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1.
EBioMedicine ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31735556

RESUMO

BACKGROUND: Current guidelines recommend surgical resection as the first-line option for patients with solitary hepatocellular carcinoma (HCC); unfortunately, postoperative recurrence rate remains high and there is no reliable prediction tool. We explored the potential of radiomics coupled with machine-learning algorithms to improve the predictive accuracy for HCC recurrence. METHODS: A total of 470 patients who underwent contrast-enhanced CT and curative resection for solitary HCC were recruited from 3 independent institutions. In the training phase of 210 patients from Institution 1, a radiomics-derived signature was generated based on 3384 engineered features extracted from primary tumor and its periphery using aggregated machine-learning framework. We employed Cox modeling to build predictive models. The models were then validated using an internal dataset of 107 patients and an external dataset of 153 patients from Institution 2 and 3. FINDINGS: Using the machine-learning framework, we identified a three-feature signature that demonstrated favorable prediction of HCC recurrence across all datasets, with C-index of 0.633-0.699. Serum alpha-fetoprotein, albumin-bilirubin grade, liver cirrhosis, tumor margin, and radiomics signature were selected for preoperative model; postoperative model incorporated satellite nodules into above-mentioned predictors. The two models showed superior prognostic performance, with C-index of 0.733-0.801 and integrated Brier score of 0.147-0.165, compared with rival models without radiomics and widely used staging systems (all P < 0.05); they also gave three risk strata for recurrence with distinct recurrence patterns. INTERPRETATION: When integrated with clinical data sources, our three-feature radiomics signature promises to accurately predict individual recurrence risk that may facilitate personalized HCC management.

2.
Cell Prolif ; : e12700, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667976

RESUMO

OBJECTIVES: Long non-coding RNA (lncRNA) MATN1-AS1 is a newfound lncRNA that has been rarely explored in cancers. Herein, we would like to investigate its role in glioma. MATERIALS AND METHODS: qRT-PCR was conducted to examine gene expression in glioma. Then, MTT assay, colony formation assay and flow cytometry analysis were applied to evaluate the function of MATN1-AS1 on glioma cells. Western blot was performed to measure the protein levels of genes. Besides, the luciferase reporter assay, RNA pull-down assay, RIP assay and Spearman's correlation analysis were also performed as needed. RESULTS: Firstly, a data from TCGA showed that MATN1-AS1 might be largely implicated in glioma. Meanwhile, MATN1-AS1 upregulation confirmed in glioma predicted poor clinical outcomes. Functionally, MATN1-AS1 knockdown restrained cell proliferation but stimulated apoptosis in vitro and repressed tumour growth in vivo. Mechanistic investigations validated that MATN1-AS1 functioned as a ceRNA for miR-200b/c/429 to upregulate CHD1 which was also verified to exert a growth-promoting role in glioma cells here. Importantly, both CHD1 overexpression and miR-200b/c/429 inhibition could rescue the obstructive role of MATN1-AS1 silence in glioma cells. CONCLUSIONS: MATN1-AS1 promotes glioma progression through regulating miR-200b/c/429-CHD1 axis, suggesting MATN1-AS1 as a probable target for glioma treatment.

3.
J Biomol Struct Dyn ; : 1-21, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31684825

RESUMO

We prepared extracts of Alisma orientalis from Sichuan and Fujian Province, China. Based on the ratio of alisol B 23-acetate (23B) to alisol A 24-acetate (24A) in two Alisma orientalis extracts, we prepared two mixtures of 24A and 23B (24A:23B = 1:3 or 1:10). The antitumor molecular mechanism of the monomers 24A and 23B, the two mixtures and the effective components of Alisma orientalis from different habitats were studied. The MTT assay suggested that the difference in the antitumor activity of Alisma orientalis from different habitats was correlated to the ratio of 24A to 23B. The multi-spectroscopic analysis suggested that the effective components, the monomers and mixtures interacted with c-myc DNA in a partial intercalation manner. The binding strength of the alisol acetates to c-myc DNA was consistent with the anticancer activity, indicating that c-myc DNA was the anticancer target. The molecular simulation indicated that the mixtures were all directly bound to different base pairs of c-myc DNA for a superimposed effect, which led to the binding strength of the mixtures to c-myc DNA was stronger than that of the monomers. The molecules in the 1:3 mixture were all bound to different base pairs of c-myc DNA. However, for the 1:10 mixture, seven molecules of 23B bound to the side chain of 24A, resulting in the mixture with a long chain structure which increased the steric hindrance of 24A. As a result, affinity between 24A and c-myc DNA in the 1:10 mixture was weaker than that in the 1:3 mixture.The antitumor molecular mechanism of the alisol monomers 24A and 23B, the mixtures with different proportions and the effective components of Alisma orientalis from different habitats were studied. The order of the antitumor activity was as follows: Sichuan > Fujian, 24A-23B (1:3) > 24A-23B (1:10) > 23B > 24A. The antitumor activity of Alisma orientalis from different habitats was consistent with the mixtures which were designed according to the contents of the active ingredients of the medicinal materials, indicating that the antitumor activity of Alisma orientalis from Sichuan is better than that from Fujian which is related to the contents of 24A and 23B and the proportion of 1:3 is better than 1:10. The binding strength of the mixtures to c-myc DNA was consistent with the anticancer activity. The mixtures were all directly bound to different base pairs of c-myc DNA for a superimposed effect, which led to the strength of the interaction of the mixtures to c-myc DNA was stronger than that of the monomers. For the 24A-23B (1:3) mixture, the four small molecules bound to c-myc DNA directly and interacted with different base pairs of c-myc DNA. While for the 24A-23B (1:10) mixture, 24A and three 23B molecules interacted with c-myc DNA, the remaining seven 23B molecules bound to the side chain of 24A, which increased the steric hindrance. The binding of the mixture to c-myc DNA was decreased.

4.
J Clin Immunol ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31749032

RESUMO

miR-608 has been indicated to play an important role in the pathogenesis of various inflammation-related diseases, including sepsis and several types of cancers. However, there is little information about the underlying mechanism, especially in inflammatory cells. In this study, an hsa-miR-608-inhibition cell model was constructed in U937 cells using a lentivirus, and gene expression profiles were determined by a cDNA microarray. Altogether, 682 genes showed a difference greater than 1.2-fold, including 184 genes downregulated and 498 genes upregulated. Among these genes, one potential miR-608-target gene, ELANE, was further investigated. A positive relationship between the expression of miR-608 and that of ELANE was found both in vivo and in vitro. In addition, decreased expression of miR-608 resulted in overexpression of ELANE at both the mRNA and protein levels. Cotransfection of HEK293T cells with a miR-608 mimic inhibited reporter activity, and mutation of the miRNA seed sequences abolished the repression of reporter activity. These results suggest that miR-608 is an important posttranscriptional regulator of ELANE expression in human monocytes and may play an important role in the process of inflammation. miR-608 and neutrophil elastase may be novel targets for the diagnosis or treatment of sepsis.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31760166

RESUMO

Spiroplasma eriocheiris, a novel pathogen of Chinese mitten crab Eriocheir sinensis tremor disease, has led into catastrophic economic losses in aquaculture. S. eriocheiris invaded the hemocytes in the early stage, then invaded nerve tissue and caused typically paroxysmal tremors of pereiopod in the late stage of infection. The purpose of this study was to detect the infection mechanism of hemocytes in the early stage and thoracic ganglion in the late stage of S. eriocheiris infection at the protein level. Hemocytes and thoracic ganglion were collected at 24 h and 10 d after injection (the crabs with typical paroxysmal tremors of the pereiopod), respectively. TMT was performed with isobaric markers, followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). In hemocytes, 127 proteins were up-regulated and 85 proteins were down-regulated in 2747 quantified proteins. Many proteins and process including proPO system proteins, hemolymph coagulation system proteins and lectins were differently expressed in hemocytes and involved in the early immune process of E. sinensis against S. eriocheiris infection. Meanwhile, 545 significantly different expression proteins (292 down-regulated and 253 up-regulated protein including a number of immune-associated, nervous system development and signal transmission related proteins) were identified in thoracic ganglion in the late stage of S. eriocheiris infection. The qRT-PCR analysis results shown that the selected significantly changed proteins in hemocytes and thoracic ganglion were consistent with the TMT proteomics. This paper reported for the first time to study the responses of crab hemocyte and thoracic ganglion against the S. eriocheiris infection at different stages. These findings help us understand the infection mechanism of S. eriocheiris at different stage with the different tissue.

6.
PLoS One ; 14(11): e0224765, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721818

RESUMO

Selaginella tamariscina (Beauv.) spring, a primitive vascular resurrection plant, can survive extreme drought and recover when water becomes available. To identify drought-inducible genes and to clarify the molecular mechanism of drought tolerance, a comparative transcriptional pattern analysis was conducted between S. tamariscina and Selaginella moellendorffii Hieron (drought sensitive). 133 drought related genes were identified, including 72 functional genes and 61 regulatory genes. And several drought responsive reactions, such as antioxidant activity, osmotic balance, cuticle defense and signal transduction were highlighted in S. tamariscina under drought. Notably, besides peroxidase, catalase and L-ascorbate oxidase genes, DEGs associated with phenylalanine metabolism and polyamine catabolism could be alternative ways to enhance antioxidant ability in S. tamariscina. DEGs related to soluble carbohydrate metabolism, late embryogenesis abundant protein (LEA) and aquaporin protein (AQP) confirmed that osmotic adjustment could resist drought during desiccation. DEGs involved in xyloglucan metabolic process, pectin metabolic process and cutin biosynthesis may also contribute to drought tolerance of S. tamariscina by cuticle defense. Drought-responsive genes encoding protein kinases, calcium sensors, transcription factors (TFs) and plant hormones also help to drought resistance of S. tamariscina. The preliminary validation experiments were performed and the results were consistent with our hypothetical integrated regulatory network. The results of this study provide candidate resurrection genes and an integrated regulatory network for further studies on the molecular mechanisms of stress tolerance in S. tamariscina.

7.
Nature ; 575(7784): 618-621, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31776491

RESUMO

All stellar-mass black holes have hitherto been identified by X-rays emitted from gas that is accreting onto the black hole from a companion star. These systems are all binaries with a black-hole mass that is less than 30 times that of the Sun1-4. Theory predicts, however, that X-ray-emitting systems form a minority of the total population of star-black-hole binaries5,6. When the black hole is not accreting gas, it can be found through radial-velocity measurements of the motion of the companion star. Here we report radial-velocity measurements taken over two years of the Galactic B-type star, LB-1. We find that the motion of the B star and an accompanying Hα emission line require the presence of a dark companion with a mass of [Formula: see text] solar masses, which can only be a black hole. The long orbital period of 78.9 days shows that this is a wide binary system. Gravitational-wave experiments have detected black holes of similar mass, but the formation of such massive ones in a high-metallicity environment would be extremely challenging within current stellar evolution theories.

8.
Food Funct ; 10(11): 7131-7141, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31595923

RESUMO

Dihydromyricetin (DMY) is a natural flavonoid compound derived from Lysionotus pauciflorus Maxim and has been found to possess numerous biological activities. However, there have been few reports regarding its anti-food allergic activity. In this study, we demonstrated that DMY could upregulate the rectal temperature, suppress the development of diarrhea, decrease the levels of serum specific immunoglobulin (Ig)E, histamine, and mouse mast cell protease-1, and promote the production of interleukin-10 in ovalbumin-allergic mice. Moreover, DMY downregulated the population of B cells and mast cells and upregulated the population of regulatory T cells in the spleens of ovalbumin-allergic mice. Furthermore, DMY blocked the high affinity IgE receptor (FcεRI)-IgE interaction, inhibited the release of ß-hexosaminidase and histamine in rat basophilic leukemia-2H3 cells, and alleviated passive cutaneous anaphylaxis reactions. These findings indicated that L. pauciflorus derived DMY might have the potential to alleviate food hypersensitivity or allergic diseases.

9.
Wei Sheng Yan Jiu ; 48(5): 817-821, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31601327

RESUMO

OBJECTIVE: To compare the disease burden of diet-related chronic diseases in China between 1990 and 2016. METHODS: Based on the Global Burden of Disease 2016, we extracted the absolute number of deaths and disability-adjusted life years( DALYs) of diet-related chronic diseases and the corresponding age-standardized rates in China in 1990 and 2016. Subgroup analyses were conducted in various gender, dietary risk factors and categories of diseases. RESULTS: In 2016, the total number and rate of diet-related NCDs deaths was 2493 thousand and 182. 4/100000. The corresponding number and rate of DALYs was 54995 thousand person-year and 4023. 0/100000. Compared with those in 1990, the rates of death and DALYs in 2016 increased by19. 5% and 9. 3%, respectively. Both death rate and DALYs rate increased with the age. Death rate( 214. 6/100000) and DALYs rate( 4961. 1/100000) in males were 1. 4-fold and 1. 6-fold as that in females( 148. 2/100000 and 3028. 2/100000, respectively). High intake in sodium, low intake in whole grains and low intake in fruits were the three leading dietary risk factors and cardiovascular diseases accounted for 88. 1% DALYs in all chronic diseases. CONCLUSION: The burden of diet-related chronic diseases in China is severe and it continues increasing over years.


Assuntos
Doença Crônica/epidemiologia , Dieta , China/epidemiologia , Feminino , Humanos , Masculino , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco
10.
Ocul Immunol Inflamm ; : 1-6, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31580185

RESUMO

Purpose: To summarize the prognostic factors of cytomegalovirus (CMV) retinitis (CMVR) in HIV-negative patients treated with multiple intravitreal injections (IVs) of ganciclovir. Methods: A retrospective cohort study (70 eyes) was conducted. Clinical signs, initial and final best corrected visual acuity (BCVA), initial aqueous load of CMV DNA, course of treatment, and occurrence of complications were recorded and analyzed. Results: A positive correlation was found between the baseline and the final best corrected visual acuity (P < .001) and between the initial aqueous CMV DNA load and the number of IVs (P = .01). A lesion close to the posterior pole (P < .001) and a larger retinal lesion (P = .002) remarkably led to worse visual prognosis. Conclusions: Poor visual prognosis was significantly associated with poor initial visual acuity, proximity of lesion to the posterior pole, and an extensive CMV lesion. The treatment duration was positively correlated with the initial aqueous CMV DNA load.

11.
Int Ophthalmol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31571091

RESUMO

PURPOSE: To investigate the predictive factors of postoperative myopic regression among subjects who have undergone laser-assisted subepithelial keratomileusis (LASEK), laser-assisted in situ keratomileusis (LASIK) flap created with a mechanical microkeratome (MM), and LASIK flap created with a femtosecond laser (FS). All recruited patients had a manifest spherical equivalence (SE) from - 6.0D to - 10.0D myopia. METHODS: This retrospective, observational case series study analyzed outcomes of refraction at 1 day, 1 week, and 1, 3, 6, and 12 months postoperatively. Predictors affecting myopic regression and other covariates were estimated with the Cox proportional hazards model for the three types of surgeries. RESULTS: The study enrolled 496 eyes in the LASEK group, 1054 eyes in the FS-LASIK group, and 910 eyes in the MM-LASIK group. At 12 months, from - 6.0D to - 10.0D myopia showed that the survival rates (no myopic regression) were 52.19%, 59.12%, and 58.79% in the MM-LASIK, FS-LASIK, and LASEK groups, respectively. Risk factors for myopic regression included thicker postoperative central corneal thickness (P ≦ 0.01), older age (P ≦ 0.01), aspherical ablation (P = 0.02), and larger transitional zone (TZ) (P = 0.03). Steeper corneal curvature (Kmax) (P = 0.01), thicker preoperative central corneal thickness (P < 0.01), smaller preoperative myopia (P < 0.01), longer duration of myopia (P = 0.02), with contact lens (P < 0.01), and larger optical zone (OZ) (P = 0.02) were protective factors. Among the three groups, the MM-LASIK had the highest risk of postoperative myopic regression (P < 0.01). CONCLUSIONS: The MM-LASIK group experienced the highest myopic regression, followed by the FS-LASIK and LASEK groups. Older age, aspheric ablation used, thicker postoperative central corneal thickness, and enlarging TZ contribute to myopic regression; steeper preoperative corneal curvature (Kmax), longer duration of myopia, with contact lens, thicker preoperative central corneal thickness, lower manifest refraction SE, and enlarging OZ prevent postoperative myopic regression in myopia from - 6.0D to - 10.0D.

12.
Ocul Immunol Inflamm ; : 1-6, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573356

RESUMO

Purpose: To describe and to compare the clinical manifestation and laboratory test results of herpetic anterior uveitis (HAU) caused by Herpes simplex virus (HSV) and varicella-zoster virus (VZV). Methods: A retrospective, observational study on patients diagnosed with HAU. Etiology, clinical features, ocular complications, and recurrences of the infection were evaluated as main clinical parameters. The aqueous Interleukin-8 (IL-8) level was also measured to assess the intraocular inflammation. Results: Thirty-two eyes (32 patients) were involved. Among all involved cases, 24 had VZV-AU and 8 had HSV-AU. Common clinical features of HAU included the presence of KPs (90.6%), distorted pupil (83.3%), Iris atrophy (71.9%) and corneal edema (50%). The intraocular fluid analysis showed higher viral load and IL-8 level in VZV-AU. Conclusions: Compared with HSV-AU, the intraocular inflammation was more severe in VZV-AU. The intraocular fluid analysis was valuable for the etiological diagnosis and the evaluation of disease severity.

13.
Int J Biol Sci ; 15(10): 2110-2118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592232

RESUMO

Yes kinase-associated protein (YAP) plays an important role in angiogenesis and can promote the occurrence and development of many tumor types. However, whether YAP affects tumor angiogenesis in lung cancer, and its potential mechanism in lung cancer, are unknown. In this study, we explored the role of YAP in the angiogenesis of lung adenocarcinoma, and further illustrated its possible mechanism. The expression levels of YAP and the vascular endothelial marker protein CD31 were examined by immunohistochemistry and immunofluorescence in human lung adenocarcinoma tissues, revealing a possible positive correlation between YAP and CD31 in lung adenocarcinoma. The results of the western blotting (WB) of Human Umbilical Vein Endothelial Cells (HUVECs) after coculture with lung adenocarcinoma H1975 cells, H1975 cell-supernatants and H1975-derived EVs showed that YAP derived from H1975 cells can enter HUVECs via EVs. These results were confirmed by immunofluorescence. Finally, we generated H1975 low-YAP expression cells by transfecting the cells with a shYAP lentivirus, and confirmed that the low expression of YAP in H1975 cells inhibits HUVEC angiogenesis by reducing the amount of YAP that enters HUVECs. We found, for the first time, that YAP promotes angiogenesis in lung adenocarcinoma via EVs, at least partially. Our work may provide a promising method for lung cancer treatment by targeting angiogenesis in the future.

14.
Cell Metab ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31607564

RESUMO

Phosphoglycerate mutase 1 (PGAM1) plays a pivotal role in cancer metabolism and tumor progression via its metabolic activity and interaction with other proteins like α-smooth muscle actin (ACTA2). Allosteric regulation is considered to be an innovative strategy to discover a highly selective and potent inhibitor targeting PGAM1. Here, we identified a novel PGAM1 allosteric inhibitor, HKB99, via structure-based optimization. HKB99 acted to allosterically block conformational change of PGAM1 during catalytic process and PGAM1-ACTA2 interaction. HKB99 suppressed tumor growth and metastasis and overcame erlotinib resistance in non-small-cell lung cancer (NSCLC). Mechanistically, HKB99 enhanced the oxidative stress and altered multiple signaling pathways including the activation of JNK/c-Jun and suppression of AKT and ERK. Collectively, the study highlights the potential of PGAM1 as a therapeutic target in NSCLC and reveals a distinct mechanism by which HKB99 inhibits both metabolic activity and nonmetabolic function of PGAM1 by allosteric regulation.

15.
HPB (Oxford) ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31607637

RESUMO

BACKGROUND: A clear definition of "early recurrence" after hepatocellular carcinoma (HCC) resection is still lacking. This study aimed to determine the optimal cutoff between early and late HCC recurrence, and develop nomograms for pre- and postoperative prediction of early recurrence. METHODS: Patients undergoing HCC resection were identified from a multi-institutional Chinese database. Minimum P-value approach was adopted to calculate optimal cut-off to define early recurrence. Pre- and postoperative risk factors for early recurrence were identified and further used for nomogram construction. The results were externally validated by a Western cohort. RESULTS: Among 1501 patients identified, 539 (35.9%) were recurrence-free. The optimal length to distinguish between early (n = 340, 35.3%) and late recurrence (n = 622, 64.7%) was 8 months. Multivariable logistic regression analyses identified 5 preoperative and 8 postoperative factors for early recurrence, which were further incorporated into preoperative and postoperative nomograms (C-index: 0.785 and 0.834). The calibration plots for the probability of early recurrence fitted well. The nomogram performance was maintained using the validation dataset (C-index: 0.777 for preoperative prediction and 0.842 for postoperative prediction). CONCLUSIONS: An interval of 8 months was the optimal threshold for defining early HCC recurrence. The two web-based nomograms have been published to allow accurate pre- and postoperative prediction of early recurrence. These may offer useful guidance for individual treatment or follow up for patients with resectable HCC.

16.
Eur J Obstet Gynecol Reprod Biol ; 242: 114-121, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31580963

RESUMO

OBJECTIVE: To explore factors that can be used to predict successful vaginal births after cesarean (VBAC) and its outcome. METHODS: This is a prospective study involving women with a previous low-segment cesarean section, singleton pregnancy and cephalic presentation who desire for vaginal trial delivery. Delivery modes were observed and the pregnancy outcomes were followed up. The data were analyzed to identify the factors associated with the success of vaginal births after cesarean (VBAC). Then, there were elaborated the models, and their predictive capacity was determined by receiver-operator curve (ROC). RESULTS: The multivariate logistic regression showed Bishop's score and spontaneous labour independently influenced vaginal births after cesarean (VBAC) success. The prediction model is established and validated. The fitting degree and prediction accuracy of the model is good. The vaginal births after cesarean (VBAC) group had less postpartum hemorrhage (Median 270 ml vs. 300 ml, P < 0.05), a lower puerperal infection rate (1.62% vs 5.88%, P < 0.01), and shorter postpartum hospitalization (Median 2 days vs. 3 days, P < 0.01) than the trial of labor after cesarean (TOLAC)-failure groups. It also had less postpartum hemorrhage (Median 270 ml vs. 320 ml, P < 0.01), a lower puerperal infection rate (1.62% vs 6.23%, P < 0.05), and shorter postpartum hospitalization (Median 2 days vs. 3 days, P < 0.01) than the elective repeat cesarean section (ERCS) groups. The use of labor analgesia in the vaginal births after cesarean (VBAC) group had no effect on pregnancy outcomes. CONCLUSION: The predictive factors are conducive to making rational choices about delivery mode and should improve pregnancy outcomes.

17.
Zhen Ci Yan Jiu ; 44(9): 686-92, 2019.
Artigo em Chinês | MEDLINE | ID: mdl-31532140

RESUMO

Ischemic stroke is a major cause of permanent disability and death in adults, and electroacupuncture (EA) intervention has a positive role in improving neurological function in patients with ischemic stroke through a series of complex processes. In the present paper, we make a review about the development of researches on the involvement of micro-ribonucleic acid (miRNA) in ischemic stroke from excitatory amino acid toxicity, oxidative stress, inflammatory response, apoptosis and necrosis, and particularly sum up outcomes of researches about the roles of miRNAs in EA-induced improvement of neurological function in experimental cerebral ischemia animals. EA treatment can 1) balance levels of miRNAs (such as mir-126 and mir-328, etc.) to promote angiogenesis of ischemic cerebral cortex tissue by regulating expression of vascular endothelial growth factor family genes and proteins; 2) promote nerve regeneration by up-regulating serum miR-124 and hippocampal miR-132 expression to possibly facilitate cerebral repair and reduce cognitive dysfunction respectively via related proteins; 3) reduce cerebral edema via modulating expression of some miRNAs to control expression of aquaporin, matrix metalloproteinases, etc. and 4) suppress inflammatory response via up-regulating expression of miRNAs to inhibit expression of NF-κB, TNF-α, etc. in the local cerebral tissue. As a result, the neurological function is bettered after EA intervention.


Assuntos
Isquemia Encefálica , Eletroacupuntura , Acidente Vascular Cerebral , Isquemia Encefálica/terapia , Humanos , Acidente Vascular Cerebral/terapia , Fator A de Crescimento do Endotélio Vascular
18.
Hepatol Int ; 13(6): 736-747, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31486964

RESUMO

BACKGROUND AND AIMS: Surgical resection for hepatocellular carcinoma (HCC) is potentially curative, but long-term survival remains unsatisfactory. There is currently no effective neoadjuvant or adjuvant therapy for HCC. We sought to evaluate the impact of preoperative transcatheter arterial chemoembolization (TACE) on long-term prognosis after surgical resection of huge HCCs (≥ 10 cm). METHODS: Using a multicenter database, consecutive patients who underwent curative-intent resection for huge HCC without macrovascular invasion between 2004 and 2014 were identified. The association between preoperative TACE with perioperative outcomes, long-term overall survival (OS), and recurrence-free survival (RFS) was assessed before and after propensity score matching (PSM). RESULTS: Among the 377 enrolled patients, 88 patients (23.3%) received preoperative TACE. The incidence of perioperative mortality and morbidity was comparable among patients who did and did not undergo preoperative TACE (3.4% vs. 2.4%, p= 0.704, and 33.0% vs. 31.1%, p= 0.749, respectively). PSM analysis created 84 matched pairs of patients. In examining the entire cohort as well as the PSM cohort, median OS (overall cohort: 32.8 vs. 22.3 months, p= 0.035, and PSM only: 32.8 vs. 18.1 months, p= 0.023, respectively) and RFS (12.9 vs. 6.4 months, p= 0.016, and 12.9 vs. 4.1 months, p= 0.009, respectively) were better among patients who underwent preoperative TACE vs. patients who did not. After adjustment for other confounding factors on multivariable analyses, preoperative TACE remained independently associated with a favorable OS and RFS after the resection of huge HCC. CONCLUSION: Preoperative TACE did not increase perioperative morbidity or mortality, yet was associated with an improved OS and RFS after liver resection of huge HCC (≥ 10 cm).

19.
Biomed Pharmacother ; 118: 109265, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545282

RESUMO

Kaempferol-3-O-rhamnoside (KOR) has multiple potency involved in anti-cancer, anti-inflammatory and antibacterial actions. However, the potential roles of KOR and the analogues isolated from the leaves of Cyclocarya paliurus in anti-erythroleukemia remain unclear. In the present study, KOR and the two analogues (Kaempferol-3-O-(4″-O-acetyl-a-L-rhamnopyranoside) (KLR) and (kaempferol-3-O-α-L-(4″-E-p-coumaroyl) rhamnoside) (KCR) were isolated from leaves of Cyclocarya paliurus. Cell viability assay showed that KCR exerted an excellent anti-erythroleukemia activity. We observed that KCR not only significantly increased the percentage of G2 phase and apoptotic cells compared with control group, but also induced megakaryocytic differentiation in HEL and K562 cells by flow cytometry, indicating that KCR might inhibit cell proliferation through inducing differentiation-mediated apoptosis and cell cycle arrest. Mechanism investigation revealed that KCR treatment obviously increased phosphorylation levels of PKCδ and ERK1/2 as well as GATA1 expression. Taken together, these findings demonstrate that KCR induces megakaryocytic differentiation and suppresses leukemogenesis at least partly through activation of PKCδ/ERK1/2 signaling pathway in erythroleukemia cells. KCR may also serve as a promising natural compound for human erythroleukemia treatment.

20.
Eur J Surg Oncol ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31543386

RESUMO

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) categorizes a patient with performance status (PS)-1 as advanced stage of hepatocellular carcinoma (HCC) and surgical resection is not recommended. In real-world clinical practice, PS-1 is often not a contraindication to surgery for HCC. The aim of current study was to define the impact of PS on the surgical outcomes of patients undergoing liver resection for HCC. METHODS: 1,531 consecutive patients who underwent a curative-intent resection of HCC between 2005 and 2015 were identified using a multi-institutional database. After categorizing patients into PS-0 (n = 836) versus PS-1 (n = 695), perioperative mortality and morbidity, overall survival (OS) and recurrence-free survival (RFS) were compared. RESULTS: Overall perioperative mortality and major morbidity among patients with PS-0 (n = 836) and PS-1 (n = 695) were similar (1.4% vs. 1.6%, P = 0.525 and 9.7% vs. 10.2%, P = 0.732, respectively). In contrast, median OS and RFS was worse among patients who had PS-1 versus PS-0 (34.0 vs. 107.6 months, and 20.5 vs. 60.6 months, both P < 0.001, respectively). On multivariable Cox-regression analyses, PS-1 was independently associated with worse OS (HR: 1.301, 95% CI: 1.111-1.523, P < 0.001) and RFS (HR: 1.184, 95% CI: 1.034-1.358, P = 0.007). CONCLUSIONS: Patients with PS-1 versus PS-0 had comparable perioperative outcomes. However, patients with PS-1 had worse long-term outcomes as PS-1 was independently associated with worse OS and RFS. Routine exclusion of HCC patients with PS-1 from surgical resection as recommended by the BCLC guidelines is not warranted.

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