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1.
Nutr Metab Cardiovasc Dis ; 34(1): 55-63, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38036325

RESUMO

BACKGROUND AND AIMS: Limited evidence exists on the prognostic outcomes of the blood urea nitrogen to serum albumin ratio (B/A ratio) in congestive heart failure (CHF), particularly in developing countries with scarce heart failure epidemiological data. We aimed to investigate the association between B/A ratio and short-term outcomes in Chinese patients with CHF. METHODS AND RESULTS: We included 1761 CHF patients with available B/A ratio data from a cohort of 2008 patients. Patients were categorized into three groups based on B/A ratio (low to high). The primary endpoint was death or readmission within 28 days, and the secondary endpoint was death or readmission within 90 days. We employed restricted cubic spline analysis, Cox proportional hazards regression, and Kaplan-Meier curves to evaluate the relationship between B/A ratio at admission and the endpoints. Even after adjusting for other variables, higher B/A ratios were associated with increased rates of 28 days and 90 days mortality or readmission (HR: 2.4, 95% CI: 1.81-3.18 and HR: 1.74, 95% CI: 1.48-2.05). Significant differences in the risks of both primary and secondary endpoints were observed among the three B/A ratio groups. The association between B/A ratio and CHF was stable in the different subgroups (all P for interaction>0.05). CONCLUSION: Higher B/A ratios are associated with an increased risk of short-term mortality or readmission in Chinese patients with CHF. The B/A ratio shows promise as a prognostic indicator for short-term outcomes in CHF patients.


Assuntos
Nitrogênio da Ureia Sanguínea , Albumina Sérica , Albumina Sérica/análise , China , Estudos Retrospectivos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Valor Preditivo dos Testes , Estudos de Coortes , Humanos , Masculino , Feminino , Idoso
2.
Differentiation ; 131: 49-58, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37120964

RESUMO

The beating of motile cilia requires the coordinated action of diverse machineries that include not only the axonemal dynein arms, but also the central apparatus, the radial spokes, and the microtubule inner proteins. These machines exhibit complex radial and proximodistal patterns in mature axonemes, but little is known about the interplay between them during motile ciliogenesis. Here, we describe and quantify the relative rates of axonemal deployment for these diverse cilia beating machineries during the final stages of differentiation of Xenopus epidermal multiciliated cells.


Assuntos
Axonema , Dineínas , Animais , Axonema/metabolismo , Dineínas/metabolismo , Cílios/metabolismo , Vertebrados/metabolismo
3.
Artigo em Inglês | MEDLINE | ID: mdl-38330559

RESUMO

Context: Early intervention and treatment are key measures for tuberculosis (TB) prevention and control, making early, rapid, and accurate diagnostic methods crucial. The Liquid-solid (Biphasic) rapid cultures is a novel tool for the differential diagnosis of tuberculosis. Objective: The study intended to evaluate the value of the biphasic cultures by comparing it to the acid-fast staining and liquid cultures, which have been the traditional gold-standard technology, to determine its value in the diagnosis of TB. Design: The research team conducted an experimental study. Setting: The study took place at the Affiliated Wuxi Fifth Hospital of Jiangnan University in Wuxi, China. Participants: Participants were 221 patients with suspected pulmonary tuberculosis who had been admitted to the hospital between July 2020 and December 2021. Outcome Measures: Using three methods-liquid-solid (biphasic) culture, acid-fast staining, and mycobacterial growth indicator tube (MGIT) 960 liquid culture, the research team tested participants' sputum samples: (1) for sensitivity; (2) for time to positive culture results, and (3) for differential diagnosis. Results: The biphasic culture's sensitivity was significantly higher than that of acid-fast staining, (P = .0003), and no significant difference existed between it and the MGIT 960 liquid cultures. The biphasic cultures's mean time to positivity was significantly shorter than that of the MGIT 960 liquid culture at the intervals 11-20 d (P < .0001) and 21-35 days (P = .0001). Moreover, the biphasic cultures could preliminarily differentiate nontuberculous mycobacteria (NTM) from mycobacterium tuberculosis (MTB), which is a significant advantage in tuberculosis diagnosis. Conclusions: This study highlights the potential of a biphasic culture as a reliable tool for the rapid differential diagnosis of tuberculosis, with a faster detection cycle and a higher sensitivity than conventional methods. The biphasic cultures is a valuable addition to the tuberculosis diagnostic armamentarium and can help improve patients' outcomes by enabling earlier diagnosis and treatments.

4.
BMC Infect Dis ; 23(1): 899, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129788

RESUMO

BACKGROUND: Klebsiella pneumoniae is a pathogen that often infects patients in clinical practice. Due to its high virulent and drug resistance, infected patients are difficult to treat. In clinical practice, Klebsiella pneumoniae can infect patients' intestines, intestines, blood, etc., causing pathological changes. However, there is relatively little information on the impact of Klebsiella pneumoniae on intestinal inflammation and microbial populations. Zebrafish is an excellent biomedical model that has been successfully applied to the virulence assessment of Klebsiella pneumoniae. METHODS: In this study, three clinically isolated representative strains of Klebsiella pneumoniae (high virulence non-resistant, high virulence resistant, and low virulence resistant) were used to infect zebrafish, and their effects on intestinal colonization, inflammation, pathology, and microbial diversity were tested. RESULTS: Enzyme-linked immunoassay (ELISA) showed that Klebsiella pneumoniae significantly increased levels of the cytokines interleukin-1α (Il-1α), interleukin-1ß (Il-1ß), and tumor necrosis factor-α (Tnf-α), which increased inflammatory symptoms. Hematoxylin eosin staining(H&S) showed that Klebsiella pneumoniae treatment caused intestinal lesions in zebrafish, in which KP1053 exposure significantly decreased the number of goblet cells, KP1195 caused epithelial dissolution and exfoliation. In addition, Klebsiella pneumoniae disturbed the composition of intestinal microbiota, and the Shannon index increased, which increased the number of harmful bacteria. CONCLUSIONS: Klebsiella pneumoniae infection can lead to intestinal colonization, inflammation, pathological changes, and changes in microbial biodiversity. This study provides a reference for the intestinal pathology of clinical Klebsiella pneumoniae infection.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Animais , Adulto , Humanos , Virulência , Peixe-Zebra , Inflamação , Intestinos/microbiologia , Infecções por Klebsiella/microbiologia , Antibacterianos , Testes de Sensibilidade Microbiana
5.
Cell Mol Biol (Noisy-le-grand) ; 69(1): 131-136, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-37213145

RESUMO

To analyze the application effect of anti-tuberculosis therapy (ATT) combined with all-in-one nursing care on pulmonary tuberculosis (PT). Seventy-four PT patients who received ATT in our hospital between December 2015 and June 2016 were selected as the research participants and randomized into a research group (RG; n=37) and a control group (CG; n=37) that were given all-in-one nursing care and routine care, respectively. The cure rate and treatment compliance were compared between groups, and the awareness of disease prevention and treatment was investigated. Patients' psychological status and quality of life were evaluated using the Self-Rating Depression/Anxiety Scale (SAS/SDS) and the Quality of Life Questionnaire Core 30 (QLQ-C30), respectively. RG and CG were not statistically different in the clinical cure rate (P>0.05), but the X-ray cure rate was higher and the recurrence rate was lower in RG (P<0.05). In addition, RG showed higher medication compliance rate, regular reexamination rate and awareness of disease prevention and treatment than CG (P<0.05). Reductions in SAS/SDS scores were observed in both groups after care, with even lower levels in RG, while the QLQ-C30 score increased and was higher in RG as compared to CG (P<0.05). Therefore, All-in-one nursing care can effectively enhance the level of treatment compliance and awareness of disease prevention and treatment of PT patients. In the future, when treating PT patients in the clinic, the effectiveness of ATT can be improved by implementing all-in-one nursing care to provide more reliable prognosis for patients.


Assuntos
Tuberculose Pulmonar , Tuberculose , Humanos , Antituberculosos/uso terapêutico , Inflamação , Qualidade de Vida , Tuberculose Pulmonar/tratamento farmacológico
6.
Nanomedicine ; 48: 102640, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36549558

RESUMO

OBJECTIVE: To investigate the efficacy and safety of neutrophil membrane-coated nanoparticles mediated KLA peptides (KLAKLAKKLAKLAK) and gentamicin in the targeted therapy of anti-microbial resistant Klebsiella pneumoniae (K. pneumonia) lung infection. METHODS: The characteristics of KLA-neutrophils nanoparticles (NNPs) are identified via dynamic light scattering (DLS), transmission electron microscope (TEM), SDS-PAGE, Western blot, quantitative flow cytometry (QFCM) and confocal microscopy. The safety of KLA-NNPs both in vitro and in vivo is evaluated by hemolysis test, platelet α granule membrane protein concentration, protein adsorption capacity, in vitro macrophage phagocytosis, weight change, liver function indicators, blood biochemical indicators, and pathological changes of vital organs in mice. The efficacy of KLA-NNPs is determined by time-kill assay, fluorescent label test, intracellular bacterial content, caspase-1 activity, survival rate, and HE staining both in vitro and in vivo. RESULTS: The prepared KLA-NNPs have a typical "core-shell" structure, uniform nanometer size, and retain the membrane proteins on the neutrophil membrane that achieve functional effects. In vitro safety analysis showed that KLA-NNPs have good blood compatibility and can inhibit macrophage phagocytosis in vitro. KLA-NNPs can effectively release KLA and significantly reduce intracellular bacteria and caspase-1 activity. In vivo safety analysis and efficacy analysis revealed that KLA-NNPs have good biocompatibility and could effectively improve the survival rate of mice. CONCLUSION: The prepared KLA-NNPs have good nano-medicine chemical and physical properties and safety. It can evade immune system clearance, achieve high-efficiency targeted aggregation and drug delivery to bacterial infection sites, and effectively inhibit the development of pneumonia induced by drug-resistant K. pneumonia.


Assuntos
Anti-Infecciosos , Nanopartículas , Pneumonia , Camundongos , Animais , Neutrófilos , Pneumonia/patologia , Anti-Infecciosos/uso terapêutico , Anticorpos , Nanopartículas/química , Caspases/uso terapêutico
7.
Int J Med Microbiol ; 312(6): 151561, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36087399

RESUMO

Klebsiella pneumoniae is a gram-negative bacterium that can cause many diseases in hospitals and communities. Intestinal K. pneumoniae infections are relatively rare. Most K. pneumoniae infections begin with the colonization of the gastrointestinal system. In this study, clinically isolated K. pneumoniae strains were used to infect intestinal epithelial Caco-2 cells to study the possible intestinal translocation mechanism of K. pneumoniae. We found that of the three K. pneumoniae strains tested, KP1821 exhibited the strongest adhesive and invasive abilities and that the adhesion to Caco-2 intestinal epithelial cells was affected by the acidic environment of the stomach. Transcriptome sequencing revealed the involvement of molecules associated with the extracellular matrix and cell adhesion, inflammatory response, calcium ion and transforming growth factor ß (TGF-ß) signaling pathways, and other abnormalities in biological processes and cell signaling pathways. Additionally, tolloid-like protein 1 (TLL1) was significantly upregulated. Knocking down TLL1 with shRNA significantly reduced KP1821's ability to invade and adhere to intestinal epithelial cells. TLL1 is involved in the activation of the TGF-ß signaling pathway. Inhibition of this pathway using the inhibitor SB431542 induced significantly reduced adhesion and invasion capabilities of KP1821. Our findings demonstrate that TLL1 participates in K. pneumoniae adhesion and invasion of intestinal epithelial cells by activating the TGF-ß signaling pathway.


Assuntos
Cálcio , Klebsiella pneumoniae , Células CACO-2 , Células Epiteliais/microbiologia , Humanos , Klebsiella pneumoniae/fisiologia , RNA Interferente Pequeno , Transdução de Sinais , Metaloproteases Semelhantes a Toloide , Fator de Crescimento Transformador beta , Fator de Crescimento Transformador beta1
8.
BMC Infect Dis ; 22(1): 630, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35854212

RESUMO

BACKGROUND: Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for sepsis management. As an emerging rapid and sensitive pathogen detection tool, digital droplet PCR (ddPCR) has shown promising potential in rapid identification of pathogens and antimicrobial resistance genes. However, the diagnostic value and clinical impact of ddPCR tests remains to be studied in patients with suspected sepsis. PROGRESS trial is aimed to evaluate the clinical effectiveness of a novel ddPCR assay compared with standard practice. METHODS: PROGRESS is a multicenter, open-label, pragmatic randomized controlled trial (pRCT) set in ten hospitals, including departments of infectious disease and intensive care units. In this study, a total of 2292 patients with suspected sepsis will be randomly assigned to two arms: the ddPCR group and the control group with a ratio of 3:1. The primary outcome is the diagnostic efficacy, that is, the sensitivity and specificity of the ddPCR assay compared with the synchronous blood culture. Secondary outcomes include the mortality rates and the mean Sequential Organ Failure Assessment (SOFA) score at follow-up time points, the length of stay in the hospital, the time to directed antimicrobial therapy, duration of broad-spectrum antibiotic use, and the EQ-5D-5L score on day 90. DISCUSSION: It is the first multicenter pragmatic RCT to explore the diagnostic efficacy and clinical impact of the ddPCR assay in patients with suspected sepsis, taking advantage of both RCT's ability to establish causality and the feasibility of pragmatic approaches in real-world studies (RWS). This trial will help us to get a comprehensive view of the assay's capacity for precise diagnosis and treatment of sepsis. It has the potential to monitor the pathogen load change and to guide the antimicrobial therapy, making a beneficial impact on the prognosis of sepsis patients. TRIAL REGISTRATION: ClinicalTrial.gov, NCT05190861. Registered January 13, 2022-'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT05190861 .


Assuntos
Sepse , Humanos , Estudos Multicêntricos como Assunto , Escores de Disfunção Orgânica , Reação em Cadeia da Polimerase , Ensaios Clínicos Pragmáticos como Assunto , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/diagnóstico , Sepse/tratamento farmacológico , Resultado do Tratamento
9.
Biotechnol Appl Biochem ; 69(5): 2091-2101, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34664729

RESUMO

By studying the expression in patients and cell modeling in vitro, antimicrobial peptides for Klebsiella were screened. Killing curve and membrane permeability experiments are used to study the antibacterial effect of antimicrobial peptides in vitro. Cytotoxicity-related indicators including lipopolysaccharide (LPS), capsule polysaccharide (CPS), and outer membrane protein expression were measured. Intranasal inoculation of pneumoconiosis was used to construct a mouse infection model, and the survival rate and cytokine expression level were tested. Human neutrophil peptide 1 (HNP-1) showed a significant antibacterial effect, which improved the permeability of the outer membrane of K. pneumoniae. Moreover, HNP-1 decreased LPS, CPS content, and outer membrane proteins. K. pneumoniae infection decreased antimicrobial peptide, oxidative stress, and autophagy-related genes, while HNP-1 increased these genes. After coculture with macrophages, the endocytosis of macrophages is enhanced and the bacterial load is greater in the K. pneumoniae + peptide group. Besides, higher levels of pp38 and pp65 in the K. pneumoniae + peptide group. HNP-1 rescued the cytotoxicity induced by K. pneumoniae. The survival rate is significantly improved after K. pneumoniae is treated by HNP-1. All cytokines in the peptide group were significantly higher. HNP-1 promotes immune sterilization by reducing the virulence of multidrug-resistant K. pneumoniae and increasing the ability of macrophages.


Assuntos
Klebsiella pneumoniae , Lipopolissacarídeos , Animais , Humanos , Camundongos , Antibacterianos/metabolismo , Klebsiella pneumoniae/metabolismo , Macrófagos , Esterilização , Virulência , Peptídeos
10.
Nature ; 525(7569): 339-44, 2015 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-26344197

RESUMO

Macromolecular complexes are essential to conserved biological processes, but their prevalence across animals is unclear. By combining extensive biochemical fractionation with quantitative mass spectrometry, here we directly examined the composition of soluble multiprotein complexes among diverse metazoan models. Using an integrative approach, we generated a draft conservation map consisting of more than one million putative high-confidence co-complex interactions for species with fully sequenced genomes that encompasses functional modules present broadly across all extant animals. Clustering reveals a spectrum of conservation, ranging from ancient eukaryotic assemblies that have probably served cellular housekeeping roles for at least one billion years, ancestral complexes that have accrued contemporary components, and rarer metazoan innovations linked to multicellularity. We validated these projections by independent co-fractionation experiments in evolutionarily distant species, affinity purification and functional analyses. The comprehensiveness, centrality and modularity of these reconstructed interactomes reflect their fundamental mechanistic importance and adaptive value to animal cell systems.


Assuntos
Evolução Molecular , Complexos Multiproteicos/química , Complexos Multiproteicos/metabolismo , Mapas de Interação de Proteínas , Animais , Conjuntos de Dados como Assunto , Humanos , Mapeamento de Interação de Proteínas , Reprodutibilidade dos Testes , Biologia de Sistemas , Espectrometria de Massas em Tandem
11.
J Cell Sci ; 131(3)2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29180514

RESUMO

Multiciliated cells (MCCs) drive fluid flow in diverse tubular organs and are essential for the development and homeostasis of the vertebrate central nervous system, airway and reproductive tracts. These cells are characterized by dozens or hundreds of motile cilia that beat in a coordinated and polarized manner. In recent years, genomic studies have not only elucidated the transcriptional hierarchy for MCC specification but also identified myriad new proteins that govern MCC ciliogenesis, cilia beating and cilia polarization. Interestingly, this burst of genomic data has also highlighted that proteins with no obvious role in cilia do, in fact, have important ciliary functions. Understanding the function of proteins with little prior history of study presents a special challenge, especially when faced with large numbers of such proteins. Here, we define the subcellular localization in MCCs of ∼200 proteins not previously implicated in cilia biology. Functional analyses arising from the screen provide novel links between actin cytoskeleton and MCC ciliogenesis.


Assuntos
Cílios/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus laevis/metabolismo , Animais , Axonema/metabolismo , Corpos Basais/metabolismo , Movimento Celular , Polaridade Celular , Doença , Feminino , Humanos , Miosinas/metabolismo , Organogênese , Transporte Proteico
12.
J Cell Sci ; 130(2): 420-428, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-28089989

RESUMO

Homeostatic replacement of epithelial cells from basal precursors is a multistep process involving progenitor cell specification, radial intercalation and, finally, apical surface emergence. Recent data demonstrate that actin-based pushing under the control of the formin protein Fmn1 drives apical emergence in nascent multiciliated epithelial cells (MCCs), but little else is known about this actin network or the control of Fmn1. Here, we explore the role of the small GTPase RhoA in MCC apical emergence. Disruption of RhoA function reduced the rate of apical surface expansion and decreased the final size of the apical domain. Analysis of cell shapes suggests that RhoA alters the balance of forces exerted on the MCC apical surface. Finally, quantitative time-lapse imaging and fluorescence recovery after photobleaching studies argue that RhoA works in concert with Fmn1 to control assembly of the specialized apical actin network in MCCs. These data provide new molecular insights into epithelial apical surface assembly and could also shed light on mechanisms of apical lumen formation.


Assuntos
Actinas/metabolismo , Polaridade Celular , Cílios/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Animais , Membrana Celular/metabolismo , Feminino , Proteínas Fetais/metabolismo , Forminas , Humanos , Proteínas dos Microfilamentos/metabolismo , Modelos Biológicos , Proteínas Nucleares/metabolismo , Xenopus
13.
J Virol ; 91(9)2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28202764

RESUMO

Zinc finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses by binding to viral mRNAs and repressing the translation and/or promoting the degradation of target mRNA. In addition, ZAP regulates the expression of certain cellular genes. Here, we report that tripartite motif-containing protein 25 (TRIM25), a ubiquitin E3 ligase, is required for the antiviral activity of ZAP. Downregulation of endogenous TRIM25 abolished ZAP's antiviral activity. The E3 ligase activity of TRIM25 is required for this regulation. TRIM25 mediated ZAP ubiquitination, but the ubiquitination of ZAP itself did not seem to be required for its antiviral activity. Downregulation of endogenous ubiquitin or overexpression of the deubiquitinase OTUB1 impaired ZAP's activity. We provide evidence indicating that TRIM25 modulates the target RNA binding activity of ZAP. These results uncover a mechanism by which the antiviral activity of ZAP is regulated.IMPORTANCE ZAP is a host antiviral factor that specifically inhibits the replication of certain viruses, including HIV-1, Sindbis virus, and Ebola virus. ZAP binds directly to target mRNA, and it represses the translation and promotes the degradation of target mRNA. While the mechanisms by which ZAP posttranscriptionally inhibits target RNA expression have been extensively studied, how its antiviral activity is regulated is not very clear. Here, we report that TRIM25, a ubiquitin E3 ligase, is required for the antiviral activity of ZAP. Downregulation of endogenous TRIM25 remarkably abolished ZAP's activity. TRIM25 is required for ZAP optimal binding to target mRNA. These results help us to better understand how the antiviral activity of ZAP is regulated.


Assuntos
Antivirais/metabolismo , Proteínas de Ligação a RNA/metabolismo , Sindbis virus/crescimento & desenvolvimento , Fatores de Transcrição/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Replicação Viral/genética , Linhagem Celular , Cisteína Endopeptidases/metabolismo , Enzimas Desubiquitinantes , Células HEK293 , Humanos , Interferência de RNA , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , RNA Viral/genética , Sindbis virus/genética , Ubiquitinação , Dedos de Zinco
14.
Mol Syst Biol ; 13(6): 932, 2017 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-28596423

RESUMO

Macromolecular protein complexes carry out many of the essential functions of cells, and many genetic diseases arise from disrupting the functions of such complexes. Currently, there is great interest in defining the complete set of human protein complexes, but recent published maps lack comprehensive coverage. Here, through the synthesis of over 9,000 published mass spectrometry experiments, we present hu.MAP, the most comprehensive and accurate human protein complex map to date, containing > 4,600 total complexes, > 7,700 proteins, and > 56,000 unique interactions, including thousands of confident protein interactions not identified by the original publications. hu.MAP accurately recapitulates known complexes withheld from the learning procedure, which was optimized with the aid of a new quantitative metric (k-cliques) for comparing sets of sets. The vast majority of complexes in our map are significantly enriched with literature annotations, and the map overall shows improved coverage of many disease-associated proteins, as we describe in detail for ciliopathies. Using hu.MAP, we predicted and experimentally validated candidate ciliopathy disease genes in vivo in a model vertebrate, discovering CCDC138, WDR90, and KIAA1328 to be new cilia basal body/centriolar satellite proteins, and identifying ANKRD55 as a novel member of the intraflagellar transport machinery. By offering significant improvements to the accuracy and coverage of human protein complexes, hu.MAP (http://proteincomplexes.org) serves as a valuable resource for better understanding the core cellular functions of human proteins and helping to determine mechanistic foundations of human disease.


Assuntos
Doenças Genéticas Inatas , Complexos Multiproteicos/genética , Mapeamento de Interação de Proteínas , Proteínas/genética , Humanos , Espectrometria de Massas , Transporte Proteico/genética
15.
Angew Chem Int Ed Engl ; 54(32): 9235-8, 2015 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-26088393

RESUMO

A method for the region-selective deposition of nanoparticles (NPs) by the Huisgen 1,3-dipolar cycloaddition is presented. The approach enables defined stacking of various oxide NPs in any order with control over layer thickness. Thereby the reaction is performed between a substrate, functionalized with a self-assembled monolayer of an azide-bearing phosphonic acid (PA) and aluminum oxide (AlO(x)) NPs functionalized with an alkyne bearing PA. The layer of alkyne functionalized AlO(x) NPs is then used as substrate for the deposition of azide-functionalized indium tin oxide (ITO) NPs to provide a binary stack. This progression is then conducted with alkyne-functionalized CeO2 NPs, yielding a ternary stack of NPs with three different NP cores. The stacks are characterized by AFM and SEM, defining the region-selectivity of the deposition technique. Finally, these assemblies have been tested in devices as a dielectric to form a capacitor resulting in a dramatic increase in the measured capacitance.

17.
bioRxiv ; 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37745461

RESUMO

The need to accurately survey proteins and their modifications with ever higher sensitivities, particularly in clinical settings with limited samples, is spurring development of new single molecule proteomics technologies. Fluorosequencing is one such highly parallelized single molecule peptide sequencing platform, based on determining the sequence positions of select amino acid types within peptides to enable their identification and quantification from a reference database. Here, we describe substantial improvements to fluorosequencing, including identifying fluorophores compatible with the sequencing chemistry, mitigating dye-dye interactions through the use of extended polyproline linkers, and developing an end-to-end workflow for sample preparation and sequencing. We demonstrate by fluorosequencing peptides in mixtures and identifying a target neoantigen from a database of decoy MHC peptides, highlighting the potential of the technology for high sensitivity clinical applications.

18.
Bosn J Basic Med Sci ; 22(3): 453-459, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34491890

RESUMO

The objective of the study was to investigate the levels of plasma exosome-derived fragile site-associated tumor suppressor (FATS) and evaluate its prognostic predictive ability in ovarian cancer (OC) patients. Exosome-rich fractions were isolated from the plasma of 90 patients with OC enrolled in this study. The levels of plasma exosome-derived FATS were detected by ELISA. The levels of exosome-derived FATS in OC patients were significantly lower as compared to the healthy controls (P < 0.001). The levels of plasma exosome-derived FATS were higher in OC patients with low grade (1/2), and Federation International of Gynecology and Obstetrics (FIGO) Stages I/II than those in high grade (3/4) and Stages III/IV of the disease (p = 0.003; p < 0.001), respectively. The levels of plasma exosome-derived FATS were significantly higher in OC patients with no lymph node metastasis or no ascites as compared to those with lymph node metastasis or ascites, respectively (both p < 0.001). The levels of plasma exosome-derived FATS were higher in OC patients having CA-125 below 35 U/ml as compared to those with CA-125 greater than 35 U/ml (p < 0.001). Among all enrolled OC patients, both 5-DFS and 5-OS were shorter in patients with lower plasma exosome-derived FATS levels than those with higher levels (both p < 0.001). The area under the receiver operating characteristic curve of plasma exosome-derived FATS was 0.85 (95% CI: 0.76-0.91) for 5-DFS and 0.91 (95% CI: 0.83-0.96) for 5-OS prediction in patients with OC. Plasma exosome-derived FATS levels in OC patients were significantly downregulated. Low levels of plasma exosome-derived FATS had a significant relationship with FIGO Stages III/IV, high grade, ascites, higher levels of CA-125, lymph node metastasis, and prognosis of OC patients. Thus, our findings may provide insights for the development of a new strategy OC treatment.


Assuntos
Exossomos , Neoplasias Ovarianas , Ascite , Exossomos/patologia , Feminino , Humanos , Metástase Linfática , Neoplasias Ovarianas/diagnóstico , Prognóstico
19.
Front Microbiol ; 13: 901979, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783411

RESUMO

Sepsis is a systemic inflammatory response syndrome caused by infection, with high incidence and mortality. Therefore, it is necessary to carry out an effective anti-infection treatment. In this work, we designed and synthesized red blood cell (RBC) membrane-coated PLGA nanoparticles named γ3-RBCNPs, which target the highly expressed intercellular adhesion molecule-1 (ICAM-1) at the site of infection through the γ3 peptide on its surface and kill the Klebsiella pneumoniae through ciprofloxacin encapsulated in its core. In addition, the homogenous RBC membrane coated on the surface of the nanoparticles helps them avoid immune surveillance and prolong the circulation time of the drug in the body. We found that the γ3-RBCNPs target human umbilical vein endothelial cells (HUVECs) activated by TNF-α in vitro and the infected lung of mice in the sepsis model very well. In vitro evaluation suggested that γ3-RBCNPs have a low risk of acute hemolysis and are less likely to be engulfed by macrophages. In vivo evaluation showed that γ3-RBCNPs has a long half-life and good bio-safety. More importantly, we confirmed that γ3-RBCNPs have the good antibacterial and anti-infection ability in vivo and in vitro. Our research provides a new strategy for the nano-drug treatment of Klebsiella pneumoniae-induced sepsis.

20.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 2): m269-70, 2011 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-21522919

RESUMO

In the title coordinaltion polymer, [Cd(C(8)H(4)O(4))(C(8)H(7)N(3))(2)](n), the Cd(II) atom, lying on a twofold rotation axis, is six-coordinated by two carboxyl-ate O atoms from two benzene-1,3-dicarboxyl-ate (m-BDC) ligands and four N atoms from two chelating 2-(2-pyrid-yl)imidazole mol-ecules, forming a slightly distorted octa-hedral geometry. The m-BDC ligand is located over a twofold rotation axis. The Cd(II) atoms are bridged by the m-BDC ligands, leading to a wave-shaped chain structure along [010]. N-H⋯O hydrogen bonds connect the chains.

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