Dual [68Ga]DOTATATE and [18F]FDG PET/CT in patients with metastatic gastroenteropancreatic neuroendocrine neoplasms: a multicentre validation of the NETPET score.

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) are heterogeneous in clinical course, biology, and outcomes. The NETPET score predicts survival by scoring uptake on dual [68Ga]DOTATATE and [18F]FDG PET/CT scans. We aimed to validate previous single-centre findings in a multicentre, international study. METHODS: Dual scans were assigned a NETPET score of P1 (DOTATATE positive/FDG negative), P2-4 (DOTATATE positive/FDG positive), or P5 (DOTATATE negative/FDG positive). NETPET score, histological grade, age at diagnosis, and presence/absence of extrahepatic disease were compared to overall survival/time to progression on univariate and multivariate analysis. RESULTS: 319 metastatic/unresectable GEPNEN patients were included. The NETPET score was significantly associated with overall survival and time to progression on univariate and multivariate analysis (all p < 0.01). Median overall survival/time to progression was 101.8/25.5 months for P1, 46.5/16.7 months for P2-4, and 11.5/6.6 months for P5. Histological grade correlated with overall survival and time to progression on univariate and multivariate analysis (all p < 0.01), while presence/absence of extrahepatic disease did not. Age at diagnosis correlated with overall survival on univariate and multivariate analysis (p < 0.01). The NETPET score also correlated with histological grade (p < 0.001). CONCLUSION: This study validates the NETPET score as a prognostic biomarker in metastatic GEPNENs, capturing the complexity of dual PET imaging.

I-PET score: Combining whole body iodine and 18 F-FDG PET/CT imaging to predict progression in structurally or biochemically incomplete thyroid cancer.

OBJECTIVE: We propose a new scoring system (I-PET) combining whole body scan (WBS) and FDG findings to identify patients who have or are likely to become refractory to radioactive iodine. DESIGN: Retrospective analysis of 142 patients age >18 with differentiated thyroid cancer who had a F-18 labelled fluoro-2-deoxyglucose (18 F-FDG) positron emission tomography (PET) and WBS within a 6-month period between 2010 and 2020. Pairs of 18 F-FDG PET and WBS were reviewed by three independent nuclear medicine physicians and an I-PET score was assigned: I-PET [0]: Iodine -ve/FDG -ve, I-PET [1]: Iodine +ve/FDG -ve, I-PET [2]: Iodine +ve/FDG +ve and I-PET [3]: Iodine -ve/FDG +ve. Patients with FDG +ve lesions (I-PET [2] and I-PET [3]) were further classified into groups A and B if SUVmax was ≤5 or >5, respectively. Follow-up data were obtained by chart review. Progression was defined as structural progression as per RECIST 1.1 or further surgical intervention; or biochemical progression as unstimulated thyroglobulin increasing >20% from baseline. RESULTS: Of 142 patients included in the study 121 patients had follow-up data available for review. At baseline, 49 patients were classified as I-PET [0], 10 as I-PET [1], 16 as I-PET [2] and 46 as I-PET [3]. Progression was seen in 11/49 (22%) of I-PET [0], 4/10 (40%) of I-PET [1], 10/16 (63%) of I-PET [2] and 34/46 (74%) of I-PET [3] (p < 0.001). I-PET [2B] and I-PET [3B] had a progression rate of 88% (7/8) and 78% (25/32), respectively. I-PET [3B] were 9.6 times more likely to commence multikinase inhibitor therapy (p = 0.001) and had 8 times greater mortality (p = 0.003) than patients in other I-PET groups combined. CONCLUSION: I-PET is a simple readily acquired imaging biomarker that potentially enhances the dynamic risk stratification and guide treatment in thyroid cancer.

Australasian Consensus Statement on the Identification, Prevention, and Management of Hormonal Crises in Patients with Neuroendocrine Neoplasms Undergoing Peptide Receptor Radionuclide Therapy.

Hormonal crises are a rare but increasingly recognized phenomenon following peptide receptor radionuclide therapy (PRRT) in patients with neuroendocrine neoplasms (NENs). Due to the paucity of published studies, approaches to the identification, prevention, and management of risk factors are inconsistent between different institutions. This consensus statement aimed to provide guidance for NEN patients undergoing PRRT. Our statement has been created on the basis of clinical demand and concerns regarding the precipitation of hormonal crises. A formal literature review was conducted to identify available studies. A total of 19 Australian and New Zealand experts in the fields of medical oncology, nuclear medicine, anaesthetics, and endocrinology collaborated on this consensus statement. The main focus is on carcinoid crises. Other hormonal crises seen in patients with functional pancreatic NENs are addressed briefly. These recommendations are relevant to PRRT centres internationally and should be tailored to local experience and available resources.

Exploring the microstructure of hydrated collagen hydrogels under scanning electron microscopy.

Collagen hydrogels are a rapidly expanding platform in bioengineering and soft materials engineering for novel applications focused on medical therapeutics, medical devices and biosensors. Observations linking microstructure to material properties and function enables rational design strategies to control this space. Visualisation of the microscale organisation of these soft hydrated materials presents unique technical challenges due to the relationship between hydration and the molecular organisation of a collagen gel. Scanning electron microscopy is a robust tool widely employed to visualise and explore materials on the microscale. However, investigation of collagen gel microstructure is difficult without imparting structural changes during preparation and/or observation. Electrons are poorly propagated within liquid-phase materials, limiting the ability of electron microscopy to interrogate hydrated gels. Sample preparation techniques to remove water induce artefactual changes in material microstructure particularly in complex materials such as collagen, highlighting a critical need to develop robust material handling protocols for the imaging of collagen hydrogels. Here a collagen hydrogel is fabricated, and the gel state explored under high-vacuum (10-6  Pa) and low-vacuum (80-120 Pa) conditions, and in an environmental SEM chamber. Visualisation of collagen fibres is found to be dependent on the degree of sample hydration, with higher imaging chamber pressures and humidity resulting in decreased feature fidelity. Reduction of imaging chamber pressure is used to induce evaporation of gel water content, revealing collagen fibres of significantly larger diameter than observed in samples dehydrated prior to imaging. Rapid freezing and cryogenic handling of the gel material is found to retain a porous 3D structure following sublimation of the gel water content. Comparative analysis of collagen hydrogel materials demonstrates the care needed when preparing hydrogel samples for electron microscopy.

Evaluation of Polymeric Particles for Modular Tissue Cultures in Developmental Engineering.

Developmental engineering (DE) aims to culture mammalian cells on corresponding modular scaffolds (scale: micron to millimeter), then assemble these into functional tissues imitating natural developmental biology processes. This research intended to investigate the influences of polymeric particles on modular tissue cultures. When poly(methyl methacrylate) (PMMA), poly(lactic acid) (PLA) and polystyrene (PS) particles (diameter: 5-100 µm) were fabricated and submerged in culture medium in tissue culture plastics (TCPs) for modular tissue cultures, the majority of adjacent PMMA, some PLA but no PS particles aggregated. Human dermal fibroblasts (HDFs) could be directly seeded onto large (diameter: 30-100 µm) PMMA particles, but not small (diameter: 5-20 µm) PMMA, nor all the PLA and PS particles. During tissue cultures, HDFs migrated from the TCPs surfaces onto all the particles, while the clustered PMMA or PLA particles were colonized by HDFs into modular tissues with varying sizes. Further comparisons revealed that HDFs utilized the same cell bridging and stacking strategies to colonize single or clustered polymeric particles, and the finely controlled open pores, corners and gaps on 3D-printed PLA discs. These observed cell-scaffold interactions, which were then used to evaluate the adaptation of microcarrier-based cell expansion technologies for modular tissue manufacturing in DE.

Event-free survival after radical prostatectomy according to prostate-specific membrane antigen-positron emission tomography and European Association of Urology biochemical recurrence risk groups.

OBJECTIVE: To assess European Association of Urology (EAU) risk groups for biochemical recurrence (BCR) of prostate cancer relative to prostate-specific membrane antigen-positron emission tomography (PSMA-PET) status and oncological outcomes. PATIENTS AND METHODS: A retrospective analysis of a study that incorporated PSMA-PET for men with BCR after radical prostatectomy (RP) was undertaken. EAU risk groups were considered relative to clinical variables, PSMA-PET findings, and deployment of salvage radiotherapy (SRT). The primary oncological outcome was event-free survival (EFS) and this was analysed relative to clinical and imaging variables. An 'event' occurred if prostate-specific antigen (PSA) level rose >0.2 ng/mL above nadir or additional therapies were introduced. RESULTS: A total of 137 patients were included, most of whom had EAU high-risk disease (76%) and/or low PSA levels (80% <0.5 ng/mL) at the time of PSMA-PET. EAU risk group was not associated with regional nodal/distant metastasis on PSMA-PET. Regional nodal/distant metastasis on PSMA PET (compared to negative/local recurrence: hazard ratio [HR] 2.2; P = 0.002) and SRT use (vs no SRT: HR 0.44; P = 0.004) were associated with EFS. EAU high-risk status was not significantly associated with worse EFS (HR 1.7, P = 0.12) compared to EAU low-risk status. Among patients who received SRT, both regional/distant metastasis on PSMA-PET (HR 3.1; P < 0.001) and EAU high-risk status (HR 2.9; P = 0.04) were independently associated with worse EFS, which was driven by patients in the EAU high-risk group with regional/distant metastases (38%; HR 3.1, P = 0.001). CONCLUSIONS: In patients with post-RP BCR, PSMA-PET findings and receipt of SRT predicted EFS. In patients receiving SRT, PSMA status combined with EAU risk grouping was most predictive of EFS. These findings suggest that the EAU risk groups could be improved with the addition of PSMA-PET.

Immobilization of Wnt Fragment Peptides on Magnetic Nanoparticles or Synthetic Surfaces Regulate Wnt Signaling Kinetics.

Wnt signaling plays an important role in embryogenesis and adult stem cell homeostasis. Its diminished activation is implicated in osteoporosis and degenerative neural diseases. However, systematic administration of Wnt-signaling agonists carries risk, as aberrantly activated Wnt/ß-catenin signaling is linked to cancer. Therefore, technologies for local modulation and control of Wnt signaling targeted to specific sites of disease or degeneration have potential therapeutic value in the treatment of degenerative diseases. We reported a facile approach to locally activate the canonical Wnt signaling cascade using nanomagnetic actuation or ligand immobilized platforms. Using a human embryonic kidney (HEK293) Luc-TCF/LEF reporter cell line, we demonstrated that targeting the cell membrane Wnt receptor, Frizzled 2, with peptide-tagged magnetic nanoparticles (MNPs) triggered canonical Wnt signaling transduction when exposed to a high-gradient, time-varying magnetic field, and the induced TCF/LEF signal transduction was shown to be avidity-dependent. We also demonstrated that the peptide retained signaling activity after functionalization onto glass surfaces, providing a versatile platform for drug discovery or recreation of the cell niche. In conclusion, these results showed that peptide-mediated Wnt signaling kinetics depended not only on ligand concentration but also on the presentation method of the ligand, which may be further modulated by magnetic actuation. This has important implications when designing future therapeutic platforms involving Wnt mimetics.

Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study.

BACKGROUND: Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management. METHODS: In this multicentre, two-arm, randomised study, we recruited men with biopsy-proven prostate cancer and high-risk features at ten hospitals in Australia. Patients were randomly assigned to conventional imaging with CT and bone scanning or gallium-68 PSMA-11 PET-CT. First-line imaging was done within 21 days following randomisation. Patients crossed over unless three or more distant metastases were identified. The primary outcome was accuracy of first-line imaging for identifying either pelvic nodal or distant-metastatic disease defined by the receiver-operating curve using a predefined reference-standard including histopathology, imaging, and biochemistry at 6-month follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry, ANZCTR12617000005358. FINDINGS: From March 22, 2017 to Nov 02, 2018, 339 men were assessed for eligibility and 302 men were randomly assigned. 152 (50%) men were randomly assigned to conventional imaging and 150 (50%) to PSMA PET-CT. Of 295 (98%) men with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease. PSMA PET-CT had a 27% (95% CI 23-31) greater accuracy than that of conventional imaging (92% [88-95] vs 65% [60-69]; p<0·0001). We found a lower sensitivity (38% [24-52] vs 85% [74-96]) and specificity (91% [85-97] vs 98% [95-100]) for conventional imaging compared with PSMA PET-CT. Subgroup analyses also showed the superiority of PSMA PET-CT (area under the curve of the receiver operating characteristic curve 91% vs 59% [32% absolute difference; 28-35] for patients with pelvic nodal metastases, and 95% vs 74% [22% absolute difference; 18-26] for patients with distant metastases). First-line conventional imaging conferred management change less frequently (23 [15%] men [10-22] vs 41 [28%] men [21-36]; p=0·008) and had more equivocal findings (23% [17-31] vs 7% [4-13]) than PSMA PET-CT did. Radiation exposure was 10·9 mSv (95% CI 9·8-12·0) higher for conventional imaging than for PSMA PET-CT (19·2 mSv vs 8·4 mSv; p<0·001). We found high reporter agreement for PSMA PET-CT (κ=0·87 for nodal and κ=0·88 for distant metastases). In patients who underwent second-line image, management change occurred in seven (5%) of 136 patients following conventional imaging, and in 39 (27%) of 146 following PSMA PET-CT. INTERPRETATION: PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning. FUNDING: Movember and Prostate Cancer Foundation of Australia. VIDEO ABSTRACT.

Therapeutic Effects of Hypoxic and Pro-Inflammatory Priming of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Inflammatory Arthritis.

Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling, including via secretion of extracellular vesicles (EVs) in the cell secretome. We evaluated the therapeutic potential of MSCs-derived small EVs in an antigen-induced model of arthritis (AIA). EVs isolated from MSCs cultured normoxically (21% O2, 5% CO2), hypoxically (2% O2, 5% CO2) or with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed post-arthritis induction through swelling and histopathological analysis of synovial joint structure. Activated CD4+ T cells from healthy mice were cultured with EVs or MSCs to assess deactivation capabilities prior to application of standard EVs in vivo to assess T cell polarisation within the immune response to AIA. All EVs treatments reduced knee-joint swelling whilst only normoxic and pro-inflammatory primed EVs improved histopathological outcomes. In vitro culture with EVs did not achieve T cell deactivation. Polarisation towards CD4+ helper cells expressing IL17a (Th17) was reduced when normoxic and hypoxic EV treatments were applied in vitro. Normoxic EVs applied into the AIA model reduced Th17 polarisation and improved Regulatory T cell (Treg):Th17 homeostatic balance. Normoxic EVs present the optimal strategy for broad therapeutic benefit. EVs present an effective novel technology with the potential for cell-free therapeutic translation.

High Metabolic Tumour Volume on 18-Fluorodeoxyglucose Positron Emission Tomography Predicts Poor Survival from Neuroendocrine Neoplasms.

INTRODUCTION: 18-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) avidity in neuroendocrine neoplasms (NENs) has been associated with higher-grade disease. 18F-FDG avidity and high SUVmax have been demonstrated to predict poor outcome. Quantitative metrics of 18F-FDG PET, specifically metabolic tumour volume (MTV) and total lesion glycolysis (TLG), have been shown to be prognostic factors in other malignancies, but these have not been investigated to date in NENs. METHODS: Patients with NEN undergoing 18F-FDG at Royal North Shore Hospital from 2012 to 2018 were included. Images were analysed with automated segmentation (SUV cut-off of 4) followed by contour verification by a nuclear medicine physician and manual segmentation where required. Variables collected included patient age, histological grade, MTV, TLG, and SUVmax/SUVmean. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Univariate (UV) and multivariate (MV) analyses were performed for OS and PFS for MTV and TLG separately. For UV analysis, the median MTV and TLG were used to dichotomise the cohort. MTV/TLG for NENs of different histological grade were compared using ANOVA. RESULTS: One hundred and ninety patients were included (median age 63.5, 49% female). Primary site: 42% small bowel, 32% pancreas, 15% other gastrointestinal, 6% lung, 6% other. Grade for gastroenteropancreatic NENs and bronchial NEN: G1/typical carcinoid 37%, G2/atypical carcinoid 40%, G3/large-cell/small-cell neuroendocrine carcinoma 16%, unknown 8%. Median MTV was 4.83 mL (range 0-3,161 mL) and median TLG was 29.22. Patients with high MTV had worse median OS compared to those with low MTV (29.7 months vs. not reached, HR 4.1, 95% CI 2.25-7.49, p < 0.00001). Considered as a continuous variable, MTV predicted for poorer OS on UV (p < 0.00001) and MV (p = 0.003) analyses. Whilst histological grade was significant on both UV and MV, SUVmax was significant on UV (p < 0.00001) but not MV (p = 0.76). Tumours of higher grade had higher MTV (mean MTV - G1: 39.6 mL, G2: 107 mL, G3: 337 mL; p = 0.0001 by ANOVA). CONCLUSIONS: Quantitative analysis of 18F-FDG PET in NEN is feasible. High MTV/TLG are predictors of poor prognosis in NEN. Further analyses are underway to investigate a larger cohort of NEN patients.

Safety and outcomes of 177 Lu-DOTATATE for neuroendocrine tumours: experience in New South Wales, Australia.

BACKGROUND: Peptide receptor radionuclide therapy with 177 Lu-DOTATATE is a promising treatment for inoperable or metastatic neuroendocrine tumours (NET). In 2015, the NSW Ministry of Health provided funding for 177 Lu-DOTATATE treatment of NET under an evaluation framework. AIMS: To examine the safety and outcomes of NET patients treated with 177 Lu-DOTATATE under the evaluation framework and assess the statewide implementation of the NSW Lutate therapy referral and protocol for neuroendocrine cancer patients. METHODS: A quality of care clinical audit was conducted on all NET patients treated with 177 Lu-DOTATATE from October 2010 to October 2015 at St George Hospital, and from August 2013 to March 2017 at Royal North Shore Hospital. Percentage of patients who met protocol selection criteria was calculated. Survival was estimated using the Kaplan-Meier method. Adjusted regression analyses assessed associations between key clinical factors and outcomes. RESULTS: A total of 279 patients was treated. Statewide protocol implementation led to an increase from 60.5 to 83.8% in patients meeting selection criteria. Estimated median overall survival was significantly longer for patients who met selection criteria compared with those who did not (50.7 vs 34.2 months) (P = 0.018). This was driven by the significantly worse overall survival in patients who failed exclusion criteria (P < 0.001). 177 Lu-DOTATATE was well tolerated with haematological, renal and hepatic treatment-related serious adverse events experienced by 9.7, 0.4 and 0.4% of patients respectively. CONCLUSIONS: 177 Lu-DOTATATE is a promising treatment for advanced NET. Superior survival in patients who met selection criteria emphasise the importance of protocol adherence.

The Olive Biophenols Oleuropein and Hydroxytyrosol Selectively Reduce Proliferation, Influence the Cell Cycle, and Induce Apoptosis in Pancreatic Cancer Cells.

Current chemotherapy drugs for pancreatic cancer only offer an increase in survival of up to six months. Additionally, they are highly toxic to normal tissues, drastically affecting the quality of life of patients. Therefore, the search for novel agents, which induce apoptosis in cancer cells while displaying limited toxicity towards normal cells, is paramount. The olive biophenols, oleuropein, hydroxytyrosol and tyrosol, have displayed cytotoxicity towards cancer cells without affecting non-tumorigenic cells in cancers of the breast and prostate. However, their activity in pancreatic cancer has not been investigated. Therefore, the aim of this study was to determine the anti-pancreatic cancer potential of oleuropein, hydroxytyrosol and tyrosol. Pancreatic cancer cells (MIA PaCa-2, BxPC-3, and CFPAC-1) and non-tumorigenic pancreas cells (HPDE) were treated with oleuropein, hydroxytyrosol and tyrosol to determine their effect on cell viability. Oleuropein displayed selective toxicity towards MIA PaCa-2 cells and hydroxytyrosol towards MIA PaCa-2 and HPDE cells. Subsequent analysis of Bcl-2 family proteins and caspase 3/7 activation determined that oleuropein and hydroxytyrosol induced apoptosis in MIA PaCa-2 cells, while oleuropein displayed a protective effect on HPDE cells. Gene expression analysis revealed putative mechanisms of action, which suggested that c-Jun and c-Fos are involved in oleuropein and hydroxytyrosol induced apoptosis of MIA PaCa-2 cells.

Development of an objective measure of quality and commercial value of Japanese-styled green tea (Camellia L. sinensis): the Quality Index Tool.

A novel approach to evaluate the commercial value of green tea products is explored in this paper. The green tea Quality Index Tool (QI-Tool) is based on high performance liquid chromatography (HPLC), capable of identifying and understanding the constituents that are important to create superior consumer and commercially valuable green tea beverages in the Japanese-style. This tool will allow producers to better identify a product's potential value within the various levels of green tea retail quality structure. Via the quantification of theanine, caffeine and the catechins: epicatechin (EC), epicatechin gallate (ECG), epigallocatchin (EGC), epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG) within a green tea beverage, the QI-Tool provides categorisation of a product against the green tea market retail competitive set. This allows a better understanding of the product's potential commercial value, as well as a comparison to other products within that market category. The QI-Tool is an alternative and promising method for objectively evaluating commercial value of green tea products using HPLC analysis.

Effects of four different drying methods on the carotenoid composition and antioxidant capacity of dried Gac peel.

BACKGROUND: Gac fruit (Momordica cochinchinensis Spreng.) is a rich source of carotenoids for the manufacture of powder, oil and capsules for food, cosmetic and pharmaceutical uses. Currently, only the aril of the Gac fruit is processed and the peel, similar to the other components, is discarded, although it contains high level of carotenoids, which could be extracted for commercial use. In the present study, four different drying methods (hot-air, vacuum, heat pump and freeze drying), different temperatures and drying times were investigated for producing dried Gac peel suitable for carotenoid extraction. RESULTS: The drying methods and drying temperatures significantly affected the drying time, carotenoid content and antioxidant capacity of the dried Gac peel. Among the investigated drying methods, hot-air drying at 80 o C and vacuum drying at 50 o C produced dried Gac peel that exhibited the highest retention of carotenoids and the strongest antioxidant capacity. CONCLUSION: Hot-air drying at 80 o C and vacuum drying at 50 o C are recommended for the drying of Gac peel. © 2016 Society of Chemical Industry.

A Mathematical Model of a Novel 3D Fractal-Inspired Piezoelectric Ultrasonic Transducer.

Piezoelectric ultrasonic transducers have the potential to operate as both a sensor and as an actuator of ultrasonic waves. Currently, manufactured transducers operate effectively over narrow bandwidths as a result of their regular structures which incorporate a single length scale. To increase the operational bandwidth of these devices, consideration has been given in the literature to the implementation of designs which contain a range of length scales. In this paper, a mathematical model of a novel Sierpinski tetrix fractal-inspired transducer for sensor applications is presented. To accompany the growing body of research based on fractal-inspired transducers, this paper offers the first sensor design based on a three-dimensional fractal. The three-dimensional model reduces to an effective one-dimensional model by allowing for a number of assumptions of the propagating wave in the fractal lattice. The reception sensitivity of the sensor is investigated. Comparisons of reception force response (RFR) are performed between this novel design along with a previously investigated Sierpinski gasket-inspired device and standard Euclidean design. The results indicate that the proposed device surpasses traditional design sensors.

Development of a nanomaterial bio-screening platform for neurological applications.

Nanoparticle platforms are being intensively investigated for neurological applications. Current biological models used to identify clinically relevant materials have major limitations, e.g. technical/ethical issues with live animal experimentation, failure to replicate neural cell diversity, limited control over cellular stoichiometries and poor reproducibility. High-throughput neuro-mimetic screening systems are required to address these challenges. We describe an advanced multicellular neural model comprising the major non-neuronal/glial cells of the central nervous system (CNS), shown to account for ~99.5% of CNS nanoparticle uptake. This model offers critical advantages for neuro-nanomaterials testing while reducing animal use: one primary source and culture medium for all cell types, standardized biomolecular corona formation and defined/reproducible cellular stoichiometry. Using dynamic time-lapse imaging, we demonstrate in real-time that microglia (neural immune cells) dramatically limit particle uptake in other neural subtypes (paralleling post-mortem observations after nanoparticle injection in vivo), highlighting the utility of the system in predicting neural handling of biomaterials.

Phytochemical properties and anti-proliferative activity of Olea europaea L. leaf extracts against pancreatic cancer cells.

Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds; especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the fifth leading cause of cancer related death in Western countries. Therefore, water, 50% ethanol and 50% methanol extracts of Corregiola and Frantoio variety Olea europaea L. leaves were investigated for their total phenolic compounds, total flavonoids and oleuropein content, antioxidant capacity and anti-proliferative activity against MiaPaCa-2 pancreatic cancer cells. The extracts only had slight differences in their phytochemical properties, and at 100 and 200 µg/mL, all decreased the viability of the pancreatic cancer cells relative to controls. At 50 µg/mL, the water extract from the Corregiola leaves exhibited the highest anti-proliferative activity with the effect possibly due to early eluting HPLC peaks. For this reason, olive leaf extracts warrant further investigation into their potential anti-pancreatic cancer benefits.

Greenhouse-grown bitter melon: production and quality characteristics.

BACKGROUND: Bitter melon (Momordica charantia L.) is a medicinal fruit reported to have antidiabetic properties. To grow this tropical fruit year-round in temperate climates, greenhouse production is necessary, sometimes without insect pollinators. Suitable high-yielding varieties with good bioactivity need to be identified. This experiment evaluated the yield of six varieties of bitter melon under greenhouse conditions and their bioactivity in terms of total phenolic and saponin compounds and total antioxidant activity determined using four assays. RESULTS: The larger varieties (Big Top Medium, Hanuman, Jade and White) were more productive than the small varieties (Indra and Niddhi) in terms of total fruit weight and yield per flower pollinated. The bioactivity (total phenolic and saponin compounds and antioxidant activity) of the two small varieties and Big Top Medium was significantly higher than that of the other three large varieties. Two antioxidant assays, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing antioxidant power (FRAP), were shown to provide the strongest correlations with phenolic and saponin compounds of bitter melon. CONCLUSION: Preliminary research has identified Big Top Medium as the most suitable variety for greenhouse production. The rich source of phenolic and saponin compounds and their associated antioxidant activity highlight bitter melon as a valuable food.

Turmeric (Curcuma longa L.) drying: an optimization approach using microwave-vacuum drying.

This study investigated the effect of microwave power (2,400-4,000 W) and drying times (10-30 min) on the quality of dried turmeric in terms of colour (L, a*, b*), moisture content, water activity (aw), ash, antioxidant activity (2,2-dipheneyl-1-picrylhydrazyl; DPPH), total phenolic and curcuminoids content. In addition, Response Surface Methodology (RSM) was implemented to optimize the drying conditions for turmeric. A range of quality parameters, microwave power (W) and time (min) were fitted to quadratic models using a central composite design. The Analysis of Variance (ANOVA) statistic results suggested that the optimal qualities (i.e., aw, value, moisture content, phenolic content, curcuminoid content and EC50 and L value) of dried turmeric were achieved at high vacuum-microwave power (3,500-4,000 W) and long duration (27-30 min). The improvement in the quality of dried turmeric microwave-vacuum drying in these conditions was illustrated through the enzymatic browning reaction via inhibition of polyphenol oxidase which suppressed the formation of the brown pigments and increased the phenol substrates.