 9, 2020. Primary outcome was critical illness, including admission to the intensive care unit (ICU), need for invasive mechanical ventilation (IMV), or death. Clinical data were collected within 24 hours after admission to hospitals. The predictive performance of BAR was tested by multivariate logistic regression analysis and receiver operating characteristic (ROC) curve and then a nomogram was developed. Results: A total of 1370 patients with COVID-19 were included and 113 (8.2%) patients eventually developed critical illness in the study. Baseline age (OR: 1.031, 95% CI: 1.014, 1.049), respiratory rate (OR: 1.063, 95% CI: 1.009, 1.120), unconsciousness (OR: 40.078, 95% CI: 5.992, 268.061), lymphocyte counts (OR: 0.352, 95% CI: 0.204, 0.607), total bilirubin (OR: 1.030, 95% CI: 1.001, 1.060) and BAR (OR: 1.319, 95% CI: 1.183, 1.471) were independent risk factors for critical illness. The predictive AUC of BAR was 0.821 (95% CI: 0.784, 0.858; P<0.01) and the optimal cut-off value of BAR was 3.7887 mg/g (sensitivity: 0.690, specificity: 0.786; positive predictive value: 0.225, negative predictive value: 0.966; positive likelihood ratio: 3.226, negative likelihood ratio: 0.394). The C index of nomogram including above six predictors was 0.9031125 (95% CI: 0.8720542, 0.9341708). Conclusion: Elevated BAR at admission is an independent risk factor for critical illness of COVID-19. The novel predictive nomogram including BAR has superior predictive performance.

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