Neocollagenesis in human tissue injected with a polycaprolactone-based dermal filler.

A novel dermal filler containing polycaprolactone (PCL) has been introduced into the aesthetic market. A recently published study has shown that the PCL-based dermal filler induces neocollagenesis, a process associated with improvement in appearance of the skin, in rabbit tissue. In this pilot study, we investigated whether the PCL-based dermal filler induces neocollagenesis in human tissue by histological analysis. Two patients who were enrolled in the study, and were willing to undergo temple lifting surgery, were injected intra-dermally with the PCL-based dermal filler. Thirteen months post-injection, biopsies were obtained for subsequent histological analysis. Histological analysis of tissue obtained from the biopsies (13 months post-injection) revealed that the PCL-based dermal filler shows collagen formation around the PCL particles and, therefore, supports similar findings previously shown in rabbit tissue. In conclusion, PCL particles are maintained in their original state 13 months post-injection.

The STOX1 genotype associated with pre-eclampsia leads to a reduction of trophoblast invasion by alpha-T-catenin upregulation.

By using complementary in vitro and ex vivo approaches, we show that the risk allele (Y153H) of the pre-eclampsia susceptibility gene STOX1 negatively regulates trophoblast invasion by upregulation of the cell-cell adhesion protein alpha-T-catenin (CTNNA3). This is effectuated at the crucial epithelial-mesenchymal transition of proliferative into invasive extravillous trophoblast. This STOX1-CTNNA3 interaction is direct and includes Akt-mediated phosphorylated control of nucleo-cytoplasmic shuttling and ubiquitin-mediated degradation as shared with the FOX multigene family. This, to our knowledge, is the first time a genotype associated with pre-eclampsia has been shown to directly limit first trimester extravillous trophoblast invasion, the earliest hallmark of pre-eclampsia.

Stox1 as a novel transcriptional suppressor of Math1 during cerebellar granule neurogenesis and medulloblastoma formation.

Cerebellar granule neuronal progenitors (GNPs) are the precursors of cerebellar granule cells (CGCs) and are believed to be the cell of origin for medulloblastoma (MB), yet the molecular mechanisms governing GNP neurogenesis are poorly elucidated. Here, we demonstrate that storkhead box 1 (Stox1), a forkhead transcriptional factor, has a pivotal role in cerebellar granule neurogenesis and MB suppression. Expression of Stox1 is upregulated along with GNP differentiation and repressed by activation of sonic hedgehog (SHH) signaling. Stox1 exerts its neurogenic and oncosuppressing effect via direct transcriptional repression of Math1, a basic helix-loop-helix transcription activator essential for CGC genesis. This study illustrates a SHH-Stox1-Math1 regulatory axis in normal cerebellar development and MB formation.

A randomized, prospective, blinded, split-face, single-center study comparing polycaprolactone to hyaluronic acid for treatment of nasolabial folds.

BACKGROUND: Dermal fillers have continuingly been under development to increase safety, efficacy, and longevity. Biostimulatory dermal fillers, such as calcium hydroxylapatite fillers, have already been shown to be superior in efficacy compared to nonanimal stabilized hyaluronic acid (NASHA)-based fillers. AIMS: In this randomized split-face study, we compared a novel biostimulatory polycaprolactone (PCL)-based dermal filler with a NASHA-based dermal filler, for safety, efficacy, and duration of cosmetic correction for the treatment of nasolabial folds (NLFs). PATIENTS/METHODS: Forty subjects received a PCL-based dermal filler in one of their NLFs, and a NASHA-based dermal filler on the contralateral side. Efficacy was evaluated based on the Wrinkle Severity Rating Scale and Global Aesthetic Improvement Scale. RESULTS: After 6, 9, and 12 months post-treatment, NLFs treated with the PCL-based dermal filler showed statistically significant improvements on the Wrinkle Severity Rating Scale and greater improvements on the GAIS compared to NLFs treated with the NASHA-based dermal filler. Both products were found to be equally safe and well tolerated. CONCLUSION: Our results suggest that PCL-based dermal fillers offer longer-lasting performance over NASHA-based dermal fillers in NLFs treatment.

STOX1A induces phosphorylation of tau proteins at epitopes hyperphosphorylated in Alzheimer's disease.

Intraneuronal fibrillary tangles are a major hallmark of several neurodegenerative diseases including Alzheimer's disease. The major constituents of these hallmarks are hyper-phosphorylated tau. In this study we used a neuronal cellular model which over-expresses transcription factor STOX1A in combination with the longest human tau isoform to test the effect of STOX1A on tau phosphorylation. Our results show that STOX1A induces phosphorylation of the longest human tau isoform at phospho-epitopes typically found in neurofibrillary tangles in Alzheimer's disease. In conclusion, our results show a STOX1A-dependent effect on tau phosphorylation found in neurodegenerative diseases such as Alzheimer's disease.

Direct downregulation of CNTNAP2 by STOX1A is associated with Alzheimer's disease.

STOX1A is a transcription factor which is functionally and structurally similar to the forkhead box protein family. STOX1A has been shown to be associated with pre-eclampsia, a pregnancy associated disease, and to have potential implications in late onset Alzheimer's disease. However, the exact function of STOX1A and its target genes are still largely unknown. Therefore, in this study we performed chromatin immunoprecipitation coupled to shotgun cloning to discover novel STOX1A target genes. Our results show that CNTNAP2, a member of the neurexin family, is directly downregulated by STOX1A. Additionally, we show that CNTNAP2 expression is downregulated in the hippocampus of Alzheimer's disease patients where STOX1A expression has been shown to be upregulated. In conclusion, these results further indicate the potential involvement of STOX1A and its target genes in the etiology of Alzheimer's disease.

SFRS7-mediated splicing of tau exon 10 is directly regulated by STOX1A in glial cells.

BACKGROUND: In this study, we performed a genome-wide search for effector genes bound by STOX1A, a winged helix transcription factor recently demonstrated to be involved in late onset Alzheimer's disease and affecting the amyloid processing pathway. METHODOLOGY/PRINCIPAL FINDINGS: Our results show that out of 218 genes bound by STOX1A as identified by chromatin-immunoprecipitation followed by sequencing (ChIP-Seq), the serine/arginine-rich splicing factor 7 (SFRS7) was found to be induced, both at the mRNA and protein levels, by STOX1A after stable transfection in glial cells. The increase in SFRS7 was followed by an increase in the 4R/3R ratios of the microtubule-associated protein tau (MAPT) by differential exon 10 splicing. Secondly, STOX1A also induced expression of total tau both at the mRNA and protein levels. Upregulation of total tau expression (SFRS7-independent) and tau exon 10 splicing (SFRS7-dependent), as shown in this study to be both affected by STOX1A, is known to have implications in neurodegeneration. CONCLUSIONS: Our data further supports the functional importance and central role of STOX1A in neurodegeneration.