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1.
Eye (Lond) ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001821

RESUMO

Anti-vascular endothelial growth factors (anti-VEGF) have become the most common treatment modality for many retinal diseases. These include neovascular age-related macular degeneration (n-AMD), proliferative diabetic retinopathy (PDR) and retinal vein occlusions (RVO). However, these drugs are administered via intravitreal injections that are associated with sight-threatening complications. The most feared of these complications is endophthalmitis, a severe infection of the eye with extremely poor visual outcomes. Patients with retinal diseases typically have to undergo multiple injections before achieving the desired therapeutic effect. Each injection incurs the risk of the sight-threatening complications. As such, there has been great interest in developing sustained delivery platforms for anti-VEGF agents to the posterior segment of the eye. In recent years, there have been various strategies that have been conceptualised. These include non-biodegradable implants, nano-formulations and hydrogels. In this review, the barriers of drug delivery to the posterior segment of the eye will be explained. The characteristics of an ideal sustained delivery platform will then be discussed. Finally, the current available strategies will be analysed with the above-mentioned characteristics in mind to determine the advantages and disadvantages of each sustained drug delivery modality. Through the above, this review attempts to provide an overview of the sustained delivery platforms in their various phases of development.

2.
Dev Comp Immunol ; 106: 103635, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32014470

RESUMO

Thioredoxin-like protein 5 (Trxlp-5) is a thioredoxin isoform associated with cellular redox homeostasis through the activity of thiol-disulfide reductase. In our study, Trxlp-5 was identified and characterized in Pinctada fucata martensii. The expression of PmTrxlp-5 was detected in response to polyinosinic: polycytidylic acid (poly I:C) and lipopolysaccharides (LPS) stimulation. The differences in PmTrxlp-5 expression were evaluated between the black coloured selected line and the control stock after grafting operation. The open reading frame (ORF) consisted of 1167bp encoding a 388 amino acid, 5'-UTR of 41bp and a 3'-UTR of 846bp. PmTrxlp-5 exhibited a conserved WCXXC functional motif similar to thioredoxins from other species. Tissue analysis showcased the highest relative mRNA expressions of PmTrxlp-5 in the haemocytes. Interestingly, after the grafting operation, mRNA expression of PmTrxlp-5 in the haemocytes was differentially expressed post grafting with a peak 6 h after grafting suggesting the high involvement of the gene in immune response in the early stage after grafting. The black coloured selected line group (BS) had significantly higher expression than the control group (CG) at 24 h, 6 d and 30 d after grafting operation. PmTrxlp-5 also showed a wave-like pattern in mRNA expression after bacterial endotoxin LPS and viral mimic poly I:C. These results suggested that PmTrxlp-5 plays a vital function in cellular redox homeostasis and immune response against grafting operation and pathogenic infections and can be used as a gene marker for selective breeding programs.

3.
Chin Med J (Engl) ; 133(1): 1-8, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31923098

RESUMO

BACKGROUND: The Chinese appropriate use criteria (AUC) for coronary revascularization was released in 2016 to improve the use of coronary revascularization. This study aimed to evaluate the association between the appropriateness of coronary revascularization based on the Chinese AUC and 1-year outcomes in stable coronary artery disease (CAD) patients. METHODS: We conducted a prospective, multi-center cohort study of stable CAD patients with coronary lesion stenosis ≥50%. After the classification of appropriateness based on Chinese AUC, patients were categorized into the coronary revascularization group or the medical therapy group based on treatment received. The primary outcome was a composite of death, myocardial infarction, stroke, repeated revascularization, and ischemic symptoms with hospital admission. RESULTS: From August 2016 to August 2017, 6085 patients were consecutively enrolled. Coronary revascularization was associated with a lower adjusted hazard of 1-year major adverse cardiovascular and cerebrovascular events (MACCEs; hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.45-0.86; P = 0.004) than medical therapy in patients with appropriate indications (n = 1617). No significant benefit in 1-year MACCEs was found after revascularization compared to after medical therapy in patients with uncertain indications (n = 2658, HR: 0.81; 95% CI: 0.52-1.25; P = 0.338) and inappropriate indications (n = 1810, HR: 0.80; 95% CI: 0.51-1.23; P = 0.308). CONCLUSIONS: In patients with appropriate indications according to Chinese AUC, coronary revascularization was associated with significantly lower risk of MACCEs at 1 year. No benefit was found in coronary revascularization in patients with inappropriate indications. Our findings provide evidence for using Chinese AUC to guide clinical decision-making. CLINICAL TRIAL REGISTRATION: NCT02880605. https://www.clinicaltrials.gov.

4.
Korean J Radiol ; 21(2): 210-217, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31997596

RESUMO

OBJECTIVE: We sought to distinguish lipid plaques using a CT quantitative pixel density histogram, based on the pathological diagnosis of lipid cores as the gold standard. MATERIALS AND METHODS: Eight patients awaiting heart transplantation due to end-stage coronary heart disease underwent coronary CT angiography (CCTA) spectroscopy prior to heart transplantation; coronary artery pathological analysis was performed for all patients. Lipid-core plaques were defined pathologically as manifesting a lipid core diameter > 200 µm, a circumference > 60 degrees, and a cap thickness < 450 µm. The percentage distributions of CT pixel attenuation ≤ 20, 30, 40, and 50 HU were calculated using quantitative histogram analysis. RESULTS: A total of 271 transverse sections were co-registered between CCTA and pathological analysis. Overall, 26 lipid cores and 16 fibrous plaques were identified by pathological analysis. There was no significant difference in median CT attenuation between the lipid and fibrous plaques (51 HU [interquartile range, 46-63] vs. 57 HU [interquartile range, 50-64], p = 0.659). The median percentage of CT pixel attenuation ≤ 30 HU accounted for 11% (5-17) of lipid-core plaques and 0% (0-2) of fibrous plaques (p < 0.001). The sensitivity and specificity of the method for diagnosing lipid plaques by the average CT pixel attenuation ≤ 30 HU were 80.8% and 87.5%, respectively. The area under the receiver operator characteristics curve was 0.898 (95% confidence interval: 0.765-0.970; 3.0% was the best cut-off value). The diagnostic performance was significantly higher than those of the average pixel CT attenuation percentages ≤ 20, 40, and 50 HU and the mean CT attenuation (p < 0.05). CONCLUSION: In in vivo conditions, with the pathological lipid core as the gold standard, quantification of the percentage of average CT pixel attenuation ≤ 30 HU in the histogram can be useful for accurate identification of lipid plaques.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31733296

RESUMO

Chitin participates in shell formation as the main component of an organic framework. Chitin-binding protein contains domains that can bind to chitin specifically. In this study, a novel chitin-binding protein from Pinctada fucata martensii (PmCBP) with poly (chitin-binding domain) was cloned, which contains a 5'-untranslated region (UTR) of 114 bp and 3'UTR of 116 bp, and encodes a putative protein of 2044 amino acids. The predicted PmCBP protein was structurally typical of the CBP family with 20 ChtBD2 domains. Phylogenetic and linear relation analyses showed that the ChtBD2 domain has a highly conserved structure among the three species of P. f. martensii, Crassostrea gigas, and Mizuhopecten yessoensis. qRT-PCR and in-situ hybridization analysis revealed that PmCBP was most abundant in the mantle pallium whose expression level was significantly correlated with the growth traits. After RNAi, PmCBP expression was significantly inhibited in the mantle pallium (P < 0.05) and the microstructure of nacreous layers showed a disordered growth in the experiment group. These results indicated that PmCBP may be involved in nacreous layer formation through participation in the process of binding chitin in pearl oyster P. f. martensii.

6.
Fish Shellfish Immunol ; 96: 330-335, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31830566

RESUMO

Long noncoding RNA (LncRNA) regulates various life processes, including biomineralization and innate immune response through complex mechanisms. In this research, we identified a LncRNA named LncMSEN1 from pearl oyster Pinctada fucata martensii. LncMSEN1 sequence was validated by PCR, and its expression was high in mantle tissues according to qRT-PCR. LncMSEN1 was co-located with the nacre matrix protein N-U8 and fibrinogen domain-containing protein. And LncMSEN1 and N-U8 expression levels in the mantle were positively correlated. RNA interference was used to detect its effect on nacre formation in shells. Results showed that the decreased LncMSEN1 expression in mantle can cause the disordered growth of crystals on the inner surface of nacre in the shells, as well as the decrease expression of N-U8. In addition, the LncMSEN1 expression level significantly increased at 24 h after polyI:C stimulation in the mantle (P < 0.05). These findings suggested the involvement of LncMSEN1 in the formation of nacre in shells and related to innate immune response in pearl oyster, which provided additional insights into the roles of LncRNAs in pearl oysters.

7.
Bioorg Med Chem ; 28(4): 115243, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31879183

RESUMO

Glyoxalase I (GLO1) is a homodimeric Zn2+-metalloenzyme that catalyses the transformation of methylglyoxal (MG) to d-lacate through the intermediate S-d-lactoylglutathione. Growing evidence indicates that GLO1 has been identified as a potential target for the treatment cancer and other diseases. Various inhibitors of GLO1 have been discovered or developed over the past several decades including natural or natural product-based inhibitors, GSH-based inhibitors, non-GSH-based inhibitors, etc. The aim of this review is to summarize recent achievements of concerning discovery, design strategies, as well as pharmacological aspects of GLO1 inhibitors with the target of promoting their development toward clinical application.

8.
BMC Genomics ; 20(1): 937, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805848

RESUMO

BACKGROUND: Nicotinic acetylcholine receptors (nAChRs) are among the oldest and most conserved transmembrane receptors involved in signal transduction. Despite the prevalence and significance of cholinergic signaling, the diversity and evolution of nAChRs are not fully understood. RESULT: By comparative genomic analysis, we found massive expansions of nAChR genes in molluscs and some other lophotrochozoans. The expansion is particularly pronounced in stationary bivalve molluscs with simple nervous systems, with the number of nAChR genes ranging from 99 to 217 in five bivalves, compared with 10 to 29 in five ecdysozoans and vertebrates. The expanded molluscan nAChR genes tend to be intronless and in tandem arrays due to retroposition followed by tandem duplication. Phylogenetic analysis revealed diverse nAChR families in the common ancestor of bilaterians, which subsequently experienced lineage-specific expansions or contractions. The expanded molluscan nAChR genes are highly diverse in sequence, domain structure, temporal and spatial expression profiles, implying diversified functions. Some molluscan nAChR genes are expressed in early development before the development of the nervous system, while others are involved in immune and stress responses. CONCLUSION: The massive expansion and diversification of nAChR genes in bivalve molluscs may be a compensation for reduced nervous systems as part of adaptation to stationary life under dynamic environments, while in vertebrates a subset of specialized nAChRs are retained to work with advanced nervous systems. The unprecedented diversity identified in molluscs broadens our view on the evolution and function of nAChRs that are critical to animal physiology and human health.

9.
PLoS One ; 14(12): e0226367, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31830109

RESUMO

Mollusk shell matrix proteins are important for the formation of organic frameworks, crystal nucleation, and crystal growth in Pinctada fucata martensii (P. f. martensii). MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play important roles in many biological processes, including shell formation. In this study, we obtained the full-length sequence of Pif97-like gene in P. f. martensii (PfmPif97-like). PfmPif97-like was mainly distributed in mantle pallial and mantle edge. Correlation analysis indicated that the average shell thickness and weight showed a positive correlation with PfmPif97-like expression (P < 0.05). The inner surface of the nacreous layer and prismatic layer showed atypical growth when we knocked down the expression of PfmPif97-like by RNA interference (RNAi). We used a luciferase reporter assay to identify that miR-9b-5p of P. f. martensii (Pfm-miR-9b-5p) downregulated the expression of PfmPif97-like by interacting with the 3'-untranslated region (UTR) while we obtained the same result by injecting the Pfm-miR-9b-5p mimics in vivo. After injecting the mimics, we also observed abnormal growth in nacre layer and prismatic layer which is consistent with the result of RNAi. We proposed that PfmPif97-like regulated by Pfm-miR-9b-5p participates in shell formation of P. f. martensii. These findings provide important clues about the molecular mechanisms that regulate biomineralization in P. f. martensii.

10.
Nat Commun ; 10(1): 5762, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848349

RESUMO

Perfluorinated alkyl substances, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are toxic materials that are known to globally contaminate water, air, and soil resources. Strategies for the simultaneous detection and removal of these compounds are desired to address this emerging health and environmental issue. Herein, we develop a type of guanidinocalix[5]arene that can selectively and strongly bind to PFOS and PFOA, which we use to demonstrate the sensitive and quantitative detection of these compounds in contaminated water through a fluorescent indicator displacement assay. Moreover, by co-assembling iron oxide nanoparticle with the amphiphilic guanidinocalix[5]arene, we are able to use simple magnetic absorption and filtration to efficiently remove PFOS and PFOA from contaminated water. This supramolecular approach that uses both molecular recognition and self-assembly of macrocyclic amphiphiles is promising for the detection and remediation of water pollution.

11.
Chin Med J (Engl) ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31855972

RESUMO

BACKGROUND: The Chinese appropriate use criteria (AUC) for coronary revascularization was released in 2016 to improve the use of coronary revascularization. This study aimed to evaluate the association between the appropriateness of coronary revascularization based on the Chinese AUC and 1-year outcomes in stable coronary artery disease (CAD) patients. METHODS: We conducted a prospective, multi-center cohort study of stable CAD patients with coronary lesion stenosis ≥50%. After the classification of appropriateness based on Chinese AUC, patients were categorized into the coronary revascularization group or the medical therapy group based on treatment received. The primary outcome was a composite of death, myocardial infarction, stroke, repeated revascularization, and ischemic symptoms with hospital admission. RESULTS: From August 2016 to August 2017, 6085 patients were consecutively enrolled. Coronary revascularization was associated with a lower adjusted hazard of 1-year major adverse cardiovascular and cerebrovascular events (MACCEs; hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.45-0.86; P = 0.004) than medical therapy in patients with appropriate indications (n = 1617). No significant benefit in 1-year MACCEs was found after revascularization compared to after medical therapy in patients with uncertain indications (n = 2658, HR: 0.81; 95% CI: 0.52-1.25; P = 0.338) and inappropriate indications (n = 1810, HR: 0.80; 95% CI: 0.51-1.23; P = 0.308). CONCLUSIONS: In patients with appropriate indications according to Chinese AUC, coronary revascularization was associated with significantly lower risk of MACCEs at 1 year. No benefit was found in coronary revascularization in patients with inappropriate indications. Our findings provide evidence for using Chinese AUC to guide clinical decision-making. CLINICAL TRIAL REGISTRATION: NCT02880605. https://www.clinicaltrials.gov.

12.
BMJ Open ; 9(11): e032642, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31772102

RESUMO

INTRODUCTION: An initial retrospective study suggested that tranexamic acid (TXA) administration increased the incidence of seizures in paediatric patients undergoing cardiac surgery. However, the efficacy of TXA in paediatric cardiac surgery remains unclear owing to the small sample sizes of the studies. Therefore, this study will investigate the efficacy and safety of TXA in paediatric patients undergoing cardiac surgery. We hypothesised that TXA may increase the incidence of postoperative seizures with no effect on postoperative allogeneic transfusion in paediatric patients undergoing cardiac surgery. The pragmatic study will provide important implications for paediatric cardiac surgery. METHODS AND ANALYSIS: This will be a single-centre prospective, double-blind randomised controlled trial. The plan is to enrol in the study 2090 paediatric patients aged 31 days to 7 years who will be undergoing cardiac surgery with cardiopulmonary bypass (CPB). All eligible participants will be randomly assigned to either the TXA or placebo group by using a Web-based randomisation service in a 1:1 ratio. The primary safety end point will be postoperative seizures until hospital discharge, and the primary efficacy end point will be the volume of allogeneic red blood cell transfusion after termination of CPB. All patients will be followed up for 1 year postdischarge. All data will be analysed in accordance with the intention-to-treat principle. ETHICS AND DISSEMINATION: This study was approved by the institutional review board of Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (No 20191195). Written informed consent will be obtained from the parents/legal guardian of each patient because all participants will be <18 years of age. The results of the trial will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Register (ChiCTR1900024131).

13.
Target Oncol ; 14(6): 719-728, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31691892

RESUMO

BACKGROUND: Droplet digital polymerase chain reaction (ddPCR) is an emerging technology for quantitative cell-free DNA oncology applications. However, a ddPCR assay for the epidermal growth factor receptor (EGFR) p.Thr790Met (T790M) mutation suitable for clinical use remains to be established with analytical and clinical validations. OBJECTIVE: We aimed to develop and validate a new ddPCR assay to quantify the T790M mutation in plasma for monitoring and predicting the progression of advanced non-small-cell lung cancer (NSCLC). METHODS: Specificity of the ddPCR assay was evaluated with genomic DNA samples from healthy individuals. The inter- and intraday variations of the assay were evaluated using mixtures of plasmid DNA containing wild-type EGFR and T790M mutation sequences. We assessed the clinical utility of the T790M assay in a multicenter prospective study in patients with advanced NSCLC receiving tyrosine kinase inhibitor (TKI) treatment by analyzing longitudinal plasma DNA samples. RESULTS: We set the criteria for a positive call when the following conditions were satisfied: (1) T790M mutation frequency > 0.098% (3 standard deviations above the background signal); (2) at least two positive droplets in duplicate ddPCR reactions. Among the 62 patients with advanced NSCLC exhibiting resistance to TKI treatment, 15 had one or more serial plasma samples that tested positive for T790M. T790M mutation was detected in the plasma as early as 205 days (median 95 days) before disease progression, determined by imaging analysis. Plasma T790M concentrations also correlated with intervention after disease progression. CONCLUSIONS: We developed a ddPCR assay to quantify the T790M mutation in plasma. Quantification of longitudinal plasma T790M mutation may allow noninvasive assessment of drug resistance and guide follow-up treatment in TKI-treated patients with NSCLC. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02804100.

14.
Neuroscience ; 419: 72-82, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682827

RESUMO

Previous studies reported that long-term nociceptive stimulation could result in neurovascular coupling (NVC) dysfunction in brain, but these studies were based mainly on unimodal imaging biomarkers, thus could not comprehensively reflect NVC dysfunction. We investigated the potential NVC dysfunction in chronic migraine by exploring the relationship between neuronal activity and cerebral perfusion maps. The Pearson correlation coefficients between these 2 maps were defined as the NVC biomarkers. NVC biomarkers in migraineurs were significantly lower in left inferior parietal gyrus (IPG), left superior marginal gyrus (SMG) and left angular gyrus (AG), but significantly higher in right superior occipital gyrus (SOG), right superior parietal gyrus (SPG), and precuneus. These brain regions were located mainly in parietal or occipital lobes and were related to visual or sensory information processing. ALFF-CBF in right SPG was positively correlated with disease history and that in right precuneus was negatively correlated with migraine persisting time. fALFF-CBF in left SMG and AG were negatively related to headache frequency and positively related to health condition and disease history. In conclusion, multi-modal MRI could be used to detect NVC dysfunction in chronic migraine patients, which is a new method to assess the impact of chronic pain on the brain.

15.
Adv Mater ; 31(49): e1905087, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31625638

RESUMO

Chromium-doped zinc gallate, ZnGa2 O4 :Cr3+ (ZGC), is viewed as a long-lasting luminescence (LLL) phosphor that can avoid tissue autofluorescence interference for in vivo imaging detection. ZGC is a cubic spinel structure, a typical agglomerative or clustered morphology lacking a defined cubic shape, but a sphere-like feature is commonly obtained for the nanometric ZGC. The substantial challenge remains achieving a well-defined cubic feature in nanoscale. The process by which dispersed and well-defined concave cubic ZGC is obtained is described, exhibiting much stronger LLL in UV and X-ray excitation for the dispersed cubic ZGC compared with the agglomerative form that cannot be excited using X-rays with a low dose of 0.5 Gy. The cubic ZGC reveals a specific accumulation in liver and 0.5 Gy used at the end of X-ray excitation is sufficient for imaging of deep-seated hepatic tumors. The ZGC nanocubes show highly passive targeting of orthotopic hepatic tumors.

16.
Ann Thorac Surg ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31541633

RESUMO

BACKGROUND: To meet the demand of increasing surgical volume and changing of patient's risk profiles of coronary artery bypass grafting in China, we developed a new risk model that predicts in-hospital mortality. METHODS: The analysis included patients who underwent coronary artery bypass grafting between January 2013 and December 2016 at 87 hospitals in the Chinese Cardiac Surgery Registry. Patients in years 2013 to 2015 were randomly divided into training (n = 31,297 [75%]) and test (n = 10,432 [25%]) samples; 2016 patients (n = 15047) comprised the validation sample. Demographic and clinical risk factors were identified. The Harrell C statistic was used to evaluate model discrimination, and the Hosmer-Lemeshow goodness-of-fit test was used to assess calibration. RESULTS: The 56,776 patients were a mean age of 61.8 (SD, 8.8) years, and 24.6% were women. Overall, in-hospital mortality was 2.1%. The final model included 21 risk factors represented by 16 unique variables. The model achieved good discrimination, with a C statistic of 0.79 (95% confidence interval [CI], 0.77-0.80) in the training sample, 0.79 (95% CI, 0.76-0.82) in the test sample, and 0.78 (95% CI, 0.76-0.81) in the validation sample. Model calibration was good according to the Hosmer-Lemeshow test (P > .05 in the 3 samples). Compared with the European System for Cardiac Operative Risk Evaluation 2011 revision (EuroSCORE II) and the Sino(Chinese) System for Coronary artery bypass grafting Operative Risk Evaluation (SinoSCORE), the model had better discrimination and calibration. CONCLUSIONS: We developed and evaluated a model with 16 risk factors that predicted in-hospital mortality risk after coronary artery bypass grafting in China. This updated model may help surgeons and hospitals better identify high-risk patient.

17.
Ann Thorac Surg ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31472132

RESUMO

BACKGROUND: This study aims to compare the mid-term outcomes of left ventricular reconstruction with those of left ventricular reconstruction plus mitral valve surgery in patients with left ventricular aneurysm due to anterior myocardial infarction and moderate mitral regurgitation. METHODS: A total of 523 patients (75 who underwent left ventricular reconstruction plus mitral valve surgery and 448 who underwent left ventricular reconstruction) with concomitant moderate mitral regurgitation were included in the study population. All-cause mortality was considered the primary endpoint. Major adverse cardiovascular and cerebrovascular events (MACCE), including death, myocardial infarction, stroke and subsequent mitral valve surgery, were considered secondary endpoints. Multivariable proportional hazards Cox regression models were used to assess the associations between groups and outcomes. In the sensitivity analysis, we excluded patients who did not undergo coronary artery bypass graft (CABG) and repeated the statistical analysis above. RESULTS: The median follow-up time among all patients was 41 months. There was no significant difference between the left ventricular reconstruction plus mitral valve surgery and the left ventricular reconstruction groups with regard to all-cause mortality (p=0.208) and MACCE (p=0.817) after adjustment for covariates. In the sensitivity analysis, there was no significant difference between the left ventricular reconstruction plus mitral valve surgery and left ventricular reconstruction groups with regard to all-cause mortality (p=0.158) and MACCE (p=0.651) after adjustment for covariates. CONCLUSIONS: The clinical outcomes of left ventricular reconstruction are comparable to those of left ventricular reconstruction plus mitral valve surgery in patients with left aneurysm and moderate mitral regurgitation.

18.
Fish Shellfish Immunol ; 93: 904-910, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31415902

RESUMO

HSP40, also called DnaJ, functions as a molecular chaperone by binding to Hsp70 and plays critical roles in the growth, development, and response to heat stress. However, this gene family is rarely reported in pearl oyster. In this study, 31 putative HSP40 genes from Pinctada fucata martensii (PmHSP40) were identified through bioinformatics methods and classified into three groups according to the presence of the complete three domains (J, G/F zinc finger domain, and cysteine rich domain). Further analysis showed that the PmHSP40 genes are highly diverse in sequence, domain structure, and tissue and development expression profile, implying diversified functions. In addition, one highly induced PmHSP40 in low-temperature (PmHSP40LT) was cloned, and its function in temperature response was explored. PmHSP40LT has a full length of 1741 bp, containing 1059 bp ORF, 152 bp 5'UTR, and a 507 bp 3'UTR, and encodes 352 amino acids. PmHSP40LT expression was significantly induced at low (17 °C) and high temperature (32 °C) at 6 h, 1 d, and 3 d relative to the control group. Thus, PmHSP40LT possibly participates in response to high and low temperatures in pearl oyster. In conclusion, all these results provide a comprehensive basis for the further analysis of PmHSP40 function in pearl oysters.


Assuntos
Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/imunologia , Imunidade Inata/genética , Penaeidae/genética , Penaeidae/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Temperatura Baixa , Perfilação da Expressão Gênica , Proteínas de Choque Térmico HSP70/química , Filogenia , Pinctada , Alinhamento de Sequência
19.
Theranostics ; 9(16): 4624-4632, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367245

RESUMO

Detection and quantification of trimethylamine N-oxide (TMAO), a metabolite from gut microbial, is important for the disease diagnosis such as atherosclerosis, thrombosis and colorectal cancer. In this study, a novel method was established for the sensing and quantitative detection of TMAO via molecular recognition of guanidinium-modified calixarene from complex matrix. Methods: Various macrocycles were tested for their abilities to serve as an artificial TMAO receptor. Using the optimized receptor, we developed an indicator displacement assay (IDA) for the facile fluorescence detection of TMAO. The quantification of TMAO was accomplished by the established calibration line after excluding the interference from the various interfering substances in artificial urine. Results: Among various macrocycles, water-soluble guanidinium-modified calix[5]arene (GC5A), which binds TMAO in submicromolar-level, was identified as the optimal artificial receptor for TMAO. With the aid of the GC5A•Fl (fluorescein) reporter pair, TMAO fluorescence "switch-on" sensing was achieved by IDA. The fluorescence intensity increased linearly with the elevated TMAO concentration. The detection was not significantly interfered by the various interfering substances. TMAO concentration in artificial urine was quantified using a calibration line with a detection limit of 28.88 ± 1.59 µM, within the biologically relevant low µM range. Furthermore, the GC5A•Fl reporter pair was successfully applied in analyzing human urine samples, by which a significant difference in fluorescence response was observed between the [normal + TMAO] and normal group. Conclusion: The proposed supramolecular approach provides a facile, low-cost and sensitive method for TMAO detection, which shows promise for tracking TMAO excretion in urine and studying chronic disease progression in humans.

20.
Beilstein J Org Chem ; 15: 1394-1406, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293689

RESUMO

We herein describe the comprehensive investigation of the complexation behavior of a guanidinium-modified calix[5]arene pentaisohexyl ether (GC5A) with a variety of typical luminescent dyes. Fluorescein, eosin Y, rose bengal, tetraphenylporphine sulfonate and sulfonated aluminum phthalocyanine were employed as classical aggregation-induced quenching dyes. 2-(p-Toluidinyl)naphthalene-6-sulfonic acid and 1-anilinonaphthalene-8-sulfonic acid were selected as representatives of intramolecular charge-transfer dyes. Phosphated tetraphenylethylene was involved as the classical aggregation-induced emission dye. Sulfonated acedan representing one example of two-photon fluorescent probes, was also investigated. A ruthenium(II) complex with carboxylated bipyridyl ligands was included as a representative candidate of luminescent transition-metal complexes. We determined the association constants of the GC5A-dye complexes by fluorescence titration and discuss the complexation-induced photophysical changes. In addition, a comparison of the complexation behavior of GC5A with that of other macrocycles and potential applications according to the diverse photophysical responses are provided.

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