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Targeted Systemic Combinatorial Delivery of siRNA Polyplexes–Functional Quantum Dot-siRNA Nanoplexes
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
In this study section, it has been developed [107] functional QD nanoplexes by sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo-SMCC) activation of PEG-coated CdSe/ZnS QDs as the gene carrier of siRNA to study the effect of SOX9 RNA interference on the chondrogenic differentiation of MSCs. This study confirmed the importance of SOX9 in chondrogenesis, as evidenced by the findings that SOX9 knockdown significantly inhibited the expression of cartilage-specific markers including acan and col2a1 in MSCs and further delayed cartilage repair. Moreover, QD-SMCC has an intrinsic signal for noninvasive imaging of siRNA transport. The results indicate that SOX9 is imperative for the chondrogenesis of MSCs and QD-SMCC has great potential for real-time tracking of transfection.
Articular Cartilage Development
Published in Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi, Articular Cartilage, 2017
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi
Other relevant transcription factors during cartilage development include Pax1 and scleraxis (Table 2.2), which activate cartilage-specific genes (Cserjesi et al. 1995; Sosic et al. 1997). Members of the Sox protein family, specifically Sox9, Sox5, and Sox6, are also expressed in prechondrogenic cells, with Sox9 being necessary for the mesenchymal aggregation (Bi et al. 1999). This differentiation of mesenchymal cells into chondroblasts and further into chondrocytes is under the control of BMP2, BMP4 and 7, and TGF-β (Cole et al. 2003; Tickle 2003). A temporal expression profile of various transcription factors is depicted in Figure 2.11.
Efficient computational implementation of polymer physics models to explore chromatin structure
Published in International Journal of Parallel, Emergent and Distributed Systems, 2022
Mattia Conte, Andrea Esposito, Luca Fiorillo, Raffaele Campanile, Carlo Annunziatella, Alfonso Corrado, Maria Gabriella Chiariello, Simona Bianco, Andrea M. Chiariello
The performance of the procedure has been successfully tested on several loci (see, e.g. [19,32] and reviews in [33–35]). Here, we review the test case of the Sox9 locus, an important genomic region in mammals, involved in male sexual development, whose mutations are linked to genetic diseases, such as skeletal malformation and sex-reversal syndromes [36]. The procedure has been applied on a L = 6 Mb region around the Sox9 gene (chr11:109-115 Mb). The corresponding contact map (Hi-C data in mouse embryonic cells mESC-J1 from [4]) is shown in Figure 7, panel a. In this case, the experimental resolution is n = 40 kb, so M = L/n = 150 and the matrix is 150 × 150. Taking in input such matrix, PRISMR extracts the number of types and the position of the binding sites along the chain. For the Sox9 locus, 15 different types of binding sites were found, with their cognate binders [19]. Such types are found to correlate with epigenetics marks as well as combinations of those [14,19]. We can then perform MD simulations with the above-described methods and study the 3D conformations. From them, we can re-compute the contact map, based on the physical distances between the beads of the polymer, and compare it with the experimental map. In Figure 7, panel a, bottom matrix, the resulting simulated map is shown, which captures very accurately most of the features contained in the experimental Hi-C map. This proves that the simulated 3D structures could represent the real 3D architecture of the locus. In Figure 7, panel b, a snapshot from a real MD simulation is shown.