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1.
IEEE Trans Cybern ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32413946

RESUMO

Canonical correlation analysis (CCA) is a typical statistical model used to analyze the correlation components between different view representations of the same objects. When the label information is available with the data representations, CCA can be extended to its discriminative counterparts by incorporating supervision in the analysis. Although most discriminative variants of CCA have achieved improved results, nearly all of their objective functions are nonconvex, implying that optimal solutions are difficult to obtain. More important, that cross-view representations from the same sample should be consistent, that is, the cross-view semantic consistency has however not been modeled. To overcome these drawbacks, in this article, we propose a discriminant semantic correlation analysis (DSCA) model by modeling the cross-view semantic consistency for each object in the sample space rather than in the commonly used feature space. To boost the nonlinear discriminating capability of DSCA, we extend it from the Euclidean to the geodesic space by transforming the metric and incorporating both the cross-view semantic and representation correlation information and consequently obtain our final model with convex objective, namely, convex DSCA (C-DSCA). Finally, with extensive experiments and comparisons, we validate the effectiveness and superiority of the proposed method.

2.
J Cell Mol Med ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32364678

RESUMO

Acidosis, a common feature of cerebral ischaemia and hypoxia, plays a key role in these pathological processes by aggravating the ischaemic and hypoxic injuries. To explore the mechanisms, in this research, we cultured primary neurons in an acidic environment (potential of hydrogen [pH]6.2, 24 hours) to mimic the acidosis. By proteomic analysis, 69 differentially expressed proteins in the acidic neurons were found, mainly related to stress and cell death, synaptic plasticity and gene transcription. And, the acidotic neurons developed obvious alterations including increased neuronal death, reduced dendritic length and complexity, reduced synaptic proteins, tau hyperphosphorylation, endoplasmic reticulum (ER) stress activation, abnormal lysosome-related signals, imbalanced oxidative stress/anti-oxidative stress and decreased Golgi matrix proteins. Then, melatonin (1 × 10-4  mol/L) was used to pre-treat the cultured primary neurons before acidic treatment (pH6.2). The results showed that melatonin partially reversed the acidosis-induced neuronal death, abnormal dendritic complexity, reductions of synaptic proteins, tau hyperphosphorylation and imbalance of kinase/phosphatase. In addition, acidosis related the activations of glycogen synthase kinase-3ß and nuclear factor-κB signals, ER stress and Golgi stress, and the abnormal autophagy-lysosome signals were completely reversed by melatonin. These data indicate that melatonin is beneficial for neurons against acidosis-induced injuries.

3.
Br J Nutr ; : 1-29, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32378502

RESUMO

The effects of macronutrient intake on obesity are controversial. This research aims to investigate the associations between macronutrient intake and new-onset overweight/obesity. The relationship between the consumption of carbohydrate and total fat and obesity was assessed by the multivariable Cox model in this 11-year cohort, which included 6,612 adults (3,321 women and 3,291 men) who were free of overweight and obesity at baseline. The dietary intake was recorded using a 24-h recall method for three consecutive days. Moreover, substitution models were developed to distinguish the effects of macronutrient composition alteration from energy intake modification. During 7.5 person years (IQR 4.3-10.8) of follow-up, 1,807 participants became overweight or obesity. After adjusting for risk factors, the HR of overweight/obesity in extreme quintiles of fat was 1.48 (quintile 5 vs quintile 1, 95% CI, 1.16-1.89; Ptrend =0.02) in women. Additionally, replacing 5% of energy from carbohydrate with equivalent energy from fat was associated with an estimated 4.3% (HR, 1.043; 95% CI, 1.007-1.081) increase in overweight/obesity in women. Moreover, dietary carbohydrate was inversely associated with overweight/obesity (quintile 5 vs quintile 1, HR, 0.70; 95% CI, 0.55-0.89; Ptrend =0.02) in women. Total fat was related to a higher risk of overweight/obesity, whereas high carbohydrate intake was related to a lower risk of overweight/obesity in women, which was not observed in men.

4.
Am J Trop Med Hyg ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32431274

RESUMO

Adequate dietary intake is critically important for child growth and development. This study aimed to analyze the prevalence of undernutrition and its association with infant and child feeding index (ICFI). This cross-sectional study was conducted among children (younger than5 years) and their mothers from Lhaviyani Atoll, Maldives. The data were obtained by interviewing the children's mothers via pretested questionnaires. Infant and child feeding index scores were calculated from the dietary information. Weight-for-age z-scores (WAZ), length/height-for-age z-scores (LAZ/HAZ), and weight-for-length/height z-scores were calculated from anthropometric data taken according to the WHO criterion. Linear regression tests were used to find the association of nutritional status with ICFI scores. A total of 800 children and their mothers participated in this study. The prevalence of underweight, stunting, and wasting was 24.6%, 32.4%, and 16.3%, respectively. The mean ICFI scores (13.0) of children aged 6-8 months were better than those of children in other age-groups. In food groups, the intake of fish was higher among the respondents, whereas the consumption of vegetables and fruits was lower. Infant and child feeding index scores were significantly associated (P < 0.05) with WAZ and LAZ/HAZ after adjustment for confounders. Overall, the findings showed that Maldivian children consumed the limited number of food items that resulted in an inadequate intake of nutrients which further resulted in the high prevalence of malnutrition.

5.
Ren Fail ; 42(1): 350-357, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32338107

RESUMO

Background: Nephrotoxicity, especially acute kidney injury (AKI), is the main dose-limiting toxicity of cisplatin. Although recent studies showed that curcumin prevented cisplatin-induced AKI effectively, further studies to understand the mechanism are required.Methods: We established an AKI mouse model. Male C57BL/6 mice were assigned to three groups: saline group (control), cisplatin group (CP), and curcumin + cisplatin group (CP + Cur). The CP group received a single intraperitoneal (i.p.) injection of cisplatin, while the control group received saline. The CP + Cur group received i.p. curcumin three days before cisplatin injection and curcumin administered for another three days until the day before euthanization. Renal injury was assessed by serological and histological analysis. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the phosphatase and tensin homolog (PTEN), and microRNA (miR)-181a expression in the renal tissues. Bioinformatics prediction and western blotting methods validated the targets of miR-181a in vitro.Results: Curcumin treatment alleviated cisplatin-induced nephrotoxicity as validated by the blood urea nitrogen (BUN) values, and histological analysis of kidneys. At the molecular level, curcumin treatment decreased miR-181a expression level, which was induced by cisplatin and restored the in vivo expression of PTEN, which was suppressed by cisplatin. We verified the direct regulation of PTEN by miR-181a in cultured human embryonic kidney 293T cells.Conclusions: We showed the involvement of miR-181a/PTEN axis in the renoprotective effect of curcumin against cisplatin-induced AKI, and provide new evidence on the ability of curcumin to alleviate cisplatin-induced nephrotoxicity.

6.
Psychother Psychosom ; : 1-9, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32272480

RESUMO

OBJECTIVE: We explored whether medical health workers had more psychosocial problems than nonmedical health workers during the COVID-19 outbreak. METHODS: An online survey was run from February 19 to March 6, 2020; a total of 2,182 Chinese subjects participated. Mental health variables were assessed via the Insomnia Severity Index (ISI), the Symptom Check List-revised (SCL-90-R), and the Patient Health Questionnaire-4 (PHQ-4), which included a 2-item anxiety scale and a 2-item depression scale (PHQ-2). RESULTS: Compared with nonmedical health workers (n = 1,255), medical health workers (n = 927) had a higher prevalence of insomnia (38.4 vs. 30.5%, p < 0.01), anxiety (13.0 vs. 8.5%, p < 0.01), depression (12.2 vs. 9.5%; p< 0.04), somatization (1.6 vs. 0.4%; p < 0.01), and obsessive-compulsive symptoms (5.3 vs. 2.2%; p < 0.01). They also had higher total scores of ISI, GAD-2, PHQ-2, and SCL-90-R obsessive-compulsive symptoms (p ≤ 0.01). Among medical health workers, having organic disease was an independent factor for insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms (p < 0.05 or 0.01). Living in rural areas, being female, and being at risk of contact with COVID-19 patients were the most common risk factors for insomnia, anxiety, obsessive-compulsive symptoms, and depression (p < 0.01 or 0.05). Among nonmedical health workers, having organic disease was a risk factor for insomnia, depression, and obsessive-compulsive symptoms (p < 0.01 or 0.05). CONCLUSIONS: During the COVID-19 outbreak, medical health workers had psychosocial problems and risk factors for developing them. They were in need of attention and recovery programs.

7.
Cell Cycle ; : 1-10, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32324084

RESUMO

Ring1 and Yin Yang 1-Binding Protein (RYBP) is a member of non-canonical polycomb repressive complex 1 to mediate monoubiquitination of histone H2A at lysine 119. It plays an important role in development, but its role in reproduction remains illusive. In this study, we used Rybp conditional knockout mouse model to genetically ablate Rybp in male germ cells. We found that Rybp deficiency during spermatogenesis led to smaller testes, loss of germline cells, disturbed meiosis, increased apoptosis of spermatocytes, decreased sperm motility, and reduced global H3K9me3, without impacting retrotransposon expression. Meanwhile, we depleted Rybp during oogenesis, but oocyte maturation and preimplantation development were normal. Our findings demonstrate that RYBP plays important roles in spermatogenesis through regulating meiosis and sperm motility.

8.
Schizophr Res ; 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32265087

RESUMO

Alteration of visual scanpaths under emotional facial expression in schizophrenia patients has been described in recent years; however, it is not clear whether such results are different when they transfer to faces in natural social scenes. The present study was designed to investigate the effects of emotional faces in natural social scenes on the gaze patterns of patients with schizophrenia, compared to gaze at isolated faces. A novel theme identification task was used where participants selected a positive, neutral or negative word to describe an emotional picture. Participants were 29 patients with schizophrenia and 31 healthy controls. The Positive and Negative Syndrome Scale (PANSS) and the Scale of Social Function in Psychosis Inpatients (SSPI) were used to assess symptoms and social functioning. In total, patients with schizophrenia showed significantly fewer fixations, saccades numbers and decreased fixations in areas of interest. As expected, patients showed shorter scanpath length, but only in the pictures with social settings. Furthermore, the effect size of scanpaths parameters under social scene was all greater than isolated face. In addition, patients compared to controls showed more abnormal scanpath parameters processing negative and neutral faces than positive faces, especially in social scene. The present study suggests that scanpath length for social scene faces may be more sensitive than for isolated face pictures. Our findings further support restricted scanpath whilst recognizing emotional facial expressions in natural social scenes as a favorable topic for further investigation as a trait marker.

9.
Oxid Med Cell Longev ; 2020: 3894309, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273941

RESUMO

The aim of this study was to investigate the mechanisms underlying the reduced milk production during mastitis. We hypothesized that bacterial endotoxin induces hypoxia, oxidative stress, and cell apoptosis while inhibiting milk gene expression in the mammary gland. To test this hypothesis, the left and right sides of the 4th pair of mouse mammary glands were alternatively injected with either lipopolysaccharide (LPS, E. coli 055: B5, 100 µL of 0.2 mg/mL) or sterile PBS through the teat meatus 3 days postpartum. At 10.5 and 22.5 h postinjection, pimonidazole HCl, a hypoxyprobe, was injected intraperitoneally. At 12 or 24 h after the LPS injection, the 4th glands were individually collected (n = 8) and analyzed. LPS treatment induced mammary inflammation at both 12 and 24 h but promoted cell apoptosis only at 12 h. Consistently, H2O2 content was increased at 12 h (P < 0.01), but dropped dramatically at 24 h (P < 0.01) in the LPS-treated gland. Nevertheless, the total antioxidative capacity in tissue tended to be decreased by LPS at both 12 and 24 h (P = 0.07 and 0.06, respectively). In agreement with these findings, LPS increased or tended to increase the mRNA expression of antioxidative genes Nqo1 at 12 h (P = 0.05) and SLC7A11 at 24 h (P = 0.08). In addition, LPS inhibited mammary expression of Csn2 and Lalba across time and protein expression of Csn1s1 at 24 h (P < 0.05). Furthermore, hypoxyprobe staining intensity was greater in the alveoli of the PBS-treated gland than the LPS-treated gland at both 12 and 24 h, demonstrating a rise in oxygen tension by LPS treatment. In summary, our observations indicated that while intramammary LPS challenge incurs inflammation, it induces oxidative stress, increases cell apoptosis and oxygen tension, and differentially inhibits the milk protein expression in the mammary gland.

10.
J Epidemiol ; 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32224596

RESUMO

BACKGROUND: The diagnosis of hypertension should be based on the mean of two or more properly measured BP readings on each of two visits for clinical practice, but one-visit strategy was applied in most epidemiological surveys. The impact of hypertension definition based on two visits on estimates of hypertension burden is unknown. This study aims to assess the impact of hypertension diagnosis based on a two-visit strategy for estimating hypertension burden in China. METHODS: The one-visit and two-visit strategies were applied to investigate the incidence of hypertension in a cohort study based on the China Health and Nutrition Survey (CHNS) 1989-2011. Additionally the prevalence of hypertension was investigated in a cross-sectional study based on the CHNS 2006-2009/2011 and the hypertension burden in China was estimated with data from the 2012-2015 China hypertension survey. RESULTS: Overall, the age-adjusted incidence of hypertension based on the two-visit strategy (1.82%; 95% confidence interval [Cl] = 1.74%, 1.90%) was 62.1% lower than estimation based on the one-visit strategy (4.80%; 95% Cl = 4.68%, 4.93%). Similar results were found in the prevalence of hypertension (the one-visit: 18.13% [17.34, 18.92]; the two-visit: 9.47% [8.87, 10.07]). When the two-visit strategy was applied to the 2012-2015 China hypertension survey, the hypertension burden was predicted to be overestimated by 25.5%-47.8% (based on JNC 7) and 23.5%-48.2% (based on the 2017 ACC/AHA). CONCLUSION: The hypertension burden would decrease from 244.5 million persons to 127.5-182.3 million persons in China if the two-visit strategy was applied.

11.
Hum Genet ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239398

RESUMO

Aiming to uncover a shared genetic basis of abdominal obesity and osteoporosis, we performed a bivariate GWAS meta-analysis of femoral neck BMD (FNK-BMD) and trunk fat mass adjusted by trunk lean mass (TFMadj) in 11,496 subjects from 6 samples, followed by in silico replication in the large-scale UK Biobank (UKB) cohort. A series of functional investigations were conducted on the identified variants. Bivariate GWAS meta-analysis identified two novel pleiotropic loci 12q15 (lead SNP rs73134637, p = 3.45 × 10-7) and 10p14 (lead SNP rs2892347, p = 2.63 × 10-7) that were suggestively associated and that were replicated in the analyses of related traits in the UKB sample (osteoporosis p = 0.06 and 0.02, BMI p = 0.03 and 4.61 × 10-3, N up to 499,520). Cis-eQTL analysis demonstrated that allele C at rs73134637 was positively associated with IFNG expression in whole blood (N = 369, p = 0.04), and allele A at rs11254759 (10p14, p = 9.49 × 10-7) was negatively associated with PRKCQ expression in visceral adipose tissue (N = 313, p = 0.04) and in lymphocytes (N = 117, p = 0.03). As a proof-of-principle experiment, the function of rs11254759, which is 235 kb 5'-upstream from PRKCQ gene, was investigated by the dual-luciferase reporter assay, which clearly showed that the haplotype carrying rs11254759 regulated PRKCQ expression by upregulating PRKCQ promoter activity (p = 4.60 × 10-7) in an allelic specific manner. Mouse model analysis showed that heterozygous PRKCQ deficient mice presented decreased fat mass compared to wild-type control mice (p = 3.30 × 10-3). Mendelian randomization analysis demonstrated that both FNK-BMD and TFMadj were causally associated with fracture risk (p = 1.26 × 10-23 and 1.18 × 10-11). Our findings may provide useful insights into the genetic association between osteoporosis and abdominal obesity.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32340945

RESUMO

Building assessment is highly prioritized during rescue operations and damage relief after hurricane disasters. Although machine learning has made remarkable improvement in building damage classification, it remains challenging because classifiers must be trained using a massive amount of labeled data. Furthermore, data labeling is labor intensive, costly, and unavailable after a disaster. To address this issue, we propose an unsupervised domain adaptation method with aligned discriminative and representative features (ADRF), which leverage a substantial amount of labeled data of relevant disaster scenes for new classification tasks. The remote sensing imageries of different disasters are collected using different sensors, viewpoints, times, even at various places. Compared with the public datasets used in the domain adaptation community, the remote sensing imageries are more complicated which exhibit characteristics of lower discrimination between categories and higher diversity within categories. As a result, pursuing domain invariance is a huge challenge. To achieve this goal, we build a framework with ADRF to improve the discriminative and representative capability of the extracted features to facilitate the classification task. The ADRF framework consists of three pipelines: a classifier for the labeled data of the source domain and one autoencoder each for the source and target domains. The latent variables of autoencoders are forced to observe unit Gaussian distributions by minimizing the maximum mean discrepancy (MMD), whereas the marginal distributions of both domains are aligned via the MMD. As a case study, two challenging transfer tasks using the hurricane Sandy, Maria, and Irma datasets are investigated. Experimental results demonstrate that ADRF achieves overall accuracy of 71.6% and 84.1% in the transfer tasks from dataset Sandy to dataset Maria and dataset Irma, respectively.

13.
J Ethnopharmacol ; 257: 112871, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32325182

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sinomenii Caulis (SC) is a well-konwn traditional Chinese medicine used for treatment of rheumatoid arthritis (RA), dermatophytosis and paralysis. Patients with RA are usually secondary to osteoporosis, but the potential protective effect of SC on osteoporosis (OP) is seldom reported and its possible action mechanism is little known. AIM: The purpose of this study was to demonstrate the anti-osteoporosis effects of SC extract and alkaloids in prednisolone (Pre)-induced OP of zebrafish, and then to explore the potential mechanism of SC on system level by network pharmacology. METHODS: Firstly, zebrafish OP model was established to investigate the anti-osteoporosis effect of SC. Secondly, the targets of SC and OP from multiple databases were collected, and Compound-Target-Pathway network based on protein-protein interaction (PPI) was constructed. Moreover, gene enrichment and annotation were performed via the DAVID server. Finally, the reliability of the network pharmacology prediction results in Pre-induced OP of zebrafish was verified by qRT-PCR. RESULTS: The results indicated that SC extract and alkaloids have remarkable ability to promote bone formation of cranial bones and reduce TRAP contents in Pre-induced OP of zebrafish. 32 OP-related ingredients in SC and 77 OP-related targets were screened from multiple databases, and 15 OP-related pathways were enriched by the KEGG database. Further experimental validation indicated that SC extract and alkaloids could regulate the expression of MAPK14, CASP3, CXCL8, IL-1ß, IL6, PTGS2, TNF-α, ESR1, and MMP9 for treatment of OP. CONCLUSION: In summary, we conducted an integrative analysis to provide convincing evidence that SC may partially alleviate OP by inhibiting pro-inflammatory cytokines and regulating of RANK/RANKL/OPG system.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32203034

RESUMO

Although the least-squares regression (LSR) has achieved great success in regression tasks, its discriminating ability is limited since the margins between classes are not specially preserved. To mitigate this issue, dragging techniques have been introduced to remodel the regression targets of LSR. Such variants have gained certain performance improvement, but their generalization ability is still unsatisfactory when handling real data. This is because structure-related information, which is typically contained in the data, is not exploited. To overcome this shortcoming, in this article, we construct a multioutput regression model by exploiting the intraclass correlations and input-output relationships via a structure matrix. We also discriminatively enlarge the regression margins by embedding a metric that is guided automatically by the training data. To better handle such structured data with ordinal labels, we encode the model output as cumulative attributes and, hence, obtain our proposed model, termed structure-exploiting discriminative ordinal multioutput regression (SEDOMOR). In addition, to further enhance its distinguishing ability, we extend the SEDOMOR to its nonlinear counterparts with kernel functions and deep architectures. We also derive the corresponding optimization algorithms for solving these models and prove their convergence. Finally, extensive experiments have testified the effectiveness and superiority of the proposed methods.

15.
Acta Diabetol ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32206903

RESUMO

AIMS: This study aimed to compare the efficacy and safety of generic exenatide with branded exenatide Byetta® in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues. METHODS: A multicenter, randomized, controlled, non-inferiority trial was performed. A total of 240 patients with T2DM and glycated hemoglobin (HbA1c) ≥ 7% (53 mmol/mol) to ≤ 9.0% (75 mmol/mol) on monotherapy or combination therapy of metformin and insulin secretagogues for at least 3 months were randomized into generic exenatide or branded exenatide groups with a 1:1 ratio for 16 weeks of treatment. The primary endpoint was the change in HbA1c levels from baseline at week 16, with a non-inferiority margin of - 0.35% (- 3.83 mmol/mol) (lower bound of one-sided 95% confidence interval (CI) > - 0.35% (- 3.83 mmol/mol)). Secondary endpoints included the proportion of participants achieving HbA1c < 7% (53 mmol/mol), the changes in fasting plasma glucose (FPG), 2-h postprandial glucose (2hPG) following a standard meal, 7-point self-monitoring blood glucose (SMBG) profiles, body weight change from baseline at week 16 and the change in HbA1c levels from baseline at week 8. Safety issues were also evaluated. RESULTS: After 16 weeks of treatment, HbA1c levels decreased significantly from baseline in the two groups, with a reduction of - 1.10% ± 1.31% (- 12.0 mmol/mol ± 14.3 mmol/mol) in the generic exenatide group and - 1.08% ± 1.11% (- 11.8 mmol/mol ± 12.1 mmol/mol) in the branded exenatide group (both P < 0.001). The least-squares mean difference of HbA1c reduction between the two groups was - 0.03% (- 0.33 mmol/mol), with a lower one-sided 95% CI limit of - 0.27% (- 2.95 mmol/mol), which was higher than the prespecified non-inferiority margin of - 0.35% (- 3.83 mmol/mol). Moreover, there were no significant differences in the proportion of participants achieving HbA1c < 7% (53 mmol/mol) and the changes in FPG, 2hPG, 7-point SMBG profiles and body weight at week 16 and the change in HbA1c levels from baseline at week 8 (all P > 0.05) between the two groups. The incidence of adverse events, including the incidence of hypoglycemia (18.3% and 17.5%, respectively), was similar for the generic and branded exenatide groups (P > 0.05). CONCLUSIONS: In patients with T2DM inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues, add-on treatment with generic exenatide demonstrated non-inferiority to branded exenatide in terms of improvements in HbA1c after 16 weeks of treatment. Furthermore, the two drugs were also similar for other efficacy endpoints and safety profile. Trial registration Chinese Clinical Trial Registry: ChiCTR-IPR-15006558, Date registered May 27, 2015.

16.
Sci Rep ; 10(1): 4293, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152362

RESUMO

Whole body lean mass (WBLM) is a heritable trait predicting sarcopenia. To identify genomic locus underlying WBLM, we performed a genome-wide association study of fat-adjusted WBLM in the Framingham Heart Study (FHS, N = 6,004), and replicated in the Kansas City Osteoporosis Study (KCOS, N = 2,207). We identified a novel locus 3p27.1 that was associated with WBLM (lead SNP rs3732593 P = 7.19 × 10-8) in the discovery FHS sample, and the lead SNP was successfully replicated in the KCOS sample (one-sided P = 0.04). Bioinformatics analysis found that this SNP and its adjacent SNPs had the function of regulating enhancer activity in skeletal muscle myoblasts cells, further confirming the regulation of WBLM by this locus. Our finding provides new insight into the genetics of WBLM and enhance our understanding of sarcopenia.

17.
Sci Rep ; 10(1): 5057, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193455

RESUMO

Sarcopenia is characterized by low skeletal muscle, a complex trait with high heritability. With the dramatically increasing prevalence of obesity, obesity and sarcopenia occur simultaneously, a condition known as sarcopenic obesity. Fat mass and obesity-associated (FTO) gene is a candidate gene of obesity. To identify associations between lean mass and FTO gene, we performed a genome-wide association study (GWAS) of lean mass index (LMI) in 2207 unrelated Caucasian subjects and replicated major findings in two replication samples including 6,004 unrelated Caucasian and 38,292 unrelated Caucasian. We found 29 single nucleotide polymorphisms (SNPs) in FTO significantly associated with sarcopenia (combined p-values ranging from 5.92 × 10-12 to 1.69 × 10-9). Potential biological functions of SNPs were analyzed by HaploReg v4.1, RegulomeDB, GTEx, IMPC and STRING. Our results provide suggestive evidence that FTO gene is associated with lean mass.

18.
J Colloid Interface Sci ; 569: 235-243, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113021

RESUMO

Positively charged gold nanoclusters (AuNCs) hold great promises as novel nanoagents in many biomedical applications, but their controllable synthesis in a simple and efficient manner remains a challenge. In the present work, by using a commercial cationic ligand, (11-mercaptoundecyl) - N,N,N-trimethylammonium bromide (MUTAB), we demonstrated that water-soluble, positively charged AuNCs can be facilely synthesized in a one-step reaction. These MUTAB-AuNCs possess near-infrared luminescence, ultra-small size, good stability and biocompatibility as well as abundant positive charges in a wide pH range. Importantly, these positively charged MUTAB-AuNCs exhibit efficient antibacterial activity against both Gram-negative bacteria and Gram-positive bacteria without inducing drug-resistance, including multidrug-resistant (MDR) bacteria and clinical bacteria. The unique antibacterial mechanism of these positively charged AuNCs was also systematically investigated by different techniques, including surface plasmon resonance, scanning electron microscopy, fluorescence imaging, DNA leakage and reactive oxygen species (ROS) assays.

19.
J Ethnopharmacol ; 253: 112679, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32101773

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gardenia Fructus (GF), a traditional Chinese medicine for clearing heat and purging fire, has been reported to use to treat thrombotic related diseases, but the antithrombotic components are not clear. AIM OF THE STUDY: To develop efficient research methods for discovering some representative antithrombotic compounds of GF. MATERIALS AND METHODS: AB line zebrafish induced by arachidonic acid (AA) was used as a fast and trace-sample-required valuation model for antithrombptic effect of GF samples. Among nine samples of GF from different production areas, two samples with the largest difference in bioactivity were selected for downstream analysis. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF/MS) was applied to detect compounds in the GF samples. And herbal metabolomics and grey correlation analysis (GCA) were used to identify crucial compounds with potential antithrombotic activity. Then the bioactivity of those important compounds was verified on the zebrafish model. Network pharmacology was used to explore the protein targets and signaling pathways of these compounds. RESULTS: Among the GF samples, S1 (Huoshan City, Anhui Province), and S6 (Jichun City, Hubei Province), significantly differed in thrombus inhibiting bioactivity. HPLC-Q-TOF/MS identified a total of 614 compounds in each GF sample. 19 compounds were selected as important potential variables from metabolomics data by orthogonal partial least squares discriminant analysis (OPLS-DA). And 10 compounds among them were further found to be positively correlated with the antithrombotic bioactivity of GF by GCA. Finally, 3 compounds in them, geniposide, citric acid, and quinic acid, were confirmed as representative antithrombotic chemical markers of GF. Using network pharmacology analysis, some key protein targets, such as proto-oncogene tyrosine-protein kinase Src (SRC) and cyclin-dependent kinase 2 (CDK2), and some signaling pathways were found to supply powerful evidence about antithrombotic mechanisms of three compounds and GF. CONCLUSIONS: This research have succeeded to discover and identify three representative antithrombotic compounds of GF using an efficient integrated research strategy we established, an Omics Discriminant-Grey Correlation-Biological Activity strategy. The antithrombotic chemical makers we found could also contribute to provided more accurate index components for comprehensive quality control of GF.

20.
J Reprod Dev ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32051348

RESUMO

Changes in histone modifications always correlate with altered transcriptional activities of genes. Recent studies have shown that the mutation of certain lysine residues to methionine in the histone variant H3.3 can act as a valuable tool to reduce specific H3 methylation levels. In our study, we used the mouse spermatogenic cell line GC-2 as a model to generate cells stably expressing H3.3 K4, H3.3 K9, H3.3 K27, and H3.3 K36M. The expression of these H3.3 K-to-M mutants influenced the expression of different subsets of genes, and a total of 891 differentially expressed genes were identified through global gene expression profiling. Moreover, the H3.3 K-to-M transgenes, especially H3.3 K36M, impacted the expression of endogenous retrovirus ERVK. This study gives a global view of how different H3 modifications regulate transcriptomes in spermatogenic cell lines, and identifies potential targets of H3 modifications in male germ line.

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