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1.
Environ Sci Technol ; 58(20): 8643-8653, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38676641

RESUMO

Antimicrobial nanomaterials frequently induce inflammatory reactions within lung tissues and prompt apoptosis in lung cells, yielding a paradox due to the inherent anti-inflammatory character of apoptosis. This paradox accentuates the elusive nature of the signaling cascade underlying nanoparticle (NP)-induced pulmonary inflammation. In this study, we unveil the pivotal role of nano-microflora interactions, serving as the crucial instigator in the signaling axis of NP-induced lung inflammation. Employing pulmonary microflora-deficient mice, we provide compelling evidence that a representative antimicrobial nanomaterial, silver (Ag) NPs, triggers substantial motility impairment, disrupts quorum sensing, and incites DNA leakage from pulmonary microflora. Subsequently, the liberated DNA molecules recruit caspase-1, precipitating the release of proinflammatory cytokines and activating N-terminal gasdermin D (GSDMD) to initiate pyroptosis in macrophages. This pyroptotic cascade culminates in the emergence of severe pulmonary inflammation. Our exploration establishes a comprehensive mechanistic axis that interlinks the antimicrobial activity of Ag NPs, perturbations in pulmonary microflora, bacterial DNA release, macrophage pyroptosis, and consequent lung inflammation, which helps to gain an in-depth understanding of the toxic effects triggered by environmental NPs.


Assuntos
Pneumonia , Piroptose , Piroptose/efeitos dos fármacos , Camundongos , Animais , Pneumonia/induzido quimicamente , Pneumonia/patologia , Prata/toxicidade , Nanopartículas Metálicas/toxicidade , Macrófagos/efeitos dos fármacos , Inflamação
2.
Angew Chem Int Ed Engl ; 63(39): e202408277, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-38979699

RESUMO

Since the discovery of the first peroxidase nanozyme (Fe3O4), numerous nanomaterials have been reported to exhibit intrinsic enzyme-like activity toward inorganic oxygen species, such as H2O2, oxygen, and O2 -. However, the exploration of nanozymes targeting organic compounds holds transformative potential in the realm of industrial synthesis. This review provides a comprehensive overview of the diverse types of nanozymes that catalyze reactions involving organic substrates and discusses their catalytic mechanisms, structure-activity relationships, and methodological paradigms for discovering new nanozymes. Additionally, we propose a forward-looking perspective on designing nanozyme formulations to mimic subcellular organelles, such as chloroplasts, termed "nano-organelles". Finally, we analyze the challenges encountered in nanozyme synthesis, characterization, nano-organelle construction and applications while suggesting directions to overcome these obstacles and enhance nanozyme research in the future. Through this review, our goal is to inspire further research efforts and catalyze advancements in the field of nanozymes, fostering new insights and opportunities in chemical synthesis.


Assuntos
Nanoestruturas , Nanoestruturas/química , Catálise , Compostos Orgânicos/química , Organelas/metabolismo , Organelas/química
3.
J Am Chem Soc ; 145(5): 3108-3120, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36700857

RESUMO

Nicotinamide adenine dinucleotide (NAD) is a critical regulator of metabolic networks, and declining levels of its oxidized form, NAD+, are closely associated with numerous diseases. While supplementing cells with precursors needed for NAD+ synthesis has shown poor efficacy in combatting NAD+ decline, an alternative strategy is the development of synthetic materials that catalyze the oxidation of NADH into NAD+, thereby taking over the natural role of the NADH oxidase (NOX) present in bacteria. Herein, we discovered that metal-nitrogen-doped graphene (MNGR) materials can catalyze the oxidation of NADH into NAD+. Among MNGR materials with different transition metals, Fe-, Co-, and Cu-NGR displayed strong catalytic activity combined with >80% conversion of NADH into NAD+, similar specificity to NOX for abstracting hydrogen from the pyridine ring of nicotinamide, and higher selectivity than 51 other nanomaterials. The NOX-like activity of FeNGR functioned well in diverse cell lines. As a proof of concept of the in vivo application, we showed that FeNGR could specifically target the liver and remedy the metabolic flux anomaly in obesity mice with NAD+-deficient cells. Overall, our study provides a distinct insight for exploration of drug candidates by design of synthetic materials to mimic the functions of unique enzymes (e.g., NOX) in bacteria.


Assuntos
Grafite , NAD , Camundongos , Animais , NAD/metabolismo , Oxirredução , Mamíferos/metabolismo , Bactérias/metabolismo , Suplementos Nutricionais
4.
Anal Chem ; 95(14): 6009-6019, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37005435

RESUMO

Fine particulates (FPs) are a major class of airborne pollutants. In mammals, FPs may reach the alveoli through the respiratory system, cross the air-blood barrier, spread into other organs, and induce hazardous effects. Although birds have much higher respiratory risks to FPs than mammals, the biological fate of inhaled FPs in birds has rarely been explored. Herein, we attempted to disclose the key properties that dictate the lung penetration of nanoparticles (NPs) by visualizing a library of 27 fluorescent nanoparticles (FNPs) in chicken embryos. The FNP library was prepared by combinational chemistry to tune their compositions, morphologies, sizes, and surface charges. These NPs were injected into the lungs of chicken embryos for dynamic imaging of their distributions by IVIS Spectrum. FNPs with diameters <16 nm could cross the air-blood barrier in 20 min, spread into the blood, and accumulate in the yolk sac. In contrast, large FNPs (>30 nm) were mainly retained in the lungs and rarely detected in other tissues/organs. In addition to size, surface charge was the secondary determinant for NPs to cross the air-blood barrier. Compared to cationic and anionic particles, neutrally charged FNPs showed the fastest lung penetration. A predictive model was therefore developed to rank the lung penetration capability of FNPs by in silico analysis. The in silico predictions could be well validated in chicks by oropharyngeal exposure to six FNPs. Overall, our study discovered the key properties of NPs that are responsible for their lung penetration and established a predictive model that will greatly facilitate respiratory risk assessments of nanoproducts.


Assuntos
Galinhas , Nanopartículas , Embrião de Galinha , Animais , Barreira Alveolocapilar , Nanopartículas/química , Pulmão , Corantes , Tamanho da Partícula , Mamíferos
5.
Exp Appl Acarol ; 91(1): 133-137, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37548825

RESUMO

We present a field-collected Hyalomma anatolicum gynandromorph in Xinjiang, China. Compared to the normal H. anatolicum, the gynandromorphic tick was a typical bipartite protogynander: half of the tick body displayed normal female traits, whereas the other side showed normal male traits. The engorged gynandromorphic tick laid hundreds of eggs, and the eggs looked normal.


Assuntos
Ixodidae , Infestações por Carrapato , Carrapatos , Animais , Feminino , Masculino , China , Fenótipo
6.
Angew Chem Int Ed Engl ; 62(27): e202305485, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37138171

RESUMO

Biofilm formation is a major threat to industry, the environment and human health. While killing of embedded microbes in biofilms may inevitably lead to the evolution of antimicrobial resistance (AMR), catalytic quenching of bacterial communications by lactonase is a promising antifouling approach. Given the shortcomings of protein enzymes, it is attractive to engineer synthetic materials to mimic the activity of lactonase. Herein, an efficient lactonase-like Zn-Nx -C nanomaterial was synthesized by tuning the coordination environment around zinc atoms to mimic the active domain of lactonase for catalytical interception of bacterial communications in biofilm formation. The Zn-Nx -C material could selectively catalyze 77.5 % hydrolysis of N-acylated-L-homoserine lactone (AHL), a critical bacterial quorum sensing (QS) signal in biofilm construction. Consequently, AHL degradation downregulated the expression of QS-related genes in antibiotic resistant bacteria and significantly prevented biofilm formation. As a proof of concept, Zn-Nx -C-coated iron plates prevented 80.3 % biofouling after a month exposure in river. Overall, our study provides a nano-enabled contactless antifouling insight to avoid AMR evolution by engineering nanomaterials for mimicking the key bacterial enzymes (e.g., lactonase) functioning in biofilm construction.


Assuntos
Biofilmes , Percepção de Quorum , Humanos , Bactérias/metabolismo , Acil-Butirolactonas/metabolismo , Proteínas de Bactérias/metabolismo
7.
Angew Chem Int Ed Engl ; 62(17): e202217345, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-36718001

RESUMO

Antimicrobial resistance (AMR) is one of the biggest threats to the environment and health. AMR rapidly invalidates conventional antibiotics, and antimicrobial nanomaterials have been increasingly explored as alternatives. Interestingly, several antimicrobial nanomaterials show AMR-independent antimicrobial effects without detectable new resistance and have therefore been suggested to prevent AMR evolution. In contrast, some are found to trigger the evolution of AMR. Given these seemingly conflicting findings, a timely discussion of the two faces of antimicrobial nanomaterials is urgently needed. This review systematically compares the killing mechanisms and structure-activity relationships of antibiotics and antimicrobial nanomaterials. We then focus on nano-microbe interactions to elucidate the impacts of molecular initiating events on AMR evolution. Finally, we provide an outlook on future antimicrobial nanomaterials and propose design principles for the prevention of AMR evolution.


Assuntos
Antibacterianos , Nanoestruturas , Antibacterianos/farmacologia , Farmacorresistência Bacteriana
8.
Anal Chem ; 94(35): 12060-12069, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36001466

RESUMO

Luminescence detection is a sensitive approach for high-resolution visualization of nano-/macrosized objects, but it is challenging to light invisible insulators owing to their inert surfaces. Herein, we discovered a steric restriction-induced emission (SRIE) effect on nanoscale insulators to light them by fluorogenic probes. The SRIE effect enabled us to specifically differentiate a representative nanoscale insulator, boron nitride (BN) nanosheets, from 18 tested nanomaterials with 420-fold increments of photoluminescence intensity and displayed 3 orders of magnitude linearity for quantitative analysis as well as single-particle level detection. Molecular dynamics simulations indicated that the hydrophobic and electron-resistant surfaces of BN nanosheets restricted intramolecular motions of fluorogenic molecules for blockage of the nonradiative path of excited electrons and activation of the radiative electron transition. Moreover, the lighted BN nanosheets could be successfully visualized in complex cellular and tissue biocontexts. Overall, the SRIE effect will inspire more analytical techniques for inert materials.


Assuntos
Iluminação , Nanoestruturas , Elétrons , Nanoestruturas/química
9.
Int J Syst Evol Microbiol ; 72(11)2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36748686

RESUMO

A novel, Gram-stain-negative, rod-shaped, strictly anaerobic bacterium of genus Proteiniphilum of the phylum Bacteroidota, named strain JNU-WLY501T, was isolated from pit clay used to produce strong aroma-type liquor in PR China. The genomic DNA G+C content and genome size of JNU-WLY501T were 41.4 % and 3.9 Mbp, respectively. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that JNU-WLY501T was closely related to Proteiniphilum acetatigenes DSM 18083T (95.7 %) and Proteiniphilum saccharofermentans M3/6T (94.9 %). The pairwise average nucleotide identity based on blast and average amino acid identity values of JNU-WLY501T compared with Proteiniphilum saccharofermentans M3/6T were 73.6 and 77.3 %, respectively, which both were lower than the threshold values for bacterial species delineation. The strain grew at 20-40 °C, with optimum growth at 37 °C. The pH range for growth was 5.4-9.1, with optimum growth at pH 7.5. The sodium chloride range for growth was 0.0-4.0 %, with optimum growth at 0 %. The strain did not use glucose, maltose, fructose or starch. Yeast extract, tryptone and peptone supported the growth of JNU-WLY501T, and the main fermentation products were acetate and propionate. The predominant cellular fatty acids (>5 %) of JNU-WLY501T were anteiso-C15 : 0 (30.6 %), anteiso-C17 : 0 (26.1 %), C16 : 0 (7.7 %), iso-C16 : 0 (5.0 %) and iso-C17 : 0 (5.0 %). The respiratory quinone of JNU-WLY501T was MK-5. On the basis of the morphological, physiological, biochemical, chemotaxonomic, genotypic and phylogenetic results, JNU-WLY501T represents a novel species of the genus Proteiniphilum, for which the name Proteiniphilum propionicum sp. nov. is proposed. The type strain is JNU-WLY501T (=GDMCC 1.2686T=JCM 34753T).


Assuntos
Bebidas Alcoólicas , Bacteroidetes , Argila , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , Argila/microbiologia , DNA Bacteriano/genética , Ácidos Graxos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Bacteroidetes/classificação , Bacteroidetes/isolamento & purificação
10.
Exp Appl Acarol ; 86(2): 283-298, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35133525

RESUMO

Hyalomma asiaticum and H. anatolicum are tick species in Eurasia and Africa with major medical and veterinary significance. Beside their direct pathogenic effects, H. asiaticum and H. anatolicum are vectors of important diseases of livestock and in some instances of zoonoses. In search of ways to address the increasing incidence of global acaricide resistance, tick control through vaccination is regarded as a sustainable alternative approach. Cathepsin L-like cysteine protease (CPL) is a potent hemoglobinase, and plays important roles in the digestion of blood acquired from a host. CPL from H. anatolicum (HanCPL) with high similarity (> 90%) for H. asiaticum CPL (HasCPL) were aligned by in silico analysis. After further in vitro validation, the anti-HasCPL sera have cross-reactivity between the different total native protein of life stages and tissues for H. asiaticum and H. anatolicum. Furthermore, we further confirmed that recombinant HasCPL (rHasCPL) immunized rabbits were partially cross-protected (54.8%) by H. anatolicum infestation.


Assuntos
Acaricidas , Ixodidae , Infestações por Carrapato , Carrapatos , Animais , Antígenos , Catepsina L , Coelhos , Infestações por Carrapato/veterinária
11.
Part Fibre Toxicol ; 18(1): 17, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902647

RESUMO

BACKGROUND: Disruption of microbiota balance may result in severe diseases in animals and phytotoxicity in plants. While substantial concerns have been raised on engineered nanomaterial (ENM) induced hazard effects (e.g., lung inflammation), exploration of the impacts of ENMs on microbiota balance holds great implications. RESULTS: This study found that rare earth oxide nanoparticles (REOs) among 19 ENMs showed severe toxicity in Gram-negative (G-) bacteria, but negligible effects in Gram-positive (G+) bacteria. This distinct cytotoxicity was disclosed to associate with the different molecular initiating events of REOs in G- and G+ strains. La2O3 as a representative REOs was demonstrated to transform into LaPO4 on G- cell membranes and induce 8.3% dephosphorylation of phospholipids. Molecular dynamics simulations revealed the dephosphorylation induced more than 2-fold increments of phospholipid diffusion constant and an unordered configuration in membranes, eliciting the increments of membrane fluidity and permeability. Notably, the ratios of G-/G+ reduced from 1.56 to 1.10 in bronchoalveolar lavage fluid from the mice with La2O3 exposure. Finally, we demonstrated that both IL-6 and neutrophil cells showed strong correlations with G-/G+ ratios, evidenced by their correlation coefficients with 0.83 and 0.92, respectively. CONCLUSIONS: This study deciphered the distinct toxic mechanisms of La2O3 as a representative REO in G- and G+ bacteria and disclosed that La2O3-induced membrane damages of G- cells cumulated into pulmonary microbiota imbalance exhibiting synergistic pulmonary toxicity. Overall, these findings offered new insights to understand the hazard effects induced by REOs.


Assuntos
Metais Terras Raras , Microbiota , Nanopartículas , Animais , Biotransformação , Camundongos , Óxidos
12.
Mar Drugs ; 19(8)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34436295

RESUMO

The intestinal flora is recognized as a significant contributor to the immune system. In this research, the protective effects of oyster peptides on immune regulation and intestinal microbiota were investigated in mice treated with cyclophosphamide. The results showed that oyster peptides restored the indexes of thymus, spleen and liver, stimulated cytokines secretion and promoted the relative mRNA levels of Th1/Th2 cytokines (IL-2, IFN-γ, IL-4 and IL-10). The mRNA levels of Occludin, Claudin-1, ZO-1, and Mucin-2 were up-regulated, and the NF-κB signaling pathway was also activated after oyster peptides administration. Furthermore, oyster peptides treatment reduced the proportion of Firmicutes/Bacteroidetes, increased the relative abundance of Alistipes, Lactobacillus, Rikenell and the content of short-chain fatty acids, and reversed the composition of intestinal microflora similar to that of normal mice. In conclusion, oyster peptides effectively ameliorated cyclophosphamide-induced intestinal damage and modified gut microbiota structure in mice, and might be utilized as a beneficial ingredient in functional foods for immune regulation.


Assuntos
Gastroenterite/tratamento farmacológico , Fatores Imunológicos/farmacologia , Ostreidae , Peptídeos/farmacologia , Animais , Organismos Aquáticos , Ciclofosfamida , Citocinas/metabolismo , Modelos Animais de Doenças , Gastroenterite/induzido quimicamente , Gastroenterite/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imunomodulação/efeitos dos fármacos , Imunossupressores , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fitoterapia , Organismos Livres de Patógenos Específicos
13.
J Am Chem Soc ; 142(46): 19602-19610, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33108194

RESUMO

NADPH oxidase (NOX) as a transmembrane enzyme complex controls the generation of superoxide that plays important roles in immune signaling pathway. NOX inactivation may elicit immunodeficiency and cause chronic granulomatous disease (CGD). Biocompatible synthetic materials with NOX-like activities would therefore be interesting as curative and/or preventive approaches in case of NOX deficiency. Herein, we synthesized a Fe-N doped graphene (FeNGR) nanomaterial that could mimic the activity of NOX by efficiently catalyzing the conversion of NADPH into NADP+ and triggering the generation of oxygen radicals. The resulting FeNGR nanozyme had similar cellular distribution to NOX and is able to mimic the enzyme function in NOX-deficient cells by catalyzing the generation of superoxide and retrieving the immune activity, evidenced by TNF-α, IL-1ß, and IL-6 production in response to Alum exposure. Overall, our study discovered a synthetic material (FeNGR) to mimic NOX and demonstrated its biological function in immune activation of NOX-deficient cells.


Assuntos
Materiais Biomiméticos/química , Grafite/química , Ferro/química , NADPH Oxidases/química , Nitrogênio/química , Materiais Biomiméticos/metabolismo , Corantes Fluorescentes/química , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Modelos Moleculares , NADP/metabolismo , NADPH Oxidases/metabolismo , Oxirredução , Peroxidase/metabolismo , Espécies Reativas de Oxigênio/química , Transdução de Sinais , Superóxidos/química , Superóxidos/metabolismo , Células THP-1 , Fator de Necrose Tumoral alfa/metabolismo
14.
Small ; 16(36): e1907663, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32406193

RESUMO

It is a big challenge to reveal the intrinsic cause of a nanotoxic effect due to diverse branches of signaling pathways induced by engineered nanomaterials (ENMs). Biotransformation of toxic ENMs involving biochemical reactions between nanoparticles (NPs) and biological systems has recently attracted substantial attention as it is regarded as the upstream signal in nanotoxicology pathways, the molecular initiating event (MIE). Considering that different exposure routes of ENMs may lead to different interfaces for the arising of biotransformation, this work summarizes the nano-bio interfaces and dose calculation in inhalation, dermal, ingestion, and injection exposures to humans. Then, five types of biotransformation are shown, including aggregation and agglomeration, corona formation, decomposition, recrystallization, and redox reactions. Besides, the characterization methods for investigation of biotransformation as well as the safe design of ENMs to improve the sustainable development of nanotechnology are also discussed. Finally, future perspectives on the implications of biotransformation in clinical translation of nanomedicine and commercialization of nanoproducts are provided.


Assuntos
Nanoestruturas , Medição de Risco , Toxicologia , Biotransformação , Humanos , Nanomedicina , Nanopartículas/toxicidade , Nanoestruturas/toxicidade , Nanotecnologia , Segurança , Toxicologia/tendências
15.
BMC Infect Dis ; 20(1): 197, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32138688

RESUMO

BACKGROUND: The incidence rate of measles in China reached a nadir in 2012 after 2 supplementary immunization activities (SIAs) were undertaken in 2009 and 2010. However, the disease began re-emerging in 2013, with a high prevalence rate observed in 2013-2014 in the southern province of Guangdong. In this study, we assessed the changes that occurred in measles epidemiology during 2009-2016, particularly between 2009 and 2011 (when the influence of the SIAs were in full effect) and between 2012 and 2016 (when this influence subsided). METHODS: Data from 22,362 patients with measles diagnosed between 2009 and 2016, and whose diagnoses were confirmed clinically and/or with laboratory testing, were extracted from the National Infectious Disease Monitoring Information System. Descriptive analyses were performed, and changes in epidemiological characteristics between 2009 and 2011 and 2012-2016 were compared. RESULTS: There was a substantial surge in 0-8-month-old patients after 2012; the incidence rate increased from 4.0 per 100,000 population in 2011 (10.3% of the total) to 280 per 100,000 population in 2013 (32.8% of the total). Patients aged 0-6 years represented 73.4% of the total increase between 2011 and 2013. Compared with 2009-2011, adults aged ≥25 years accounted for a higher proportion of patients in 2013 and after (p < 0.01), and were highest in 2016 (31% of the patient total). CONCLUSION: Despite the remarkable results achieved by SIAs in terms of providing herd immunity, the 2013 resurgence of measles revealed insufficient immunization coverage among children. Therefore routine immunization programs should be strengthened, and supplementary vaccinations targeting adults should also be contemplated.


Assuntos
Sarampo/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Imunidade Coletiva , Programas de Imunização/métodos , Programas de Imunização/tendências , Incidência , Lactente , Recém-Nascido , Masculino , Sarampo/imunologia , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Estudos Retrospectivos , Cobertura Vacinal/estatística & dados numéricos , Cobertura Vacinal/tendências , Adulto Jovem
16.
Mediators Inflamm ; 2020: 6914878, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061829

RESUMO

BACKGROUND: COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has threatened every civilian as a global pandemic. The immune system poses the critical interactive chain between the human body and the virus. Here, we make efforts to examine whether comorbidity with type 2 diabetes (T2D) affects the immunological response in COVID-19 patients. METHODS: We conducted a retrospective pilot study investigating immunological characteristics of confirmed cases of COVID-19 with or without comorbid T2D. Two subcohorts of sex- and age-matched participants were eligible for data analysis, of which 33 participants were with T2D and the remaining 37 were nondiabetic (NDM). Cellular immunity was assessed by flow cytometric determination of surface markers including CD3, CD4, CD8, CD19, CD16, and CD56 in peripheral blood. Levels of C reactive protein, immunoglobulin (IgG, IgM, IgA, and IgE), and complements (C3, C4) were detected by rate nephelometry immunoassay. And Th1/Th2 cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were detected by Cytometric Bead Array. RESULTS: Neutrophil counts were found to be significantly higher in the T2D group than in the NDM group and had a significant relevance with clinical severity. Lymphocyte frequencies showed no significant differences in the two groups. However, the proportions and absolute counts of T, Tc, Th, and NK cells decreased in both groups to different degrees. An abnormal increase in neutrophil count and a decrease in lymphocyte subpopulations may represent risk factors of COVID-19 severity. The level of IgG, IgM, IgA, C3, and C4 showed no significant difference between the two groups, while the IgE levels were higher in the T2D group than in the NDM group (p < 0.05). Th1 cytokines including IFN-γ, TNF-α, and IL-6, as well as CRP, appeared significantly higher in the T2D group. CONCLUSIONS: The COVID-19 patients comorbid with T2D demonstrated distinguishable immunological parameters, which represented clinical relevancies with the predisposed disease severity in T2D.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Diabetes Mellitus Tipo 2/imunologia , Pneumonia Viral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , China/epidemiologia , Estudos de Coortes , Comorbidade , Proteínas do Sistema Complemento/metabolismo , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Citocinas/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Imunidade Celular , Imunoglobulinas/sangue , Mediadores da Inflamação/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Projetos Piloto , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Células Th1/imunologia , Células Th2/imunologia
17.
Biochem Genet ; 58(6): 901-913, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32627107

RESUMO

We attempt to explore the role of miR-217 during the process of type 2 diabetes mellitus (T2DM). Mouse ß-TC-tet was dealt with 16.7 mM glucose (HG) to imitate the cells in T2DM. Cell proliferation and apoptosis were determined by cell counting kit-8 and flow cytometry. The correlation between miR-217 and Mafb was predicted with biological software and confirmed by dual lucifierase assay. Western blot was applied to detect protein expression. The data from GEO database exhibited that miR-217 was upregulated in T2DM patients. HG treatment upregulated the expression of miR-217, inhibited the proliferation, and promoted the apoptosis and inflammation of ß-TC-tet cell. Depletion of miR-217 alleviated the damage of ß-TC-tet cell caused by HG. Mafb was affirmed as a target of miR-217 and was negatively modulated by miR-217. Knockdown of Mafb attenuated the alleviation of miR-217 inhibitor on ß-TC-tet cell damage. The expression of key proteins in NF-κB signaling pathway was upregulated by HG, and this upregulation tendency was inhibited by miR-217 inhibitor. Moreover, silencing Mafb could alleviate the inhibition of miR-217 inhibitor on these proteins. Our findings insinuated that inhibition of miR-217 could relieve ß-TC-tet damage induced by HG through regulating Mafb and NF-κB signaling.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Fator de Transcrição MafB/metabolismo , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Animais , Linhagem Celular , Diabetes Mellitus Tipo 2/patologia , Células Secretoras de Insulina/patologia , Camundongos
18.
J Infect Dis ; 220(3): 392-399, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-30891604

RESUMO

BACKGROUND: This study tested the hypothesis that the immunogenicity and safety of the simultaneous administration of enterovirus 71 (EV71) vaccine (dose 1) with recombinant hepatitis B vaccine (HepB) on day 1 and EV71 vaccine (dose 2) with group A meningococcal polysaccharide vaccine (MenA) on day 30 is not inferior to separate administration of each vaccine. METHODS: The study was designed as a randomized, open-label, noninferiority trial. A total of 775 healthy infants aged 6 months were randomly assigned in a ratio of 1:1:1 to receive simultaneous administration of EV71 vaccine (dose 1) and HepB on day 1 and EV71 vaccine (dose 2) and MenA on day 30 (the SI group); administration of doses 1 and 2 of EV71 vaccine on days 1 and 30, respectively (the SE1 group); or administration of HepB and MenA on days 1 and 30, respectively (the SE2 group). RESULTS: According to the per protocol set, antibody responses against EV71, hepatitis B virus (HBV), and group A meningococcal polysaccharide were similar regardless of administration schedule. With the non-inferiority margin setting at 10%, the seroconversion rates of the three pathogens in the SI group (100% [98.25, 100], 44.84% [38.20, 51.63] and 27.83% [21.91, 34.38]) were not inferior to those in SE1 or SE2 group (100% [98.31, 100], 44.35% [37.82, 51.02] and 29.17% [23.20, 35.72], respectively). Frequencies of adverse reactions to each vaccination regimen were comparable (60.62% in the SI group vs 52.33% in the SE1 group and 56.98% in the SE2 group; P = .16). CONCLUSIONS: Simultaneous administration of combined EV71 vaccine with HepB and MenA has noninferior immunogenicity and safety, compared with separate administration of these vaccines. CLINICAL TRIALS REGISTRATION: NCT03274102.


Assuntos
Formação de Anticorpos/imunologia , Vacinas contra Hepatite B/imunologia , Vacinas Meningocócicas/imunologia , Polissacarídeos Bacterianos/imunologia , Vacinas Combinadas/imunologia , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Anticorpos Antivirais/imunologia , Enterovirus/imunologia , Infecções por Enterovirus/imunologia , Feminino , Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Lactente , Masculino , Infecções Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Vacinação/efeitos adversos
19.
Angew Chem Int Ed Engl ; 59(9): 3618-3623, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-31828919

RESUMO

While dehydrogenases play crucial roles in tricarboxylic acid (TCA) cycle of cell metabolism, which are extensively explored for biomedical and chemical engineering uses, it is a big challenge to overcome the shortcomings (low stability and high costs) of recombinant dehydrogenases. Herein, it is shown that two-dimensional (2D) SnSe is capable of mimicking native dehydrogenases to efficiently catalyze hydrogen transfer from 1-(R)-2-(R')-ethanol groups. In contrary to susceptible native dehydrogenases, lactic dehydrogenase (LDH) for instance, SnSe is extremely tolerant to reaction condition changes (pH, temperature, and organic solvents) and displays extraordinary reusable capability. Structure-activity analysis indicates that the single-atom structure, Sn vacancy, and hydrogen binding affinity of SnSe may be responsible for their catalytic activity. Overall, this is the first report of a 2D SnSe nanozyme to mimic key dehydrogenases in cell metabolism.


Assuntos
Materiais Biomiméticos/química , Nanoestruturas/química , Selênio/química , Estanho/química , Materiais Biomiméticos/metabolismo , Catálise , Concentração de Íons de Hidrogênio , Oxirredutases/química , Oxirredutases/metabolismo , Temperatura , Termodinâmica
20.
Angew Chem Int Ed Engl ; 59(50): 22431-22435, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-32794297

RESUMO

The application of NIR-II emitters for gastrointestinal (GI) tract imaging remains challenging due to fluorescence quenching in the digestive microenvironment. Herein, we report that red-shifting of the fluorescence emission of Au nanoclusters (AuNCs) into NIR-II region with improved quantum yields (QY) could be achieved by engineering a protein corona structure consisting of a ribonuclease-A (RNase-A) on the particle surfaces. RNase-A-encapsulated AuNCs (RNase-A@AuNCs) displayed emissions at 1050 nm with a 1.9 % QY. Compared to rare earth and silver-based NIR-II emitters, RNase-A@AuNCs had excellent biocompatibility, showing >50-fold higher sensitivity in GI tract, and migrated homogenously during gastrointestinal peristalsis to allow visualization of the detailed structures of the GI tract. RNase-A@AuNCs could successfully examine intestinal tumor mice from healthy mice, indicating a potential utility for early diagnosis of intestinal tumors.


Assuntos
Trato Gastrointestinal/diagnóstico por imagem , Ouro/química , Neoplasias Intestinais/diagnóstico por imagem , Nanopartículas Metálicas/química , Coroa de Proteína/química , Engenharia de Proteínas , Animais , Raios Infravermelhos , Camundongos , Estrutura Molecular
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