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Influenza A virus (IAV) infection while primarily affects the lungs, it is often associated with cardiovascular complications. However, the mechanisms underlying this association are not fully understood. Here, we investigated the potential role of FBXL19, a member of the Skp1-Cullin-F-box family of E3 ubiquitin ligase, in IAV-induced cardiac inflammation. We demonstrated that FBXL19 overexpression in endothelial cells (ECs) reduced viral titers and IAV matrix protein 1 (M1) levels, while increasing antiviral genes expression, including interferon (IFN)-α, ß, γ and RANTES in the cardiac tissue of IAV-infected mice. Moreover, EC-specific overexpression of FBXL19 attenuated the IAV infection-reduced interferon regulatory factor 3 (IRF3) level without altering its mRNA level, and suppressed cardiac inflammation. Furthermore, IAV infection triggered cellular senescence programs in the heart as indicated by the upregulation of p16 and p21 mRNA levels, and the downregulation of lamin B1 levels, which were partially reversed by FBXL19 overexpression in ECs. Our findings indicate that EC-specific overexpression of FBXL19 protects against IAV-induced cardiac damage by enhancing interferon-mediated antiviral signaling, reducing cardiac inflammation, and suppressing cellular senescence programs.
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INTRODUCTION: This study aimed to evaluate whether the addition of a hemoadsorption (HA) cartridge, HA-380, in the cardiopulmonary bypass (CPB) circuit in acute type A aortic dissection (ATAAD) surgery reduced inflammatory cytokine levels and decreased postoperative complications. METHODS: A retrospective observational cohort study was conducted between March 1, 2021, and February 28, 2022. Patients with ATAAD undergoing emergent total arch replacement surgery were divided into the control (CON) and HA groups on the basis of the addition of the HA-380 cartridge in the CPB circuit. RESULTS: Overall, 121 patients met the eligibility criteria; 2 patients in each group who died within the first postoperative week were excluded. Further, 57 and 60 patients in the CON and HA groups, respectively, were included in the pooled analysis. The major perioperative data, baseline values of interleukin-6 (IL-6) and C-reactive protein, and therapeutic interventions were similar in the two groups (all, p > 0.05). The serum IL-6 levels increased more rapidly in the CON group than those in the HA group postoperatively (205.73 ± 174.72 vs. 146.13 ± 64.15 pg/mL, p = 0.020). The HA group had a lower incidence of postoperative acute kidney injury (AKI) and severe acute respiratory distress syndrome than the CON group (25.4 vs. 44.6%, p = 0.032 and 18.3 vs. 35.1%, p = 0.040, respectively). Logistic regression analyses showed that HA may be a protective factor against postoperative AKI. The incidence of bleeding, delirium, and stroke as well as the lengths of intensive care unit and hospital stay in both groups were similar (all, p > 0.05). CONCLUSIONS: The use of HA-380 in the CPB circuit may attenuate inflammatory response and reduce major complications following ATAAD surgery. HA may be associated with lower rate of postoperative AKI.
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Lesión Renal Aguda , Disección Aórtica , Humanos , Estudios Retrospectivos , Interleucina-6 , Disección Aórtica/cirugía , Citocinas , Complicaciones Posoperatorias/terapia , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Factores de RiesgoRESUMEN
BACKGROUND: In the evolutionary study of gene families, exploring the duplication mechanisms of gene families helps researchers understand their evolutionary history. The tubby-like protein (TLP) family is essential for growth and development in plants and animals. Much research has been done on its function; however, limited information is available with regard to the evolution of the TLP gene family. Herein, we systematically investigated the evolution of TLP genes in seven representative Poaceae lineages. RESULTS: Our research showed that the evolution of TLP genes was influenced not only by whole-genome duplication (WGD) and dispersed duplication (DSD) but also by transposed duplication (TRD), which has been neglected in previous research. For TLP family size, we found an evolutionary pattern of progressive shrinking in the grass family. Furthermore, the evolution of the TLP gene family was at least affected by evolutionary driving forces such as duplication, purifying selection, and base mutations. CONCLUSIONS: This study presents the first comprehensive evolutionary analysis of the TLP gene family in grasses. We demonstrated that the TLP gene family is also influenced by a transposed duplication mechanism. Several new insights into the evolution of the TLP gene family are presented. This work provides a good reference for studying gene evolution and the origin of duplication.
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Duplicación de Gen , Poaceae , Evolución Molecular , Genoma de Planta , Filogenia , Poaceae/genéticaRESUMEN
Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel anti-inflammatory and proresolving lipid mediator biosynthesized from docosahexaenoic acid. Excessive activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and consequent pyroptosis are involved in diverse inflammatory diseases. However, how PCTR1 affects NLRP3 inflammasome activation and pyroptosis are still unclear. Here, we demonstrated that PCTR1 inhibited NLRP3 inflammasome activation and pyroptosis. These results show that PCTR1 dose-dependently inhibited gasdermin D cleavage in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin stimulation. Additionally, PCTR1 treatment after LPS priming inhibited caspase-1 activation and subsequent mature interleukin-1ß release independent of the nuclear factor-kappa B pathway. PCTR1 exerted its inhibitory effects by blocking NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC) interaction and ASC oligomerization, thereby restricting NLRP3 inflammasome assembly. However, the inhibitory effect of PCTR1 could be reversed by KH7 and H89, which are the inhibitors of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway. Moreover, PCTR1 treatment alleviated lung tissue damage and improved mouse survival in LPS-induced sepsis. Our study unveils the molecular mechanism of negative regulation of NLRP3 inflammasome activation and pyroptosis by a novel lipid mediator and suggests that PCTR1 may serve as a potential treatment option for NLRP3-inflammasome driven diseases.
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Inflamasomas , Sepsis , Ratones , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , Antígenos CD59/metabolismo , Antígenos CD59/farmacología , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Interleucina-1beta/metabolismo , Caspasa 1/metabolismoRESUMEN
BACKGROUND: When researchers perform gene family analysis, they often analyze the structural characteristics of the gene, such as the distribution of introns and exons. At the same time, characteristic structural analysis of amino acid sequence is also essential, for example, motif and domain features. Researchers often integrate these analyses into one image to dig out more information, but the tools responsible for this integration are lacking. RESULTS: Here, we developed a tool (CFVisual) for drawing gene structure and protein architecture. CFVisual can draw the phylogenetic tree, gene structure, and protein architecture in one picture, and has rich interactive capabilities, which can meet the work needs of researchers. Furthermore, it also supports arbitrary stitching of the above analysis images. It has become a useful helper in gene family analysis. The CFVisual package was implemented in Python and is freely available from https://github.com/ChenHuilong1223/CFVisual/ . CONCLUSION: CFVisual has been used by some researchers and cited by some articles. In the future, CFVisual will continue to serve as a good helper for researchers in the study of gene structure and protein architecture.
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Proteínas , Programas Informáticos , Secuencia de Aminoácidos , Intrones , Filogenia , Proteínas/genéticaRESUMEN
BACKGROUND: Follow-up study of coronavirus disease 2019 (COVID-19) survivors has rarely been reported. We aimed to investigate longitudinal changes in the characteristics of COVID-19 survivors after discharge. METHODS: A total of 594 COVID-19 survivors discharged from Tongji Hospital in Wuhan from February 10 to April 30, 2020 were included and followed up until May 17, 2021. Laboratory and radiological findings, pulmonary function tests, electrocardiogram, symptoms and signs were analyzed. RESULTS: 257 (51.2%) patients had at least one symptom at 3 months post-discharge, which decreased to 169 (40.0%) and 138 (28.4%) at 6-month and 12-month visit respectively. During follow-up period, insomnia, chest tightness, and fatigue were the most prevalent symptoms. Most laboratory parameters returned to normal, whereas increased incidence of abnormal liver and renal function and cardiovascular injury was evidenced after discharge. Fibrous stripes (213; 42.4%), pleural thickening and adhesions (188; 37.5%) and enlarged lymph nodes (120; 23.9%) were the most common radiographical findings at 3 months post-discharge. The abnormalities of pulmonary function included obstructive, restrictive, and mixed, which were 5.5%, 4.0%, 0.9% at 6 months post, and 1.9%, 4.7%, 0.2% at 12 months. Electrocardiogram abnormalities occurred in 256 (51.0%) patients at 3 months post-discharge, including arrhythmia, ST-T change and conduction block, which increased to 258 (61.1%) cases at 6-month visit and were maintained at high frequency (242;49.8%) at 12-month visit. CONCLUSIONS: Physiological, laboratory, radiological, or electrocardiogram abnormalities, particularly those related to renal, cardiovascular, and liver functions are common in patients who recovered from coronavirus disease 2019 (COVID-19) up to 12 months post-discharge.
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COVID-19 , Cuidados Posteriores , China/epidemiología , Estudios de Seguimiento , Hospitales , Humanos , Alta del Paciente , Estudios Prospectivos , SARS-CoV-2RESUMEN
PURPOSE: We aimed to estimate the burden of UTIs by age, sex, and socioeconomic status in 204 countries and territories from 1990 to 2019. METHODS: We used data from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to analyse the incidence, mortality, and disability-adjusted life-years (DALYs) due to UTIs at the global, regional, and national levels. Estimates are presented as numbers and age-standardised or age-specific rates per 100,000 population, with 95% uncertainty intervals (UIs). We further explored the associations between the incidence, mortality, DALYs, and socio-demographic index (SDI) as a proxy for the development status of regions and countries. RESULTS: In 2019, more than 404.6 million (95% UI 359.4-446.5) individuals had UTIs globally and nearly 236,786 people (198,433-259,034) died of UTIs, contributing to 5.2 million (4.5-5.7) DALYs. The age-standardised incidence rate increased from 4715.0 (4174.2-5220.6) per 100,000 population in 1990 to 5229.3 (4645.3-5771.2) per 100,000 population in 2019. At the GBD regional level, the highest age-standardised incidence rate in 2019 occurred in Tropical Latin America (13,852.9 [12,135.6-15,480.3] per 100,000 population). At the national level, Ecuador had the highest age-standardised incidence rate (15,511.3 [13,685.0-17,375.6] per 100,000 population). The age-standardised death rates were highest in Barbados (19.5 [13.7-23.5] per 100,000 population). In addition, age-standardised incidence, death, and DALY rates generally increased across the SDI. CONCLUSIONS: Our study results suggest a globally rising trend of UTI burden between 1990 and 2019.
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Carga Global de Enfermedades , Infecciones Urinarias , Salud Global , Humanos , Incidencia , Años de Vida Ajustados por Calidad de Vida , Factores de Riesgo , Infecciones Urinarias/epidemiologíaRESUMEN
BACKGROUND: Maternal sepsis and other maternal infections (MSMI) have considerable impacts on women's and neonatal health, but data on the global burden and trends of MSMI are limited. Comprehensive knowledge of the burden and trend patterns of MSMI is important to allocate resources, facilitate the establishment of tailored prevention strategies and implement effective clinical treatment measures. METHODS: Based on data from the Global Burden of Disease database, we analysed the global burden of MSMI by the incidence, death, disability-adjusted life year (DALY) and maternal mortality ratio (MMR) in the last 30 years. Then, the trends of MSMI were assessed by the estimated annual percentage change (EAPC) of MMR as well as the age-standardized rate (ASR) of incidence, death and DALY. Moreover, we determined the effect of sociodemographic index (SDI) on MSMI epidemiological parameters. RESULTS: Although incident cases almost stabilized from 1990 to 2015, the ASR of incidence, death, DALY and MMR steadily decreased globally from 1990 to 2019. The burden of MSMI was the highest in the low SDI region with the fastest downward trends. MSMI is still one of the most important causes of maternal death in the developed world. Substantial diversity of disease burden and trends occurred in different regions and individual countries, most of which had reduced burden and downward trends. The MMR and ASR were negatively correlated with corresponding SDI value in 2019 in 204 countries/territories and 21 regions. CONCLUSION: These findings highlight significant improvement in MSMI care in the past three decades, particularly in the low and low-middle SDI regions. However, the increased burden and upward trends of MSMI in a few countries and regions are raising concern, which poses a serious challenge to maternal health. More tailored prevention measures and additional resources for maternal health are urgently needed to resolve this problem.
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Carga Global de Enfermedades , Complicaciones Infecciosas del Embarazo , Femenino , Salud Global , Humanos , Incidencia , Recién Nacido , Embarazo , Años de Vida Ajustados por Calidad de VidaRESUMEN
Background: For coronavirus disease 2019 (COVID-19), early identification of patients with serious symptoms at risk of critical illness and death is important for personalized treatment and balancing medical resources. Methods: Demographics, clinical characteristics, and laboratory tests data from 726 patients with serious COVID-19 at Tongji Hospital (Wuhan, China) were analyzed. Patients were classified into critical group (n = 174) and severe group (n= 552), the critical group was sub-divided into survivors (n = 47) and non-survivors (n = 127). Results: Multivariable analyses revealed the risk factors associated with critical illness in serious patients were: Advanced age, high respiratory rate (RR), high lactate dehydrogenase (LDH) level, high hypersensitive cardiac troponin I (hs-cTnI) level, and thrombocytopenia on admission. High hs-cTnI level was the independent risk factor of mortality among critically ill patients in the unadjusted and adjusted models. ROC curves demonstrated that hs-cTnI and LDH were predictive factors for critical illness in patients with serious COVID-19 whereas procalcitonin and D-Dimer with hs-cTnI and LDH were predictive parameters in mortality risk. Conclusions: Advanced age, high RR, LDH, hs-cTnI, and thrombocytopenia, constitute risk factors for critical illness among patients with serious COVID-19, and the hs-cTnI level helps predict fatal outcomes in critically ill patients.
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COVID-19/metabolismo , COVID-19/virología , SARS-CoV-2/patogenicidad , Troponina I/metabolismo , Anciano , COVID-19/patología , Enfermedad Crítica , Humanos , L-Lactato Deshidrogenasa/genética , L-Lactato Deshidrogenasa/metabolismo , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
To determine what exacerbate severity of the COVID-19 among patients without comorbidities and advanced age and investigate potential clinical indicators for early surveillance, we adopted a nested case-control study, design in which severe cases (case group, n = 67) and moderate cases (control group, n = 67) of patients diagnosed with COVID-19 without comorbidities, with ages ranging from 18 to 50 years who admitted to Wuhan Tongji Hospital were matched based on age, sex and BMI. Demographic and clinical characteristics, and risk factors associated with severe symptoms were analysed. Percutaneous oxygen saturation (SpO2), lymphocyte counts, C-reactive protein (CRP) and IL-10 were found closely associated with severe COVID-19. The adjusted multivariable logistic regression analyses revealed that the independent risk factors associated with severe COVID-19 were CRP (OR 2.037, 95% CI 1.078-3.847, P = 0.028), SpO2 (OR 1.639, 95% CI 0.943-2.850, P = 0.080) and lymphocyte (OR 1.530, 95% CI 0.850-2.723, P = 0.148), whereas the changes exhibited by indicators influenced incidence of disease severity. Males exhibited higher levels of indicators associated with inflammation, myocardial injury and kidney injury than the females. This study reveals that increased CRP levels and decreased SpO2 and lymphocyte counts could serve as potential indicators of severe COVID-19, independent of comorbidities, advanced age and sex. Males could at higher risk of developing severe symptoms of COVID-19 than females.
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Betacoronavirus , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/etiología , Neumonía Viral/epidemiología , Neumonía Viral/etiología , Adolescente , Adulto , Factores de Edad , Área Bajo la Curva , Proteína C-Reactiva/análisis , COVID-19 , Estudios de Casos y Controles , China/epidemiología , Infecciones por Coronavirus/complicaciones , Femenino , Humanos , Incidencia , Inflamación/etiología , Tiempo de Internación , Modelos Logísticos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Oxígeno/metabolismo , Pandemias , Neumonía Viral/complicaciones , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores Sexuales , Adulto JovenRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease and rapidly escalating epidemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pathogenesis of COVID-19 remains to be elucidated. We aimed to clarify correlation of systemic inflammation with disease severity and outcomes in COVID-19 patients. METHODS: In this retrospective study, baseline characteristics, laboratory findings, and treatments were compared among 317 laboratory-confirmed COVID-19 patients with moderate, severe, or critically ill form of the disease. Moreover, the longitudinal changes of serum cytokines, lactate dehydrogenase (LDH), high-sensitivity C-reactive protein (hsCRP), and hsCRP to lymphocyte count ratio (hsCRP/L) as well as their associations with disease severity and outcomes were investigated in 68 COVID-19 patients. RESULTS: Within 24 h of admission, the critically ill patients showed higher concentrations of inflammatory markers including serum soluble interleukin (IL)-2 receptor, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), ferritin, procalcitonin, LDH, hsCRP, and hsCRP/L than patients with severe or moderate disease. The severe cases displayed the similar response patterns when compared with moderate cases. The longitudinal assays showed the levels of pro-inflammatory cytokines, LDH, hsCRP, and hsCRP/L gradually declined within 10 days post admission in moderate, severe cases or those who survived. However, there was no significant reduction in cytokines, LDH, hsCRP, and hsCRP/L levels in critically ill or deceased patients throughout the course of illness. Compared with female patients, male cases showed higher serum concentrations of soluble IL-2R, IL-6, ferritin, procalcitonin, LDH, and hsCRP. Multivariate logistic regression analysis revealed that IL-6 > 50 pg/mL and LDH > 400 U/L on admission were independently associated with disease severity in patients with COVID-19. CONCLUSION: Exuberant inflammatory responses within 24 h of admission in patients with COVID-19 may correlate with disease severity. SARS-CoV-2 infection appears to elicit a sex-based differential immune response. IL-6 and LDH were independent predictive parameters for assessing the severity of COVID-19. An early decline of these inflammation markers may be associated with better outcomes.
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Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/terapia , Citocinas/sangre , Inflamación/sangre , Neumonía Viral/sangre , Neumonía Viral/terapia , Anciano , COVID-19 , China/epidemiología , Infecciones por Coronavirus/epidemiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
The aim of the study was to determine the expression profiles of message RNAs and long non-coding RNAs in CD4+T cells of asthmatic patients and to explore the clinical value and biological function. Expression profiles in CD4+T cells of asthmatic patients and healthy controls were analyzed by microarray. We found 2725 lncRNAs and 3167 mRNAs differentially expressed. The data were validated by quantitative real time polymerase chain reaction, with 3 up-regulated (ENST00000444682, ENST00000566098, ENST00000583179) and 1 down-regulated (ENST00000579468) lncRNAs found. Receiver operating characteristic curve analysis showed the area under the curve was 0.7058, 0.9026, 0.8361, 0.8316, respectively. Spearman correlation analysis showed that ENST00000566098 was positively related with IL-13 and ENST00000579468 was positively related with peak expiratory flow. Bioinformatics analyses were performed to explore the function of lncRNAs. Specific lncRNAs aberrantly expressed in CD4+T cells may take part in the development of asthma and may be used as biomarkers for diagnosis.
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Asma/genética , Linfocitos T CD4-Positivos/química , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Largo no Codificante/genética , Adolescente , Adulto , Anciano , Asma/diagnóstico , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , ARN Largo no Codificante/análisis , ARN Mensajero/análisis , ARN Mensajero/genética , Curva ROC , Adulto JovenRESUMEN
Persistent fibroblast activation is a predominant feature of idiopathic pulmonary fibrosis (IPF), but the transcriptional and epigenetic mechanisms controlling this process are not well understood. Silent information regulator type-1 (Sirt1) is a member of class â ¢ histone deacetylase with important regulatory roles in a variety of pathophysiologic processes, but its role in fibrotic lung diseases is not clearly elucidated. Sirt1 expression in lung tissues of IPF patients and in a mouse model of bleomycin (BLM)-induced lung fibrosis were evaluated by immunofluorescence. The function of Sirt1 in BLM-induced lung fibrosis in the mouse model or transforming growth factor ß1 (TGF-ß1)-mediated lung fibroblast cellular model was investigated by Sirt1 activation, overexpression and knockdown of Sirt1. Finally, the involvement of p300 signaling pathways was assessed. In this study, we found up-regulation of Sirt1 in BLM-induced lung fibrosis, as well as in the lungs of IPF patients, including in the aggregated pulmonary fibroblasts of fibrotic foci. Activation or overexpression of Sirt1 attenuated TGF-ß1-mediated lung fibroblast differentiation and activation and diminished the severity of experimental lung fibrosis in mice. Whereas knockdown of Sirt1 promoted the pro-fibrogenic activity of TGF-ß1 in lung fibroblasts. A potential mechanism for the role of Sirt1 in lung fibrosis was through regulating the expression of p300. Thus, we characterized Sirt1 as an important regulator of lung fibrosis and provides a proof of principle for activation or overexpression of Sirt1 as a potential novel therapeutic strategy for IPF.
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Proteína p300 Asociada a E1A/inmunología , Fibroblastos/inmunología , Fibrosis Pulmonar/inmunología , Sirtuina 1/inmunología , Animales , Fibroblastos/patología , Humanos , Ratones , Ratones Endogámicos C57BL , Regulación hacia Arriba/inmunologíaRESUMEN
BACKGROUND: Interleukin (IL)-17 has been implicated in the pathogenesis of asthma and the progression of airway inflammation. Here, we used a model of allergic asthma and found that the frequencies of IL-17-secreting T helper (Th)17 and CD8 (Tc)17 cells were both significantly increased, as was the expression of the CC chemokine receptor (CCR2) on the surface of these cells. CC chemokine ligand 2 (CCL2) has been shown to mediate the activation and recruitment of inflammatory cells in asthma, which are also skewed after ovalbumin (OVA) challenge. However, the role of CCL2 on Th17 cells and Tc17 cells in asthma has not been illuminated. METHODS: Mice that were sensitized and challenged with OVA received anti-CCL2 antibody (Ab; 5 µg/day intratracheally) or CCR2 antagonist (RS504393, 2 mg/kg/day intraperitoneally) prior to the challenge. Some mice received an isotype control Ab or vehicle alone. We then assessed the effects of allergic asthma and anti-CCL2 Ab or CCR2 antagonist treatment on the levels of IL-17 and CCL2, the Th17 and Tc17 cell frequencies and lung tissue inflammation. RESULTS: We demonstrated that CCL2 and IL-17 levels and the frequency of Th17 and Tc17 cells in lung tissues and bronchoalveolar lavage fluid increased in the asthma group compared with the normal control mice. Blocking the CCL2/CCR2 axis greatly reduced the Th17 but not the Tc17 cell frequency, and revealed a suppressive effect on airway inflammation. CONCLUSION: These findings indicate a role for the CCL2/CCR2 axis in mediating Th17 but not Tc17 cell migration during acute allergic airway inflammation.
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Asma/inmunología , Linfocitos T CD8-positivos/inmunología , Quimiocina CCL2/inmunología , Pulmón/inmunología , Receptores CCR2/inmunología , Células Th17/inmunología , Animales , Anticuerpos Neutralizantes/farmacología , Asma/inducido químicamente , Asma/genética , Asma/patología , Benzoxazinas/farmacología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Linfocitos T CD8-positivos/patología , Quimiocina CCL2/antagonistas & inhibidores , Quimiocina CCL2/genética , Modelos Animales de Enfermedad , Femenino , Expresión Génica , Humanos , Interleucina-17/biosíntesis , Interleucina-17/inmunología , Pulmón/patología , Recuento de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ovalbúmina , Receptores CCR2/antagonistas & inhibidores , Receptores CCR2/genética , Compuestos de Espiro/farmacología , Células Th17/patologíaRESUMEN
BACKGROUND: Lysophosphatidylcholine (LPC) is generated through the hydrolysis of phospha-tidylcholine (PC) by phospholipase A2 and is converted back to PC by lysophosphatidylcholine acyltransferase 1 (LPCAT1). Elevated levels of (LPC) are known to play a pathogenic role in the inflammatory injury of asthma. However, the role of LPCAT1 in asthma has not yet been reported. OBJECTIVE: To determine whether the exogenous expression of LPCAT1, delivered by using a recombinant lentiviral vector, could attenuate airway inflammation in asthmatic mice. METHODS: Recombinant lentivirus carrying cDNA encoding LPCAT1 (Lenti-LPCAT1), or EGFP (Lenti-EGFP) as a control, was constructed. BALB/c mice were sensitised with ovalbumin (OVA), and intratracheally pre-treated with an endobronchial administration of the recombinant lentivirus intratracheally 72 hours before the first challenge. After the last OVA challenges, the mice were assessed for airway inflammation, airway hyper-responsiveness and lipid levels. RESULTS: Lenti-LPCAT1-infected HEK293T cells expressed exogenous recombinant LPCAT1 protein that showed high activity of the LPC acyltransferase. OVA sensitisation and challenge significantly increased the levels of saturated species LPC 16:0 and LPC 18:0 levels in the bronchoalveolar lavage fluid (BALF) compared with wild-type mice respectively. The intratracheal Lenti-LPCAT1 instillation obviously down-regulated the OVA-induced release of LPC 16:0 and LPC 18:0. Treatment with Lenti-LPCAT1 ameliorated OVA-induced airway hyper-responsiveness and reduced airway eosinophilia infiltration in lung tissue. Furthermore, the secretion of eotaxin and Th2-associated cytokines IL-5 and IL-13 were inhibited in BALF. The level of OVA-specific IgE in serum was suppressed. CONCLUSIONS: These results suggested that the exogenous expression of LPCAT1 may attenuate eosinophil inflammation in the airway by down-regulating the LPC 16:0 and LPC 18:0 BALF levels in asthmatic mice.
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1-Acilglicerofosfocolina O-Aciltransferasa/genética , Asma/terapia , Lentivirus/genética , Animales , Líquido del Lavado Bronquioalveolar/química , Citocinas/análisis , Femenino , Vectores Genéticos , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Ratas , Ratas Sprague-DawleyRESUMEN
Model reuse is a key issue to be resolved in parallel and distributed simulation at present. However, component models built by different domain experts usually have diversiform interfaces, couple tightly, and bind with simulation platforms closely. As a result, they are difficult to be reused across different simulation platforms and applications. To address the problem, this paper first proposed a reusable component model framework. Based on this framework, then our reusable model development approach is elaborated, which contains two phases: (1) domain experts create simulation computational modules observing three principles to achieve their independence; (2) model developer encapsulates these simulation computational modules with six standard service interfaces to improve their reusability. The case study of a radar model indicates that the model developed using our approach has good reusability and it is easy to be used in different simulation platforms and applications.
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Diseño de Software , Programas Informáticos , Simulación por ComputadorRESUMEN
BACKGROUND: IL-35 has been found to be involved in many inflammatory diseases in humans but its role in asthma and chronic obstructive pulmonary disease (COPD) is not clear. The plasma level of IL-35 in patients with asthma and COPD needs to be measured. OBJECTIVE: The aim of this study was to examine the plasma concentrations of IL-35 in newly diagnosed asthmatic and COPD patients and control subjects and investigate correlations of lung function, age, sex, smoking history with the levels of IL-35 in plasma in these diseases. METHODS: Blood samples were collected from patients with newly diagnosed asthma (44, 12 males, aged 33.75?8.94), newly diagnosed COPD (36, 36 males, aged 68.03 ± 8.94), and healthy control groups (23, 9 males, aged 30.06 ± 7.50). We determined the IL-35 levels in plasma by enzyme-linked immunosorbent assay. RESULT: The median and the range of values for IL-35 were 118.55 pg/ml (range 74.43~1767.22 pg/ml) in patients with asthma, 136.09 pg/ml (range 62.54~697.49 pg/ml) in patients with COPD and 275.86 pg/ml (range 26.11~1766.20 pg/ml) in control subjects. The levels of IL-35 in plasma showed a positive correlation with FEV1% and FVC% in asthmatic patients whose plasma IL-35 values were over 150 pg/ml. A positive correlation was also found between plasma IL-35 and FVC% in COPD patients whose plasma IL-35 values were over 150 pg/ml. CONCLUSIONS: These findings suggest that IL-35 may very probably be involved in the Th2 and Th17 mediated inflammation process of asthma and COPD. Its role in the mechanisms of COPD and asthma in human beings, as well as its therapeutic value in these diseases, need further investigation.
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Asma/sangre , Interleucinas/sangre , Enfermedad Pulmonar Obstructiva Crónica/sangre , Adolescente , Adulto , Asma/inmunología , Asma/patología , Femenino , Humanos , Inflamación/sangre , Inflamación/inmunología , Inflamación/patología , Interleucinas/inmunología , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/patología , Células Th17/inmunología , Células Th17/metabolismo , Células Th17/patología , Células Th2/inmunología , Células Th2/metabolismo , Células Th2/patologíaRESUMEN
OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial lung disease with a poor prognosis. Alpinetin (ALP), derived from Alpinia katsumadai Hayata, has shown potential as a therapeutic measure of various diseases. However, the utilization of ALP in managing pulmonary fibrosis and its underlying mechanisms are still not fully understood. METHODS: A well-established mouse model of pulmonary fibrosis induced by bleomycin (BLM) was used in this study. The antifibrotic effects of ALP on histopathologic manifestations and expression levels of fibrotic markers were examined. Subsequently, the impact of ALP on fibroblast differentiation, proliferation, apoptosis, and associated signaling pathways was investigated to elucidate the underlying mechanisms. RESULTS: In the present study, we observed that ALP effectively mitigated BLM-induced pulmonary fibrosis in mice, as evidenced by histopathological manifestations and the expression levels of fibrotic markers. Furthermore, the in vitro experiments demonstrated that ALP treatment attenuated the ability of fibroblasts to differentiate into myofibroblasts. Mechanically, our findings provided evidence that ALP suppressed fibroblast-to-myofibroblast differentiation by repressing TGF-ß/ALK5/Smad signaling pathway. ALP was found to possess the capability of inhibiting fibroblast proliferation and promoting apoptosis of fibroblasts induced by TGF-ß. CONCLUSION: In general, ALP may exert therapeutic effects on pulmonary fibrosis by modulating the differentiation, proliferation, and apoptosis of fibroblasts. Although its safety has been demonstrated in mice, further studies are required to investigate the efficacy of ALP in treatment of patients with IPF.
Asunto(s)
Bleomicina , Flavanonas , Fibrosis Pulmonar Idiopática , Humanos , Ratones , Animales , Bleomicina/farmacología , Fibroblastos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Factor de Crecimiento Transformador beta/metabolismo , Proliferación Celular , Pulmón , Ratones Endogámicos C57BL , Diferenciación CelularRESUMEN
BACKGROUND: To explore the role and mechanism of triptolide in regulating esophageal squamous cell carcinoma (ESCC) progression by mediating the circular RNA (circRNA)-related pathway. METHODS: The expression levels of circNOX4, miR-153-3p and special AT-rich sequence binding protein-1 (SATB1) were measured by qRT-PCR. Cell proliferation was confirmed by cell counting kit-8 assay and colony formation assay. Flow cytometry was employed to measure cell apoptosis and cell cycle process. Moreover, cell migration and invasion were detected using transwell assay. The protein levels of epithelial-mesenchymal transformation markers and SATB1 were determined by western blot analysis. Furthermore, dual-luciferase reporter assay and RIP assay were performed to confirm the interaction between miR-153-3p and circNOX4 or SATB1. Xenograft tumor models were built to verify the effects of triptolide and circNOX4 on ESCC tumor growth. RESULTS: CircNOX4 was highly expressed in ESCC tissues and cells, and its expression could be reduced by triptolide. Triptolide could inhibit ESCC proliferation, cell cycle process, migration, invasion, EMT process, and promote apoptosis, while these effects were reversed by circNOX4 overexpression. MiR-153-3p could be sponged by circNOX4, and the promotion effect of circNOX4 on the progression of triptolide-treated ESCC cells was abolished by miR-153-3p overexpression. SATB1 was a target of miR-153-3p. Also, SATB1 knockdown reversed the enhancing effect of miR-153-3p inhibitor on the progression of triptolide-treated ESCC cells. Triptolide reduced ESCC tumor growth by regulating the circNOX4/miR-153-3p/SATB1 axis. CONCLUSION: Triptolide could hinder ESCC progression, which was mainly achieved by regulating the circNOX4/miR-153-3p/SATB1 axis.
Asunto(s)
Diterpenos , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Proteínas de Unión a la Región de Fijación a la Matriz , MicroARNs , Fenantrenos , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Proteínas de Unión a la Región de Fijación a la Matriz/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Transducción de Señal , Compuestos EpoxiRESUMEN
In this work, a colorimetric aptasensor based on magnetic beads (MBs), gold nanoparticles (AuNPs) and Horseradish Peroxidase (HRP) was prepared for the detection of mucin 1 (MUC1). Complementary DNA of the MUC1 aptamer (Apt) immobilized on the MBs was combined with the prepared AuNPs-Apt-HRP complex (AuNPs@Apt-HRP). In the presence of MUC1, it specifically bound to Apt, resulting in the detachment of gold nanoparticles from the MBs. After magnetic separation, AuNPs@Apt-HRP was separated into the supernatant and reacted with 3,3',5,5'-Tetramethylbenzidine (TMB) to produce color reaction from colorless to blue. The linear range of MUC1 was from 75 to 500 µg/mL (R2 = 0.9878), and the detection limit was 41.95 µg/mL. The recovery rate of MUC1 in human serum was 99.18 %â¼101.15 %. This method is simple and convenient. Moreover, it does not require complex and expensive equipment for detection of MUC1. It provides value for the development of MUC1 colorimetric sensors and a promising strategy for the determination of MUC1 in clinical diagnosis.