| 1. |
- Wan, Yi, et al.
(författare)
-
Osteogenic and antibacterial ability of micro-nano structures coated with ZnO on Ti-6Al-4V implant fabricated by two-step laser processing
- 2022
-
Ingår i: Journal of Materials Science & Technology. - : Elsevier BV. - 1005-0302. ; 131, s. 240-252
-
Tidskriftsartikel (refereegranskat)abstract
- The biological performance of Ti-6Al-4V implant is primarily determined by their surface properties. However, traditional surface modification methods, such as acid etching, hardly make improvement in their osseointegration ability and antibacterial capacity. In this study, we prepared a multi-scale composite structure coated with zinc oxide (ZnO) on Ti-6Al-4V implant by an innovative technology of two-step laser processing combined with solution-assistant. Compared with the acid etching method, the physicochemical properties of surface significantly improved. The in vitro results showed that the particular dimension of micro-nano structure and the multifaceted nature of ZnO synergistically affected MC3T3-E1 osteogenesis and bacterial activities: (1) The surface morphology showed a 'contact guidance' effect on cell arrangement, which was conducive to the adhesion of filopodia and cell spreading, and the osteogenesis level of MC3T3-E1 was enhanced due to the release of zinc ions (Zn2+); (2) the characterization of bacterial response revealed that periodic nanostructures and Zn2+ released could cause damage to the cell wall of E. coli and reduce the adhesion and aggregation of S. aureus. In conclusion, the modified surface showed a synergistic effect of physical topography and chemical composition, making this a promising method and providing new insight into bone defect repairment.
|
|
| 2. |
- Ji, Zhenbing, et al.
(författare)
-
Effects of surface morphology and composition of titanium implants on osteogenesis and inflammatory responses : a review
- 2023
-
Ingår i: Biomedical Materials. - : IOP Publishing. - 1748-6041 .- 1748-605X. ; 18:4
-
Forskningsöversikt (refereegranskat)abstract
- Titanium and its alloys have been widely used in bone tissue defect treatment owing to their excellent comprehensive properties. However, because of the biological inertness of the surface, it is difficult to achieve satisfactory osseointegration with the surrounding bone tissue when implanted into the body. Meanwhile, an inflammatory response is inevitable, which leads to implantation failure. Therefore, solving these two problems has become a new research hotspot. In current studies, various surface modification methods were proposed to meet the clinical needs. Yet, these methods have not been classified as a system to guide the follow-up research. These methods are demanded to be summarized, analyzed, and compared. In this manuscript, the effect of physical signal regulation (multi-scale composite structure) and chemical signal regulation (bioactive substance) generated by surface modification in promoting osteogenesis and reducing inflammatory responses was generalized and discussed. Finally, from the perspective of material preparation and biocompatibility experiments, the development trend of surface modification in promoting titanium implant surface osteogenesis and anti-inflammatory research was proposed.
|
|
| 3. |
- Li, Peng, et al.
(författare)
-
Transcriptional reactivation of OTX2, RX1 and SIX3 during reprogramming contributes to the generation of RPE cells from human iPSCs
- 2016
-
Ingår i: International Journal of Biological Sciences. - : Ivyspring International Publisher. - 1449-2288. ; 12:5, s. 505-517
-
Tidskriftsartikel (refereegranskat)abstract
- Directed differentiation of human induced pluripotent stem cells (iPSCs) into retinal pigmented epithelium (RPE) holds great promise in cell replacement therapy for patients suffering from degenerative eye diseases, including age-related macular degeneration (AMD). In this study, we generated iPSCs from human dermal fibroblasts (HDFs) by electroporation with episomal plasmid vectors encoding OCT4, SOX2, KLF4, L-MYC together with p53 suppression. Intriguingly, cell reprogramming resulted in a metastable transcriptional activation and selective demethylation of neural and retinal specification-associated genes, such as OTX2, RX1 and SIX3. In contrast, RPE progenitor genes were transcriptionally silent in HDFs and descendant iPSCs. Overexpression of OCT4 and SOX2 directly stimulated the expression of OTX2, RX1 and SIX3 in HDFs and iPSCs. Luciferase and chromatin immunoprecipitation (ChIP) assays further identified an OCT4- and two SOX2-binding sites located in the proximal promoter of OTX2. Histone acetylation and methylation on the local promoter also participated in the reactivation of OTX2. The transcriptional conversion of RX1 and SIX3 genes partially attributed to DNA demethylation. Subsequently, iPSCs were induced into the RPE cells displaying the characteristics of polygonal shapes and pigments, and expressing typical RPE cell markers. Taken together, our results establish readily efficient and safe protocols to produce iPSCs and iPSC-derived RPE cells, and underline that the reactivation of anterior neural transcription factor OTX2, eye field transcription factor RX1 and SIX3 in iPSCs is a feature of pluripotency acquisition and predetermines the potential of RPE differentiation.
|
|
| 4. |
- Yang, Chen, et al.
(författare)
-
Nuclear IGF1R interact with PCNA to preserve DNA replication after DNA-damage in a variety of human cancers
- 2020
-
Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 15:7
-
Tidskriftsartikel (refereegranskat)abstract
- Nuclear IGF1R has been linked to poor outcome in cancer. We recently showed that nuclear IGF1R phosphorylates PCNA and increases DNA damage tolerance. In this paper we aimed to describe this mechanism in cancer tissue as well as in cancer cell lines. In situ proximity ligation assay identified frequent IGF1R and PCNA colocalization in many cancer types. IGF1R/PCNA colocalization was more frequently increased in tumor cells than in adjacent normal, and more prominent in areas with dysplasia and invasion. However, the interaction was often lost in tumors with poor response to neoadjuvant treatment and most metastatic lesions. In two independent cohorts of serous ovarian carcinomas and oropharyngeal squamous cell carcinomas, stronger IGF1R/PCNA colocalization was significantly associated with a higher overall survival. Ex vivo irradiation of ovarian cancer tissue acutely induced IGF1R/PCNA colocalization together with ?H2AX-foci formations. In vitro, RAD18 mediated mono-ubiquitination of PCNA during replication stress was dependent on IGF1R kinase activity. DNA fiber analysis revealed that IGF1R activation could rescue stalled DNA replication forks, but only in cancer cells with baseline IGF1R/PCNA interaction. We believe that the IGF1R/PCNA interaction is a basic cellular mechanism to increase DNA stress tolerance during proliferation, but that this mechanism is lost with tumor progression in conjunction with accumulated DNA damage and aberrant strategies to tolerate genomic instability. To exploit this mechanism in IGF1R targeted therapy, IGF1R inhibitors should be explored in the context of concomitant induction of DNA replication stress as well as in earlier clinical stages than previously tried.
|
|
| 5. |
- Zhu, Zhenshuo, et al.
(författare)
-
Histone demethylase complexes KDM3A and KDM3B cooperate with OCT4/SOX2 to define a pluripotency gene regulatory network
- 2021
-
Ingår i: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 35:6
-
Tidskriftsartikel (refereegranskat)abstract
- The pluripotency gene regulatory network of porcine induced pluripotent stem cells(piPSCs), especially in epigenetics, remains elusive. To determine the biological function of epigenetics, we cultured piPSCs in different culture conditions. We found that activation of pluripotent gene- and pluripotency-related pathways requires the erasure of H3K9 methylation modification which was further influenced by mouse embryonic fibroblast (MEF) served feeder. By dissecting the dynamic change of H3K9 methylation during loss of pluripotency, we demonstrated that the H3K9 demethylases KDM3A and KDM3B regulated global H3K9me2/me3 level and that their co-depletion led to the collapse of the pluripotency gene regulatory network. Immunoprecipitation-mass spectrometry (IP-MS) provided evidence that KDM3A and KDM3B formed a complex to perform H3K9 demethylation. The genome-wide regulation analysis revealed that OCT4 (O) and SOX2 (S), the core pluripotency transcriptional activators, maintained the pluripotent state of piPSCs depending on the H3K9 hypomethylation. Further investigation revealed that O/S cooperating with histone demethylase complex containing KDM3A and KDM3B promoted pluripotency genes expression to maintain the pluripotent state of piPSCs. Together, these data offer a unique insight into the epigenetic pluripotency network of piPSCs.
|
|
