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1.
Front Biosci (Landmark Ed) ; 25: 1600-1616, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32114446

RESUMO

Reactive oxygen species (ROS) and iron play important roles in the innate immune response. ROS are released by immune cells and are highly reactive and indiscriminately destructive in response to pathogens. In addition, ROS act as signaling molecules and play a role in apoptosis, therefore excessive ROS production can damage host molecules, leading to more harm than benefit for the host. Iron acts as a catalyst for the formation of ROS, therefore, manipulation of iron levels is a way in controlling ROS production. Iron metabolism and ROS production may affect many disease processes and must be tightly regulated for the host to generate an appropriate response. Current researches examine the roles of iron and ROS in various conditions, including neurodegeneration, inflammation, infection and cancer. Therapies directed at regulating ROS production through regulating iron levels are a major focus in these fields today.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32163573

RESUMO

BACKGROUND: Observational studies have shown a link between elevated body mass index (BMI) and the risk of polycystic ovary syndrome (PCOS). While Mendelian randomization (MR) studies in Europeans have suggested a causal role of increased BMI in PCOS, whether the same role is suggested in Asians has yet to be investigated. We used MR studies to infer causal effects using genetic data from East Asian populations. METHODS AND FINDINGS: We performed a two-sample bidirectional MR using summary statistics from genome-wide association studies (GWAS) of BMI (with up to 173,430 individuals) and PCOS (4,386 cases and 8,017 controls) in East Asian populations. Seventy-eight single nucleotide polymorphisms (SNPs) correlated with BMI were selected as genetic instrumental variables to estimate the causal effect of BMI on PCOS using the inverse-variance weighted (IVW) method. To test the reliability of the results, further sensitivity analyses included MR-Egger regression, weighted median estimates, and leave-one-out analysis. The IVW analysis indicated a significant association between high BMI and the risk of PCOS (odds ratio (OR) per-SD higher BMI, 2.208; 95% Confidence interval (CI) 1.537 to 3.168, P=1.77×10-5). In contrast, the genetic risk of PCOS had no significant effect on BMI. CONCLUSIONS: The results of our bidirectional MR study showed that an increase in BMI causes PCOS, while PCOS does not cause an increased BMI. This study provides further genetic support for a link between BMI and PCOS. Further research is needed to interpret the potential mechanisms of this association.

3.
J Clin Pharm Ther ; 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32170986

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Combination regimens of six-month duration may increase the incidence of anti-tuberculosis drug-induced liver injury (ATLI), which is clinically characterized by mild cholestasis and hepatocanalicular lesions. UGT2B4 is a predominant UDP-glucuronosyltransferase enzyme in the human liver that plays an important role in the detoxification of bile acids, which yields water-soluble inactive compounds that can easily be excreted in the bile or urine. This study aimed to investigate the potential association between UGT2B4 variants and the susceptibility to ATLI. METHODS: Genomic DNA was extracted from whole blood sample of each patient, and all SNPs were genotyped using an improved multiplex ligation detection reaction method. Clinical symptoms and laboratory results were recorded regularly. Five genetic variants at UGT2B4 (rs1131878, rs1966151, rs28361541, rs4557343 and rs79407331) were identified in a prospective study of 118 ATLI cases and 628 non-ATLI controls. All participants were treated by first-line anti-TB drugs in Western China Hospital. The potential association between SNPs, ATLI risk and clinical phenotypes were determined based on the distribution of allelic frequencies and different genetic models. RESULTS AND DISCUSSION: Statistical comparisons of cases and controls after correction for multiple testing did not yield any significant association between genetic variants at UGT2B4 and risk of ATLI via the analyses of single locus and subgroup differences. WHAT IS NEW AND CONCLUSION: This is the first study aimed to investigate the association of UGT2B4 polymorphisms with ATLI risk. Our results revealed that UGT2B4 genetic variants are unlikely to confer susceptibility to ATLI in the Western Chinese Han population.

4.
World J Biol Psychiatry ; : 1-7, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32129128

RESUMO

Objectives: Chromosome 8p12 was first identified as a schizophrenia (SCZ) risk locus in Chinese populations and replicated in European populations. However, the underlying functional variants still need to be further explored. In this study, we sought to identify plausible causal variants within this locus.Methods: A total of 386 potentially functional variants from 29 genes within the 8p12 locus were analysed in 2403 SCZ cases and 2594 control subjects in the Han Chinese population using Affymetrix customised genotyping assays. SHEsisplus was used for association analysis. A multiple testing corrected p value (false discovery rate (FDR)) < .05 was considered significant, and an unadjusted p value < .05 was considered nominal evidence of an association.Results: We did not find significant associations between the tested variants and SCZ. However, nominal associations were found for rs201292574 (unadjusted p = .033, FDR p = .571; 95% confidence interval (CI): 0.265-0.945; TACC1, NP_006274.2:p.Ala211Thr) and rs45563241 (unadjusted p = .039, FDR p = .571; 95% CI: 1.023-1.866; a synonymous mutation in ADRB3).Conclusions: Our results provide limited evidence for the associations between variants from protein coding regions in 8p12 and SCZ in the Chinese population. Analyses of both coding and regulatory variants in larger sample sizes are required to further clarify the causal variants for SCZ with this risk locus.

5.
Ecotoxicol Environ Saf ; 194: 110381, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32145529

RESUMO

Combined with sediment pollutant analysis, the gastropod Cipangopaludina cahayensis was chosen as an indicator organism to evaluate the environmental behavior of trace metals and the aquatic ecological risk that they present in a backwater area of Xian'nv Lake. Based on hydrological characteristics, 24 sampling sites representing the main stream (MS), tributaries (TR), lake area (LA) and lake tributaries (LT) were collected. The results revealed that cadmium (Cd) was the main pollutant and that it significantly accumulated in sediments of the research area. Based on the pollutant concentrations, the degree of Cd pollution was ranked in the following order: LA > MS > TR > LT. Several intersections between the rivers and Xian'nv Lake, including LA1, LA7 and LA 10, were observed to have higher Cd deposition. There was a significant difference in the spatial distribution of pollutants, which resulted in a higher accumulation of trace metals in the backwater area and its tributary. The Cd content in the visceral sac of C. cahayensis was positively correlated with the concentration of heavy metals in the sediment. The response of multiple antioxidant biomarkers, including superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), as well as the glutathione (GSH) content and the level of by-products of lipid peroxidation (TBARS), in C. cahayensis revealed a potential relationship to the environmental behavior of the pollutants. By combining the different biomarkers responses, the integrated biomarker response index (IBR) corresponded well with the pollution distribution characteristics in different areas.

6.
Chemistry ; 2020 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-32201995

RESUMO

The past decade has witnessed the increasing interest in cesium lead halide perovskite quantum dots (PQDs) for their excellent optical properties with higher photoluminescence efficiency and tunable emission wavelengths widely applied in white LED, photovoltaic devices etc. Here we report the preparation of CsPbBr 3 PQDs by a facile anti-solvent method by using a conventional quaternary ammonium bromide  (CTAB) as a double modifier, both proper alkyl group protection and bromine source donator. The as-formed PQDs are well-monodispersed cube with a size of 10-15 nm and high photoluminescence quantum yield (PLQY) up to 43%. To enhance the stability of PQDs,CsPbBr 3 @PS microspheres were formed by electrospraying process, not only maintain excellent luminous properties, but also exhibit much higher stability against air and light irradiation due to the super hydrophobic property of polystyrene.

7.
Mol Genet Genomic Med ; : e1190, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32180374

RESUMO

BACKGROUND: ZDHHC2 is a member of the DHHC protein family, mediating palmitoylation of postsynaptic density-95 (PSD-95) and A-kinase-anchoring protein 79/150 (AKAP79/150). Genome-wide association studies (GWASs) have identified ZDHHC2 as a candidate gene for schizophrenia (SCZ). We aimed to fine-map variants of ZDHHC2 conferring risk to SCZ in the Han Chinese population. METHODS: Targeted sequencing of whole-exome sequences including untranslated regions (UTRs) along with neighboring regions in 1,827 schizophrenic patients and 1,004 normal controls of Han Chinese origin. RESULTS: A total of 123 variants, including five common and 118 rare variants, were identified. Among common variants, rs73198534, rs530313445, and rs74406481 were significantly associated with SCZ. Nine nonsynonymous rare variants, p.Glu96fs, p.Arg127X, p.Val145Ile, p.Ala177Thr, p.Arg269Gln, p.Asn312His, p.Glu319Lys, p.Gln340X, and p.Ile347Val, identified only in patients; eight are located in the important domains, including two stop-gain variants. The 3D structural analysis and functional prediction revealed that all these eight variants may affect AMPAR expression or function, and influence the synaptic plasticity by regulating the palmitoylation of PSD95 and AKAP79/150. CONCLUSION: Our results first show strong supportive evidences of the association between the ZDHHC2 and SCZ, and also provide a fine-mapping of variants of this gene in Han Chinese SCZ patients.

8.
Technol Cancer Res Treat ; 19: 1533033819901117, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32167027

RESUMO

PURPOSE: To establish an efficient new risk index for screening patients with endometrial cancer from patients with abnormal vaginal bleeding or discharge. METHOD: A total of 254 patients with abnormal vaginal bleeding or discharge were included in this study. Several candidate markers, including HE4, CA125, CA199, CA153, AFP, CEA, d-dimer, and fibrinogen, were employed. A new risk index for endometrial cancer screening was established by binary logistic regression. The diagnostic value of the candidate markers and the new risk index were assessed by a receiver operating characteristic curve, sensitivity, and specificity. RESULTS: The most valuable diagnostic indicator for endometrial cancer was HE4, followed by d-dimer and then fibrinogen (area under the receiver operating characteristic curve: HE4 = 0.794, d-dimer = 0.717, fibrinogen = 0.690). The new risk index was superior to a single application of markers and a widely used combination (HE4 and CA125). At the ideal cutoff level, the sensitivity and specificity were 91.34% and 70.08%, respectively. In addition, only patients without organic disease served as controls, which further increase its performance (area under the receiver operating characteristic curve = 0.932, sensitivity = 94.49%, and specificity = 77.42%). CONCLUSIONS: The new risk index combining HE4, d-dimer, fibrinogen, and CA199 was the ideal combination for the screening of endometrial cancer. As a simple, rapid, nondestructive detection method, the new risk index is worth promotion in clinical practice, especially in primary medical institutions.

9.
BMC Psychiatry ; 20(1): 135, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32213169

RESUMO

BACKGROUND: Recent genome-wide association study showed rs10940346 locus near EMB gene was significantly associated with schizophrenia and suggested that EMB gene is one of the potentially causal genes for schizophrenia, but no causal variant has been identified. Our study aims to further verify EMB gene is a susceptibility gene for schizophrenia and to identify potentially causal variants in EMB gene that lead to schizophrenia. METHODS: Targeted sequencing for the un-translated region and all exons of EMB gene was performed among 1803 patients with schizophrenia and 997 healthy controls recruited from Chinese Han population. RESULTS: A total of 58 high-quality variants were identified in case and control groups. Seven of them are nonsynonymous rare variations, EMB: p.(Ala52Thr), p.(Glu66Gly), p.(Ser93Cys), p.(Ala118Val), p.(Ile131Met), p.(Gly163Arg) and p.(Arg238Tyr), but none of them reached statistical significance. Among them, p.(Ile131Met), p.(Gly163Arg) and p.(Arg238Tyr), were predicted to be deleterious variants. In addition, a common variant, rs3933097 located in 3'-UTR of EMB gene, achieved allelic and genotypic significance with schizophrenia (Pallele = 3.82 × 10- 6, Pgenotype = 3.18 × 10- 5). CONCLUSIONS: Our research first presented a comprehensive mutation spectrum of exons and un-translated region in EMB gene for schizophrenia and provided additional evidence of EMB gene being a susceptibility gene for schizophrenia. However, further functional validations are necessary to reveal its role in the etiology of schizophrenia.

10.
Pathol Res Pract ; : 152873, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32107087

RESUMO

BACKGROUND: Lung cancer is one of the leading causes of cancer death worldwide, and genetic risk factors account for a large part of its carcinogenesis. The low economic requirements and high efficiency of next-generation sequencing (NGS) make it widely used in detecting genetic alterations in pathogenesis. METHODS: We performed targeted panel sequencing in 780 Han Chinese lung cancer patients using a commercial probe, and the correlations between dozens of susceptible sites were verified in 1113 healthy controls. This study used Fisher's exact test and Benjamini-Hochberg FDR correction to analyze the mutual exclusion between mutated genes, and Pearson's p was used to verify the correlations between mutations and lung cancer susceptibility. RESULTS: Our results determined the mutation spectrum and showed that each lung cancer patient carried at least one DNA mutation. The most frequently mutated gene was BRCA2 (mutation rate,10.6 %.). The co-occurrence and mutual exclusion analysis of DNA damage related genes showed that gene ATM was mutually exclusive from MSH6. We conducted a further case-control study in different subtypes of lung cancer and the results described 14 mutations associated with adenocarcinoma, 9 with squamous cell carcinoma, and 4 with small cell lung cancer. These variants were novel de-novo germline mutations in lung cancer. Particularly, rs3864017 in FANCD2 showed a protective effect of lung adenocarcinoma for carriers (OR = 0.146, 95 % CI = 0.052∼0.405, Padjusted = 3.37 × 10-4). CONCLUSIONS: 18 candidate mutations might alter the risk of lung cancer in the Han Chinese population, including polymorphisms rs3864017(FANCD2), rs55740729(MSH6) and 16 rare variants. The underlying mechanisms of candidate genes in lung cancer remain unclear and we suggest more functional studies on exploring how these genes affect the risk of lung cancer.

11.
Med Sci Monit ; 26: e920531, 2020 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-32008036

RESUMO

BACKGROUND The prognosis of epithelial ovarian cancer (EOC) remains poor. Cause-specific survival (CSS) is an overall survival measure of cancer survival that excludes other causes of death. This retrospective population study used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate prognostic factors associated with one-year CSS in women with stage III-IV EOC between 2004-2014. MATERIAL AND METHODS Data from the SEER program included a cohort of patients with stage III-IV EOC between 2004-2014. Binomial logistic regression analysis, Kaplan-Meier survival curves, and multivariate Cox proportional hazards models were used for analysis of patient outcome, including the one-year CSS. RESULTS There were 14,798 patients with stage III-IV EOC identified from SEER between 2004-2014, including 13,134 (88.8%), 892 (6.0%), 448 (3.0%), and 324 (2.2%) patients with serous, endometrioid, clear cell, and mucinous ovarian cancer, respectively. The overall one-year CSS was 91.2%. One-year CSS was 92.5%, 92.2%, 74.0%, and 62.5% in patients with serous, endometrioid, clear cell, and mucinous ovarian cancer, respectively (P<0.001). Histological tumor type was an independent prognostic factor of one-year CSS. Patients with mucinous EOC (HR, 8.807; 95% CI, 6.563-9.965; P<0.001) and clear cell EOC (HR, 4.581; 95% CI, 3.774-5.560; P<0.001) had a significantly lower one-year CSS compared with patients with endometrioid and serous EOC who had comparable one-year CSS (HR, 1.247; 95% CI, 0.978-1.590; P=0.075). CONCLUSIONS A retrospective population study of the SEER database between 2004-2014 identified that histological tumor type was associated with one-year CSS in women with stage III-IV EOC.

12.
Chemosphere ; 248: 126015, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32032874

RESUMO

Sixteen polycyclic aromatic hydrocarbons (PAHs) in a sediment core from Dianchi Lake, southwest China, were analysed. The influence of changes in China's energy structure for 2-6 ringed PAHs was investigated to assess sources and the impact of socioeconomic development on temporal changes in concentrations. The concentration of the ΣPAH16 ranged from 746 to 2293 ng g-1. Prior to the 1960s relatively low concentrations of the ΣPAH16 and a larger proportion of 2-3-ring PAHs indicated that biomass combustion was the main source of PAHs. A rapid increase in the concentrations of 2-3 ring PAHs between 1975 and 2004 was attributed to population growth and coal consumption. A declining trend since 2004 was interpreted as being due to local changes in household energy usage. Increased concentrations of 4-ring PAH between 1975-2005 and 5-6-ring PAHs between the 1980s to 2004 showed correlations with increased coal consumption and the number of motor vehicles, respectively. These were caused by rapid urbanization and industrialization in the Dianchi watershed following the implementation of the Reform and Open Policy in 1978. A subsequent decline in the concentrations of 4-ring and 5-6-ring PAHs may have been due to decreased coal consumption and improvements in emission standards, respectively. Source apportionment by a PMF model revealed that coal combustion (29.2%), vehicle emissions (24.2%), petrogenic sources (21.8%), and biomass combustion (24.9%) were the sources of PAHs in the lake sediment core, and that coal combustion was the most important regional source of PAHs pollution.

13.
Sci Rep ; 10(1): 1976, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029793

RESUMO

The study aimed to investigate whether the glucose level improves and what factors affect the improvement in glucose control after the eradication of hepatitis C virus (HCV). A total of 1090 patients with HCV infections were enrolled, among which 278 (25.5%) patients were diagnosed with prediabetes, and 89 (8.16%) patients were diagnosed with diabetes. In the cohort, 990 patients belonged to sustained virological response (SVR) group and 100 belonged to non-SVR group. Decreases in the fasting plasma glucose (FPG) level were found in the SVR group but not in the non-SVR group (p < 0.001; p = 0.267). In the SVR group, subjects with baseline FPG ≥ 5.6 mmol/L were further stratified into glycometabolism-improved (N = 182) and unimproved (N = 150) groups according to their FPG after viral eradication. Multivariate analysis showed that older age, higher baseline HCV RNA, glucose, total bilirubin and alanine aminotransferase levels were independent risk factors for insufficient glucose improvement. In conclusion, patients with HCV infection had a higher prevalence of abnormal glycometabolism. It could be improved after viral eradication, indicating that HCV may influence glycometabolism. Moreover, Age, baseline HCV RNA, glucose, total bilirubin and alanine aminotransferase levels were impact factor for glycometabolism improvement after viral eradication.

14.
Clin Chim Acta ; 506: 1-8, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32109431

RESUMO

Autophagy, an evolutionarily conserved catabolic process, is the most important pathogenic events in the development and progression of liver diseases. Deregulation of Nrf2 is proposed to play a key pathogenic role in hepatocellular carcinoma (HCC). Under certain pathophysiological conditions, such as oxidative stress, impaired autophagy is accompanied by the Nrf2 activation that leads to the detrimental effects favoring the proliferation and survival of HCC. Elucidating its role and potential mechanism is essential for understanding tumorigenesis and the development of effective clinical application. Nrf2 is participated in HCC proliferation, migration and invasion through autophagy pathways. These includes the negatively regulated-Nrf2 by Keap1 that participates in HCC tumorigenesis via regulating ROS production, in which autophagy may contribute to oxidant metabolic reprogramming of HCC cells. Post-transcriptional modifications, such as phosphorylation and ubiquitination of Nrf2, can be positively or negatively induced by multiple transcription factors. Nrf2 exhibits chemoresistance through its binding sites in the promoter region of the target genes. Nrf2 may be a valuable potential biomarker and therapeutic strategy for diagnostics, prognostics and treatment of HCC.

15.
Brain Cogn ; 140: 105526, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32007788

RESUMO

OBJECTIVE: Pregnancy causes many changes in our body and some of them may affect our ability of learning and memory. We examined the cerebral cortical volume of brain during pregnancy and measured changes in the brain electrical activity and cerebral blood flow. METHOD: 35 women (20 normal full-term primigravida and 15 non-pregnant women) received the Electroencephalography (EEG) and Transcranial Doppler ultrasonography (TCD). 8 non-pregnant women and 9 primigravida after vaginal delivery underwent brain magnetic resonance imaging (MRI) voluntarily within 24 h. RESULTS: Compared with the non-pregnant, changes were shown by EEG through electrodes of T5, Pz, Cz, T6, F3 and F8. The results displayed increased activity in the central parietal area of pregnant women, while that in the temporoparietal junction decreased. The result of TCD revealed that pulsation index (PI) values of left and right internal and external carotid arteries were asymmetrical, but they all decreased in pregnancy. Atrophy of cortical volume had been found in many brain functional areas of pregnant women. The percentage of atrophy varied between 6.76% and 13.17%. CONCLUSION: Atrophy of cerebral cortex, changes in cerebral blood flow and neuron electrophysiology may be the physiological basis of the emotional, cognitive changes in pregnant women.

16.
Hum Brain Mapp ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31944479

RESUMO

Hippocampal atrophy and abnormal ß-Amyloid (Aß) deposition are established markers of Alzheimer's disease (AD). Nonetheless, longitudinal trajectory of Aß-associated hippocampal subfield atrophy prior to dementia remains unclear. We hypothesized that elevated Aß correlated with longitudinal subfield atrophy selectively in no cognitive impairment (NCI), spreading to other subfields in mild cognitive impairment (MCI). We analyzed data from two independent longitudinal cohorts of nondemented elderly, including global PET-Aß in AD-vulnerable cortical regions and longitudinal subfield volumes quantified with a novel auto-segmentation method (FreeSurfer v.6.0). Moreover, we investigated associations of Aß-related progressive subfield atrophy with memory decline. Across both datasets, we found a converging pattern that higher Aß correlated with faster CA1 volume decline in NCI. This pattern spread to other hippocampal subfields in MCI group, correlating with memory decline. Our results for the first time suggest a longitudinal focal-to-widespread trajectory of Aß-associated hippocampal subfield atrophy over disease progression in nondemented elderly.

17.
Trials ; 21(1): 32, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907080

RESUMO

BACKGROUND: The prevalence of central obesity is constantly increasing, and visceral fat is associated with increased production of inflammatory factors and metabolic risk factors. Lutein might retard the development of metabolic disease through its antioxidant and anti-inflammatory properties. Furthermore, epidemiological studies have associated higher dietary intake and serum levels of lutein with decreased adiposity. However, few randomised controlled trials have shown the effects of lutein supplementation on inflammatory biomarkers and metabolic risk factors, especially in adults with central obesity. METHODS: This study will be conducted as a double-blind, parallel placebo-controlled clinical trial in which 120 people who have central obesity, are 18 to 60 years old and are willing to provide informed consent will be randomly assigned to the intervention or placebo group in a 1:1 ratio according to sex, age and waist circumference. The intervention group will receive 10 mg daily lutein supplementation for 12 weeks to explore the effect of lutein supplementation on serum lutein, glycaemic and lipid profiles, inflammatory factors and body composition. Two populations (intention-to-treat population and per-protocol population) will be used in the data analyses. DISCUSSION: Our findings from this trial will contribute to the knowledge of the association between lutein supplementation and inflammatory biomarkers and metabolic risk factors in people with central obesity and will offer a possibility for the prevention of inflammatory diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800018098. Registered on 30 August 2018.

18.
Clin Transl Gastroenterol ; 11(1): e00089, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31922993

RESUMO

OBJECTIVES: Conventional colonoscopy with white light illumination detects colonic adenomas based on structural changes alone and is limited by a high miss rate. We aim to demonstrate an integrated imaging strategy that combines wide-field endoscopy and confocal endomicroscopy in real time to visualize molecular expression patterns in vivo to detect premalignant colonic mucosa. METHODS: A peptide specific for claudin-1 is labeled with Cy5.5 and administrated intravenously in genetically engineered mice that develop adenomas spontaneously in the distal colon. Wide-field endoscopy is used to identify the presence of nonpolypoid and polypoid adenomas. Anatomic landmarks are used to guide placement of a confocal endomicroscope with side-view optics to visualize claudin-1 expression patterns with subcellular resolution. RESULTS: Wide-field fluorescence images show peak uptake in colon adenoma at ∼1 hour after systemic peptide administration, and lesion margins are clearly defined. Further examination of the lesion using a confocal endomicroscope shows dysplastic crypts with large size, elongated shape, distorted architecture, and variable dimension compared with normal. The mean fluorescence intensity is significantly higher for dysplasia than normal. Increased claudin-1 expression in dysplasia vs normal is confirmed ex vivo, and the binding pattern is consistent with the in vivo imaging results. DISCUSSION: Wide-field endoscopy can visualize molecular expression of claudin-1 in vivo to localize premalignant colonic mucosa, and confocal endomicroscopy can identify subcellular feature to distinguish dysplasia from normal.

19.
Int J Mol Med ; 45(2): 401-416, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894294

RESUMO

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia and significantly increases the risks of morbidity, mortality and health care expenditure; however, treatment for AF remains unsatisfactory due to the complicated and incompletely understood underlying mechanisms. In the present study, weighted gene co­expression network analysis (WGCNA) was conducted to identify key modules and hub genes to determine their potential associations with AF. WGCNA was performed in an AF dataset GSE79768 obtained from the Gene Expression Omnibus, which contained data from paired left and right atria in cardiac patients with persistent AF or sinus rhythm. Differentially expressed gene (DEG) analysis was used to supplement and validate the results of WGCNA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were also performed. Green and magenta modules were identified as the most critical modules associated with AF, from which 6 hub genes, acetyl­CoA Acetyltransferase 1, death domain­containing protein CRADD, gypsy retrotransposon integrase 1, FTX transcript, XIST regulator, transcription elongation factor A like 2 and minichromosome maintenance complex component 3 associated protein, were hypothesized to serve key roles in the pathophysiology of AF due to their increased intramodular connectivity. Functional enrichment analysis results demonstrated that the green module was associated with energy metabolism, and the magenta module may be associated with the Hippo pathway and contain multiple interactive pathways associated with apoptosis and inflammation. In addition, the blue module was identified to be an important regulatory module in AF with a higher specificity for the left atria, the genes of which were primarily correlated with complement, coagulation and extracellular matrix formation. These results suggest that may improve understanding of the underlying mechanisms of AF, and assist in identifying biomarkers and potential therapeutic targets for treating patients with AF.

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