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1.
Cell Commun Signal ; 18(1): 34, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32122386

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy and its mortality continues to rise globally. Because of its high heterogeneity and complex molecular landscapes, published gene signatures have demonstrated low specificity and robustness. Functional signatures containing a group of genes involved in similar biological functions may display a more robust performance. METHODS: The present study was designed to excavate potential functional signatures for PDAC by analyzing maximal number of datasets extracted from available databases with a recently developed method of FAIME (Functional Analysis of Individual Microarray Expression) in a comprehensive and integrated way. RESULTS: Eleven PDAC datasets were extracted from GEO, ICGC and TCGA databases. By systemically analyzing these datasets, we identified a robust functional signature of subpathway (path:00982_1), which belongs to the drug metabolism-cytochrome P450 pathway. The signature has displayed a more powerful and robust capacity in predicting prognosis, drug response and chemotherapeutic efficacy for PDAC, particularly for the classical subtype, in comparison with published gene signatures and clinically used TNM staging system. This signature was verified by meta-analyses and validated in available cell line and clinical datasets with chemotherapeutic efficacy. CONCLUSION: The present study has identified a novel functional PDAC signature, which has the potential to improve the current systems for predicting the prognosis and monitoring drug response, and to serve a linkage to therapeutic options for combating PDAC. However, the involvement of path:00982_1 subpathway in the metabolism of anti-PDAC chemotherapeutic drugs, particularly its biological interpretation, requires a further investigation. Video Abstract.

2.
Psychiatry Res ; 286: 112851, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32087448

RESUMO

To identify the genetic factors related to antipsychotic-induced QTc interval prolongation (AIQTIP), we analyzed the associations between single nucleotide polymorphisms (SNPs) of candidate genes and quantitative traits of AIQTIP in a Han Chinese population. In total, we collected 112 hospitalized patients suffered from schizophrenia meeting the entry criteria, including 34 first-episode drug-naïve patients (FENP). All patients were treated with a single atypical antipsychotic drug (AAPD) for 4 weeks. We analyzed the quantitative genetic association between 10 SNPs in 8 candidate genes and AIQTIP using PLINK software. After 4 weeks of treatment, QTc interval of all patients was significantly prolonged and QTc interval of female patients was significantly longer compared with baseline. Antipsychotics have different effects on the prolongation of QTc. Quetiapine had the most distinct effect on AIQTIP. In all subjects, we found a significant association between the EPB41L4A gene SNP rs7732687 and AIQTIP. In male patients, we also found a significant association between the EPB41L4A gene SNP rs7732687 and AIQTIP. In female patients, we found the LEP gene SNP rs7799039 was significantly associated with AIQTIP. Our results provide preliminary evidence to support the genetic role of EPB41L4A and LEP in AIQTIP.

3.
Stem Cell Res ; 44: 101722, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32097875

RESUMO

Hundreds of rare risk factors have been identified for ASD, however, the underlying causes for ~70% of sporadic cases are unknown. Sporadic ASD models are thus essential for validating phenotypic commonality and drug suitability to the majority of patients. Here, we derived induced pluripotent stem cells (iPSCs) from one sporadic ASD child and one paternal control, using non-integrating Sendai viral methods. The iPSCs strongly expressed pluripotency markers and could be differentiated into three germ layers. Their normal karyotype was validated by genome SNP array. The availability of sporadic ASD-derived iPSCs offers an opportunity for phenotypic comparison with genetic ASD models.

4.
FEBS Open Bio ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32069381

RESUMO

Astrocytomas often recur after surgical resection, but the underlying mechanism remains enigmatic. Elucidation of clonal evolution in primary and relapse tumors may provide important information on tumor progression. Here, we examined genetic factors underlying recurrence in a patient with astrocytoma initially diagnosed with World Health Organization (WHO) grade II astrocytoma, who then relapsed with glioblastoma (WHO grade IV) complicated with local anaplastic astrocytoma (WHO grade III). We performed genomic DNA sequencing and data analysis of paired tumor tissue specimens and a peripheral blood sample (control), and used expands software for subclone analysis. A germline NOTCH1 missense mutation was identified in the peripheral blood sample, the primary tumor and the relapse tumor; in addition, we identified a tumor protein p53 (TP53) heterozygous nonsense mutation in the primary tumor and a TP53 homozygous nonsense mutation and an IDH1 heterozygous missense mutation in the relapse tumor. Clonal evolution trees indicated higher heterogeneity in the relapse tumor. Although germline mutations might contribute to the driving force of the primary tumor, aggressive chemotherapy and radiation may apply selective pressure for tumor clonal evolution; furthermore, a total loss of function of gatekeeping genes (TP53) may result in impaired DNA repair and catastrophic chromosomal aberrations.

5.
Phys Chem Chem Phys ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32107519

RESUMO

Two-dimensional (2D) molybdenum diselenide (MoSe2) as one of the ultrathin transition metal dichalcogenides (TMDs) has attracted considerable attention because of its potential applications in thermoelectric and nano-electronic devices. Here, the thermal conductivity of monolayer MoSe2 and its responses to simulated size and defects are studied by nonequilibrium molecular dynamics simulations. With the increase of sample length, the thermal conductivity of monolayer MoSe2 nanoribbons exhibits an enhancement whereas it is insensitive to the width. At room temperature, the thermal conductivities of monolayer MoSe2 along armchair and zigzag directions are 17.758 and 18.932 W (m K)-1, respectively, which are consistent with previous results. The impact of defects on thermal conductivity has also been studied by varying the concentration of the vacancy from 0.1% to 0.5%. The results show that an increase of the defect concentration will greatly suppress the thermal conductivity. The 0.5% defect concentration with a Mo vacancy can result in a thermal conductivity reduction of ∼43%. Such a study would provide a good insight into the tunable thermal transport for potential applications of not only monolayer MoSe2, but also many other TMDs.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32036531

RESUMO

The continuous development of industrialization and urbanization resulted in increased pollution in plain river network areas. In response to water environment issues, water transfer can be a countermeasure to improve water environment. There are five basic elements to be determined of water transfer, i.e., water sources, water transfer patterns, regulating rules, water transfer routes, and flow rate of water transfer. In Wuxi City, needs for water transfer were analyzed from the five aspects above. The former three elements were determined based on the results of water transfer measurements. The water source was Yangtze River, the pattern was continuous water transfer, and regulating rules were water transferred by pumping stations and drained by sluices and pumping stations. Besides, a water quantity and quality coupling model was constructed to analyze routes and flow rate of water transfer. Different flow rate of water transfer, from 80 to 130 m3/s, were analyzed. According to the characteristics of regional river system and the requirements of flood control, the Baiqugang River was taken as the clean water route, and the urban flood control enclosure was taken as the clean water transfer station. In the end, it was concluded that the optimal flow rate is 110 m3/s based on the results of different schemes. It indicates that a proper scheme of water transfer can better improve the water environment in plain river network areas.

7.
Stem Cell Res Ther ; 11(1): 62, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059748

RESUMO

BACKGROUND: The process of bone repair is heavily dependent on the ability of human bone marrow mesenchymal stem cells (hMSCs) to undergo osteogenic differentiation. MicroRNAs have been shown to regulate this osteogenic process. This study aimed to investigate the role of miR-765 in the osteogenic differentiation of hMSCs. METHODS: We transfected hMSCs with lentiviral constructs to knock down or overexpress this miRNA, allowing us to assess its role in osteogenesis via assessing the expression of the relevant markers alkaline phosphatase (ALP), runt-related gene-2 (RUNX-2), and osteocalcin (OCN), with further functional measurements made via quantifying ALP activity and conducting Alizarin Red S staining. The targeting of the 3'-untranslated region (UTR) of BMP6 by miR-765 was examined via luciferase assay. We used hMSCs with altered miR-765 expression to assess p-Smad1/5/9 levels via Western blotting over the course of osteogenic differentiation. We also assessed the osteogenic differentiation of hMSCs in which miR-765 was knocked down and at the same time as a BMP/Smad signaling inhibitor was added to disrupt Smad1/5/9 phosphorylation. RESULTS: We found miR-765 overexpression to inhibit osteogenesis-associated gene upregulation during osteogenic differentiation of hMSCs, whereas knockdown of this miRNA was associated with increased expression of these genes. Using luciferase reporter assays, we confirmed direct miR-765 binding to the 3'-untranslated region (UTR) of BMP6. We also found that miR-765 overexpression reduced Smad1/5/9 phosphorylation, and knockdown of this miRNA enhanced this phosphorylation on BMP6/Smad1/5/9 signaling. The osteogenic differentiation of hMSCs in which miR-765 had been knocked down was further weakened upon the addition of a BMP/Smad signaling inhibitor relative to miR-765 knockdown alone. CONCLUSIONS: Together, these results thus suggest that miR-765 is able to inhibit hMSC osteogenic differentiation by targeting BMP6 via regulation of the BMP6/Smad1/5/9 signaling pathway. Our findings may offer molecular insights of value for the development of novel therapeutic treatments for bone diseases including osteoporosis.

8.
Med Mol Morphol ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32067111

RESUMO

To explore impact of Ataxia telangiectasia mutated (ATM) kinase on immunoreactions in lymphocyte-predominant breast cancer (LPBC), particularly its role in triple negative breast cancer (TNBC), 194 cases of LPBC were identified with pertinent clinical information retrieved. The expressions of ATM, activated ATM (P-ATM), Fas ligand (FASL), tumor necrosis factor-related apoptosis-induced ligand (TRAIL), major histocompatibility complex class I chain-related protein A (MICA), CD8, and Forkhead box P3 (FOXP3) were assessed by immunohistochemically. We found that ATM expressed on tumor cells was correlated with upregulated expression of P-ATM and MICA (P < 0.05), down-regulated expression of FASL and TRAIL (P < 0.01), and decreased Ki-67 tumor labeling (P < 0.05). However, within the TNBC group, only a negative correlation with FASL expression was found (P = 0.001). ATM and MICA expressions were significantly down -regulated in TNBC (P < 0.01) compared to non-TNBC, while TRAIL was significantly upregulated (P < 0.01). Tregs were increased in TNBC (P < 0.05), with CD8 + TILs decreased (P < 0.01). Ki-67 index was higher in TNBC than in non-TNBC (P < 0.01). ATM may play an important role in immunoreaction of LPBC, probably through upregulation of MICA and down-regulation of FASL and TRAIL. The down-regulated ATM expression in TNBC might be responsible for impaired tumor immunoactivity, rapid tumor growth, and aggressive clinical course.

9.
Res Q Exerc Sport ; : 1-9, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053464

RESUMO

Background/Purpose: The purpose of the present study was to review intervention studies in school physical education, with a goal of identifying the gaps and future trends of intervention research in the field of physical education. Methods: A total of 71 quantitative experimental studies were identified by manually examining all the articles published in the Journal of Teaching in Physical Education and Research Quarterly for Exercise and Sport from January 1998 to December 2018. All the studies were coded using a coding template. The interrater reliability among three coders exceeded 85%. The frequencies and percentages for each category were calculated as appropriate. Results: Eighty-five percent of experimental studies were guided by a theoretical framework. Interventions used various types of research designs. A variety of dependent variables were measured with the majority of studies focusing on student motivation and psychomotor skills. The intervention length ranged from 5 min to 2 years. Fifty-six percent of studies reported effect sizes. The reported types and strength of effect size varied. Forty-nine percent of them reported an intervention fidelity check. Conclusion: A limited number of experimental studies had been conducted from 1998 to 2018. The rigor of these experimental studies needs significant improvement. More experimental studies with a randomized controlled trial design are needed.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32054368

RESUMO

A number of same species of Cerithiidae are morphologically unlike, whereas most of species in the same genus are morphologically similar and just exhibit subtle differences. It is difficult to identify them by morphological methods alone. DNA barcoding is a modern molecular technique that can be used to identify species accurately, and is particularly helpful when distinguishing morphologically similar species. In order to identify species of Cerithiidae using DNA barcoding technology based on mitochondrial cytochrome oxidase subunit I (COI) and 16S ribosomal RNA (16S rRNA) genes, this study calculated intraspecific and interspecific genetic distance and constructed the phylogenetic trees. A total of 80 COI and 16S rRNA barcode sequences were obtained from 10 species and 3 genera. Some unknown specimens were further identified and a cryptic species may exist in Cerithium traillii, showing that DNA barcoding technology has the potential to discover new species and cryptic species. The phylogenetic trees revealed that all of the cerithiids could converge upon a monophyly with high support values and two genera (Cerithium and Clypeomorus) maybe support the reclassification. It is necessary for traditional morphological methods to combine with the DNA barcoding for classification and identification of Cerithiidae.

11.
Oncol Rep ; 43(2): 635-645, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31922233

RESUMO

MicroRNA­936 (miR­936) has been reported to play important roles in the progression of non­small cell lung cancer and glioma. However, the expression and functions of miR­936 in retinoblastoma (RB) remain elusive and need to be further elucidated. Herein, the aims were to measure miR­936 expression in RB, identify the functional importance of miR­936 in the oncogenicity of RB, and investigate the underlying molecular mechanisms. Reverse­transcription quantitative PCR was carried out to determine miR­936 expression in RB tissues and cell lines. Cell proliferation, colony formation, apoptosis, migration, and invasion in vitro and tumor growth in vivo were examined respectively by Cell Counting Kit­8, colony formation, flow cytometric, and Transwell migration and invasion assays and a subcutaneous heterotopic xenograft experiment. The potential target of miR­936 was predicted by bioinformatic analysis and was subsequently validated by luciferase reporter assay, reverse­transcription quantitative PCR, and western blotting. miR­936 expression was weak in both RB tissues and cell lines and was correlated with differentiation, lymph node metastasis and TNM staging in RB. RB cell proliferation, colony formation, migration, and invasion in vitro and tumor growth in vivo were attenuated by exogenous miR­936, whereas apoptosis was enhanced by miR­936 overexpression. Further molecular investigation identified histone deacetylase 9 (HDAC9) as a direct target gene of miR­936 in RB cells. HDAC9 depletion had effects similar to those of miR­936 overexpression in RB cells. Recovery of HDAC9 expression counteracted the tumor­suppressive action of miR­936 on the oncogenicity of RB cells. Ectopic miR­936 expression deactivated the PI3K/AKT pathway in RB cells in vitro and in vivo by decreasing HDAC9 expression. Downregulated miR­936 is related to poor prognosis in RB, and its upregulation inhibits RB aggressiveness via direct targeting of HDAC9 mRNA and thereby inactivation of the PI3K/AKT pathway.

12.
Breast Cancer Res Treat ; 180(2): 311-319, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31993861

RESUMO

INTRODUCTION: Triple negative breast cancer (TNBC) is an aggressive cancer subtype and lack of effective targeted therapies. It has been recently reported that Interleukin 17 (IL-17), a family of cytokines secreted in tumor microenvironment, affects tumor progression through a variety of molecular pathways. Its role in TNBC is so far still poorly explored. MATERIALS AND METHODS: We employed immunohistochemistry to evaluate the distribution of IL-17+ cells in TNBC with no special type features (TNBC-NST), their association with tumor microangiogenesis, as well as their impact on prognosis of the patients. RESULTS: In comparison to medullary carcinoma with triple-negative molecular features (TNBC-MC), we found a significant increase in IL-17+ cell infiltrates in intratumoral stroma and extratumoral stroma of TNBC-NST. Similarly, stromal cells with co-expression of CD4 and IL-17 were noted in intratumoral and extratumoral stroma in both TNBC-NST and TNBC-MC. In addition, intratumoral IL-17+ cells were positively associated with tumor cell expression of vascular endothelial growth factor A (VEGFA) and with intratumoral tumor microvascular density (MVD). Multivariate analysis identified that intratumoral IL-17+ cells (P = 0.018), MVD (P = 0.039), and TNM stage (P = 0.002) were independent prognostic factors for predicting poor PFS. CONCLUSION: The study indicates that IL-17 is overexpressed in intratumoral stromal cells of TNBC-NST. The overexpression of IL-17 might engage in active tumor microangiogenesis through its signal transduction pathways resulting in increased tumor secretion of VEGFA, and then promote tumor progression. IL-17 might serve as a potential new target for individualized therapy to TNBC-NST patients by development of specific antibodies. Additional study is deemed to further explore the role of IL-17+ stromal cells in breast cancer.

13.
Biochem Biophys Res Commun ; 524(1): 163-168, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-31982135

RESUMO

Stanniocalcin-2 (STC2) is a glycoprotein that has been found to play key roles in the regulation of cancer, diabetes mellitus, and osteogenesis. Herein we sought to extend these past studies by examining the importance of STC2 in the context of human mesenchymal stem cell (hMSC) adipogenic differentiation and exploring the mechanisms underlying such importance. We found that STC2 expression was significantly reduced on day 7 of hMSC adipogenesis. When we deliberately overexpressed STC2 in these cells, this resulted in significantly decreased expression of both peroxisome proliferator-activated receptor γ (PPARγ) and Fatty Acid Binding Protein-4 (FABP4) together with increased extracellular-signal regulated kinase 1/2 (ERK1/2) phosphorylation and markedly reduced lipid droplet formation within cells. Treatment of cells using the ERK inhibitor U0126 disrupted this ERK1/2 phosphorylation and restored the adipogenic differentiation of these hMSCs. When we instead knocked down STC2 expression, the opposite phenotypes were observed. Together these findings thus reveal that STC2 modulates ERK1/2 signaling in hMSCs so as to suppress their adipogenic differentiation.

14.
J Ethnopharmacol ; 252: 112600, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31981745

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis were prone to develop into ulcerrelated colorectal cancer with high risk of mortality. Shaoyao Decoction (SYD), a compound prescription of Chinese traditional medicine, was reported to have anti-colorectal cancer effect. Thus this study mainly investigated the protective and preventive effect of SYD against oxidative damages and inflamatory response through in vivo and in vitro experiments. AIM OF THE STUDY: Shaoyao decoction (SYD), a compound prescription of traditional Chinese medicine, is effective in treating ulcerative colitis. The increased levels of reactive oxygen species (ROS) in inflammatory cells potentially drive the development of carcinomas. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has became a novel target for the prevention of colorectal cancer (CRC). In this study, we assessed the antioxidation effect of SYD against colitis associated colorectal cancer through in vivo and in vitro experiments. MATERIALS AND METHODS: In vivo AOM/DSS-induced murine model of colon cancer and in vitro H2O2-induced oxidative stress in HT-29 cells model were conducted. To determine the antioxidant activity of SYD, protein expression of Nrf2 and its downstream genes were detected by western blot, RT-PCR and Enzyme-linked immunosorbent assay. RESULTS: Both in vivo and in vitro experiments demonstrated that SYD exerts antioxidant effect through activation of Nrf2 pathway and upregulation expression of Nrf2 downstream genes. SYD is shown to have preventive effect against colitis-associated colorectal cancer. CONCLUSIONS: These observations suggest that SYD is effective in the enhancement of antioxidant ability via activation of Nrf2 pathway and the up-regulation of Nrf2-downstream phase II enzymes expression. The anti-inflammation and antioxidant action of SYD together contributes to the prevention and treatment of ulcerrelated colorectal cancer.

15.
Sleep Med ; 67: 232-236, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31978671

RESUMO

OBJECTIVE: Sleep is an essential physiological process that protects our physical and mental health. However, the causality of the association between sleep and coronary heart disease (CHD) is unknown. Mendelian randomization (MR), using genetic variants as instrumental variables to test for causality, can infer credible causal associations. We applied a two-sample MR framework to determine the causal association between sleep (sleeplessness, sleep duration, and daytime dozing) and CHD by integrating summary-level genome-wide association study (GWAS) data. METHODS: Data included in this study were the GWAS summary statistics datasets from the C4D Consortium for CHD; Neale Lab UKB-a:13 Consortium for sleeplessness; Neale Lab UKB-a:9 Consortium for sleep duration and Neale Lab UKB-a:15 Consortium for daytime dozing. The conventional MR approach (inverse variance weighted, IVW) method and Egger method were used. Heterogeneity was calculated using each of the different MR methods where possible. Horizontal pleiotropy was evaluated by p-value of the MR-Egger intercept. RESULTS: The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval, CI) for CHD was 3.924 (1.345-11.447) per standard deviation increase in sleeplessness (p = 0.012). Results were consistent in MR-Egger method (OR, 4.654; 95% CI, 1.191-18.186; p = 0.009). The genetically predicted sleeplessness was positively casually associated with CHD. The causal association between sleep duration (or daytime dozing) and CHD was not established. CONCLUSION: Our analysis provided evidence supporting a causal relationship between sleeplessness (not sleep duration or daytime dozing) and CHD.

16.
Am J Trop Med Hyg ; 102(1): 142-146, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31701862

RESUMO

Imported malaria in Anhui Province, China, remains a significant public health issue with frequent reporting of severe and fatal cases, partly because of globalization and increased international communication. A retrospective evaluation using surveillance data from 2012 to 2018 was conducted to draw lessons on diagnosis of imported malaria. Epidemiological characteristics, together with diagnostic information, were analyzed using descriptive and comparative statistics. Simultaneously, blinded rechecking of malaria blood slides was performed at general hospitals in Anhui Province in 2018. The results showed that, in their first medical visits, 238 (28.2%) of 844 imported cases were not correctly diagnosed. Notably, the proportion of patients who were misdiagnosed at the first clinic visit was 104/120 (86.7%) at private and village clinics, and 41/81 (50.6%) at primary hospitals. The species identification rates for Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae were 85.2%, 66.7%, 23.2%, and 32.3% (χ2 = 224, P < 0.001), respectively. Nearly 7% of cases lacked laboratory evidence and were classified as presumed cases. Our findings suggest that physicians and health care providers, especially those at the primary level, lacked the awareness of diagnosing imported malaria. The training of physicians in malaria diagnosis needs to be enhanced. In addition, polymerase chain reactions (previously only carried out at the provincial level) should be performed at municipal CDC for rapid species identification, thereby guiding clinical treatment.

17.
Angew Chem Int Ed Engl ; 59(4): 1718-1726, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31799763

RESUMO

A challenging but pressing task to design and synthesize novel, efficient, and robust pH-universal hydrogen evolution reaction (HER) electrocatalysts for scalable and sustainable hydrogen production through electrochemical water splitting. Herein, we report a facile method to prepare an efficient and robust Ru-M (M=Ni, Mn, Cu) bimetal nanoparticle and carbon quantum dot hybrid (RuM/CQDs) for pH-universal HER. The RuNi/CQDs catalysts exhibit outstanding HER performance at all pH levels. The unexpected low overpotentials of 13, 58, and 18 mV shown by RuNi/CQDs allow a current density of 10 mA cm-2 in 1 m KOH, 0.5 m H2 SO4 , and 1 m PBS, respectively, for Ru loading at 5.93 µgRu cm-2 . This performance is among the best catalytic activities reported for any platinum-free electrocatalyst. Theoretical studies reveal that Ni doping results in a moderate weakening of the hydrogen bonding energy of nearby surface Ru atoms, which plays a critical role in improving the HER activity.

18.
Nutr Metab Cardiovasc Dis ; 30(2): 233-240, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31648883

RESUMO

BACKGROUND AND AIMS: Evidence on the effect of omega-6 fats on coronary heart disease (CHD) risk remains inconclusive. We applied a network MR framework to determine the causal effects between omega-6 levels and CHD and the potential cholesterol metabolic risk factors (Total cholesterol, TC; Low-density lipoprotein cholesterol, LDL-C; High-density lipoprotein cholesterol, HDL-C; Triglycerides, TG) which might act as mediators in the link between omega-6 levels and CHD by integrating summary-level genome wide association study (GWAS) data. METHODS AND RESULTS: Network MR analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed to examine the causal effects between omega-6 levels and CHD and cholesterol metabolic risk factors. Summary statistics from the Kettunen et al. 's consortium were used (n = 13506) for omega-6, CARDIoGRAMplusC4D consortium data were used (n = 184305) for CHD, and GLGC consortia data were used (n = 108363) for TC, LDL-C, HDL-C, and TG. The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval [CI]) for CHD was 1.210 (1.118-1.310) per standard deviation increase in omega-6. Results were consistent in MR Egger method (OR, 1.418; 95% CI, 1.087-1.851; P = 0.050) and weighted median methods (OR, 1.239; 95% CI, 1.125-1.364; P = 0.000). Omega-6 was positively causal associated with TC, LDL-C, and TG but was not associated with HDL-C. Moreover, TC, LDL-C, and TG were positively associated with CHD. CONCLUSIONS: Using a network MR framework, we provided evidence supporting a positive causal relationship between omega-6 and CHD, which might be partially mediated by TC, LDL-C, and TG.

19.
Glycoconj J ; 37(1): 47-56, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30937676

RESUMO

Protein O-glycosylation is the attachment of carbohydrate structures to the oxygen atom in the hydroxyl group of Serine and Threonine residues. This post-translational modification is commonly found on the majority of proteins trafficking through the secretory pathway and is reported to influence protein characteristics such as folding, secretion, stability, solubility, oligomerization and intracellular localization. In addition, O-glycosylation is essential for cell-cell interactions, protein-protein interactions and many biological processes, such as stress response, immunization, phosphorylation, ubiquitination, cell division, metabolism and cell signaling. The availability of sequenced genomes and genetic tools to create mutants with clear phenotypes makes insects an interesting model system to study O-glycosylation. In this review, we provide an overview of the current knowledge of O-glycosylation, mainly obtained from the model organism Drosophila melanogaster, with a focus on the synthesis and biological roles of the common O-glycans in insects.

20.
J Cell Physiol ; 235(1): 304-316, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31206189

RESUMO

Adipogenesis, the developmental process of progenitor-cell differentiating into adipocytes, leads to fat metabolic disorders. Alternative splicing (AS), a ubiquitous regulatory mechanism of gene expression, allows the generation of more than one unique messenger RNA (mRNA) species from a single gene. Till now, alternative splicing events during adipogenesis from human mesenchymal stem cells (hMSCs) are not yet fully elucidated. We performed RNA-Seq coupled with bioinformatics analysis to identify the differentially expressed AS genes and events during adipogenesis from hMSCs. A global survey separately identified 1262, 1181, 1167, and 1227 ASE involved in the most common types of AS including cassette exon, alt3, and alt5, especially with cassette exon the most prevalent, at 7, 14, 21, and 28 days during adipogenesis. Interestingly, 122 differentially expressed ASE referred to 118 genes, and the three genes including ACTN1 (alt3 and cassette), LRP1 (alt3 and alt5), and LTBP4 (cassette, cassette_multi, and unknown), appeared in multiple AS types of ASE during adipogenesis. Except for all the identified ASE of LRP1 occurred in the extracellular topological domain, alt3 (84) in transmembrane domain significantly differentially expressed was the potential key event during adipogenesis. Overall, we have, for the first time, conducted the global transcriptional profiling during adipogenesis of hMSCs to identify differentially expressed ASE and ASE-related genes. This finding would provide extensive ASE as the regulator of adipogenesis and the potential targets for future molecular research into adipogenesis-related metabolic disorders.

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