Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 466
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Stat Med ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32232863

RESUMO

Dengue has been as an endemic with year-round presence in Singapore. In the recent years 2013, 2014, and 2016, there were several severe dengue outbreaks, posing serious threat to the public health. To proactively control and mitigate the disease spread, early warnings of dengue outbreaks, at which there are rapid and large-scale spread of dengue incidences, are extremely helpful. In this study, a two-step framework is proposed to predict dengue outbreaks and it is evaluated based on the dengue incidences in Singapore during 2012 to 2017. First, a generalized additive model (GAM) is trained based on the weekly dengue incidence data during 2006 to 2011. The proposed GAM is a one-week-ahead forecasting model, and it inherently accounts for the possible correlation among the historical incidence data, making the residuals approximately normally distributed. Then, an exponentially weighted moving average (EWMA) control chart is proposed to sequentially monitor the weekly residuals during 2012 to 2017. Our investigation shows that the proposed two-step framework is able to give persistent signals at the early stage of the outbreaks in 2013, 2014, and 2016, which provides early alerts of outbreaks and wins time for the early interventions and the preparation of necessary public health resources. In addition, extensive simulations show that the proposed method is comparable to other potential outbreak detection methods and it is robust to the underlying data-generating mechanisms.

2.
Int J Oncol ; 56(3): 807-820, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32124947

RESUMO

Previous studies have demonstrated that long non­coding RNAs (lncRNAs) are involved in breast cancer development, progression and metastasis. However, the association between lncRNAs and breast cancer stem cells (BCSCs) has been poorly explored. To address this issue, microarray analyses were performed to detect the lncRNA profile of BCSCs. In addition, bioinformatics analyses, including Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analyses, were performed to explore the functional roles of lncRNAs in BCSCs. Lastly, loss of function assays were used to explore the potential function of lncRNA CUE domain containing 1 (lncCUEDC1). A total of 142 differentially expressed lncRNAs were identified. Among these, 25 were downregulated and 117 were upregulated in BCSCs compared with in non­BCSCs. In addition, the present study revealed that the lncRNAs were largely associated with stemness­related signaling pathways. Furthermore, it was demonstrated that lncCUEDC1 negatively regulated the phenotype and biological functions of BCSCs in vitro. Mechanistically, lncCUEDC1 could bind NANOG to inhibit the stemness. To the best of our knowledge, the present study was the first to established the lncRNA profile of BCSCs. These findings provided evidence for exploring the functions of lncRNAs in BCSCs and indicated that lncCUEDC1 is a prospective target in BCSCs.

4.
Cancer Med ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32168429

RESUMO

BACKGROUND: ROS1 gene fusion represents a specific subtype of non-small cell lung cancer (NSCLC). Crizotinib is recommended for ROS1-positive NSCLC due to its favorable outcome in published clinical trials. However, due to the low incidence of ROS1-positive NSCLC, there is limited information on real-world clinical outcomes in patients treated with either crizotinib or platinum-based doublet chemotherapy. METHODS: Outcomes were recorded in 102 patients with stage Ⅲb or Ⅳ NSCLC who were treated at four Chinese hospitals between April, 2010 and June, 2019. RESULTS: Of the 102 patients followed, 71.6% were females, 81.4% were non-smokers, and 98.0% had adenocarcinoma. First-line treatment with crizotinib achieved a significantly longer median progression-free survival (PFS) compared with platinum-based chemotherapy (14.9 months vs 8.5 months, respectively; P < .001). Next-generation sequencing (NGS) identified 61 patients who had ROS1 fusion variants, including CD74 (n = 33) and non-CD74 (n = 28) variants. In patients harboring CD74 fusion variants, the median PFS with first-line crizotinib treatment was significantly longer than in those harboring non-CD74 fusion variants (20.1 months vs 12.0 months, respectively; P = .046). However, in patients treated with platinum-based chemotherapy, there was no significant difference in PFS between the CD74 and non-CD74 variant groups (8.6 months vs 4.3 months, respectively; P = .115). Overall survival (OS) was not reached. CONCLUSIONS: First-line therapy with crizotinib is more beneficial than platinum-based chemotherapy in patients with advanced NSCLC with different ROS1 fusion variants. Patients harboring CD74 fusion variants appear to respond better to crizotinib.

5.
Medicine (Baltimore) ; 99(9): e19296, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118744

RESUMO

OBJECTIVE: The aim of this study was to compare tissue doppler imaging (TDI) and equilibrium radionuclide angiography (ERNA) for detection of right ventricular (RV) dyssynchrony and prediction of the acute response to cardiac resynchronization therapy (CRT). METHODS: This study was approved by the local ethics committee of Huai'an First People's Hospital. Patient consent was not provided due to the use of completely anonymous images from which the individual could not be identified in this study. Thirty-three patients with nonischemic dilated cardiomyopathy underwent both TDI and ERNA before and within 48 hour after CRT implantation. RV dyssynchrony was measured with TDI using the difference in time to peak systolic velocity between the RV free wall and ventricular septum (RV-T). With ERNA, the standard of RV mean phase angle and RV phase standard deviation (RVmPA% and RVPSD%) were assessed. RESULTS: Moderate positive correlations were observed among baseline RVmPA%, RVPSD% and RV-T (r = 0.689 and 0.716, P < .001). Twenty patients (61%) with a reduction of at least 15% in LV end-systolic volume were categorized as acute responders after CRT. Responders showed significant reduction in RVmPA% and RVPSD% after CRT (53.60 ±â€Š4.15% to 43.95 ±â€Š6.88% and 14.00 ±â€Š2.41% to 10.40 ±â€Š1.67%, P < .05), whereas RV-T remained unchanged (50.10 ±â€Š10.28 ms to 49.25 ±â€Š13.64ms, NS). Receiver operating characteristic curve showed that the cut-off value of RV-T was 48.5ms, yielding 65% sensitivity and 77% specificity to predict acute respond to CRT. The cut-off value of RVmPA% was 49.5%, yielding 85% sensitivity and 85% specificity and the cut-off value of RVPSD% was 11.5%, yielding 85% sensitivity and 92% specificity. CONCLUSION: ERNA might be an appropriate alternative to TDI for assessment of RV dyssynchrony. Either RVmPA% or RVPSD% was highly predictive for acute response to CRT.


Assuntos
Terapia de Ressincronização Cardíaca/normas , Imagem do Acúmulo Cardíaco de Comporta/normas , Cardiopatias/diagnóstico , Função Ventricular Direita , Idoso , Terapia de Ressincronização Cardíaca/métodos , Terapia de Ressincronização Cardíaca/estatística & dados numéricos , Feminino , Imagem do Acúmulo Cardíaco de Comporta/métodos , Imagem do Acúmulo Cardíaco de Comporta/estatística & dados numéricos , Cardiopatias/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC
6.
Microbiol Res ; 236: 126455, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32179389

RESUMO

Echinenone and canthaxanthin are important carotenoid pigments with food and industrial applications. Biosynthesis of echinenone and/or canthaxanthin is catalyzed by ß-carotene ketolase (CrtO), with ß-carotene as the substrate. In this study, we generated transgenic Nostoc sp. PCC 7120 overexpressing a heterologous crtO gene from Nostoc flagelliforme and evaluated the productivity of both pigments. Normal (BG11 medium, 30 °C) and osmotic stress (BG11 medium supplemented with 0.4 M mannitol, 30 °C) conditions were used for cultivation. As compared to control strain, production of echinenone and canthaxanthin in transgenic strain were respectively increased by more than 16 % and 80 %, under either normal or osmotic stress conditions. Especially upon the stress condition, higher proportion of echinenone and canthaxanthin in total pigments was achieved, which should be beneficial for downstream separation and purification. In addition, transgenic strain showed drought tolerance and could revive from desiccation treatment after rewetting. Thus, this study provided technical clues for production of both pigments in engineered cyanobacteria as well as for cyanobacterial anhydrobiotic engineering.

7.
Medicine (Baltimore) ; 99(5): e19026, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000449

RESUMO

INTRODUCTION: Entropion and secondary trichiasis can lead to irritative symptoms and essential damage of ocular surface. There is no literature reporting the lower eyelid entropion related to thyroid-associated ophthalmopathy (TAO), let alone the treatment. Treatment based on etiology may yield effective and sustained results. We report 3 case reports of lower eyelid entropion associated with TAO, and provide an effective and persistent alternative to cure this entropion via the administration of shallow periorbital injections of triamcinolone acetonide (TA). PATIENT CONCERNS: Three patients presented irritative symptoms of ocular surface and diplopia. DIAGNOSIS: According to thyroid dysfunction, physical examination, and imaging findings of extraocular muscle involvement, TAO and unilateral or bilateral lower eyelid entropion were diagnosed. INTERVENTIONS: We administered shallow periorbital injections of TA to the affected eye at 3- to 4-week intervals depending on clinical response. OUTCOMES: All patients underwent complete correction of the lower eyelid entropion and no recurrence was found. CONCLUSION: The cause of lower eyelid entropion related to TAO might be the immunoinflammatory reaction of the lower eyelid retractors, enhancing the traction of pulling the lower eyelid inferoposteriorly. This condition can be treated with shallow periorbital injections of TA. Histopathological evidence and randomized controlled trials are expected to confirm our hypothesis.


Assuntos
Entrópio/tratamento farmacológico , Entrópio/etiologia , Glucocorticoides/administração & dosagem , Oftalmopatia de Graves/complicações , Triancinolona Acetonida/administração & dosagem , Adulto , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade
8.
J Neurotrauma ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32024456

RESUMO

We prospectively evaluated serum concentrations of glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), total tau (T-Tau), and neurofilament light (NF-L) from collegiate athletes at baseline and acutely after sport-related concussion (SRC) using the Quanterix Neurology 4Plex "B" (N4PB) multiplex assay. Uninjured controls were matched on age, sex, race, sport, and concussion history. Clinical outcomes included acute symptom severity, balance, rapid automated naming, computerized cognitive testing, and recovery duration. Baseline (n = 110; median [interquartile range] age = 19 [18-20] years, 54% male, 61% white/Caucasian) and post-SRC (n = 36; median [interquartile range] age = 19 [18-20] years, 50% male, 61% white/Caucasian) blood samples were analyzed. We observed post-SRC elevations from baseline for GFAP (p = 0.001, d = 1.7), T-Tau (p = 0.004, d = 1.3), and NF-L (p = 0.010, d = 1.1). GFAP (area under the curve [AUC] = 0.958, 95% confidence interval [CI] 0.927-0.989, p < 0.001) and NF-L (AUC = 0.904, 95% CI 0.851-0.957, p < 0.001) accurately discriminated SRC from control cases. There were no associations between biomarker concentrations and clinical measurements post-SRC or recovery duration. These findings suggest that, using the multiplex assay, GFAP, T-Tau, and NF-L elevate from baseline acutely after SRC, and both GFAP and NF-L excellently distinguished concussed from control cases. Serum biomarker changes do not necessarily correspond with clinical measurements or recovery duration.

9.
Int J Mol Sci ; 21(2)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936206

RESUMO

With the increasing applications of silver nanoparticles (Ag NPs), the concerns of widespread human exposure as well as subsequent health risks have been continuously growing. The acute and chronic toxicities of Ag NPs in cellular tests and animal tests have been widely investigated. Accumulating evidence shows that Ag NPs can induce inflammation, yet the overall mechanism is incomplete. Herein, using gold nanorod core/silver shell nanostructures (Au@Ag NRs) as a model system, we studied the influence on mice liver and lungs from the viewpoint of metabolism. In agreement with previous studies, Au@Ag NRs' intravenous exposure caused inflammatory reaction, accompanying with metabolic alterations, including energy metabolism, membrane/choline metabolism, redox metabolism, and purine metabolism, the disturbances of which contribute to inflammation. At the same time, dopamine metabolism in liver was also changed. This is the first time to observe the production of dopamine in non-neural tissue after treatment with Ag NPs. As the upregulation of dopamine resists inflammation, it indicates the activation of antioxidant defense systems against oxidative stress induced by Au@Ag NRs. In the end, our findings deepened the understanding of molecular mechanisms of Ag NPs-induced inflammation and provide assistance in the rational design of their biomedical applications.

10.
Thorac Cancer ; 11(3): 679-685, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31975535

RESUMO

BACKGROUND: HER2 mutation is found in 1%-2% of lung cancer patients. Studies comparing chemotherapy to HER2-TKIs are limited. This study aimed to investigate the molecular and clinical patterns of HER2 mutations in advanced non-small cell lung cancer (NSCLC), and compare the different outcomes between chemotherapy and HER2-TKIs. METHODS: Advanced or recurrent non-small cell lung cancer patients with de novo HER2 mutations (N = 75) were included in this study. Molecular information, clinical features, and treatment outcomes were retrospectively collected from a web-based patient registry and hospital chart review. RESULTS: Between October 2012 and December 2018, 65 patients with in-frame insertion mutations, eight with point mutations and two with gene amplification were found. The most common subtypes of insertion mutations were A775_G776insYVMA, G776delinsVC, and V777_G778insGSP. HER2 mutated patients were mostly young-aged, females, never or light smokers, with adenocarcinoma. Chemotherapy achieved better outcomes than HER2-TKIs (median PFS: 5.5 vs. 3.7 months in the first-line setting and 4.2 vs. 2.0 months in the second-line setting, P = 0.001 and 0.031, respectively). In particular for the most common subtype, YVMA insertions, PFS was significantly longer in chemotherapy than HER2-TKIs both in the first-line (6.0 vs. 2.6 months, P = 0.008) and the second-line (4.2 vs. 2.6 months P < 0.001). CONCLUSIONS: HER2 mutated lung cancer patients were younger, mostly females, never or light smokers, with histologically diagnosed adenocarcinomas. Compared with afatinib, chemotherapy might bring more benefit to HER2 mutated advanced lung cancer patients, especially the most common type of HER2 exon 20 insertions, A775_G776insYVMA subtype. KEY POINTS: Chemotherapy achieved better outcomes than afatinib for Chinese HER2 mutated advanced NSCLC patients, especially for the most common subtype, YVMA insertions.

11.
Nutrients ; 12(2)2020 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-31991934

RESUMO

This study aimed to investigate the effect of sesamol (SEM) on the protein kinase A (PKA) pathway in obesity-related hepatic steatosis treatment by using high-fat diet (HFD)-induced obese mice and a palmitic acid (PA)-treated HepG2 cell line. SEM reduced the body weight gain of obese mice and alleviated related metabolic disorders such as insulin resistance, hyperlipidemia, and systemic inflammation. Furthermore, lipid accumulation in the liver and HepG2 cells was reduced by SEM. SEM downregulated the gene and protein levels of lipogenic regulator factors, and upregulated the gene and protein levels of the regulator factors responsible for lipolysis and fatty acid ß-oxidation. Meanwhile, SEM activated AMP-activated protein kinase (AMPK), which might explain the regulatory effect of SEM on fatty acid ß-oxidation and lipogenesis. Additionally, the PKA-C and phospho-PKA substrate levels were higher after SEM treatment. Further research found that after pretreatment with the PKA inhibitor, H89, lipid accumulation was increased even with SEM administration in HepG2 cells, and the effect of SEM on lipid metabolism-related regulator factors was abolished by H89. In conclusion, SEM has a positive therapeutic effect on obesity and obesity-related hepatic steatosis by regulating the hepatic lipid metabolism mediated by the PKA pathway.

12.
J Am Chem Soc ; 142(8): 3862-3872, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31991082

RESUMO

The lack of blood-brain barrier (BBB) penetrating ability has hindered the delivery of many therapeutic agents for tauopathy treatment. In this study, we report the synthesis of a circular bifunctional aptamer to enhance the in vivo BBB penetration for better tauopathy therapy. The circular aptamer consists of one reported transferrin receptor (TfR) aptamer to facilitate TfR-aptamer recognition-induced transcytosis across BBB endothelial cells, and one Tau protein aptamer that we recently selected to inhibit Tau phosphorylation and other tauopathy-related pathological events in the brain. This novel circular Tau-TfR bifunctional aptamer displays significantly improved plasma stability and brain exposure, as well as the ability to disrupt tauopathy and improve traumatic brain injury (TBI)-induced cognitive/memory deficits in vivo, providing important proof-of-principle evidence that circular Tau-TfR aptamer can be further developed into diagnostic and therapeutic candidates for tauopathies.

13.
Chem Commun (Camb) ; 56(8): 1255-1258, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31898700

RESUMO

Here we demonstrated that the stiffness of cationized gelatin nanoparticles determined the efficiency of RNAi in myeloid leukemia cells when the particle size and surface charges were kept constant. The siRNA delivery system with an elastic modulus of 0.87 MPa showed the largest siRNA uptake and RNAi efficiency for hard-to-transfect suspension cells.


Assuntos
Gelatina/química , Leucemia Mieloide/patologia , Nanopartículas/química , Interferência de RNA , Cátions/química , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Células K562 , Leucemia Mieloide/tratamento farmacológico , Tamanho da Partícula , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacologia , Propriedades de Superfície
14.
Food Funct ; 11(1): 662-679, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31895380

RESUMO

Our previous studies have demonstrated that the total triterpenes from the fruits of Chaenomeles speciosa (CSTT) exhibit effective therapeutic effects on gastric ulcer patients and animals. The present aim is to further investigate the mechanisms involved. The results indicated that CSTT could ameliorate IND-induced gastric injury, which was related to promoting IND-damaged GES-1 cell proliferation and migration, improving the IND-damaged rat GBF, ulcer area, inhibition rate and pathologic changes of gastric mucous tissue, increasing the amount of adhered gastric mucus, attenuating the volume and total acidity of the gastric effluents, and augmenting the gastric pH; further studies showed that CSTT obviously downregulated miR-423-5p mRNA, NAG-1 mRNA and protein expression, Bax, Bad, cytosol cytochrome C, Apaf-1, cleaved-caspase-3, and cleaved-caspase-9 protein expression and cytosol cytochrome C concentration, and upregulated TFF1, TFF2 and TFF3 mRNA and protein expression, Bcl-2, Bcl-xl, pro-caspase-3, and pro-caspase-9 protein expression, mitochondrial viability, mitochondrial cytochrome C concentration and Bcl-2/Bax, Bcl-xl/Bad ratios. These findings demonstrated that CSTT protected against IND-induced gastric damage by depressing miR-423-5p expression and modulating the TFF/NAG-1 pathway, which in turn restrained mitochondrion-mediated apoptosis.

15.
Asia Pac J Clin Oncol ; 16(1): 63-69, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31721468

RESUMO

AIM: Valuable and convenient prognostic predictors are essential for targeted therapy of non-small cell lung cancer (NSCLC). Patients with early-stage cancer and EGFR mutations who's neutrophils-to-lymphocytes rate (NLR) could be prognostic factor to evaluate efficacy. However, the prognostic role of NLR in patients receiving ALK inhibitors has not been established. Additionally, the relation between the efficacy of ALK inhibitors and derived NLR (dNLR), platelets-to-lymphocytes rate (PLR), white blood cells (WBC) and hemoglobin (HGB) are still unknown. METHODS: This is a retrospective single-center study and enrolled 113 staged IIIB-IV ALK-positive NSCLC patients who had received crizotinib treatment. Pretreatment NLR, dNLR, PLR, WBC, HGB were collected and calculated. Cox regression analysis were conducted to study the prognostic roles of NLR, dNLR, PLR, WBC, and HGB on progression-free survival (PFS) and overall survival (OS). Z-test was utilized to identify the difference among all predictive factors' receiver-operating characteristics (ROC) curves. RESULTS: The median PFS and OS were 10.1 and 23.4 months. Elevated NLR, dNLR, PLR and decreased HGB were associated with worse PFS (95% confidence interval [CI], 1.078-2.304, P = 0.018; 95% CI, 1.043-2.222, P = 0.028; 95% CI, 1.257-2.757, P = 0.002; 95% CI, 0.368-0.843, P = 0.005, respectively) and OS (95% CI, 1.698-5.721, P < 0.001; 95% CI, 1.273-3.984, P = 0.005; 95% CI, 2.174-6.347, P < 0.001; 95% CI, 0.246-0.710, P = 0.001, respectively). Z-test revealed there were no significant differences between single factors or combination of them to predict the efficacy. CONCLUSIONS: Trend of NLR, dNLR, PLR and WBC could be used to identify patients progress status in ALK-positive NSCLC patients receiving crizotinib. Combination of all biomarkers is no superior to single biomarker.

16.
Cancer Lett ; 470: 95-105, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31644929

RESUMO

Immune checkpoint inhibitors against PD-1/PD-L1 yield improved survival rates of KRAS-mutant NSCLC patients, who conferred a poor prognosis without effective targeted therapy until now. Yet, the underlying association between KRAS mutations and immune responses remains unclear. We performed an integrated analysis of the data from publicly available repositories and from clinical center cohorts to explore the association between KRAS mutation status and tumor immunity-associated features, including PD-L1 expression, CD8+ tumor-infiltrating lymphocytes (TILs) and tumor mutational burden (TMB). Our results revealed that KRAS mutations are correlated with an inflammatory tumor microenvironment and tumor immunogenicity, resulting in superior patient response to PD-1/PD-L1 inhibitors. Meanwhile, three-pool analysis further confirmed that KRAS-mutant NSCLC patients show remarkable clinical benefit from anti-PD-1/PD-L1 immunotherapy. In addition, a KRAS-mutant lung adenocarcinoma mouse model was established to estimate the relative efficacy of anti-PD-L1 monoclonal antibody monotherapy or combination treatment with docetaxel versus docetaxel alone. Most surprisingly, we found that PD-L1 blockade combined with docetaxel did not promote an anti-tumor response. These findings uncover that PD-1/PD-L1 blockade monotherapy may be the optimal therapeutic schedule in NSCLC patients harboring KRAS mutations.

17.
J Pharm Pharmacol ; 72(3): 409-423, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31863472

RESUMO

OBJECTIVES: Our previous studies indicated that the triterpenes from the fruits of Chaenomeles speciosa (Sweet) Nakai (TCS) owned effectively therapeutic effects on gastric ulcer patients and animals, but its mechanisms have not been fully understood. The current study was to further investigate its protective effect on indomethacin (IND)-damaged RGM-1 cells and rats, as well as its mechanisms involved. METHODS: The gastroprotection of TCS was evaluated with IND-induced gastric lesions model in RGM-1 cells and rats. In vitro, the proliferation, migration, mitochondrial viability and apoptosis were assessed. In vivo, ulcer index, ulcer inhibition rate, gastric juice acidity, gastric wall mucus (GWM) and histopathology of gastric mucosa were detected. The gastroprotective effects of TCS through the TFF1-mediated EGF/EGFR and apoptotic pathways were measured by qRT-PCR and Western blot assays. KEY FINDINGS: The results demonstrated that TCS had gastroprotective function, which was related to the amelioration in promoting IND-damaged RGM-1 cell proliferation and migration, hoisting gastric juice acidity and GWM, improving ulcer index and ulcer inhibition rate, attenuating the haemorrhage, oedema, epithelial cell loss and inflammatory cell infiltration of gastric mucosa, upregulating PCNA, Bcl-2, Bcl-xl mRNA and TFF1, EGF, p-EGFR, p-Src, pro-caspase-3, pro-caspase-9 protein expressions, mitochondrial viability, mitochondrial cytochrome c concentration and p-EGFR/EGFR, p-Src/Src, Bcl-2/Bax, Bcl-xl/Bad ratioes, downregulating Bax, Bad, Apaf-1 mRNA and cleaved-caspase-3, cleaved-caspase-9, cleaved PARP-1 protein expressions and cytosol cytochrome c concentration. CONCLUSIONS: Our present study demonstrated that TCS's gastroprotective effect was closely connected with boosting TFF1 expression, activating TFF1-mediated EGF/EGFR pathway, thus restraining mitochondrial-dependent apoptosis, which provided new insights into interpreting its underlying mechanism and promised to act as a candidate drug to treat gastric mucosal injury.

18.
Food Nutr Res ; 632019.
Artigo em Inglês | MEDLINE | ID: mdl-31692782

RESUMO

Background: Obesity has currently become a serious social problem to be solved. Sesamol, a natural bioactive substance extracted from sesame oil, has shown multiple physiological functions, and it might have an effect on the treatment of obesity. Objective: This study was conducted to investigate the therapeutic effect and potential mechanisms of sesamol on the treatment of obesity and metabolic disorders in high-fat diet (HFD)-induced obese mice. Methods: C57BL/6J male mice were fed HFD for 8 weeks to induce obesity, followed by supplementation with sesamol (100 mg/kg body weight [b.w.]/day [d] by gavage) for another 4 weeks. Hematoxylin and eosin staining was used to observe lipid accumulation in adipose tissues and liver. Chemistry reagent kits were used to measure serum lipids, hepatic lipids, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels. ELISA kits were used to determine the serum insulin and free fatty acid (FFA) levels. Western blotting was used to detect the protein levels involved in lipid metabolism in the liver. Results: Sesamol significantly reduced the body weight gain of obese mice and suppressed lipid accumulation in adipose tissue and liver. Sesamol also improved serum and hepatic lipid profiles, and increased insulin sensitivity. In the sesamol-treated group, the levels of serum ALT and AST decreased significantly. Furthermore, after sesamol treatment, the hepatic sterol regulatory element binding protein-1 (SREBP-1c) decreased, while the phosphorylated hormone sensitive lipase (p-HSL), the carnitine palmitoyltransferase 1α (CPT1α), and the peroxisome proliferator-activated receptor coactivator-1α (PGC1α) increased, which were responsible for the fatty acid synthesis, lipolysis, and fatty acid ß-oxidation, respectively. Conclusions: Sesamol had a positive effect on anti-obesity and ameliorated the metabolic disorders of obese mice. The possible mechanism of sesamol might be the regulation of lipid metabolism in the liver.

19.
Biomater Sci ; 7(12): 5516-5527, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670734

RESUMO

Exogenous antigens processed in the cytosol and subsequently cross-presented on major histocompatibility complex class I (MHC-I) molecules activate cytotoxic CD8+ lymphocytes (CTL), which are crucial in cancer immunotherapy. Here, we reported a nanovaccine, which was produced by encapsulating OVA (ovalbumin, a model antigen) chemically modified with MPGΔNLS (MPGΔNLS-OVA conjugate) into poly(lactide-co-glycolide) acid (PLGA) nanoparticles. We hypothesized that after the uptake of the nanovaccine into immune cells, MPGΔNLS, a cell-penetrating peptide (CPP), would assist the escape of the antigens from lysosomes into the cytosol, increase the amount of antigens processed in the cytosol and subsequently enhance antigen cross-presentation via MHC-I molecules to elicit cytotoxic CD8+ T cell responses. The results of the in vitro experiments demonstrated that the MPGΔNLS-OVA-loaded PLGA NPs not only elevated the release of OVA into the cytosol of dendritic cells (BMDCs), but also promoted the maturation and activation of BMDCs. It was also observed in mice vaccinated with MPGΔNLS-OVA-loaded PLGA NPs that the MPGΔNLS modification could stimulate the expansion of OVA-specific T-cells, generation of OVA-specific IgG antibodies and proliferation of OVA-specific memory T cells. Moreover, the treatment of E·G7-OVA tumor-bearing mice with MPGΔNLS-OVA-loaded PLGA NPs resulted in significantly suppressed tumor growth and prolonged survival periods of the mice compared to the treatment with unmodified OVA-PLGA NPs or free OVA. In summary, cell-penetrating peptides linked with antigens encapsulated in nanovaccines can spatiotemporally affect the intracellular localization of antigens, promote antigen cross-presentation and stimulate antigen-specific immune responses, especially CTL responses. Therefore, the CPP modification on antigens is an innovative approach to enhance the efficacy of nanovaccines for cancer immunotherapy.

20.
Chin Med J (Engl) ; 132(19): 2286-2291, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31567475

RESUMO

BACKGROUND: Patients with ST-segment elevation myocardial infarction (STEMI) who present without typical chest pain are associated with a poor outcome. However, whether angiographic characteristics are related to a higher risk of mortality in this population is unclear. This study aimed to investigate whether the higher mortality risk in patients with STEMI without chest pain could be explained by their "high-risk" angiographic characteristics. METHODS: We used data of 12,145 patients with STEMI who was registered in China Acute Myocardial Infarction registry from January 2013 to September 2014. We compared the infarct-related artery (IRA), thrombolysis in myocardial infarction (TIMI) flow grade in the IRA, and other angiographic characteristics between patients without and those with chest pain. Multivariable logistic regression model was used to identify independent risk factor of in-hospital mortality. RESULTS: The 2922 (24.1%) patients with STEMI presented without typical chest pain. These patients had a higher TIMI flow grade (mean TIMI flow grade: 1.00 vs. 0.94, P = 0.02) and a lower rate of IRA disease of the left anterior descending artery (44.6% vs. 51.2%, χ = 35.63, P < 0.01) than did those with typical chest pain. Patients without chest pain were older, more likely to have diabetes, longer time to hospital and higher Killip classification, and less likely to receive optimal medication treatment and primary percutaneous coronary intervention and higher In-hospital mortality (3.3% vs. 2.2%, χ = 10.57, P < 0.01). After adjusting for multi-variables, presentation without chest pain was still an independent predictor of in-hospital death among patients with STEMI (adjusted odds ratio: 1.36, 95% confidence interval: 1.02-1.83). CONCLUSIONS: Presentation without chest pain is common and associated with a higher in-hospital mortality risk in patients with acute myocardial infarction. Our results indicate that their poor prognosis is associated with baseline patient characteristics and delayed treatment, but not angiographic lesion characteristics. CLINICAL TRIAL REGISTRATION: NCT01874691, https://clinicaltrials.gov.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA