Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24.203
Filtrar
3.
Appl Microbiol Biotechnol ; 104(18): 7777-7785, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32780290

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, is the main pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects much more people, especially the elder population, around the world than other coronavirus, such as SARS-CoV and MERS-CoV, which is challenging current global public health system. Beyond the pathogenesis of SARS-CoV-2, microbial coinfection plays an important role in the occurrence and development of SARS-CoV-2 infection by raising the difficulties of diagnosis, treatment, prognosis of COVID-19, and even increasing the disease symptom and mortality. We summarize the coinfection of virus, bacteria and fungi with SARS-CoV-2, their effects on COVID-19, the reasons of coinfection, and the diagnosis to emphasize the importance of microbial coinfection in COVID-19. KEY POINTS: • Microbial coinfection is a nonnegligible factor in COVID-19. • Microbial coinfection exacerbates the processes of the occurrence, development and prognosis of COVID-19, and the difficulties of clinical diagnosis and treatment. • Different virus, bacteria, and fungi contributed to the coinfection with SARS-CoV-2.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/epidemiologia , Linfopenia/epidemiologia , Micoses/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Viroses/epidemiologia , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Coinfecção , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/microbiologia , Síndrome da Liberação de Citocina/virologia , Citocinas/biossíntese , Progressão da Doença , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Linfócitos/microbiologia , Linfócitos/virologia , Linfopenia/tratamento farmacológico , Linfopenia/microbiologia , Linfopenia/virologia , Micoses/tratamento farmacológico , Micoses/microbiologia , Micoses/virologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/microbiologia , Pneumonia Viral/virologia , Viroses/tratamento farmacológico , Viroses/microbiologia , Viroses/virologia
4.
Signal Transduct Target Ther ; 5(1): 157, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814760

RESUMO

Identification of a suitable nonhuman primate (NHP) model of COVID-19 remains challenging. Here, we characterized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in three NHP species: Old World monkeys Macaca mulatta (M. mulatta) and Macaca fascicularis (M. fascicularis) and New World monkey Callithrix jacchus (C. jacchus). Infected M. mulatta and M. fascicularis showed abnormal chest radiographs, an increased body temperature and a decreased body weight. Viral genomes were detected in swab and blood samples from all animals. Viral load was detected in the pulmonary tissues of M. mulatta and M. fascicularis but not C. jacchus. Furthermore, among the three animal species, M. mulatta showed the strongest response to SARS-CoV-2, including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues. Collectively, these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M. mulatta as the most suitable for modeling COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Callithrix/virologia , Infecções por Coronavirus/epidemiologia , Modelos Animais de Doenças , Macaca fascicularis/virologia , Macaca mulatta/virologia , Pandemias , Pneumonia Viral/epidemiologia , Animais , Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Temperatura Corporal , Peso Corporal , Callithrix/imunologia , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Citocinas/biossíntese , Citocinas/classificação , Citocinas/imunologia , Suscetibilidade a Doenças , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macaca fascicularis/imunologia , Macaca mulatta/imunologia , Masculino , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Especificidade da Espécie , Tomografia Computadorizada por Raios X , Carga Viral , Replicação Viral
6.
PLoS One ; 15(8): e0237015, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760098

RESUMO

Graves' orbitopathy (GO) is characterised in early stages by orbital fibroblast inflammation, which can be aggravated by oxidative stress and often leads to fibrosis. Protein tyrosine protein 1B (PTP1B) is a regulator of inflammation and a therapeutic target in diabetes. We investigated the role of PTP1B in the GO mechanism using orbital fibroblasts from GO and healthy non-GO subjects. After 24 hours of transfection with PTPN1 siRNA, the fibroblasts were exposed to interleukin (IL)-1ß, cigarette smoke extract (CSE), H2O2, and transforming growth factor (TGF)-ß stimulations. Inflammatory cytokines and fibrosis-related proteins were analysed using western blotting and/or enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) release was detected using an oxidant-sensitive fluorescent probe. IL-1ß, tumor necrosis factor (TNF)-α, bovine thyroid stimulating hormone (bTSH), high-affinity human stimulatory monoclonal antibody of TSH receptor (M22), and insulin-like growth factor-1 (IGF-1) significantly increased PTP1B protein production in GO and non-GO fibroblasts. PTPN1 silencing significantly blocked IL-1ß-induced inflammatory cytokine production, CSE- and H2O2-induced ROS synthesis, and TGF-ß-induced expression of collagen Iα, α-smooth muscle actin (SMA), and fibronectin in GO fibroblasts. Silencing PTPN1 also decreased phosphorylation levels of Akt, p38, and c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER)-stress response proteins in GO cells. PTP1B may be a potential therapeutic target of anti-inflammatory, anti-oxidant and anti-fibrotic treatment of GO.


Assuntos
Oftalmopatia de Graves/enzimologia , Oftalmopatia de Graves/terapia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Adulto , Animais , Apoptose , Bovinos , Sobrevivência Celular , Citocinas/biossíntese , Estresse do Retículo Endoplasmático , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Inativação Gênica , Oftalmopatia de Graves/patologia , Humanos , Técnicas In Vitro , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
7.
Front Immunol ; 11: 1949, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849654

RESUMO

After the 1918 flu pandemic, the world is again facing a similar situation. However, the advancement in medical science has made it possible to identify that the novel infectious agent is from the coronavirus family. Rapid genome sequencing by various groups helped in identifying the structure and function of the virus, its immunogenicity in diverse populations, and potential preventive measures. Coronavirus attacks the respiratory system, causing pneumonia and lymphopenia in infected individuals. Viral components like spike and nucleocapsid proteins trigger an immune response in the host to eliminate the virus. These viral antigens can be either recognized by the B cells or presented by MHC complexes to the T cells, resulting in antibody production, increased cytokine secretion, and cytolytic activity in the acute phase of infection. Genetic polymorphism in MHC enables it to present some of the T cell epitopes very well over the other MHC alleles. The association of MHC alleles and its downregulated expression has been correlated with disease severity against influenza and coronaviruses. Studies have reported that infected individuals can, after recovery, induce strong protective responses by generating a memory T-cell pool against SARS-CoV and MERS-CoV. These memory T cells were not persistent in the long term and, upon reactivation, caused local damage due to cross-reactivity. So far, the reports suggest that SARS-CoV-2, which is highly contagious, shows related symptoms in three different stages and develops an exhaustive T-cell pool at higher loads of viral infection. As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. A classical immunotherapy of convalescent plasma transfusion from recovered patients has also been initiated for the neutralization of viremia in terminally ill COVID-19 patients. Due to the limitations of plasma transfusion, researchers are now focusing on developing neutralizing antibodies against virus particles along with immuno-modulation of cytokines like IL-6, Type I interferons (IFNs), and TNF-α that could help in combating the infection. This review highlights the similarities of the coronaviruses that caused SARS and MERS to the novel SARS-CoV-2 in relation to their pathogenicity and immunogenicity and also focuses on various treatment strategies that could be employed for curing COVID-19.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Pneumonia Viral/imunologia , Vírus da SARS/genética , Síndrome Respiratória Aguda Grave/imunologia , Animais , Apresentação do Antígeno/imunologia , Antivirais/uso terapêutico , Betacoronavirus/química , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Citocinas/biossíntese , Genoma Viral , Humanos , Evasão da Resposta Imune , Imunização Passiva/métodos , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/química , Pandemias , Filogenia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Vírus da SARS/química , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/virologia , Linfócitos T/imunologia , Replicação Viral
8.
Protein Cell ; 11(10): 740-770, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32780218

RESUMO

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.


Assuntos
Envelhecimento/imunologia , Betacoronavirus , Infecções por Coronavirus/imunologia , Sistema Imunitário/imunologia , Pandemias , Pneumonia Viral/imunologia , Análise de Célula Única , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Linfócitos T CD4-Positivos/metabolismo , Linhagem da Célula , Montagem e Desmontagem da Cromatina , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Citocinas/biossíntese , Citocinas/genética , Suscetibilidade a Doenças , Citometria de Fluxo/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Rearranjo Gênico , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/crescimento & desenvolvimento , Imunocompetência/genética , Inflamação/genética , Inflamação/imunologia , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Análise de Sequência de RNA , Transcriptoma , Adulto Jovem
9.
Science ; 369(6500): 202-207, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32647003

RESUMO

Immunodeficiency often coincides with hyperactive immune disorders such as autoimmunity, lymphoproliferation, or atopy, but this coincidence is rarely understood on a molecular level. We describe five patients from four families with immunodeficiency coupled with atopy, lymphoproliferation, and cytokine overproduction harboring mutations in NCKAP1L, which encodes the hematopoietic-specific HEM1 protein. These mutations cause the loss of the HEM1 protein and the WAVE regulatory complex (WRC) or disrupt binding to the WRC regulator, Arf1, thereby impairing actin polymerization, synapse formation, and immune cell migration. Diminished cortical actin networks caused by WRC loss led to uncontrolled cytokine release and immune hyperresponsiveness. HEM1 loss also blocked mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, T cell proliferation, and selected effector functions, leading to immunodeficiency. Thus, the evolutionarily conserved HEM1 protein simultaneously regulates filamentous actin (F-actin) and mTORC2 signaling to achieve equipoise in immune responses.


Assuntos
Actinas/metabolismo , Citocinas/biossíntese , Síndromes de Imunodeficiência/genética , Transtornos Linfoproliferativos/genética , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Proteínas de Membrana/fisiologia , Fator 1 de Ribosilação do ADP/metabolismo , Linfócitos T CD4-Positivos/imunologia , Proliferação de Células , Humanos , Síndromes de Imunodeficiência/imunologia , Transtornos Linfoproliferativos/imunologia , Proteínas de Membrana/genética , Linhagem , Fosforilação , Família de Proteínas da Síndrome de Wiskott-Aldrich/química , Família de Proteínas da Síndrome de Wiskott-Aldrich/metabolismo
10.
Ann Hematol ; 99(10): 2315-2322, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32728937

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by lower platelet count resulting from immune cells-mediated platelet clearance. Tacrolimus is an immunosuppressive agent which selectively inhibits T cell activation. Whether tacrolimus plays a role in ITP remains unclear. This study aimed to investigate the effect of tacrolimus on ITP in mice. An ITP mouse model was established by injection of rat anti-mouse integrin GPIIb/CD41 immunoglobulin and treated with tacrolimus followed by isolation of peripheral blood mononuclear cells and plasma. The mRNA expression of T-bet, GATA3, and Foxp3 was measured by RT-PCR, and level of IFN-γ, IL-12p70, IL-4, IL-13, and TGF-ß in plasma was measured by ELISA. Tacrolimus inhibited antiplatelet antibody-mediated platelet clearance in ITP mouse model. Meanwhile, tacrolimus-treated ITP mice displayed a significant decrease in the mRNA expression of T-bet and plasma level of IFN-γ and IL-12p70 compared with ITP mice but without differences when compared with normal mice. Furthermore, the expression of GATA3, Foxp3, and plasma level of IL-4 and TGF-ß were upregulated in tacrolimus-treated ITP mice without significant differences to normal mice (except TGF-ß). Tacrolimus prevents antiplatelet antibody-mediated thrombocytopenia in ITP mice possibly through regulating T cell differentiations, suggesting it might be a novel approach for preventing ITP.


Assuntos
Imunossupressores/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Tacrolimo/uso terapêutico , Animais , Plaquetas/imunologia , Citocinas/biossíntese , Citocinas/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Isoanticorpos/sangue , Camundongos , Camundongos Endogâmicos C57BL , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Organismos Livres de Patógenos Específicos , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética
11.
PLoS One ; 15(7): e0236106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673362

RESUMO

Alfalfa is a forage legume commonly associated with ruminant livestock production that may be a potential source of health-promoting phytochemicals. Anecdotal evidence from producers suggests that later cuttings of alfalfa may be more beneficial to non-ruminants; however, published literature varies greatly in measured outcomes, supplement form, and cutting. The objective of this study was to measure body weight, average daily feed intake, host immunity, and the colon microbiota composition in mice fed hay, aqueous, and chloroform extracts of early (1st) and late (5th) cutting alfalfa before and after challenge with Citrobacter rodentium. Prior to inoculation, alfalfa supplementation did not have a significant impact on body weight or feed intake, but 5th cutting alfalfa was shown to improve body weight at 5- and 6-days post-infection compared to 1st cutting alfalfa (P = 0.02 and 0.01). Combined with the observation that both chloroform extracts improved mouse body weight compared to control diets in later stages of C. rodentium infection led to detailed analyses of the immune system and colon microbiota in mice fed 1st and 5th cutting chloroform extracts. Immediately following inoculation, 5th cutting chloroform extracts significantly reduced the relative abundance of C. rodentium (P = 0.02) and did not display the early lymphocyte recruitment observed in 1st cutting extract. In later timepoints, both chloroform extracts maintained lower splenic B-cell and macrophage populations while increasing the relative abundance of potentially beneficially genera such as Turicibacter (P = 0.02). At 21dpi, only 5th cutting chloroform extracts increased the relative abundance of beneficial Akkermansia compared to the control diet (P = 0.02). These results suggest that lipid soluble compounds enriched in late-cutting alfalfa modulate pathogen colonization and early immune responses to Citrobacter rodentium, contributing to protective effects on body weight.


Assuntos
Citrobacter rodentium/fisiologia , Colo/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Lipídeos/química , Medicago sativa/química , Extratos Vegetais/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Colo/microbiologia , Citocinas/biossíntese , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Feminino , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/uso terapêutico , Solubilidade
12.
Anticancer Res ; 40(6): 3231-3237, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487617

RESUMO

BACKGROUND/AIM: We previously established a novel type of epidermal growth factor receptor variant III (EGFRvIII)-specific chimeric antigen receptor (CAR)-expressing natural killer (NK) cell line, designated EvCAR-KHYG-1, which inhibited the growth of glioblastoma (GBM) cells in vitro via apoptosis. MATERIALS AND METHODS: We investigated the cytokine-producing effect of EvCAR-KHYG-1 cells on GBM-like cell lines and their antitumour effect using in vivo xenograft assays. RESULTS: EvCAR-KHYG-1 cells produced interleukin-2, interferon-γ, and tumour necrosis factor-α on EGFRvIII-expressing U87MG cells. In vivo xenograft assays showed that EvCAR-KHYG-1 cells did not reduce the volume of subcutaneous tumours derived from EGFRvIII-expressing U87MG cells but did reduce tumour cell occupancy. CONCLUSION: EvCAR-KHYG-1 cells led to expression of cellular immunity-related cytokines on EGFRvIII-expressing U87MG in vitro but did not inhibit tumour progression due to the induction of a pseudo progression-like pathological feature. Future studies investigating the effect of different conditions in vivo are required to study the inhibition of tumour progression in GBM.


Assuntos
Neoplasias Encefálicas/terapia , Receptores ErbB/imunologia , Glioblastoma/terapia , Células Matadoras Naturais/imunologia , Receptores de Antígenos Quiméricos/imunologia , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Citocinas/biossíntese , Citocinas/imunologia , Progressão da Doença , Feminino , Glioblastoma/genética , Glioblastoma/imunologia , Glioblastoma/patologia , Células HEK293 , Humanos , Células Matadoras Naturais/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Distribuição Aleatória , Receptores de Antígenos Quiméricos/genética , Ensaios Antitumorais Modelo de Xenoenxerto
13.
ACS Nano ; 14(6): 6383-6406, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32519842

RESUMO

The COVID-19 outbreak has fueled a global demand for effective diagnosis and treatment as well as mitigation of the spread of infection, all through large-scale approaches such as specific alternative antiviral methods and classical disinfection protocols. Based on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to cope with this emergency. Here, through a multidisciplinary Perspective encompassing diverse fields such as virology, biology, medicine, engineering, chemistry, materials science, and computational science, we outline how nanotechnology-based strategies can support the fight against COVID-19, as well as infectious diseases in general, including future pandemics. Considering what we know so far about the life cycle of the virus, we envision key steps where nanotechnology could counter the disease. First, nanoparticles (NPs) can offer alternative methods to classical disinfection protocols used in healthcare settings, thanks to their intrinsic antipathogenic properties and/or their ability to inactivate viruses, bacteria, fungi, or yeasts either photothermally or via photocatalysis-induced reactive oxygen species (ROS) generation. Nanotechnology tools to inactivate SARS-CoV-2 in patients could also be explored. In this case, nanomaterials could be used to deliver drugs to the pulmonary system to inhibit interaction between angiotensin-converting enzyme 2 (ACE2) receptors and viral S protein. Moreover, the concept of "nanoimmunity by design" can help us to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively. In addition to disease prevention and therapeutic potential, nanotechnology has important roles in diagnostics, with potential to support the development of simple, fast, and cost-effective nanotechnology-based assays to monitor the presence of SARS-CoV-2 and related biomarkers. In summary, nanotechnology is critical in counteracting COVID-19 and will be vital when preparing for future pandemics.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Betacoronavirus/genética , Betacoronavirus/imunologia , Biomimética , Simulação por Computador , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Desinfecção , Sistemas de Liberação de Medicamentos , Microbiologia Ambiental , Humanos , Imunomodulação , Máscaras , Nanomedicina , Nanotecnologia/tendências , Pandemias/prevenção & controle , Equipamento de Proteção Individual , Fotoquimioterapia , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Vacinas Virais/genética , Vacinas Virais/farmacologia
14.
Transplantation ; 104(9): 1842-1852, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32590607

RESUMO

BACKGROUND: Lung ischemia-reperfusion injury after transplantation is associated with worse clinical outcomes. MicroRNA (miR) are critical regulators of gene expression that could provide potential targets for novel gene therapy. Herein, we aim to examine the feasibility of using the ex vivo lung perfusion (EVLP) platform to examine the changes in miR expression in human lungs in response to cold ischemia and ex vivo reperfusion (CI/EVR). METHODS: Twenty-four human lungs were perfused in cellular EVLP system for 2 h, and tissue samples were obtained before and after EVLP as well as from control donors. MicroRNA expression profiling of the lung tissue was performed using next-generation sequencing and downstream predicted target genes were examined. In situ hybridization assay of the validated miR was used to identify the expressing cell type. RESULTS: After 2 h of EVLP, cytokines production was significantly increased (IL-1ß, IL-6, IL-8, IL-10, and TNF-α). MicroRNA sequencing identified a significant change in the expression of a total of 21 miR after CI and 47 miR after EVR. Validation using quantitative polymerase chain reaction showed significant upregulation of miR-17 and miR548b after CI/EVR. Downstream analysis identified abundant inflammatory and immunologic targets for miR-17 and miR-548b that are known mediators of lung injury. In situ hybridization assays detected positive signals of the 2 miR expression in alveolar epithelial cells. CONCLUSIONS: This study demonstrates the feasibility of using the EVLP platform to study miR signature in human lungs in response to CI/EVR. We found that miR-17 and miR-548b were upregulated in alveolar epithelial cells after CI/EVR, which merit further exploration.


Assuntos
Isquemia Fria , Transplante de Pulmão , Pulmão/metabolismo , MicroRNAs/fisiologia , Reperfusão , Citocinas/biossíntese , Humanos , Traumatismo por Reperfusão/etiologia , Análise de Sequência de RNA , Regulação para Cima
15.
Aging (Albany NY) ; 12(9): 7639-7651, 2020 05 02.
Artigo em Inglês | MEDLINE | ID: covidwho-185611

RESUMO

Currently, we are on a global pandemic of Coronavirus disease-2019 (COVID-19) which causes fever, dry cough, fatigue and acute respiratory distress syndrome (ARDS) that may ultimately lead to the death of the infected. Current researches on COVID-19 continue to highlight the necessity for further understanding the virus-host synergies. In this study, we have highlighted the key cytokines induced by coronavirus infections. We have demonstrated that genes coding interleukins (Il-1α, Il-1ß, Il-6, Il-10), chemokine (Ccl2, Ccl3, Ccl5, Ccl10), and interferon (Ifn-α2, Ifn-ß1, Ifn2) upsurge significantly which in line with the elevated infiltration of T cells, NK cells and monocytes in SARS-Cov treated group at 24 hours. Also, interleukins (IL-6, IL-23α, IL-10, IL-7, IL-1α, IL-1ß) and interferon (IFN-α2, IFN2, IFN-γ) have increased dramatically in MERS-Cov at 24 hours. A similar cytokine profile showed the cytokine storm served a critical role in the infection process. Subsequent investigation of 463 patients with COVID-19 disease revealed the decreased amount of total lymphocytes, CD3+, CD4+, and CD8+ T lymphocytes in the severe type patients which indicated COVID-19 can impose hard blows on human lymphocyte resulting in lethal pneumonia. Thus, taking control of changes in immune factors could be critical in the treatment of COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Infecções por Coronavirus/epidemiologia , Citocinas/biossíntese , Citocinas/imunologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Linfócitos T/imunologia
16.
Cytokine Growth Factor Rev ; 53: 38-42, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32360420

RESUMO

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/patologia , Citocinas/sangue , Insuficiência de Múltiplos Órgãos/mortalidade , Pneumonia Viral/patologia , Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Terapia de Substituição Renal Contínua/métodos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Citocinas/biossíntese , Feminino , Humanos , Interferon-alfa/uso terapêutico , Masculino , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/patologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos
17.
Aging (Albany NY) ; 12(9): 7639-7651, 2020 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-32364527

RESUMO

Currently, we are on a global pandemic of Coronavirus disease-2019 (COVID-19) which causes fever, dry cough, fatigue and acute respiratory distress syndrome (ARDS) that may ultimately lead to the death of the infected. Current researches on COVID-19 continue to highlight the necessity for further understanding the virus-host synergies. In this study, we have highlighted the key cytokines induced by coronavirus infections. We have demonstrated that genes coding interleukins (Il-1α, Il-1ß, Il-6, Il-10), chemokine (Ccl2, Ccl3, Ccl5, Ccl10), and interferon (Ifn-α2, Ifn-ß1, Ifn2) upsurge significantly which in line with the elevated infiltration of T cells, NK cells and monocytes in SARS-Cov treated group at 24 hours. Also, interleukins (IL-6, IL-23α, IL-10, IL-7, IL-1α, IL-1ß) and interferon (IFN-α2, IFN2, IFN-γ) have increased dramatically in MERS-Cov at 24 hours. A similar cytokine profile showed the cytokine storm served a critical role in the infection process. Subsequent investigation of 463 patients with COVID-19 disease revealed the decreased amount of total lymphocytes, CD3+, CD4+, and CD8+ T lymphocytes in the severe type patients which indicated COVID-19 can impose hard blows on human lymphocyte resulting in lethal pneumonia. Thus, taking control of changes in immune factors could be critical in the treatment of COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Infecções por Coronavirus/epidemiologia , Citocinas/biossíntese , Citocinas/imunologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Linfócitos T/imunologia
20.
Invest Ophthalmol Vis Sci ; 61(5): 55, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32460319

RESUMO

Purpose: To investigate the differential expression of cytokines and growth factors in the cornea and aqueous humor after small incision lenticule extraction (SMILE) compared with femtosecond LASIK (FS-LASIK) using rabbit model. Methods: Sixteen eyes of 16 rabbits in each group underwent SMILE or FS-LASIK with refractive correction of -6.00 DS/-1.00 DC. Eight additional rabbits served as controls. Pre- and 24 hours, 1 week, 1 month, and 3 months postoperatively, slit-lamp and anterior segment optical coherence tomography were performed, followed by cornea and aqueous humor collection. Apoptosis and proliferation were evaluated with TUNEL assay and Ki-67 immunostaining, respectively. The mRNA and protein expression of cytokines and growth factors was determined by RT-qPCR and Western blotting, respectively. Cytokine levels in the aqueous humor were detected with ELISA. Results: Compared with FS-LASIK, SMILE induced less apoptosis and proliferation in the cornea within 1 week postoperatively. Levels of IL-1ß, TNF-α, and EGFR in the cornea were significantly increased after FS-LASIK compared with SMILE within 24 hours. Levels of IL-8 in the aqueous humor remained elevated until 1 week after FS-LASIK but not SMILE. TGF-ß1 level was elevated up to 1 month after both procedures, while BFGF level was kept high within 1 month after SMILE but not FS-LASIK. Conclusions: SMILE could induce significantly less acute inflammation than FS-LASIK in the cornea and aqueous humor. The differential expression of TGF-ß1 and BFGF between two procedures until 1 month might contribute to the post-SMILE delayed recovery and underline the importance of continued treatment postoperatively.


Assuntos
Humor Aquoso/metabolismo , Córnea/metabolismo , Córnea/cirurgia , Citocinas/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Ceratomileuse Assistida por Excimer Laser In Situ , Procedimentos Cirúrgicos Refrativos , Animais , Feminino , Período Pós-Operatório , Coelhos , Procedimentos Cirúrgicos Refrativos/métodos , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA