Development and characterisation of novel electrospun polylactic acid/tubular clay nanocomposites

A novel material formulation method of polylactic acid /tubular clay nanocomposites via electrospinning was introduced and the important processing parameters such as solution concentration, clay loading, material feed rate were particularly investigated. The hybrid fibre diameter, the clay dispersability and the thermal properties of such nanocomposites were then characterised by using the scanning electron microscopy, wide-angle X-ray diffraction and differential scanning calorimetry, respectively, to establish a fundamental structure–property relationship for the future application

Multi-response analysis in the material characterisation of electrospun poly (lactic acid)/halloysite nanotube composite fibres based on Taguchi design of experiments: fibre diameter, non-intercalation and nucleation effects

Poly (lactic acid) (PLA)/halloysite nanotube (HNT) composite fibres were prepared by using a simple and versatile electrospinning technique. The systematic approach via Taguchi design of experiments (DoE) was implemented to investigate factorial effects of applied voltage, feed rate of solution, collector distance and HNT concentration on the fibre diameter, HNT non-intercalation and nucleation effects. The HNT intercalation level, composite fibre morphology, their associated fibre diameter and thermal properties were evaluated by means of X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), imaging analysis and differential scanning calorimetry (DSC), respectively. HNT non-intercalation phenomenon appears to be manifested as reflected by the minimal shift of XRD peaks for all electrospun PLA/HNT composite fibres. The smaller-fibre-diameter characteristic was found to be sequentially associated with the feed rate of solution, collector distance and applied voltage. The glass transition temperature (T g) and melting temperature (T m) are not highly affected by varying the material and electrospinning parameters. However, as the indicator of the nucleation effect, the crystallisation temperature (T c) of PLA/HNT composite fibres is predominantly impacted by HNT concentration and applied voltage. It is evident that HNT’s nucleating agent role is confirmed when embedded with HNTs to accelerate the cold crystallisation of composite fibres. Taguchi DoE method has been found to be an effective approach to statistically optimise critical parameters used in electrospinning in order to effectively tailor the resulting physical features and thermal properties of PLA/HNT composite fibres

Individual and combined soy isoflavones exert differential effects on metastatic cancer progression

To investigate the effects soy isoflavones in established cancers, the role of genistein, daidzein, and combined soy isoflavones was studied on progression of subcutaneous tumors in nude mice created from green fluorescent protein (GFP) tagged-MDA-MB-435 cells. Following tumor establishment, mice were gavaged with vehicle or genistein or daidzein at 10 mg/kg body weight (BW) or a combination of genistein (10 mg/kg BW), daidzein (9 mg/kg BW), and glycitein (1 mg/kg BW) three times per week. Tumor progression was quantified by whole body fluorescence image analysis followed by microscopic image analysis of excised organs for metastases. Results show that daidzein increased while genistein decreased mammary tumor growth by 38 and 33% respectively, compared to vehicle. Daidzein increased lung and heart metastases while genistein decreased bone and liver metastases. Combined soy isoflavones did not affect primary tumor growth but increased metastasis to all organs tested, which include lung, liver, heart, kidney, and bones. Phosphoinositide-3-kinase (PI3-K) pathway real time PCR array analysis and western blotting of excised tumors demonstrate that genistein significantly downregulated 10/84 genes, including the Rho GTPases RHOA, RAC1, and CDC42 and their effector PAK1. Daidzein significantly upregulated 9/84 genes that regulate proliferation and protein synthesis including EIF4G1, eIF4E, and survivin protein levels. Combined soy treatment significantly increased gene and protein levels of EIF4E and decreased TIRAP gene expression. Differential regulation of Rho GTPases, initiation factors, and survivin may account for the disparate responses of breast cancers to genistein and daidzein diets. This study indicates that consumption of soy foods may increase metastasis

Inhibition of cancer cell invasion and metastasis by genistein

Genistein is a small, biologically active flavonoid that is found in high amounts in soy. This important compound possesses a wide variety of biological activities, but it is best known for its ability to inhibit cancer progression. In particular, genistein has emerged as an important inhibitor of cancer metastasis. Consumption of genistein in the diet has been linked to decreased rates of metastatic cancer in a number of population-based studies. Extensive investigations have been performed to determine the molecular mechanisms underlying genistein’s antimetastatic activity, with results indicating that this small molecule has significant inhibitory activity at nearly every step of the metastatic cascade. Reports have demonstrated that, at high concentrations, genistein can inhibit several proteins involved with primary tumor growth and apoptosis, including the cyclin class of cell cycle regulators and the Akt family of proteins. At lower concentrations that are similar to those achieved through dietary consumption, genistein can inhibit the prometastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the transforming growth factor (TGF)-β signaling pathway. Several in vitro findings have been corroborated in both in vivo animal studies and in early-phase human clinical trials, demonstrating that genistein can both inhibit human cancer metastasis and also modulate markers of metastatic potential in humans, respectively. Herein, we discuss the variety of mechanisms by which genistein regulates individual steps of the metastatic cascade and highlight the potential of this natural product as a promising therapeutic inhibitor of metastasis

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

GATA3 upregulates BMP5 in MB-231 cells.

<p>(A) Q-RT-PCR showing expression of BMP2, BMP4 and BMP5 in 231-Empty and 231-GATA3 cells. GATA3 significantly upregulates BMP5 expression in MB-231 cells. (B) Western Blot analysis showing increased pSMAD1/5/8 in TGFß1+BMP5 treated 231-GATA3 cells compared to 231-Empty cells. ß-actin was used as a loading control. (C) BrdU incorporation in pulse-labeled 231-Empty and 231-GATA3 cells as measured by flow cytometry. Bar graph shows % cells in S phase (mean +/− SEM).</p

Network of genes involved in cell cycle regulation.

<p>Network of genes that were differentially expressed between 231-Empty and 231-GATA3 by >1.5 fold and p<0.001 (Ingenuity Pathway Analysis). Green represents reduced gene expression upon TGFß1 stimulation compared to untreated cells and red represent increased gene expression compared to untreated cells. Intensity of the color represents the degree of change for (A) 231-Emtpy cells and (B) 231-GATA3 cells. Many more genes in this network are downregulated by TGFß1in 231-GATA3 cells compared to 231-Empty cells.</p

GATA3 confers growth inhibitory response to TGFß1 in MB-231 cells.

<p>(A) Flow cytometric analysis of 231-Empty and 231-GATA3 cells grown in full serum, SR (serum replacement) or SR +TGFß for 24 hrs. 231-GATA3 cells show a reduction in %S-phase cells upon TGF-ß1 treatment compared to SR conditions whereas 231-Empty cells continue to proliferate with TGF-ß1 treatment. (B) Western blot analysis of GATA3 downregulation by siRNA and flow cytometric analysis of TGFb effect in control or GATA-3 siRNA transfected cells. Percentage of cells in S-phase is provided on each panel.</p

GATA3 reduces the TGFß1 transcriptional response in MB-231 cells and abrogates TGFß1 mediated EMT.

<p>(A) Luciferase activity of 231-Empty and 231-GATA3 cells using the TGFß response reporter construct CAGA12. 231-GATA3 cells exhibited a reduced TGF-ß1-dependent activation of CAGA12 compared to 231-Empty cells. (B) Western blot analysis of 231-Empty and 231-GATA3 cells showing changes in activation of SMAD signaling in response to TGF-ß1. 231-GATA3 cells treated with TGF-ß1 for 1 hr. showed reduced p-SMAD 3 and p-SMAD 2 levels compared to 231-Empty cells. ß-actin was used as loading control. (C) Western blot analysis showing differences in expression of EMT markers at the indicated times. Cells were grown in SR media and treated with TGF-ß1 for 12, 24 or 48 hrs.</p

GATA3 reduces effectors in the TGFß1 pathway in MB-231 cells.

<p>(A) Ingenuity network analysis of 231-Empty vs. 231-GATA3 cells. Genes that were differentially expressed in 231-Empty vs. 231-GATA3 cells (p<0.001, fold change >1.5) were input into Ingenuity Pathway analysis. One of the top networks identified demonstrated changes in several TGFß1 effectors. (B) Western blot of 231-Empty and 231-GATA3 cells validating changes in expression of Smad2, Smad3 and Smad1 between 231-Emtpy and 231-GATA3 cells.</p