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1.
Gene ; 806: 145928, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34455027

RESUMO

Cytochrome P450 Family 19 (CYP19) is a crucial enzyme to catalyze the conversion of androgens to estrogens. However, the regulatory mechanism of goose CYP19 gene remains poorly understood. The present study attempted to obtain the full-length coding sequence (CDS) and 5'-flanking sequence of CYP19 gene, to investigate its expression and distribution profiles in different sized follicles, and to analyze the transcriptional regulatory mechanism of CYP19 gene in goose. Results showed that its CDS consisted of 1512 nucleotides and the encoded amino acid sequence contained a classical P450 structural domain. Homology analysis showed that there were high homologies of nucleotide and amino acid sequences between goose and other avian species. Its promoter sequence spanned from -1925 bp to the transcription start site (ATG) and several transcriptional factors were predicted in this region. Further analysis from luciferase assay showed that the luciferase activity was the highest spanning from -118 to -1 bp by constructing deletion promoter reporter vector. In addition, result from quantitative real-time polymerase chain reaction indicated that the mRNA level of CYP19 gene were highly expressed in theca layer of the fifth largest follicle, and the cellular location was in the theca externa cells by immunohistochemistry. Taken together, it could be concluded that the transcription activity of CYP19 gene was activated by transcriptional factors in its proximal region of promoter to promote the synthesis of estrogens, regulating the selection of pre-hierarchical into hierarchical follicle in goose.


Assuntos
Proteínas Aviárias/genética , Família 19 do Citocromo P450/genética , Gansos/genética , Regulação Enzimológica da Expressão Gênica , RNA Mensageiro/genética , Transcrição Genética , Sequência de Aminoácidos , Animais , Proteínas Aviárias/metabolismo , Família 19 do Citocromo P450/metabolismo , Feminino , Gansos/classificação , Regulação da Expressão Gênica no Desenvolvimento , Folículo Ovariano/citologia , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/metabolismo , Filogenia , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Sítio de Iniciação de Transcrição
2.
Parasitol Int ; 86: 102470, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34560288

RESUMO

During an investigation of parasitic ciliates in northern China, two Trichodina species, T. acuta Lom, 1970 and T. nigra Lom, 1960, were isolated from the freshwater fish Cyprinus carpio Linnaeus, 1758. The morphology of each species was investigated based on dry silver nitrate-stained specimens. In addition, the molecular phylogeny of each was analyzed based on small subunit ribosomal DNA (SSU rDNA) sequence data. Trichodina acuta can be distinguished from its congeners by the undefined periphery of the central circle, the distinct gap between the rays and the central circle, and the distinctly sickle-shaped blades. Trichodina nigra is a cosmopolitan ciliate and is characterized by its densely linked denticles, broad, rounded spatula-shaped blades, robust central parts, and well developed rays. Phylogenetic analyses revealed that T. acuta and T. nigra nest within different clades, supporting the assertion that the GC content of SSU rDNA sequences could reflect evolutionary relationships among Trichodina species.


Assuntos
Carpas , Infecções por Cilióforos/veterinária , Doenças dos Peixes/epidemiologia , Oligoimenóforos/classificação , Animais , China/epidemiologia , Infecções por Cilióforos/epidemiologia , Infecções por Cilióforos/parasitologia , Doenças dos Peixes/parasitologia , Oligoimenóforos/citologia , Oligoimenóforos/genética , Oligoimenóforos/isolamento & purificação , Filogenia , Prevalência
3.
Scand J Immunol ; 94(4): e13094, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34780092

RESUMO

The thymus produces self-limiting and self-tolerant T cells through the interaction between thymocytes and thymus epithelial cells (TECs), thereby generating central immune tolerance. The TECs are composed of cortical and medullary thymic epithelial cells, which regulate the positive and negative selection of T cells, respectively. During the process of negative selection, thymocytes with self-reactive ability are deleted or differentiated into regulatory T cells (Tregs). Tregs are a subset of suppressor T cells that are important for maintaining immune homeostasis. The differentiation and development of Tregs depend on the development of TECs and other underlying molecular mechanisms. Tregs regulated by thymic epithelial cells are closely related to human health and are significant in autoimmune diseases, thymoma and pregnancy. In this review, we summarize the current molecular and transcriptional regulatory mechanisms by which TECs affect the development and function of thymic Tregs. We also review the pathophysiological models of thymic epithelial cells regulating thymic Tregs in human diseases and specific physiological conditions.


Assuntos
Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Imunidade Adaptativa , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Diferenciação Celular/imunologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Células Epiteliais/classificação , Células Epiteliais/citologia , Células Epiteliais/imunologia , Feminino , Homeostase , Humanos , Masculino , Modelos Imunológicos , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/imunologia , Gravidez , Transdução de Sinais/imunologia , Linfócitos T Reguladores/classificação , Timócitos/classificação , Timócitos/citologia , Timócitos/imunologia , Timoma/imunologia , Timo/citologia , Timo/imunologia , Neoplasias do Timo/imunologia
4.
Int J Mol Sci ; 22(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34769350

RESUMO

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin-angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.


Assuntos
COVID-19/patologia , Células Endoteliais/metabolismo , COVID-19/complicações , COVID-19/virologia , Síndrome da Liberação de Citocina/etiologia , Células Endoteliais/citologia , Células Endoteliais/virologia , Insuficiência Cardíaca/etiologia , Humanos , Insuficiência Renal/etiologia , Sistema Renina-Angiotensina/fisiologia , SARS-CoV-2/isolamento & purificação , Trombose/etiologia
5.
Int J Mol Sci ; 22(21)2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34769471

RESUMO

Heparin and its derivatives are saving thousands of human lives annually, by successfully preventing and treating thromboembolic events. Although the mode of action during anticoagulation is well studied, their influence on cell behavior is not fully understood as is the risk of bleeding and other side effects. New applications in regenerative medicine have evolved supporting production of cell-based therapeutics or as a substrate for creating functionalized matrices in biotechnology. The currently resurgent interest in heparins is related to the expected combined anti-inflammatory, anti-thrombotic and anti-viral action against COVID-19. Based on a concise summary of key biochemical and clinical data, this review summarizes the impact for manufacturing and application of cell therapeutics and highlights the need for discriminating the different heparins.


Assuntos
Anticoagulantes/química , Terapia Baseada em Transplante de Células e Tecidos/métodos , Heparina/análogos & derivados , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Adesão Celular , Hemorragia/etiologia , Heparina/efeitos adversos , Heparina/uso terapêutico , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Medicina Regenerativa , Tromboembolia/tratamento farmacológico
6.
Front Biosci (Landmark Ed) ; 26(10): 948-961, 2021 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-34719217

RESUMO

Background: Corona Virus Disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary pathogenesis is over-activation of the immune system. SARS-CoV-2 continues to mutate and spread rapidly and no effective treatment options are yet available. Mesenchymal stem cells (MSCs) are known to induce anti-inflammatory macrophages, regulatory T cells and dendritic cells. There are a rapidly increasing number of clinical investigations of cell-based therapy approaches for COVID-19. Objective: To summarize the pathogenic mechanism of SARS-CoV-2, and systematically formulated the immunomodulation of COVID-19 by MSCs and their exosomes, as well as research progress. Method: Searching PubMed, clinicaltrials.gov and Chictr.cn for eligible studies to be published or registered by May 2021. Main keywords and search strategies were as follows: ((Mesenchymal stem cells) OR (MSCs)) AND (COVID-19). Results: MSCs regulate the immune system to prevent cytokine release syndrome (CRS) and to promote endogenous repair by releasing various paracrine factors and exosomes. Conclusions: MSC therapy is thus a promising candidate for COVID-19.


Assuntos
COVID-19/terapia , Exossomos/transplante , Imunomodulação/imunologia , Lesão Pulmonar/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , COVID-19/epidemiologia , COVID-19/virologia , Ensaios Clínicos como Assunto , Exossomos/imunologia , Exossomos/metabolismo , Humanos , Lesão Pulmonar/fisiopatologia , Lesão Pulmonar/virologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Pandemias , Regeneração/imunologia , Regeneração/fisiologia , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia
8.
Cell Transplant ; 30: 9636897211054481, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34757857

RESUMO

Biological and cellular interleukin-6 (IL-6)-related therapies have been used to treat severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure, which prompted further exploration of the role of IL-6 in human umbilical cord mesenchymal stem cell (hUCMSC) therapy. Peripheral blood mononuclear cells (PBMCs) were responders cocultured with hUCMSCs or exogenous IL-6. A PBMC suppression assay was used to analyze the anti-inflammatory effects via MTT assay. The IL-6 concentration in the supernatant was measured using ELISA. The correlation between the anti-inflammatory effect of hUCMSCs and IL-6 levels and the relevant roles of IL-6 and IL-6 mRNA expression was analyzed using the MetaCore functional network constructed from gene microarray data. The location of IL-6 and IL-6 receptor (IL-6R) expression was further evaluated. We reported that hUCMSCs did not initially exert any inhibitory effect on PHA-stimulated proliferation; however, a potent inhibitory effect on PHA-stimulated proliferation was observed, and the IL-6 concentration reached approximately 1000 ng/mL after 72 hours. Exogenous 1000 ng/mL IL-6 inhibited PHA-stimulated inflammation but less so than hUCMSCs. The inhibitory effects of hUCMSCs on PHA-stimulated PBMCs disappeared after adding an IL-6 neutralizing antibody or pretreatment with tocilizumab (TCZ), an IL-6R antagonist. hUCMSCs exert excellent anti-inflammatory effects by inducing higher IL-6 levels, which is different from TCZ. High concentration of IL-6 cytokine secretion plays an important role in the anti-inflammatory effect of hUCMSC therapy. Initial hUCMSC therapy, followed by TCZ, seems to optimize the therapeutic potential to treat COVID-19-related acute respiratory distress syndrome (ARDS).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/complicações , Interleucina-6/biossíntese , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Síndrome do Desconforto Respiratório/terapia , SARS-CoV-2 , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Neutralizantes/imunologia , Células Cultivadas , Técnicas de Cocultura , Terapia Combinada , DNA Complementar/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação , Interleucina-6/genética , Interleucina-6/farmacologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Fito-Hemaglutininas/farmacologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores de Interleucina-6/antagonistas & inibidores , Receptores de Interleucina-6/biossíntese , Receptores de Interleucina-6/genética , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/etiologia , Cordão Umbilical/citologia
9.
Int J Mol Sci ; 22(21)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34768820

RESUMO

Disseminated intravascular coagulation (DIC) is a severe condition characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. In the last years, it represents one of the most frequent consequences of coronavirus disease 2019 (COVID-19). The pathogenesis of DIC is complex, with cross-talk between the coagulant and inflammatory pathways. The objective of this study is to investigate the anti-inflammatory action of ultramicronized palmitoylethanolamide (um-PEA) in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by continual infusion of LPS (30 mg/kg) for 4 h through the tail vein. Um-PEA (30 mg/kg) was given orally 30 min before and 1 h after the start of intravenous infusion of LPS. Results showed that um-PEA reduced alteration of coagulation markers, as well as proinflammatory cytokine release in plasma and lung samples, induced by LPS infusion. Furthermore, um-PEA also has the effect of preventing the formation of fibrin deposition and lung damage. Moreover, um-PEA was able to reduce the number of mast cells (MCs) and the release of its serine proteases, which are also necessary for SARS-CoV-2 infection. These results suggest that um-PEA could be considered as a potential therapeutic approach in the management of DIC and in clinical implications associated to coagulopathy and lung dysfunction, such as COVID-19.


Assuntos
Amidas/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Coagulação Intravascular Disseminada/tratamento farmacológico , Etanolaminas/uso terapêutico , Ácidos Palmíticos/uso terapêutico , Sepse/complicações , Amidas/química , Amidas/farmacologia , Animais , Transtornos da Coagulação Sanguínea/etiologia , COVID-19/patologia , COVID-19/virologia , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Coagulação Intravascular Disseminada/etiologia , Etanolaminas/química , Etanolaminas/farmacologia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Lipopolissacarídeos/toxicidade , Pulmão/metabolismo , Pulmão/patologia , Masculino , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Ácidos Palmíticos/química , Ácidos Palmíticos/farmacologia , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Ratos , Ratos Sprague-Dawley , SARS-CoV-2/isolamento & purificação , Sepse/patologia , Serina Proteases/metabolismo
10.
Sci Rep ; 11(1): 21519, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728719

RESUMO

A high neutrophil to lymphocyte ratio (NLR) is considered an unfavorable prognostic factor in various diseases, including COVID-19. The prognostic value of NLR in other respiratory viral infections, such as Influenza, has not hitherto been extensively studied. We aimed to compare the prognostic value of NLR in COVID-19, Influenza and Respiratory Syncytial Virus infection (RSV). A retrospective cohort of COVID-19, Influenza and RSV patients admitted to the Tel Aviv Medical Center from January 2010 to October 2020 was analyzed. Laboratory, demographic, and clinical parameters were collected. Two way analyses of variance (ANOVA) was used to compare the association between NLR values and poor outcomes among the three groups. ROC curve analyses for each virus was applied to test the discrimination ability of NLR. 722 COVID-19, 2213 influenza and 482 RSV patients were included. Above the age of 50, NLR at admission was significantly lower among COVID-19 patients (P < 0.001). NLR was associated with poor clinical outcome only in the COVID-19 group. ROC curve analysis was performed; the area under curve of poor outcomes for COVID-19 was 0.68, compared with 0.57 and 0.58 for Influenza and RSV respectively. In the COVID-19 group, multivariate logistic regression identified a high NLR (defined as a value above 6.82) to be a prognostic factor for poor clinical outcome, after adjusting for age, sex and Charlson comorbidity score (odds ratio of 2.9, P < 0.001). NLR at admission is lower and has more prognostic value in COVID-19 patients, when compared to Influenza and RSV.


Assuntos
COVID-19/patologia , Influenza Humana/patologia , Infecções por Vírus Respiratório Sincicial/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , COVID-19/imunologia , COVID-19/virologia , Feminino , Humanos , Influenza Humana/imunologia , Linfócitos/citologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Neutrófilos/metabolismo , Prognóstico , Curva ROC , Infecções por Vírus Respiratório Sincicial/imunologia , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação
11.
Medicine (Baltimore) ; 100(41): e27521, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731142

RESUMO

ABSTRACT: To investigate the effect of a combined immune score including the lymphocyte-to-monocyte ratio (LMR) and uninvolved immunoglobulin (u-Ig) levels on the prognosis of newly diagnosed multiple myeloma (NDMM) patients treated with bortezomib.Clinical data of 201 NDMM patients were retrospectively analyzed. Patients with LMR ≥ 3.6 and LMR < 3.6 were scored 0 and 1, respectively. Patients with preserved u-Ig levels, suppression of 1 u-Ig, and suppression of at least 2 u-Igs were scored 0, 1, and 2, respectively. The immune score, established from these individual scores, was used to separate patients into good (0-1 points), intermediate (2 points), and poor (3 points) risk groups. The baseline data, objective remission rate (ORR), whether receive maintenance treatment regularly and overall survival of patients before treatment were analyzed.The ORR of the good-risk group was significantly higher than that of the intermediate-risk group (75.6% vs 57.7%, P = .044) and the poor-risk group (75.6% vs 48.2%, P = .007). The multivariate analysis results showed that age ≥ 65 years, International Staging System stage III, platelet count ≤ 100 × 109/L, lactate dehydrogenase (LDH) > 250 U/L, serum calcium > 2.75 mmol/L, no receipt of regular maintenance treatment, LMR < 3.6, suppressed u-Igs = 1, suppressed u-Igs ≥ 2, intermediate-risk group and poor-risk group were independent predictors of poor overall survival.In the bortezomib era, the LMR, u-Ig levels, and the immune score play an important role in the prognosis of NDMM patients. Among them, the immune score showed the strongest prognostic value, and it could be a beneficial supplement for the early identification of high-risk patients.


Assuntos
Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Fatores Etários , Idoso , Antineoplásicos/administração & dosagem , Bortezomib/administração & dosagem , Cálcio/sangue , Estudos de Casos e Controles , Feminino , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/imunologia , Imunoglobulinas/efeitos dos fármacos , Imunoglobulinas/imunologia , L-Lactato Desidrogenase/análise , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/imunologia , Estadiamento de Neoplasias/métodos , Contagem de Plaquetas/estatística & dados numéricos , Contagem de Plaquetas/tendências , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco
12.
Braz Dent J ; 32(3): 65-74, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34755791

RESUMO

This study investigated the effect of three commercial calcium silicate-based materials (CSBM) on cytotoxicity and pro-and anti-inflammatory cytokines production in cultured human periodontal ligament stem cells (hPDLSCs). Culture of hPDLSCs was established and characterized. Extracts of Bio-C Sealer (Angelus, Londrina, PR, Brazil), MTA Fillapex (Angelus, Londrina, PR, Brazil) and PBS Cimmo HP (Cimmo Soluções em Saúde, Pouso Alegre, MG, Brazil) were prepared by placing cement specimens (5 x 3 mm) in culture medium. Then, the extracts were serially two-fold diluted (1, 1:2, 1:4, 1:8, 1:16) and inserted into the cell-seeded wells for 24, 48 and 72 h for MTT assays. TNF-α and IL-10 cytokines were quantified by ELISA at 24h-cell supernatants. Data were analyzed by ANOVA and Tukey's test (α = 0.05). All CSBM exhibited some cytotoxicity that varied according to extract concentration and time of evaluation. MTA Fillapex presented the highest cytotoxic effects with significant reduction of metabolic activity/cell viability when compared to Bio-C Sealer and Cimmo HP®. TNF-α was significantly upregulated by the three tested cements (p < 0.05) while only MTA Fillapex significantly upregulated IL-10 in comparison to control. Taken collectively, the results showed that PBS Cimmo HP®, Bio-C Sealer and MTA Fillapex present mild and transient cytotoxicity and slightly induced TNF-α production. MTA Fillapex upregulated IL-10 release by hPDLSCs.


Assuntos
Compostos de Cálcio/efeitos adversos , Ligamento Periodontal , Materiais Restauradores do Canal Radicular/efeitos adversos , Silicatos/efeitos adversos , Células-Tronco/efeitos dos fármacos , Compostos de Alumínio , Citocinas/metabolismo , Humanos , Teste de Materiais , Óxidos , Ligamento Periodontal/citologia
13.
Front Immunol ; 12: 689065, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733269

RESUMO

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The US FDA has approved several therapeutics and vaccines worldwide through the emergency use authorization in response to the rapid spread of COVID-19. Nevertheless, the efficacies of these treatments are being challenged by viral escape mutations. There is an urgent need to develop effective treatments protecting against SARS-CoV-2 infection and to establish a stable effect-screening model to test potential drugs. Polyclonal antibodies (pAbs) have an intrinsic advantage in such developments because they can target rapidly mutating viral strains as a result of the complexity of their binding epitopes. In this study, we generated anti-receptor-binding domain (anti-RBD) pAbs from rabbit serum and tested their safety and efficacy in response to SARS-CoV-2 infection both in vivo and ex vivo. Primary human bronchial epithelial two-dimensional (2-D) organoids were cultured and differentiated to a mature morphology and subsequently employed for SARS-CoV-2 infection and drug screening. The pAbs protected the airway organoids from viral infection and tissue damage. Potential side effects were tested in mouse models for both inhalation and vein injection. The pAbs displayed effective viral neutralization effects without significant side effects. Thus, the use of animal immune serum-derived pAbs might be a potential therapy for protection against SARS-CoV-2 infection, with the strategy developed to produce these pAbs providing new insight into the treatment of respiratory tract infections, especially for infections with viruses undergoing rapid mutation.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Sítios de Ligação , Brônquios/citologia , COVID-19/genética , COVID-19/terapia , Células Epiteliais , Perfilação da Expressão Gênica , Humanos , Imunização Passiva , Camundongos , Mutação , Testes de Neutralização , Organoides , Coelhos , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética
14.
Vestn Oftalmol ; 137(5): 86-92, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34726862

RESUMO

Effective and safe antiseptic eye preparations are necessary for prevention and treatment of infectious and inflammatory eye diseases. PURPOSE: in vitro evaluation of the effect of antiseptic eye drops on corneal and conjunctival epithelial cells. MATERIAL AND METHODS: Antiseptic eye drops «Bactavit¼, «Vitabact¼ and «Ocomistin¼ were the object of the study. Immortalized human corneal epithelial cell lines (HCE) and human conjunctiva (Chang Conjunctiva, Clone 1-5c-4) were used as the test systems. The viability of the cells was assessed by their metabolic activity and morphology using the MTT test and phase-contrast microscopy. RESULTS: Antiseptic eye drops belonging to different groups of chemical compounds induced cytotoxic effects on the cells of corneal epithelium (HCE) and human conjunctiva (Chang Conjunctiva, Clone 1-5c-4) of varying degrees, leading to morphological and functional changes in those cells. CONCLUSION: The study confirms the possibility of using cultured cells for the in vitro comparative assessment of the cytotoxic effect of antiseptic ophthalmic agents.


Assuntos
Anti-Infecciosos Locais , Células Epiteliais/efeitos dos fármacos , Anti-Infecciosos Locais/farmacologia , Células Cultivadas , Túnica Conjuntiva/citologia , Córnea/citologia , Humanos , Soluções Oftálmicas
15.
Front Immunol ; 12: 740249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594343

RESUMO

Objective: To assess in rheumatoid arthritis (RA) patients, treated with different immunosuppressive therapies, the induction of SARS-CoV-2-specific immune response after vaccination in terms of anti-region-binding-domain (RBD)-antibody- and T-cell-specific responses against spike, and the vaccine safety in terms of clinical impact on disease activity. Methods: Health care workers (HCWs) and RA patients, having completed the BNT162b2-mRNA vaccination in the last 2 weeks, were enrolled. Serological response was evaluated by quantifying anti-RBD antibodies, while the cell-mediated response was evaluated by a whole-blood test quantifying the interferon (IFN)-γ-response to spike peptides. FACS analysis was performed to identify the cells responding to spike stimulation. RA disease activity was evaluated by clinical examination through the DAS28crp, and local and/or systemic clinical adverse events were registered. In RA patients, the ongoing therapeutic regimen was modified during the vaccination period according to the American College of Rheumatology indications. Results: We prospectively enrolled 167 HCWs and 35 RA patients. Anti-RBD-antibodies were detected in almost all patients (34/35, 97%), although the titer was significantly reduced in patients under CTLA-4-inhibitors (median: 465 BAU/mL, IQR: 103-1189, p<0.001) or IL-6-inhibitors (median: 492 BAU/mL, IQR: 161-1007, p<0.001) compared to HCWs (median: 2351 BAU/mL, IQR: 1389-3748). T-cell-specific response scored positive in most of RA patients [24/35, (69%)] with significantly lower IFN-γ levels in patients under biological therapy such as IL-6-inhibitors (median: 33.2 pg/mL, IQR: 6.1-73.9, p<0.001), CTLA-4-inhibitors (median: 10.9 pg/mL, IQR: 3.7-36.7, p<0.001), and TNF-α-inhibitors (median: 89.6 pg/mL, IQR: 17.8-224, p=0.002) compared to HCWs (median: 343 pg/mL, IQR: 188-756). A significant correlation between the anti-RBD-antibody titer and spike-IFN-γ-specific T-cell response was found in RA patients (rho=0.432, p=0.009). IFN-γ T-cell response was mediated by CD4+ and CD8+ T cells. Finally, no significant increase in disease activity was found in RA patients following vaccination. Conclusion: This study showed for the first time that antibody-specific and whole-blood spike-specific T-cell responses induced by the COVID-19 mRNA-vaccine were present in the majority of RA patients, who underwent a strategy of temporary suspension of immunosuppressive treatment during vaccine administration. However, the magnitude of specific responses was dependent on the immunosuppressive therapy administered. In RA patients, BNT162b2 vaccine was safe and disease activity remained stable.


Assuntos
Anticorpos Antivirais/imunologia , Artrite Reumatoide/terapia , Vacinas contra COVID-19/imunologia , Imunoterapia/efeitos adversos , Linfócitos T/imunologia , Idoso , Artrite Reumatoide/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , COVID-19/prevenção & controle , Feminino , Humanos , Interferon gama/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/citologia , Vacinas Sintéticas/imunologia
16.
Front Immunol ; 12: 744799, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594344

RESUMO

Sepsis is a global health emergency, which is caused by various sources of infection that lead to changes in gene expression, protein-coding, and metabolism. Advancements in "omics" technologies have provided valuable tools to unravel the mechanisms involved in the pathogenesis of this disease. In this study, we performed shotgun mass spectrometry in peripheral blood mononuclear cells (PBMC) from septic patients (N=24) and healthy controls (N=9) and combined these results with two public microarray leukocytes datasets. Through combination of transcriptome and proteome profiling, we identified 170 co-differentially expressed genes/proteins. Among these, 122 genes/proteins displayed the same expression trend. Ingenuity Pathway Analysis revealed pathways related to lymphocyte functions with decreased status, and defense processes that were predicted to be strongly increased. Protein-protein interaction network analyses revealed two densely connected regions, which mainly included down-regulated genes/proteins that were related to the transcription of RNA, translation of proteins, and mitochondrial translation. Additionally, we identified one module comprising of up-regulated genes/proteins, which were mainly related to low-density neutrophils (LDNs). LDNs were reported in sepsis and in COVID-19. Changes in gene expression level were validated using quantitative real-time PCR in PBMCs from patients with sepsis. To further support that the source of the upregulated module of genes/proteins found in our results were derived from LDNs, we identified an increase of this population by flow cytometry in PBMC samples obtained from the same cohort of septic patients included in the proteomic analysis. This study provides new insights into a reprioritization of biological functions in response to sepsis that involved a transcriptional and translational shutdown of genes/proteins, with exception of a set of genes/proteins related to LDNs and host-defense system.


Assuntos
Leucócitos Mononucleares/metabolismo , Neutrófilos/metabolismo , Sepse/metabolismo , Bases de Dados Factuais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Leucócitos Mononucleares/citologia , Células Supressoras Mieloides/citologia , Células Supressoras Mieloides/metabolismo , Neutrófilos/citologia , Mapas de Interação de Proteínas , Proteômica , Sepse/genética , Sepse/imunologia
17.
Arch Oral Biol ; 131: 105264, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34598025

RESUMO

OBJECTIVE: Insulin-like growth factor 1 (IGF1) is one of the vital factors in regenerative endodontics. Previous studies have focused on the role of IGF1 in the mineralization of dental tissues. However, the role of IGF1 in the neural differentiation of dental stem cells was little discussed. DESIGN: IGF1 was overexpressed in human stem cells from the apical papilla (hSCAPs) by lentivirus and knocked down in hSCAPs by small interfering RNA. The neural differentiation level of hSCAPs was investigated histologically by HE staining and Nissl staining after neural induction for 3 days. The expression of proteins was examined by western blot and immunofluorescence. RESULTS: IGF1 promoted neural differentiation of hSCAPs, more cell processes and Nissl-positive body stained cells. IGF1 overexpression could both promote glial differentiation in hSCAPs, characterized by the increase of S100ß and GFAP proteins, and neuronal differentiation, characterized by the increase of ßIII-tubulin and functional GAD67/vGLUT1 proteins. Conversely, IGF1 knockdown suppressed both glial and neuronal differentiation. IGF1 activated AKT to regulate the early neural differentiation of hSCAPs. CONCLUSIONS: The results indicate IGF1 could promote neural differentiation of hSCAPs by activating AKT signaling and provide a cue for the candidate of induced neural seeding cells in regenerative endodontics.


Assuntos
Diferenciação Celular , Fator de Crescimento Insulin-Like I , Células-Tronco , Células Cultivadas , Papila Dentária/citologia , Humanos , Lentivirus , Transdução de Sinais , Células-Tronco/citologia
18.
Front Immunol ; 12: 705646, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603282

RESUMO

COVID-19 is a disease with a spectrum of clinical responses ranging from moderate to critical. To study and control its effects, a large number of researchers are focused on two substantial aims. On the one hand, the discovery of diverse biomarkers to classify and potentially anticipate the disease severity of patients. These biomarkers could serve as a medical criterion to prioritize attention to those patients with higher prone to severe responses. On the other hand, understanding how the immune system orchestrates its responses in this spectrum of disease severities is a fundamental issue required to design new and optimized therapeutic strategies. In this work, using single-cell RNAseq of bronchoalveolar lavage fluid of nine patients with COVID-19 and three healthy controls, we contribute to both aspects. First, we presented computational supervised machine-learning models with high accuracy in classifying the disease severity (moderate and severe) in patients with COVID-19 starting from single-cell data from bronchoalveolar lavage fluid. Second, we identified regulatory mechanisms from the heterogeneous cell populations in the lungs microenvironment that correlated with different clinical responses. Given the results, patients with moderate COVID-19 symptoms showed an activation/inactivation profile for their analyzed cells leading to a sequential and innocuous immune response. In comparison, severe patients might be promoting cytotoxic and pro-inflammatory responses in a systemic fashion involving epithelial and immune cells without the possibility to develop viral clearance and immune memory. Consequently, we present an in-depth landscape analysis of how transcriptional factors and pathways from these heterogeneous populations can regulate their expression to promote or restrain an effective immune response directly linked to the patients prognosis.


Assuntos
Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , COVID-19/patologia , Pulmão/citologia , SARS-CoV-2/imunologia , Linfócitos B/imunologia , Biomarcadores , Líquido da Lavagem Broncoalveolar/química , Células Dendríticas/imunologia , Células Epiteliais/citologia , Células Epiteliais/virologia , Humanos , Células Matadoras Naturais/imunologia , Pulmão/química , Aprendizado de Máquina , Macrófagos/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , RNA Viral/genética , Análise de Sequência de RNA , Índice de Gravidade de Doença , Análise de Célula Única , Linfócitos T/imunologia
19.
Front Immunol ; 12: 731100, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603308

RESUMO

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious infectious disease that has led to a global pandemic with high morbidity and mortality. High-affinity neutralizing antibody is important for controlling infection, which is closely regulated by follicular helper T (Tfh) cells. Tfh cells play a central role in promoting germinal center reactions and driving cognate B cell differentiation for antibody secretion. Available studies indicate a close relationship between virus-specific Tfh cell-mediated immunity and SARS-CoV-2 infection progression. Although several lines of evidence have suggested that Tfh cells contribute to the control of SARS-CoV-2 infection by eliciting neutralizing antibody productions, further studies are needed to elucidate Tfh-mediated effector mechanisms in anti-SARS-CoV-2 immunity. Here, we summarize the functional features and roles of virus-specific Tfh cells in the immunopathogenesis of SARS-CoV-2 infection and in COVID-19 vaccines, and highlight the potential of targeting Tfh cells as therapeutic strategy against SARS-CoV-2 infection.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Células T Auxiliares Foliculares/imunologia , Formação de Anticorpos/imunologia , Linfócitos B/imunologia , COVID-19/patologia , Vacinas contra COVID-19/imunologia , Diferenciação Celular/imunologia , Centro Germinativo/citologia , Centro Germinativo/imunologia , Humanos , Ativação Linfocitária/imunologia , Células T Auxiliares Foliculares/citologia
20.
Nat Commun ; 12(1): 5740, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593806

RESUMO

NG2 glia, also known as oligodendrocyte precursor cells (OPCs), play an important role in proliferation and give rise to myelinating oligodendrocytes during early brain development. In contrast to other glial cell types, the most intriguing aspect of NG2 glia is their ability to directly sense synaptic inputs from neurons. However, whether this synaptic interaction is bidirectional or unidirectional, or its physiological relevance has not yet been clarified. Here, we report that NG2 glia form synaptic complexes with hippocampal interneurons and that selective photostimulation of NG2 glia (expressing channelrhodopsin-2) functionally drives GABA release and enhances inhibitory synaptic transmission onto proximal interneurons in a microcircuit. The mechanism involves GAD67 biosynthesis and VAMP-2 containing vesicular exocytosis. Further, behavioral assays demonstrate that NG2 glia photoactivation triggers anxiety-like behavior in vivo and contributes to chronic social defeat stress.


Assuntos
Ansiedade/psicologia , Hipocampo/patologia , Células Precursoras de Oligodendrócitos/metabolismo , Estresse Psicológico/complicações , Ácido gama-Aminobutírico/metabolismo , Animais , Ansiedade/etiologia , Ansiedade/patologia , Diferenciação Celular , Modelos Animais de Doenças , Exocitose , Glutamato Descarboxilase/biossíntese , Hipocampo/citologia , Humanos , Interneurônios/patologia , Masculino , Camundongos , Camundongos Transgênicos , Técnicas de Patch-Clamp , Derrota Social , Estresse Psicológico/patologia , Estresse Psicológico/psicologia , Sinapses/patologia , Transmissão Sináptica/fisiologia , Proteína 2 Associada à Membrana da Vesícula/metabolismo
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