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1.
Int J Cancer ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33728681

RESUMO

Notch signaling pathway plays crucial roles in progression of colorectal cancer (CRC), likely affecting overall survival (OS). In a two-stage survival analysis of 1116 CRC patients in East China, we found that one locus at MINAR1 out of 133 genes in the Notch signaling pathway was significantly associated with OS (P < 1 × 10-6 , false discovery rate < 0.01). This locus containing seven single-nucleotide polymorphisms (SNPs) in high linkage disequilibrium (R2 = 1) is located on chromosome 15, of which the MINAR1 rs72430409 G allele was associated with a greater death risk (HR = 1.98, 95% CI = 1.55-2.54, P = 6.8 × 10-8 ). Further analysis of ChIP-sequencing data from the encyclopedia of DNA Elements showed that rs72430409 and rs72630408 were potential cis-regulatory elements for the MINAR1 promoter. Additional expression quantitative trait loci analysis revealed that rs72430409 G>A and rs72630408 A>G were correlated with increased MINAR1 expression levels in both blood cells and colon tissues. Dual luciferase assays revealed that the rs72430409 A allele increased MINAR1 promoter activity. The Cancer Genome Atlas data showed that expression levels of MINAR1 in CRC samples were significantly higher than that in normal colorectal tissue and that high expression of MINAR1 was associated with a shortened OS, likely via activating the epithelial mesenchymal transition (EMT) pathway as shown in the gene-set enrichment analysis. In vitro, RNAi-mediated silencing of MINAR1 led to decreased migration and proliferation in CRC cancer cells, and MINAR1 silencing could downregulate the expression of key effector genes in EMT and glycolysis. Larger cohort studies and further experiments are needed to validate our findings.

2.
Oncogene ; 40(13): 2382-2394, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33658628

RESUMO

Although genome-wide association studies (GWASs) have successfully revealed many common risk variants for bladder cancer, the heritability is still largely unexplained. We hypothesized that low-frequency variants involved in bladder cancer risk could reveal the unexplained heritability. Next-generation sequencing of 113 patients and 118 controls was conducted on 81 genes/regions of known bladder cancer GWAS loci. A two-stage validation comprising 3,350 cases and 4,005 controls was performed to evaluate the effects of low-frequency variants on bladder cancer risk. Biological experiments and techniques, including electrophoretic mobility shift assays, CRISPR/Cas9, RNA-Seq, and bioinformatics approaches, were performed to assess the potential functions of low-frequency variants. The low-frequency variant rs28898617 was located in the first exon of UGT1A3 and was significantly associated with increased bladder cancer risk (odds ratio = 1.50, P = 3.10 × 10-6). Intriguingly, rs28898617 was only observed in the Asian population, but monomorphism was observed in the European population. The risk-associated G allele of rs28898617 increased UGT1A3 expression, facilitated UGT1A3 transcriptional activity, and enhanced the binding activity. In addition, UGT1A3 deletion significantly inhibited the proliferation, invasion, and migration of bladder cancer cells and xenograft tumor growth. Mechanistically, UGT1A3 induced LAMC2 expression by binding CBP and promoting histone acetylation, which remarkably promoted the progression of bladder cancer. This is the first targeted sequencing study to reveal that the novel low-frequency variant rs28898617 and its associated gene UGT1A3 are involved in bladder cancer development, providing new insights into the genetic architecture of bladder cancer.

3.
Phytochemistry ; 184: 112678, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33550198

RESUMO

Phytochemical investigations on the fresh fruits of Kadsura coccinea (Lem.) A. C. Sm. have led to the isolation of fourteen undescribed 2,2'-cyclolignans named heilaohuguosus A-N, four undescribed aryltetrahydronaphthalene lignans, heilaohuguosus O-R and one tetrahydrofuran lignan, heilaohuguosu S, with twenty-seven previously described lignan analogues. Their structures and absolute configurations of heilaohuguosus A-S were established by spectroscopic methods including 1D and 2D-NMR techniques and CD experiments. All isolated compounds were evaluated for their hepatoprotective activity against APAP-induced toxicity in HepG-2 cells, four 2,2'-cyclolignans, heilaohuguosus A and L, tiegusanin I and kadsuphilol I showed good hepatoprotective activities against APAP toxicity in HepG-2 cells with cell survival rates of 53.5 ± 1.7%, 55.2 ± 1.2%, 52.5 ± 2.4%, and 54.0 ± 2.2% (positive control bicyclol, 52.1 ± 1.3%) at 10 µM, respectively.


Assuntos
Kadsura , Lignanas , Frutas , Lignanas/farmacologia , Estrutura Molecular , Compostos Fitoquímicos
4.
Neuroscience ; 459: 50-58, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33556458

RESUMO

The neural cognitive mechanism in processing static facial expressions (FEs) has been well documented, whereas the one underlying perceiving dynamic faces remains unclear. In this study, Fourier transformation and time-frequency analysis of Electroencephalography (EEG) data were carried out to detect the brain activation underlying dynamic or static FEs while twenty-one participants were viewing dynamic or static faces flicking at 10 Hz. In particular, steady-state visual evoked potentials (SSVEPs) were quantified through spectral power analysis of EEG recordings. Besides, Granger causality (GC) analysis (GCA) was also performed to capture the causal cortical network dynamics during dynamic or static FEs of emotion. It was discovered that the dynamic (from neural to happy (N2H) or vice versa (H2N)) FEs elicited larger SSVEPs than the static ones. Additionally, GCA demonstrated that the H2N case, in which happy FEs were being gradually changed into neutral ones, exhibited larger GC measure during the late processing stage than that from the early stage. Consequently, enhanced SSVEPs and effective brain connectivity for dynamic FEs illustrated that participants might need consume more attentional resources to process the dynamic faces, particularly for the change from happy to neutral faces. The new neural index might facilitate us to better understand the cognitive processing of dynamic and static FEs.

5.
Development ; 148(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33472846

RESUMO

In mammals, sperm-borne regulators can be transferred to oocytes during fertilization and have different effects on the formation of pronuclei, the first cleavage of zygotes, the development of preimplantation embryos and even the metabolism of individuals after birth. The regulatory role of sperm microRNAs (miRNAs) in the development of bovine preimplantation embryos has not been reported in detail. By constructing and screening miRNA expression libraries, we found that miR-202 was highly enriched in bovine sperm. As a target gene of miR-202, co-injection of SEPT7 siRNA can partially reverse the accelerated first cleavage of bovine embryos caused by miR-202 inhibitor. In addition, both a miR-202 mimic and SEPT7 siRNA delayed the first cleavage of somatic cell nuclear transfer (SCNT) embryos, suggesting that miR-202-SEPT7 mediates the delay of first cleavage of bovine embryos. By further exploring the relationship between miR-202/SEPT7, HDAC6 and acetylated α-tubulin during embryonic development, we investigated how sperm-borne miR-202 regulates the first cleavage process of bovine embryos by SEPT7 and demonstrate the potential of sperm-borne miRNAs to improve the efficiency of SCNT.

6.
Chemosphere ; 270: 129448, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33401075

RESUMO

A spectrophotometric method for the rapid measurement of hydrogen peroxide (H2O2) in aqueous solutions was developed in this study. This method is based on a reaction catalyzed by peroxidase (POD) in which potassium iodide (KI) is oxidized to generate the stable yellow-colored I3- within 15 s. The absorbance of the generated I3- at both 350 nm and 400 nm had good linear relationships with H2O2 concentration in the range of 0-70 µM (R2 > 0.999) with sensitivities of 2.34 × 104 M-1 cm-1 and 5.30 × 103 M-1 cm-1 respectively. Meanwhile, through calculation, the detection limits of the proposed POD-KI method at 350 nm and 400 nm were 0.09 µM and 0.33 µM, respectively. Even when the concentration of H2O2 was up to 350 µM, the absorbance of the generated I3- at 350 nm did not decrease observably. The generated I3- was found to be stable enough in ultrapure water, underground water, reservoir water and samples containing the strong reducing agent hydroxylamine. Moreover, the proposed POD-KI method was successfully used to analyze trace H2O2 in rainwater, and to monitor the change of H2O2 concentration in the Fenton, hydroxylamine/Fenton and hydroxylamine/Cu(II)/H2O2 systems. Overall, the POD-KI method could be adopted as a candidate method to determine H2O2 in Fenton and Fenton-like systems, and especially in those involving hydroxylamine.


Assuntos
Peróxido de Hidrogênio , Peroxidase , Catálise , Hidroxilamina , Hidroxilaminas , Oxirredução , Iodeto de Potássio , Água
7.
Biosens Bioelectron ; 174: 112870, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33334636

RESUMO

Correlating in-brain pH fluctuations with the pathophysiology has been impeded by the lack of in vivo techniques to precisely determine local pH changes. Here, we developed an all-in-one pH probe for spatially-resolved and label-free pH sensing in vivo, based on a field-effect pH sensor, i.e., a light-addressable potentiometric sensor (LAPS), coupled to a flexible multimodal fiber. A readout photocurrent from the LAPS, elicited from a modulated light source, registers the localized surface potential change, proportional to the pH change. Upon simultaneous illuminations at multi-spot by a plurality of light sources with different modulation frequencies, pH changes at multiple designated spots are obtained via demultiplexing this photocurrent. To enable its in vivo applications, we combined the LAPS with a multimodal fiber fabricated by the convergence thermal drawing. Such fiber seamlessly integrates a multicore optical waveguide in the center for the light delivery, surrounded by electrodes for leading out photocurrent and serving as a pseudo-reference electrode, respectively. Such hybrid all-in-one pH probes can measure pH changes at 14 pixels simultaneously with a spatial resolution of 250 µm and a temporal resolution of 30 Hz. The pH sensitivity was characterized as 57.5 ± 2.2 mV/pH homogeneously across all measurable pixels. Such probes have been implanted into the hippocampal formation of rats and their capabilities to capture pH changes at multiple pixels were evaluated at both physiological and pathological conditions. Technologies developed here represents a new class of in vivo chemical sensing technologies enabling the spatially-resolved investigation of intrinsic chemical signals in deep brain structures with high spatial and temporal resolutions.

8.
Addict Behav ; 112: 106601, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32942097

RESUMO

The present study examined the relationship between perceived interparental conflict and problematic social media use (PSMU) among adolescents, as well as the mediating effects of self-esteem and maladaptive cognition toward social network sites (SNS). A sample of 688 middle school students (56.1% females; Mage = 13.44 years; SDage = 0.99) was asked to complete a survey. Surveyed items included demographics, the Children's Perception of Interparental Conflict Scale, the Rosenberg Self-esteem Scale, the Chinese Adolescents' Maladaptive Cognitions Scale, and the Facebook Intrusion Questionnaire. After controlling for gender and age, the results showed that: (a) perceived interparental conflict was positively associated with PSMU; (b) this association was significantly mediated by maladaptive cognition toward SNS; and (c) self-esteem and maladaptive cognition toward SNS sequentially mediated this association. This study provides useful insight into the understanding of how perceived interparental conflict increases the risk of PSMU. The results further indicate that concrete approaches are required for the prevention and intervention of PSMU among adolescents.

9.
Vis Comput Ind Biomed Art ; 3(1): 28, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33258067

RESUMO

Brain oscillations are vital to cognitive functions, while disrupted oscillatory activity is linked to various brain disorders. Although high-frequency neural oscillations (> 1 Hz) have been extensively studied in cognition, the neural mechanisms underlying low-frequency hemodynamic oscillations (LFHO) < 1 Hz have not yet been fully explored. One way to examine oscillatory neural dynamics is to use a facial expression (FE) paradigm to induce steady-state visual evoked potentials (SSVEPs), which has been used in electroencephalography studies of high-frequency brain oscillation activity. In this study, LFHO during SSVEP-inducing periodic flickering stimuli presentation were inspected using functional near-infrared spectroscopy (fNIRS), in which hemodynamic responses in the prefrontal cortex were recorded while participants were passively viewing dynamic FEs flickering at 0.2 Hz. The fast Fourier analysis results demonstrated that the power exhibited monochronic peaks at 0.2 Hz across all channels, indicating that the periodic events successfully elicited LFHO in the prefrontal cortex. More importantly, measurement of LFHO can effectively distinguish the brain activation difference between different cognitive conditions, with happy FE presentation showing greater LFHO power than neutral FE presentation. These results demonstrate that stimuli flashing at a given frequency can induce LFHO in the prefrontal cortex, which provides new insights into the cognitive mechanisms involved in slow oscillation.

10.
J Ethnopharmacol ; : 113567, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33171272

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kadsura heteroclita (Roxb.) Craib (traditionally known as "Xue Tong") is an important member of the economically and medicinally important plant family Schisandraceae. "Xue Tong" is an imperative ingredient of the Tujia ethnomedicine, traditionally used for the treatment of rheumatoid arthritis (RA), hepatitis, and muscles and joint spasm. The plant is known to be a rich source of lignans and triterpenoids. These classes of natural products have been known to possess various pharmacological activities. AIM OF REVIEW: This review was motivated by the importance of K. heteroclita in traditional Chinese medicine (TCM). It aims to compile the available information on its botanical distribution and description, traditional uses, phytochemistry, pharmacological activities, toxicity, and quality control to provide a solid base for further research and development. MATERIALS AND METHODS: Relevant literature was collected by several scientific databases including PubMed, CNKI, Scifinder, The Plant List, Google Scholar, Baidu Scholar, Books (Tujia pharmaceutical records, Guangxi Chinese herbal medicine, Hunan pharmaceutical records and Field identification manual of Chinese herbal medicine) and other literature sources (Flora of China, Pharmacopoeia of the People's Republic of China) which helped in collecting maximum data about the studied species. RESULTS: Traditional uses of K. heteroclita have proven its medicinal importance, providing a rationale for scientific research. Phytochemical studies on the stem of K. heteroclita resulted in the identification of 187 chemical constituents, among which lignans and triterpenoids are the predominant groups. The isolates and crude extracts have been found to exhibit a wide spectrum of in vivo and in vitro pharmacological activities such as anti-RA, anti-inflammatory and analgesic, hepatoprotection, anti-HIV, anti-cancer and anti-HBV. Schisanlactone E (xuetongsu), a triterpenoid, is one of the major components of K. heteroclita exhibiting anti-cancer, neuroprotective and anti-neuroinflammation activities. Interestingly and luckily, this plant has been found to be safe and non-toxic within the therapeutic dose range. CONCLUSION: Pharmacological investigations have validated the use of K. heteroclita in traditional Chinese medicine (TCM). Literature review has demonstrated that lignans and triterpenoids are possibly responsible for most of the biological activities exhibited by this plant. To conclude, this plant shows immense potential for the discovery of more potent bioactive secondary metabolites and therefore further phytochemical and biological studies on other parts of K. heteroclita need to be conducted and more compounds need to be tested regarding their biological activities to completely explore its value as a tremendously important medicinal plant species.

11.
Lancet Oncol ; 21(10): 1378-1386, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002439

RESUMO

BACKGROUND: Genetic variants and lifestyle factors have been associated with gastric cancer risk, but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unknown. We aimed to establish a genetic risk model for gastric cancer and assess the benefits of adhering to a healthy lifestyle in individuals with a high genetic risk. METHODS: In this meta-analysis and prospective cohort study, we first did a fixed-effects meta-analysis of the association between genetic variants and gastric cancer in six independent genome-wide association studies (GWAS) with a case-control study design. These GWAS comprised 21 168 Han Chinese individuals, of whom 10 254 had gastric cancer and 10 914 geographically matched controls did not. Using summary statistics from the meta-analysis, we constructed five polygenic risk scores in a range of thresholds (p=5 × 10-4 p=5 × 10-5 p=5 × 10-6 p=5 × 10-7, and p=5 × 10-8) for gastric cancer. We then applied these scores to an independent, prospective, nationwide cohort of 100 220 individuals from the China Kadoorie Biobank (CKB), with more than 10 years of follow-up. The relative and absolute risk of incident gastric cancer associated with healthy lifestyle factors (defined as not smoking, never consuming alcohol, the low consumption of preserved foods, and the frequent intake of fresh fruits and vegetables), was assessed and stratified by genetic risk (low [quintile 1 of the polygenic risk score], intermediate [quintile 2-4 of the polygenic risk score], and high [quintile 5 of the polygenic risk score]). Individuals with a favourable lifestyle were considered as those who adopted all four healthy lifestyle factors, those with an intermediate lifestyle adopted two or three factors, and those with an unfavourable lifestyle adopted none or one factor. FINDINGS: The polygenic risk score derived from 112 single-nucleotide polymorphisms (p<5 × 10-5) showed the strongest association with gastric cancer risk (p=7·56 × 10-10). When this polygenic risk score was applied to the CKB cohort, we found that there was a significant increase in the relative risk of incident gastric cancer across the quintiles of the polygenic risk score (ptrend<0·0001). Compared with individuals who had a low genetic risk, those with an intermediate genetic risk (hazard ratio [HR] 1·54 [95% CI 1·22-1·94], p=2·67 × 10-4) and a high genetic risk (2·08 [1·61-2·69], p<0·0001) had a greater risk of gastric cancer. A similar increase in the relative risk of incident gastric cancer was observed across the lifestyle categories (ptrend<0·0001), with a higher risk of gastric cancer in those with an unfavourable lifestyle than those with a favourable lifestyle (2·03 [1·46-2·83], p<0·0001). Participants with a high genetic risk and a favourable lifestyle had a lower risk of gastric cancer than those with a high genetic risk and an unfavourable lifestyle (0·53 [0·29-0·99], p=0·048), with an absolute risk reduction of 1·12% (95% CI 0·62-1·56). INTERPRETATION: Chinese individuals at an increased risk of incident gastric cancer could be identified by use of our newly developed polygenic risk score. Compared with individuals at a high genetic risk who adopt an unhealthy lifestyle, those who adopt a healthy lifestyle could substantially reduce their risk of incident gastric cancer. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, 333 High-Level Talents Cultivation Project of Jiangsu Province, and China Postdoctoral Science Foundation.


Assuntos
Predisposição Genética para Doença/genética , Estilo de Vida Saudável , Neoplasias Gástricas/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Feminino , Seguimentos , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/psicologia , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/psicologia
12.
Neural Plast ; 2020: 8882207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082780

RESUMO

The current study is aimed at establishing links between brain network examination and neural plasticity studies measured by optical neuroimaging. Sixteen healthy subjects were recruited from the University of Macau to test the Granger Prediction Estimation (GPE) method to investigate brain network connectivity during figurative language comprehension. The method is aimed at mapping significant causal relationships across language brain networks, captured by functional near-infrared spectroscopy measurements (fNIRS): (i) definition of regions of interest (ROIs) based on significant channels extracted from spatial activation maps; (ii) inspection of significant causal relationships in temporal resolution, exploring the experimental task agreement; and (iii) early identification of stronger causal relationships that guide neuromodulation intervention, targeting impaired connectivity pathways. Our results propose top-down mechanisms responsible for perceptive-attention engagement in the left anterior frontal cortex and bottom-up mechanism in the right hemispheres during the semantic integration of figurative language. Moreover, the interhemispheric directional flow suggests a right hemisphere engagement in decoding unfamiliar literal sentences and fine-grained integration guided by the left hemisphere to reduce ambiguity in meaningless words. Finally, bottom-up mechanisms seem activated by logographic-semantic processing in literal meanings and memory storage centres in meaningless comprehension. To sum up, our main findings reveal that the Granger Prediction Estimation (GPE) integrated strategy proposes an effective link between assessment and intervention, capable of enhancing the efficiency of the treatment in language disorders and reducing the neuromodulation side effects.

13.
J Cancer ; 11(23): 6850-6860, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123276

RESUMO

Chemotherapy resistance remains a blockade for successful treatment and longer overall survival of patients with epithelial ovarian cancer (EOC). CTNNBIP1 is an inhibitor of ß-catenin that is a chemotherapeutic target for EOC treatment. In the present study, we investigated associations between single nucleotide polymorphisms (SNPs) of CTNNBIP1 and platinum treatment response of Han Chinese EOC patients and subsequently performed functional prediction and validation of the resultant SNPs. We found that CTNNBIP1 rs935072 AT/TT variant genotypes were associated with platinum treatment response in the multivariate logistic regression analysis of EOC patients. Specifically, the CTNNBIP1 rs935072 AT/TT genotypes were associated with a decreased risk of developing chemoresistance ([adjusted odds ratio (OR)] = 0.89, 95% confidence interval (CI) = 0.82-0.97 and P=0.010), compared with the AA genotype. Further experiments showed that the underlying mechanism for the CTNNBIP1 rs935072 A>T change in chemotherapy treatment response resulted from a lower binding affinity of miR-27a-3p, thereby leading to up-regulation of the CTNNBIP1 expression. We further found that overexpression of CTNNBIP1 sensitized ovarian cancer cells to platinum treatment. Thus, the present study provides evidence that functional variants of CTNNBIP1 may regulate the expression of CTNNBIP1, a possible mechanism affecting platinum treatment response of EOC patients.

14.
J Psychiatr Res ; 131: 60-68, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32937251

RESUMO

BACKGROUND: The human brain activity is inherently dynamic over time. Conventional neuroimaging studies have reported abnormalities of static intrinsic brain activity or connectivity in adolescent patients with conduct disorder (CD). Little is known, however, regarding the temporal dynamics alterations of brain activity in CD. METHODS: In this study, resting-state functional magnetic resonance imaging examinations were performed on adolescent patients with pure CD and age-matched typically developing (TD) controls. The dynamic amplitude of low-frequency fluctuation (dALFF) was first measured using a sliding-window method. The temporal variability (TV) was then quantified as the variance of dALFF over time and compared between the two groups. Further, the relationships between aberrant TV of dALFF and clinical features were evaluated. RESULTS: CD patients showed reduced brain dynamics (less temporal variability) in the default-mode network, frontal-limbic cortices, sensorimotor areas, and visual regions which are involved in cognitive, emotional and perceptional processes. Importantly, receiver operating characteristic curve analysis revealed that regions with altered TV of dALFF exhibited a better ability to distinguish CD patients than the results from static ALFF in the current data set. CONCLUSIONS: Our findings extended previous work by providing a novel perspective on the neural mechanisms underlying adolescent patients with CD and demonstrated that the altered dynamic local brain activity may be a potential biomarker for CD diagnosis.

15.
Cancer Med ; 9(19): 7310-7316, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32777176

RESUMO

Genome-wide association studies (GWAS) have identified some single nucleotide polymorphisms (SNPs) associated with the risk of gastric cancer (GCa). However, currently, there is no published predictive model to assess the risk of GCa. In the present study, risk-associated SNPs derived from GWAS and large meta-analyses were selected to construct a predictive model to assess the risk of GCa. A total of 1115 GCa cases and 1172 controls from the eastern Chinese population were included. Logistic regression models were used to identify SNPs that correlated with the risk of GCa. A predictive model to assess the risk of GCa was established by receiver operating characteristic curve analysis. Multifactor dimensionality reduction (MDR) and classification and regression tree (CART) were applied to calculate the effect of high-order gene-environment interactions on risk of the cancer. A total of 42 SNPs were selected for further analysis. The results revealed that ASH1L rs80142782, PKLR rs3762272, PRKAA1 rs13361707, MUC1 rs4072037, PSCA rs2294008, and PLCE1 rs2274223 polymorphisms were associated with a risk of GCa. The area under curve considering both genetic factors and BMI was 3.10% higher than that of BMI alone. MDR analysis revealed that rs13361707 and rs4072307 variants and BMI had interaction effects on susceptibility to GCa, with the highest predictive accuracy (61.23%) and cross-validation consistency (100/100). CART analysis also supported this interaction model that non-overweight status and a six SNP panel could synergistically increase the susceptibility to GCa. The six SNP panel for predicting the risk of GCa may provide new tools for prevention of the cancer based on GWAS and large meta-analyses derived genetic variants.

16.
Carcinogenesis ; 41(9): 1229-1237, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32663249

RESUMO

Acquired platinum resistance impedes successful treatment of epithelial ovarian cancer (EOC), and this resistance may be associated with inherited DNA damage-repair response. In the present study, we performed a two-phase analysis to assess associations between 8191 single-nucleotide polymorphisms within 127 genes of nucleotide excision repair pathway from a genome-wide association study dataset and platinum treatment response in 803 Han Chinese EOC patients. As a result, we identified that platinum-based chemotherapeutic response was associated with two potentially functional variants MNAT1 rs2284704 T>C [TC + CC versus TT, adjusted odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.83-0.95 and P = 0.0005] and HUS1B rs61748571 A>G (AG + GG versus AA, OR = 1.10, 95% CI = 1.03-1.18 and P = 0.005). Compared with the prediction model for clinical factors only, models incorporating HUS1B rs61748571 [area under the curve (AUC) 0.652 versus 0.672, P = 0.026] and the number of unfavorable genotypes (AUC 0.652 versus 0.668, P = 0.040) demonstrated a significant increase in the AUC. Further expression quantitative trait loci analysis suggested that MNAT1 rs2284704 T>C significantly influenced mRNA expression levels of MNAT1 (P = 0.003). These results indicated that MNAT1 rs2284704 T>C and HUS1B rs61748571 A>G may serve as potential biomarkers for predicting platinum treatment response of Chinese EOC patients, once validated by further functional studies.

17.
Brain Imaging Behav ; 2020 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-32623563

RESUMO

Conduct disorder (CD) is a common psychiatric disorder defined by a repetitive and persistent pattern of aggressive and antisocial behaviors. Although numerous task-based and resting-state functional magnetic resonance imaging (rsfMRI) studies have emphasized the disrupted functional connectivity in CD, the CD-related alterations in functional interactions between the bilateral cerebral hemispheres are rarely investigated directly. In this study, a voxel-mirrored homotopic connectivity (VMHC) method based on rsfMRI was employed for the first time to examine the abnormalities of interhemispheric functional connectivity in patients with CD. The VMHC was compared between eighteen pure CD patients and eighteen typically developing (TD) healthy controls. In CD patients, reduced homotopic connectivity was observed relative to TDs in the middle occipital gyrus (MOG), pre- and postcentral gyrus, rolandic operculum and paracentral lobe (PCL) which were the components of visual and motor networks. Furthermore, the VMHC of the MOG and PCL was found to be negatively correlated with clinical scores in the CD group. Moreover, the regions with altered VMHC exhibited a relative good and robust ability to discriminate CD patients from TDs. This study provided a novel angle to identify the important role of interhemispheric coordination in the pathophysiology underlying CD and further indicated that the aberrant homotopic connectivity could be a potential clinical neural marker for CD diagnosis.

18.
Sci Rep ; 10(1): 11573, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32665670

RESUMO

miRNAs play an indispensable role in human carcinogenesis. Dysregulated miR-1180-3p has been observed in several types of cancer, including hepatocellular carcinoma (HCC). This study intends to correlate the expression level of miR-1180-3p with clinical features and overall survival in HCC patients. The expression and clinical significance of miR-1180-3p, selected from GEO and TCGA databases, were verified using an RT-qPCR method. The target genes of miR-1180-3p were obtained using 3 miRNA target gene prediction databases, and their functions were analyzed using the online tool WebGestalt. miR-1180-3p expression was significantly upregulated in 88 HCC tissues compared with non-tumor liver tissues (0.004 ± 0.009 vs. 0.002 ± 0.002, t = - 2.099, P = 0.038). Additionally, we found that the expression levels of miR-1180-3p were significantly correlated with tumor number (χ2 = 9.157, P = 0.006) and MVI (χ2 = 11.354, P = 0.003). Based on Kaplan-Meier analysis, patients with high miR-1180 expression had a shorter overall survival than those with low miR-1180-3p expression (P = 0.002). Furthermore, multivariate Cox analyses indicated that miR-1180-3p expression was an independent prognostic factor for overall survival (HR = 13.36, 95% CI 1.16, 153.69, P = 0.038). In addition, a total of 733 target genes of miR-1180-3p were found from three prediction databases. The GO analyses demonstrated that the target genes were closely related to the proliferation and malignancy of tumors. The KEGG analysis showed that target genes were enriched in several key cancer-related signaling pathways, including the Pathways in cancer, the Ras signaling pathway, and the MAPK signaling pathway. In conclusion, we demonstrate that miR-1180-3p is upregulated in HCC and is associated with a poor prognosis. Thus, miR-1180-3p might be useful as a prognostic marker for HCC.

19.
Carcinogenesis ; 41(9): 1203-1212, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32614429

RESUMO

Human leukocyte antigen (HLA) is highly polymorphic, driving antigen presentation, complement cascade and leukocyte maturation against cancer cells. Therefore, we extracted genotyping data in the HLA region from an ongoing Chinese genome-wide association study of non-small cell lung cancer (NSCLC). Using deep sequencing data of 10 689 healthy Han Chinese, we imputed for untyped genetic variants in the HLA region, followed by a two-stage survival analysis of 1531 NSCLC patients. In the discovery stage of 758 patients, we identified 301 out of 15 138 single-nucleotide polymorphisms to be independently associated with overall survival [P < 0.05 and Bayesian false-discovery probability < 0.8]. In further validation of another 773 patients, we confirmed chromosome 6p21, rs241424 (located at intron 3 of TAP2) and rs6457642 as two independent survival predictors. In the combined analysis of 1531 NSCLC patients, rs241424 G>A and rs6457642 C>T were associated with a hazards ratio of 1.26 [95% confidence interval (CI) = 1.14-1.40 and P = 4.04 × 10-6] and 0.76 (95% CI = 0.66-0.87 and P = 1.16 × 10-4), respectively. The analysis of publically available ChIP-sequencing and Hi-C data found that the rs241424 locus was involved in potential cis-regulatory element by a long-range interaction with the HLA-DQA1 promoter. Additional expression quantitative trait loci analysis showed that the rs241424 G>A change decreased HLA-DQA1 mRNA expression. Furthermore, expression levels of HLA-DQA1 were lower in lung cancer tissues than in adjacent normal tissues, and the lower expression was associated with a worse prognosis for patients with lung adenocarcinoma. Collectively, HLA genetic variants may modulate OS of NSCLC patients, possibly via a mechanism of long-range promoter interaction regulating HLA-DQA1 expression.

20.
Ann Transl Med ; 8(7): 484, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32395528

RESUMO

Background: Although microsatellite instability (MSI) is a powerful predictive biomarker for the efficacy of immunotherapy, the mechanism of MSI in sporadic gastrointestinal cancer is not fully understood. However, epigenetics, particularly microRNAs, has been suggested as one of the main regulators that contribute to the MSI formation. Methods: We used microRNA expression data of 386 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) database to identify differential microRNA expression profiles by different MSI status. We also obtained putative common target genes of the top differential microRNAs with miRanda online tools, and we analyzed these data by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment (KEGG). Results: We found that 56 and 67 gastric adenocarcinoma samples were positive for low and high MSI, respectively, and that a high MSI status was associated with age, sex and subregion (P=0.049, 0.014 and 0.007, respectively). In the 67 samples with a high MSI status, expression levels of 14 microRNAs were upregulated but five microRNAs were downregulated as assessed by the fold change (FC), compared with that of the 56 samples with a low MSI status (P<0.05, |FC| >2). Further analysis suggested that the expression of miR-210-3p, miR-582-3p, miR-30a-3p and miR-105-5p predicted a high MSI status (P=4.93×10-10, 5.63×10-10, 3.23×10-9 and 7.64×10-4, respectively). Regulation of the transcription pathways ranked the top of lists from both GO and KEGG analyses, and these microRNAs might regulate DNA damage-repair genes that were also associated with a high MSI status. Conclusions: MiR-30a-3p and miR-105-5p are potential biomarkers for the MSI-H gastric adenocarcinoma, possibly by altering expression of DNA damage-repair genes.

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