ROS release by PPARβ/δ-null fibroblasts reduces tumor load through epithelial antioxidant response.

Tumor stroma has an active role in the initiation, growth, and propagation of many tumor types by secreting growth factors and modulating redox status of the microenvironment. Although PPARβ/δ in fibroblasts was shown to modulate oxidative stress in the wound microenvironment, there has been no evidence of a similar effect in the tumor stroma. Here, we present evidence of oxidative stress modulation by intestinal stromal PPARβ/δ, using a FSPCre-Pparb/d mouse model and validated it with immortalized cell lines.

Sustained-releasing hollow microparticles with dual-anticancer drugs elicit greater shrinkage of tumor spheroids.

Polymeric particulate delivery systems are vastly explored for the delivery of chemotherapeutic agents. However, the preparation of polymeric particulate systems with the capability of providing sustained release of two or more drugs is still a challenge. Herein, poly (D, L-lactic-co-glycolic acid, 50:50) hollow microparticles co-loaded with doxorubicin and paclitaxel were developed through double-emulsion solvent evaporation technique.

Targeting nuclear receptors in cancer-associated fibroblasts as concurrent therapy to inhibit development of chemoresistant tumors.

Most anticancer therapies to date focus on druggable features of tumor epithelia. Despite the increasing repertoire of treatment options, patient responses remain varied. Moreover, tumor resistance and relapse remain persistent clinical challenges.

ANGPTL4 T266M variant is associated with reduced cancer invasiveness.

Angiopoietin-like 4 (ANGPTL4) is a secretory protein that can be cleaved to form an N-terminal and a C-terminal protein. Studies performed thus far have linked ANGPTL4 to several cancer-related and metabolic processes. Notably, several point mutations in the C-terminal ANGPTL4 (cANGPTL4) have been reported, although no studies have been performed that ascribed these mutations to cancer-related and metabolic processes.

Nanomechanically Visualizing Drug-Cell Interaction at the Early Stage of Chemotherapy.

A detailed understanding of chemotherapy is determined by the response of cell to the formation of the drug-target complex and its corresponding sudden or eventual cell death. However, visualization of this early but important process, encompassing the fast dynamics as well as complex network of molecular pathways, remains challenging. Herein, we report that the nanomechanical traction force is sensitive enough to reflect the early cellular response upon the addition of chemotherapeutical molecules in a real-time and noninvasive manner, due to interactions between chemotherapeutic drug and its cytoskeleton targets.

Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin.

Many gastrointestinal diseases exhibit a protracted and aggravated inflammatory response that can lead to hypercytokinaemia, culminating in extensive tissue damage. Recently, angiopoietin-like 4 (ANGPTL4) has been implicated in many inflammation-associated diseases. However, how ANGPTL4 regulates colonic inflammation remains unclear.

Cancer-associated fibroblasts enact field cancerization by promoting extratumoral oxidative stress.

Histological inspection of visually normal tissue adjacent to neoplastic lesions often reveals multiple foci of cellular abnormalities. This suggests the presence of a regional carcinogenic signal that spreads oncogenic transformation and field cancerization. We observed an abundance of mutagenic reactive oxygen species in the stroma of cryosectioned patient tumor biopsies, indicative of extratumoral oxidative stress.

Comparative study of adipose-derived stem cells and bone marrow-derived stem cells in similar microenvironmental conditions.

Mesenchymal stem cells (MSCs), which were first isolated from the bone marrow, are now being extracted from various other tissues in the body, including the adipose tissue. The current study presents systematic evidence of how the adipose tissue-derived stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (Bm-MSCs) behave when cultured in specific pro-adipogenic microenvironments. The cells were first characterized and identified as MSCs in terms of their morphology, phenotypic expression, self-renewal capabilities and multi-lineage potential.

Surface modification of PVDF using non-mammalian sources of collagen for enhancement of endothelial cell functionality.

Although polyvinylidene fluoride (PVDF) is non-toxic and stable in vivo, its hydrophobic surface has limited its bio-applications due to poor cell-material interaction and thrombus formation when used in blood contacting devices. In this study, surface modification of PVDF using naturally derived non-mammalian collagen was accomplished via direct surface-initiated atom transfer radical polymerisation (SI-ATRP) to enhance its cytocompatibility and hemocompatibility. Results showed that Type I collagen was successfully extracted from fish scales and bullfrog skin.

Cell-secreted extracellular matrix formation and differentiation of adipose-derived stem cells in 3D alginate scaffolds with tunable properties.

Three dimensional (3D) alginate scaffolds with tunable mechanical and structural properties are explored for investigating the effect of the scaffold properties on stem cell behavior and extracellular matrix (ECM) formation. Varying concentrations of crosslinker (20 - 60%) are used to tune the stiffness, porosity, and the pore sizes of the scaffolds post-fabrication. Enhanced cell proliferation and adipogenesis occur in scaffolds with 3.

A Periosteum-Inspired 3D Hydrogel-Bioceramic Composite for Enhanced Bone Regeneration .

A 3D injectable hydrogel-bioceramic composite consisting of gelatin-3-(4-hydroxyphenyl) propionic acid (Gtn-HPA) and carboxymethyl cellulose-tyramine (CMC-Tyr), incorporated with fish scale-derived calcium phosphate (CaP), is developed for bone applications. The hydrogel-bioceramic composite has significantly improved the elastic modulus compared to the non-filled hydrogel, of which the addition of 10 w/v% CaP showed zero order fluorescein isothiocyanate (FITC)-dextran release profile and a significantly higher proliferation rate of encapsulated cells. All the samples promote the nucleation and growth of CaP minerals when exposed to 1× SBF.

Bio-conjugated polycaprolactone membranes: a novel wound dressing.

Background: The combination of polycaprolactone and hyaluronic acid creates an ideal environment for wound healing. Hyaluronic acid maintains a moist wound environment and accelerates the in-growth of granulation tissue. Polycaprolactone has excellent mechanical strength, limits inflammation and is biocompatible.

Sedation guidelines, protocols, and algorithms in PICUs: a systematic review.

Objective: To evaluate the impact of sedation guidelines, protocols, and algorithms on clinical outcomes in PICUs.

Data Sources: CINAHL, Medline, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews,

Study Selection: : English-only publications from 1966 to December 2013, which included keywords "sedation," "guideline," "algorithm," "protocol," and "pediatric intensive care." We included all primary studies involving critically ill children on sedation guidelines, protocols, and algorithms and excluded those which focused mainly on diagnostic or procedural purposes.

Decidualised fallopian tube endometriotic implant causing spontaneous haemoperitoneum in a twin pregnancy.

Spontaneous haemoperitoneum in pregnancy (SHiP) is a rare but serious condition associated with an adverse pregnancy outcome. We present a case of previable twin pregnancy presenting with SHiP secondary to endometriosis, necessitating an emergency laparotomy and hysterotomy as a life-saving measure to achieve haemostasis. At laparotomy there was massive haemoperitoneum with active bleeding from the left fallopian tube and a left salpingectomy was performed.

Leiomyomatosis peritonealis disseminata and subcutaneous myoma--a rare complication of laparoscopic myomectomy.

We present a case of leiomyomatosis peritonealis disseminata (LPD) after laparoscopic myomectomy with imaging features corroborating laparoscopic tract dissemination of the tumor. This would suggest a subset cases of LPD may be secondary to transcoelomic dissemination of a primary uterine leiomyoma rather than de novo peritoneal metaplasia. To our knowledge, this is the first case report of LPD and subcutaneous leiomyoma complicating laparoscopic surgery.

Immunogenicity and reactogenicity of two regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio and Haemophilus influenzae type b vaccines administered to infants primed at birth with hepatitis B vaccine.

An open, randomized study evaluated the immune response and safety of two different regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPa-HBV-IPV-Hib) immunization in infants primed at birth with hepatitis B vaccine. One-half of the 150 healthy, full-term infants received a DTPa HBV-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age; the other received a DTPa-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age with separate HBV vaccine at 1 and 5 months of age. Immune response was similar following the two regimens with 100% of the vaccinees seroprotected for HBV, diphtheria, tetanus, Hib and poliovirus types 2 and 3 diseases after the full vaccination course.