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Background: It is crucial to distinguish unstable from stable intracranial aneurysms (IAs) as early as possible to derive optimal clinical decision-making for further treatment or follow-up. The aim of this study was to investigate the value of a deep learning model (DLM) in identifying unstable IAs from computed tomography angiography (CTA) images and to compare its discriminatory ability with that of a conventional logistic regression model (LRM). Methods: From August 2011 to May 2021, a total of 1,049 patients with 681 unstable IAs and 556 stable IAs were retrospectively analyzed. IAs were randomly divided into training (64%), internal validation (16%), and test sets (20%). Convolutional neural network (CNN) analysis and conventional logistic regression (LR) were used to predict which IAs were unstable. The area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the discriminating ability of the models. One hundred and ninety-seven patients with 229 IAs from Banan Hospital were used for external validation sets. Results: The conventional LRM showed 11 unstable risk factors, including clinical and IA characteristics. The LRM had an AUC of 0.963 [95% confidence interval (CI): 0.941-0.986], a sensitivity, specificity and accuracy on the external validation set of 0.922, 0.906, and 0.913, respectively, in predicting unstable IAs. In predicting unstable IAs, the DLM had an AUC of 0.771 (95% CI: 0.582-0.960), a sensitivity, specificity and accuracy on the external validation set of 0.694, 0.929, and 0.782, respectively. Conclusions: The CNN-based DLM applied to CTA images did not outperform the conventional LRM in predicting unstable IAs. The patient clinical and IA morphological parameters remain critical factors for ensuring IA stability. Further studies are needed to enhance the diagnostic accuracy.
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Exposure to metals increases the risk of many diseases and has become a public health concern. However, few studies have focused on the effect of metal on abdominal aortic calcification (AAC), especially the combined effects of metal mixtures. In this study, we aim to investigate the combined effect of metals on AAC risk and determine the key components in the multiple metals. We tried to investigate the relationship between multiple metal exposure and AAC risk. Fourteen urinary metals were analyzed with five statistical models as follows: generalized linear regression, weighted quantile sum regression (WQS), quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) models. A total of 838 participants were involved, of whom 241 (28.8%) had AAC. After adjusting for covariates, in multiple metal exposure logistic regression, cadmium (Cd) (OR = 1.364, 95% CI = 1.035-1.797) was positively associated with AAC risk, while cobalt (Co) (OR = 0.631, 95% CI = 0.438-0.908) was negatively associated with AAC risk. A significant positive effect between multiple metal exposure and AAC risk was observed in WQS (OR = 2.090; 95% CI = 1.280-3.420, P < 0.01), Qgcomp (OR = 1.522, 95% CI = 1.012-2.290, P < 0.05), and BKMR models. It was found that the positive association may be driven primarily by Cd, lead (Pb), uranium (U), and tungsten (W). Subgroups analysis showed the association was more significant in participants with BMI ≥ 25 kg/m2, abdominal obesity, drinking, and smoking. Our study shows that exposure to multiple metals increases the risk of AAC in adults aged ≥ 40 years in the USA and that Cd, Pb, U, and W are the main contributors. The association is stronger in participants who are obese, smoker, or drinker.
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Cádmio , Metais Pesados , Adulto , Humanos , Teorema de Bayes , Chumbo , Inquéritos Nutricionais , Cobalto , ObesidadeRESUMO
The effects of far infrared radiation drying (FID) on physical properties (drying kinetics, color, shrinkage ratio, rehydration ratio, and microstructural characterization) and volatile odor characteristics (volatile odor profile distinction and volatile compounds) of shiitake mushrooms were evaluated in this study. During the FID, the drying time decreased with the increase in drying temperature, and it had a less significant effect in the lower temperature range. The increase in drying temperature led to increasing shrinkage and collapse in the microstructure, resulting in a decreased rehydration rate and highlighting the influence of microstructure characteristics on macroscopic properties. Higher drying temperatures employed in the FID process were found to be associated with a decreasing L* value and an increasing ΔE value. The application of principal component analysis can effectively distinguish the significant effect of FID on the volatile odor profiles of shiitake mushrooms. Compared to raw shiitake mushrooms, FID treatment has endowed samples with a greater variety of volatile compounds. After processing with FID, there have been increases in volatile components such as sulfur compounds, acids, nitrogen compounds, and aldehydes, while volatile components like alcohols, ketones, and hydrocarbons have shown decreases.
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A quantitative analysis method for corrosion products based on terahertz spectroscopy is proposed in this paper. Mixture samples consisting of three major corrosion products (magnetite, hematite, and goethite) were prepared in 51 different concentrations. The refractive index spectra measured by terahertz time-domain spectroscopy were projected to the 2D score diagram by performing principal component analysis. The Euclidean distances between the mixtures and pure analyte on the diagram were used to build a concentration prediction model. The results indicate that the established model can precisely predict the concentration of magnetite, which is essential for a stability evaluation of the corrosion system.
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Fresh mother's own milk (MOM) can protect preterm infants from many complications. Often MOM is pasteurized for safety, which can deactivate cellular and bioactive components with protective benefits. Questions remain regarding whether pasteurized MOM provides the same benefits as fresh MOM. The aim of this study was to evaluate the association and feasibility of feeding very preterm infants with fresh MOM. This prospective cohort study included 157 very preterm infants born before 32 weeks' gestational age and with a birthweight below 1500 g. Of these, 82 infants were included in the fresh MOM without any processing group and 75 infants were included in the pasteurized never-frozen MOM (PNFMOM) group. The mortality rate, survival rate without severe complication, incidence of complications, feeding indexes and growth velocities were compared to assess the association and feasibility of feeding fresh MOM. Compared with the PNFMOM group, the fresh MOM group had a higher survival rate without severe complications (p = 0.014) and a lower incidence of bronchopulmonary dysplasia (p = 0.010) after adjustment for confounders. The fresh MOM group regained birthweight earlier (p = 0.021), reached total enteral feeding earlier (p = 0.024), and received total parenteral nutrition for less time (p = 0.045). No adverse events associated with fresh MOM feeding were recorded. Feeding fresh MOM may reduce the incidence of complications in very premature infants. Fresh MOM was shown to be a feasible feeding strategy to improve preterm infants' outcomes.
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Recém-Nascido Prematuro , Mães , Lactente , Feminino , Recém-Nascido , Humanos , Peso ao Nascer , Estudos Prospectivos , Leite Humano , Aleitamento Materno , Unidades de Terapia Intensiva Neonatal , Recém-Nascido de muito Baixo PesoRESUMO
Background: Ventricular septal rupture (VSR) is a type of cardiac rupture, usually complicated by acute myocardial infarction (AMI), with a high mortality rate and often poor prognosis. The aim of our study was to investigate the factors influencing the long-term prognosis of patients with VSR from different aspects, comparing the evaluation performance of the Gensini score, Sequential Organ Failure Assessment (SOFA) score and European Heart Surgery Risk Assessment System II (EuroSCORE II) score systems. Methods: This study retrospectively enrolled 188 patients with VSR between Dec 9, 2011 and Nov 21, 2021at the First Affiliated Hospital of Zhengzhou University. All patients were followed up until Jan 27, 2022 for clinical data, angiographic characteristics, echocardiogram outcomes, intraoperative, postoperative characteristics and major adverse cardiac events (MACEs) (30-day mortality, cardiac readmission). Cox proportional hazard regression analysis was used to explore the predictors of long-term mortality. Results: The median age of 188 VSR patients was 66.2 ± 9.1 years and 97 (51.6%) were males, and there were 103 (54.8%) patients in the medication group, 34 (18.1%) patients in the percutaneous transcatheter closure (TCC) group, and 51 (27.1%) patients in the surgical repair group. The average follow-up time was 857.4 days. The long-term mortality of the medically managed group, the percutaneous TCC group, and the surgical repair group was 94.2, 32.4, and 35.3%, respectively. Whether combined with cardiogenic shock (OR 0.023, 95% CI 0.001-0.054, P = 0.019), NT-pro BNP level (OR 0.027, 95% CI 0.002-0.34, P = 0.005), EuroSCORE II (OR 0.530, 95% CI 0.305-0.918, P = 0.024) and therapy group (OR 3.518, 95% CI 1.079-11.463, P = 0.037) were independently associated with long-term mortality in patients with VSR, and this seems to be independent of the therapy group. The mortality rate of surgical repair after 2 weeks of VSR was much lower than within 2 weeks (P = 0.025). The cut-off point of EuroSCORE II was determined to be 14, and there were statistically significant differences between the EuroSCORE II < 14 group and EuroSCORE II≥14 group (HR = 0.2596, 95%CI: 0.1800-0.3744, Logrank P < 0.001). Conclusion: Patients with AMI combined with VSR have a poor prognosis if not treated surgically, surgical repair after 2 weeks of VSR is a better time. In addition, EuroSCORE II can be used as a scoring system to assess the prognosis of patients with VSR.
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Myocardial Ischemic Injury is a serious threat to human health, and DJ-1 is involved in cardioprotection. The research intended to explore the effects and mechanism of DJ-1 to protect myocardium against ischemia injury. DJ-1 overexpression lentivirus vectors were transduced into the myocardium of SD rats and H9c2 cells, and an AMI model in vivo and a hypoxia model in vitro were established, respectively. Results showed that DJ-1 overexpression alleviated myocardial ischemia injury, as demonstrated by reduced the extent of myocardial infarction, improved cell survival, decreased LDH activity and CK-MB release. Furthermore, DJ-1 interacted with RACK1, activated AMPK/mTOR pathway, induced adaptive autophagy and protected the myocardium. However, RACK1 siRNA or compound C (an AMPK inhibitor) could weaken the above effect of DJ-1 on myocardium. In conclusion, DJ-1 could activate adaptive autophagy by the RACK1/AMPK/mTOR pathway and protect the myocardium against ischemia injury.
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Proteínas Quinases Ativadas por AMP , Traumatismos Cardíacos , Proteína Desglicase DJ-1 , Animais , Humanos , Ratos , Autofagia , Hipóxia , Isquemia , Miocárdio , Proteínas de Neoplasias , Ratos Sprague-Dawley , Receptores de Quinase C Ativada , Serina-Treonina Quinases TOR , Proteína Desglicase DJ-1/metabolismoRESUMO
OBJECTIVE: Nurses' palliative care practice ability is the key to evaluating the quality of palliative care. This study aimed to identify the current situation of palliative care practices, competence and difficulties among nurses and determine whether difficulties play a mediating role between practices and competence. METHODS: A cross-sectional study was conducted. The online survey comprised demographics, the Palliative Care Self-Reported Practices Scale, the Palliative Care Nursing Self-competence Scale and the Palliative Care Difficulties Scale. Data were analysed by using descriptive statistics, univariate analysis, linear regression and mediation analysis. RESULTS: A total of 284 questionnaires were included for statistical analysis. The mean scores for practices, competence and difficulties were 67.81 (SD = 13.60), 124.28 (41.21) and 44.32 (12.68), respectively. There was a correlation between practices, competence and difficulties (p < 0.01). Competence and difficulties were independent predictors of practices (R2 adj = 0.384, p < 0.001). Furthermore, difficulties mediated the relationship between practices and competence (b = 0.052, 95% confidence interval: 0.008-0.155). CONCLUSIONS: Continuous efforts should be made to enhance nurses' practices, competence and problem-solving abilities in palliative care. This study suggested further targeted education programmes, especially in special symptom management, interagency and multidisciplinary communication.
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Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Enfermeiras e Enfermeiros , Humanos , Cuidados Paliativos , Estudos Transversais , Autorrelato , Inquéritos e Questionários , Competência ClínicaRESUMO
In this study, we aimed to evaluate the effect of Nobiletin (NOB) on the placenta of Sprague-Dawley (SD) rats that had undergone reduced uterine perfusion pressure (RUPP) surgery and to evaluate the safety of NOB intervention during pregnancy. The results showed that NOB alleviated placental hypoxia, attenuated placental cell apoptosis, and inhibited placental damage in RUPP rats. No side effect of NOB intervention during pregnancy was observed. BeWo cell lines with P53 knockdown were then constructed using lentiviral transfection, and the P53 signaling pathway was found to be essential for NOB to reduce hypoxia-induced apoptosis of the BeWo cell lines. In summary, NOB attenuated hypoxia-induced placental damage by regulating the P53 signaling pathway, and those findings may contribute some insights into the role of NOB in placental development and the prevention of placental-related diseases.
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Placenta , Pré-Eclâmpsia , Animais , Feminino , Flavonas , Humanos , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Isquemia/tratamento farmacológico , Isquemia/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/prevenção & controle , Gravidez , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
BS-HH-002 is a newly developed drug with excellent antitumor activity, which resulted from the modification and optimization of the side structure of the homoharringtonine (HHT). It is particularly efficient in treatment for acute myeloid leukemia and myelodysplastic syndromes. Here we tested whether BS-HH-002 also had anti-cancer effects on solid tumors, especially pancreatic cancer. The results showed that BS-HH-002 treatment resulted in the complete degradation of the anti-apoptosis protein MCL-1, thereby inhibiting proliferation and inducing apoptosis of pancreatic cancer cells. In contrast, BCL-2 and BCL-XL protein levels were still detected in apoptotic cells. Further, we compared HHT and BS-HH-002 in terms of PK and heart toxicity in animals. Compared to HHT, BS-HH-002 quickly reached high blood concentration after intravenous injection or oral administration, without causing obvious cardiac toxicity. These results indicate that BS-HH-002 is a promising new anti-cancer drug to treat pancreatic and other solid tumors.
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Retinoblastoma, also known as ocular cancer, usually affects children under the age of five. The standard of care for managing early-stage retinoblastoma is a combination of vincristine, carboplatin, and etoposide. However, this combination-based modality has limited applications owing to its side and late effects. Moreover, in advanced tumor stages, nearly 50% of patients would suffer a partial or full loss of vision. Therefore, therapies that preserve vision and reduce side effects are urgently required. Here, we focused mainly on the common loss-of-function (LOF) mutation of retinoblastoma gene 1 (RB1) in advanced retinoblastoma and investigated the synthetic lethality between RB1-LOF and Aurora kinase inhibition. We showed that Aurora kinase A inhibition could lead to cell mitotic abnormality and apoptosis, and demonstrated in vivo efficacy in a mouse model xenografted with RB1-deficient retinoblastoma. Our findings provide a promising druggable molecular target and potential clinical strategy for tackling retinoblastoma disease.
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Antineoplásicos/uso terapêutico , Aurora Quinase A/antagonistas & inibidores , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Animais , Apoptose , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Genes do Retinoblastoma/genética , Humanos , Mutação com Perda de Função , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitose , Neoplasias da Retina/genética , Neoplasias da Retina/patologia , Retinoblastoma/genética , Retinoblastoma/patologiaRESUMO
Aim: Long noncoding RNA (lncRNA) BC032469-dependent gold nanoparticle molecular beacons (AuNP-MB) were constructed for the detection of gastric cancer cells. Materials & methods: The AuNP-MBs were prepared according to well-established procedures based on the Au-S interaction between the gold lattice and thiol functionalized oligonucleotides. More importantly, the stability and targeting ability of AuNP-MB were verified by a series of in vitro and in vivo experiments. Results: The lncRNA-dependent probes were successfully utilized for AuNP-MB-based intracellular imaging, with fluorescence effectively emitted in GC cells, but not in normal cells. Notably, such fluorescent emission was positively correlated with lncRNA BC032469 expression. Conclusion: The authors developed an effective fluorescent imaging probe for the recognition of gastric cancer cells.
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Nanopartículas Metálicas , RNA Longo não Codificante , Neoplasias Gástricas , Corantes Fluorescentes , Ouro , Humanos , RNA Longo não Codificante/genética , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/genéticaRESUMO
Objectives: Ventricular septal rupture (VSR) is a rare but lethal complication of acute myocardial infarction (AMI). We conducted a retrospective analysis of the clinical characteristics of VSR patients and explored the risk factors for long-term mortality. Methods: In this single-center cohort study, 127 patients diagnosed with post-AMI VSR between May 2012 and April 2019 were included. Demographic, clinical, operative, and outcome data were collected. The 30-day and long-term mortality were outcomes of interest. Cox proportional hazard regression analysis was used to explore the predictors of long-term mortality. Results: The mean age of the VSR cohort was 66.6 ± 8.7 years, 67 (52.8%) were males. Among the 127 patients, 78 patients (61.4%) were medically managed, 31 (24.4%) patients underwent percutaneous transcatheter closure (TCC), and 18 (14.2%) patients received surgical repair. The median follow-up time was 1129 days [interquartile range: 802-2019 days]. The 30-day mortality of the medically managed group, percutaneous TCC group, and surgical management group was 93.6, 22.6, and 11.1%, respectively; and the long-term mortality was 96.2, 25.8, and 22.2%, respectively. VSR repair treatment including surgical management (HR 0.01, 95% CI 0.001-0.09, p < 0.001) and percutaneous TCC (HR 0.09, 95% CI 0.03-0.26, p < 0.001) was associated with a better prognosis, and cardiogenic shock (CS) (HR 9.30, 95% CI 3.38-25.62, p < 0.001) was an independent risk factor of long-term mortality. Conclusions: The prognosis of VSR patients without operative management remains poor, especially in those complicated with CS. Timely and improved surgery treatment is needed for better outcomes in VSR patients.
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BACKGROUND: The use of magnetically controlled capsules for gastroscopy is in the early stages of clinical adoption. We aimed to evaluate the safety and efficacy of a fully automated magnetically controlled capsule endoscopy (FAMCE) system in clinical practice for gastroscopy and small bowel examination. METHODS: We did a prospective, comparative study to evaluate the safety and efficacy of FAMCE. Patients from two hospitals in Chongqing, China were consecutively enrolled. Eligible participants were aged 18-80 years with suspected gastric pathology and no previous surgery. Participants underwent FAMCE for screening of gastric lesions, then conventional transoral gastroscopy 2 h later, and stomach examination results were compared. The primary outcome was the rate of complete detection of gastric anatomy landmarks (cardia, fundus, body, angulus, antrum, and pylorus) by FAMCE. Secondary outcomes were the time required for gastric completion by FAMCE, the rate of detection of gastric lesions by FAMCE compared with conventional transoral gastroscopy, and the rate of complete small bowel examination. Adverse events were also evaluated. The study was registered in the Chinese Clinical Trial Registry, ChiCTR2000040507. FINDINGS: Between May 12 and Aug 17, 2020, 114 patients (mean age 44·0 years [IQR 34·0-55·0]; 63 [55%] female) were enrolled. The rate of complete detection of gastric anatomical structures by FAMCE was 100% (95% CI 99·3-100·0). The concordance between FAMCE and conventional transoral gastroscopy was 99·61% (99·45-99·78). The mean completion time of a gastroscopy with FAMCE was 19·17 min (SD 1·43; median 19·00, IQR 19·00-20·00), compared with 5·21 min (2·00; 5·18, 3·68-6·45) for conventional transoral gastroscopy. In 114 enrolled patients, 214 lesions were detected by FAMCE and conventional transoral gastroscopy. Of those, 193 were detected by both modalities. FAMCE missed five pathologies (four cases of gastritis and one polyp), whereas conventional transoral gastroscopy missed 16 pathologies (12 cases of gastritis, one polyp, one fundal xanthoma, and two antral erosions). FAMCE was able to provide a complete small bowel examination for all 114 patients and detected intestinal lesions in 50 (44%) patients. During the study, two (2%) patients experienced adverse events. No serious adverse events were recorded, and there was no evidence of capsule retention. INTERPRETATION: The performance of FAMCE is similar to conventional transoral gastroscopy in completion of gastric examination and lesion detection. Furthermore, it can provide a complete small bowel examination. Therefore, FAMCE could be effective method for examination of the gastrointestinal tract. FUNDING: Chinese National Key Research and Development Program.
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Endoscopia por Cápsula/métodos , Gastroscopia/métodos , Enteropatias/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Imãs , Gastropatias/diagnóstico por imagem , Estômago/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscopia por Cápsula/instrumentação , Estudos de Viabilidade , Feminino , Seguimentos , Gastroscopia/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Estômago/anatomia & histologia , Adulto JovemRESUMO
BACKGROUND: Endometrial cancer is generally one of the most evident malignant tumours of the female reproductive system, and the mechanisms underlying its cell proliferation and apoptosis are key to research in gynaecological oncology. In the paper, the in-depth molecular mechanism by which DJ-1 protein regulates the proliferation and apoptosis of Ishikawa cells was investigated. METHODS AND RESULTS: DJ-1 knockdown and overexpressing Ishikawa stable cell lines were established by lentiviral transduction. The levels of DJ-1 and noncanonical NF-κB signaling key proteins were evaluated by Western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were applied to analyze the cell viability and apoptosis. Co-immunoprecipitation experiment was utilized to assess the DJ-1-Cezanne interaction. The results showed that DJ-1 overexpression conferred apoptosis resistance and high proliferation on Ishikawa cells, while DJ-1 knockdown in Ishikawa cells produced the opposite results. These findings again suggested that DJ-1 inhibits the apoptosis and promotes the proliferation of Ishikawa cells. More crucially, further data showed that the noncanonical NF-κB activation was required for the regulation of Ishikawa cell proliferation and apoptosis by DJ-1. Meanwhile, it was found that noncanonical NF-κB pathway may be activated by DJ-1 interacting with and negatively regulating Cezanne in Ishikawa cells. CONCLUSIONS: Overall, this work revealed that DJ-1 associates with and negatively regulates Cezanne and consequently triggers the noncanonical NF-κB activation, thereby regulating Ishikawa cell proliferation and apoptosis.
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Neoplasias do Endométrio/metabolismo , NF-kappa B/metabolismo , Proteína Desglicase DJ-1/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Neoplasias do Endométrio/genética , Endopeptidases/metabolismo , Endopeptidases/fisiologia , Feminino , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteína Desglicase DJ-1/genética , Transdução de Sinais/genéticaRESUMO
It has been reported that morphine pretreatment (MP) can exert neuroprotective effects, and that protein kinase C (PKC) participates in the initiation and development of ischemic/hypoxic preconditioning in the brain. However, it remains unknown whether PKC is involved in MP-induced neuroprotection. The aim of the present study, which included in vivo and in vitro experiments, was to determine whether the conventional γ isoform of PKC (cPKCγ) was involved in the protective effects of MP against cerebral ischemic injury. The present study included an in vivo experiment using a mouse model of middle cerebral artery occlusion and an in vitro experiment using neuroblastoma N2a cells with oxygen-glucose deprivation (OGD). Furthermore, a cPKCγ antagonist, Go6983, was used to determine the involvement of cPKCγ in the protective effects of MP against cerebral ischemic injury. In the in vivo experiment, neurological deficits, ischemic infarct volume, neural cell damage, apoptosis and caspase-3 activation were evaluated. In the in vitro experiment, flow cytometry was used to determine the activation of caspase-3 in N2a cells with OGD. It was found that MP protected against cerebral ischemic injury. However, intracerebroventricular injection of the cPKCγ antagonist before MP attenuated the neuroprotective effect of MP and increased the activation of cleaved caspase-3. These findings suggested that MP may provide protection against cerebral ischemic injury via a cPKCγ-mediated anti-apoptosis pathway.
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INTRODUCTION: The negative relationship between maternal high-density lipoprotein-cholesterol (HDL-c) level during pregnancy and infant birth weight has been found. Syncytialization (differentiation and fusion) of trophoblast cells is important to fetal development. HDL has an antioxidant effect, and has been proved to protect trophoblast functions including hormone secretion and invasion. However, HDL is susceptible to oxidation, and high concentrations of HDL impair cell growth and oxidized HDL (oxHDL) inhibits cell proliferation and migration. Moreover, the effects of HDL and oxHDL on trophoblast syncytialization have not been characterized. The aim of this study was to investigate the effects of HDL and oxHDL on trophoblast syncytialization. METHODS: Human choriocarcinoma trophoblasts (BeWo cells) were treated with human HDL or oxHDL and then induced to differentiate by forskolin in syncytialization assays. Expression levels of mRNAs and proteins regulating syncytialization were detected by real-time PCR and western blotting, respectively. RESULTS: Treatments of HDL at high concentrations reduced human chorionic gonadotropin (hCG) secretion, placental alkaline phosphatase activity and fusion rates, and decreased the expressions of GCM1 and ERVW-1 mRNA as well as phospho-MAPK1/3 (p-MAPK1/3) and total MAPK1/3 protein in the forskolin-induced syncytialization of BeWo cells. Furthermore, treatment of oxHDL (20 µg/ml) decreased hCG secretion, but increased the expression of p-MAPK1/3 protein. DISCUSSION: These data suggested that both HDL at high concentrations and oxHDL inhibited BeWo cells syncytialization, and might be harmful to placental and fetal development.
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Lipoproteínas HDL/farmacologia , Lipoproteínas LDL/farmacologia , Trofoblastos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Fusão Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Colforsina/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Placenta/citologia , Placenta/efeitos dos fármacos , Placenta/fisiologia , Gravidez , Trofoblastos/fisiologiaRESUMO
Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays an important pathogenic role. However, the current drugs for IBD treatment are far from optimal. Previous researches indicated that parthenolide (PTL) had not only anti-cancer properties but also strong anti-inflammatory activities. Rationale: To investigate the protective effect of PTL on colon inflammation and demonstrate the underlying gut microbiota-dependent mechanism. Methods: Colon inflammation severity in mouse model was measured by body weight change, mortality, colon length, disease activity index (DAI) score, H&E staining and colonoscopy evaluation. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Luminex cytokine microarray and Enzyme-linked immunosorbent assay (ELISA) were conducted to measure the colon cytokines profile. The frequency of immune cells in lamina propria (LP) and spleen were phenotyped by flow cytometry. Results: The PTL-treated mice showed significantly relieved colon inflammation, as evidenced by a reduction in body weight loss, survival rate, shortening of colon length, DAI score, histology score and colonoscopy score. Notably, when the gut microbiota was depleted using antibiotic cocktails, the protective effect of PTL on colon inflammation disappeared. PTL treatment downregulated the level of proinflammatory cytokines, including IL-1ß, TNF-α, IL-6, and IL-17A and upregulated the immunosuppressive cytokine IL-10 in colon tissue. 16S rRNA sequencing indicated that PTL-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased SCFAs production in PTL-treated mice. Additionally, PTL administration selectively upregulated the frequency of colonic regulatory T (Treg) cells as well as downregulated the ratio of colonic T helper type 17 (Th17) cells, improving the Treg/Th17 balance to maintain intestinal homeostasis. Gut microbiota depletion and fecal microbiota transplantation (FMT) was performed to confirm this gut microbiota-dependent mechanism. Conclusions: PTL ameliorated colon inflammation in a gut microbiota-dependent manner. The underlying protective mechanism was associated with the improved Treg/Th17 balance in intestinal mucosa mediated through the increased microbiota-derived SCFAs production. Collectively, our results demonstrated the role of PTL as a potential gut microbiota modulator to prevent and treat IBD.
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Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Animais , Colonoscopia , Sulfato de Dextrana/toxicidade , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Microbioma Gastrointestinal/efeitos dos fármacos , Doenças Inflamatórias Intestinais/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/metabolismoRESUMO
Coal tar pitch (CTP) with high carbon content and wide source of raw materials was an excellent precursor for the preparation of porous carbons (PCs). CTP was composed of polycyclic aromatic hydrocarbons (PAHs) with complex molecular size and chemical structure, the separation of CTP into several fractions with relatively narrow molecular weight by solvent extraction was of significance for CTP utilization. In this paper, CTP was treated by single-solvent extraction (carbon disulfide, acetone and ethyl acetate), and the six fractions were used as raw materials to prepare PCs as electrode material for electric double layer capacitor. The fractions were well characterized and the effect of mass distribution of different narrow fractions on structure property and electrochemical performance of the PCs was studied. The PCs prepared by carbon disulfide extract, acetone raffinate and ethyl acetate extract, containing more PAHs, exhibited the excellent specific capacitance performance in comparison with its residual components. The remarkable performance might contribute in the enhanced transport of electrolyte ions via the molecular graphene structure of PAHs. Additionally, the PC prepared by carbon disulfide raffinate showed outstanding cycling performance (99.7% at 2 A g-1 after 15,000 cycles) which was related to its unique layered porous structure.