Pyrintegrin Induces Soft Tissue Formation by Transplanted or Endogenous Cells

Focal adipose deficiency, such as lipoatrophy, lumpectomy or facial trauma, is a formidable challenge in reconstructive medicine, and yet scarcely investigated in experimental studies. Here, we report that Pyrintegrin (Ptn), a 2,4-disubstituted pyrimidine known to promote embryonic stem cells survival, is robustly adipogenic and induces postnatal adipose tissue formation in vivo of transplanted adipose stem/progenitor cells (ASCs) and recruited endogenous cells. In vitro, Ptn stimulated human adipose tissue derived ASCs to differentiate into lipid-laden adipocytes by upregulating peroxisome proliferator-activated receptor (PPARγ) and CCAAT/enhancer-binding protein-α (C/EBPα), with differentiated cells increasingly secreting adiponectin, leptin, glycerol and total triglycerides. Ptn-primed human ASCs seeded in 3D-bioprinted biomaterial scaffolds yielded newly formed adipose tissue that expressed human PPARγ, when transplanted into the dorsum of athymic mice. Remarkably, Ptn-adsorbed 3D scaffolds implanted in the inguinal fat pad had enhanced adipose tissue formation, suggesting Ptn’s ability to induce in situ adipogenesis of endogenous cells. Ptn promoted adipogenesis by upregulating PPARγ and C/EBPα not only in adipogenesis induction medium, but also in chemically defined medium specifically for osteogenesis, and concurrently attenuated Runx2 and Osx via BMP-mediated SMAD1/5 phosphorylation. These findings suggest Ptn’s novel role as an adipogenesis inducer with a therapeutic potential in soft tissue reconstruction and augmentation

Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury

Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment. Wnt signals deplete the reservoir of FCSCs and cause cartilage degeneration. We also show that intra-articular treatment with the Wnt inhibitor sclerostin sustains the FCSC pool and regenerates cartilage in a TMJ injury model. We demonstrate the promise of exploiting resident FCSCs as a regenerative therapeutic strategy to substitute cell transplantation that could be beneficial for patients suffering from fibrocartilage injury and disease. These data prompt the examination of utilizing this strategy for other musculoskeletal tissues

Extracellular matrix turnover and inflammation in chemically-induced TMJ arthritis mouse models.

The temporomandibular joint (TMJ) is a fibrocartilaginous tissue critical for chewing and speaking. In patients with temporomandibular disorders (TMDs), permanent tissue loss can occur. Recapitulating the complexity of TMDs in animal models is difficult, yet critical for the advent of new therapies. Synovial fluid from diseased human samples revealed elevated levels of tumor necrosis factor alpha (TNF-alpha). Here, we propose to recapitulate these findings in mice by subjecting murine TMJs with TNF-alpha or CFA (Complete Freund's Adjuvant) in mandibular condyle explant cultures and by local delivery in vivo using TMJ intra-articular injections. Both TNF-alpha and CFA delivery to whole mandibular explants and in vivo increased extracellular matrix deposition and increased cartilage thickness, while TNF-alpha treated explants had increased expression of inflammatory cytokines and degradative enzymes. Moreover, the application of TNF-alpha or CFA in both models reduced cell number. CFA delivery in vivo caused soft tissue inflammation, including pannus formation. Our work provides two methods of chemically induced TMJ inflammatory arthritis through a condyle explant model and intra-articular injection model that replicate findings seen in synovial fluid of human patients, which can be used for further studies delineating the mechanisms underlying TMJ pathology

Study of soft magnetic thin films and patterned devices with MOKE imaging technique

While the conventional microelectronic integrated circuits based on the electron charge are approaching the theoretical limitation in foreseeable future, next generation nonvolatile logic units based on electron spin have potential to build logic networks of low-power consumption. Central to this work is to investigate the magnetic properties of soft magnetic materials and develop a method for in-memory computing based on patterned soft magnetic materials logic units. The mainly result were carried out by Magneto-optical Kerr effect (MOKE) microscopy. By inverting the growth order, the amount of defects can be artificially tuned, and skyrmions are shown to be preferentially formed in samples with more defects. The stable region and the density of the skyrmions can be efficiently controlled in the return magnetization loops by utilizing first-order reversal curves (FORCs). The major contribution of these findings establish a general internal link from sample preparation to skyrmion generation and provides a general method for controlling skyrmion density. Next, the temperature-dependent magnetic properties of MgO/CoFeB/Ta thin films have been investigated. The perpendicular magnetic anisotropy (PMA) gradient in MgO/CoFeB/Ta thin films via the temperature gradient generation sample stage has been studied. This study provides a new easy method to create a PMA gradient that will contribute to the simplification of field-free spintronic devices. Eventually, Y-shaped NiFe nanowire has been investigated. The quasi-static micromagnetic simulations correspond to the experimental results and reveal the principle of device operations. The use of programmable logic units and potential applications for in-memory computing have been further extended based on this nanostructure. The major contribution of this part proposes a feasible paradigm for in-memory computing programmable logic gate, which can significantly reduce the complexity of conventional logic circuits. The results conclusion and discussion for the future works are proposed in the final chapter

CCDC 176993: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.,Related Article: J.R.Downs, S.P.Grant, J.D.Townsend, D.A.Schady, S.J.Pastine, M.C.Embree, C.R.Metz, W.T.Pennington, R.D.B.Walsch, C.F.Beam|2004|Can.J.Chem.|82|659|doi:10.1139/v04-02

CCDC 176994: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.,Related Article: J.R.Downs, S.P.Grant, J.D.Townsend, D.A.Schady, S.J.Pastine, M.C.Embree, C.R.Metz, W.T.Pennington, R.D.B.Walsch, C.F.Beam|2004|Can.J.Chem.|82|659|doi:10.1139/v04-02

CCDC 665082: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.,Related Article: M.A.Meierhoefer, S.P.Dunn, L.M.Hajiaghamohseni, M.J.Walters, M.C.Embree, S.P.Grant, J.R.Downs, J.D.Townsend, C.R.Metz, C.F.Beam, W.T.Pennington, D.G.VanDerveer, N.D.Camper|2005|J.Heterocycl.Chem.|42|1095|doi:10.1002/jhet.557042060