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1.
J Acad Nutr Diet ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31473155

RESUMO

BACKGROUND: There is a disproportionate burden of low diet quality among young adults compared with other adult subpopulations that is not understood. Perceived and objective diet qualities are studied to understand possible barriers to change. OBJECTIVE: To explore the association between perceived diet quality and objective diet quality in young adults in the United States. DESIGN: This cross-sectional study used data from the 2013-2014 National Health and Nutrition Examination Survey to calculate total Healthy Eating Index-2010 (HEI-2010) score and component scores and study their relationships with perceived diet quality scores. PARTICIPANTS/SETTING: The sample consisted of 1,261 young adults, aged 18 to 30, with 24-hour recall data. MAIN OUTCOME MEASURES: Perceived and objective diet quality were evaluated. STATISTICAL ANALYSES PERFORMED: Multiple regression analysis was used to test the ability to predict total HEI-2010 scores from perceived diet quality scores. Ordered logit was used to test whether HEI-2010 component scores predicted the odds of having higher perceived diet quality. RESULTS: Excellent (b=8.442, P<0.001), very good (b=9.733, P<0.001), and good (b=5.527, P<0.001) perceived diet quality were significant predictors of total HEI-2010 score, compared with the referent category of poor perceived diet quality. The full regression model predicted 17.0% of the variance in total HEI-2010 score. Whole fruit (odds ratio [OR]=1.098, P=.017), whole grains (OR=1.046, P=.023), and empty calories (OR=1.054, P<0.001) were each significantly associated with the odds of having a higher rating of perceived diet quality (fair, good, very good, excellent) instead of a poor rating of diet quality; the difference in odds was low across categories. CONCLUSIONS: There are significant relationships between perceived and objective diet quality, but other variables play a substantial role in explaining these two types of diet quality.

2.
BMC Neurol ; 19(1): 215, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472692

RESUMO

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most frequent types of autoimmune encephalitis. However, the instigating mechanisms are as yet not fully ascertained. Cardinal clinical manifestations of anti-NMDAR encephalitis include acute behavioural change, psychosis, and catatonia. As the level of diagnosis increases, encephalitis becomes more common, but there are never been published in patients with anti-NMDAR encephalitis and simultaneous hypertrophic pachymeningitis. CASE PRESENTATION: A sixty-eight-year-old man who presented with mental, behavioral abnormalities, unstable walking, headaches, and erratic hand movements. The neuropsychiatric symptoms and cerebrospinal fluid examination was consistent with the diagnosis criteria of anti-NMDAR encephalitis. Magnetic resonance imaging of the brain showed a thickening of dura mater localized at the left tentorium cerebelli, left cerebral hemisphere, and cerebral falx; the thickening dura mater was characterized by an intense contrast enhancement after the administration of gadolinium. High doses of intravenous methylprednisolone were administrated during his hospitalization. After 5 days, the patient's condition improved. CONCLUSIONS: We herein describe a rare case of a 68-year-old man with anti-NMDAR encephalitis presenting with concomitant hypertrophic pachymeningitis. We systematically expounded anti-NMDAR encephalitis and hypertrophic pachymeningitis, and made bold conjectures on the etiology and pathogenesis of these two diseases, hoping to stimulate new ideas from clinicians and basic medical researchers.

3.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(9): 1116-1120, 2019 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-31512452

RESUMO

Objective: To evaluate the mid- and long-term effectiveness of total hip arthroplasty (THA) with Ribbed femoral stem prosthesis. Methods: A clinical data of 354 patients (384 hips) with hip disease who underwent THA with Ribbed femoral stem prostheses between October 2006 and May 2016 was retrospectively analyzed. There were 171 males and 183 females, with an average age of 53.4 years (range, 20-82 years). There were 324 cases of single hip and 30 cases of bilateral hips. The cause of THA included the avascular necrosis of the femoral head in 151 cases (159 hips), hip osteoarthritis in 134 cases (136 hips), rheumatoid arthritis in 43 cases (43 hips), ankylosing spondylitis in 20 cases (40 hips), and trauma in 6 cases (6 hips). The Harris score of total 354 patients before operation was 42.34±8.89. Harris scores were used to evaluate hip function after operation. X-ray films were used to determine the length of the lower limb, the radiolucent line on the femur side, the stability of the prosthesis, and the occurrence of stress shielding. Results: The incisions healed by first intention. All patients were followed up 2-11 years with an average of 7.4 years. The Harris score at last follow-up was 80.52±7.61, which significantly increased when compared with preoperative score ( t=134.804, P=0.000). Two cases (2 hips) of prosthetic infections, 3 cases (3 hips) of prothesis loosening, and 4 cases (4 hips) of periprosthetic fractures, and 48 cases (48 hips) of mild to moderate thigh pain occurred after operation. X-ray films showed 76 cases (78 hips) with radiolucent lines on the femur side and stress shielding. According to the Engh's method, there were 364 hips of bone ingrowth, 15 hips of fibrosis ingrowth, and 5 hips of prosthesis instability. The femoral stem subsidence occurred in 25 cases (25 hips), and the difference in leg length discrepancy was more than 10 mm in 5 patients. Conclusion: THA with Ribbed femoral stem prosthesis can achieve satisfactory effectiveness with good initial stability and rapid bone growth. The incidence of stress shielding is relatively high, but the stress shielding has no significant impact on the mid- and long-term survival rate and effectiveness of femoral prosthesis.

4.
World J Urol ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502032

RESUMO

PURPOSE: To compare the perioperative and functional outcomes of holmium laser enucleation of the prostate (HoLEP) and thulium laser enucleation of the prostate (ThuLEP) for the treatment of large-volume benign prostatic hyperplasia (BPH) (> 80 ml). METHODS: A total of 116 consecutive patients with BPH were randomized to be treated surgically with either HoLEP (n = 58) or ThuLEP (n = 58), following the classical three-lobe enucleation technique. Follow-up was assessed at 1, 3, 6, 12 and 18 months after surgery. RESULTS: At 18 months, the lower urinary tract symptom index was improved significantly in both groups compared with the baseline values. The operative time (78.4 ± 8.0 vs. 71.4 ± 6.4 min) and enucleation time (61.2 ± 5.4 vs. 56.4 ± 8.4 min) were significantly shorter for ThuLEP compared to HoLEP (both p < 0.001). There were no significant differences between the two groups regarding morcellation time, resected weight, hemoglobin decrease, catheter time and hospital stay (p > 0.05). The HoLEP and ThuLEP groups had equivalent International Prostate Symptom Scores (3 [3-3] vs. 3 [3-3], p = 0.776), quality of life (1 [1-2] vs. 2 [1-2], p = 0.809), Qmax (25.3 ± 4.8 ml/s vs. 24.7 ± 4.4 ml/s, p = 0.470), postvoid residual urine (PVR) (6.1 [2.6-20.8] vs. 7.7 [3.1-22.8] ml, p = 0.449) and PSA (0.84 ± 0.32 vs. 0.90 ± 0.34 ml, p = 0.309) at 18 months postoperatively. CONCLUSION: Both HoLEP and ThuLEP relieve lower urinary tract symptoms in a comparable way with high efficacy and safety. ThuLEP was statistically superior to HoLEP in operation time and enucleation time, although the differences were clinically negligible.

5.
BMJ Open ; 9(9): e028904, 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31501106

RESUMO

OBJECTIVES: Upper body fat has been associated with an unfavourable cardiometabolic risk. We aimed to investigate the associations between mid-upper arm circumference (MUAC), a novel indicator of upper body fat, and a wide spectrum of cardiometabolic risk profiles in Chinese population. DESIGN AND SETTING: Cross-sectional analyses were performed using data from a well-defined community in 2014, Shanghai, China. PARTICIPANTS: A total of 6287 Chinese adults (2310 men and 3977 women) aged 40 years or older. OUTCOME MEASURES: Multivariable logistic regression model was used to examine the associations of MUAC with cardiometabolic disorders including central obesity, diabetes, hypertension, hypertriglyceridaemia, low high-density lipoprotein (HDL) cholesterol and subclinical atherosclerosis. RESULTS: In the overall participants, after multivariable adjustment, each 1 SD (3.13 cm) increment in MUAC was positively associated with central obesity (OR 2.05; 95% CI 1.85 to 2.28), hypertension (OR 1.10; 95% CI 1.03 to 1.19) and low HDL cholesterol (OR 1.10; 95% CI 1.01 to 1.22). Multivariable-adjusted ORs for subclinical atherosclerosis were gradually increased across increasing quartiles of MUAC with the lowest quartile as reference (quartile 2: OR 1.31; 95% CI 1.09 to 1.58; quartile 3: OR 1.33; 95% CI 1.10 to 1.62; quartile 4: OR 1.45; 95% CI 1.16 to 1.80; p for trend=0.005). Similar but more prominent associations were observed among women than men. In addition, MUAC was significantly interacted with diabetes (p for interaction=0.04) and insulin resistance (p for interaction=0.01) on subclinical atherosclerosis. CONCLUSION: A greater MUAC was positively associated with higher risks of several cardiometabolic disorders and subclinical atherosclerosis in Chinese adults.

6.
Transl Stroke Res ; 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31494833

RESUMO

The aim of this study was to assess the association between admission to stroke centers for acute ischemic stroke and complications and mortality during hospitalization in a Chinese population by means of an observational study using data from the China Stroke Center Data-Sharing Platform. We compared in-hospital complications and mortality for patients admitted with acute ischemic stroke (N = 13,236) between November 1, 2018 and December 31, 2018 at stroke center (SH) and non-stroke center (CH) hospitals using distance to hospitals as an instrumental variable to adjust for potential prehospital selection bias. The results showed that complication rates during hospitalization among ischemic stroke patients who received thrombolytic therapy (n = 11,203) were lower in the SH group than in the CH group: 11.1% vs 15.7% (absolute difference, - 5.11% [95% CI, - 6.05 to - 3.99%], odds ratio [OR] 0.85 [95% CI, 0.74 to 0.92]). The incidence of intracranial hemorrhage was reduced from 4.2 to 3.2%: SH group vs CH group, 3.2% vs 4.2% (absolute difference, - 1.24% [95% CI, - 1.65 to - 0.82%], OR 0.83 [95% CI, 0.69 to 0.0.98]). Furthermore, the total mortality rate in the SH group was also lower than in the CH group: SH group vs CH group, 2.2% vs 3.0% (absolute difference, - 0.92% [95% CI, - 1.48 to - 0.53%], OR 0.85 [95% CI, 0.73 to 0.96]). The data showed that admission to SH hospitals was associated with a lower risk of treatment complications and death for patients with an acute ischemic stroke receiving thrombolytic therapy.

7.
Acta Pharmacol Sin ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444477

RESUMO

Cathepsin L (CTSL), a cysteine protease, is responsible for the degradation of a variety of proteins. It is known to participate in neuronal apoptosis associated with abnormal cell cycle. However, the mechanisms underlying CTSL-induced cell apoptosis remain largely unclear. We reported here that rotenone caused an activation of CTSL expression in PC-12 cells, while knockdown of CTSL by small interfering RNAs or its inhibitor reduced the rotenone-induced cell cycle arrest and apoptosis. Moreover, elevation of CTSL and increased-apoptosis were accompanied by induction of B-Myb, a crucial cell cycle regulator. We found that B-Myb was increased in rotenone-treated PC-12 cells and knockdown of B-Myb ameliorated rotenone-stimulated cell apoptosis. Further analysis demonstrated that CTSL influenced the expression of B-Myb as suppression of CTSL activity led to a decreased B-Myb expression, whereas overexpression of CTSL resulted in B-Myb induction. Reduction of B-Myb in CTSL-overexpressing cells revealed that regulation of cell cycle-related proteins, including cyclin A and cyclin B1, through CTSL was mediated by the transcription factor B-Myb. In addition, we demonstrated that the B-Myb target, Bim, and its regulator, Egr-1, which was also associated with CTSL closely, were both involved in rotenone-induced apoptosis in PC-12 cells. Our data not only revealed the role of CTSL in rotenone-induced neuronal apoptosis, but also indicated the involvement of B-Myb in CTSL-related cell cycle regulation.

8.
Front Immunol ; 10: 1888, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440257

RESUMO

The impairment of immunity characterized by T cell exhaustion is the main cause of death in patients with sepsis after the acute phase. Although PD-1 blockade is highly touted as a promising treatment for improving prognosis, the role of PD-1 plays in sepsis and particularly its different roles in different periods are still very limited. A recent study revealed LAG3 can resist the therapeutic effect of PD-1 blockade in tumor, which inspired us to understand their role in sepsis. We enrolled 26 patients with acute sepsis from 422 candidates using strict inclusion criteria. Follow-up analysis revealed that the expression levels of PD-1 were rapidly increased in the early stage of sepsis but did not change significantly as infection continued (P < 0.05). However, the expression of LAG3 was contrary to that of PD-1. Compared with LAG3 or PD-1 single-positive T cells, T cells coexpressing LAG3 and PD-1 were significantly exhausted (P < 0.05). The proportion of coexpressing T cells was negatively correlated with the total number of lymphocytes (r = -0.653, P = 0.0003) and positively correlated with the SOFA score (r = 0.712, P < 0.0001). In addition, the higher the proportion of coexpressing T cells was, the longer the hospital stay and the higher the mortality. These results showed that LAG3 and PD-1 had a potential synergistic effect in regulating the gradual exhaustion of T cells in sepsis, which seriously affected the clinical prognosis of patients. Therefore, LAG3 and PD-1 double-positive T cells are an important indicator for immunity detection and prognostic evaluation. In the future, precision therapy may pay more attention to the different expression patterns of these two molecules.

9.
Am J Med ; 132(7): e627, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31400797
10.
Medicine (Baltimore) ; 98(35): e17053, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464965

RESUMO

BACKGROUND: Bronchial asthma is one of the most common chronic diseases in the world and has become a serious public health problem. Combination therapy has become the first choice for clinical treatment of bronchial asthma. In addition to the combined use of routine medication, traditional Chinese medicine as an adjuvant therapy is also considered. Xiaoqinglong Decoction (XQLD) is an effective prescription of traditional Chinese medicine in treating asthma, and there are more and more clinical reports about its combination with western medicine in treating asthma. Therefore, we designed this study protocol to evaluate the adjuvant role of XQLD in the treatment of bronchial asthma. METHOD: The following electronic databases will be systematically searched from inception to April 2019: PubMed, EMBASE database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang, Chinese Scientific Journals Database (VIP), and China Biology Medicine disc, (CBM). And the following primary outcomes will be tested, including effective rate (ER), pulmonary function (FEV1, PEF, FEV1/FVC), adverse reactions (AR). RevMan5 software will be used for literature quality evaluation and stata14.0 software will be used for data synthesis and analysis. RESULT: To evaluate the efficacy and safety of Xiaoqinglong decoction in combination therapy by observing the outcomes of efficacy, adverse reactions and pulmonary function. CONCLUSION: This study protocol will be used to evaluate the efficacy and safety of XQLD in combination with conventional drugs in the treatment of bronchial asthma, as well as the adjuvant role of XQLD in combination. PROSPERO REGISTRATION NUMBER: CRD42019133549.

11.
Molecules ; 24(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426301

RESUMO

Two-dimensional aluminophosphate is an important precursor of phosphate-based zeolites; a new Sun Yat-sen University No. 6 (SYSU-6) with |Hada|2[Al2(HPO4)(PO4)2] has been synthesized in the hydrothermal synthesis with organic structure-directing agent (OSDA) of N,N,3,5-tetramethyladamantan-1-amine. In this paper, SYSU-6 is characterized by single-crystal/powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray analysis, transmission electron microscopy, infrared and UV Raman spectroscopy, solid-state 27Al, 31P and 13C magic angle spinning (MAS) NMR spectra, and elemental analysis. The single-crystal X-ray diffraction structure indicates that SYSU-6 crystallized in the space group P21/n, with a = 8.4119(3), b = 36.9876(12), c = 12.5674(3), α = 90°, ß = 108.6770(10)°, γ = 90°, V = 3704.3(2) Å3, Z = 4, R = 5.12%, for 8515 observed data (I > 2σ(I)). The structure has a new 4,12-ring layer framework topology linked by alternating AlO4 and PO4 tetrahedra. The organic molecules reside between the layers and are hydrogen-bonded to the inorganic framework. The new type of layer provides a greater opportunity to construct zeolite with novel topology.

12.
Int J Mol Med ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31432099

RESUMO

The primary mechanism underlying sepsis­induced cardiac dysfunction is loss of endothelial barrier function. Neuregulin­1 (NRG­1) exerts its functions on multiple targets. The present study aimed to identify the protective effects of NRG­1 in myocardial cells, including endothelial, anti­inflammatory and anti­apoptotic effects. Subsequent to lipopolysaccharide (LPS)­induced sepsis, rats were administered with either a vehicle or recombinant human NRG­1 (rhNRG­1; 10 µg/kg/day) for one or two days. H9c2 cardiomyoblasts were subjected to LPS (10 µg/ml) treatment for 12 and 24 h with or without rhNRG­1 (1 µg/ml). Survival rates were recorded at 48 h following sepsis induction. The hemodynamic method was performed to evaluate cardiac function, and myocardial morphology was observed. Von Willebrand Factor levels were detected using an immunofluorescence assay. Serum levels of tumor necrosis factor α, interleukin­6, intercellular cell adhesion molecule­1 and vascular endothelial growth factor were detected using an enzyme­linked immunosorbent assay; the reductase method was performed to detect serum nitric oxide levels. Apoptosis rates were determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Ras homolog family member A (RhoA) and Rho­associated protein kinase 1 (ROCK1) protein levels were assessed using western blotting. Transmission electron microscopy was used to observe endothelial cells and myocardial ultrastructure changes. Results revealed that NRG­1­treated rats displayed less myocardial damage compared with sham rats. NRG­1 administration strengthened the barrier function of the vasculature, reduced the secretion of endothelial­associated biomarkers and exerted anti­inflammatory and anti­apoptotic effects. In addition, NRG­1 inhibited RhoA and ROCK1 signaling. The results revealed that NRG­1 improves cardiac function, increases the survival rate of septic rats and exerts protective effects via multiple targets throughout the body. The present results contribute to the development of a novel approach to reverse damage to myocardial and endothelial cells during sepsis.

13.
Mikrochim Acta ; 186(9): 652, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31463802

RESUMO

Non-conjugated polymer carbon dots (PCDs) with a 9% fluorescence quantum yield were synthesized by a pyrolytic method using polyethyleneimine as the sole precursor. The PCDs have an average size about 2.1 nm and a blue fluorescence, with excitation/emission maxima at 380/457 nm, that is quenched by the drug metronidazole. The method has a linear response in the 0.06-15 µg mL-1 metronidazole concentration range and a 20 ng mL-1 detection limit. Milk samples were spiked at two levels (0.6 and 5.0 µg mL-1), and the recoveries of metronidazole are in the range of 96.7-102.2%. Graphical abstract Schematic representation of preparation of non-conjugated polymer carbon dots (PCDs) and detection of metronidazole. Metronidazole with negative charge is easy to produce electrostatic interaction with polyethyleneimine chain with positive charge, which leads to PCDs fluorescence quenching, so as to realize metronidazole detection.

14.
ACS Appl Mater Interfaces ; 11(35): 31735-31742, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31393101

RESUMO

Chemodynamic therapy based on Fe2+-catalyzed Fenton reaction holds great promise in cancer treatment. However, low-produced hydroxyl radicals in tumor cells constitute its severe challenges because of the fact that Fe2+ with high catalytic activity could be easily oxidized into Fe3+ with low catalytic activity, greatly lowering Fenton reaction efficacy. Here, we codeliver CuS with the iron-containing prodrug into tumor cells. In tumor cells, the overproduced esterase could cleave the phenolic ester bond in the prodrug to release Fe2+, activating Fenton reaction to produce the hydroxyl radical. Meanwhile, CuS could act as a nanocatalyst for continuously catalyzing the regeneration of high-active Fe2+ from low-active Fe3+ to produce enough hydroxyl radicals to efficiently kill tumor cells as well as a photothermal therapy agent for generating hyperthermia for thermal ablation of tumor cells upon NIR irradiation. The results have exhibited that the approach of photothermal therapy nanomaterials boosting transformation of Fe3+ into Fe2+ in tumor cells can highly improve Fenton reaction for efficient chemodynamic therapy. This strategy was demonstrated to have an excellent antitumor activity both in vitro and in vivo, which provides an innovative perspective to Fenton reaction-based chemodynamic therapy.

15.
Trials ; 20(1): 538, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464626

RESUMO

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN) is the most common secondary glomerular disease in children. Currently, the treatment for HSPN is always selected based on the Kidney Disease Improving Global Outcomes guidelines; however, this approach may lead to undertreatment, especially in patients with persistent proteinuria that does not reach nephrotic levels and/or hematuria and those with a pathological classification between grades 1 and 3 according to the International Study of Kidney Disease in Children. This study was performed to evaluate the curative effect and safety of a traditional Chinese medicine (TCM) integrated treatment program in this type of HSPN. METHODS: This multicenter, open-label, large-sample, randomized controlled trial was performed in China and included 500 children with HSPN exhibiting mild pathological patterns. The treatment group to control group ratio was 2:1, and each group was further stratified into two types, light and heavy, according to urinary protein quantification and pathological type. The treatment group received tripterygium glycosides (TGs), tanshinone IIa sodium sulfonate injection, and Chinese herbs selected based on syndrome differentiation in TCM. The heavy and light subgroups received treatment courses and dosages of TG. In the control groups, the light group received benazepril hydrochloride tablets, low molecular weight heparin calcium injection, dipyridamole tablets, and a Chinese medicine placebo, while the heavy group received the same treatment plus prednisone. All groups were treated for 3 months and then followed up for 9 months. The efficacy and safety of the treatments were then evaluated among the groups. DISCUSSION: Currently, few treatments are available for HSPN patients with mild pathological patterns indicating light to moderate proteinuria and/or hematuresis. In this large-sample study, we provide a new approach for HSPN that includes an integrated treatment program that incorporates TCM. TRIAL REGISTRATION: Clinical Trials.gov, NCT03591471 . Re-registered on 19 July 2018.

16.
Cell Death Dis ; 10(9): 635, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455760

RESUMO

Epidemiological studies show obvious gender differences in the incidence and the prognosis of bladder cancer (BCa). Estrogen receptor alpha (ERα) was recently shown to play a protective role in BCa. However, the mechanisms by which ERα mediates BCa progression need to be further elucidated. In the present study, we explored the mechanisms by which ERα inhibits BCa invasion by modulating circRNA levels. ERα suppressed BCa invasion by decreasing circ_0023642 expression. Chromatin immunoprecipitation (ChIP) and luciferase assays revealed that ERα reduced circ_0023642 expression by regulating the expression of its host gene, UVRAG, at the transcriptional level. ERα decreased circ_0023642 levels and subsequently increased miR-490-5p expression, resulting in decreased EGFR expression to suppress BCa cell invasion. Circ_0023642 was demonstrated to directly bind to miR-490-5p. Notably, miR-490-5p regulated EGFR expression by binding to the miR-490-5p-binding site located in the 3'-untranslated region (UTR) of the EGFR mRNA. Preclinical studies using an in vivo mouse model also confirmed that this ERα/circ_0023642/miR-490-5p/EGFR signaling pathway suppressed BCa progression. Altogether, this newly identified pathway may serve as the basis for developing novel therapeutic strategies to treat BCa.

17.
Sci Total Environ ; 691: 1212-1224, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31466202

RESUMO

The exponential growth of off-shore mariculture worldwide over the last 20 years has had significant impact on coastal sediment biogeochemistry. However, there are no long-term records of the cumulative impacts of mariculture on the benthic bacterial community. Here, total (DNA) and active (RNA) bacterial community compositions were characterized using MiSeq sequencing of 16S rRNA gene in four core sediments of the Ailian Bay, one of the typical intensive mariculture areas in China with more than fifty-year history of kelp and scallop cultivation. The γ-Proteobacteria, δ-Proteobacteria, Acidobacteria and Acitinobacteria were more abundant in the total bacterial communities, while ß-Proteobacteria, Anaerolineae, Clostridia, Spirochaetes and Cyanobacteria were enriched in the active bacterial communities. Significant differences were observed between total and active benthic bacterial communities. The influences of different mariculture modes on the total bacterial communities were more significant than those on the active bacterial communities. Only limited groups of the total bacterial communities were significant influenced by the cumulative effects of the long-term mariculture. The bacterial genera with the function in the sulfide cycling and organic consumption were enriched in the total bacterial population of the integrated multi-trophic aquaculture (IMTA) areas. The variations of both total and active bacterial communities were significantly influenced by grain sizes, total organic carbon and nutrients. Both total and active bacterial communities exhibited a slightly stronger response to environmental factors than to spatial (distance) factors. The effects of mutualism might dominate the total and active bacterial networks in the Ailian Bay. The present study demonstrated that the cumulative influences of the long-term and intensive IMTA mariculture on total benthic bacterial communities in the sub-surface sediments of the Ailian Bay were stronger than those on the active benthic bacterial communities, which provided some insights into the potential ecological roles of specific taxa in the sediments of the IMTA ecosystems.

18.
J Clin Pharm Ther ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31381817

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Regorafenib is a novel multi-targeted tyrosine kinase inhibitor approved for use in refractory metastatic colorectal cancer, advanced gastrointestinal stromal tumours and hepatocellular carcinoma. We report a case of bilateral sensorineural hearing loss caused by regorafenib. CASE SUMMARY: A 48-year-old woman was diagnosed with colon cancer that had metastasized to the liver, ureter and left ovary. She was initially treated with oral regorafenib at the lowest recommended dosage of 80 mg/d for 2 weeks, at which point the dose was increased to 120 mg/d. On the second day after the regorafenib dosage increase (ie, 15 days after starting regorafenib), she suddenly developed a bilateral hearing loss. Regorafenib was discontinued immediately, and the patient was treated with a course of intravenous steroids. Five weeks later, her bilateral hearing had subjective partial improvement. WHAT IS NEW AND CONCLUSION: This is the first report of bilateral sensorineural hearing loss induced by regorafenib.

19.
J Exp Clin Cancer Res ; 38(1): 333, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370861

RESUMO

BACKGROUND: Cathepsin L (CTSL) is a cysteine protease known to have important roles in regulating cancer cellular resistance to chemotherapy. However mechanism underlying which regulates CTSL-mediated drug resistance remain largely unknown. METHODS: We used NSCLC cell lines: A549, A549/TAX (paclitaxel-resistant), A549/DDP (cisplatin-resistant), H460 and PC9 cells, to evaluate CTSL and drug resistance changes. Tumor specimens from 53 patients with NSCLC and Xenograft models was also utilized to explore the regulatory relationship of CTSL, TGF-ß, Egr-1 and CREB. RESULTS: TGF-ß and smad3 were overexpressed only in A549/TAX cells, silencing TGF-ß or smad3 in A549/TAX cells decreased the expression of CTSL and enhanced their sensitivity to paclitaxel. Smad3 binds to the Smad-binding-element(SBE) of the CTSL promoter, resulting in increased activity of the CTSL promoter and subsequent CTSL. Egr-1 and CREB were overexpressed only in A549/DDP cells, and silencing Egr-1 or CREB reduced the expression of CTSL and increased cisplatin cytotoxicity. CREB could affect the activity of the CTSL promoter by binding to it. And the potential regulatory factors of CTSL were consistent in vivo and in human lung cancer. These different regulatory mechanisms of CTSL-mediated drug resistance exist in two other NSCLC cell lines. CONCLUSION: CTSL-mediated drug resistance to paclitaxel and cisplatin may be modulated by different mechanisms. The results of our study identified different mechanisms regulating CTSL-mediated drug resistance and identified smad3 as a novel regulator of CTSL.

20.
Acta Biomater ; 2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31386928

RESUMO

Adenovirus (Ad) is a promising viral carrier in gene therapy because of its unique attribution. However, clinical applications of Ad vectors are currently restricted by their immunogenicity and broad native tropism. To address these obstacles, a variety of nonimmunogenic polymers are utilized to modify Ad vectors chemically or physically. In this review, we systemically discuss the functions of polymers in Ad-mediated gene delivery from two aspects: evading the host immune responses to Ads and redirecting Ad tropism. With polyethylene glycol (PEG) first in order, a variety of polymers have been developed to shield the surface of Ad vectors and well accomplished to evade the host immune response, block CAR-dependant cellular uptake, and reduce accumulation in the liver. In addition, shielding Ad vectors with targeted polymers (including targeting ligand-conjugated polymers and bio-responsive polymers) can also efficiently retarget Ad vectors to tumor tissues and reduce their distribution in nontargeted tissues. With its potential to evade the immune response and retarget Ad vectors, modification with polymers has been generally regarded as a promising strategy to facilitate the clinical applications of Ad vectors for virotherapy. STATEMENT OF SIGNIFICANCE: There is no doubt that Adenovirus (Ads) are attractive vectors for gene therapy, with high sophistication and effectiveness in overcoming both extra- and intracellular barriers, which cannot be exceeded by any other nonviral gene vectors. Unfortunately, their clinical applications are still restricted by some critical hurdles, including immunogenicity and native broad tropism. Therefore, a variety of elegant strategies have been developed from various angles to address these hurdles. Among these various strategies, coating Ads with nonimmunogenic polymers has attracted much attention. In this review, we systemically discuss the functions of polymers in Ad-mediated gene delivery from two aspects: evading the host immune responses to Ads and redirecting Ad tropism. In addition, the key factors in Ad modification with polymers have been highlighted and summarized to provide guiding theory for the design of more effective and safer polymer-Ad hybrid gene vectors.

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