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1.
Diabetes Ther ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020552

RESUMO

INTRODUCTION: The aim of this study was to compare the efficacy of vildagliptin as add-on therapy to short-term continuous subcutaneous insulin infusion (CSII) with CSII monotherapy in hospitalized patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 200 hospitalized patients with inadequately controlled T2DM were randomized into groups, with one group receiving CSII monotherapy (CSII group, n =100) and the other group receiving CSII plus vildagliptin as add-on (CSII + Vig group, n = 100). Of these, 191 completed the 7-day trial (CSII group, n = 99; CSII + Vig group, n = 92) and included in the analysis. The glycemic control and variability of the patients were measured using all-day capillary blood glucose (BG) monitoring. Weight and fasting C-peptide levels were evaluated before and after the interventions. RESULTS: Mean BG concentrations during the whole treatment period were lower and the time to reach target BG was reduced in the CSII + Vig group compared with the CSII group (9.89 ± 3.37 vs. 9.46 ± 3.23 mmol/L, P < 0.01; 129 ± 4 vs. 94 ± 5 h, P < 0.01, respectively). Similarly, the indicators of glycemic variability, namely the standard deviation of BG and the largest amplitude of glycemic excursion, were significantly decreased in the CSII + Vig group compared with the CSII group (2.68 ± 1.05 vs. 2.39 ± 1.00 mmol/L, P < 0.01; 7.19 ± 2.86 vs. 6.23 ± 2.73 mmol/L, P < 0.01, respectively). CONCLUSIONS: Short-term CSII with vildagliptin as add-on therapy may be an optimized treatment for hospitalized patients with T2DM compared with short-term CSII monotherapy.

2.
Hepatology ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022277

RESUMO

The long term risk of disease for patients with NAFLD in the absence of elevated enzymes is unclear. We conducted a retrospective cohort study utilizing the Corporate Data Warehouse of the Veterans Health Administration. We classified patients into 3 groups: patients with steatosis/normal ALT, steatosis/elevated ALT, and no steatosis/normal ALT. We examined incidence rates (IR) for cirrhosis and hepatocellular carcinoma (HCC) and conducted cause specific hazard models to evaluate the risk of cirrhosis and HCC. We identified 3,522 patients with steatosis/normal ALT, 15,419 patients with steatosis/elevated ALT, and 9,267 patients with no steatosis/normal ALT. Mean age in each group was 58.9, 54.7 and 59.3 years, respectively; over 90% were men. Compared to patients with hepatic steatosis/normal ALT, those with steatosis/elevated ALT were younger and more likely to be obese (both p<0.01). In patients with steatosis/normal ALT, the IR of cirrhosis and HCC were 1.22 (95% confidence interval [CI] 0.83-1.74) and 0.20 (95% CI 0.06-0.46) per 1000-person years, respectively; this was lower than in patients with steatosis/elevated ALT (cirrhosis: 3.85, 95% CI: 3.50-4.23, HCC: 0.37 95% CI 0.26-0.49). Patients with steatosis/elevated ALT had a higher risk of developing cirrhosis (adjusted hazard ratio [HR]=3.37, 95% CI=2.34-4.86, p<0.01) than patients with steatosis/normal ALT; they also had a higher risk of HCC, although it did not reach statistical significance (HR=2.07, 95% CI=0.82-5.28, p=0.13). The risk of cirrhosis and HCC in patients with steatosis/normal ALT and those without steatosis was not significantly different. In conclusion, patients with hepatic steatosis with persistently normal ALT are at lower risk for cirrhosis compared to those with steatosis and elevated ALT and not different from the risk in a clinical cohort without hepatic steatosis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31991887

RESUMO

The aim of this study was to examine ultra-short-term and short-term heart rate variability (HRV) in under-20 (U-20) national futsal players during pre-tournament training camps and an official tournament. Fourteen male U-20 national futsal players (age = 18.07 ± 0.73 yrs; height = 169.57 ± 8.40 cm; body weight = 64.51 ± 12.19 kg; body fat = 12.42% ± 3.18%) were recruited to participate in this study. Early morning 10 min resting HRV, Borg CR-10 scale session rating of perceived exertion (sRPE), and general wellness questionnaire were used to evaluate autonomic function, training load, and recovery status, respectively. Log-transformed root mean square of successive normal-to-normal interval differences (LnRMSSD) was used to compare the first 30 s, first 1 min, first 2 min, first 3 min, and first 4 min with standard 5 min LnRMSSD. Mean (LnRMSSDmean) and coefficient of variation (LnRMSSDcv) of LnRMSSD were used to compare the different time segments of HRV analysis. The result of LnRMSSDmean showed nearly perfect reliability and relatively small bias in all comparisons. In contrast, LnRMSSDcv showed nearly perfect reliability and relatively small bias from 2-4 min time segments in all study periods. In conclusion, for accuracy of HRV measures, 30 s or 1 min ultra-short-term record of LnRMSSDmean and short-term record of LnRMSSDcv of at least 2 min during the training camps are recommended in U-20 national futsal players.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31980390

RESUMO

OBJECTIVE: The objective of this study was to compare different screw lengths combined with different fluoroscopic views to detect intraoperative dorsal screw penetration in distal radius fractures treated with volar locked plating. MATERIAL AND METHODS: From April 2014 to October 2018, one hundred and eighty patients were included. We divided the patients into four groups. Intraoperative AP and lateral views were taken and sizes of the screws were chosen based on actual measurement (Group A, 45 patients). AP, lateral and tangential views were taken and sizes of the screws were also chosen based on actual measurement (Group B, 45 patients). Intraoperative AP and lateral views were taken and the selected screws were 2mm shorter than actual measurement (Group C, 45 patients). AP, lateral and tangential views were taken and the selected screws were 2mm shorter than actual measurement (Group D, 45 patients). Prominent screws were changed intraoperatively according to each view. A computed tomography (CT) was taken postoperatively to identify residual prominent screws. RESULTS: The number of dorsally prominent screws exceeding 1mm was 6 of 301 in Group A (2.0%), 15 of 290 (5.2%) in Group B, 2 of 289 in Group C (0.7%), and 2 of 282 (0.7%) in Group D. All these prominent screws (25 screws) were exchanged for shorter screws during surgery. Group A and Group B had significant difference in detecting intraoperative dorsal screw penetration (p<0.05). Group C and Group D had no significant difference in detecting intraoperative dorsal screw penetration (p>0.05). Postoperative CT identified 12 additional prominent screws with≥1mm dorsal penetration in Group A, 2 screws in Group B, 1 screw in Group C and 0 screw in Group B respectively. Significant difference was found between Group A and Group B of CT results (p<0.05) while no statistical difference was found between Group C and Group D of CT results (p>0.05). DISCUSSIONS: Tangential view helped identify screw penetration. If tangential view was not available intraoperatively, screw penetration could also be avoided by downsizing the distal locking screw by 2mm shorter than actual measurement.

5.
Mol Plant ; 13(1): 128-143, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31698047

RESUMO

Plant plasmodesmata (PDs) are specialized channels that enable communication between neighboring cells. The intercellular permeability of PDs, which affects plant development, defense, and responses to stimuli, must be tightly regulated. However, the lipid compositions of PD membrane and their impact on PD permeability remain elusive. Here, we report that the Arabidopsis sld1 sld2 double mutant, lacking sphingolipid long-chain base 8 desaturases 1 and 2, displayed decreased PD permeability due to a significant increase in callose accumulation. PD-located protein 5 (PDLP5) was significantly enriched in the leaf epidermal cells of sld1 sld2 and showed specific binding affinity to phytosphinganine (t18:0), suggesting that the enrichment of t18:0-based sphingolipids in sld1 sld2 PDs might facilitate the recruitment of PDLP5 proteins to PDs. The sld1 sld2 double mutant seedlings showed enhanced resistance to the fungal-wilt pathogen Verticillium dahlia and the bacterium Pseudomonas syringae pv. tomato DC3000, which could be fully rescued in sld1 sld2 pdlp5 triple mutant. Taken together, these results indicate that phytosphinganine might regulate PD functions and cell-to-cell communication by modifying the level of PDLP5 in PD membranes.

6.
Cancer Chemother Pharmacol ; 85(1): 61-67, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31745592

RESUMO

PURPOSE: Chemotherapy-related cognitive impairments in breast cancer patients were usually reported through cognitive questionnaires or scales which may be subjective and insensitive. This study is to assess the effect of chemotherapy on cognitive function in breast cancer patients stratified by age using objective electrophysiological measure, the P300 component of event-related potentials (ERPs) with a large sample size. METHODS: Totally, 529 primary breast cancer patients, including 178 cases at initial diagnosis stage and before chemotherapy (Group1), 167 cases during chemotherapy (Group2), and 184 cases post chemotherapy and during follow-up period (Group3), were examined with ERPs (P300 component) to assess the effect of chemotherapy on their cognitive function. RESULTS: There were significant differences of P300 latency in Group2 (364.74 ± 15.73 ms) and Group3 (364.02 ± 17.12 ms, mean follow-up period of 2.42 years) compared with Group1 (355.13 ± 19.47 ms, P < 0.001), respectively. With further age stratification: in patients of < 50 years, P300 latency was significantly prolonged in Group2 and Group3 compared with Group1 (P < 0.001), respectively; in patients of 50-59 years, P300 latency was significantly prolonged in Group2 compared with Group1 (P < 0.05), but without difference in Group1 and Group3 (P>0.05); In patients of ≥ 60 years, there were no differences of P300 latency among three the groups (P>0.05). CONCLUSIONS: It is first suggested by our objective detection data that the side effect of chemotherapy on cognitive functions in breast cancer patients may decrease with age. Electrophysiological cognitive impairments mainly occur in younger breast cancer patients undergoing chemotherapy and would last for years after chemotherapy, which highlights the importance of early intervention for those patients, especially in younger patients.

7.
Otolaryngol Head Neck Surg ; 162(1): 121-128, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31739743

RESUMO

OBJECTIVE: Children with long-term tracheostomies are at higher risk of complications. This study aims to describe the epidemiology, outcomes, and factors associated with successful decannulation in children undergoing tracheostomy. STUDY DESIGN: Case series with chart review. SETTING: Tertiary hospital. SUBJECTS AND METHODS: A retrospective analysis was conducted on pediatric tracheostomies performed from 2006 to 2016. Demographics, preexisting comorbidities, indications for tracheostomy, and pretracheostomy ventilatory requirements were collected. A multivariate regression model with covariates of age, failure to thrive (FTT), and comorbidities was used to identify factors associated with successful decannulation. Secondary outcomes were ventilation and oxygen requirements at hospital discharge, hospital and intensive care unit length of stay, and complications. RESULTS: In total, 105 patients received a tracheostomy at a median age of 8.0 months (interquartile range, 2.0-45.0). The most common indication was anatomic airway obstruction (55 of 105, 52.5%). Forty-four (41.9%) patients had preexisting FTT. In-hospital mortality was 14 of 105 (13.3%). None were directly related to tracheostomy. At discharge, 40 of 91 (44.0%) and 12 of 91 (13.2%) required home mechanical ventilation and supplemental oxygen, respectively. Forty-one (39%) patients underwent successful decannulation at a median 408 days (interquartile range, 170-1153) posttracheostomy. On adjusted analysis, unsuccessful decannulation was more common in patients with FTT and neurologic comorbidities. Postoperative complications were more common in younger patients and those with a longer time to decannulation. CONCLUSION: Neurologic comorbidities and FTT were risk factors for unsuccessful decannulation after pediatric tracheostomy. Nutritional interventions may have a role in improving long-term outcomes following pediatric tracheostomies and should be investigated in future studies.

8.
Antiviral Res ; 174: 104698, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862503

RESUMO

BACKGROUND & AIMS: Randomized controlled trials of EBR/GZR have reported high treatment efficacy, safety and tolerability in patients undergoing dialysis. However, real world effectiveness data for EBR/GZR in this population is lacking. We evaluated the effectiveness of EBR/GZR in an HCV-infected population with all stages of CKD including dialysis compared with control patients with estimated glomerular filtration rate (eGFR) ≥60 in the US Department of Veterans Affairs (VA). METHODS: We conducted a retrospective cohort study of patients with chronic HCV genotype 1 infection with EBR/GZR prescriptions dispensed during February 1, 2016-August 31, 2017 in 128 VA Medical Centers. We collected patient information regarding history of dialysis, end stage renal disease (ESRD), and/or eGFR values. We measured SVR based on undetectable HCV RNA at least 4 weeks after the completion of treatment. We examined SVR rates by CKD stage compared to control patients and within patient subgroups using logistic regression models. RESULTS: We identified 5961 patients (42.5% genotype 1a, 55.0% genotype 1b) who met eligibility criteria and completed a EBR/GZR treatment course (≥11 weeks). Approximately 73.2% (n = 4361) had eGFR ≥60 who served as control patients, 14.4% (n = 860) had Stage 3 CKD, and 12.4% (n = 740) had Stage 4-5 CKD or ESRD. Of patients with Stage 4-5 CKD/ESRD, 76.1% underwent dialysis (n = 563). The overall SVR was 96.7% in all patients, 96.4% for eGFR≥60, 98.3% in Stage 3 CKD, and 96.5% in Stage 4-5 CKD/ESRD. No statistically significant differences were found in the SVR rates in patients with or without dialysis in the Stage 4-5 CKD/ESRD patients (adjusted OR 0.91; 95% CI 0.56-1.47 and OR 1.74; 95% CI 0.63-4.81) compared with those with eGFR≥60. CONCLUSION: We found EBR/GZR was effective in patients with HCV GT1 infection regardless of CKD severity or receipt of dialysis in the US VA population.

9.
J Neurosci Res ; 98(2): 384-403, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31407399

RESUMO

The cAMP-dependent protein kinase A family (PKAs), protein kinase C family (PKCs), and Src family kinases (SFKs) are found to play important roles in pain hypersensitivity. However, more detailed investigations are still needed in order to understand the mechanisms underlying the actions of PKAs, PKCs, and SFKs. Neurons in the hypothalamic arcuate nucleus (ARC) are found to be involved in the regulation of pain hypersensitivity. Here we report that the action potential (AP) firing activity of ARC neurons in culture was up-regulated by application of the adenylate cyclase activator forskolin or the PKC activator PMA, and that the forskolin or PMA application-induced up-regulation of AP firing activity could be blocked by pre-application of the SFK inhibitor PP2. SFK activation also up-regulated the AP firing activity and this effect could be prevented by pre-application of the inhibitors of PKCs, but not of PKAs. Furthermore, we identified that forskolin or PMA application caused increases in the phosphorylation not only in PKAs at T197 or PKCs at S660 and PKCα/ßII at T638/641, but also in SFKs at Y416. The forskolin or PMA application-induced increase in the phosphorylation of PKAs or PKCs was not affected by pre-treatment with PP2. The regulations of the SFK and AP firing activities by PKCs were independent upon the translocation of either PKCα or PKCßII. Thus, it is demonstrated that PKAs may act as an upstream factor(s) to enhance SFKs while PKCs and SFKs interact reciprocally, and thereby up-regulate the AP firing activity in hypothalamic ARC neurons.

10.
World J Gastrointest Oncol ; 11(11): 1043-1053, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31798784

RESUMO

BACKGROUND: Several models are currently available for predicting the malignancy of pancreatic intraductal papillary mucinous neoplasm (IPMN), namely, the Pancreatic Surgery Consortium (PSC), the Japan Pancreas Society (JPS), the Johns Hopkins Hospital (JHH), and the Japan-Korea (JPN-KOR) models. However, a head-to-head comparison that shows which model is more accurate for this individualized prediction is lacking. AIM: To perform a head-to-head comparison of the four models for predicting the malignancy of pancreatic IPMN. METHODS: A total of 181 patients with IPMN who had undergone surgical resection were identified from a prospectively maintained database. The characteristics of IPMN in patients were recorded from endoscopic ultrasound imaging data and report archives. The performance of all four models was examined using Harrell's concordance index (C-index), calibration plots, decision curve analyses, and diagnostic tests. RESULTS: Of the 181 included patients, 94 were categorized as having benign disease, and the remaining 87 were categorized as having malignant disease. The C-indexes were 0.842 [95% confidence interval (CI): 0.782-0.901], 0.704 (95%CI: 0.626-0.782), 0.754 (95%CI: 0.684-0.824), and 0.650 (95%CI: 0.483-0.817) for the PSC, JPS, JHH, and JPN-KOR models, respectively. Calibration plots showed that the PSC model had the least pronounced departure from ideal predictions. Of the remaining three models, the JPS and JHH models underestimated the probability of malignancy, while the JPN-KOR model overestimated the malignant potential of branch duct-IPMN. Decision curve analysis revealed that the PSC model resulted in a better clinical net benefit than the three other models. Diagnostic tests also showed a higher accuracy (0.801) for the PSC model. CONCLUSION: The PSC model exhibited the best performance characteristics. Therefore, the PSC model should be considered the best tool for the individualized prediction of malignancy in patients with pancreatic IPMN.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31839998

RESUMO

Dysregulation of dickkopf-related protein 1 (DKK1) expression has been reported in a variety of human cancers. We previously reported that DKK1 was upregulated in hepatocellular carcinoma (HCC). However, the role of DKK1 in HCC remains unclear. This study aimed to investigate the clinical significance and biological functions of DKK1 in HCC. The expression of DKK1 was examined in cirrhotic and HCC tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). DKK1 was silenced or overexpressed in HCC cell lines, and in vitro and in vivo studies were performed. Immunohistochemistry revealed that DKK1 was weakly expressed in cirrhotic tissues (8/22, 36.4%) but upregulated in HCC tissues (48/53, 90.6%, cohort 1). Significant upregulation of DKK1 was observed in 57.6% (19/33, cohort 2) of HCC tissues by qRT-PCR, and the expression of DKK1 was associated with tumor size (P = 0.024) and tumor number (P = 0.019). Genetic depletion of DKK1 impaired the proliferation, colony-forming ability, invasion, and tumor formation of HCC cells (HepG2 and HUH-7). Conversely, forced expression of DKK1 increased the proliferation, colony-forming ability, and invasion of HepG2 and HUH-7 cells in vitro and enhanced tumor formation in vivo. Subsequent investigation revealed that the DKK1-mediated proliferation and tumorigenicity of HepG2 and HUH-7 cells is dependent on the Wnt/ß-catenin signaling pathway. These findings indicate that DKK1 plays an oncogenic role in HCC by activating the Wnt/ß-catenin signaling pathway.

12.
Front Oncol ; 9: 1319, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31828041

RESUMO

Background: ALK and ROS1 rearrangement accounts for 3-6% and 1-3% of non-small cell lung cancers, respectively, while coexistence of them in the same patient is extremely rare. Only three cases have ever been reported with concurrent ALK/ROS1 fusions in the same tumor indicating tumor heterogeneity. Therefore, comprehensive genetic profiling via next-generation sequencing (NGS) is needed to provide fully molecular diagnosis. Case Presentation: A 50-year old Chinese female with resectable stage IB bilateral lung adenocarcinomas (ADCs) harbored EML4 exon 6-ALK exon 19 and TPM3 exon 8-ROS1 exon 35 fusions in the right lower and the left upper tumors, respectively, identified by clinical NGS test targeting 425 cancer-relevant genes. The results were further confirmed at RNA level using RNA-seq. Genomic evolution analysis reveals that these bilateral tumors are synchronous multiple primary lung cancers with no shared somatic alterations for both genes and arm-level copy number variations (CNVs). No recurrence was observed during 12 months of post-surgery follow-up. Conclusions: Our case is the first report of concurrent ALK/ROS1 fusions as distinct driver events of synchronous multiple primary lung cancers, and highlights the importance of individual genetic testing for each of the multiple primary tumors for fully molecular diagnosis and precise treatment decision-making.

13.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4947-4952, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872605

RESUMO

An UPLC-MS/MS method simultaneously determining contents of quercetin-3-O-ß-D-glucose-7-O-ß-D-gentiobioside and sinapic acid in rats' plasma was firstly established and applied to study the effects of processing on pharmacokinetics of Descurainiae Semen's active constituents. Complantatoside A as internal standard,methanol used for protein precipitation,the method was validated according to the instructions of CFDA. Rats' plasma was collected after being oral administrated equal dosage of 60% ethanal extract of raw or processed Descurainiae Semen at different point of time,then the concentrations were determined to calculate pharmacokinetic parameters using DAS 3. 2. 6. And the parameters were analyzed using SPSS 23. 0,meantime the concentration-time curve was drawn.The results showed that processing had no effects on the pharmacokinetics of QGG,but could improve the absorption of sinapic acid and slow down the excretion.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
15.
World J Gastroenterol ; 25(41): 6248-6257, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31749595

RESUMO

BACKGROUND: Platelets have been reported to participate in tumor cell growth, extravasation, epithelial-mesenchymal transition, metastasis, and drug resistance. However, the importance of platelets in pancreatic neuroendocrine tumor (pNET) lacks adequate literature support. The predictive value of tumor-infiltrating platelets (TIPs) in pNET remains unclear. AIM: To investigate the relationship between TIPs and the prognosis of patients with pNET following radical resection. METHODS: In total, 113 patients who had undergone radical surgical resection with a pathologic diagnosis of pNET were enrolled in this study. Immunohistochemical analysis of cluster of differentiation 42b (CD42b) expression in the tumor specimens was performed to determine the presence of TIPs. Univariate and multivariate analyses were used to analyze the prognostic value of TIPs. RESULTS: TIPs were observed in intratumoral areas in 54 patients. Neither basic characteristics nor preoperative platelet-associated indicators showed a significant relationship with the presence of TIPs (all P > 0.05). Patients with positive intratumoral CD42b expression had worse overall survival (P = 0.005) and recurrence-free survival (P < 0.001) than those with negative intratumoral CD42b expression. Multivariate analysis demonstrated that TIPs were independent prognostic factors for overall survival (P = 0.049) and recurrence-free survival (P = 0.003). Nevertheless, platelet count, mean platelet volume, and platelet-to-lymphocyte ratio were not associated with postoperative survival or recurrence in pNET patients (all P > 0.05). CONCLUSION: TIPs are a useful prognostic biomarker for patients with resectable pNET, and their detection represents a promising tool for pNET treatment strategy decisions.

16.
Int J Nanomedicine ; 14: 8499-8507, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695377

RESUMO

Background: Beyond magnetic resonance imaging (MRI), which has been widely used clinically, molecular MRI (mMRI) can further provide qualitative and quantitative information at the cellular and molecular levels. However, the diagnostic accuracy may not be satisfactory via single-contrast mMRI due to some interferences in vivo. T1/T2 dual-contrast MRI using the same contrast agent (CA) could significantly improve the detection accuracy. Therefore, in this study, we fabricated poly(ethylene glycol) (PEG)-coated, manganese-doped iron oxide nanocomposites (Mn-IONPs@PEG) as T1/T2 dual-contrast CA, and evaluated its feasibility of T1/T2 dual-contrast MRI in vitro and in vivo. Methods: Mn-IONPs were prepared by the thermal decomposition of iron-eruciate and manganese-oleate complexes and were coated with 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethylene glycol]-2000) (DSPE-PEG 2000). The physicochemical properties and cytotoxicity of the Mn-IONPs were fully characterized, followed by MRI in vitro and in vivo. Results: Ultrasmall 3 nm-sized nanoparticles were successfully prepared and were identified using transmission electron microscopy (TEM), high-resolution TEM, and X-ray diffraction. After coating with DSPE-PEG, the Mn-IONPs@PEG displayed excellent hydrophilicity and good biocompatibility. Due to the manganese-doping and PEG coating, the Mn-IONPs@PEG showed good relaxivity in vitro. Especially, the Mn-IONPs@PEG coated with DSPE-PEG following a mass ratio to Mn-IONPs of 1:20 showed harmonious longitudinal relaxivity (r 1 = 7.1 mM-1s-1) and transversal relaxivity (r 2 = 120.9 mM-1s-1), making it a better candidate for T1/T2 dual-contrast mMRI. After administrated via a caudal vein, the Mn-IONPs@PEG can induce significant enhancement in both T1-weighted and T2-weighted MR images and the time at 10 mins after injection was regarded as a suitable time for imaging because both the T1 and T2 enhancement were optimum at that time. Conclusion: The obtained Mn-IONPs@PEG exhibited good r 1 and r 2 and was a reasonable candidate for T1/T2 dual-contrast mMRI.


Assuntos
Compostos Férricos/química , Imagem por Ressonância Magnética , Compostos de Manganês/química , Nanopartículas/química , Óxidos/química , Tamanho da Partícula , Polietilenoglicóis/química , Animais , Sobrevivência Celular , Meios de Contraste/química , Células Hep G2 , Humanos , Fígado/patologia , Camundongos Endogâmicos C57BL , Nanopartículas/ultraestrutura
17.
Acta Pharmacol Sin ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700088

RESUMO

Xanthatin is a natural sesquiterpene lactone purified from Xanthium strumarium L., which has shown prominent antitumor activity against a variety of cancer cells. In the current study, we investigated the effect of xanthatin on the growth of glioma cells in vitro and in vivo, and elucidated the underlying mechanisms. In both rat glioma C6 and human glioma U251 cell lines, xanthatin (1-15 µM) dose-dependently inhibited cell viability without apparent effect on the cell cycle. Furthermore, xanthatin treatment dose-dependently induced glioma cell apoptosis. In nude mice bearing C6 glioma tumor xenografts, administration of xanthatin (10, 20, 40 mg·kg-1·d-1, ip, for 2 weeks) dose-dependently inhibited the tumor growth, but did not affect the body weight. More importantly, xanthatin treatment markedly increased the expression levels of the endoplasmic reticulum (ER) stress-related markers in both the glioma cell lines as well as in C6 xenografts, including glucose-regulated protein 78, C/EBP-homologous protein (CHOP), activating factor 4, activating transcription factor 6, spliced X-box binding protein-1, phosphorylated protein kinase R-like endoplasmic reticulum kinase, and phosphorylated eukaryotic initiation factor 2a. Pretreatment of C6 glioma cells with the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 7 mM) or knockdown of CHOP using small interfering RNA significantly attenuated xanthatin-induced cell apoptosis and increase of proapoptotic caspase-3. These results demonstrate that xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating the ER stress-related unfolded protein response pathway involving CHOP induction. Xanthatin may serve as a promising agent in the treatment of human glioma.

18.
Hepatology ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675427

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver condition. Predicting its progression could help clinicians manage and potentially prevent complications. We evaluated the independent and joint effects of metabolic traits on the risk of cirrhosis and hepatocellular carcinoma (HCC) among patients with NAFLD. We assembled a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration between 1/1/2004 and 12/31/2008 with follow-up through 12/31/2015. We performed competing risk, adjusted cause-specific Cox models to evaluate the effects of metabolic traits (diabetes, hypertension, dyslipidemia, obesity) as additive or combined indicators on time to develop cirrhosis or HCC or a composite endpoint of both. Of the 271,906 patients, 22,794 developed cirrhosis, and 253 developed HCC during a mean of 9 years follow up. At baseline, the mean BMI was 31.6 (SD, 5.6), 28.7% had diabetes, 70.3% hypertension, and 62.3% had dyslipidemia with substantial overlap among the these traits. The risk of progression was the lowest in patients with only one or no metabolic trait. There was a stepwise increase in risk with each additional metabolic trait. Compared to patients with no metabolic trait, patients with both hypertension and dyslipidemia had 1.8-fold higher risk of progression to cirrhosis/HCC (hazard ratio (HR) =1.8, 95% CI=1.59-2.06); the risk was 2.6-fold higher in patients with diabetes, obesity, dyslipidemia and hypertension (HR=2.6, 95% CI=2.3,2.9). These associations were stronger for HCC. Diabetes had the strongest association with HCC in this cohort. CONCLUSIONS: Each additional metabolic trait increased the risk of cirrhosis and HCC in patients with NAFLD. Diabetes conferred the highest risk of progression to HCC. Diabetic patients with co-existing hypertension and obesity may be important targets for secondary prevention.

20.
Nat Commun ; 10(1): 4574, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594929

RESUMO

Several recent studies have shown the presence of genes for the key enzyme associated with archaeal methane/alkane metabolism, methyl-coenzyme M reductase (Mcr), in metagenome-assembled genomes (MAGs) divergent to existing archaeal lineages. Here, we study the mcr-containing archaeal MAGs from several hot springs, which reveal further expansion in the diversity of archaeal organisms performing methane/alkane metabolism. Significantly, an MAG basal to organisms from the phylum Thaumarchaeota that contains mcr genes, but not those for ammonia oxidation or aerobic metabolism, is identified. Together, our phylogenetic analyses and ancestral state reconstructions suggest a mostly vertical evolution of mcrABG genes among methanogens and methanotrophs, along with frequent horizontal gene transfer of mcr genes between alkanotrophs. Analysis of all mcr-containing archaeal MAGs/genomes suggests a hydrothermal origin for these microorganisms based on optimal growth temperature predictions. These results also suggest methane/alkane oxidation or methanogenesis at high temperature likely existed in a common archaeal ancestor.

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