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1.
Arq. Asma, Alerg. Imunol ; 6(2): 271-284, abr.jun.2022. ilus
Article in English | LILACS | ID: biblio-1400222

ABSTRACT

Introduction: Asthma is an inflammatory airway disease that is influenced by several factors. An evolutionarily conserved serine/ threonine kinase named mTOR plays a key role in the integration of environmental signals in the form of growth factors, amino acids, and energy. In the immune system, mTOR is a critical regulator. The mTOR pathway exerts central control over processes in the immune response and in T-cell proliferation, multiplication, and differentiation. Variations in the gene responsible for mTOR complexes have been associated with different critical levels of cytokines, increased likelihood of developing asthma, and increased prevalence of atopy. Objective and method: This study aimed to investigate the association of mTOR gene variants with asthma, asthma severity, and atopy, as well as to perform a cytokine analysis. Result and conclusion: The findings reinforce the importance of mTOR gene variants in the development of asthma.


Introdução: A asma é uma doença inflamatória das vias aéreas, com diversos fatores influenciando essa condição inflamatória. A mTOR, uma serina/treonina quinase evolutivamente conservada, desempenha um papel central na integração de sinais ambientais na forma de fatores de crescimento, aminoácidos e energia. No sistema imunológico, a mTOR se apresenta como um regulador crítico. A via mTOR se destaca pelo controle central na resposta do sistema imunológico, bem como na proliferação, multiplição e diferenciação das células T. Variações no gene responsável pelos complexos mTOR têm sido associadas a diferentes níveis críticos de citocinas, aumento da probabilidade de desenvolver asma e aumento da prevalência de atopia. Objetivo e método: O objetivo do presente estudo foi investigar a associação entre as variantes do gene mTOR com asma e sua gravidade, atopia, além da análise de citocinas. Resultado e conclusão: Os achados reafirmam a importância das variantes do gene mTOR no desenvolvimento da asma.


Subject(s)
Humans , Asthma , Threonine , Protein Serine-Threonine Kinases , Serine , Signs and Symptoms , Therapeutics , Prevalence , Cytokines , Immune System , Immunity , Methods
2.
Rev. ADM ; 79(3): 165-176, mayo-jun. 2022. ilus, tab
Article in Spanish | LILACS | ID: biblio-1378976

ABSTRACT

Introducción: El hueso, reservorio de minerales y moléculas orgánicas, es un tejido dinámico que detecta y se adapta a las cargas mecánicas de los órganos y tejidos del cuerpo, el cual mantiene la estructura ósea del esqueleto durante el crecimiento y a través de la vida del ser humano. Las células óseas son sensibles a las cargas mecánicas y microvibra- ciones que recibe el esqueleto. Objetivo: El propósito de este estudio fue realizar una revisión sistemática acerca de los efectos que ejerce la microvibración de alta frecuencia-baja intensidad, en osteocitos cultivados in vitro sobre la síntesis de factores solubles, con el propósito de entender si la microvibración tiene influencia en la aceleración del movimiento dentario. Material y métodos: Se realizó una búsqueda de artículos de revisión de osteocitos y otras células óseas in vitro, a través de la estrategia PICO (Paciente, Intervención, Comparación, Resultado [Outcome]), con el empleo de palabras clave como: «os- teocitos¼, «microvibración¼, «remodelación¼, «osteoclastogénesis¼, «citocinas¼ y «osteoblastos¼. Se estructuró por medio de PRISMA (informe de revisiones sistemáticas y meta-análisis). La captación de datos finales se hizo por medio del método de puntuación de calidad Jadad y Cochrane (modelo de correlación) como herramientas para evaluar el riesgo de sesgo de cada uno de los artículos. Se incluyeron 11 artículos con alta calidad metodológica. Resultados: La mayoría de los experimentos in vitro demostraron que la microvibración tuvo un aumento estadísticamente significativo en la proliferación y dife- renciación de las células madre mesenquimales (MSC), en osteoblastos (MC3T3-E1), en la expresión de proteínas para inducir osteogénesis y en los osteocitos (MLO-Y4). Asimismo, sobrerregularon la expresión de osteoprotegerina (OPG), prostaglandina (PGE2) y óxido nitroso (NO) al alterar y regular los factores solubles como las citocinas, factores de crecimiento y quimiocinas, de las demás células, además de mostrar una disminución en la actividad de los osteoclastos (RAW246.7) en la resorción ósea. Conclusión: La microvibración induce remodelación ósea. Los osteocitos son sensibles a los estímulos mecánicos y producen factores solubles para inducir la remodelación ósea, razón por la cual se emplea la microvibración como una terapia innovadora y prometedora, no invasiva y no farmacológica en la estimulación de la formación ósea de la superficie del hueso (AU)


Subject(s)
Humans , Osteogenesis , Vibration , Bone Remodeling , Osteocytes , Bone Resorption , Analysis of Variance , Cytokines , Culture Media , RANK Ligand
3.
Int. j. cardiovasc. sci. (Impr.) ; 35(3): 410-418, May-June 2022. graf
Article in English | LILACS | ID: biblio-1375650

ABSTRACT

Abstract An acute respiratory syndrome caused by SARS-CoV2 was declared a pandemic by the World Health Organization. Current data in the world and in Brazil show that approximately 40% of patients who died have some type of cardiac comorbidity. There are also robust reports showing an increase in IL-6 / IL-1B / TNF-alpha and the presence of lymphopenia in patients with COVID-19. Our team and others have shown that increased cytokines are the link between arrhythmias/Left ventricular dysfunction and the immune system in different diseases. In addition, it has been well demonstrated that lymphopenia can not only be a good marker, but also a factor that causes heart failure. Thus, the present review focused on the role of the immune system upon the cardiac alterations observed in the SARS-CoV2 infection. Additionally, it was well described that SARS-CoV-2 is able to infect cardiac cells. Therefore, here it will be reviewed in deep.


Subject(s)
Arrhythmias, Cardiac/complications , SARS-CoV-2/pathogenicity , COVID-19/complications , Heart Failure/etiology , Myocardium/immunology , Arrhythmias, Cardiac/physiopathology , Cytokines , Cytokines/immunology , Coronavirus/pathogenicity , Ventricular Dysfunction, Left/physiopathology , Myocytes, Cardiac/pathology , Severe Acute Respiratory Syndrome , Heart Failure/complications , Lymphopenia/complications
4.
Article in English | LILACS-Express | LILACS, CUMED | ID: biblio-1410297

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has demonstrated a similar infection pattern (with a faster rate of transmission) and clinical features compared to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). However, it is of utmost interest that acute respiratory distress syndrome (ARDS), systemic inflammatory response syndrome (SIRS) and acute lung injury (ALI) occurred in both MERS-CoV- and SARS-CoV-infected individuals, as well as Coronavirus Disease-19 (COVID-19) patients.1 Specific cytokines have been observed at the core of inflammation development and have also been found to play critical roles in facilitating the exhibition of the aforementioned clinical features. According to reports from previous studies, cytokines such as Tumor Necrosis Factor-α (TNF-α), Macrophage Inflammatory Protein-1A (MIP-1A), monocyte chemoattractant protein-1 (MCP-1), IFN-γ-Inducible Protein 10 (IP10), Granulocyte colony-stimulating factor (GSCF), Interleukin-2 (IL-2), Interleukin-7 (IL-7), Interleukin-10 (IL-10) and Interleukin-17 (IL-17) are significantly increased in COVID-19 patients, with the attributes of a cytokine storm.2 Upon infection by SARS-CoV-2, the inflammatory response plays an antiviral function, but an intense cytokine storm as a result of imbalanced response, could have a harmful effect on patients.1 Therefore, employing approaches that suppresse effectively cytokine storm is required for saving the COVID-19 patients' lives and to prevent...(AU)


Subject(s)
Humans , Male , Female , Cytokines , COVID-19/drug therapy
5.
Acta méd. costarric ; 64(1)mar. 2022.
Article in Spanish | LILACS-Express | LILACS, SaludCR | ID: biblio-1402989

ABSTRACT

Resumen Objetivo: Describir la asociación de las variantes en los genes que codifican por citocinas participantes en el proceso inflamatorio con la susceptibilidad y la gravedad clínica de las enfermedades. Métodos: Se realizó un estudio documental con revisión de literatura científica encontrada en las siguientes bases de datos: Pubmed, Science Direct, Scopus, Scielo, PLOS, Hinari, Redalyc, Dialnet, Taylor, ProQuest. Se revisaron 84 referencias relacionadas con artículos de investigación, revisiones sistemáticas y metaanálisis con los términos ''variante'', ''variante en un solo nucléotido'', ''polimorfismo de nucleótido único'', ''citocinas proinflamatorias'', ''citocinas antiinflamatorias'', ''interleucinas'', ''factor de necrosis tumoral'', ''susceptibilidad genética'', ''enfermedades'' y ''patologías''. Resultados: La evidencia señala que las variantes en un solo nucleótido se detectan principalmente en regiones promotoras de genes que codifican para citocinas reguladoras de procesos inflamatorios, como son: IL-1, IL-6, IL-8, IL-10, IL-12, IL-17, IL-18, IL-22 y el factor de necrosis tumoral. Conclusiones: La expresión y la producción diferencial de estas citocinas desempeñan un papel relevante en la patogenia y la predisposición a sufrir enfermedades, especialmente metabólicas, malignas, autoinmunes e infecciosas. Se mostró también un efecto diferencial de las variantes según las características étnicas, lo que resulta ser una herramienta eficaz en la medicina preventiva.


Abstract Aim: To describe the association of variations in cytokine genes that participate in the inflammatory process with the susceptibility and clinical severity of diseases. Methods: A documentary study was carried out with a review of the scientific literature of the database: Pubmed, Science Direct, Scopus, Scielo, PLOS, Hinari, Redalyc, Dialnet, Taylor, ProQuest. Eighty-four references were reviewed that included research articles, systematic reviews and meta-analyzes, using the terms ''Variants'', ''Single Nucleotide Variation'', ''Proinflammatory cytokines'', ''Anti-inflammatory cytokines'', ''Interleukins'', ''Tumor Necrosis Factor'', ''genetic susceptibility'', ''diseases'', pathologies''. Results: The evidence indicates that Single Nucleotide Variants are detected mainly in promoter regions of genes that code for cytokines that regulate inflammatory processes such as: IL-1, IL-6, IL-8, IL-10, IL-12, IL -17, IL-18, IL-22 and tumoral necrosis factor. Conclusions: The expression and differential production of these cytokines play a role in the pathogenesis and predisposition to diseases, especially metabolic, malignant, autoimmune, and infectious. A differential effect of variants according to ethnic characteristics is also observed, which turns out to be an effective tool to be used in preventive medicine.


Subject(s)
Cytokines/analysis , Interleukins , Lymphotoxin-alpha , Polymorphism, Single Nucleotide
6.
Arq. Asma, Alerg. Imunol ; 6(1): 84-90, jan.mar.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400109

ABSTRACT

O SARS-CoV-2 é causador da doença infecciosa COVID-19. A infecção estimula o sistema imunológico a produzir citocinas próinflamatórias. A principal citocina envolvida é a IL-6, e está ligada à gravidade da doença. Devido à associação dos altos níveis de IL-6 com a mortalidade na COVID-19, investiga-se sobre o uso de tocilizumabe (TCZ), um anticorpo monoclonal humanizado antirreceptor de IL-6 humana. O objetivo desta revisão sistemática é avaliar a eficácia do uso do TCZ em pacientes com COVID-19 grave. As buscas foram feitas através das bases de dados Science Direct e PubMed em setembro de 2021. Foram incluídos os ensaios clínicos randomizados com pacientes em um único estágio de COVID-19, casos graves e sem restrição de idade, os quais receberam o TCZ como medicação de intervenção combinado a tratamentos protocolados por cada hospital e associado a corticosteroides. A análise desses estudos demonstrou resultados significantes sobre o uso de TCZ em casos severos de COVID-19. O uso de TCZ associado a glicocorticoides levou a uma redução no índice de mortalidade e de submissão a ventilações mecânicas e a uma melhora expressiva em relação à escala "WHO-endorsed 7-point ordinal scale". Entretanto, não houve melhora relevante quanto ao uso do TCZ de maneira isolada.


SARS-CoV-2 causes the COVID-19 infectious disease that affects the respiratory tract. From the beginning of the infection, the immune system starts to produce pro-inflammatory cytokines and chemokines. The main cytokine involved is IL-6 and is linked to the severity and prognosis of the disease, as it provokes a storm of cytokines and severe inflammatory responses. Due to the association of high levels of IL-6 with severity and mortality in COVID-19, the use of Tocilizumab (TCZ), a humanized anti-human IL-6 receptor monoclonal antibody, which binds to IL receptors, is being investigated. -6 and blocks intracellular signaling reducing cytokine storm and hyperinflammatory state. The aim of this review is to assess the effectiveness of using TCZ in the treatment of patients with severe COVID-19. Searches were performed using the Science Direct and PubMed databases in May 2021. Randomized clinical trials with patients in a single stage of COVID­19, severe cases and without age restriction, who received TCZ as medication for treatment, were included. Intervention was combined with treatments protocoled by each hospital and associated with corticosteroids. The analysis of these studies showed significant results regarding the use of TCZ in severe cases of COVID-19. The use of TCZ associated with glucocorticoids led to a reduction in the rate of mortality and compliance with mechanical ventilation and a significant improvement in relation to the "WHO-endorsed 7-point ordinal scale". However, there was no evidence of relevant improvement when using TCZ alone.


Subject(s)
Humans , Antibodies, Monoclonal, Humanized , SARS-CoV-2 , COVID-19 , Patients , Respiration, Artificial , Therapeutics , Cytokines , Interleukin-6 , Adrenal Cortex Hormones , Receptors, Interleukin-6 , PubMed , Cytokine Release Syndrome , Immune System
7.
Arq. Asma, Alerg. Imunol ; 6(1): 100-107, jan.mar.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400113

ABSTRACT

A asma é o produto de processos coordenados, interligados e complexos que têm origem nos genes/epigenética, microbioma e ambiente/estilo de vida. Os medicamentos atualmente disponíveis não são capazes de interferir com a inserção da asma no organismo. A abordagem terapêutica atual envolve fármacos que visam controlar os sintomas e antagonizar parte dos efeitos de algumas das citocinas envolvidas. Dessa forma, o tratamento atual visa o controle da asma e não a sua cura. Mecanismos epigenéticos traduzem os estímulos microbiômicos e ambientais em comportamento celular alterado. Por essa razão, a identificação de marcadores epigenéticos certamente apontará novos alvos terapêuticos e, idealmente, estratégias para reverter o comportamento celular alterado no trato respiratório. Aí, sim, poderíamos dizer que a asma tem cura.


Asthma is the product of coordinated, interconnected and complex processes that originate in genes/epigenetics, microbiome, and environment/lifestyle. Currently available drugs are not able to interfere with the insertion of asthma into the body. The current therapeutic approach involves drugs that aim to control symptoms and antagonize part of the effects of some of the cytokines involved. Thus, the current treatment is aimed at controlling asthma and not curing it. Epigenetic mechanisms translate the microbiological and environmental stimuli into altered cellular behavior. For this reason, the identification of epigenetic markers will certainly point out to new therapeutic targets and, ideally, strategies to reverse the altered cellular behavior in the respiratory tract. Then, yes, we could say that asthma is curable.


Subject(s)
Humans , Asthma , Therapeutics , Epigenomics , Respiratory System , Signs and Symptoms , Pharmaceutical Preparations , Cytokines , Health Strategies , Environment , Microbiota , Life Style
8.
Rev. méd. Chile ; 150(2): 266-270, feb. 2022. ilus, tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1389636

ABSTRACT

Sepsis is one of the leading causes of death in critically ill patients with COVID-19 and blood purification therapies have a role to immunomodulate the excessive inflammatory response and improve clinical results. One of the devices designed for these therapies is the oXiris® filter, allowing to perform renal replacement therapy combined with selective adsorption of endotoxins and cytokines. We report a 55-year-old male with COVID who developed a septic shock secondary to a sepsis caused by Pseudomona aeruginosa, refractory to the usual management. A veno-venous continuous hemofiltration was started using the oXiris® filter for 48 hours. Subsequently, there was an improvement in clinical perfusion parameters and a reduction in inflammatory markers. The patient was discharged from the intensive care one month later.


Subject(s)
Humans , Male , Middle Aged , Shock, Septic/complications , Shock, Septic/therapy , Sepsis/complications , COVID-19/complications , Cytokines , Endotoxins
9.
São Paulo; s.n; s.n; 2022. 116 p. tab, graf.
Thesis in English | LILACS | ID: biblio-1378343

ABSTRACT

Stem cells are undifferentiated cells that can be distinguished from others by their ability to self-renew and to differentiate into new specific cell types. Mesenchymal stem cells (MSC) are adult stem cells that can be obtained from different sources, such as adipose tissue, bone marrow, dental pulp, and umbilical cord. They can either replicate, originating new identical cells, or differentiate into cells of mesodermal origin and from other germ layers. MSC have been studied as new tools for regenerative therapy. Although encouraging results have been demonstrated, MSC-based therapies still face a great barrier: the difficulty of isolating these cells from heterogeneous environments. MSC are currently characterized by immunolabelling through a set of multiple surface membrane markers, including CD29, CD73, CD90 and CD105, which are also expressed by other cell types. Hence, the present work aimed to identify new specific biomarkers for the characterization of human MSC using DNA aptamers produced by the SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technique. Our results showed that MSC from different origins bound to DNA candidate aptamers, that is, DNA or RNA oligonucleotides selected from random libraries that bind specifically to biological targets. Aptamer-bound MSC could be isolated by fluorescenceactivated cell sorting (FACS) procedures, enhancing the induction of differentiation into specific phenotypes (chondrocytes, osteocytes and adipocytes) when compared to the whole MSC population. Flow cytometry analyses revealed that candidate aptamers bound to 50% of the MSC population from dental pulp and did not present significant binding rates to human fibroblasts or lymphocytes, both used as negative control. Moreover, immunofluorescence images and confocal analyses revealed staining of MSC by aptamers localized in the surfacemembrane of these cells. The results also showed internal staining of human monocytes by our investigated aptamers. A non-specific control aptamer (CNTR APT) obtained from the random pool was then utilized to compare the specificity of the aptamers bound to the analyzed non-apoptotic cells, showing no staining for MSC. However, 40% of the monocytes bound to the CNTR APT. Normalized data based on the cells bound to candidate aptamers compared to those bound to the CNTR APT, revealed a 10 to 16-fold higher binding rate for MSC against 2-fold for monocytes. Despite its low specificity, monocyte-aptamer binding occurs probably due to the expression of shared markers with MSC, since monocytes are derived from hematopoietic stem cells and are important for the immune system ability to internalize/phagocyte external molecules. Given that, we performed a pull-down assay followed by mass spectrometry analysis to detect which MSC-specific protein or other target epitope not coexpressed by monocytes or the CNTR APT would bind to the candidate aptamer. Distinguishing between MSC and monocyte epitopes is important, as both cells are involved in immunomodulatory effects after MSC transplantations. ADAM17 was found to be a target of the APT10, emerging as a possible biomarker of MSC, since its involvement in the inhibition of the TGF signaling cascade, which is responsible for the differentiation of MSC. Thus, MSC with a higher stemness profile should overexpress the protein ADAM17, which presents a catalytic site with affinity to APT10. Another target of Apt 10 is VAMP3, belonging to a transmembrane protein complex that is involved in endocytosis and exocytosis processes during immune and inflammatory responses. Overall, proteins identified as targets of APT10 may be cell surface MSC biomarkers, with importance for MSC-based cell and immune therapies


Células tronco são células indiferenciadas que podem ser distinguidas de outros tipos celulares por meio da habilidade de se auto renovarem e de se diferenciarem em novos tipos celulares. Células tronco mesenquimais (MSC) são células tronco adultas encontradas em diferentes tecidos como tecido adiposo, polpa de dente e cordão umbilical. Estas células podem se autodividir em células idênticas ou se diferenciarem em células de origem mesodermal. Estas células têm sido estudadas em novas aplicações que envolvem terapia regenerativas. Embora resultados encorajadores tenham sido demonstrados, terapias que utilizam MSC ainda encontram uma grande barreira: a dificuldade no isolamento destas células a partir de um ambiente heterogêneo. MSC são caracterizadas por populações positivas em ensaios de imunomarcação para os epítopos membranares CD29, CD73, CD90 e CD105, presentes também em outros tipos celulares. Assim, o presente trabalho tem o objetivo de identificar novos biomarcadores de MSC de origem humana, utilizando aptâmeros de DNA produzidos pela técnica SELEX (Systematic Evolution of Ligands by EXponential Enrichment) como ferramenta. Nossos resultados mostraram que MSC de diferentes origens ligam-se a aptâmeros (oligonucleotídeos de DNA ou RNA que atuam como ligantes específicos de alvos moleculares) de DNA candidatos que atuam no isolamento de MSC por meio da técnica FACS de separação celular, promovendo uma maior indução de diferenciação em células específicas (condrócitos, osteócitos e adipócitos) comparada com a população total de MSC. Análises de citometria de fluxo mostraram que os aptâmeros candidatos se ligam a 50% das MSC de polpa de dente e não apresentam taxa de ligação significante para fibroblastos e linfócitos de origem humana - utilizados como controles negativo. Além domais, imagens de imunofluorescência e confocal mostraram ligação na superfície da membrana de MSC e a marcação interna de monócitos a estes aptâmeros. Portanto, um aptâmero controle (CNTR APT) foi utilizado para comparar a especificidade dos aptâmeros ligados a células viáveis, mostrando a não ligação deste aptâmero a MSC. Porém, 40% da população de monócitos ligou-se ao CNTR APT. Uma normalização baseada na comparação entre as taxas de ligação entre células ligadas com aptâmeros candidatos e o aptâmero controle gerou uma taxa de especificidade entre 10-16 vezes maior para MSC contra 2,5 vezes para os monócitos. Deste modo, embora os resultados tenham mostrado uma taxa de ligação entre monócitos e aptâmeros, as MSC ligadas aos aptâmeros candidatos possuem uma maior taxa de especificidade devido a uma maior presença de antígenos que são expressos em ambas as células. Um ensaio de Pull Down seguido de espectrometria de massas foi utilizado para a identificação de biomarcadores que se ligariam aos aptâmeros candidatos, e que não seriam co-expressos por monócitos e por antígenos ligados ao aptâmero controle. Deste modo, a proteína ADAM17 foi identificada nas amostras de APT10 ligadas às MSC. Tal proteína está relacionada à inibição de uma cascata de sinalização da família de proteínas TGF, responsável pela diferenciação de MSC. Assim, MSC com maior potencial tronco deveriam expressar ADAM17 em maior quantidade. Tal proteína apresenta um sítio catalítico que demonstra interagir com o APT10, de acordo com predição Docking entre proteína e DNA. Foi identificada também, a proteína VAMP3, que pertence a um complexo proteico transmembranar responsável pelos processos de endocitose e exocitose, e que podem ter um papel importante na liberação de citocinas e outras moléculas relacionadas às respostas imune e inflamatórias. Deste modo, o APT10 identificou proteínas importantes que devem estar relacionas com a melhora de imunoterapias que utilizam MSC


Subject(s)
Stem Cells , Biomarkers/analysis , SELEX Aptamer Technique/instrumentation , Mesenchymal Stem Cells/classification , ADAM17 Protein/pharmacology , Patient Isolation , Mass Spectrometry/methods , Staining and Labeling/methods , Transplantation/adverse effects , Umbilical Cord , DNA/agonists , Transforming Growth Factors/agonists , Cell Separation/instrumentation , Cytokines/adverse effects , Adipocytes/metabolism , Chondrocytes/classification , Scientists for Health and Research for Development , Adult Stem Cells/classification , Fibroblasts/chemistry , Flow Cytometry/instrumentation , Germ Layers , Antigens/adverse effects
10.
Braz. j. biol ; 82: e231134, 2022. tab, graf
Article in English | LILACS | ID: biblio-1249257

ABSTRACT

Abstract Chronic obstructive pulmonary disease (COPD) was estimated to be the third cause of global mortality by 2020. Acute exacerbation COPD (AECOPD) is a sudden worsening of COPD symptoms and could be due to virus/bacterial infections and air pollution. Increased expression of inflammatory markers in patients with AECOPD is associated with viral infection. This study aimed to detect different viruses and analyze the expression of various inflammatory markers associated with AECOPD patients. Three hundred and forty-seven patients diagnosed with COPD according to GOLD criteria were included in this study. Swab samples and blood were collected for the detection of viruses by RT-PCR and expression of inflammatory markers, respectively. Of the swab samples, 113 (32.6%) of samples were positive for virus detection. Of these, HRV (39.8%) was the predominant virus detected followed by FluB (27.4%) and FluA (22.1%). The presence of HRV was significantly higher (p=0.044) among the other detected viruses. When compared to healthy controls the expression levels of TNF-α, IL-6 and IL-8 were significantly higher (p<0.05) in virus-positive patients. The IL-6 and IL-8 were the next predominantly expressed in markers among the samples. The higher expression rate of IL-8 was significantly (p<0.05) associated with patients having COPD GOLD III severity level and smoking history. Although HRV was the predominant virus detected the combined prevalence of Influenza A and B surpassing the rate of HRV. The high-level expression of well known inflammatory markers of AECOPD, TNF-α, IL-6 and IL-8 indicates a chronic severe illness. These markers play an important role and could be used as a marker for determining the severity of AECOPD.


Resumo Estima-se que a doença pulmonar obstrutiva crônica (DPOC) seja a terceira causa de mortalidade global em 2020. A exacerbação aguda DPOC (AECOPD) é um agravamento súbito dos sintomas da DPOC e pode ser devido a infecções por vírus/bactérias e poluição do ar. O aumento da expressão de marcadores inflamatórios em pacientes com AECOPD está associado à infecção viral. Este estudo teve como objetivo detectar diferentes vírus e analisar a expressão de vários marcadores inflamatórios associados a pacientes com AECOPD. Trezentos e quarenta e sete pacientes com diagnóstico de DPOC de acordo com os critérios GOLD foram incluídos neste estudo. Amostras de swab e sangue foram coletadas para detecção de vírus por RT-PCR e expressão de marcadores inflamatórios, respectivamente. Das amostras de esfregaço, 113 (32,6%) amostras foram positivas para detecção de vírus. Nestas, o HRV (39,8%) foi o vírus predominante detectado, seguido do FluB (27,4%) e do FluA (22,1%). A presença de VFC foi significativamente maior (p = 0,044) entre os demais vírus detectados. Quando comparados a controles saudáveis, os níveis de expressão de TNF-α, IL-6 e IL-8 foram significativamente maiores (p <0,05) em pacientes com vírus positivo. A IL-6 e a IL-8 foram as próximas predominantemente expressas em marcadores entre as amostras. A maior taxa de expressão de IL-8 foi significativamente (p <0,05) associada a pacientes com grau de gravidade GOLD III da DPOC e história de tabagismo. Embora o HRV tenha sido o vírus predominante, a prevalência combinada de Influenza A e B ultrapassou a taxa de HRV. O alto nível de expressão de marcadores inflamatórios bem conhecidos de AECOPD, TNF-α, IL-6 e IL-8 indica uma doença crônica grave. Esses marcadores desempenham um papel importante e podem ser usados como um marcador para determinar a gravidade da AECOPD.


Subject(s)
Humans , Viruses , Pulmonary Disease, Chronic Obstructive/diagnosis , China/epidemiology , Cytokines/genetics , Mongolia
11.
Article in English | LILACS, BBO | ID: biblio-1365223

ABSTRACT

Abstract Objective: To compare the Oncostatin M (OSM) concentrations in tissues of patients with chronic periodontitis with and without diabetes. Material and Methods: Sixty-four subjects visiting the dental outpatient department were categorized as "healthy" (Group 1), "periodontitis" (Group 2), and "diabetes with periodontitis" (Group 3) groups. The clinical oral examination included assessment of plaque, gingivitis, probing depth, clinical attachment level. Blood glucose was assessed for group 3 patients. OSM concentration in the tissues was assessed using ELISA in all groups. Results: The mean OSM was 0.02 ± 0.04 pg/mg in the healthy group, 0.12 ± 0.09 pg/mg in the chronic periodontitis group and 0.13 ± 0.10 pg/mg in the diabetes-periodontitis group. A significantly higher mean OSM was seen in Group 2 and Group 3 than Group 1. The amount of OSM positively correlated with probing depth and clinical attachment level. Conclusion: Periodontal disease causes a rise in Oncostatin M, independent of the diabetic status. Expression of OSM in the gingival tissues can serve as an inflammatory marker.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Dental Plaque Index , Cytokines , Diabetes Mellitus , Oncostatin M/analysis , Chronic Periodontitis/pathology , Periodontal Diseases , Blood Glucose , Chi-Square Distribution , Cross-Sectional Studies/methods , Analysis of Variance , Statistics, Nonparametric , Diagnosis, Oral , Gingiva , India/epidemiology , Inflammation
12.
São José dos Campos; s.n; 2022. 78 p. tab, ilus.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1380340

ABSTRACT

O objetivo deste estudo foi avaliar o perfil microbiológico e identificar padrões de agregação bacteriana, avaliar a associação desses padrões com os níveis de mediadores inflamatórios, MMPs e sinais e sintomas clínicos e ainda correlacionar os mediadores inflamatórios entre si e com os sinais e sintomas clínicos em dentes com infecção endodôntica primária e periodontite apical (PA). Para isso, 40 dentes uniradiculares, de pacientes com infecção endodôntica primária e PA, foram submetidos à avaliação clínica, com registro de sinais e sintomas, e tomográfica através do cálculo de volumetria das lesões periapicais com o software ITK Snap. Em seguida os dentes foram submetidos ao tratamento endodôntico. Logo após a abertura coronária, amostras foram coletadas de cada canal radicular utilizando cones de papel (S1) e submetidas ao método Checkerboard DNA-DNA hybridization para investigação de espécies bacterianas presentes. Foi realizado o preparo biomecânico (PBM) e em seguida o fluído intersticial da PA foi coletado (SF1) para a quantificação dos mediadores inflamatórios (IL1-ß, IL-6, TNF-α, IL-10, MMPs -2 e -9) através do ensaio multiplex e a quantificação de RvD2 através de ensaio imunoenzimático ELISA. Para a análise de correlação o teste de correlação de Spearman foi utilizado. A análise fatorial foi usada para identificar padrões de agregação bacteriana e regressão linear foi realizada para associar os escores fatoriais, mediadores e características clínicas dos pacientes (P=0,05). Correlação positiva foi encontrada entre MMP-2, -9, IL-10, IL-1ß, IL-6 e TNF-α, e entre RvD2, MMP-9, IL-10, IL-1ß, IL-6 e TNF-α (P<0,05), e correlação negativa foi encontrada entre IL-1ß e sensibilidade a percussão (P<0,05). A análise microbiológica revelou presença de DNA bacteriano em 100% das amostras analisadas com presença de pelo menos 2 das 40 espécies bacterianas investigadas (média = 24,62) por canal. As espécies mais frequentemente detectadas foram P. gingivalis, E. nodatum, F. nucleatum spp. vicentii, S. mitis, L. bucallis e A. actinomycetemcomitans. Das 6 espécies mais detectadas, 4 delas eram gram negativas, destacando o predomínio de gram-negativos das infecções endodônticas primárias com PA. A análise fatorial determinou 2 padrões de associação bacteriana e os resultados de regressão para o fator 1 revelaram uma associação com aumento de dor a percussão (coeficiente (coef) ß=0,788) e redução de dor a palpação (coefß=-0,753) e exsudato (coefß=- 0,479). Níveis mais altos de exsudato e menores de dor a palpação foram associados a bactérias do fator 2 (coefß=0,460 e -0,546, respectivamente). Concluímos que os mediadores inflamatórios formam uma rede inter-relacionada e que as periodontites apicais assintomáticas e sintomáticas tem uma etiologia bacteriana heterogênea e com combinações de espécies diferentes (AU)


The aim of this study was to evaluate the microbiological profile and identify patterns of bacterial aggregation, evaluate the association of these patterns with the levels of inflammatory mediators, MMPs and clinical signs and symptoms, and also correlate the inflammatory mediators with each other and with the clinical signs and symptoms in teeth with primary endodontic infection and apical periodontitis (AP). For this, 40 single-rooted teeth, from patients with primary endodontic infection and PA, were submitted to clinical evaluation, with registration of signs and symptoms, and tomography through the calculation of volumetry of periapical lesions with the ITK Snap software. Then the teeth were submitted to endodontic treatment. Immediately after the coronal opening, samples were collected from each root canal using paper cones (S1) and submitted to the Checkerboard DNA-DNA hybridization method to investigate bacterial species present. Biomechanical preparation (BMP) was performed and then the AP interstitial fluid was collected (SF1) for the quantification of inflammatory mediators (IL1-ß, IL-6, TNF-α, IL-10, MMPs -2 and -9) by the multiplex assay and the quantification of RvD2 by enzyme immunoassay ELISA. For correlation analysis, Spearman's correlation test was used. Factor analysis was used to identify bacterial aggregation patterns and linear regression was performed to associate factor scores, mediators and patients' clinical characteristics (P=0.05). Positive correlation was found between MMP-2, -9, IL-10, IL-1ß, IL-6 and TNF-α, and between RvD2, MMP-9, IL-10, IL-1ß, IL-6 and TNF- α (P<0.05), and a negative correlation was found between IL-1ß and sensitivity to percussion (P<0.05). The microbiological analysis revealed the presence of bacterial DNA in 100% of the samples analyzed with the presence of at least 2 of the 40 bacterial species investigated (mean = 24.62) per root canal. The most frequently detected species were P. gingivalis, E. nodatum, F. nucleatum spp. vicentii, S. mitis, L. buccallis and A. actinomycetemcomitans. Of the 6 most detected species, 4 of them were gram negative, highlighting the predominance of gram-negative primary endodontic infections with AP. Factor analysis determined 2 patterns of bacterial association and regression results for factor 1 revealed an association with increased pain on percussion (coefficient (coef) ß=0.788) and reduced pain on palpation (coefß=-0.753) and exudate (coefß=-0.479). Higher levels of exudate and lower levels of pain on palpation were associated with factor 2 bacteria (coefß=0.460 and -0.546, respectively). We conclude that inflammatory mediators form an interrelated network and that asymptomatic and symptomatic apical periodontitis has a heterogeneous bacterial etiology and combinations of different species (AU)


Subject(s)
Humans , Periapical Periodontitis , Bacteria , Cytokines , Matrix Metalloproteinases , Cone-Beam Computed Tomography
13.
Article in Chinese | WPRIM | ID: wpr-936370

ABSTRACT

OBJECTIVE@#To study the cytokine patterns in patients with rheumatoid arthritis (RA) and healthy individuals and identify candidate serum biomarkers for clinical diagnosis of RA.@*METHODS@#This study was conducted among 59 patients diagnosed with RA in our hospital from 2015 to 2019 with 46 age- and gender-matched healthy subjects who received regular physical examinations in our hospital as the control group. Serological autoimmune profiles of 5 RA patients and 5 healthy control subjects were obtained from human cytokine microarrays. We selected 4 differentially expressed cytokines (LIMPII, ROBO3, Periostin and IGFBP-4) and 2 soluble cytokine receptors of interest (2B4 and Tie-2) and examined their serum levels using enzyme-linked immunosorbent assay in 54 RA patients and 41 healthy control subjects. Spearman correlation test was performed to assess the correlation of serum cytokine and soluble receptor expression levels with the clinical features including rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score (DAS28) and health assessment questionnaire (HAQ). Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic capability of these cytokines.@*RESULTS@#We identified 6 dysregulated cytokines and soluble receptors (2B4, LIMPII, Tie-2, ROBO3, periostin and IGFBP-4) in RA patients (P < 0.01). The serum levels of LIMPII, ROBO3 and periostin were significantly correlated with the disease activity indicators including RF (P < 0.001), CRP (P < 0.001), DAS28 (P < 0.001) and HAQ (P < 0.001) in RA patients. Among the 6 candidate cytokines, 2B4 showed the largest area under the curve (AUC) of 0.861 for RA diagnosis (P < 0.001), followed then by LIMPII, ROBO3, periostin, Tie-2 and IGFBP-4.@*CONCLUSION@#Serum levels of LIMPII, ROBO3 and periostin can be indicative of the disease activity of RA, and serum 2B4, LIMPII, periostin, ROBO3, IGFBP-4 and Tie-2 levels may serve as biomarkers for the diagnosis of RA.


Subject(s)
Arthritis, Rheumatoid/diagnosis , Biomarkers , C-Reactive Protein , Cytokines , Humans , Insulin-Like Growth Factor Binding Protein 4 , Protein Array Analysis , Receptors, Cell Surface
14.
Article in Chinese | WPRIM | ID: wpr-936230

ABSTRACT

Objective: Transcriptome sequencing and bioinformatics analysis were performed on the gene expression of nasal epithelial cells in patients with seasonal allergic rhinitis (AR) and perennial AR, so as to obtain the differences in the gene expression of nasal epithelial cells between seasonal AR and perennial AR. Methods: The human nasal epithelial cell line(HNEpC) was cultured in vitro, treated with 100 μg/ml mugwort or house dust mite (HDM) extracts for 24 hours. Total cell RNA was extracted, and quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression of cytokines, including IL-6, IL-8, IL-33 and thymic stromal lymphopoietin (TSLP). From November 2019 to November 2020, 3 seasonal AR patients, 3 perennial AR patients, and 3 healthy controls who attended the Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University were analyzed. The patients' primary nasal epithelial cells were cultured in vitro, treated with corresponding allergens for 24 hours. Total RNA was extracted for transcriptome sequencing, and the sequencing results were analyzed by bioinformatics. Results: The qPCR results showed that the cytokines IL-6, IL-8, IL-33 and TSLP of HNEpC treated with mugworts extracts and HDM extracts had the same trend of change. After the nasal epithelial cells from patients with seasonal AR and perennial AR were treated with corresponding allergens, there were differences in biological processes and signal pathways between those and control. Gene ontology (GO) enrichment analysis showed that the differentially expressed genes (DEG) in AR patients allergic to mugwort were mainly enriched in the oxidation-reduction process, the negative regulation of apoptosis process, and the cell adhesion; the DEG in AR patients allergic to HDM were mainly enriched in cell adhesion, the negative regulation of cell proliferation and the response to drug. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway showed that the DEG of AR patients allergic to mugwort were significantly enriched in arachidonic acid metabolism, p53 signaling pathway and transforming growth factor β (TGF-β) signaling pathway, while the DEG of AR patients allergic to HDM were mainly enriched in cells cycle, Fanconi anemia pathway and DNA replication. Gene Set Enrichment Analysis (GSEA) showed that the inflammatory response, TNF-α/NF-κB signaling pathway and IL-2/STAT5 signaling pathway were significantly up-regulated in AR patients allergic to mugwort, indicating the promotion of inflammatory response; and AR patients allergic to HDM had significant down-regulation of G2M, E2F, and MYC, indicating the inhibition of cell proliferation. The protein-protein interaction network showed that TNF and CDK1 were the most interacting proteins in mugwort and HDM allergic AR patients, respectively. Conclusion: Seasonal AR and perennial AR may affect the different biological processes and signal pathways of nasal epithelial cells, leading to differences in the occurrence and development of AR.


Subject(s)
Allergens , Animals , Computational Biology , Cytokines/metabolism , Epithelial Cells/metabolism , Gene Expression , Humans , Interleukin-33/metabolism , Interleukin-6/metabolism , Interleukin-8 , Nasal Mucosa/metabolism , Plant Extracts/metabolism , Pyroglyphidae , RNA/metabolism , Rhinitis, Allergic/metabolism , Rhinitis, Allergic, Perennial , Rhinitis, Allergic, Seasonal , Seasons
15.
Journal of Integrative Medicine ; (12): 274-280, 2022.
Article in English | WPRIM | ID: wpr-929222

ABSTRACT

OBJECTIVE@#Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI.@*METHODS@#A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function.@*RESULTS@#The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization.@*CONCLUSION@#This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.


Subject(s)
Abietanes , Acute Lung Injury/drug therapy , Animals , Cytokine Release Syndrome , Cytokines , Inflammation/drug therapy , Lipopolysaccharides/toxicity , Macrophage Activation , Macrophages , Mice , Triacetoneamine-N-Oxyl/pharmacology
16.
Article in English | WPRIM | ID: wpr-929050

ABSTRACT

The onset of inflammatory bowel disease (IBD) involves many factors, including environmental parameters, microorganisms, and the immune system. Although research on IBD continues to expand, the specific pathogenesis mechanism is still unclear. Protein modification refers to chemical modification after protein biosynthesis, also known as post-translational modification (PTM), which causes changes in the properties and functions of proteins. Since proteins can be modified in different ways, such as acetylation, methylation, and phosphorylation, the functions of proteins in different modified states will also be different. Transitions between different states of protein or changes in modification sites can regulate protein properties and functions. Such modifications like neddylation, sumoylation, glycosylation, and acetylation can activate or inhibit various signaling pathways (e.g., nuclear factor-‍κB (NF-‍κB), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT)) by changing the intestinal flora, regulating immune cells, modulating the release of cytokines such as interleukin-1β (IL-‍‍1β), tumor necrosis factor-α (TNF‍-‍α), and interferon-‍γ (IFN-‍γ), and ultimately leading to the maintenance of the stability of the intestinal epithelial barrier. In this review, we focus on the current understanding of PTM and describe its regulatory role in the pathogenesis of IBD.


Subject(s)
Cytokines/genetics , Humans , Inflammatory Bowel Diseases , NF-kappa B/metabolism , Protein Processing, Post-Translational , Tumor Necrosis Factor-alpha/metabolism
17.
Article in English | WPRIM | ID: wpr-928963

ABSTRACT

OBJECTIVE@#To evaluate the effect of Shilajit, a medicine of Ayurveda, on the serum changes in cytokines and adipokines caused by non-alcoholic fatty liver disease (NAFLD).@*METHODS@#After establishing fatty liver models by feeding a high-fat diet (HFD) for 12 weeks, 35 Wistar male rats were randomly divided into 5 groups, including control (standard diet), Veh (HFD + vehicle), high-dose Shilajit [H-Sh, HFD + 250 mg/(kg·d) Shilajit], low-dose Shilajit [L-Sh, HFD + 150 mg/(kg·d) Shilajit], and pioglitazone [HFD + 10 mg/(kg·d) pioglitazone] groups, 7 rats in each group. After 2-week of gavage administration, serum levels of glucose, insulin, interleukin 1beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), adiponectin, and resistin were measured, and insulin resistance index (HOMA-IR) was calculated.@*RESULTS@#After NAFLD induction, the serum level of IL-10 significantly increased and serum IL-1β, TNF-α levels significantly decreased by injection of both doses of Shilajit and pioglitazone (P<0.05). Increases in serum glucose level and homeostasis model of HOMA-IR were reduced by L-Sh and H-Sh treatment in NAFLD rats (P<0.05). Both doses of Shilajit increased adiponectin and decreased serum resistin levels (P<0.05).@*CONCLUSION@#The probable protective role of Shilajit in NAFLD model rats may be via modulating the serum levels of IL-1β, TNF-α, IL-10, adipokine and resistin, and reducing of HOMA-IR.


Subject(s)
Adiponectin , Animals , Cytokines , Diet, High-Fat , Glucose , Insulin Resistance , Interleukin-10 , Liver , Male , Minerals , Non-alcoholic Fatty Liver Disease/pathology , Pioglitazone/therapeutic use , Rats , Rats, Wistar , Resins, Plant , Resistin/therapeutic use , Tumor Necrosis Factor-alpha
18.
Article in Chinese | WPRIM | ID: wpr-941010

ABSTRACT

OBJECTIVE@#To evaluate the protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae (Ts-MES) on sepsis-induced myocardial injury in mice.@*METHODS@#Eighty male BALB/C mice were randomized equally into sham-operated group, myocardial injury group, Ts-MES treatment group and dexamethasone treatment group. In the latter 3 groups, sepsis-induced myocardial injury models were established by cecal ligation and perforation; the sham operation was performed by exposure of the cecum without ligation or perforation. Forty minutes after the operation, the mice were given intraperitoneal injections 150 μL PBS, 20 μg TS-MES or 0.3 mg/kg dexamethasone as indicated. At 12 h after the operation, 6 mice were randomly selected from each group for echocardiography, and 8 mice were used for observing the survival rate within 72 h. The remaining 6 mice were examined for myocardial pathologies with HE staining and serum levels of NTPro-BNP and cTnI with ELISA; the expressions of TNF-α, IL-6, IL-10 and TGF-β in the serum and myocardial tissue were detected using ELISA and qRT-PCR.@*RESULTS@#Compared with the sham-operated mice, the septic mice showed significantly decreased cardiac function indexes (LVEF, LVFS, and E/A) with lowered survival rate within 72 h (P < 0.001) and significantly higher myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.01). Treatment with TS-MES significantly improved the cardiac function and 72-h survival rate (P < 0.05) and lowered the myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.05) in the septic mice. Compared with the sham-operated mice, the septic mice had obviously increased TNF-α and IL-6 levels in the serum and myocardial tissue (P < 0.001), which were significantly lowered by treatment with TS-MES (P < 0.05). TS-MES and dexamethasone both increased the levels of IL-10 and TGF-β in the septic mice, but the changes were significant only in TS-MES-treated mice (P < 0.05).@*CONCLUSION@#Ts-MES are capable of protecting against myocardial injury in septic mice by reducing the production of pro-inflammatory cytokines and enhancing the levels of regulatory cytokines.


Subject(s)
Animals , Cytokines , Dexamethasone , Heart Injuries , Interleukin-10 , Interleukin-6 , Larva , Male , Mice , Mice, Inbred BALB C , Myocardium , Sepsis , Transforming Growth Factor beta , Trichinella spiralis , Tumor Necrosis Factor-alpha
19.
Article in English | WPRIM | ID: wpr-939910

ABSTRACT

Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis. Hence, regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis. However, the underlying mechanism is unclear. Dendrobium nobile (Shihu) exhibits anti-inflammatory and immune activities. Hence, in this study, we investigated the mechanism via which Shihu may improve allergic rhinitis. Mouse models of allergic rhinitis with intestinal flora dysbiosis (Model-D, antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy) and normal intestinal flora with allergic rhinitis (Model-N, ovalbumin-induced allergy) were established. The effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed. Allergic symptoms, infiltration of hematoxylin and eosin in the lungs and nose, and the release of various factors [interleukin (IL)-2, IL-4, IFN-γ, IL-6, IL-10, and IL-17] in the lungs were evaluated. The results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis. However, treatment with the Shihu extract effectively reversed these symptoms. Besides, the Shihu extract inhibited the PI3K/AKT/mTOR pathway and increased the level of Forkhead box protein in the lungs. Additionally, the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved regulator T cell differentiation. Furthermore, in the Model-D group, the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora. Screening was performed to determine which intestinal flora was positively correlated with Treg differentiation using Spearman's correlation analysis. In conclusion, we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using Traditional Chinese Medicine to improve allergic rhinitis.


Subject(s)
Animals , Cytokines/metabolism , Dendrobium , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Dysbiosis/drug therapy , Gastrointestinal Microbiome , Inflammation/drug therapy , Mice , Mice, Inbred BALB C , Ovalbumin , Phosphatidylinositol 3-Kinases , Pneumonia , Rhinitis, Allergic/metabolism
20.
Journal of Integrative Medicine ; (12): 453-462, 2022.
Article in English | WPRIM | ID: wpr-939897

ABSTRACT

OBJECTIVE@#Rheumatoid arthritis (RA) progression is associated with the balance of T-regulatory (Treg) and T-helper 17 (Th17) cells, while the role of microRNAs (miRs) in regulating Treg/Th17 cell balance has not been clarified. This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3 (SOCS3) axis in the RA mouse model.@*METHODS@#A mouse model of collagen-induced arthritis (CIA) was established in male DBA/1J mice. Twenty-two days after CIA induction, the mice received daily treatment with moxibustion for 12 times. Pathological scores were assessed according to the levels of synovial hyperplasia. The expression levels of cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay. The cluster of differentiation 4 (CD4+) splenocytes was analyzed by fluorescence-activated cell sorting. The expression levels of RA-related miRs and target genes were subsequently detected, and the target of miR-221 was confirmed by the dual-luciferase reporter assay.@*RESULTS@#It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1β, IL-6, TNF-α, IFN-γ and IL-17, while upregulated the expression level of IL-10. The Treg/Th17 cell balance was regulated by moxibustion treatment. The expression level of miR-221 was suppressed by moxibustion treatment. Furthermore, SOCS3 was found as the direct target of miR-221, which mediated the function of moxibustion by regulating the Treg/Th17 cell balance.@*CONCLUSION@#Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.


Subject(s)
Animals , Arthritis, Experimental/therapy , Arthritis, Rheumatoid/therapy , Cytokines , Disease Models, Animal , Interleukin-10 , Interleukin-17 , Interleukin-6 , Male , Mice , Mice, Inbred DBA , MicroRNAs/genetics , Moxibustion , T-Lymphocytes, Regulatory , Th17 Cells/pathology , Tumor Necrosis Factor-alpha
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