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2.
Clin Transl Med ; 12(5): e821, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35522918

RESUMO

BACKGROUND: During pregnancy, mother-child interactions trigger a variety of subtle changes in the maternal body, which may be reflected in the status of peripheral blood mononuclear cells (PBMCs). Although these cells are easy to access and monitor, a PBMC atlas for pregnant women has not yet been constructed. METHODS: We applied single-cell RNA sequencing (scRNA-seq) to profile 198,356 PBMCs derived from 136 pregnant women (gestation weeks 6 to 40) and a control cohort. We also used scRNA-seq data to establish a transcriptomic clock and thereby predicted the gestational age of normal pregnancy. RESULTS: We identified reconfiguration of the peripheral immune cell phenotype during pregnancy, including interferon-stimulated gene upregulation, activation of RNA splicing-related pathways and immune activity of cell subpopulations. We also developed a cell-type-specific model to predict gestational age of normal pregnancy. CONCLUSIONS: We constructed a single-cell atlas of PBMCs in pregnant women spanning the entire gestation period, which should help improve our understanding of PBMC composition turnover in pregnant women.


Assuntos
Leucócitos Mononucleares , Gestantes , Feminino , Idade Gestacional , Humanos , Imunofenotipagem , Leucócitos Mononucleares/metabolismo , Gravidez , Transcriptoma
3.
Nucleic Acids Res ; 50(D1): D934-D942, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34634807

RESUMO

Viral infectious diseases are a devastating and continuing threat to human and animal health. Receptor binding is the key step for viral entry into host cells. Therefore, recognizing viral receptors is fundamental for understanding the potential tissue tropism or host range of these pathogens. The rapid advancement of single-cell RNA sequencing (scRNA-seq) technology has paved the way for studying the expression of viral receptors in different tissues of animal species at single-cell resolution, resulting in huge scRNA-seq datasets. However, effectively integrating or sharing these datasets among the research community is challenging, especially for laboratory scientists. In this study, we manually curated up-to-date datasets generated in animal scRNA-seq studies, analyzed them using a unified processing pipeline, and comprehensively annotated 107 viral receptors in 142 viruses and obtained accurate expression signatures in 2 100 962 cells from 47 animal species. Thus, the VThunter database provides a user-friendly interface for the research community to explore the expression signatures of viral receptors. VThunter offers an informative and convenient resource for scientists to better understand the interactions between viral receptors and animal viruses and to assess viral pathogenesis and transmission in species. Database URL: https://db.cngb.org/VThunter/.


Assuntos
Bases de Dados Factuais , Genoma Viral , Interações Hospedeiro-Patógeno/genética , Receptores Virais/genética , Software , Viroses/genética , Vírus/genética , Animais , Sítios de Ligação , Conjuntos de Dados como Assunto , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Internet , Anotação de Sequência Molecular , Ligação Proteica , Receptores Virais/classificação , Receptores Virais/metabolismo , Transdução de Sinais , Análise de Célula Única , Viroses/metabolismo , Viroses/transmissão , Viroses/virologia , Vírus/classificação , Vírus/metabolismo , Vírus/patogenicidade
4.
Sci Total Environ ; 796: 148927, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34271385

RESUMO

This study aimed to investigate the biotransformation of ZnO nanoparticles (NPs) in maize grown in hydroponics for ecotoxicity assessment. Maize seedlings grown for 14 days were exposed to a solution of 9 nm ZnO NPs, 40 nm ZnO NPs, and ZnSO4 at a Zn concentration of 300 mg L-1 for 1, 3, and 7 days, respectively. The results of in-situ Zn distribution in maize (Zea mays) showed that 9 nm ZnO NPs could quickly enter the roots of maize and reach the center column transport system of the stem. The results of transmission electron microscopy combined with energy dispersive X-ray spectroscopy revealed that ZnO NPs were accumulated in the vacuoles of the roots, and then transformed and transported through vesicles. Simulated studies showed that low pH (5.6) played a critical role in the transformation of ZnO NPs, and organic acids (Kf = 1011.4) could promote particle dissolution. Visual MINTEQ software simulated the species of Zn after the entry of ZnO NPs or Zn2+ into plants and found that the species of Zn was mainly Zn2+ when the Zn content of plants reached 200-300 ppm. Considering that the lowest Zn content of the roots in treatments was 1920 mg kg-1, combination of the result analysis of root effects showed that the toxicity of roots in most treatments had a direct relationship with Zn2+. However, treatment with 9 nm ZnO NPs exhibited significantly higher toxicity than ZnSO4 treatment on day 1 when the Zn2+ concentration difference was not significant, which was mainly due to the large amount of ZnO NPs deposited in the roots. To the authors' knowledge, this study was the first to confirm the process of biotransformation and explore the factors affecting the toxicity of ZnO NPs in depth.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Biotransformação , Nanopartículas Metálicas/toxicidade , Nanopartículas/toxicidade , Raízes de Plantas , Zea mays , Óxido de Zinco/toxicidade
5.
Food Funct ; 12(11): 4960-4971, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34100482

RESUMO

The composition and structure of gut microbiota plays an important role in obesity induced by a high-fat diet (HFD) and related metabolic syndrome (MetS). Previous studies have shown that galacto-oligosaccharides (GOSs) have an effective anti-obesity effect. In this study, we aimed to investigate the effect of enzymatically synthesized α-galacto-oligosaccharides (ES-α-GOSs) on MetS and gut microbiota dysbiosis in HFD-fed mice, and to further investigate whether the attenuation of MetS is associated with the modulation of gut microbiota. Our results indicated that ES-α-GOS could notably ameliorate obesity-related MetS, including hyperlipidemia, insulin resistance and mild inflammation. The subsequent analysis of gut microbiota further showed that ES-α-GOS supplements can significantly modulate the overall composition of the gut microbiota and reverse the gut microbiota disorder caused by HFD feeding. Moreover, Spearman correlation analysis showed that 40 key bacteria reversed by ES-α-GOS were highly associated with metabolic parameters. These results suggested that ES-α-GOSs could serve as a potential candidate for preventing obesity-induced MetS in association with the modulation of gut microbiota.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Síndrome Metabólica/microbiologia , Oligossacarídeos/farmacologia , Tecido Adiposo/patologia , Animais , Aspergillus niger/metabolismo , Bactérias , Glicemia , Suplementos Nutricionais , Disbiose , Dislipidemias , Galactosidases/metabolismo , Hiperlipidemias , Inflamação , Resistência à Insulina , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo
6.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34074049

RESUMO

The vegetative phase transition is a prerequisite for flowering in angiosperm plants. Mulberry miR156 has been confirmed to be a crucial factor in the vegetative phase transition in Arabidopsis thaliana. The over-expression of miR156 in transgenic Populus × canadensis dramatically prolongs the juvenile phase. Here, we find that the expression of mno-miR156 decreases with age in all tissues in mulberry, which led us to study the hierarchical action of miR156 in mulberry. Utilizing degradome sequencing and dual-luciferase reporter assays, nine MnSPLs were shown to be directly regulated by miR156. The results of yeast one-hybrid and dual-luciferase reporter assays also revealed that six MnSPLs could recognize the promoter sequences of mno-miR172 and activate its expression. Our results demonstrate that mno-miR156 performs its role by repressing MnSPL/mno-miR172 pathway expression in mulberry. This work uncovered a miR156/SPLs/miR172 regulation pathway in the development of mulberry and fills a gap in our knowledge about the molecular mechanism of vegetative phase transition in perennial woody plants.


Assuntos
Envelhecimento/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , MicroRNAs/metabolismo , Morus/metabolismo , Proteínas de Plantas/metabolismo , Envelhecimento/genética , Arabidopsis/genética , Biologia Computacional , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica de Plantas/genética , Hydrastis/genética , Hydrastis/metabolismo , MicroRNAs/genética , Morus/genética , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Populus/genética , Populus/metabolismo , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para Cima
7.
Front Plant Sci ; 12: 658590, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33889168

RESUMO

Ciboria carunculoides is the dominant causal agent of mulberry sclerotial disease, and it is a necrotrophic fungal pathogen with a narrow host range that causes devastating diseases in mulberry fruit. However, little is known about the interaction between C. carunculoides and mulberry. Here, our transcriptome sequencing results showed that the transcription of genes in the secondary metabolism and defense-related hormone pathways were significantly altered in infected mulberry fruit. Due to the antimicrobial properties of proanthocyanidins (PAs), the activation of PA biosynthetic pathways contributes to defense against pathogens. Salicylic acid (SA) and jasmonic acid (JA) are major plant defense hormones. However, SA signaling and JA signaling are antagonistic to each other. Our results showed that SA signaling was activated, while JA signaling was inhibited, in mulberry fruit infected with C. carunculoides. Yet SA mediated responses are double-edged sword against necrotrophic pathogens, as SA not only activates systemic acquired resistance (SAR) but also suppresses JA signaling. We also show here that the small secreted protein CcSSP1 of C. carunculoides activates SA signaling by targeting pathogenesis-related protein 1 (PR1). These findings reveal that the infection strategy of C. carunculoides functions by regulating SA signaling to inhibit host defense responses.

8.
Food Funct ; 11(11): 9947-9959, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33108433

RESUMO

In this study, the two enzymatic low molecular weight chitosan oligosaccharides (LMW-COSs), LMW-COS-H and LMW-COS-L, were prepared with average MWs of 879.6 Da and 360.9 Da, respectively. Compared to LMW-COS-L, the LMW-COS-H was more effective in improving high-fat diet (HFD)-induced metabolic abnormalities, such as obesity, hyperlipidemia, low-grade inflammation and insulin resistance. The subsequent analysis of gut microbiota showed that the supplement of LMW-COSs caused overall structural and genus/species-specific changes in the gut microbiota, which were significantly correlated with the metabolic parameters. Specifically, both of the LMW-COSs significantly decreased the relative abundance of inflammatory bacteria such as Erysipelatoclostridium and Alistipes, whereas that of the beneficial intestinal bacteria (such as Akkermansia and Gammaproteobacteria) increased significantly. This study suggested that there were potential prebiotic functions of LMW-COSs in HFD fed mice, which regulated the dysfunctional gut microbiota, alleviated low-grade inflammation and maintained the intestinal epithelial barrier.


Assuntos
Quitosana/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/prevenção & controle , Oligossacarídeos/administração & dosagem , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Quitosana/química , Dieta Hiperlipídica , Humanos , Resistência à Insulina , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peso Molecular , Obesidade/etiologia , Obesidade/microbiologia , Oligossacarídeos/química
9.
Drug Discov Ther ; 14(4): 197-203, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32863323

RESUMO

MicroRNAs (miRNAs) play a vital role in many biological processes, including cell growth, differentiation, apoptosis, development, differentiation, and carcinogenesis. Since miRNAs might play a part in cancer initiation and progression, they comprise an original class of promising diagnostic and prognostic molecular markers. In order to systematically understand the regulation of miRNA expression in cancers, the current study analyzed the miRNA expression profile in NCI-60 human cancer cell lines. Over 300 miRNAs exhibited unique expression profiles in cell lines derived from the same lineage. This study identified 9 lineage-specific miRNA expression patterns. Moreover, results indicated that miR-720 and miR-887 are expressed at relatively high levels in breast cancer cell lines compared to other types of cancer. Ultimately, matching NCI-60 drug response data to miR-720 and miR-887 expression profiles revealed that several FDA-approved drugs were inversely related to miR-720 and miR-887. Furthermore, the anti-cancer effect of perifosine was significantly enhanced by inhibiting miR-720 and decreased by miR-720 precursor treatment in breast cancer cell lines. 5-Fu treatment was enhanced by inhibiting miR-887 and decreased by miR-887 precursor treatment. The current results offer insight into the relationship between miRNA expression and their lineage types, and the approach used here represents a potential cancer therapy with the help of miRNAs.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , MicroRNAs/genética , Regulação para Cima , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Bases de Dados Genéticas , Feminino , Fluoruracila/farmacologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia , Análise de Sobrevida , Regulação para Cima/efeitos dos fármacos
10.
J Agric Food Chem ; 68(18): 5068-5075, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32255620

RESUMO

Zinc (Zn) deficiency is an important problem worldwide, adversely impacting human health. Using a field trial in China, we compared the foliar application of both ZnO nanoparticles (ZnO-NPs) and ZnSO4 on winter wheat (Triticum aestivum L.) for increasing the Zn concentration within the grain. We also used synchrotron-based X-ray fluorescence microscopy and laser ablation inductively coupled plasma mass spectrometry to examine the distribution of Zn within the grain. We found that ZnO-NPs increase the Zn concentration in the wheat grain, increasing from 18 mg·kg-1 in the control up to 40 mg·kg-1 when the ZnO-NPs were applied four times. These grain Zn concentrations in the ZnO-NP-treated grains are similar to those recommended for human consumption. However, the ZnO-NPs were similar in their effectiveness to ZnSO4. When examining trace element distribution in the grain, the trace elements were found to accumulate primarily in the aleurone layer and the crease region across all treatments. Importantly, Zn concentrations in the grain endosperm increased by nearly 30-fold relative to the control, with markedly increasing Zn concentrations within the edible portion. These results demonstrate that ZnO-NPs are a suitable fertilizer for increasing Zn within wheat grain and can potentially be used to improve human nutrition.


Assuntos
Fertilizantes/análise , Nanopartículas/química , Triticum/metabolismo , Óxido de Zinco/análise , Óxido de Zinco/metabolismo , Transporte Biológico , Terapia a Laser , Oligoelementos/análise , Oligoelementos/metabolismo , Triticum/química , Triticum/crescimento & desenvolvimento , Zinco/metabolismo
11.
Biosci Biotechnol Biochem ; 84(7): 1460-1466, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32195627

RESUMO

Chitooligosaccharides (COS) are derived from chitosan, which can be used as nutraceuticals and functional foods. Because of their various biological activities, COS are widely used in the food, medicine, agriculture, and other fields. COS were prepared by chitosanase  from Pseudoalteromonas sp. SY39 and their anti-obesity activity was researched in mice in this study. The effects of hydrolysis time, temperature, the ratio of enzyme to chitosan, and pH on the productivity of COS were discussed. Preparation process of COS was established in a 5-L fermenter. COS were characterized and their anti-obesity activity was studied in animal experiments. The results showed that COS could effectively reduce serum lipid levels and obesity in mice, and have a good anti-obesity activity. The preparation technology and remarkable anti-obesity activity of COS further expand their applications in the food and pharmaceutical industries.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/síntese química , Quitina/análogos & derivados , Quitosana/química , Glicosídeo Hidrolases/química , Obesidade/tratamento farmacológico , Pseudoalteromonas/enzimologia , Animais , Fármacos Antiobesidade/farmacologia , Quitina/administração & dosagem , Quitina/síntese química , Quitina/farmacologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Ácidos Graxos não Esterificados/sangue , Concentração de Íons de Hidrogênio , Hidrólise , Masculino , Camundongos , Obesidade/sangue , Obesidade/etiologia , Oligossacarídeos , Temperatura , Triglicerídeos/sangue
12.
Front Microbiol ; 11: 603927, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33519746

RESUMO

Scleromitrula shiraiana is a necrotrophic fungus with a narrow host range, and is one of the main causal pathogens of mulberry sclerotial disease. However, its molecular mechanisms and pathogenesis are unclear. Here, we report a 39.0 Mb high-quality genome sequence for S. shiraiana strain SX-001. The S. shiraiana genome contains 11,327 protein-coding genes. The number of genes and genome size of S. shiraiana are similar to most other Ascomycetes. The cross-similarities and differences of S. shiraiana with the closely related Sclerotinia sclerotiorum and Botrytis cinerea indicated that S. shiraiana differentiated earlier from their common ancestor. A comparative genomic analysis showed that S. shiraiana has fewer genes encoding cell wall-degrading enzymes (CWDEs) and effector proteins than that of S. sclerotiorum and B. cinerea, as well as many other Ascomycetes. This is probably a key factor in the weaker aggressiveness of S. shiraiana to other plants. S. shiraiana has many species-specific genes encoding secondary metabolism core enzymes. The diversity of secondary metabolites may be related to the adaptation of these pathogens to specific ecological niches. However, melanin and oxalic acid are conserved metabolites among many Sclerotiniaceae fungi, and may be essential for survival and infection. Our results provide insights into the narrow host range of S. shiraiana and its adaptation to mulberries.

13.
J Immunoassay Immunochem ; 39(4): 351-364, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30204067

RESUMO

Modern immunoassay methods and techniques are important tools in labs of basic biology, biomedicine, clinical medicine, and even in home tests, such as pregnant test, many of which utilize antibody-antigen binding mechanism as their foundational principle in common. Meanwhile, compared with polyclonal anitbody, monoclonal antibody shows obvious advantages in their application of modern immunoassays. Furthermore, the progress of other technologies have also promoted the development of modern immunoassays robustly, and widely made it extend into more research and industry fields. In this review, we will first look back to the discovery of antibody-antigen binding mechanism, antibody structure, and the development of monoclonal antibody technology. Then, a brief description of different classical immunoassays will be introduced, such as enzyme-linked immunosorbent assay, flow cytometry, Immunoprecipitation, and lateral flow immunoassays, through of which, we hope a brief and clear picture can be displayed in front of readers. ABBREVIATIONS: ELISA: Enzyme-Linked Immunosorbent Assay; WB: western blot; Mab: monoclonal antibody; IP: immunoprecipitation; LFIAs: lateral flow immunoassays.


Assuntos
Anticorpos Monoclonais/imunologia , Imunoensaio , Animais , Anticorpos Monoclonais/química , Reações Antígeno-Anticorpo , Humanos , Imunoensaio/métodos
14.
Plant Cell Rep ; 37(8): 1101-1112, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29846768

RESUMO

KEY MESSAGE: Two LysM-containing proteins, namely, MmLYP1 and MmLYK2, were identified in mulberry. These proteins might be involved in chitin signaling. The LysM1 of MmLYK2 is critical for their interactions. Chitin is a major component of fungal cell walls and acts as an elicitor in plant innate immunity. Lysin motif (LysM)-containing proteins are essential for chitin recognition. However, related studies have been rarely reported in woody plants. In this study, in mulberry, the expression of a LysM-containing protein, MmLYP1, was significantly up-regulated after treatment with chitin and pathogenic fungi. In addition, MmLYP1 has an affinity for insoluble chitin polymers. Thus, MmLYP1 might function in chitin signaling. Since MmLYP1 lacks an intracellular domain, additional protein kinases are required for this signaling. An LysM-containing kinase, MmLYK2, was then identified. Expression of the MmLYK2 did not change significantly after chitin treatment, and the affinity of MmLYK2 for insoluble chitin was not high. The structure of MmLYP1 is similar to that of the chitin elicitor-binding proteins in rice and Arabidopsis. However, MmLYK2 has two LysM motifs, while the chitin elicitor receptor kinase 1 proteins in rice and Arabidopsis have one and three LysM motifs, respectively. The LysM1 of MmLYK2 interacted with all four LysM motifs in MmLYP1 and MmLYK2 in yeast. The chimera lacking the LysM1 of MmLYK2 did not interact with MmLYP1 and MmLYK2 in yeast and Nicotiana benthamiana cells. The LysM1 in MmLYK2 is the key motif in the interaction between MmLYP1 and MmLYK2, which may be involved in chitin signaling.


Assuntos
Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Quitina/metabolismo , Motivos de Aminoácidos/genética , Motivos de Aminoácidos/fisiologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Ligação Proteica , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
15.
Bioresour Technol ; 258: 195-202, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29525594

RESUMO

Effect of bamboo biochar (BC) combined with two bacterial powders (B) on gaseous emission and variety of bacterial community during pig manure (PM) composting was investigated. The results showed that treatments of BC, BC + B1 and BC + B2 can reduce peak gaseous emission by 54%, 80% and 69% for CH4, respectively, while 37%, 45% and 45% for N2O, respectively, and 13%, 19% and 26% for NH3, respectively. The evolution of the bacterial community quantified with 16S rDNA analysis showed that in the thermophile stage, total relative abundance percentage of bacterial phyla of Firmicutes and Proteobacteria reached 97%, 97%, 93% and 96% for CK, BC, BC + B1 and BC + B2, respectively. Effects of BC on the compost bacterial community variation analysis proved bacterial activity in the thermophile stage was controlled by the content of dissolved organic carbon and temperature of the compost mixture, while electrical conductivity and total kjeldahl nitrogen also influenced compost maturity stage.


Assuntos
Carvão Vegetal , Compostagem , Esterco , Animais , Gases , Nitrogênio , Solo , Suínos
16.
J Agric Food Chem ; 66(11): 2572-2579, 2018 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-29091444

RESUMO

The effects of foliar-applied ZnO nanoparticles (ZnO NPs) and ZnSO4 on the winter wheat ( Triticum aestivum L.) grain yield and grain quality were studied under field conditions, with the distribution and speciation of Zn within the grain examined using synchrotron-based X-ray fluorescence microscopy and X-ray absorption spectroscopy. Although neither of the two Zn compounds improved the grain yield or quality, both increased the grain Zn concentration (average increments were 5 and 10 mg/kg for ZnSO4 and ZnO NP treatments, respectively). Across all treatments, this Zn was mainly located within the aleurone layer and crease of the grain, although the application of ZnO NPs also slightly increased Zn within the endosperm. This Zn within the grain was found to be present as Zn phosphate, regardless of the form in which Zn was applied. These results indicate that the foliar application of ZnO NPs appears to be a promising approach for Zn biofortification, as required to improve human health.


Assuntos
Produção Agrícola/métodos , Fertilizantes/análise , Síncrotrons/estatística & dados numéricos , Triticum/crescimento & desenvolvimento , Óxido de Zinco/química , Sulfato de Zinco/química , Produção Agrícola/instrumentação , Nanopartículas/química , Nanopartículas/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Triticum/metabolismo , Óxido de Zinco/metabolismo , Sulfato de Zinco/metabolismo
17.
Proc Natl Acad Sci U S A ; 113(37): E5434-43, 2016 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-27578867

RESUMO

Rapid clearance of adoptively transferred Cd47-null (Cd47(-/-)) cells in congeneic WT mice suggests a critical self-recognition mechanism, in which CD47 is the ubiquitous marker of self, and its interaction with macrophage signal regulatory protein α (SIRPα) triggers inhibitory signaling through SIRPα cytoplasmic immunoreceptor tyrosine-based inhibition motifs and tyrosine phosphatase SHP-1/2. However, instead of displaying self-destruction phenotypes, Cd47(-/-) mice manifest no, or only mild, macrophage phagocytosis toward self-cells except under the nonobese diabetic background. Studying our recently established Sirpα-KO (Sirpα(-/-)) mice, as well as Cd47(-/-) mice, we reveal additional activation and inhibitory mechanisms besides the CD47-SIRPα axis dominantly controlling macrophage behavior. Sirpα(-/-) mice and Cd47(-/-) mice, although being normally healthy, develop severe anemia and splenomegaly under chronic colitis, peritonitis, cytokine treatments, and CFA-/LPS-induced inflammation, owing to splenic macrophages phagocytizing self-red blood cells. Ex vivo phagocytosis assays confirmed general inactivity of macrophages from Sirpα(-/-) or Cd47(-/-) mice toward healthy self-cells, whereas they aggressively attack toward bacteria, zymosan, apoptotic, and immune complex-bound cells; however, treating these macrophages with IL-17, LPS, IL-6, IL-1ß, and TNFα, but not IFNγ, dramatically initiates potent phagocytosis toward self-cells, for which only the Cd47-Sirpα interaction restrains. Even for macrophages from WT mice, phagocytosis toward Cd47(-/-) cells does not occur without phagocytic activation. Mechanistic studies suggest a PKC-Syk-mediated signaling pathway, to which IL-10 conversely inhibits, is required for activating macrophage self-targeting, followed by phagocytosis independent of calreticulin Moreover, we identified spleen red pulp to be one specific tissue that provides stimuli constantly activating macrophage phagocytosis albeit lacking in Cd47(-/-) or Sirpα(-/-) mice.


Assuntos
Antígeno CD47/genética , Inflamação/genética , Interleucina-10/genética , Receptores Imunológicos/genética , Animais , Citocinas/biossíntese , Citocinas/genética , Endocitose/genética , Humanos , Inflamação/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Knockout , Fagocitose/genética , Proteína Quinase C/genética , Transdução de Sinais/genética
18.
J Immunol ; 195(2): 661-71, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-26085683

RESUMO

CD47, a self recognition marker expressed on tissue cells, interacts with immunoreceptor SIRPα expressed on the surface of macrophages to initiate inhibitory signaling that prevents macrophage phagocytosis of healthy host cells. Previous studies suggested that cells may lose surface CD47 during aging or apoptosis to enable phagocytic clearance. In the current study, we demonstrate that the level of cell surface CD47 is not decreased, but the distribution pattern of CD47 is altered, during apoptosis. On nonapoptotic cells, CD47 molecules are clustered in lipid rafts forming punctates on the surface, whereas on apoptotic cells, CD47 molecules are diffused on the cell surface following the disassembly of lipid rafts. We show that clustering of CD47 in lipid rafts provides a high binding avidity for cell surface CD47 to ligate macrophage SIRPα, which also presents as clusters, and elicits SIRPα-mediated inhibitory signaling that prevents phagocytosis. In contrast, dispersed CD47 on the apoptotic cell surface is associated with a significant reduction in the binding avidity to SIRPα and a failure to trigger SIRPα signal transduction. Disruption of plasma membrane lipid rafts with methyl-ß-cyclodextrin diffuses CD47 clusters, leading to a decrease in the cell binding avidity to SIRPα and a concomitant increase in cells being engulfed by macrophages. Taken together, our study reveals that CD47 normally is clustered in lipid rafts on nonapoptotic cells but is diffused in the plasma membrane when apoptosis occurs; this transformation of CD47 greatly reduces the strength of CD47-SIRPα engagement, resulting in the phagocytosis of apoptotic cells.


Assuntos
Antígenos de Diferenciação/imunologia , Apoptose/efeitos da radiação , Antígeno CD47/imunologia , Células Epiteliais/efeitos da radiação , Macrófagos/efeitos da radiação , Receptores Imunológicos/imunologia , Animais , Antígenos de Diferenciação/genética , Apoptose/efeitos dos fármacos , Sítios de Ligação , Antígeno CD47/química , Antígeno CD47/genética , Linhagem Celular Tumoral , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/imunologia , Fibroblastos/efeitos da radiação , Regulação da Expressão Gênica , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/efeitos da radiação , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Microdomínios da Membrana/efeitos dos fármacos , Microdomínios da Membrana/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose/efeitos dos fármacos , Fagocitose/efeitos da radiação , Cultura Primária de Células , Ligação Proteica , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/efeitos da radiação , Receptores Imunológicos/genética , Transdução de Sinais , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/efeitos da radiação , Raios Ultravioleta , beta-Ciclodextrinas/farmacologia
19.
J Pathol ; 237(3): 285-95, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26095930

RESUMO

CD47, a self-recognition marker, plays an important role in both innate and adaptive immune responses. To explore the potential role of CD47 in activation of autoreactive T and B cells and the production of autoantibodies in autoimmune disease, especially systemic lupus erythematosus (SLE), we have generated CD47 knockout Fas(lpr) (CD47(-/-) -Fas(lpr) ) mice and examined histopathological changes in the kidneys, cumulative survival rates, proteinuria, extent of splenomegaly and autoantibodies, serum chemistry and immunological parameters. In comparison with Fas(lpr) mice, CD47(-/-) -Fas(lpr) mice exhibit a prolonged lifespan and delayed autoimmune nephritis, including glomerular cell proliferation, basement membrane thickening, acute tubular atrophy and vacuolization. CD47(-/-) -Fas(lpr) mice have lower levels of proteinuria, associated with reduced deposition of complement C3 and C1q, and IgG but not IgM in the glomeruli, compared to age-matched Fas(lpr) mice. Serum levels of antinuclear antibodies and anti-double-stranded DNA antibodies are significantly lower in CD47(-/-) -Fas(lpr) than in Fas(lpr) mice. CD47(-/-) -Fas(lpr) mice also display less pronounced splenomegaly than Fas(lpr) mice. The mechanistic studies further suggest that CD47 deficiency impairs the antigenic challenge-induced production of IgG but not IgM, and that this effect is associated with reduction of T follicular cells and impairment of germinal centre development in lymphoid tissues. In conclusion, our results demonstrate that CD47 deficiency ameliorates lupus nephritis in Fas(lpr) mice via suppression of IgG autoantibody production.


Assuntos
Anticorpos Antinucleares/biossíntese , Antígeno CD47/metabolismo , Imunoglobulina G/biossíntese , Glomérulos Renais/metabolismo , Nefrite Lúpica/prevenção & controle , Receptor fas/deficiência , Animais , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Antígeno CD47/genética , Antígeno CD47/imunologia , Proliferação de Células , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Modelos Animais de Doenças , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Nefrite Lúpica/genética , Nefrite Lúpica/imunologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteinúria/genética , Proteinúria/imunologia , Proteinúria/metabolismo , Proteinúria/prevenção & controle , Esplenomegalia/genética , Esplenomegalia/imunologia , Esplenomegalia/metabolismo , Esplenomegalia/prevenção & controle , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Fatores de Tempo , Receptor fas/genética , Receptor fas/imunologia
20.
PLoS One ; 9(7): e103599, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25072345

RESUMO

MicroRNAs (miRNAs) secreted by cells into microvesicles (MVs) form a novel class of signal molecules that mediate intercellular communication. However, several fundamental aspects of secreted miRNAs remain unknown, particularly the mechanism that governs the function or fate of exogenous miRNAs in recipient cells. In the present study, we provide evidence indicating that Argonaute 2 (Ago2) plays a role in stabilizing miRNAs and facilitating the packaging of secreted miRNAs into MVs. More importantly, Ago2 in origin cell-secreted MVs (but not in recipient cells) directs the function of secreted miRNAs. First, Ago2 overexpression clearly increased the level of miR-16 in cells transfected with a miR-16 mimic by protecting the miRNAs from degradation in lysosomes. Second, Ago2 overexpression increased the level of miR-16 in cell-secreted MVs, suggesting that Ago2 may facilitate the packaging of secreted miRNAs into MVs. Third, exogenous miR-16 delivered by MVs within the origin cells significantly reduced the Bcl2 protein level in recipient cells, and miR-16 and Bcl2 mRNA were physically associated with exogenous HA-tagged Ago2 (HA-Ago2). Finally, the effect of MV-delivered miR-16 on the production of the Bcl2 protein in recipient cells was not abolished by knocking down Ago2 in the recipient cells.


Assuntos
Proteínas Argonauta/metabolismo , MicroRNAs/metabolismo , Vesículas Transportadoras/metabolismo , Proteínas Argonauta/antagonistas & inibidores , Proteínas Argonauta/genética , Carbocianinas/química , Citometria de Fluxo , Células HEK293 , Células HeLa , Humanos , MicroRNAs/química , Microscopia de Fluorescência , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo
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