Inducing Angiogenesis in the Nucleus Pulposus.

Bone morphogenetic protein (BMP) gene delivery to Lewis rat lumbar intervertebral discs (IVDs) drives bone formation anterior and external to the IVD, suggesting the IVD is inhospitable to osteogenesis. This study was designed to determine if IVD destruction with a proteoglycanase, and/or generating an IVD blood supply by gene delivery of an angiogenic growth factor, could render the IVD permissive to intra-discal BMP-driven osteogenesis and fusion. Surgical intra-discal delivery of naïve or gene-programmed cells (BMP2/BMP7 co-expressing or VEGF expressing) +/- purified chondroitinase-ABC (chABC) in all permutations was performed between lumbar 4/5 and L5/6 vertebrae, and radiographic, histology, and biomechanics endpoints were collected.

Zbtb20 identifies and controls a thymus-derived population of regulatory T cells that play a role in intestinal homeostasis.

The expression of BTB-ZF transcription factors such as ThPOK in CD4 T cells, Bcl6 in T follicular helper cells, and PLZF in natural killer T cells defines the fundamental nature and characteristics of these cells. Screening for lineage-defining BTB-ZF genes led to the discovery of a subset of T cells that expressed Zbtb20. About half of Zbtb20 T cells expressed FoxP3, the lineage-defining transcription factor for regulatory T cells (T).

Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1.

Spontaneous mineralization of the nucleus pulposus (NP) has been observed in cases of intervertebral disc degeneration (IDD). Inflammatory cytokines have been implicated in mineralization of multiple tissues through their modulation of expression of factors that enable or inhibit mineralization, including TNAP, ANKH or ENPP1. This study examines the underlying factors leading to NP mineralization, focusing on the contribution of the inflammatory cytokine, TNF, to this pathologic event.

The Transcription Factor PLZF Is Necessary for the Development and Function of Mouse Basophils.

Basophils are innate immune cells associated with type 2 immunity, allergic reactions, and host defense against parasite infections. In this study, we show that the transcription factor PLZF, which is known for its essential role in the function and development of several innate lymphocyte subsets, is also important for the myeloid-derived basophil lineage. PLZF-deficient mice had decreased numbers of basophil progenitors in the bone marrow and mature basophils in multiple peripheral tissues.

Deregulation of epidermal stem cell niche contributes to pathogenesis of nonhealing venous ulcers.

The epidermis is maintained by epidermal stem cells (ESCs) that reside in distinct niches and contribute to homeostasis and wound closure. Keratinocytes at the nonhealing edges of venous ulcers (VUs) are healing-incompetent, hyperproliferative, and nonmigratory, suggesting deregulation of ESCs. To date, genes which regulate ESC niches have been studied in mice only.

Surgical anatomy, transperitoneal approach, and early postoperative complications of a ventral lumbar spine surgical model in Lewis rats.

Surgical models in animals are used extensively to study small molecules and devices for lumbar intervertebral disc repair, replacement, and fusion. Although the ventral lumbar animal models themselves are well described, critical assessment of morbidity and mortality avoidance when using the models have not been reported. Hypothesizing that technique modifications and the relative prevalence and severity of complications would be correlated, we collected and examined peri- and postoperative data stratified by surgical technique.

Cortisol synthesis in epidermis is induced by IL-1 and tissue injury.

Glucocorticoids (GCs) are known inhibitors of wound healing. In this study we report the novel finding that both keratinocytes in vitro and epidermis in vivo synthesize cortisol and how this synthesis regulates wound healing. We show that epidermis expresses enzymes essential for cortisol synthesis, including steroid 11 β-hydroxylase (CYP11B1), and an enzyme that controls negative feedback mechanism, 11β-hydroxysteroid dehydrogenase 2 (11βHSD2).

Attenuation of the transforming growth factor beta-signaling pathway in chronic venous ulcers.

Transforming growth factor beta (TGFbeta) is important in inflammation, angiogenesis, reepithelialization and connective tissue regeneration during wound healing. We analyzed components of TGFbeta signaling pathway in biopsies from 10 patients with nonhealing venous ulcers (VUs). Using comparative genomics of transcriptional profiles of VUs and TGFbeta-treated keratinocytes, we found deregulation of TGFbeta target genes in VUs.

Farnesyl pyrophosphate inhibits epithelialization and wound healing through the glucocorticoid receptor.

Farnesyl pyrophosphate (FPP), a key intermediate in the mevalonate pathway and protein farnesylation, can act as an agonist for several nuclear hormone receptors. Here we show a novel mechanism by which FPP inhibits wound healing acting as an agonist for glucocorticoid receptor (GR). Elevation of endogenous FPP by the squalene synthetase inhibitor zaragozic acid A (ZGA) or addition of FPP to the cell culture medium results in activation and nuclear translocation of the GR, a known wound healing inhibitor.

Retinoid-responsive transcriptional changes in epidermal keratinocytes.

Retinoids (RA) have been used as therapeutic agents for numerous skin diseases, from psoriasis to acne and wrinkles. While RA is known to inhibit keratinocyte differentiation, the molecular effects of RA in epidermis have not been comprehensively defined. To identify the transcriptional targets of RA in primary human epidermal keratinocytes, we compared the transcriptional profiles of cells grown in the presence or absence of all-trans retinoic acid for 1, 4, 24, 48, and 72 h, using large DNA microarrays.

Deregulation of keratinocyte differentiation and activation: a hallmark of venous ulcers.

Epidermal morphology of chronic wounds differs from that of normal epidermis. Biopsies of non-healing edges obtained from patients with venous ulcers show thick and hyperproliferative epidermis with mitosis present in suprabasal layers. This epidermis is also hyper-keratotic and parakeratotic.

Effect of Vita Glucan on some antioxidant parameters of the human blood. In vitro study.

Recently, beta-glucan has been postulated to modulate antioxidant enzyme activity (superoxide dismutase-SOD) as well as to inhibit lipid peroxidation in studies concerning rats or rabbits. There are very few reports on antioxidant effect of beta-glucan in the human blood. The study was aimed to estimate influence of Vita Glucan (VG) on SOD and catalase (CAT) activities as well as on total antioxidant power measured as ferric reducing activity and ascorbate concentration (FRASC) in the human blood in vitro.