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1.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806904

RESUMO

This study was conducted to compare the effects of commercially available (C) and green synthesized (GS) Zinc oxide nanoparticles (ZnO-NPs) on immunological responses of common carp (Cyprinus carpio) skin mucus. GS ZnO-NPs were generated using Thymus pubescent and characterized by UV-vis diffuse reflectance spectroscopy (DRS), Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX). Fish (n = 150) were randomly allocated into five groups in triplicate and received a waterborne concentration of 0% (control), 25%, and 50% of LC50 96 h of commercially available (C1 and C2) and green synthesized ZnO-NPs (GS1 and GS2) for 21 days. Results from XRD displayed ZnO-NPs with 58 nm in size and UV-vis DRS, EDX, and FT-IR analysis showed that some functional groups from plant extract bonded to the surface of NPs. The SEM images showed that ZnO-NPs have conical morphology. Acute toxicity study showed a higher dose of LC5096h for green synthesized ZnO-NPs (78.9 mg.L-1) compared to the commercial source (59.95 mg.L-1). The highest activity of lysozyme and alternative complement activity (ACH50) were found in control and GS1 groups. A significant decrease in alkaline phosphatase activity (ALP) was found in C1 and C2 groups compared to other treatments. Protease activity (P) was significantly decreased in the C2 group compared to the control and GS groups. Total immunoglobulin (total Ig) content was the highest in the control. In addition, total Ig in the GS1 group was higher than GS2. The exposure to ZnO-NPs lowered total protein content in all experimental groups when compared to control. Present findings revealed lower induced immunosuppressive effects by green synthesized ZnO-NPs on key parameters of fish skin mucus.


Assuntos
Carpas/fisiologia , Fatores Imunológicos/síntese química , Fatores Imunológicos/farmacologia , Nanopartículas Metálicas/química , Muco/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Óxido de Zinco/química , Animais , Técnicas de Química Sintética , Química Verde , Nanopartículas Metálicas/ultraestrutura , Análise Espectral
2.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540792

RESUMO

The skin barrier consists of mucus, primarily comprising highly glycosylated mucins, and the epithelium. Host mucin glycosylation governs interactions with pathogens and stress is associated with impaired epithelial barrier function. We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress. Fish held at low (LD: 14-30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment. Blood parameters indicated primary and secondary stress responses at both sampling points. At the second sampling, skin barrier function towards molecules was reduced in the HD compared to the LD group (Papp mannitol; p < 0.01). Liquid chromatography-mass spectrometry revealed 81 O-glycan structures from the skin. Fish subjected to both chronic and acute stress had an increased proportion of large O-glycan structures. Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress. Stress thus impairs skin barrier function and induces glycosylation changes, which have potential to both affect interactions with pathogens and serve as stress indicators.


Assuntos
Aglomeração , Mucinas/metabolismo , Muco/química , Ácido N-Acetilneuramínico/metabolismo , Polissacarídeos/metabolismo , Salmo salar/metabolismo , Absorção Cutânea/fisiologia , Pele/metabolismo , Estresse Fisiológico/fisiologia , Estresse Psicológico/metabolismo , Animais , Biomarcadores , Cromatografia Líquida , Aglomeração/psicologia , Glicosilação , Hidrocortisona/sangue , Manitol/farmacocinética , Espectrometria de Massas , Mucinas/isolamento & purificação , Muco/metabolismo , Ácido N-Acetilneuramínico/isolamento & purificação , Oxigênio/análise , Polissacarídeos/isolamento & purificação , Processamento de Proteína Pós-Traducional , Salmo salar/sangue , Pele/ultraestrutura , Temperatura , Qualidade da Água
3.
Med Sci Monit ; 27: e928837, 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33580949

RESUMO

BACKGROUND Coronavirus 2 (SARS-CoV-2) was declared a pandemic by the World Health Organization (WHO) in March 2020. To further reveal the pathologic associations between coronavirus and hypoxemia, we report the findings of 4 complete systematic autopsies of severe acute respiratory syndrome coronavirus 2-positive individuals who died of multiple organ failure caused by severe hypoxemia. MATERIAL AND METHODS We examined the donated corpses of 4 deceased patients who had been diagnosed with severe acute respiratory syndrome coronavirus 2. A complete post-mortem examination was carried out on each corpse, and multiple organs were macroscopically examined. RESULTS The 4 corpses were 2 males and 2 females, with an average age of 69 years. Bilateral lungs showed various degrees of atrophy and consolidation, with diffusely tough and solid texture in the sections. A thromboembolism was found in the main pulmonary artery extending into the atrium in 1 corpse, and significant atherosclerotic plaques tagged in the inner wall of the aortic arch were found in 2 corpses. Two corpses were found to have slightly atrophied bilateral renal parenchyma. Atrophic changes in the spleen were found in 2 corpses. Notably, there were significantly expanded alveolar septa and prominent fibroblastic proliferation. CONCLUSIONS The laboratory data of these corpses showed a progressive decrease in blood oxygen saturation, followed by refractory and irreversible hypoxemia. Clinical and laboratory information and autopsy and histologic presentations of multiple organs showed insufficient air exchange due to abnormalities in the respiratory system, and reduced erythropoiesis in bone marrow may play a role.


Assuntos
Autopsia , /virologia , Hipóxia/complicações , Hipóxia/patologia , Pneumonia/patologia , Pneumonia/virologia , /fisiologia , Idoso , Idoso de 80 Anos ou mais , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Agregação Celular , Feminino , Humanos , Pulmão/patologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Muco/metabolismo , Miocárdio/patologia , Necrose , Pneumonia/complicações , Cavidade Torácica/patologia
4.
Int J Mol Sci ; 22(2)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445609

RESUMO

Most currently available bioreactors have some defects in the expression, activity, or purification of target protein and peptide molecules, whereas the mucus gland of fish can overcome these defects to become a novel bioreactor for the biopharmaceutical industry. In this study, we have evaluated the practicability of developing a mucus gland bioreactor in loach (Paramisgurnus dabryanus). A transgenic construct pT2-krt8-IFN1 was obtained by subcloning the promoter of zebrafish keratin 8 gene and the type I interferon (IFN1) cDNA of grass carp into the SB transposon. The IFN1 expressed in CIK cells exhibited an antiviral activity against the replication of GCRV873 and activated two genes downstream of JAK-STAT signaling pathway. A transgenic loach line was then generated by microinjection of the pT2-krt8-IFN1 plasmids and in vitro synthesized capped SB11 mRNA. Southern blots indicated that a single copy of IFN1 gene was stably integrated into the genome of transgenic loach. The expression of grass carp IFN1 in transgenic loaches was detected with RT-PCR and Western blots. About 0.0825 µg of grass carp IFN1 was detected in 20 µL mucus from transgenic loaches. At a viral titer of 1 × 103 PFU/mL, plaque numbers on plates containing mucus from transgenic loaches reduced by 18% in comparison with those of the control, indicating that mucus of IFN1-transgenic loaches exhibited an antiviral activity. Thus, we have successfully created a mucus gland bioreactor that has great potential for the production of various proteins and peptides.


Assuntos
Reatores Biológicos , Cipriniformes/fisiologia , Glândulas Exócrinas/metabolismo , Muco/metabolismo , Animais , Animais Geneticamente Modificados , Expressão Gênica , Ordem dos Genes , Vetores Genéticos/genética , Interferons/metabolismo , Mutagênese Insercional
5.
Nat Commun ; 12(1): 249, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431872

RESUMO

Airway mucus is essential for lung defense, but excessive mucus in asthma obstructs airflow, leading to severe and potentially fatal outcomes. Current asthma treatments have minimal effects on mucus, and the lack of therapeutic options stems from a poor understanding of mucus function and dysfunction at a molecular level and in vivo. Biophysical properties of mucus are controlled by mucin glycoproteins that polymerize covalently via disulfide bonds. Once secreted, mucin glycopolymers can aggregate, form plugs, and block airflow. Here we show that reducing mucin disulfide bonds disrupts mucus in human asthmatics and reverses pathological effects of mucus hypersecretion in a mouse allergic asthma model. In mice, inhaled mucolytic treatment loosens mucus mesh, enhances mucociliary clearance, and abolishes airway hyperreactivity (AHR) to the bronchoprovocative agent methacholine. AHR reversal is directly related to reduced mucus plugging. These findings establish grounds for developing treatments to inhibit effects of mucus hypersecretion in asthma.


Assuntos
Dissulfetos/metabolismo , Hipersensibilidade/fisiopatologia , Pulmão/fisiopatologia , Muco/metabolismo , Adolescente , Adulto , Animais , Asma/metabolismo , Asma/fisiopatologia , Modelos Animais de Doenças , Expectorantes/farmacologia , Feminino , Glicoproteínas/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade
6.
BMC Infect Dis ; 21(1): 67, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441105

RESUMO

BACKGROUND: Recently, many cases of pneumonia in children with Mycoplasma pneumoniae infection have been shown to have varying degrees of intrabronchial mucus plug formation. The clinical, laboratory, radiological characteristics, and treatment of patients with Mycoplasma infection are analyzed in this study. The risk factors for M. pneumoniae pneumonia (MPP) mucus plug formation in children are explored, and a risk factor scoring system is established. METHODS: MPP patients treated with bronchoscopy were retrospectively enrolled in the study from February 2015 to December 2019. The children were divided into a mucus plug group and a control group according to the presence or absence of mucus plug formation. The clinical, laboratory, radiological characteristics, and treatment of the two groups of children were compared. Univariate and multivariate logistic regression models were used to identify the risk factors for MPP mucus plug formation. The receiver operating characteristic (ROC) curve was drawn to evaluate the regression model and establish the MPP mucous plug risk factor scoring system. RESULTS: A univariate analysis showed that the children in the mucous group were older and had a longer fever duration, longer hospital stay, higher fever peak, more cases of wheezing symptoms and allergies, and azithromycin or corticosteroids were administered later. In addition, neutrophil, C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer (DD), sputum MP-DNA copy number, and total immunoglobulin A (IgA) levels were higher, while prealbumin (PA) levels were lower. The ROC curve analysis showed that children with MPP had PA ≤144.5 mg/L, had used corticosteroids during the course of the illness of ≥4.5 days, CRP ≥12.27 mg/L, an LDH ≥ 462.65 U/L, and there was a possibility of intra-airway mucus formation. The independent risk factors were scored according to their odds ratio (OR) value. Among the 255 children with MPP, the high-risk group had 44 (83.02%) mucus plugs out of 53; the middle-risk group had 35 (34.3%) mucus plugs out of 102; and the low-risk group had 11 (11%) mucus plugs out of 100. CONCLUSIONS: PA levels, timing of corticosteroid use (use in the first few days), CRP levels, and LDH levels were independent risk factors for MPP mucus plug formation. This provides a basis for the early identification of MPP in children combined with mucus plug formation.


Assuntos
Brônquios/fisiopatologia , Broncoscopia/métodos , Muco/metabolismo , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/imunologia , Pneumonia por Mycoplasma/fisiopatologia , Pneumonia por Mycoplasma/cirurgia , Corticosteroides/uso terapêutico , Proteína C-Reativa/análise , Criança , Pré-Escolar , Feminino , Febre , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Lactente , L-Lactato Desidrogenase/sangue , Tempo de Internação , Modelos Logísticos , Masculino , Neutrófilos/metabolismo , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/tratamento farmacológico , Pré-Albumina/análise , Curva ROC , Estudos Retrospectivos , Fatores de Risco
7.
Artigo em Inglês | MEDLINE | ID: mdl-32750662

RESUMO

Cystic fibrosis (CF) is a recessively inherited fatal disease that is the subject of extensive research and ongoing development of therapeutics targeting the defective protein, cystic fibrosis transmembrane conductance regulator (CFTR). Despite progress, the link between CFTR and clinical symptoms is incomplete. The severe CF phenotypes are associated with a deficiency of linoleic acid, which is the precursor of arachidonic acid. The release of arachidonic acid from membranes via phospholipase A2 is the rate-limiting step for eicosanoid synthesis and is increased in CF, which contributes to the observed inflammation. A potential deficiency of docosahexaenoic acid may lead to decreased levels of specialized pro-resolving mediators. This pathophysiology may contribute to an early and sterile inflammation, mucus production, and to bacterial colonization, which further increases inflammation and potentiates the clinical symptoms. Advances in lipid technology will assist in elucidating the role of lipid metabolism in CF, and stimulate therapeutic modulations of inflammation.


Assuntos
Ácido Araquidônico/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/metabolismo , Ácidos Docosa-Hexaenoicos/deficiência , Ácido Linoleico/deficiência , Ácido Araquidônico/deficiência , Fibrose Cística/fisiopatologia , Humanos , Inflamação/metabolismo , Ácido Linoleico/metabolismo , Metabolismo dos Lipídeos , Pulmão/metabolismo , Pulmão/microbiologia , Pulmão/fisiopatologia , Muco/metabolismo
8.
Am J Physiol Lung Cell Mol Physiol ; 319(4): L603-L619, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32783615

RESUMO

Respiratory cilia are the driving force of the mucociliary escalator, working in conjunction with secreted airway mucus to clear inhaled debris and pathogens from the conducting airways. Respiratory cilia are also one of the first contact points between host and inhaled pathogens. Impaired ciliary function is a common pathological feature in patients with chronic airway diseases, increasing susceptibility to respiratory infections. Common respiratory pathogens, including viruses, bacteria, and fungi, have been shown to target cilia and/or ciliated airway epithelial cells, resulting in a disruption of mucociliary clearance that may facilitate host infection. Despite being an integral component of airway innate immunity, the role of respiratory cilia and their clinical significance during airway infections are still poorly understood. This review examines the expression, structure, and function of respiratory cilia during pathogenic infection of the airways. This review also discusses specific known points of interaction of bacteria, fungi, and viruses with respiratory cilia function. The emerging biological functions of motile cilia relating to intracellular signaling and their potential immunoregulatory roles during infection will also be discussed.


Assuntos
Bactérias/imunologia , Cílios/metabolismo , Fungos/imunologia , Depuração Mucociliar/fisiologia , Vírus/imunologia , Células Epiteliais/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/imunologia , Muco/metabolismo , Sistema Respiratório/imunologia
9.
J Vis Exp ; (161)2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32804169

RESUMO

Mucociliary epithelium provides the first line of defense by removing foreign particles through the action of mucus production and cilia-mediated clearance. Many clinically relevant defects in the mucociliary epithelium are inferred as they occur deep within the body. Here, we introduce a tractable 3D model for mucociliary epithelium generated from multipotent progenitors that were microsurgically isolated from Xenopus laevis embryos. The mucociliary epithelial organoids are covered with newly generated epithelium from deep ectoderm cells and later decorated with distinct patterned multiciliated cells, secretory cells, and mucus-producing goblet cells that are indistinguishable from the native epidermis within 24 h. The full sequences of dynamic cell transitions from mesenchymal to epithelial that emerge on the apical surface of organoids can be tracked by high-resolution live imaging. These in vitro cultured, self-organizing mucociliary epithelial organoids offer distinct advantages in studying the biology of mucociliary epithelium with high-efficiency in generation, defined culture conditions, control over number and size, and direct access for live imaging during the regeneration of the differentiated epithelium.


Assuntos
Técnicas de Cultura de Células/métodos , Cílios/metabolismo , Embrião não Mamífero/citologia , Células Epiteliais/citologia , Imageamento Tridimensional , Muco/metabolismo , Organoides/diagnóstico por imagem , Xenopus laevis/embriologia , Animais , Ectoderma/citologia , Células Epiteliais/metabolismo , Microcirurgia , Fixação de Tecidos
10.
Proc Natl Acad Sci U S A ; 117(35): 21519-21526, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32817517

RESUMO

The intestinal epithelium is a highly dynamic structure that rejuvenates in response to acute stressors and can undergo alterations in cellular composition as animals age. The microbiota, acting via secreted factors related to indole, appear to regulate the sensitivity of the epithelium to stressors and promote epithelial repair via IL-22 and type I IFN signaling. As animals age, the cellular composition of the intestinal epithelium changes, resulting in a decreased proportion of goblet cells in the colon. We show that colonization of young or geriatric mice with bacteria that secrete indoles and various derivatives or administration of the indole derivative indole-3 aldehyde increases proliferation of epithelial cells and promotes goblet cell differentiation, reversing an effect of aging. To induce goblet cell differentiation, indole acts via the xenobiotic aryl hydrocarbon receptor to increase expression of the cytokine IL-10. However, the effects of indoles on goblet cells do not depend on type I IFN or on IL-22 signaling, pathways responsible for protection against acute stressors. Thus, indoles derived from the commensal microbiota regulate intestinal homeostasis, especially during aging, via mechanisms distinct from those used during responses to acute stressors. Indoles may have utility as an intervention to limit the decline of barrier integrity and the resulting systemic inflammation that occurs with aging.


Assuntos
Células Caliciformes/efeitos dos fármacos , Células Caliciformes/microbiologia , Indóis/farmacologia , Interleucina-10/metabolismo , Microbiota/fisiologia , Receptores de Hidrocarboneto Arílico/metabolismo , Envelhecimento/metabolismo , Animais , Bactérias/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Feminino , Células Caliciformes/citologia , Células Caliciformes/metabolismo , Interleucina-10/biossíntese , Interleucinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Muco/metabolismo , Transdução de Sinais
11.
Int J Nanomedicine ; 15: 4877-4898, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753869

RESUMO

Background: Although dynamics and uses of modified nanoparticles (NPs) as orally administered macromolecular drugs have been researched for many years, measures of molecule stability and aspects related to important transport-related mechanisms which have been assessed in vivo remain as relatively under characterized. Thus, our aim was to develop a novel type of oral-based delivery system for insulin and to overcome barriers to studying the stability, transport mechanisms, and efficacy in vivo of the delivery system. Methods: NPs we developed and tested were composed of insulin (INS), dicyandiamide-modified chitosan (DCDA-CS), cell-penetrating octaarginine (r8), and hydrophilic hyaluronic acid (HA) and were physically constructed by electrostatic self-assembly techniques. Results: Compared to free-insulin, levels of HA-DCDA-CS-r8-INS NPs were retained at more desirable measures of biological activity in our study. Further, our assessments of the mechanisms for NPs suggested that there were high measures of cellular uptake that mainly achieved through active transport via lipid rafts and the macropinocytosis pathway. Furthermore, investigations of NPs indicated their involvement in caveolae-mediated transport and in the DCDA-CS-mediated paracellular pathway, which contributed to increasing the efficiency of sequential transportation from the apical to basolateral areas. Accordingly, high efficiency of absorption of NPs in situ for intestinal loop models was realized. Consequently, there was a strong induction of a hypoglycemic effect in diabetic rats of NPs via orally based administrations when compared with measures related to free insulin. Conclusion: Overall, the dynamics underlying and influenced by HA-DCDA-CS-r8-INS may hold great promise for stability of insulin and could help overcome interference by the epithelial barrier, and thus showing a great potential to improve the efficacy of orally related treatments.


Assuntos
Quitosana/química , Ácido Hialurônico/química , Insulina/administração & dosagem , Nanopartículas Multifuncionais/química , Nanopartículas/química , Administração Oral , Animais , Transporte Biológico/efeitos dos fármacos , Células CACO-2 , Morte Celular/efeitos dos fármacos , Quitosana/síntese química , Diabetes Mellitus Experimental/tratamento farmacológico , Impedância Elétrica , Endocitose/efeitos dos fármacos , Guanidinas/síntese química , Guanidinas/química , Humanos , Ácido Hialurônico/síntese química , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Insulina/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Masculino , Muco/metabolismo , Nanopartículas/ultraestrutura , Ratos , Solubilidade , Suínos
12.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(2): 97-100, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32743998

RESUMO

Objective: To investigate the therapeutic effects of Radix Angelicae Sinensis (RADA) on airway mucus hypersecretion and the tumor necrosis factor-α/ nuclear factor- κB (TNF-α/NF-κB) signaling pathway in Yin-deficiency asthma mice. Methods: KM mice were randomly divided into control group, model group, ambroxol group and RADA low, medium and high dose (2, 4 and 8 g/kg) group(n=12). Ovalbumin and the thyroid gland were used to replicate the model of Yin-deficiency asthma. Asthma symptoms in mice , immune globulin E (IgE) , TNF-α , and the expressions of Mucin 5ac (Muc5ac) and NF- κB in lung tissue were observed under the intervention of RADA. Results: RADA at the doses of 2,4 and 8 g/kg could alleviate the asthma symptoms of Yin-deficiency asthma mice significantly, reduce the levels of IgE in serum and TNF-α in bronchoalveolar lavage fluid (BALF), and inhibite the overexpressions of Muc5ac and NF- κB in lung tissue. Conclusion: RADA has significant anti-asthmatic effect. One of its mechanisms is to inhibit TNF-α/NF- κB signaling pathway and to alleviate airway mucus hypersecretion.


Assuntos
Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Muco/metabolismo , NF-kappa B , Transdução de Sinais , Animais , Líquido da Lavagem Broncoalveolar , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Ovalbumina , Distribuição Aleatória , Fator de Necrose Tumoral alfa/metabolismo
13.
Med Hypotheses ; 143: 110066, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32629204

RESUMO

The COVID-19 pandemic has not spared any continent. The disease has affected more than 7,500,000 individuals globally and killed approximately 450,000 individuals. The disease is caused by a very small virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an enveloped single-stranded RNA virus with a spike-like structure on its envelope that can interact with the angiotensin-converting enzyme 2 (ACE2) receptor after cleavage. ACE2 receptors are present in the human lungs and other organs. SARS-CoV-2 is a new virus that belongs to the subgenus Sarbecovirus; viruses in this subgenus have spread widely in the previous years and caused outbreaks of severe acute respiratory syndromes.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Modelos Imunológicos , Pneumonia Viral/imunologia , Ageusia/etiologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Expectorantes/uso terapêutico , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/virologia , Muco/metabolismo , Transtornos do Olfato/etiologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/virologia , Fatores de Transcrição SOXB1/metabolismo
14.
Parasite Immunol ; 42(8): e12766, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32564378

RESUMO

Gill health is one of the main health challenges for Atlantic salmon (Salmo salar L.) mariculture worldwide, and amoebic gill disease (AGD), caused by the marine ectoprotozoan Neoparamoeba perurans, is currently one of the most significant diseases in terms of prevalence and economic impact. This review describes the host response of Atlantic salmon to the disease, focusing on the pathological changes, immune response and mechanisms underlying the prominent epithelial proliferation and mucus hypersecretion occurring in affected fish. Health management strategies and risk factors are also discussed.


Assuntos
Amebíase/imunologia , Amebozoários/imunologia , Doenças dos Peixes/patologia , Brânquias/parasitologia , Salmo salar/parasitologia , Amebíase/patologia , Animais , Doenças dos Peixes/imunologia , Doenças dos Peixes/parasitologia , Brânquias/imunologia , Brânquias/patologia , Muco/metabolismo , Salmo salar/imunologia
15.
Nature ; 583(7814): 78-82, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32494011

RESUMO

Many animals build complex structures to aid in their survival, but very few are built exclusively from materials that animals create 1,2. In the midwaters of the ocean, mucoid structures are readily secreted by numerous animals, and serve many vital functions3,4. However, little is known about these mucoid structures owing to the challenges of observing them in the deep sea. Among these mucoid forms, the 'houses' of larvaceans are marvels of nature5, and in the ocean twilight zone giant larvaceans secrete and build mucus filtering structures that can reach diameters of more than 1 m6. Here we describe in situ laser-imaging technology7 that reconstructs three-dimensional models of mucus forms. The models provide high-resolution views of giant larvacean houses and elucidate the role that house structure has in food capture and predator avoidance. Now that tools exist to study mucus structures found throughout the ocean, we can shed light on some of nature's most complex forms.


Assuntos
Organismos Aquáticos/metabolismo , Muco/metabolismo , Urocordados/anatomia & histologia , Urocordados/metabolismo , Animais , Ciclo do Carbono , Comportamento Alimentar , Cadeia Alimentar , Imageamento Tridimensional/instrumentação , Lasers , Conformação Molecular , Muco/química , Oceanos e Mares , Comportamento Predatório , Água do Mar
17.
Cochrane Database Syst Rev ; 4: CD006842, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32352564

RESUMO

BACKGROUND: Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis. Oscillating devices generate intra- or extra-thoracic oscillations orally or external to the chest wall. Internally they create variable resistances within the airways, generating controlled oscillating positive pressure which mobilises mucus. Extra-thoracic oscillations are generated by forces outside the respiratory system, e.g. high frequency chest wall oscillation. This is an update of a previously published review. OBJECTIVES: To identify whether oscillatory devices, oral or chest wall, are effective for mucociliary clearance and whether they are equivalent or superior to other forms of airway clearance in the successful management of secretions in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conference proceedings. Latest search of the Cystic Fibrosis Trials Register: 29 July 2019. In addition we searched the trials databases ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Latest search of trials databases: 15 August 2019. SELECTION CRITERIA: Randomised controlled studies and controlled clinical studies of oscillating devices compared with any other form of physiotherapy in people with cystic fibrosis. Single-treatment interventions (therapy technique used only once in the comparison) were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria to publications, assessed the quality of the included studies and assessed the evidence using GRADE. MAIN RESULTS: The searches identified 82 studies (330 references); 39 studies (total of 1114 participants) met the inclusion criteria. Studies varied in duration from up to one week to one year; 20 of the studies were cross-over in design. The studies also varied in type of intervention and the outcomes measured, data were not published in sufficient detail in most of these studies, so meta-analysis was limited. Few studies were considered to have a low risk of bias in any domain. It is not possible to blind participants and clinicians to physiotherapy interventions, but 13 studies did blind the outcome assessors. The quality of the evidence across all comparisons ranged from low to very low. Forced expiratory volume in one second was the most frequently measured outcome and while many of the studies reported an improvement in those people using a vibrating device compared to before the study, there were few differences when comparing the different devices to each other or to other airway clearance techniques. One study identified an increase in frequency of exacerbations requiring antibiotics whilst using high frequency chest wall oscillation when compared to positive expiratory pressure (low-quality evidence). There were some small but significant changes in secondary outcome variables such as sputum volume or weight, but not wholly in favour of oscillating devices and due to the low- or very low-quality evidence, it is not clear whether these were due to the particular intervention. Participant satisfaction was reported in 13 studies but again with low- or very low-quality evidence and not consistently in favour of an oscillating device, as some participants preferred breathing techniques or techniques used prior to the study interventions. The results for the remaining outcome measures were not examined or reported in sufficient detail to provide any high-level evidence. AUTHORS' CONCLUSIONS: There was no clear evidence that oscillation was a more or less effective intervention overall than other forms of physiotherapy; furthermore there was no evidence that one device is superior to another. The findings from one study showing an increase in frequency of exacerbations requiring antibiotics whilst using an oscillating device compared to positive expiratory pressure may have significant resource implications. More adequately-powered long-term randomised controlled trials are necessary and outcomes measured should include frequency of exacerbations, individual preference, adherence to therapy and general satisfaction with treatment. Increased adherence to therapy may then lead to improvements in other parameters, such as exercise tolerance and respiratory function. Additional evidence is needed to evaluate whether oscillating devices combined with other forms of airway clearance is efficacious in people with cystic fibrosis.There may also be a requirement to consider the cost implication of devices over other forms of equally advantageous airway clearance techniques. Using the GRADE method to assess the quality of the evidence, we judged this to be low or very low quality, which suggests that further research is very likely to have an impact on confidence in any estimate of effect generated by future interventions.


Assuntos
Oscilação da Parede Torácica/instrumentação , Fibrose Cística/complicações , Pneumopatias Obstrutivas/terapia , Depuração Mucociliar , Muco/metabolismo , Vibração/uso terapêutico , Adolescente , Adulto , Exercícios Respiratórios , Criança , Fibrose Cística/fisiopatologia , Progressão da Doença , Fluxo Expiratório Forçado , Volume Expiratório Forçado , Humanos , Pneumopatias Obstrutivas/etiologia , Pessoa de Meia-Idade , Satisfação do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Escarro/metabolismo
18.
Nat Commun ; 11(1): 2265, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404934

RESUMO

The mucosal epithelium secretes a host of protective disulfide-rich peptides, including the trefoil factors (TFFs). The TFFs increase the viscoelasticity of the mucosa and promote cell migration, though the molecular mechanisms underlying these functions have remained poorly defined. Here, we demonstrate that all TFFs are divalent lectins that recognise the GlcNAc-α-1,4-Gal disaccharide, which terminates some mucin-like O-glycans. Degradation of this disaccharide by a glycoside hydrolase abrogates TFF binding to mucins. Structural, mutagenic and biophysical data provide insights into how the TFFs recognise this disaccharide and rationalise their ability to modulate the physical properties of mucus across different pH ranges. These data reveal that TFF activity is dependent on the glycosylation state of mucosal glycoproteins and alludes to a lectin function for trefoil domains in other human proteins.


Assuntos
Lectinas/metabolismo , Muco/metabolismo , Fator Trefoil-1/metabolismo , Fator Trefoil-3/metabolismo , Cristalografia por Raios X , Dissacarídeos/metabolismo , Glicosídeo Hidrolases/metabolismo , Humanos , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Espectrometria de Massas , Mucinas/metabolismo , Filogenia , Polissacarídeos/metabolismo , Fator Trefoil-1/química , Fator Trefoil-1/genética , Fator Trefoil-3/química , Fator Trefoil-3/genética
19.
J Food Sci ; 85(6): 1939-1947, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32468578

RESUMO

Mucin 2 (MUC2) is the skeleton of colonic mucus that comprises the physical intestinal barrier. Different dietary polysaccharides may affect colonic mucus at different extents. The effect of pectin on MUC2 production is contradictory. To investigate whether and how pectin affected hosts' colonic mucus, the amount of MUC2 in colon, the cecal, mucosal microbiota, and metabolites profiles were analyzed and compared with inulin. The results showed pectin stimulated the production of MUC2 at a similar level to inulin. Both interventions increased the abundance of cecal Lachnospira and Christensenellaceae_R-7_group, and enhanced the production of specific metabolites including soyasapogenol B 24-O-b-d-glucoside, lucyoside Q, trans-EKODE-(E)-Ib, and 1,26-dicaffeoylhexacosanediol. Additionally, pectin increased the relative abundance (RA) of cecal Lactobacillus, and induced less RA of potentially harmful bacteria such as Helicobacter in mucosal microbiota than inulin. In conclusion, we first reported that pectin and inulin stimulated the mucus formation at a similar level. Two genera of cecal bacteria and four metabolites may play an important role in enhancing the production of MUC2. Moreover, the MUC2 production may be unrelated to several traditional health-beneficial bacteria; pectin possibly performed as good as or better than the inulin in rats' gut.


Assuntos
Inulina/metabolismo , Muco/metabolismo , Pectinas/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Ceco/metabolismo , Ceco/microbiologia , Microbioma Gastrointestinal , Masculino , Mucina-2/metabolismo , Muco/microbiologia , Polissacarídeos/metabolismo , Ratos , Ratos Wistar
20.
Sci Rep ; 10(1): 6692, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317678

RESUMO

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of incompletely understood pathophysiology predominantly affecting premature infants. While NEC is associated with microbial invasion of intestinal tissues, and mucus modulates interactions between microbes and underlying tissues, variations in mucus barrier properties with NEC-associated risk factors have not been investigated. This study explored differences in mucus composition (total protein, DNA, mucin content, sialic acid, and immunoregulatory proteins), as well as structural and transport properties, assessed by tracking of particles and bacteria (E. coli and E. cloacae) with developmental age and exposure to NEC stressors in Sprague Dawley rats. Early developmental age (5 day old) was characterized by a more permeable mucus layer relative to 21 day old pups, suggesting immaturity may contribute to exposure of the epithelium to microbes. Exposure to NEC stressors was associated with reduced mucus permeability, which may aid in survival. Feeding with breastmilk as opposed to formula reduces incidence of NEC. Thus, NEC-stressed (N-S) rat pups were orally dosed with breastmilk components lysozyme (N-S-LYS) or docosahexaenoic acid (N-S-DHA). N-S-LYS and N-S-DHA pups had a less permeable mucus barrier relative to N-S pups, which suggests the potential of these factors to strengthen the mucus barrier and thus protect against disease.


Assuntos
Envelhecimento/patologia , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/uso terapêutico , Enterocolite Necrosante/tratamento farmacológico , Muco/metabolismo , Muramidase/administração & dosagem , Muramidase/uso terapêutico , Estresse Fisiológico , Administração Oral , Animais , DNA/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Enterobacter cloacae/fisiologia , Enterocolite Necrosante/microbiologia , Escherichia coli/fisiologia , Fucose/metabolismo , Íleo/patologia , Íleo/ultraestrutura , Imunoglobulina G/metabolismo , Mucinas/metabolismo , Muco/efeitos dos fármacos , Muramidase/farmacologia , Ácido N-Acetilneuramínico/metabolismo , Permeabilidade , Polietilenoglicóis/química , Ratos Sprague-Dawley , Estresse Fisiológico/efeitos dos fármacos
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