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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 3. |
- Bock (Seifert), Oliver, et al.
(författare)
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Studies of Transforming Growth Factors Beta 1–3 and their Receptors I and II in Fibroblast of Keloids and Hypertrophic Scars
- 2005
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555. ; 85:3, s. 216-220
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Tidskriftsartikel (refereegranskat)abstract
- Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. They are characterized by an abnormal deposition of extracellular matrix components, particularly collagen. There is uncertain evidence that transforming growth factor-beta (TGFβ) is involved in keloid formation. Therefore we investigated the expression of TGFβ1, 2 and 3 and their receptors in keloids, hypertrophic scars and normal skin. Dermal fibroblasts were obtained from punch biopsies of patients with keloids and hypertrophic scars and from normal skin of healthy individuals. Total RNA was isolated and the expression of TGFβ1, 2 and 3 and of TGFβ receptors I and II (TGFβRI and II) was analysed by real-time PCR using the Lightcycler technique. Our data demonstrate significantly lower TGFβ2 mRNA expression in hypertrophic scar fibroblasts as compared with fibroblasts derived from keloids and normal skin (p<0.05). In contrast, TGFβ3 mRNA expression was significantly lower in keloid fibroblasts in comparison with fibroblasts derived from hypertrophic scar and normal skin (p<0.01). TGFβRI mRNA expression was significantly decreased in hypertrophic scar fibroblasts (p<0.01) and TGFβRII mRNA expression was decreased in keloids compared with hypertrophic scar fibroblasts (p<0.001), The ratio of TGFβRI/TGFβRII expression was increased in keloids compared with hypertrophic scar and normal skin fibroblasts. As recently supposed, an increased TGFβRI/TGFβRII ratio could promote fibrosis. Therefore our data support a possible role of TGFβRI and TGFβRII in combination with a certain TGFβ expression pattern as fibrosis-inducing factors in keloids.
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| 4. |
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| 5. |
- Yu, Haiyan, et al.
(författare)
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Decreased expression of inhibitory SMAD6 and SMAD7 in keloid scarring
- 2006
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Ingår i: Journal of Plastic, Reconstructive and Aesthetic Surgery. - : Elsevier BV. - 1748-6815. ; 59:3, s. 221-229
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Tidskriftsartikel (refereegranskat)abstract
- Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. They are characterised by an abnormal deposition of extracellular matrix components, in particular collagen. There is evidence that transforming growth factor-beta (TGFβ) is involved in keloid formation. SMAD proteins play a crucial role in TGFβ signaling and in terminating the TGFβ signal by a negative feedback loop through SMAD6 and 7. It is unclear how TGFβ signalling is connected to the pathogenesis of keloids. Therefore, we investigated the expression of SMAD mRNA and proteins in keloids, in normal skin and in normal scars. Dermal fibroblasts were obtained from punch-biopsies of keloids, normal scars and normal skin. Cells were stimulated with TGFβ1 and the expression of SMAD2, 3, 4, 6 and 7 mRNA was analysed by real time RT-PCR. Protein expression was determined by Western blot analysis. Our data demonstrate a decreased mRNA expression of the inhibitory SMAD6 and 7 in keloid fibroblasts as compared to normal scar (p<0.01) and normal skin fibroblasts (p<0.05). SMAD3 mRNA was found to be lower in keloids (p<0.01) and in normal scar fibroblasts (p<0.001) compared to normal skin fibroblasts. Our data showed for the first time a decreased expression of the inhibitory SMAD6 and SMAD7 in keloid fibroblasts. This could explain why TGFβ signaling is not terminated in keloids leading to overexpression of extracellularmatrix in keloids. These data support a possible role of SMAD6 and 7 in the pathogenesis of keloids.
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| 6. |
- Yu, Haiyan, et al.
(författare)
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Imiquimod induced vitiligo-like lesions-A consequence of modified melanocyte function
- 2022
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Ingår i: Immunity, Inflammation and Disease. - : Wiley. - 2050-4527. ; 10:1, s. 70-77
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Imiquimod plays an important role in the management of condyloma and premalignant lesions. Successively, an increase of hypopigmented lesions following imiquimod application has been reported. However, the mechanisms of imiquimod on melanocytes remain unclear. This study was designed to assess the effect of Imiquimod on the functions of melanocytes in vitro. Methods Primary cultured melanocytes were isolated from normal control skin tissue. After incubation with imiquimod for 48 h in vitro, cell viability was analyzed by cell counting kit-8 assay. Apoptosis was detected using the Annexin V-fluorescein-5-isothiocyanate flow cytometry assay. Melanin content and tyrosinase activity in melanocytes were measured by colorimetric method and the modified dopachrome method. The production of inflammatory cytokine interleukin 8 (IL-8), IL-6, and soluble ICAM-1 (soluble Intercellular Adhesion Molecule-1[sICAM-1]) in melanocytes were measured by enzyme-linked immunosorbent assay (ELISA). Toll-like receptor 7 (TLR7), toll-like receptor 9 (TLR9) protein, and autophagy-related proteins microtubule-associated protein 1A/1B-light chain 3 (LC3-II), p62, mechanistic target of rapamycin (mTOR), and Atg5 were assessed using western blot analysis. Results Imiquimod significantly inhibited the activity of tyrosinase activity and decreased melanin content in melanocytes and significantly increased apoptosis and IL-6, IL-8, and sICAM-1 production in melanocytes. Moreover, the expression of TLR7 and TLR9 proteins were significantly increased, and the expression of mTOR, p62 protein were markedly decreased, but the expression of LC3II/I and Atg5 protein were significantly increased in melanocytes after incubating with imiquimod. Conclusions This study shows that imiquimod directly inhibits melanogenesis and increases melanocyte apoptosis rates. These effects combined with the upregulation of TLR7 and TLR9 together with increased autophagy activity and inflammatory cytokines production, might be the main reasons leading to hypopigmented lesions after imiquimod application.
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| 7. |
- Yu, Haiyan, et al.
(författare)
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The Difference in Expression of Autophagy-Related Proteins in Lesional and Perilesional Skin in Adult Patients with Active and Stable Generalized Vitiligo-A Cross-Sectional Pilot Study
- 2021
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Ingår i: Indian Journal of Dermatology. - : WOLTERS KLUWER MEDKNOW PUBLICATIONS. - 0019-5154 .- 1998-3611. ; 66:4, s. 331-336
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autophagy plays an important role in maintaining intracellular homeostasis and is essential for cell survival and cell death. Dysfunction of autophagy has been described in many autoimmune diseases but data on vitiligo are scarce. Aims: The aim of this pilot study was to investigate the expression of autophagy-related proteins in patients with vitiligo. Methods: Western blotting was used to analyze the expression of microtubule-associated protein light chain 3 (LC3II/I), autophagy-related gene 5 (Agt5), mammalian target of rapamycin (mTOR) and p62 in lesional and perilesional vitiligo skin from seven patients with active generalized vitiligo and nine patients with stable generalized vitiligo compared to control skin from six healthy subjects. Results: Our data showed increased expression of the autophagy marker LC3II/I and decreased p62 protein expression in lesional skin of active and stable vitiligo compared to control skin (P < 0.01). No significant difference in the expression of LC3II/I and p62 was found in perilesional skin of active vitiligo patients (P > 0.05) compared to control skin. Expression of LC3II/I in stable vitiligo lesional skin was higher and p62 expression was lower compared to active vitiligo lesional skin (P < 0.01). Decreased p62 expression was shown in perilesional skin of stable vitiligo patients (P < 0.05). Agt5 protein in lesional and perilesional skin of both active and stable vitiligo patients were increased (P < 0.01 and P< 0.05) compared to control skin. The expression of mTOR protein in lesional and perilesional skin of active and stable vitiligo patients was significantly lower than in control skin (P < 0.01). Conclusions: The present study indicates increased autophagy in lesional skin in vitiligo patients. Stable vitiligo lesional skin showed increased autophagy compared to active vitiligo lesional skin. Missing activation of autophagy in active vitiligo perilesional skin suggests disturbed autophagy to be associated with vitiligo.
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| 8. |
- Zhang, Haiyan, et al.
(författare)
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Geographical Differences in Dietary Exposure to Perfluoroalkyl Acids between Manufacturing and Application Regions in China
- 2017
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:10, s. 5747-5755
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Tidskriftsartikel (refereegranskat)abstract
- Emissions of perfluoroalkyl acids (PFAAs) have increased in China over the past decade, but human exposure pathways are poorly understood. Here we analyzed 15 PFAAs in commonly consumed food items and calculated body weight normalized dietary intake rates (estimated dietary intake, EDIs) in an area with ongoing PFAA production (Hubei province; n = 121) and an urbanized coastal area (Zhejiang province; n = 106). Geographical differences in concentrations were primarily observed for perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) in animal food items and short chain PFAAs in vegetable food items. The average EDI of Sigma PFAAs for adults in Hubei (998 ng kg(-1) day(-1)) was more than 2 orders of magnitude higher than that in Zhejiang (9.03 ng kg-1 day(-1)). In Hubei province, the average EDI of PFOS for adults (87 ng kg(-1) day(-1)) was close to or exceeded advisory guidelines used in other countries indicating health risks for the population from long-term exposure. Yet, PFOS could only account for about 10% of the EDI of Sigma PFAAs in the Hubei province, which was dominated by short-chain PFAAs through consumption of vegetables. The large contribution of short-chain PFAAs to the total EDIs in manufacturing areas emphasize the need for improved exposure and hazard assessment tools of these substances.
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| 9. |
- Zhang, Haiyan, et al.
(författare)
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Levels and distributions of hexachlorobutadiene and three chlorobenzenes in biosolids from wastewater treatment plants and in soils within and surrounding a chemical plant in China.
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:3, s. 1525-1531
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Tidskriftsartikel (refereegranskat)abstract
- Although hexachlorobutadiene (HCBD) was recently proposed as a candidate persistent organic pollutant (POP) under the Stockholm Convention, information about its environmental levels and distributions is still very limited. In this work, HCBD was determined in the sewage sludge from 37 wastewater treatment plants (WWTPs) in 23 cities and 17 soils near a chemical plant in China. Three chlorobenzenes (CBs) (1,2,4-trichlorobenzene, 1,2,4,5-tetrachlorobenzene, and hexachlorobenzene) were simultaneously studied to help better understand the environmental behavior of HCBD. Concentrations of HCBD in sludge samples ranged from <0.03 to 74.3 ng/g dry weight (dw) with a median value of 0.30 ng/g dw, which was lower than those of the three CBs. Levels of HCBD were not correlated with capacity of the WWTPs and total organic carbon. For soils, high level of HCBD was found in the sample within the plant, with a rapid decreasing concentration trend with the increase of distance from the plant. It was suspected that releasing as a byproduct during manufacturing of chlorinated chemicals was the primary source of HCBD in the studied location. Further risk assessment indicated that the environmental risk of HCBD to soil organisms and the health risk to employees were very low through soil exposure within the plant.
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| 10. |
- Zhang, Yanan, et al.
(författare)
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Identifying discriminative features for diagnosis of Kashin-Beck disease among adolescents
- 2021
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Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central. - 1471-2474. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Diagnosing Kashin-Beck disease (KBD) involves damages to multiple joints and carries variable clinical symptoms, posing great challenge to the diagnosis of KBD for clinical practitioners. However, it is still unclear which clinical features of KBD are more informative for the diagnosis of Kashin-Beck disease among adolescent.METHODS: We first manually extracted 26 possible features including clinical manifestations, and pathological changes of X-ray images from 400 KBD and 400 non-KBD adolescents. With such features, we performed four classification methods, i.e., random forest algorithms (RFA), artificial neural networks (ANNs), support vector machines (SVMs) and linear regression (LR) with four feature selection methods, i.e., RFA, minimum redundancy maximum relevance (mRMR), support vector machine recursive feature elimination (SVM-RFE) and Relief. The performance of diagnosis of KBD with respect to different classification models were evaluated by sensitivity, specificity, accuracy, and the area under the receiver operating characteristic (ROC) curve (AUC).RESULTS: Our results demonstrated that the 10 out of 26 discriminative features were displayed more powerful performance, regardless of the chosen of classification models and feature selection methods. These ten discriminative features were distal end of phalanges alterations, metaphysis alterations and carpals alterations and clinical manifestations of ankle joint movement limitation, enlarged finger joints, flexion of the distal part of fingers, elbow joint movement limitation, squatting limitation, deformed finger joints, wrist joint movement limitation.CONCLUSIONS: The selected ten discriminative features could provide a fast, effective diagnostic standard for KBD adolescents.
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