Hydrogel Encapsulation of Genome-Engineered Stem Cells for Long-Term Self-Regulating Anti-Cytokine Therapy.

Biologic therapies have revolutionized treatment options for rheumatoid arthritis (RA) but their continuous administration at high doses may lead to adverse events. Thus, the development of improved drug delivery systems that can sense and respond commensurately to disease flares represents an unmet medical need. Toward this end, we generated induced pluripotent stem cells (iPSCs) that express interleukin-1 receptor antagonist (IL-1Ra, an inhibitor of IL-1) in a feedback-controlled manner driven by the macrophage chemoattractant protein-1 (Ccl2) promoter.

Multi-directional mechanical analysis of synthetic scaffolds for hernia repair.

Hernias remain one of the most common ailments to affect men and women worldwide. Surgical mesh materials were first used to reinforce hernia defects during surgery in the late 1950s (Laker, n.d.

The suture pullout characteristics of human and porcine linea alba.

There is a substantial prevalence of post-operative incisional hernia for both laparoscopic and laparotomy procedures, but there have been few attempts at quantifying abdominal wound closure methodology in the literature. One method to ascertain a more robust method of wound closure is the identification of the influence of suture placement parameters on suture pullout force. Current surgical practice involves a recommended bite depth and bite separation of 10mm, but the evidence base for this is not clear.

Uniaxial and biaxial tensile stress-stretch response of human linea alba.

There are few studies on the stress-stretch behaviour of human linea alba, yet understanding the mechanics of this tissue is important for developing better methods of abdominal wound closure. Published data focuses mainly on porcine linea alba and for human tissue there are conflicting results and no bi-axial data available. This variability is likely due to challenges with the physical dimensions of the tissue and differences in experimental methodology.

Pore size and pore shape--but not mesh density--alter the mechanical strength of tissue ingrowth and host tissue response to synthetic mesh materials in a porcine model of ventral hernia repair.

Background: Over 100 types of soft tissue repair materials are commercially available for hernia repair applications. These materials vary in characteristics such as mesh density, pore size, and pore shape. It is difficult to determine the impact of a single variable of interest due to other compounding variables in a particular design.

Evaluation of absorbable mesh fixation devices at various deployment angles.

Background: Hernia repair failure may occur due to suboptimal mesh fixation by mechanical constructs before mesh integration. Construct design and acute penetration angle may alter mesh-tissue fixation strength. We compared acute fixation strengths of absorbable fixation devices at various deployment angles, directions of loading, and construct orientations.

Biaxial analysis of synthetic scaffolds for hernia repair demonstrates variability in mechanical anisotropy, non-linearity and hysteresis.

Background: Over the past 60 years, the soft tissue repair market has grown to include over 50 types of hernia repair materials. Surgeons typically implant these materials in the orientation that provides maximum overlap of the mesh over the defect, with little regard for mechanical properties of the mesh material. If the characteristics of the meshes were better understood, an appropriate material could be identified for each patient, and meshes could be placed to optimize integration with neighboring tissue and avoid the mechanical mis-match that can lead to impaired graft fixation.

Lithium chloride and inhibition of glycogen synthase kinase 3β as a potential therapy for serous ovarian cancer.

Objective: Lithium chloride (LiCl) has been shown to demonstrate anticancer properties at supratherapeutic doses. This study was designed to determine whether LiCl, as a single agent or in combination with cytotoxic agents, reduces ovarian cancer cell growth and metabolic activity at clinically achievable levels.

Methods: We studied the effects of LiCl on 2 high-grade serous ovarian cancer cell lines, SKOV3 and OVCA 433, and primary cultures developed from ascitic fluid collected from patients with metastatic high-grade serous ovarian cancer.

Frequent mutations in the RPL22 gene and its clinical and functional implications.

Objective: To determine the frequency and spectrum of mutations in RPL22 a gene identified by The Cancer Genome Atlas (TCGA) as mutated in endometrioid endometrial cancer, and determine the relationship between RPL22 defects and clinicopathologic features.

Methods: Direct sequencing of the entire coding region of the RPL22 cDNA and exons 2/4 was performed in tumors with/without microsatellite instability (MSI). RPL22 expression was assessed by immunofluorescence microscopy in the KLE, RL952 and AN3CA cell lines, wildtype, heterozygous and homozygous mutants, respectively.

Geminin regulates the transcriptional and epigenetic status of neuronal fate-promoting genes during mammalian neurogenesis.

Regulating the transition from lineage-restricted progenitors to terminally differentiated cells is a central aspect of nervous system development. Here, we investigated the role of the nucleoprotein geminin in regulating neurogenesis at a mechanistic level during both Xenopus primary neurogenesis and mammalian neuronal differentiation in vitro. The latter work utilized neural cells derived from embryonic stem and embryonal carcinoma cells in vitro and neural stem cells from mouse forebrain.

Aberrant methylation of the X-linked ribosomal S6 kinase RPS6KA6 (RSK4) in endometrial cancers.

Purpose: Effective treatments for advanced endometrial cancer are lacking. Novel therapies that target specific pathways hold promise for better treatment outcomes with less toxicity. Mutation activation of the FGFR2/RAS/ERK pathway is important in endometrial tumorigenesis.

Genome remodelling in a basal-like breast cancer metastasis and xenograft.

Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations.

Subcellular translocation signals regulate Geminin activity during embryonic development.

Background Information: Geminin (Gem) is a protein with roles in regulating both the fidelity of DNA replication and cell fate during embryonic development. The distribution of Gem is predominantly nuclear in cells undergoing the cell cycle. Previous studies have demonstrated that Gem performs multiple activities in the nucleus and that regulation of Gem activation requires nuclear import in at least one context.