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BACKGROUND: The function of kallistatin in airway inflammation, particularly chronic rhinosinusitis with nasal polyps (CRSwNP), has not been elucidated. OBJECTIVE: We sought to investigate the role of kallistatin in airway inflammation. METHODS: Kallistatin and proinflammatory cytokine expression levels were detected in nasal polyps. For the in vivo studies, we constructed the kallistatin-overexpressing transgenic mice to elucidate the role of kallistatin in airway inflammation. Furthermore, the levels of plasma IgE and proinflammatory cytokines in the airways were evaluated in the kallistatin-/- rat in vivo model under a type 2 inflammatory background. Finally, the Notch signaling pathway was explored to understand the role of kallistatin in CRSwNP. RESULTS: We showed that the expression of kallistatin was significantly higher in nasal polyps than in the normal nasal mucosa and correlated with IL-4 expression. We also discovered that the nasal mucosa of kallistatin-overexpressing transgenic mice expressed higher levels of IL-4 expression, associating to TH2-type inflammation. Interestingly, we observed lower IL-4 levels in the nasal mucosa and lower total plasma IgE of the kallistatin-/- group treated with house dust mite allergen compared with the wild-type house dust mite group. Finally, we observed a significant increase in the expression of Jagged2 in the nasal epithelium cells transduced with adenovirus-kallistatin. This heightened expression correlated with increased secretion of IL-4, attributed to the augmented population of CD4+CD45+Notch1+ T cells. These findings collectively may contribute to the induction of TH2-type inflammation. CONCLUSIONS: Kallistatin was demonstrated to be involved in the CRSwNP pathogenesis by enhancing the TH2 inflammation, which was found to be associated with more expression of IL-4, potentially facilitated through Jagged2-Notch1 signaling in CD4+ T cells.
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Linfócitos T CD4-Positivos , Mucosa Nasal , Rinossinusite , Serpinas , Células Th2 , Animais , Feminino , Humanos , Masculino , Camundongos , Ratos , Linfócitos T CD4-Positivos/imunologia , Quimiotaxia de Leucócito/imunologia , Doença Crônica , Citocinas/metabolismo , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Inflamação/imunologia , Interleucina-4/imunologia , Interleucina-4/metabolismo , Camundongos Transgênicos , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Pólipos Nasais/imunologia , Rinossinusite/imunologia , Serpinas/imunologia , Serpinas/genética , Serpinas/metabolismo , Transdução de Sinais , Células Th2/imunologiaRESUMO
BACKGROUND: Based on past epidemiological investigations, the cardiovascular role of estrogen replacement therapy (ERT) in postmenopausal women has always been controversial. The real efficacy of ERT for heart failure (HF) among postmenopausal women remains to be further investigated. This article is based on research into European and American populations. PURPOSE: To determine the impact of estrogen replacement therapy on HF using meta-analysis. METHODS AND MATERIAL: Electronic literature was searched on Web of Science, PubMed, and Embase databases to identify randomized controlled trials (RCTs) comparing the hospitalization for heart failure between ERT users and non-users among postmenopausal women. Pairs of reviewers screened eligible articles independently, extracted data, and evaluated the risk of bias. Summary relative risks were estimated for the composite endpoint of first hospitalized heart failure and admission to the hospital for heart failure. RESULTS: A pooled study of five randomized controlled trials found that estrogen replacement therapy had no significant effect on the composite endpoint in postmenopausal women, with a relative risk of 1.02 (95% CI 0.94-1.10). CONCLUSION: This systematic review demonstrated that estrogen replacement therapy did not significantly change the risk of first hospitalized heart failure and admission to the hospital for heart failure in postmenopausal women.
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Terapia de Reposição de Estrogênios , Insuficiência Cardíaca , Pós-Menopausa , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Feminino , Terapia de Reposição de Estrogênios/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Hospitalização/estatística & dados numéricos , Pessoa de Meia-Idade , IdosoRESUMO
Abdominal aortic aneurysm (AAA) is a dangerous vascular disease without any effective drug therapies so far. Emerging evidence suggests the phenotypic differences in perivascular adipose tissue (PVAT) between regions of the aorta are implicated in the development of atherosclerosis evidenced by the abdominal aorta more vulnerable to atherosclerosis than the thoracic aorta in large animals and humans. The prevalence of thoracic aortic aneurysms (TAA) is much less than that of abdominal aortic aneurysms (AAA). In this study we investigated the effect of thoracic PVAT (T-PVAT) transplantation on aortic aneurysm formation and the impact of T-PVAT on vascular smooth muscle cells. Calcium phosphate-induced mouse AAA model was established. T-PVAT (20 mg) was implanted around the abdominal aorta of recipient mice after removal of endogenous abdominal PVAT (A-PVAT) and calcium phosphate treatment. Mice were sacrificed two weeks after the surgery and the maximum external diameter of infrarenal aorta was measured. We found that T-PVAT displayed a more BAT-like phenotype than A-PVAT; transplantation of T-PVAT significantly attenuated calcium phosphate-induced abdominal aortic dilation and elastic degradation as compared to sham control or A-PVAT transplantation. In addition, T-PVAT transplantation largely preserved smooth muscle cell content in the abdominal aortic wall. Co-culture of T-PVAT with vascular smooth muscle cells (VSMCs) significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. RNA sequencing analysis showed that T-PVAT was enriched by browning adipocytes and anti-apoptotic secretory proteins. We further verified that the secretome of mature adipocytes isolated from T-PVAT significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. Using proteomic and bioinformatic analyses we identified cartilage oligomeric matrix protein (COMP) as a secreted protein significantly increased in T-PVAT. Recombinant COMP protein significantly inhibited VSMC apoptosis. We conclude that T-PVAT exerts anti-apoptosis effect on VSMCs and attenuates AAA formation, which is possibly attributed to the secretome of browning adipocytes.
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Aneurisma da Aorta Abdominal , Aneurisma Aórtico , Aterosclerose , Humanos , Camundongos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Peróxido de Hidrogênio/metabolismo , Secretoma , Músculo Liso Vascular/metabolismo , Cicloeximida/metabolismo , Proteômica , Tecido Adiposo/metabolismo , Aneurisma Aórtico/metabolismo , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/metabolismo , Aorta Abdominal/cirurgia , Aterosclerose/metabolismo , Adipócitos Marrons , Camundongos Endogâmicos C57BLRESUMO
PURPOSE: Colchicine, a multipotent anti-inflammatory drug, has been reported to alleviate cardiac remodeling and improve cardiac function after acute myocardial infarction (AMI). However, the underlying mechanism remains incompletely understood. Because neutrophils extracellular traps (NETs) enhance inflammation and participate in myocardial ischemia injury, and colchicine can inhibit NETosis, we thus aimed to determine whether colchicine exerts cardioprotective effects on AMI via suppressing NETs. METHODS: Adult C57BL/6 mice were subjected to permanent ligation of the left anterior descending coronary artery and treated with colchicine (0.1 mg/kg/day) or Cl-amidine (10 mg/kg/day) for 7 or 28 days after AMI. Cardiac function was evaluated by echocardiography, and NETs detected by immunofluorescence. ROS production was detected using 2',7'-dichlorodihydrofluorescein diacetates (DCFH-DA) fluorometry. Intracellular Ca2+ concentration was assessed by a fluorometric ratio technique. RESULTS: We found that colchicine treatment significantly increased mice survival (89.8% in the colchicine group versus 67.9% in control, n = 32 per group; log-rank test, p < 0.05) and improved cardiac function at day 7 (left ventricular ejection fraction (LVEF): 28.0 ± 9.2% versus 12.6 ± 3.9%, n = 8 per group; p < 0.001) and at day 28 (LVEF: 26.2 ± 7.2% versus 14.8 ± 6.7%, n = 8 per group; p < 0.001) post-AMI. In addition, the administration of colchicine inhibited NETs formation and inflammation. Furthermore, colchicine inhibited NETs formation by reducing NOX2/ROS production and Ca2+ influx. Moreover, prevention of NETs formation with Cl-amidine significantly alleviated AMI-induced cardiac remodeling. CONCLUSIONS: Colchicine inhibited NETs and cardiac inflammation, and alleviated cardiac remodeling after acute myocardial infarction.
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OBJECTIVES: To assess the impact of risk factors on the disease control among chronic rhinosinusitis (CRS) patients, following 1 year of functional endoscopic sinus surgery (FESS), and combining the risk factors to formulate a convenient, visualised prediction model. DESIGN: A retrospective and nonconcurrent cohort study. SETTING AND PARTICIPANTS: A total of 325 patients with CRS from June 2018 to July 2020 at the First Affiliated Hospital of Sun Yat-sen University, the Third Affliated Hospital of Sun Yat-sen University, the Seventh Affiliated Hospital of Sun Yat-sen University. MAIN OUTCOMES MEASURES: Outcomes were time to event measures: the disease control of CRS after surgery 1 year. The presence of nasal polyps, smoking habits, allergic rhinitis (AR), the ratio of tissue eosinophil (TER) and peripheral blood eosinophil count (PBEC) and asthma was assessed. The logistic regression models were used to conduct multivariate and univariate analyses. Asthma, TER, AR, PBEC were also included in the nomogram. The calibration curve and area under curve (AUC) were used to evaluate the forecast performance of the model. RESULTS: In univariate analyses, most of the covariates had significant associations with the endpoints, except for age, gender and smoking. The nomogram showed the highest accuracy with an AUC of 0.760 (95% CI, 0.688-0.830) in the training cohort. CONCLUSIONS: In this cohort study that included the asthma, AR, TER, PBEC, which had significantly affected the disease control of CRS after surgery. The model provided relatively accurate prediction in the disease control of CRS after FESS and served as a visualised reference for daily diagnosis and treatment.
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Asma , Pólipos Nasais , Rinite Alérgica , Rinite , Sinusite , Asma/complicações , Doença Crônica , Estudos de Coortes , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/diagnóstico , Pólipos Nasais/cirurgia , Estudos Retrospectivos , Rinite/complicações , Rinite/diagnóstico , Rinite/cirurgia , Rinite Alérgica/complicações , Fatores de Risco , Sinusite/diagnóstico , Sinusite/etiologia , Sinusite/cirurgiaRESUMO
Myocardial ischemia/reperfusion (I/R) injury greatly contributes to myocardial tissue damage in patients with coronary disease, which eventually leads to heart failure. Long noncoding RNAs (lncRNAs) have an emerging role in the process of myocardial I/R injury. Our previous work revealed the protective role of miR-374a-5p against myocardial I/R injury. In this study, we explored the role of lncRNA TTTY15 and its potential interaction mechanisms with miR-374a-5p in myocardial I/R injury. The expression of TTTY15 was increased both in vitro and in vivo after myocardial I/R injury models according to quantitative real-time polymerase chain reaction. Various assays were conducted to evaluate the regulatory relationship among TTTY15, miR-374a-5p, FOXO1, and autophagy in H9c2 and HL-1 cells. The results showed that TTTY15 suppresses autophagy and myocardial I/R injury by targeting miR-374a-5p. We found that TTTY15 regulates miR-374a-5p, thus affecting FOXO1 expression and autophagy in myocytes during I/R. Furthermore, in an in vivo mouse model of myocardial I/R injury, suppression of TTTY15 successfully alleviated myocardial I/R injury. Our results reveal a novel feedback mechanism in which TTTY15 regulates miRNA processing and a potential target in myocardial I/R injury. TTTY15 is a promising therapeutic target for treating myocardial I/R injury.
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Apoptose , Autofagia , Proteína Forkhead Box O1/metabolismo , Regulação da Expressão Gênica , MicroRNAs/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , RNA Longo não Codificante/antagonistas & inibidores , Animais , Hipóxia Celular , Proteína Forkhead Box O1/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , RNA Longo não Codificante/genética , Transdução de SinaisRESUMO
BACKGROUND: Increasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established. METHODS: This study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were included. The Pearson's chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p-value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram. RESULTS: The c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups. CONCLUSIONS: The nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.
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Estesioneuroblastoma Olfatório/mortalidade , Nomogramas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de SobrevidaRESUMO
In this paper, the following questions were investigated: the proportion of mass loss, the mass fraction of oil, the structure, composition and ultimate analysis of solid residues and gas products. By comparing the treatment effect of using both microwave and electric as the source of heat to dispose the oil-based drilling cuttings (OBDC), the advantages of microwave heating treatment were demonstrated. Meanwhile, the composition of liquid products by microwave pyrolysis was analyzed. The results show that the microwave heating is better than electric heating and the former can promote the pyrolysis of petroleum hydrocarbons. The results of component analysis of the liquid products from OBDC by microwave pyrolysis show that C12â¼C20 components pyrolyze at 500⯰C. At the same time, a mass of C21â¼C24 components volatilize. At the temperature above 500⯰C, the thermal cracking reactions of >C25 components occur and a maximum content of paraffin in liquid products is obtained. As the temperature increases, the components obtained by pyrolysis become more and more complex.
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Micro-Ondas , Temperatura Alta , Hidrocarbonetos/química , Óleos/química , Petróleo , PiróliseRESUMO
RATIONALE: The disruption of the balance between fatty acid (FA) uptake and oxidation (FAO) leads to cardiac lipotoxicity, serving as the driving force behind diabetic cardiomyopathy (DbCM). Sirtuin 5 (Sirt5), a lysine de-succinylase, could impact diverse metabolic pathways, including FA metabolism. Nevertheless, the precise roles of Sirt5 in cardiac lipotoxicity and DbCM remain unknown. OBJECTIVE: This study aims to elucidate the role and underlying mechanism of Sirt5 in the context of cardiac lipotoxicity and DbCM. METHODS AND RESULTS: The expression of myocardial Sirt5 was found to be modestly elevated in diabetic heart failure patients and mice. Cardiac dysfunction, hypertrophy and lipotoxicity were exacerbated by ablation of Sirt5 but improved by forced expression of Sirt5 in diabetic mice. Notably, Sirt5 deficiency impaired FAO without affecting the capacity of FA uptake in the diabetic heart, leading to accumulation of FA intermediate metabolites, which mainly included medium- and long-chain fatty acyl-carnitines. Mechanistically, succinylomics analyses identified carnitine palmitoyltransferase 2 (CPT2), a crucial enzyme involved in the reconversion of fatty acyl-carnitines to fatty acyl-CoA and facilitating FAO, as the functional succinylated substrate mediator of Sirt5. Succinylation of Lys424 in CPT2 was significantly increased by Sirt5 deficiency, leading to the inactivation of its enzymatic activity and the subsequent accumulation of fatty acyl-carnitines. CPT2 K424R mutation, which mitigated succinylation modification, counteracted the reduction of enzymatic activity in CPT2 mediated by Sirt5 deficiency, thereby attenuating Sirt5 knockout-induced FAO impairment and lipid deposition. CONCLUSIONS: Sirt5 deficiency impairs FAO, leading to cardiac lipotoxicity in the diabetic heart through the succinylation of Lys424 in CPT2. This underscores the potential roles of Sirt5 and CPT2 as therapeutic targets for addressing DbCM.
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Carnitina O-Palmitoiltransferase , Cardiomiopatias Diabéticas , Ácidos Graxos , Metabolismo dos Lipídeos , Miócitos Cardíacos , Sirtuínas , Animais , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/patologia , Carnitina O-Palmitoiltransferase/metabolismo , Carnitina O-Palmitoiltransferase/genética , Sirtuínas/metabolismo , Sirtuínas/genética , Camundongos , Ácidos Graxos/metabolismo , Miócitos Cardíacos/metabolismo , Humanos , Masculino , Oxirredução , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaçõesRESUMO
Introduction: Adriamycin (ADR) is commonly used in tumor chemotherapy, but its nonreversible cardiotoxicity severely hampers its clinical application. Ferroptosis is an implicated cause of ADR-induced injury. However, the underlying molecular mechanisms remain poorly understood. This study explored whether ferroptosis is a pivotal pathogenic pathway underlying ADR-induced cardiotoxicity and the possible molecular mechanisms involved. Methods: In vivo and in vitro experimental models were used to study the mechanism of ADR-mediated ferroptosis. Ferroptosis levels were examined in mice and human/rat cardiomyocytes. Mechanistically, the expression levels of SLC7A11 and related miRNAs were examined. Bioinformatics prediction and luciferase reporter assays were used to verify the potential interaction between miR-16-5p and SLC7A11. The biological functions and interaction of SLC7A11 and miR-16-5p were investigated in vivo and in vitro. Results: Our study observed that ADR treatment significantly increased ferroptosis levels in vivo and in vitro. Ferroptosis-related pharmacological interventions further confirmed these results. Our data displayed that the SLC7A11 level was significantly decreased in cardiac tissues and cells, while an increased expression level of miR-16-5p was observed. Moreover, upregulation of SLC7A1 and inhibition of miR-16-5p attenuated ADR-induced cardiomyocyte ferroptosis injury. Interactive rescue experiments showed that the protective effects of miR-16-5p inhibition on ADR-induced cardiomyocyte injury were blocked by SLC7A11 knockdown. Discussion: Based on these findings, targeting miR-16-5p could partially reverse the ADR-induced cardiotoxicity by rescuing the SLC7A11 to attenuate ferroptosis. This study presents a pre-clinical basis to identify miR-16-5p/SLC7A11 as a potential treatment target for ADR-induced cardiotoxicity.
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BACKGROUND: Patients with coronary heart disease (CHD) are susceptible to lung function problems caused by respiratory muscle weakness. Many CHD patients show complications of respiratory muscle weakness, but the risk factors remain unclear. OBJECTIVE: To explore the risk factors for inspiratory muscle weakness in CHD. METHODS: This study enrolled 249 patients with CHD who underwent maximal inspiratory pressure (MIP) measurement between April 2021 and March 2022.According to the percentage of MIP (MIP/Predicted normal value [PNV]), patients were divided into the inspiratory muscle weakness (IMW) (n = 149) (MIP/PNV<70%) and control groups (n = 100) (MIP/PNV≥70༠). Clinical information and MIP of the two groups were collected and analyzed. RESULTS: The incidence of IMW was 59.8% (n = 149). Age (P < 0.001); history of heart failure (P < 0.001), hypertension (P = 0.04), and peripheral artery disease (PAD) (P = 0.001); left ventricular end-systolic dimension (P = 0.035); presence of segmental motion abnormality of the ventricular wall (P = 0.030); and high density lipoprotein cholesterol (P = 0.001) and N-terminal brain natriuretic peptide (NT-proBNP) levels (P < 0.001) in the IMW group were significantly higher than those in the control group. The proportion of anatomic complete revascularization (P = 0.009), left ventricular ejection fraction (P = 0.010), and alanine transaminase (P = 0.014) and triglycerides levels (P = 0.014) in the IMW group were significantly lower than those in the control group. Logistic regression analysis showed that anatomic complete revascularization (OR=0.350, 95%CI 0.157-0.781) and NT-proBNP level (OR=1.002, 95%CI 1.000-1.004) were independent risk factors for IMW. CONCLUSION: The independent risk factors for decreased IMW in patients with CAD were anatomic incomplete revascularization and NT-proBNP level.
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Doença das Coronárias , Função Ventricular Esquerda , Humanos , Volume Sistólico , Doença das Coronárias/complicações , Doença das Coronárias/epidemiologia , Debilidade Muscular/epidemiologia , Debilidade Muscular/etiologia , Fatores de Risco , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , BiomarcadoresRESUMO
SGLT-2 inhibitors, such as empagliflozin, have been shown to reduce the occurrence of cardiovascular events and delay the progression of atherosclerosis. However, its role in atherosclerotic calcification remains unclear. In this research, ApoE-/- mice were fed with western diet and empagliflozin was added to the drinking water for 24 weeks. Empagliflozin treatment significantly alleviated arterial calcification assessed by alizarin red and von kossa staining in aortic roots and reduced the lipid levels, while had little effect on body weight and blood glucose levels in ApoE-/- mice. In vitro studies, empagliflozin significantly inhibits calcification of primary vascular smooth muscle cells (VSMCs) and aortic rings induced by osteogenic media (OM) or inorganic phosphorus (Pi). RNA sequencing of VSMCs cultured in OM with or without empagliflozin showed that empagliflozin negatively regulated the osteogenic differentiation of VSMCs. And further studies confirmed that empagliflozin significantly inhibited osteogenic differentiation of VSMCs via qRT-PCR. Our study demonstrates that empagliflozin alleviates atherosclerotic calcification by inhibiting osteogenic differentiation of VSMCs, which addressed a critical need for the discovery of a drug-based therapeutic approach in the treatment of atherosclerotic calcification.
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Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction without overt central nervous system infection. Caffeine citrate has therapeutic effect on different brain diseases, while its role in SAE remains unclear. The expression levels of interleukin (IL)-18 and IL-1ß were upregulated in the cerebrospinal fluid of the subjects. In this study, a rat model of SAE was established by cecal ligation and puncture. Caffeine citrate inhibited SAE-induced neuronal apoptosis and astrocytic activation, decreased reactive oxygen species (ROS) generation, and elevated mitochondrial membrane potential (MMP) level in the cerebral cortex. In vitro, primary astrocytes were isolated from rat cerebral cortex and incubated with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Caffeine citrate reduced ROS and MMP levels and mitochondrial complex enzyme activities in LPS plus IFN-γ-induced astrocytes. Moreover, caffeine citrate inhibited the activation of nucleotide-binding and oligomerization domain (NOD)-like receptor (NLRP3) inflammasome and decreased the production of IL-1ß and IL-18 in vivo and in vitro. Notably, caffeine citrate promoted UCP2 expression in astrocytes. The neuroprotective role of UCP2 has been reported in several experimental brain diseases. These results suggest that caffeine citrate inhibits neuronal apoptosis, astrocytic activation, mitochondrial dysfunction in rat cerebral cortex, thereby alleviating SAE. The protection of caffeine citrate against SAE may be achieved by the UCP2-mediated NLRP3 pathway inhibition in astrocytes.
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Encefalopatia Associada a Sepse , Animais , Humanos , Ratos , Astrócitos/metabolismo , Cafeína , Citratos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Encefalopatia Associada a Sepse/tratamento farmacológico , Encefalopatia Associada a Sepse/metabolismo , Proteína Desacopladora 2/genética , Proteína Desacopladora 2/metabolismoRESUMO
BACKGROUND: The histopathology of pediatric chronic rhinosinusitis with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is rarely reported due to low prevalence or the unavailability of tissue samples. Hence, we aimed to characterize and compare the histologic features and protein expression of Th1/Th2/Th17-related cytokines in pediatric CRSsNP and CRSwNP. METHODS: The histologic characteristics of 15 children with CRSsNP, 52 children with CRSwNP, and 12 control participants were analyzed using hematoxylin and eosin staining. The expression of Th1/Th2/Th17-related cytokines were examined using immunohistochemistry and the enzyme-linked immunosorbent assay. RESULTS: Pediatric subjects with CRSwNP had more intact epithelium and less submucosal mucous glands compared to those with CRSsNP. Tissue eosinophils were more prevalent in the younger CRSwNP group compared to the older CRSwNP or the CRSsNP groups. The protein concentrations of Th2 cytokines were significantly higher in the CRSwNP group than the CRSsNP group or the control group. Moreover, the protein concentrations of Th17 cytokines were significantly higher in the younger CRSwNP group than the older CRSwNP group or the CRSsNP and control groups. The protein concentrations of Th1 and Th17 cytokines were also significantly higher in the CRSsNP group than the control group. Compared with non-eosinophilic CRSwNP, eosinophilic CRSwNP presented with elevated protein concentrations of Th1 and Th17 cytokines. CONCLUSION: For the first time, we showed that pediatric CRSwNP presents as eosinophilic with Th2/Th17 inflammation, whereas CRSsNP presents as Th1/Th17 inflammation. Our study may provide a theoretical basis for the precise treatment of pediatric CRS in the future.
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BACKGROUND: Nowadays, the heterogeneity of chronic rhinosinusitis (CRS) has attracted extensive attention. The histological patterns and clinical characteristics may vary greatly in different areas and among different groups of people. Prior studies found a shift from the neutrophilic inflammatory pattern to the eosinophilic inflammatory pattern in Asian cities. This study set out with the aim of investigating the changes that have occurred in the past 18 years of southern China and exploring the causes. METHODS: Tissues, clinical, and demographic characteristics were obtained from 473 patients (91 in 2000-2001, 170 in 2010-2011, 212 in 2017-2018) who satisfied the criteria of diffuse (bilateral) chronic rhinosinusitis. The clinical characteristics, including the previous history of allergic rhinitis and asthma, and the major symptoms of rhinosinusitis, were collected. Formalin-fixed nasal tissue was obtained from each patient for calculating inflammatory cells. We also performed immunohistochemistry to evaluate the expression levels of eosinophilic cationic protein (ECP), IgE, myeloperoxidase (MPO), and other Type 1, Type 2, and Type 3 related inflammatory cytokines. RESULTS: The comorbidity of asthma and atopic disease was higher in 2017-2018 compared to 2000-2001. The histological characteristics revealed a significant increase in tissue eosinophils and decrease in neutrophils in 2017-2018 as compared with 2000-2001. Meanwhile, the proportion of eosinophilic CRS (eCRS) increased significantly from 2000 to 2001 to 2017-2018 (P = 0.03). The tissue eosinophil increase was higher in overweight patients (Body Mass Index, BMI≥24) as compared with non-overweight. There was an increasing trend of ECP, IL-13 and IL-17. Besides, IFN-γ and TNF-α decreased. CONCLUSIONS: There was an eosinophilic shift of diffuse rhinosinusitis inflammatory pattern in southern China over the last 18 years. The proportion of eCRS and difficult-to-treat rhinosinusitis has steadily increased, which is associated with the increase of Type 2, Type 3 cytokines and the decrease of Type 1 cytokines. This study also provided firstly evidence of a strong relationship between overweight and eosinophil shift in the southern Chinese population.
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To investigate the correlation between uric acid (UA) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and coronary artery severity in acute coronary syndrome patients of different sexes.A total of 134 patients with acute coronary syndrome (ACS) were investigated. According to sex, there were 96 cases in male group and 38 cases in female group. According to the number of diseased vessels, the degree of coronary artery lesion was determined and divided into negative group (nâ=â21), single vessel lesion group (nâ=â43), double vessel lesion group (nâ=â38), and 3 vessel lesion group (nâ=â32).Univariate analysis showed that UA, NT-proBNP was correlated with the severity of ACS (Pâ<â.05). UA was an independent risk factor for the severity of coronary artery disease in female group (Pâ<â.05), but not in male group (Pâ>â.05). There was no significant correlation between NT-proBNP and severity of coronary artery disease in different sex (Pâ>â.05).UA was significantly correlated with the severity of coronary heart disease, especially in women, but not in men. The level of NT-proBNP was positively correlated with the severity of coronary artery, but no significant difference was found in different sexes.
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Síndrome Coronariana Aguda/metabolismo , Doença da Artéria Coronariana/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Ácido Úrico/sangue , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Caracteres SexuaisRESUMO
Lung adenocarcinoma is a form of non-small-cell lung cancer with high mortality in the advanced stages, and is one of the most common histological subtypes of lung cancer in most countries. Prognosis of lung adenocarcinoma is generally poor, with a median survival of 4-13 months. We report a case of unusually prolonged survival of a patient with advanced lung adenocarcinoma complicated by hypothyroidism. A 71-year-old man with stage IV lung adenocarcinoma presented with hypothyroidism. Surprisingly, without any anti-tumor and anti-hypothyroidism therapy, he survived this lung cancer for longer than 2.5 years before his last follow-up visit. Patients with advanced lung adenocarcinoma rarely survive for longer than 2 years, even after therapy. We hypothesize that hypothyroidism is the cause for this discrepancy. Thyroid hormones can promote growth of carcinoma. Therefore, hypothyroidism appears to be beneficial to anti-cancer therapy. We believe that hypothyroidism, as an adverse event commonly occurring in anti-tumor therapy (e.g., an immune checkpoint inhibitor), might not be able to be completely eliminated.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Hipotireoidismo , Neoplasias Pulmonares , Adenocarcinoma/complicações , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão/complicações , Adenocarcinoma de Pulmão/tratamento farmacológico , Idoso , Humanos , Hipotireoidismo/complicações , Hipotireoidismo/tratamento farmacológico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , MasculinoRESUMO
BACKGROUND: Local and systemic glucocorticoids are mainstay therapies for chronic rhinosinusitis. With respect to local glucocorticoids, nasal spray is used extensively, but some patients do not benefit from short-course treatment. Recently, some clinicians have focused on the effects of high-dose local glucocorticoids in chronic rhinosinusitis with nasal polyps (CRSwNP), such as treatment using nasal irrigation, transnasal nebulization, and nose-dripping therapy (nasal drop) with high-dose budesonide. However, there are little data comparing the effect of short-course high-dose local glucocorticoids with regular nasal spray and oral steroids in the treatment of preoperative CRSwNP patients. Furthermore, the appropriate use of different types of glucocorticoids in different endotypes of CRSwNP remains unclear. METHODS: This randomized controlled clinical research study was performed at a single academic center. Patients who satisfied the criteria of chronic rhinosinusitis with bilateral nasal polyps were randomly assigned in a 1:1:1 ratio to receive oral methylprednisolone, 24 mg/d and budesonide nasal spray, 256 µg/d, or intranasal budesonide suspension, 1 mg/d and budesonide nasal spray, 256 µg/d, or budesonide nasal spray, 256 µg/d for one week. Symptoms, endoscopic scores, and tissue and blood inflammatory cells were recorded before and after the study. Adverse events were recorded by clinicians. RESULTS: A total of 127 patients with CRSwNP underwent randomization. The total nasal symptoms scores (TNSS) decreased significantly in all groups compared to those at baseline. The assessment of the reduction in TNSS demonstrated that the change was significantly greater in the nasal drop group than in the nasal spray group (-7.47 vs -4.10, P = 0.032), and it was also greater in the oral steroid group than in the nasal spray group (-7.30 vs -4.10, P = 0.039). A similar trend also appeared in the reduction in Sinonasal-Outcome Test 22 (SNOT-22). After treatment, a significantly reduction in NP score was observed in the nasal drop group (-0.82) and oral steroid group (-0.85) compared with that in the nasal spray group (-0.10), and there was no significant difference between the nasal drop and oral steroid groups (P = 0.98). While calculating the percentage of patients who were sensitive to glucocorticoid treatment, there was 10.26% in the nasal spray group, 47.37% in the nasal drop group, and 52.50% in the oral steroid group that were sensitive to glucocorticoid treatment. The reduction in NP score was more significant in patients with eosinophilic CRSwNP in the nasal drop group and oral steroid group than in the nasal spray group. However, in patients with non-eosinophilic CRSwNP, the change in NP size was similar in the different treatment groups. CONCLUSION: Budesonide suspension nasal drop can significantly improve the quality of life and reduce the endoscopic score following short-course treatment, and the treatment effect of nasal drop was better than that of regular nasal spray. Budesonide nasal suspension can be used as a regular treatment for eosinophilic CRSwNP and can be an alternative choice for patients with a high percentage of tissue eosinophil infiltration who cannot use oral glucocorticoids.
RESUMO
BACKGROUND: The study aimed to investigate the relationship between the aerobic exercise intensity determined by 6-minute walking distance (6MWD) and its counterpart based on anaerobic threshold (AT) in chronic heart failure (CHF) individuals for exploring suitable means for CHF exercise rehabilitation. METHODS: We retrospectively analyzed data in patient with CHF, who performed cardiopulmonary exercise test (CPET) and 6-minute walking test (6MWT) uniformly. Anthropometric characteristics, left ventricular ejection fraction (LVEF), and multiple parameters of 6MWT and AT were collected. RESULTS: The results of the analysis revealed that the 6MWD was correlated with the AT positively [CHF group: r=0.433, heart failure with reduced ejection fraction (HFrEF) group: r=0.395, heart failure with intermediate ejection fraction (HFmEF) group: r=0.477, heart failure with preserved ejection fraction (HFpEF) group: r=0.445; all P<0.05]. The regression analysis showed that the linear equation model developed can predict exercise intensity based on AT (EIAT) by exercise intensity based on 6MWD (EI6MWD), the aerobic exercise intensity based on AT and 6MWD respectively, of CHF patients. CONCLUSIONS: There is a correlation between EI6MWD and EIAT. 74.6-87.4% of EI6MWD in patients with CHF is equivalent to EIAT. It is feasible to establish the aerobic exercise intensity of patients with CHF equivalent to AT based on 6MWD.
Assuntos
Insuficiência Cardíaca , Limiar Anaeróbio , Humanos , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda , CaminhadaRESUMO
AIMS: Clinical treatment strategies for patients with myocardial ischemia typically include coronary artery recanalization to restore myocardial blood supply. However, myocardial reperfusion insult often induces oxidative stress and inflammation, which further leads to apoptosis and necrosis of myocardial cells. Increasing evidence suggests that microRNAs (miRNAs) participate in the pathological and physiological processes associated with myocardial ischemia reperfusion. MAIN METHODS: In this study, we established a myocardial H/R H9C2 cell model and a mouse I/R model to detect molecules implicated in myocardial I/R regulation and to determine the underlying signal transduction pathways. KEY FINDINGS: Herein, we showed that the expression of miR-374a-5p decreased in a myocardial cell model (H9C2 cells) of hypoxia/reoxygenation (H/R) and mouse model of ischemia/reperfusion (I/R). Alternatively, overexpression of miR-374a-5p was found to ameliorate myocardial cell damage within both in vivo and in vitro models of ischemia. Further, mitogen-activated protein kinase 6 (MAPK6) was identified as a direct target of miR-374a-5p. Thus, by targeting MAPK6, miR-374a-5p was found to negatively regulate MAPK6 expression. However, up-regulation of MAPK6 functioned to inhibit the previously observed protective effect of miR-374a-5p in the H9C2 H/R model. SIGNIFICANCE: Taken together, our study suggests that miR-374a-5p may have protective effects against cardiac I/R injury in vivo, and H/R injury in vitro, thereby providing novel insights into the molecular mechanisms associated with ischemia/reperfusion injury and a potential novel therapeutic target.