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1.
Int J Biol Macromol ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31473314

RESUMO

Nanogels have been recently attracted attention because they exhibit significantly different behaviors compared with nanoparticles. Among them, chitosan (CS) nanogels have gained considerable attention from researchers for in vivo applications due to bioactivity, biodegradability, mucoadhesiveness, and biocompatibility of CS. In this review, we have summarized the applications of CS nanogels for efficient drug delivery. Specifically, CS nanogels can be modified by pH-sensitive groups or specific ligands to obtain the corresponding functions. These functional CS nanogels have been used to deliver therapeutic agents, such as anti-cancer drugs, genes, and vaccines. By reviewing the recent research progress on CS nanogels in pharmaceutical applications, it will provide biomaterial researchers potential help for the development of CS nanogel delivery system to meet clinical needs.

2.
Life Sci ; : 116828, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31479679

RESUMO

AIMS: The renal tubule cells require a large number of mitochondria to supply ATP due to their high-energy demand during reabsorption and secretion against chemical gradients and result in mitochondria susceptible to disorder and injury during stress conditions. Injured mitochondria are eventually degraded by mitophagy, and disturbances in mitophagy are associated with the pathogenesis of acute kidney injury (AKI) such as diabetic nephropathy and glomerulosclerosis. However, whether a disturbance in mitophagy has occurred and the role it plays in (SAKI) is still unclear. Therefore, the aim of this study was to investigate the key features of mitophagy and mitochondrial dynamics in sepsis-induced acute kidney injury (SAKI). MAIN METHODS: In this study, a murine septic AKI model induced by cecal ligation and puncture (CLP) was built; mitophagy and mitochondrial dynamics were measured in mice kidney in different time point. KEY FINDINGS: The results showed that mitochondrial dynamics were characterized by fission/fusion aberrant, however more inclined to fission, and mitochondrial associated apoptosis was elevated over-time during SAKI. Furthermore, mitophagy was impaired in the later phase of SAKI, although elevated in early stage of SAKI. The results indicate that the underlying mechanisms of impaired mitophagy may associate with the cleavage of Parkin via caspases activated by NLRP3, at least partly. SIGNIFICANCE: It is conceivable that this selective autophagic process and quality control machinery was impaired, leading to the accumulation of damaged mitochondria, oxidative stress, and cell death. Therefore, a targeted approach, by enhancing mitophagy during SAKI, may be a promising therapeutic strategy.

3.
Expert Rev Mol Diagn ; : 1-6, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31482753

RESUMO

Background: We evaluated the Wellion Galileo GLU/KET blood and ketone (ß-Hydroxybutyrate, ß-OHB) meter to demonstrate that it meets ISO15107:2015 regulatory approval criteria. Research Design and Methods: A total of 100 subjects (52 female, age: 30 to 84 years, diabetes: 10 type 1/90 type 2) with blood glucose levels distributed over the entire measurement range as required by the ISO15197 protocol were tested (double determinations with 3 strip lots and two devices). A similar test protocol was followed to test ß-OHB strip performance (reference devices: YSI 2300plus for glucose and STANBIO ß-HOB LiquiColor TestKit for ß-OHB). Precision was tested for glucose with 3 blood glucose concentrations (ß-OHB: 2 control solutions). Results: All glucose test-strip lots met the strict ISO acceptance criteria. Mean absolute relative difference (MARD) was 4.9% and all data pairs were in zone A of the consensus error grid. The ß-OHB test-strips also met the pre-defined acceptance criteria. Within-run and between-run precision was calculated to be 2.3% and 0.7% for the glucose strips (3.7%/0.8% for the ketone strips). Conclusions: When tested according to the ISO15197:2015 guideline, the device showed very accurate measurement performance for glucose and ß-OHB testing and fully met regulatory accuracy approval criteria.

4.
BMC Bioinformatics ; 20(1): 444, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455207

RESUMO

BACKGROUND: Mining epistatic loci which affects specific phenotypic traits is an important research issue in the field of biology. Bayesian network (BN) is a graphical model which can express the relationship between genetic loci and phenotype. Until now, it has been widely used into epistasis mining in many research work. However, this method has two disadvantages: low learning efficiency and easy to fall into local optimum. Genetic algorithm has the excellence of rapid global search and avoiding falling into local optimum. It is scalable and easy to integrate with other algorithms. This work proposes an epistasis mining approach based on genetic tabu algorithm and Bayesian network (Epi-GTBN). It uses genetic algorithm into the heuristic search strategy of Bayesian network. The individual structure can be evolved through the genetic operations of selection, crossover and mutation. It can help to find the optimal network structure, and then further to mine the epistasis loci effectively. In order to enhance the diversity of the population and obtain a more effective global optimal solution, we use the tabu search strategy into the operations of crossover and mutation in genetic algorithm. It can help to accelerate the convergence of the algorithm. RESULTS: We compared Epi-GTBN with other recent algorithms using both simulated and real datasets. The experimental results demonstrate that our method has much better epistasis detection accuracy in the case of not affecting the efficiency for different datasets. CONCLUSIONS: The presented methodology (Epi-GTBN) is an effective method for epistasis detection, and it can be seen as an interesting addition to the arsenal used in complex traits analyses.

5.
J Ren Nutr ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31466888

RESUMO

OBJECTIVE: This study aimed to investigate the effect of antioxidant vitamins, including vitamins E and C, on patients with diabetes and albuminuria by conducting a meta-analysis of randomized controlled trials. DESIGN: The PubMed, Embase, CENTRAL (the Cochrane Central Register of Controlled Trials at the Cochrane Library), Web of Science, OVID, and www.clinicaltrials.gov (latest search: December 10, 2018) databases were searched. This study was limited to randomized controlled trials. Patients with diabetes and albuminuria were included regardless of diabetic type, and patients must have received treatment with vitamins C or E. RESULTS: Ten studies, representing 445 participants, were identified for analysis. Antioxidant vitamins had significant effects on serum creatinine levels (mean difference = -0.11 mg/dL, 95% confidence interval -0.19 to -0.03, P = .007) and systolic pressure (mean difference = -6.02 mm Hg, 95% confidence interval -9.65 to -2.40, P = .001) with low heterogeneity. Antioxidant vitamins had no effect on albuminuria or proteinuria, diastolic blood pressure, glucose, or lipid metabolism. CONCLUSION: This meta-analysis indicated that antioxidant vitamins can benefit kidney function and systolic blood pressure in patients with diabetes and albuminuria. Further studies with larger sample sizes and longer follow-up are needed to completely understand the effect of antioxidant vitamins in these patients.

6.
Int J Cancer ; 2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31376289

RESUMO

Yes-associated protein (YAP) is a transcriptional coactivator that promotes cell proliferation, stem cell maintenance and tissue homeostasis. The YAP activity is primarily regulated through an inhibitory phosphorylation by the serine/threonine kinases of Hippo pathway. Here, we show that receptor tyrosine kinase (RTK) erythropoietin-producing hepatocellular receptor A2 (EphA2) interacts with and phosphorylates YAP protein, leading to stabilization, nuclear translocation and activation of YAP in gastric cancer (GC) cells. EphA2 induces chemotherapy-resistance by increasing YAP stability and nuclear YAP protein. Knockdown of YAP blocks EphA2-induced tumor growth in GC xenograft mouse models. Importantly, the coactivation of EphA2 and YAP is manifested in clinical human GC, and is related to GC recurrence. Thus, our results establish a novel EphA2-to-YAP pathway that drives GC growth, progression and therapy-resistance, targeting this pathway would be an efficient way for the treatment of GC, particularly chemotherapy-resistant GC.

7.
Ann Hematol ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31396670

RESUMO

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic disease with thrombosis as a major complication. The mechanism of thrombosis and related risk factors in PNH patients are still not well characterized. We retrospectively enrolled 99 patients with newly diagnosed PNH at our institute from 2011 to 2016. According to binary logistic regression model analysis, we first identified four baseline clinical risk factors which may be associated with incidence of thrombosis in the PNH cohort, including PNH clone sizes (fluorescent aerolysin of neutrophil) ≤ 80 (OR 1.056, 95%CI 1.016-1.097, P = 0.005), hemoglobin ≤ 75 g/L (OR 4.202, 95%CI 0.984-17.954, P = 0.053), platelet > 100 × 109/L (OR 6.547, 95%CI 1.490-28.767, P = 0.013) and rs495828 = G (OR 5.243, 95%CI 1.314-20.916, P = 0.019). These independent risk factors were combined together to develop a risk model to evaluate thrombosis risk (AUC = 0.756, 95%CI 0.607-0.905, P < 0.001). Our risk model revealed a higher cumulative incidence of thrombosis and an earlier thrombosis events in PNH patients with high risk (risk score ≥ 23) compared with those with low risk (risk score < 23, P < 0.001 and P = 0.043, respectively). Although with some limitations, we set up a prediction model for thrombosis risk in patients with PNH for the first time, but it needed to be verified in a prospective study with larger patients and longer follow-up time in the future.

8.
J Transl Med ; 17(1): 251, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382970

RESUMO

BACKGROUND: Diabetic cardiomyopathy (DCM) is a common complication of diabetes and is characterized by chronic myocardial inflammation. Mesenchymal stem cell (MSC) infusions have recently been suggested to alleviate myocardial injury and ameliorate cardiac function. However, few studies have focused on the effects of MSCs in DCM. Therefore, we explored the effects of MSC-regulated macrophage polarization on myocardial repair in DCM. METHODS: A DCM rat model was induced by a high-fat diet and streptozotocin (STZ) administration and infused 4 times with MSCs. Rat blood and heart tissue were analyzed for blood glucose levels, lipid levels, echocardiography, histopathology, macrophage phenotype ratios and inflammatory cytokines, respectively. We mimicked chronic inflammation in vitro by inducing peritoneal macrophages with high glucose and LPS, then cocultured these macrophages with MSCs to explore the specific mechanism of MSCs on macrophage polarization. RESULTS: DCM rats exhibited abnormal blood glucose levels and lipid metabolism, cardiac inflammation and dysfunction. MSC infusion ameliorated metabolic abnormalities and preserved cardiac structure and function in DCM rats. Moreover, MSC infusion significantly increased the M2 phenotype macrophages and alleviated cardiac inflammation. Interestingly, this in vitro study revealed that the MSCs pretreated with a COX-2 inhibitor had little effect on M2 macrophage polarization, but this phenomenon could be reversed by adding prostaglandin E2 (PGE2). CONCLUSIONS: Our results suggested that MSC infusions can protect against cardiac injury in DCM rats. The underlying mechanisms may include MSC-enhanced M2 macrophage polarization via the COX-2-PGE2 pathway.

9.
Cardiovasc Diabetol ; 18(1): 100, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391045

RESUMO

BACKGROUND: Adverse cardiac remodeling after ST-segment elevation myocardial infarction (STEMI) is a major cause for poor cardiovascular outcomes such as heart failure. The predisposing factors and underlying mechanisms remain not fully understood. This study investigates the association of insulin resistance and dysglycemia with left ventricular (LV) remodeling after STEMI in non-diabetic patients. METHODS: A total of 485 non-diabetic subjects with STEMI who underwent primary percutaneous coronary intervention were consecutively enrolled and followed up for 12 months. Relation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and glucose levels to changes in echocardiography parameters was studied. RESULTS: Left ventricular dilation was detected in 49.1% of subjects at 12-month follow-up after STEMI, and was more severe in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and high HOMA-IR levels. HOMA-IR remained correlated to changes in LV dimensions after adjusting for confounding risk factors. Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI. A significant interaction term was present between HOMA-IR and IGT in the model (P = 0.001). CONCLUSIONS: Our study reveals that insulin resistance and dysglycemia are prevalent in non-diabetic patients with STEMI and are predictors of the post-infarction LV dilation. Trial registration Trials number, NCT02089360; registered on March 17, 2014.

10.
BMC Musculoskelet Disord ; 20(1): 361, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391055

RESUMO

BACKGROUND: Extramedullary systems are commonly used in knee arthroplasty, with the rod location being determined from the tibial torsion line during surgery. The traditional method for tibial torsion measurement is not in accordance with clinical practice. This study aimed to evaluate proximal and distal tibial torsion using 3-dimensional (3D) computed technology to establish a new evaluation method, as well as to investigate the association between tibial torsion and postoperative alignment deviation. METHODS: Fifty-five osteoarthritis tibias with >10°varus preoperatively were divided into valgus, neutral, and varus groups based on their postoperative alignment deviation. A new method based on clinical practice was built using a 3D tibial model. Proximal and distal tibial torsions were measured by both the new and traditional methods. In addition, tibial osteotomy that followed the intramedullary osteotomy system was simulated on the 3D model in the varus and valgus groups to investigate the association between tibial torsion and alignment deviation. RESULTS: Proximal tibial torsion was smaller and distal torsion was greater in the valgus group than the other two groups, according to the new method (p = 0.03 and p = 0.02, respectively). No significant difference was found when comparing these torsions by the traditional method (p = 0.782 and p = 0.753, respectively). In the valgus group, the postoperative alignment deviation improved after simulated osteotomy guided by the intramedullary system, while no significant improvement was found in the varus group. CONCLUSION: According to this new tibial-rotation evaluation method, valgus deviation in knee arthroplasty was identified as the main cause for knees in which the proximal tibial internal torsion is too small and the distal external torsion is too great. The use of an intramedullary system may help reduce this deviation. TRIAL REGISTRATION: Prospectively registered.

11.
J Orthop Surg Res ; 14(1): 253, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395063

RESUMO

BACKGROUND: This study aims to investigate the curative effects of total hip arthroplasty (THA) in treating hip bony fusion for young and middle-aged patients with ankylosing spondylitis (AS). METHODS: The clinical data of 26 young and middle-aged patients with AS (31 coxae), who were treated with THA and followed-up for more than 3 years in the period between February 1998 and May 2013, were retrospectively analyzed. Among these patients, 22 patients were male (25 coxae) and 4 patients were female (6 coxae). Patients' age ranged within 19-50 years old, with an average of 31.5 years old. The intervals from arthroplasty to the occurrence of hip joint lesions caused by AS ranged within 2-26 years, with an average of 11.2 years. The average Harris score before the surgery was 19.0 ± 11.5 points. RESULTS: Femoral proximal cleavage fracture occurred in one coxa during the surgery and was fixed by the steel wire cerclage. Sciatic nerve traction injury occurred in one coxa after the surgery, which recovered after 6 months. Posterior hip dislocation occurred in one coxa and was immediately treated with manual reduction. All patients were followed-up, and follow-up duration ranged within 36-123 months, with an average of 46.5 months. In the last follow-up, the average Harris score was 87.1 ± 13.1 points, total passive range of motion was 215.0 ± 22.0°, and passive range of flexion was 90.8 ± 9.3°. All these indexes significantly increased compared with pretreatment (P < 0.01). A periacetabular radiolucent line occurred in one coxa with a width of < 2 mm, and no femoral radiolucent line was found during follow-ups in any patient. Heterotopic ossification occurred in four coxae. CONCLUSION: THA treatment for hip bony fusion caused by AS can achieve satisfactory hip function recovery and excellent prosthesis survival rate.

13.
Phytomedicine ; 64: 152911, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-31454653

RESUMO

Background Garcimultiflorone K is a novel polyprenylated polycyclic acylphloroglucinol isolated from the stems of Garcinia multiflora that exhibits promising anti-angiogenic activity in human endothelial progenitor cells (EPCs). Purpose This study sought to determine the underlying anti-angiogenic mechanisms and pharmacological properties of garcimultiflorone K. Methods We examined the anti-angiogenic effects of garcimultiflorone K and its mechanisms of action using in vitro EPC models and in vivo zebrafish embryos. Results EPCs proliferation, migration, differentiation and capillary-like tube formation were effectively and concentration-dependently inhibited by garcimultiflorone K without any signs of cytotoxicity. Our investigations revealed that garcimultiflorone K suppressed EPCs angiogenesis through Akt, mTOR, p70S6K, and eNOS signaling cascades. Notably, garcimultiflorone K dose-dependently impeded angiogenesis in zebrafish embryos. Conclusion Our data demonstrate the anti-angiogneic effects of garcimultiflorone K in both in vitro and in vivo models. Garcimultiflorone K appears to have potential in the treatment of angiogenesis-related diseases.

14.
Metabolism ; 100: 153961, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31422054

RESUMO

AIMS: Obesity and early puberty have been reported to be mutually causative. We investigated the causal relationship between adiposity and early puberty by performing bidirectional Mendelian randomization (MR) and longitudinal data analyses. METHODS: We used information from the Taiwan Children Health Study (3109 adolescents aged 11-12 years) with 17 body mass index (BMI)- and 10 puberty-related single-nucleotide polymorphisms (SNPs) to produce genetic instrumental variables (IVs). The two-stage least squares (2SLS) method, MR sensitivity analysis, and survival analysis were used to explore and confirm causality. RESULTS: Regression estimates from IVs revealed that significantly increased association of BMI with early puberty was noted (coefficients: 0.13, 0.10, and 0.09; 95% CI: 0.07-0.19, 0.02-0.19, and 0.02-0.16 for all participants, male adolescents, and female adolescents, respectively). Genetic IVs for puberty were not associated with BMI. MR sensitivity and two-sample MR analyses produced similar results. Longitudinal analysis results revealed that prepubertal overweight and obesity could predict early onset of puberty. However, after excluding children with a history of overweight and obesity at the age of 7-12 years, early puberty was not found to trigger new-onset of overweight and obesity at the age of 18 years in either sex. CONCLUSIONS: Higher adiposity may lead to early puberty. However, the causal effects of early puberty on adiposity accumulation were not supported by our data. Targeted interventions to reduce childhood obesity are strongly recommended to prevent obesity-related comorbidities, as well as early puberty onset.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31425028

RESUMO

Based on the Fresnel half-wave band interference and laser engraving, a high frequency self-focusing piezoelectric composite ultrasound transducer was presented in this paper. The theoretical analysis was deduced based on the concept of constructive interference of acoustic waves and electromechanical response of piezoelectric composites. The calculated and simulation results showed that it combined the advantages of composite transducer and plate self-focusing transducer, and can achieve high electromechanical coupling coefficient (> 0.66), low acoustic impedance (~15 MRayl), high intensity and short focal length. Furthermore, a 30 MHz self-focusing piezoelectric composite transducer prototype was fabricated and tested. It is composed of 11 PZT and 10 epoxy annuluses. A UV engraving laser with line width of 10 lm was used to each the PZT to form the annuluses and the kerf among the annuluses was filled with epoxy. The measured center frequency, bandwidth and focal length was 27 MHz, 50.37% and 3.7 mm, respectively. A vertical wire phantom was imaged using fabricated transducer and contrast flat transducer, the images showed a significant improvement in lateral resolution over a range of 9 mm. Because this self-focusing piezoelectric composite transducer was based on the precise laser engraving systems, the fabrication process was accurate and controllable, which made it have good potential for medical imaging and industrial nondestructive testing applications.

16.
Int J Biol Macromol ; 139: 85-93, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31369783

RESUMO

The poly(lactic acid) (PLA)/nano-TiO2 composite films with different nano-TiO2 loading (0 wt%, 1 wt%, 5 wt%, 10 wt%, 15 wt%, and 20 wt%) were prepared and contacted with 50% (v/v) ethanol solution as food simulant to study the behavior of nano-TiO2 migration. The structural changes and intermolecular interactions were determined by scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The migration amount increased with the increase of initial nano-TiO2 content. SEM images demonstrated that the microstructure of PLA nanocomposite films became rougher as exposure to ethanol solution in a few days. XRD spectra indicated that a decrease in the intensity of specific diffraction peak occurred as the decrease in nano-TiO2 content of PLA nanocomposite films during exposure to ethanol simulant. DSC analysis confirmed that the higher crystallinity percentage obtained during the different degradation times. The reasonable food packaging application of the nano-TiO2 composite films with restrained nano-TiO2 migration could be accomplished by controlling the nano-TiO2 loading.

17.
Allergy ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31386217

RESUMO

BACKGROUND: Studies on early puberty and incident asthma have reported inconsistent results and are mainly performed in females. In this longitudinal study, we investigated the causal relationship between pubertal maturation and asthma through Mendelian randomization (MR) and explored the joint effect of overweightness and early pubertal maturation on asthma. METHODS: We used data from the Taiwan Children Health Study with longitudinal follow-ups of 2991 children aged 11-17 years. Six puberty-related single-nucleotide polymorphisms (combined into a weighted allelic score) were used to yield genetic instrumental variables for early puberty. Early pubertal maturation was defined as reaching a certain pubertal stage earlier than the median age for that stage. Incident asthma cases were calculated by excluding children with a history of asthma prior to that age. RESULTS: The results of MR analysis revealed that early pubertal maturation was associated with active asthma (OR = 1.18; 95% CI: 1.08-1.28); this effect was significant in male children. Early pubertal maturation significantly increased the risk of incident asthma outcomes at 12 and 17 years of age in both sexes (hazard ratio = 2.15; 95% CI: 1.21-3.84). Taking non-overweight and non-early puberty children as the reference group, we observed a synergistic effect of overweightness and early pubertal maturation on asthma risk (OR = 1.08; 95% CI: 1.04-1.11) in children of both sexes. CONCLUSIONS: Early screening and intervention for obesity are recommended to prevent future early pubertal onset and asthma occurrence.

18.
Turk Neurosurg ; 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31452175

RESUMO

AIM: We aimed to predict the overall survival (OS) and the cancer-specific survival (CSS) of patients with high-grade glioma (HGG) using nomograms and the Surveillance, Epidemiology, and End Results (SEER) database (2000-2013). MATERIAL AND METHODS: A total of 3706 patients with high-grade glioma were identified by the SEER database (2000-2013). Based on the relevant information of these patients, we divided the primary cohort into a training cohort (n = 3336) and a validation cohort (n = 370). The nomograms were constructed by the training cohort and corroborated by the validation cohort. RESULTS: According to the multivariate analysis of the training cohort, the nomograms of OS and CSS indicated that patient age at diagnosis, laterality, radiation, and the extent of resection are significantly correlated with the survival rate. The c-indexes of the nomograms of OS and CSS of the training cohort are 0.682 [95% confidence interval (CI): 0.671-0.693] and 0.678 (95%CI: 0.666-0.690), respectively. The calibration curve plots of 1- and 3-year OS and CSS showed that the nomogram predictions are consistent with the observed outcomes for both the training and validation cohorts. CONCLUSION: Based on the data obtained, we established a scoring model to predict the OS and the CSS of patients with HGG. All calibration curves showed high consistency between the predicted and actual survival.

19.
Chem Biol Interact ; 311: 108793, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31421117

RESUMO

Polyphyllin I (PPI), a bioactive component extracted from Paris polyphylla, was reported to have potent anticancer activities in previous studies. However, there were few reports on the effects and underlying mechanism of PPI in human acute myeloid leukemia cells. The present study demonstrated that PPI had an inhibitory effect through inducing apoptosis and autophagy in THP-1 and NB4 cells. PPI induced apoptosis via activating JNK pathway, as evidenced by the decreased Bcl-2 levels and increased Bax, cleaved-caspase-3 and phosphorylated-JNK expressions. In addition, PPI promoted autophagy as evidenced with increased expressions of LC3-II and Beclin-1 in western blot and autophagic vacuoles in MDC staining, which was associated with the inhibition of AKT-mTOR pathway. Furthermore, JNK inhibitor SP600125 and autophagy inhibitor 3-MA were employed to evaluate the role of apoptosis and autophagy in PPI-induced cell death. We found that autophagy and apoptosis were both causes of cell death induced by PPI. These data suggested that PPI could be a potent therapeutic agent for the treatment of human acute myeloid leukemia.

20.
Ophthalmic Genet ; 40(3): 237-241, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31269845

RESUMO

Background: It has been shown that genetic factors play an important role in the pathogenesis of primary open-angle glaucoma (POAG). This study was conducted to investigate the association between the polymorphism rs11656696 located in the growth arrest-specific 7 gene (GAS7) and POAG. Methods: A cohort of 799 unrelated POAG patients and 799 unrelated control subjects was enrolled in this case-control association study. The polymorphism rs11656696 was genotyped using the SNaPshot method. The genotype and allele frequencies were evaluated using the χ2 tests. Results: The allele frequency distribution of rs11656696 in the GAS7 gene showed that there was significant difference between POAG cases and controls (P= .006448, OR = 0.82, 95%CI = (0.72-0.95). The minor "A" allele frequency of this polymorphism was 0.477 in the POAG cases, whereas it was 0.526 in controls, suggesting a protective effect for POAG. Significant associations were detected under the homozygous model (p = .006425, OR = 0.68, 95%CI = 0.51-0.90) and recessive model (p = .0003432, OR = 0.66, 95%CI = 0.52-0.84), indicating that subjects carrying rs11656696 AA genotype were less likely to suffer from POAG than those carrying AC/CC genotypes. Conclusion: This case-control association study showed that polymorphism rs11656696 in GAS7 is related to POAG and might be a protective factor against POAG.

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