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1.
Carbohydr Polym ; 227: 115339, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590870

RESUMO

Poor buffering capacity of chitosan (CS) results in insufficient intracellular gene release which poses the major barrier in gene delivery. Herein, we reconstructed pristine CS with propylamine (PA), (diethylamino) propylamine (DEAPA), and N, N-dimethyl- dipropylenetriamine (DMAMAPA) to obtain a series of alkylamine-chitosan (AA-CS). The introduction of multiple amino groups with rational ratios functionally enhance the buffering capacity of AA-CS, among which DMAPAPA-CS showed buffering capacity of 1.58 times that of chitosan. The reconstructed AA-CS functionally enhance the ability of gene binding and endosomal escape. It was observed that the DMAPAPA-CS/pDNA complexes exhibit a notable gene delivery efficiency, which promotes the functionalization of loaded pDNA. Importantly, the in vivo delivery assay reveals that the deep penetration issue can be resolved using DMAPAPA-CS gene delivery vector. Finally, the DMAPAPA-CS is applied to deliver the therapeutic p53 gene in A549 bearing mice, showing efficient therapeutic potential for cancer.

2.
Nat Commun ; 10(1): 4593, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597916

RESUMO

Charged defects at the surface of the organic-inorganic perovskite active layer are detrimental to solar cells due to exacerbated charge carrier recombination. Here we show that charged surface defects can be benign after passivation and further exploited for reconfiguration of interfacial energy band structure. Based on the electrostatic interaction between oppositely charged ions, Lewis-acid-featured fullerene skeleton after iodide ionization (PCBB-3N-3I) not only efficiently passivates positively charged surface defects but also assembles on top of the perovskite active layer with preferred orientation. Consequently, PCBB-3N-3I with a strong molecular electric dipole forms a dipole interlayer to reconfigure interfacial energy band structure, leading to enhanced built-in potential and charge collection. As a result, inverted structure planar heterojunction perovskite solar cells exhibit the promising power conversion efficiency of 21.1% and robust ambient stability. This work opens up a new window to boost perovskite solar cells via rational exploitation of charged defects beyond passivation.

3.
Medicine (Baltimore) ; 98(41): e17453, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593101

RESUMO

RATIONALE: Intracranial hemorrhage occurs infrequently in Japanese encephalitis (JE), and even less frequently with hemorrhage occurring twice. In this report, we describe the clinical features and outcomes of a patient with confirmed JE combined with hemorrhage twice. PATIENT CONCERNS: The patient, a 71-year-old Asian woman, was admitted to the hospital with symptoms of hemiplegia following fever and diarrhea. Soon her condition worsened and a decreased level of consciousness, respiratory failure, and paralysis of extremities occurred.The brain diffusion-weighted imaging sequence showed suspicious abnormal signals in bilateral thalami. Japanese encephalitis virus immunoglobulin M antibody was detected in her serum and cerebrospinal fluid samples, so the patient was diagnosed with JE. During treatment, her condition became aggravated and the brain computed tomography (CT) scan showed multiple lobar hemorrhages. One month later, the multiple lobar hemorrhages occurred again, as observed by a brain CT scan. DIAGNOSIS: JE with multiple intracranial hemorrhages. INTERVENTIONS: The patient was treated comprehensively, including surgery, lowering her intracranial pressure and ventilator-assisted breathing. OUTCOMES: One month later, the patient underwent another surgical procedure for intracranial hemorrhage and suffered a serious neurological disorder. LESSONS: Severe intracranial hemorrhage may occur in elderly patients with JE, especially in those with poor vascular condition. Therefore, when treating such patients, great caution, as well as early detection and prevention, should be taken in case of the occurrence of severe intracranial hemorrhage.

4.
Dis Markers ; 2019: 3863458, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565098

RESUMO

Objective: Circular RNAs (circRNAs) have been reported to be widely involved in pathological processes of various cancers. However, little is known about their diagnostic values in early gastric cancer (EGC). This study is aimed at exploring whether circulating circRNAs in plasma could act as biomarkers for EGC diagnosis. Materials and Methods: Mass spectrometry (MS) was performed to identify the proteins that at significantly aberrantly levels in gastric cancer (GC) tissues. The target circRNA was identified by bioinformatics analysis. A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic utility. Results: MS revealed that the ribosomal protein L6 (RPL6) expression was significantly downregulated only in EGC tissues vs. nontumorous tissues; this was validated by western blotting (n = 30, p = 0.0094). Bioinformatics analysis predicted that there is a hsa_circ_0006848/hsa_miR-329-5p/RPL6 axis in GC progression. The hsa_circ_0006848 expression was significantly downregulated in EGC tissues (vs. nontumorous tissues, n = 30, p = 0.0073) and plasma samples from EGC patients (vs. paired healthy volunteers, n = 30, p = 0.0089). In addition, the hsa_circ_0006848 plasma level in postoperative patients was significantly higher than that of preoperative patients (n = 30, p = 0.047). Furthermore, the decreased hsa_circ_0006848 expression in plasma was negatively correlated with poor differentiation (p = 0.037) and tumor size (p = 0.046). The area under the ROC curve (AUC) of hsa_circ_0006848 in plasma was 0.733, suggesting a good diagnostic value. The plasma hsa_circ_0006848 level combined with the carcinoembryonic antigen (CEA), carbohydrate-associated antigen 19-9 (CA19-9), and carbohydrate-associated antigen 72-4 (CA72-4) level increased the AUC to 0.825. Conclusion: Our results indicated that plasma hsa_circ_0006848 may be a novel noninvasive biomarker in EGC diagnosis.

5.
Br J Cancer ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31588122

RESUMO

BACKGROUND: The progression and metastasis of pancreatic ductal adenocarcinoma (PDAC) is highly dependent on the tumour microenvironment. Most tumour-associated macrophages (TAMs) are M2 phenotype macrophages, which normally show anti-inflammatory functions in numerous disorders. Previously, we found that alternatively activated macrophages showed pro-inflammatory characteristics upon stimulation with hepatoma cell-derived debris; however, the molecular mechanism was unclear. METHODS: In vitro and in vivo experiments were employed to investigate the molecular mechanism. Using pancreatic cancer cell lines, mouse models and human tissues, we obtained a general picture of tumour cell-derived debris promoting metastasis of pancreatic cancer by inducing inflammation via TAMs. RESULTS: We showed that M2 macrophage-derived inflammation also exists in PDAC. Debris from PDAC cells induced potent IL-1ß release by M2 macrophages via TLR4/TRIF/NF-κB signalling, and this effect was further boosted by IgG that was also derived from PDAC cells. Increased IL-1ß promoted epithelial-mesenchymal transition and consequent metastasis of PDAC cells. A selective COX-2 inhibitor, celecoxib, enhanced the anti-tumoural efficacy of gemcitabine. CONCLUSIONS: These data revealed a pro-inflammatory mechanism in PDAC, which indicated that IL-1ß and COX-2 could be therapeutic targets of an anti-inflammatory strategy to treat PDAC.

6.
Theranostics ; 9(22): 6424-6442, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588227

RESUMO

Atherosclerosis is the main pathological basis of ischemic cardiovascular and cerebrovascular diseases and has attracted more attention in recent years. Multiple studies have demonstrated that the signal transducer and activator of transcription 3 (STAT3) plays essential roles in the process of atherosclerosis. Moreover, aberrant STAT3 activation has been shown to contribute to the occurrence and development of atherosclerosis. Therefore, the study of STAT3 inhibitors has gradually become a focal research topic. In this review, we describe the crucial roles of STAT3 in endothelial cell dysfunction, macrophage polarization, inflammation, and immunity during atherosclerosis. STAT3 in mitochondria is mentioned as well. Then, we present a summary and classification of STAT3 inhibitors, which could offer potential treatment strategies for atherosclerosis. Furthermore, we enumerate some of the problems that have interfered with the development of mature therapies utilizing STAT3 inhibitors to treat atherosclerosis. Finally, we propose ideas that may help to solve these problems to some extent. Collectively, this review may be useful for developing future STAT3 inhibitor therapies for atherosclerosis.

7.
World J Gastroenterol ; 25(36): 5515-5529, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31576097

RESUMO

BACKGROUND: Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM: To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS: Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS: Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, a P < 0.001 and r = 0.270, b P < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively; P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION: The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.

8.
Medicine (Baltimore) ; 98(40): e17460, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577775

RESUMO

BACKGROUND: This study aimed to perform a network meta-analysis to evaluate the therapeutic effect and safety of various modalities in treating advanced hepatocellular carcinoma (HCC). Typically, the modalities of interest were comprised of sorafenib, transarterial chemoembolization (TACE), sorafenib combined with TACE, TACE combined with traditional Chinese medicine (TCM), and sorafenib combined with hepatic arterial infusion chemotherapy (HAIC). METHODS: Potentially eligible studies were systemically retrieved from the electronic databases (including PubMed and Cochrane Library) up to September 2018. The overall survival (OS) associated with the 5 modalities of interest enrolled in this study was compared by means of network meta-analysis. Meanwhile, major adverse events (AEs) were also evaluated. RESULTS: The current network meta-analysis enrolled 7 published randomized controlled trials (RCTs), and the pooled results indicated that the TACE-TCM regimen displayed the highest efficacy in treating advanced HCC, followed by HAIC-sorafenib. By contrast, the TACE alone and sorafenib alone regimens had the least efficacy. Relative to other regimens of interest, the TACE-TCM regimen was associated with less incidence of treatment-associated AEs. CONCLUSION: The TACE-TCM regimen was associated with higher treatment responses in advanced HCC patients than those of the other regimens of interest.

9.
Wei Sheng Yan Jiu ; 48(4): 583-593, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31601339

RESUMO

OBJECTIVE: To understand the differences in the types and levels of antibiotic resistance genes contamination in the dust of air conditioning filters in hospital inpatient wards. METHODS: Wet cotton swabs were used to collect dust samples from air conditioning filters in 19 wards of 7 departments of a third-grade general hospital in Wuhan. The 24 antibiotic resistance genes related to 6 major antibiotics were qualitatively detected by PCR, and 6 typical resistance genes were detected by real-time PCR. RESULTS: Sulfonamides(sulI, sulII), ß-lactams(mecA, blaOXA-51, blaTEM, blaCTX-M, blaSHV, blaKPC, blaNDM-1, blaIMP, blaVIM), aminoglycosides(aac(6᾿-aph(2᾿, aacC2), macrolides(ermA, ermC, ereA), quinolones(qnrA, qnrB, qnrS), a total of five categories of 19 antibiotic resistance genes were detected in the dust of the filter. These include four carbapenem resistance genes(blaNDM-1, blaIMP, blaVIM, blaKPC). The average of absolute content(copies/g) of the six typical resistance genes from high to low was: sulI(1. 06×10~9)>sulII(1. 78×10~8)>blaNDM-1(3. 97×10~7)>aac(6᾿-aph(2᾿(3. 20×10~7)>blaTEM(1. 03×10~7)>aacC2(1. 13×10~6). Among the seven tested departments, traumatic surgery detected up to 18 resistant gene species and 6 typical genes with the highest absolute content. The absolute content of six typical genes in ICU and surgical wards was higher than medical wards. CONCLUSION: A variety of antibiotic resistance genes are detected in the dust of some hospital ward air conditioning filters, suggesting that there may be current or past pollution of resistant bacteria in the relevant environment.

10.
World J Gastroenterol ; 25(37): 5641-5654, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31602164

RESUMO

BACKGROUND: Robotic surgery has been considered to be significantly better than laparoscopic surgery for complicated procedures. AIM: To explore the short-term effect of robotic and laparoscopic spleen-preserving splenic hilar lymphadenectomy (SPSHL) for advanced gastric cancer (GC) by Huang's three-step maneuver. METHODS: A total of 643 patients who underwent SPSHL were recruited from April 2012 to July 2017, including 35 patients who underwent robotic SPSHL (RSPSHL) and 608 who underwent laparoscopic SPSHL (LSPSHL). One-to-four propensity score matching was used to analyze the differences in clinical data between patients who underwent robotic SPSHL and those who underwent laparoscopic SPSHL. RESULTS: In all, 175 patients were matched, including 35 patients who underwent RSPSHL and 140 who underwent LSPSHL. After matching, there were no significant differences detected in the baseline characteristics between the two groups. Significant differences in total operative time, estimated blood loss (EBL), splenic hilar blood loss (SHBL), splenic hilar dissection time (SHDT), and splenic trunk dissection time were evident between these groups (P < 0.05). Furthermore, no significant differences were observed between the two groups in the overall noncompliance rate of lymph node (LN) dissection (62.9% vs 60%, P = 0.757), number of retrieved No. 10 LNs (3.1 ± 1.4 vs 3.3 ± 2.5, P = 0.650), total number of examined LNs (37.8 ± 13.1 vs 40.6 ± 13.6, P = 0.274), and postoperative complications (14.3% vs 17.9%, P = 0.616). A stratified analysis that divided the patients receiving RSPSHL into an early group (EG) and a late group (LG) revealed that the LG experienced obvious improvements in SHDT and length of stay compared with the EG (P < 0.05). Logistic regression showed that robotic surgery was a significantly protective factor against both SHBL and SHDT (P < 0.05). CONCLUSION: RSPSHL is safe and feasible, especially after overcoming the early learning curve, as this procedure results in a radical curative effect equivalent to that of LSPSHL.

11.
Curr Eye Res ; : 1-9, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31595798

RESUMO

Objective: To investigate changes in retinal capillary density (RCD) that occur in Graves' ophthalmopathy (GO) and explore their association with the clinical manifestations for GO. Material and Methods: A total of 125 participants (93 GO patients and 32 normal subjects) were enrolled. All participants underwent ophthalmology and endocrinology examinations. Retinal microvasculature was imaged by spectral domain optical coherence tomographic angiography (OCT-A). The RCDs in the superficial and deep retinal capillary plexuses (SRCP and DRCP) were quantified by the custom software from the OCT-A images, which were divided into total annular zones (TAZ) and four quadrants. Multiple linear regression analysis was used to explore the associations between RCD and the relevant factors. Results: Significant reduction was seen in the TAZ zone in SRCP and DRCP of GO group (P < .05) when compared to the healthy subjects; significant differences remained after adjustment of vascular relevant factors. According to the univariate analysis, the relevant factors of higher IOP, larger proptosis, higher clinical activity scoring (CAS), thyroid stimulating hormone-receptor autoantibodies (TRAb), and 131I therapy were significantly associated with decreased RCDs in GO patients (P < .05). Multivariate linear regression analysis showed that CAS and TRAb were the most important relevant factors for decreased RCDs. Conclusions: The RCD of GO patients was significantly decreased compared to the healthy controls. The activity status and serum antibodies associated with GO were the relevant factors for reduced RCD.

12.
J Hepatol ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31568800

RESUMO

BACKGROUND AND AIMS: Clinical evidence has indicated a close relationship between non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD). However, the underlying mechanism remains to be elucidated. This study aimed to explore a potential role of hepatocyte-derived extracellular vesicles (EVs) in endothelial inflammation and atherogenesis under NAFLD status. METHODS AND RESULTS: By using an endothelial cell-specific PCR array, we identified that hepatocyte-derived EVs from the fatty liver are a potent inducer of endothelial inflammation. Through profiling and functional analysis of the global microRNA in the EVs, we found that microRNA-1 (miR-1) is a key EV cargo that mediates the pro-inflammatory effect of EVs by down-regulation of KLF4 and activation of the NF-κB pathway in endothelial cells. Moreover, not only did the inhibition of miR-1 reduce endothelial inflammation in vitro but also attenuated atherogenesis in ApoE-deficient mice. CONCLUSION: Steatotic hepatocyte-derived EVs promote endothelial inflammation and facilitate atherogenesis by miR-1 delivery, KLF4 suppression and the NF-κB pathway activation. The findings illustrate an important role for hepatocyte-derived EVs in distant communications between the liver and vasculature, suggesting a new mechanism underlying the link between NAFLD and CVD. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD), a condition highly prevalent in obese or diabetic patients, is emerging at a high risk for the development of cardiovascular diseases (CVD). In the current study, we identified a kind of toxic particles, namely extracellular vesicles, released by hepatocytes under NAFLD conditions, which causes vascular endothelial inflammation and promotes atherosclerosis. Furthermore, we identified a small molecular cargo in the toxic particles, which is a potent inducer of endothelial inflammation. By inhibiting this cargo function, a specific gene-based inhibitor profoundly attenuated atherogenesis in mice. Thus, our study uncovers a novel mechanism for distant communications between the liver and blood vessels and suggests a new way to prevention and treatment of CVD, especially for NAFLD patients.

14.
J Am Chem Soc ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573191

RESUMO

Cell adhesive and other functional peptides (such as RGD, KRSR, YIGSR, VAPG, and BMP-2 peptides) are extensively studied and utilized in tissue engineering scaffolds and biomedical devices to modulate cell functions. Though PEG is frequently used as the antifouling layer, it is unclear how it affects the performance of functional peptides. By analyzing the impact of PEG at short (OEG4), medium (OEG8), and long chain length (PEG2K), we reveal that PEG chain length is critical and a medium-length PEG enables functional peptides to display their optimal and genuine functions in cell adhesion, migration, and differentiation by providing excellent antifouling to minimize background noise of unwanted cell adhesion and high enough surface density of functional peptides. Our result provides new avenues for maximizing the genuine functions of peptides. This study also provides a solution to prevent the heterogeneous and even divergent results caused by inappropriate choice of antifouling PEG and provides a general guidance in identifying new functional peptides.

15.
Pharmacol Res ; : 104440, 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31479750

RESUMO

Targeting on the IKKß to discover anti-inflammatory drugs has been launched for ten years, due to its predominant role in canonical NF-κB signaling. In the current study, we identified a novel IKKß inhibitor, ellipticine (ELL), an alkaloid isolated from Ochrosia elliptica and Rauvolfia sandwicensis. We found that ELL reduced the secretion and mRNA expression of TNF-α and IL-6 and decreased the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in bone marrow derived macrophages (BMDMs) stimulated with LPS. In coincided with the results, ELL suppressed PGE2 and NO production in BMDMs. Underlying mechanistic study showed that ELL inhibited IκBα phosphorylation and degradation as well as NF-κB nuclear translocation, which was attributed to suppression of IKKα/ß activation. Furthermore, kinase assay and binding assay results indicated that ELL inhibited IKKß activity via directly binding to IKKß and in turn resulted in suppression of NF-κB signaling. To identify the binding sites of ELL on IKKß, IKKßC46A plasmid was prepared and the kinase assay was performed. The results demonstrated that the inhibitory effect of ELL on IKKß activity was impaired in the mutation, implying that anti-inflammatory effect of ELL was partially attributed to binding on cysteine 46. Furthermore, ELL up-regulated LC3 II expression and reduced p62 expression, suggesting that autophagy induction contributed to the anti-inflammatory effect of ELL as well. In coincided with the in vitro results, ELL increased the survival and antagonized the hypothermia in the mice with LPS-induced septic shock. Consistently, ELL reduced TNF-α and IL-6 production in the serum of the mice treated with LPS. Collectively, our study provides evidence that ELL is an IKKß inhibitor and has potential to be developed as a lead compound for treatment inflammatory diseases in the future.

17.
Environ Int ; 132: 105119, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31491607

RESUMO

Bike-sharing as a common public transportation has been booming in China in recent years. Previous studies showed that the surfaces of public transport can act as reservoirs of antimicrobial-resistant (AR) bacteria, but AR bacterial contamination of shared bikes has not been investigated. Otherwise, the AR-Enterobacteriaceae is considered as a global health threat for humans. Herein, we aimed to investigate the prevalence of AR Enterobacteriaceae on shared bikes and examine correlations between AR Enterobacteriaceae from shared bikes and public buildings around Metro stations in Beijing. We collected 2117 samples from shared bikes at 240 Metro stations in Beijing. A total of 444 non-duplicate Enterobacteriaceae were isolated from 418 samples at 166 stations. The isolates exhibited low rates of resistance (0.5%-6.3%) to all antimicrobial agents except sulfamethoxazole-trimethoprim (31.5%). Three ceftazidime-resistant E. coli isolates were positive for blaCTX-M-199 and two of them were positive for carbapenemase-producing gene blaNDM-5. Multivariable logistic regression model revealed that variable "secondary/tertiary non-profit hospital nearby" was significantly (p < 0.05) associated with isolation of AR Enterobacteriaceae from the shared bikes around the Metro stations. Low AR rates of Enterobacteriaceae observed in this study suggested the risk of dissemination of AR-Enterobacteriaceae via shared bikes is limited. However, we identified hospitals as a risk factor for the dissemination of AR Enterobacteriaceae among shared bike users. More attention should be paid to both comprehensive hygiene managements in the surrounding environment of hospitals and the increasing of public awareness on the personal hygienic habits.

18.
Sci Rep ; 9(1): 13727, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551429

RESUMO

An object's location can be represented either relative to an observer's body effectors (egocentric reference frame) or relative to another external object (allocentric reference frame). In non-spatial tasks, an object's task-irrelevant egocentric position conflicts with the side of a task-relevant manual response, which defines the classical Simon effect. Growing evidence suggests that the Simon effect occurs not only based on conflicting positions within the egocentric but also within the allocentric reference frame. Although neural mechanisms underlying the egocentric Simon effect have been extensively researched, neural mechanisms underlying the allocentric Simon effect and their potential interaction with those underlying its egocentric variant remain to be explored. In this fMRI study, spatial congruency between the task-irrelevant egocentric and allocentric target positions and the task-relevant response hand was orthogonally manipulated. Behaviorally, a significant Simon effect was observed for both reference frames. Neurally, three sub-regions in the frontoparietal network were involved in different aspects of the Simon effect, depending on the source of the task-irrelevant object locations. The right precentral gyrus, extending to the right SMA, was generally activated by Simon conflicts, irrespective of the spatial reference frame involved, and showed no additive activity to Simon conflicts. In contrast, the right postcentral gyrus was specifically involved in Simon conflicts induced by task-irrelevant allocentric, rather than egocentric, representations. Furthermore, a right lateral frontoparietal network showed increased neural activity whenever the egocentric and allocentric target locations were incongruent, indicating its functional role as a mismatch detector that monitors the discrepancy concerning allocentric and egocentric object locations.

19.
Curr Mol Med ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533600

RESUMO

PURPOSE: Retinal ganglion cells (RGCs) apoptosis is a common characteristic of optic neuropathies. p53-induced protein with a death domain (PIDD) is a well-known regulator of genotoxic stress-induced apoptosis, which is constitutively cleaved into three main fragments: PIDD-N, PIDD-C and PIDD-CC. Thus, we aim to determine the physiological relevance of PIDD in RGCs apoptosis in an optic nerve crush (ONC) model. METHODS: All animals were evenly randomized into four groups: sham-control group, con-siRNA group, ONC group, and PIDD-siRNA group (ONC + PIDD-siRNA). Expressions of PIDD, caspase-2, Brn3a and tBid in ONC model were analyzed by Western blot and immunofluorescence. Mean densities of RGCs/mm2 were calculated with Fluoro-Gold (FG). Moreover, we tested the effect of PIDD-siRNA on ONC-induced RGCs apoptosis using TUNEL staining. RESULTS: The level of full-length PIDD was weakly present and showed no significant differences at any time points. PIDD-CC and PIDD-C were significantly up-regulated in the retina at 3 days after ONC. Meanwhile, the expression of PIDD was significantly increased in Brn3a (a marker of RGCs) positive cells, indicating that the localization of PIDD appeared to be confined to RGCs. Furthermore, inhibition of PIDD prevented RGCs apoptosis by inhibiting caspase-2 and tBid activation. CONCLUSIONS: Taken together, PIDD may play a crucial role in RGCs apoptosis after ONC, and this process may be relevant to caspase-2 and tBid.

20.
World J Gastroenterol ; 25(35): 5266-5282, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31558872

RESUMO

BACKGROUND: Hepatitis B virus (HBV) has been recognized as a leading cause of hepatocellular carcinoma (HCC). Numerous reports suggest that immune infiltration can predict the prognosis of HCC. Nonetheless, no creditable markers for prognosis of HBV-related HCC have been established by systematically assessing the immune-related markers based on tumor transcriptomes. AIM: To establish an immune-related marker based on the cell compositions of immune infiltrate obtained based on tumor transcriptomes, so as to enhance the prediction accuracy of HBV-related HCC prognosis. METHODS: RNA expression patterns as well as the relevant clinical data of HCC patients were obtained from The Cancer Genome Atlas. Twenty-two immunocyte fraction types were estimated by cell type identification by estimating relative subsets of RNA transcripts. Subsequently, the least absolute shrinkage and selection operator (LASSO) Cox regression model was employed to construct an immunoscore based on the immunocyte fraction types. Afterwards, the receiver operating characteristic (ROC) curve, Kaplan-Meier, and multivariate Cox analyses were performed. Additionally, a nomogram for prognosis that integrated the immunoscore as well as the clinical features was established. Meanwhile, the correlation of immunoscore with immune genes was also detected, and gene set enrichment analysis (GSEA) of the immunoscore was conducted. RESULTS: A total of 22 immunocyte fraction types were predicted and compared among the tumor as well as non-tumor samples. An immunoscore was constructed through adopting the LASSO model, which contained eight immunocyte fraction types. Meanwhile, the areas under the ROC curves for the immunoscore biomarker prognostic model were 0.971, 0.912, and 0.975 for 1-, 3-, and 5-year overall survival (OS), respectively. Difference in OS between the high-immunoscore group and the low-immunoscore group was statistically significant [hazard ratio (HR) = 66.007, 95% confidence interval (CI): 8.361-521.105; P < 0.0001]. Moreover, multivariable analysis showed that the immunoscore was an independent factor for predicting the prognosis (HR = 2.997, 95%CI: 1.737-5.170). A nomogram was established, and the C-index was 0.757 (95%CI: 0.648-0.866). The immunoscore showed a significant negative correlation with the expression of PD-1 (P = 0.024), PD-L1 (P = 0.026), PD-L2 (P = 0.029), and CD27 (P = 0.033). Eight pathways were confirmed by GSEA. CONCLUSION: The established immunoscore can potentially serve as a candidate marker to estimate the OS for HBV-related HCC cases.

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