RESUMO
N6-methyladenosine (m6A) plays a role in various diseases, but it has rarely been reported in acute lung injury (ALI). The FTO (fat mass and obesity-associated) protein can regulate mRNA metabolism by removing m6A residues. The aim of this study was to examine the role and mechanism of the m6A demethylase FTO in LPS-induced ALI. Lung epithelial FTO-knockout mice and FTO-knockdown/overexpression human alveolar epithelial (A549) cell lines were constructed to evaluate the effects of FTO on ALI. Bioinformatics analysis and a series of in vivo and in vitro assays were used to examine the mechanism of FTO regulation. Rescue assays were conducted to examine whether the impact of FTO on ALI depended on the TXNIP/NLRP3 pathway. In LPS-induced ALI, RNA m6A modification amounts were upregulated, and FTO expression was downregulated. In vivo, lung epithelial FTO knockout alleviated alveolar structure disorder, tissue edema, and pulmonary inflammation and improved the survival of ALI mice. In vitro, FTO knockdown reduced A549 cell damage and death induced by LPS, whereas FTO overexpression exacerbated cell damage and death. Mechanistically, bioinformatics analysis revealed that TXNIP was a downstream target of FTO. FTO deficiency mitigated pyroptosis in LPS-induced ALI via the TXNIP/NLRP3 pathway. Rescue assays confirmed that the impact of FTO on the TXNIP/NLRP3 pathway was significantly reversed by the TXNIP inhibitor SRI-37330. Deficiency of FTO alleviates LPS-induced ALI via TXNIP/NLRP3 pathway-mediated alveolar epithelial cell pyroptosis, which might be a novel therapeutic strategy for combating ALI.
Assuntos
Lesão Pulmonar Aguda , Adenosina/análogos & derivados , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Células Epiteliais Alveolares , Proteínas de Transporte , Lipopolissacarídeos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/genética , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Humanos , Lipopolissacarídeos/farmacologia , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/patologia , Piroptose/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Camundongos , Células A549 , Camundongos Endogâmicos C57BL , Tiorredoxinas/metabolismo , Tiorredoxinas/genética , Masculino , Transdução de SinaisRESUMO
BACKGROUND: The importance of the lipid-related biomarkers has been implicated in the pathological process and prognosis of acute myocardial infarction (AMI). Our work was conducted to discuss and compare the predictive ability of the neutrophil to high-density lipoprotein cholesterol (HDL-C) ratio (NHR) with other existing prognostic indices, for instance, the monocyte to HDL-C ratio (MHR) and the low-density lipoprotein cholesterol (LDL-C) to HDL-C ratio (LDL-C/HDL-C) in elderly patients with AMI. METHODS: Our population was 528 consecutive elderly AMI patients (65-85 years) who were enrolled from Tongji Hospital and grouped according to the cutoff points which were depicted by the receiver operating characteristic (ROC). The Kaplan-Meier curves were plotted with the survival data from the follow-up to investigate the difference between cutoff point-determined groups. Moreover, we assessed the impact of NHR, MHR, LDL-C/HDL-C on the long-term mortality and recurrent myocardial infarction (RMI) with Cox proportional hazard models. RESULTS: Mean duration of follow-up was 673.85 ± 14.32 days (median 679.50 days). According to ROC curve analysis, NHR ≥ 5.74, MHR ≥ 0.67, LDL-C/HDL-C ≥ 3.57 were regarded as high-risk groups. Kaplan-Meier analysis resulted that the high-NHR, high-MHR and high-LDL-C/HDL-C groups presented higher mortality and RMI rate than the corresponding low-risk groups in predicting the long-term clinical outcomes (log-rank test: all P < 0.050). In multivariate analysis, compared with MHR and LDL-C/HDL-C, only NHR was still recognized as a latent predictor for long-term mortality (harzard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.02 to 3.75, P = 0.044) and long-term RMI (HR: 2.23, 95% CI: 1.04 to 4.79, P = 0.040). Furthermore, the positive correlation between NHR and Gensini score (r = 0.15, P < 0.001) indicated that NHR was relevant to the severity of coronary artery to some extent. CONCLUSIONS: NHR, a novel laboratory marker, might be a predictor of the long-term clinical outcomes of elderly patients with AMI, which was superior to MHR and LDL-C/HDL-C.
Assuntos
HDL-Colesterol/sangue , Infarto do Miocárdio/sangue , Infarto do Miocárdio/metabolismo , Neutrófilos/metabolismo , Idoso , Idoso de 80 Anos ou mais , LDL-Colesterol/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Infarto do Miocárdio/patologia , Neutrófilos/citologia , Prognóstico , Modelos de Riscos Proporcionais , Curva ROCRESUMO
BACKGROUND: Fetuin-A is an anti-inflammation and anti-calcification factor involved in the course of coronary artery disease (CAD). But the association between serum fetuin-A level and the prognosis of CAD patients was still controversial. To clarify the association between serum fetuin-A level and the prognosis of CAD patients, we conducted the present meta-analysis. METHODS: The included studies should be potentially relevant prospective studies published in English language before January 2019. The target population of the present meta-analysis was restricted to patients with CAD. The results of studies must report hazard ratio (HR) or Kaplan-Meier survival curve for all-cause mortality or incidence of secondary cardiovascular disease (CVD) events. The pooled HRs were analysed by the method of meta-analysis. RESULTS: A total of four prospective studies, including 4256 participants with CAD disease, were chosen to be included. The pooled HR for all-cause mortality was 0.57 (95% CI: 0.37-0.87), showing a statistically significant association between high serum fetuin-A level and low all-cause mortality in CAD patients. For the incidence of secondary CVD events, the pooled HR was 0.86 (95% CI: 0.60-1.23), indicating no statistically significant association between serum fetuin-A level and incidence of secondary CVD events in CAD patients. CONCLUSION: High serum fetuin-A level associated with lower all-cause mortality in patients with CAD. No association between serum fetuin-A level and incidence of secondary CVD events was found in patients with CAD.
Assuntos
Doença da Artéria Coronariana/mortalidade , alfa-2-Glicoproteína-HS/metabolismo , Idoso , Biomarcadores/metabolismo , Causas de Morte , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Incidência , Masculino , Prognóstico , Estudos ProspectivosRESUMO
PURPOSE: This meta-analysis aimed to evaluate the performance of the Injury Severity Score (ISS), Trauma and Injury Severity Score (TRISS), and the Geriatric Trauma Outcome Score (GTOS) in predicting mortality in geriatric trauma patients. METHODS: The MEDLINE, Web of Science, and EMBASE databases were searched for studies published from January 2008 to October 2023. Studies assessing the performance of the ISS, TRISS, or GTOS in predicting mortality in geriatric trauma patients (over 60 years old) and reporting data for the analysis of the pooled area under the receiver operating characteristic curve (AUROC) and the hierarchical summary receiver operating characteristic curve (HSROC) were included. Studies that were not conducted in a group of geriatric patients, did not consider mortality as the outcome variable, or had incomplete data were excluded. The Critical Appraisal Skills Programme (CASP) Clinical Prediction Rule Checklist was utilized to assess the risk of bias in included studies. STATA 16.0. was used for the AUROC analysis and HSROC analysis. RESULTS: Nineteen studies involving 118,761 geriatric trauma patients were included. The pooled AUROC of the TRISS (AUC = 0.82, 95% CI: 0.77-0.87) was higher than ISS (AUC = 0.74, 95% CI: 0.71-0.79) and GTOS (AUC = 0.80, 95%CI: 0.77-0.83). The diagnostic odds ratio (DOR) calculated from HSROC curves also suggested that the TRISS (DOR = 21.5) had a better performance in predicting mortality in geriatric trauma patients than the ISS (DOR = 6.27) and GTOS (DOR = 4.76). CONCLUSION: This meta-analysis suggested that the TRISS showed better accuracy and performance in predicting mortality in geriatric trauma patients than the ISS and GTOS.
RESUMO
Geochemical background and baseline values are important parameters for understanding the geochemical characteristics of soil elements, but the research degree of these two parameters is lacking in Hebei Province. Therefore, data from the multi-purpose regional geochemical survey and land quality geochemical assessment in Hebei Province from 2004 to 2018 were collected, covering approximately 71% of the land area of the whole province. Based on the data of surface soil and deep soil, scientific and robust methods including median value and median absolute deviation were used to calculate the geochemical background values, geochemical baseline values, as well as variation ranges of 54 indexes (Ag, Al2O3, As, Au, B, Ba, Be, Bi, Br, CaO, Cd, Ce, Cl, Co, Cr, Cu, F, Fe2O3, Ga, Ge, Hg, I, K2O, La, Li, MgO, Mn, Mo, N, Na2O, Nb, Ni, P, Pb, pH, Rb, S, Sb, Sc, Se, SiO2, Sn, Sr, Th, Ti, Tl, U, V, W, Y, Zn, Zr, total carbon (TC), and organic carbon (Corg)) in Hebei Province and 11 prefecture-level cities. The change rate in geochemical background for each index was also calculated. The results showed that the geochemical background and baseline values of most soil chemical elements in Hebei Province were lower than those nationwide, but the values of Ba, Br, Cl, MgO, Na2O, P, pH, S, Sr, and TC were higher, with CaO being the highest. Compared with those in north China, there was no significant difference in the geochemical background and baseline values for the 54 indexes, with the ratios of 0.83-1.17 and 0.79-1.19, respectively. Significant changes in the geochemical background for Corg, Hg, N, P, S, and Se were observed in Hebei Province, indicating that these indexes were greatly influenced by human factors. Preliminary analysis suggests that coal burning emissions and agricultural chemical use were two very important inducing factors.
RESUMO
BACKGROUND AND PURPOSE: Endothelium-derived hyperpolarizing factor (EDHF) has been suggested as a therapeutic target for vascular protection against ischaemic brain injury. However, the molecular entity of EDHF and its action on neurons remains unclear. This study was undertaken to demonstrate whether the hydrogen sulfide (H2 S) acts as EDHF and exerts neuroprotective effect via large-conductance Ca2+ -activated K+ (BKCa /KCa 1.1) channels. EXPERIMENTAL APPROACH: The whole-cell patch-clamp technology was used to record the changes of BKCa currents in rat neurons induced by EDHF. The cerebral ischaemia/reperfusion model of mice and oxygen-glucose deprivation/reoxygenation (OGD/R) model of neurons were used to explore the neuroprotection of EDHF by activating BKCa channels in these neurons. KEY RESULTS: Increases of BKCa currents and membrane hyperpolarization in hippocampal neurons induced by EDHF could be markedly inhibited by BKCa channel inhibitor iberiotoxin or endothelial H2 S synthase inhibitor propargylglycine. The H2 S donor, NaHS-induced BKCa current and membrane hyperpolarization in neurons were also inhibited by iberiotoxin, suggesting that H2 S acts as EDHF and activates the neuronal BKCa channels. Besides, we found that the protective effect of endothelium-derived H2 S against mice cerebral ischaemia/reperfusion injury was disrupted by iberiotoxin. Importantly, the inhibitory effect of NaHS or BKCa channel opener on OGD/R-induced neuron injury and the increment of intracellular Ca2+ level could be inhibited by iberiotoxin but enhanced by co-application with L-type but not T-type calcium channel inhibitor. CONCLUSION AND IMPLICATIONS: Endothelium-derived H2 S acts as EDHF and exerts neuroprotective effects via activating the BKCa channels and then inhibiting the T-type calcium channels in hippocampal neurons.
Assuntos
Sulfeto de Hidrogênio , Fármacos Neuroprotetores , Canais de Potássio Cálcio-Ativados , Animais , Fatores Biológicos , Endotélio , Sulfeto de Hidrogênio/farmacologia , Camundongos , Fármacos Neuroprotetores/farmacologia , RatosRESUMO
BACKGROUND: Contrast-induced nephropathy (CIN) is acute renal failure observed after administration of iodinated contrast media during angiographic or other medical procedures. In recent years, many studies have focused on biomarkers that recognize CIN and/or predict its development in advance. One of the many biomarkers studied is the platelet-to-lymphocyte ratio (PLR). We performed a systematic review and meta-analysis to evaluate the correlation between PLR level and CIN. METHODS: Relevant studies were searched in PUBMED, EMBASE, and Web of Science until September 15, 2018. Case-control studies reporting admission PLR levels in CIN and non-CIN group in patients with acute coronary syndrome (ACS) were included. The pooled weighted mean difference (WMD) and 95% confidence intervals (95%CI) were calculated to assess the association between PLR level and CIN using a random-effect model. RESULTS: Six relevant studies involving a total of 10452 ACS patients (9720 non-CIN controls and 732 CIN patients) met our inclusion criteria. A meta-analysis of 6 case-control studies showed that PLR levels were significantly higher in CIN group than those in non-CIN group (WMDâ=â33.343, 95%CIâ=â18.863 to 47.823, P < .001, Iâ=â88.0%). CONCLUSION: For patients with ACS after contrast administration, our meta-analysis shows that on-admission PLR levels in CIN group are significantly higher than those of non-CIN group. However, large and matched cohort studies are needed to validate these findings and assess whether there is a real connection or just an association.
Assuntos
Síndrome Coronariana Aguda/epidemiologia , Injúria Renal Aguda/induzido quimicamente , Plaquetas/metabolismo , Meios de Contraste/efeitos adversos , Linfócitos/metabolismo , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/cirurgia , Angiografia Coronária/efeitos adversos , Angiografia Coronária/métodos , Humanos , Contagem de Linfócitos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodosRESUMO
Mining induced generally adverse effect to the environmental ecosystems. This paper studied the beneficial element Se produced in the process of coal mining and burning. The occurrence form of Se in soil and surface water influx into the mine water and the enrichment of Se by crops such as wheat, maize and rice were analyzed. The results indicated that organic and residual forms are the dominant forms of Se in soil, with the soluble form accounting for only 1%. Se4+ and Se6+ accounted for 23.89% and 32.99% in total soluble Se in soil, respectively. In the surface water influx into the mine water, the percentages were 37.78% and 40.24%, respectively. The mean contents of Se in wheat, maize and rice were 0.169 mg x kg(-1), 0.094 mg x kg(-1) and 0.26 mg x kg(-1), respectively. Rice was irrigated using the mine water, which did not only solve the problem of waste water, but also produced Se-enriched rice, moreover, the contents of deleterious elements were not high. Therefore, making full use of the Se-enriched resource in the mining area would weaken the adverse effect of mining.