| 1. |
- Zhang, Ruyang, et al.
(författare)
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Independent Validation of Early-Stage Non-Small Cell Lung Cancer Prognostic Scores Incorporating Epigenetic and Transcriptional Biomarkers With Gene-Gene Interactions and Main Effects
- 2020
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Ingår i: Chest. - : Elsevier BV. - 0012-3692. ; 158:2, s. 808-819
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Tidskriftsartikel (refereegranskat)abstract
- Background: DNA methylation and gene expression are promising biomarkers of various cancers, including non-small cell lung cancer (NSCLC). Besides the main effects of biomarkers, the progression of complex diseases is also influenced by gene-gene (G×G) interactions. Research Question: Would screening the functional capacity of biomarkers on the basis of main effects or interactions, using multiomics data, improve the accuracy of cancer prognosis? Study Design and Methods: Biomarker screening and model validation were used to construct and validate a prognostic prediction model. NSCLC prognosis-associated biomarkers were identified on the basis of either their main effects or interactions with two types of omics data. A prognostic score incorporating epigenetic and transcriptional biomarkers, as well as clinical information, was independently validated. Results: Twenty-six pairs of biomarkers with G×G interactions and two biomarkers with main effects were significantly associated with NSCLC survival. Compared with a model using clinical information only, the accuracy of the epigenetic and transcriptional biomarker-based prognostic model, measured by area under the receiver operating characteristic curve (AUC), increased by 35.38% (95% CI, 27.09%-42.17%; P = 5.10 × 10–17) and 34.85% (95% CI, 26.33%-41.87%; P = 2.52 × 10–18) for 3- and 5-year survival, respectively, which exhibited a superior predictive ability for NSCLC survival (AUC3 year, 0.88 [95% CI, 0.83-0.93]; and AUC5 year, 0.89 [95% CI, 0.83-0.93]) in an independent Cancer Genome Atlas population. G×G interactions contributed a 65.2% and 91.3% increase in prediction accuracy for 3- and 5-year survival, respectively. Interpretation: The integration of epigenetic and transcriptional biomarkers with main effects and G×G interactions significantly improves the accuracy of prognostic prediction of early-stage NSCLC survival.
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| 2. |
- Abraham, Roshan Mammen, et al.
(författare)
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Tau neutrinos in the next decade : from GeV to EeV
- 2022
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Ingår i: Journal of Physics G. - : Institute of Physics Publishing (IOPP). - 0954-3899 .- 1361-6471. ; 49:11
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Tidskriftsartikel (refereegranskat)abstract
- Tau neutrinos are the least studied particle in the standard model. This whitepaper discusses the current and expected upcoming status of tau neutrino physics with attention to the broad experimental and theoretical landscape spanning long-baseline, beam-dump, collider, and astrophysical experiments. This whitepaper was prepared as a part of the NuTau2021 Workshop.
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| 3. |
- Al-Saffar, Anas, 1969-, et al.
(författare)
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Parallel Changes in Harvey-Bradshaw Index, TNFα, and Intestinal Fatty Acid Binding Protein in Response to Infliximab in Crohn’s Disease
- 2017
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Ingår i: Gastroenterology Research and Practice. - Egypt : Hindawi Publishing Corporation. - 1687-6121 .- 1687-630X. ; , s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal fatty acid binding protein (I-FABP) indicates barrier integrity. Aims: determine if I-FABP is elevated in active Crohn's disease (CD) and if I-FABP parallels anti-TNF alpha antibody (infliximab) induced lowering of TNF alpha and Harvey-Bradshaw Index (HBI) as potential indicator of mucosal healing. I-FABP distribution along human gut was determined. Serum from 10 CD patients collected during first three consecutive infliximab treatments with matched pretreatment and follow-up samples one week after each treatment and corresponding HBI data were analyzed. I-FABP reference interval was established from 31 healthy subjects with normal gut permeability. I-FABP and TNF alpha were measured by ELISA; CRP was measured by nephelometry. Healthy tissue was used for I-FABP immunohistochemistry. Pretreatment CD patient TNF alpha was 1.6-fold higher than in-house reference interval, while I-FABP was 2.5-fold higher, which lowered at follow-ups. Combining all 30 infusion/follow-up pairs also revealed changes in I-FABP. HBI followed this pattern; CRP declined gradually. I-FABP was expressed in epithelium of stomach, jejunum, ileum, and colon, with the highest expression in jejunum and ileum. I-FABP is elevated in active CD with a magnitude comparable to TNF alpha. Parallel infliximab effects on TNF alpha, HBI, and I-FABP were found. I-FABP may be useful as an intestine selective prognostic marker in CD.
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| 4. |
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| 5. |
- Deng, Qihong, et al.
(författare)
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Early life exposure to traffic-related air pollution and allergic rhinitis in preschool children
- 2016
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 121, s. 67-73
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence linking long-term exposure to outdoor air pollution with allergic rhinitis (AR) in children is scare, and the role of components of air pollution and timing of exposure remains unclear. Objective: To assess the association of pre- and post-natal exposure to air pollution with life-time prevalence of AR in preschool children. Methods: We conducted a cohort study of 2598 children aged 3-6 years in Changsha, China. The lifetime prevalence of AR was assessed by a questionnaire administered by parents. Children's exposures to dioxide nitrogen (NO2), sulfur dioxide (SO2) and particulate matter with an aerodynamic diameter <= 10 mu m (PM10) during different pre-and post-natal timing windows were estimated using the measured concentrations at monitoring stations. The odds ratio (OR) and 95% confidence interval (CI) of childhood AR for exposure to different air pollutants during different timing windows were assessed by logistic regression model in terms of an interquartile range (IQR) increase in exposure level. Results: Life-time prevalence of AR in preschool children (7.3%) was associated with both pre-and postnatal exposure to traffic-related air pollution (TRAP), but only significant during the third trimester of pregnancy with adjusted OR = 1.40 (95% CI: 1.08-1.82) for a 15 mu g/m(3) increase in NO2 and during the first-year of life with adjusted OR = 1.36 (95% CI: 1.03-1.78) and 1.54 (95% CI: 1.07-2.21) respectively for 11 and 12 mu g/m(3) increase in NO2 and PM10. The association of early life exposure to TRAP with childhood AR was robust by adjusting for other air pollutants and timing windows. Sensitivity analysis indicated that the association was higher in the children who are male, young, with genetic predisposition by parental atopy, and living in damp houses. Conclusion: Early life exposure to traffic-related air pollutant during pregnancy and first-year of life may contribute to childhood AR.
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| 6. |
- El-Sayed, Ramy, et al.
(författare)
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Single-Walled Carbon Nanotubes Inhibit the Cytochrome P450 Enzyme, CYP3A4
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- We report a detailed computational and experimental study of the interaction of single-walled carbon nanotubes (SWCNTs) with the drug-metabolizing cytochrome P450 enzyme, CYP3A4. Dose-dependent inhibition of CYP3A4-mediated conversion of the model compound, testosterone, to its major metabolite, 6 beta-hydroxy testosterone was noted. Evidence for a direct interaction between SWCNTs and CYP3A4 was also provided. The inhibition of enzyme activity was alleviated when SWCNTs were pre-coated with bovine serum albumin. Furthermore, covalent functionalization of SWCNTs with polyethylene glycol (PEG) chains mitigated the inhibition of CYP3A4 enzymatic activity. Molecular dynamics simulations suggested that inhibition of the catalytic activity of CYP3A4 is mainly due to blocking of the exit channel for substrates/products through a complex binding mechanism. This work suggests that SWCNTs could interfere with metabolism of drugs and other xenobiotics and provides a molecular mechanism for this toxicity. Our study also suggests means to reduce this toxicity, eg., by surface modification.
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| 7. |
- Guo, Yichen, et al.
(författare)
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DNA Methylation of LRRC3B : A Biomarker for Survival of Early-Stage Non-Small Cell Lung Cancer Patients
- 2018
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Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755. ; 27:12, s. 1527-1535
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies support a tumor-suppressor role for LRRC3B across various types of cancers. We aimed to investigate the association between DNA methylation of LRRC3B and overall survival (OS) for patients with early-stage non-small cell lung cancer (NSCLC).Methods: This study included 1,230 patients with early-stage NSCLC. DNA was extracted from lung tumor tissues and DNA methylation was measured using Illumina Infinium HumanMethylation450 BeadChips. The association between DNA methylation and OS was first tested using Cox regression on a discovery cohort and then validated in an independent cohort. Next, the association between DNA methylation and gene expression was investigated in two independent cohorts. Finally, the association between gene expression and OS was investigated in three independent groups of patients.Results: Three novel DNA methylation sites in LRRC3B were significantly associated with OS in two groups of patients. Patients with hypermethylation in the DNA methylation sites had significantly longer survival than the others in both the discovery cohort (HR, 0.62; P = 2.02 × 10-05) and validation cohort (HR, 0.55; P = 4.44 × 10-04). The three DNA methylation sites were significantly associated with LRRC3B expression, which was also associated with OS.Conclusions: Using clinical data from a large population, we illustrated the association between DNA methylation of LRRC3B and OS of early-stage NSCLC.Impact: We provide evidence of plausibility for building biomarkers on DNA methylation of LRRC3B for OS of early-stage NSCLC, thus filling a gap between previous in vitro studies and clinical applications. Cancer Epidemiol Biomarkers Prev; 27(12); 1-9. ©2018 AACR.
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| 8. |
- Jin, Yukun, et al.
(författare)
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Mixed Insulating State for van der Waals CoPS3
- 2022
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Ingår i: Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 13:45, s. 10486-10493
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale high-quality van der Waals CoPS3single crystals are synthesized using a chemical vapor transport (CVT) method. The crystallographic structure and electronic properties of this layered material are systematically studied using different spectroscopic methods (XPS, NEXAFS, and resonant photoelectron spectroscopy) accompanied by density functional theory (DFT) calculations. All experimental and theoretical data allow assignment of this material to the class of mixed Mott-Hubbard/charge-transfer insulator with Udd≅ Δ. All obtained results can enrich the information on the new class of van der Waals materials, transition metal phosphorus trichalcogenides, and help to further effectively exploit their electronic, optical, and transport properties, which are important for adopting this kind of materials into different application areas, such as spintronics and catalysis.
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| 9. |
- Li, Zhuona, et al.
(författare)
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Effects of polycyclic musks HHCB and AHTN on steroidogenesis in H295R cells
- 2013
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 90:3, s. 1227-1235
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Tidskriftsartikel (refereegranskat)abstract
- 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(γ)-2-benzopyran (HHCB) and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) are widely used in personal care products. Previous studies showed that HHCB and AHTN can be found in various environmental matrices and have potential endocrine disrupting effects. However, the effects on adrenocortical function of HHCB and AHTN are not fully understood. This study evaluated the influences of HHCB and AHTN on seven steroid hormones (progesterone, aldosterone, cortisol, 17α-OH-progesterone, androstenedione, 17β-estradiol, and testosterone) and 10 genes involved in steroidogenic pathways (HMGR, StAR, CYP11A1, 3βHSD2, CYP17, CYP21, CYP11B1, CYP11B2, 17βHSD, and CYP19) using the H295R cell line in the absence and presence of 8-Br-cAMP. MC2R transcription on the cell membrane was also examined to further investigate the effects of HHCB and AHTN on adrenal steroidogenesis. The results demonstrated that HHCB and AHTN could inhibit progesterone and cortisol production mainly by the suppression of 3βHSD2 and CYP21. Meanwhile, high concentrations of AHTN can affect the sensitivity of H295R cells to ACTH by disrupting MC2R transcription. Overall, the results indicate that high concentrations of HHCB and AHTN can affect steroidogenesis in vitro using the H295R cell line.
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| 10. |
- Lobov, Gleb, et al.
(författare)
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Dynamic manipulation of optical anisotropy of suspended Poly-3-hexylthiophene nanofibers
- 2016
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Ingår i: Advanced Optical Materials. - : Wiley. - 2162-7568 .- 2195-1071. ; 4:10, s. 1651-1656
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Tidskriftsartikel (refereegranskat)abstract
- Poly-3-hexylthiophene (P3HT) nanofibers are 1D crystalline semiconducting nanostructures, which are known for their application in photovoltaics. Due to the internal arrangement, P3HT nanofibers possess optical anisotropy, which can be enhanced on a macroscale if nanofibers are aligned. Alternating electric field, applied to a solution with dispersed nanofibers, causes their alignment and serves as a method to produce solid layers with ordered nanofibers. The transmission ellipsometry measurements demonstrate the dichroic absorption and birefringence of ordered nanofibers in a wide spectral range of 400–1700 nm. Moreover, the length of nanofibers has a crucial impact on their degree of alignment. Using electric birefringence technique, it is shown that external electric field applied to the solution with P3HT nanofibers can cause direct birefringence modulation. Dynamic alignment of dispersed nanofibers changes the refractive index of the solution and, therefore, the polarization of transmitted light. A reversible reorientation of nanofibers is organized by using a quadrupole configuration of poling electrodes. With further development, the described method can be used in the area of active optical fiber components, lab-on-chip or sensors. It also reveals the potential of 1D conducting polymeric structures as objects whose highly anisotropic properties can be implemented in electro-optical applications..
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