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The markets for plant-based meat analogues (PBMAs) are growing worldwide, showing the increasing consumer demand for and acceptance of these new products. Three-dimensional (3D) food printing is a new technology with huge potential for printing products customised to suit consumers' wants and needs. There is a broad acceptance from consumers regarding the safety and desirability of consuming food products that are produced using 3D printing. As this is a new technology, consumers must be provided with relevant information from a trusted source, with further research needing to be conducted within the context of the identified market and culture. By embracing the strength of customisation of 3D printing and coupling this with the global demand for plant-based products, 3D printed PBMAs could be a future challenger to the currently popular production method of extrusion. Therefore, this article reviews consumer interests in PBMAs and summarises opportunities for using 3D printing technology to produce plant-based meat analogues.

In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases such as viral hepatitis and acute and chronic cirrhosis. In an effort to search for Vietnamese natural compounds capable of inhibiting coronavirus based on molecular docking screening, two new dimeric coumarin glycosides, namely cis-paratrimerin B (1) and cis-paratrimerin A (2), and two previously identified coumarins, the trans-isomers paratrimerin B (3) and paratrimerin A (4), were isolated from the roots of P. trimera and tested for their anti-angiotensin-converting enzyme 2 (ACE-2) inhibitory properties in vitro. It was discovered that ACE-2 enzyme was inhibited by cis-paratrimerin B (1), cis-paratrimerin A (2), and trans-paratrimerin B (3), with IC 50 values of 28.9, 68, and 77 µM, respectively. Docking simulations revealed that four biscoumarin glycosides had good binding energies (∆G values ranging from -10.6 to -14.7 kcal/mol) and mostly bound to the S1' subsite of the ACE-2 protein. The key interactions of these natural ligands include metal chelation with zinc ions and multiple H-bonds with Ser128, Glu145, His345, Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots occur naturally in both cis- and trans-diastereomeric forms. The biscoumarin glycosides Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots hold potential for further studies as natural ACE-2 inhibitors for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

From lead 1, ( N -(4-((4-(3-(4-(3-methoxyphenyl)-1 H -1,2,3-triazol-1-yl)propyl)piperazin-1-yl)sulfonyl)-phenyl)acetamide), a S100A2-p53 protein-protein interaction inhibitor based on an in silico modelling driven hypothesis, four focused libraries were designed and synthesised. Growth inhibition screening was performed against 16 human cancer cell lines including the pancreatic cell lines MiaPaCa2, BxPC3, AsPC-1, Capan-2, HPAC, PANC-1 and the drug resistant CFPAC1. Modification of 1's phenylacetamide moiety, gave Library 1 with only modest pancreatic cancer activity. Modification of the 3-OCH 3 Ph moiety ( Library 2 ) gave 4-CH 3 (26), 4-CH 2 CH 3 (27), 4-CF 3 (31) and 4-NO 2 (32) with sterically bulky groups more active. A 4-CF 3 acetamide replacement enhanced cytotoxicity ( Library 3 ). The 4-C(CH 3 ) 3 36 resulted in a predicted steric clash in the S100A2-p53 binding groove, with a potency decrease. Alkyl moieties afforded more potent analogues, 34 (4-CH 3 ) and 35 (CH 2 CH 3 ), a trend evident against pancreatic cancer: GI 50 3.7 (35; BxPC-3) to 18 (40; AsPC-1) μM. Library 4 analogues with a 2-CF 3 and 3-CF 3 benzenesulfonamide moiety were less active than the corresponding Library 3 analogues. Two additional analogues were designed: 51 (4-CF 3 ; 4-OCH 3 ) and 52 (4-CF 3 ; 2-OCH 3 ) revealed 52 to be 10-20 fold more active than 51, against the pancreatic cancer cell lines examined with sub-micromolar GI 50 values 0.43 (HPAC) to 0.61 μM (PANC-1). MOE calculated binding scores for each pose are also consistent with the observed biological activity with 52. The obtained SAR data is consistent with the proposed interaction within the S100A2-p53 bonding groove., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Early research has shown variations in salt taste qualities in depression, anxiety, and stress. These studies evaluated changes to salt taste intensity and liking (pleasantness) of salt solutions but not of salty foods. Therefore, an Australian population survey (n = 424) was conducted where participants rated recalled intensity and liking of salt index foods and completed the Depression, Anxiety, and Stress Scale (DASS-21) to measure these states. Standard least squares regression (post hoc Tukey's HSD) compared means between groups, and nominal logistic regression assessed differences in distributions between categories. Higher salt liking was found in participants with DASS-21 scores indicative of severe depression (68.3 vs. 60.0, P = 0.005) and severe anxiety (68.4 vs. 60.0, P = 0.001) in comparison to those with normal scores, in all models. Higher salt liking was found in participants with DASS-21 scores indicative of moderate stress (67.7 vs. 60.2, P = 0.009) in the unadjusted model only. Higher salt liking was found in females with DASS-21 scores indicative of anxiety and stress, and in males with indicative depression and anxiety. No relationships between salt taste intensity ratings and the mood states were found. Results indicate that liking salty foods is positively correlated with depression, anxiety, and stress scores. Further research on the relationships between salt liking and intake of salt and salty foods, and the biological mechanisms of these mood states are needed to direct the application of findings toward potential new risk assessment measures, dietary interventions, or therapeutics., (© The Author(s) 2023. Published by Oxford University Press.)

Introduction: Despite the prevalence of depression and anxiety worldwide, their aetiologies remain unclear, and they can be difficult to diagnose and treat. Changes in salt-taste perception have been found in both conditions. Single-nucleotide polymorphisms (SNPs) in the salt-taste-related gene, TRPV1, have been associated with alterations to salt-taste perception, preference, and sodium consumption. Diet quality is a known modifier of depression and anxiety and recently, sodium intake has been studied in mental health. However, the relationships between salt-taste genetics, depression, anxiety, and these dietary factors are yet to be elucidated., Methods: Data from the well-characterized cross-sectional Retirement Health and Lifestyle Study (n = 536, ≥65 y) were used to explore the relationships between the salt-taste SNP TRPV1-rs8065080, levels of depression and anxiety (Hospital Anxiety and Depression Scale, HADS), estimated sodium intake, and diet quality in this secondary analysis. Standard least-squares regression and nominal logistic regression modelling were used to compare continuous and categorical variables, respectively, with analyses stratified by sex., Results: Presence of the TRPV1-rs8065080 variant allele (C) was found to increase the likelihood of having depression (HADS) in the total population and in males. The associations remained significant after adjusting for sodium intake, three diet quality indices, and demographic variables, suggesting that TRPV1-rs8065080 genotype is driving the association with depression., Discussion/conclusion: Future studies should explore extra-oral functions of the SNP and salt-taste receptors in the brain and the roles of neurotransmitters common to both depression and salt taste to improve the management of this increasingly prevalent and difficult-to-treat condition., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

The commercial production of soy milk renders a large quantity of wet soybean by-product (SMB), which is typically dumped, incinerated, or partially used as animal fodder. This wet SMB has a high moisture content that is rich in nutritional and biologically active compounds. This study aimed to characterise the composition and properties of a flour milled from SMB dried at 100 °C (SMB100) and assess its possible application as a fibre substitute in white bread. The results showed that SMB100 has high levels of dietary fibre (40.6%) and protein (26.5%). It also contains high levels of saponins (31.4 mg/g) and isoflavones (698.0 µg/g). SMB100 has a light-yellow colour with low moisture content and water activity (8.2% and 0.55, respectively). The results also indicated that replacement of wheat flour with SMB100 at 10 or 12.5% by flour weight negatively impacted the raising volume, density, and texture of white bread. Alternatively, substituting wheat flour with 5% of SMB100, did not significantly impact the physical properties of white bread, while significantly improving its dietary fibre content in comparison with the control, revealing that SMB100 is a potential substitute of wheat flour for improvement of dietary fibre in bread. Future studies are needed to optimise bread formulation and improve the processing condition which produces quality white bread with high dietary fibre using SMB100.

Mammalian sirtuins (SIRT1-7) are involved in a myriad of cellular processes, including apoptosis, proliferation, differentiation, epithelial-mesenchymal transition, aging, DNA repair, senescence, viability, survival, and stress response. In this review, we discuss the current information on the mechanistic roles of SIRT1-7 and their downstream effects (tumor promotion or suppression) in cancers of the breast and prostate. Specifically, we highlight the involvement of sirtuins in the regulation of various proteins implicated in proliferation, apoptosis, autophagy, chemoresistance, invasion, migration, and metastasis of breast and prostate cancer. Additionally, we highlight the available information regarding SIRT1-7 regulation by miRNAs, laying much emphasis on the consequences in the progression of breast and prostate cancer.

This study aimed to determine the phytochemical, antioxidant, and anticancer activities of the crude extract and its fractions of Cupaniopsis anacardioides . The results showed that total phenolic content (TPC), their secondary metabolites (flavonoids-TFC; proanthocyanidins-TPro), and antioxidant activity were significantly different between the crude extract and its fractions. The butanol fraction (F3) had the highest levels of TPC, TFC, and TPro, followed by the crude extract, aqueous fraction (F4), dichloromethyl fraction (F2), and hexane fraction (F1). High-Pressure Liquid Chromatography (HPLC) analysis revealed 14 major bioactive compounds were identified in the C. anacardioides extract. Further analysis showed F3 fraction contained the highest levels of the major bioactive compounds, while F1 fraction had the lowest. A similar pattern was observed for antioxidant activities. The crude extract, F3 and F4 fractions were further tested for cytotoxicity against 10 cancer cell lines, including HT29 (colon); U87, SJG2 (glioblastoma); MCF-7 (Breast); A2780 (ovarian); H460 (lung); A431 (skin); Du145 (prostate); BE2-C (neuroblastoma); MIA PaCa-2 (pancreas); and one non-tumour-derived normal breast cell line (MCF10A). Except for Du145 (prostate), the crude extract, F3 and F4 fractions inhibited the cancer cell lines at 100 µg/mL, with F3 possessing greater activity against these cancer cell lines. Future studies are recommended to isolate and identify the major bioactive compounds of the F3 fraction, and further tested their impact against cancer cell lines. This could identify the potential of anticancer agents from C. anacardioides ., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s) 2022.)

Virtual screening identified N-(6-((4-bromobenzyl)amino)hexyl)-3,5-bis(trifluoromethyl)benzenesulfonamide (1) a lead compound that bound to the S100A2-p53 binding groove. S100A2 is a Ca 2+ binding protein with implications in cell signaling and is known to be upregulated in pancreatic cancer. It is a validated pancreatic cancer drug target. Lead 1, inhibited the growth of the MiaPaCa-2 pancreatic cancer cell line (GI 50  = 2.97 μM). Focused compound libraries were developed to explore the SAR of this compound class with 4 libraries and 43 compounds total. Focused library (Library 1) development identified lipophillic sulfonamides as preferred for MiaPaCa-2 activity, with -CF 3 and -C(CH 3 ) 3 substituents well tolerated (MiaPaCa-2 GI 50  < 6 μM). Contraction of the hexylamino spacer to ethyl (Library 2) and propyl (Library 3) proved beneficial to activity against a broad spectrum panel of cancer cell lines: HT29 (lung), MCF-7 (breast), A2780 (ovarian), H460 (colon), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), U87 and SJ-G2 (glioblastoma) (cohort-1); and a pancreatic cancer cell line panel: MiaPaCa-2, BxPC-3, AsPC-1, Capan-2, HPAC and PANC-1 (cohort-2). With a marked preference for a propyl linker the observed GI 50 values ranged from 1.4 to 30 μM against cohort-1 and 1.4-30 μM against cohort-2 cell lines. In Library 4 the terminal aromatic moiety was explored with 4-substituted analogues preferred (with activity of 48 (4-Cl) > 47 (3-Cl) > 46 (2-Cl)) against the cell lines examined. The introduction of bulky aromatic moieties was well tolerated, e.g. dihydrobenzo[b][1,4]dioxine (51) returned cohort-2 GI 50 values of 1.2-3.4 μM. In all instances the observed docked binding poses and binding scores were consistent with the observed cytotoxicity. This in turn supports, but does not prove, that these analogues function via S100A2-p53 binding groove inhibition., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Objective: To test the "vitamin D-folate hypothesis for the evolution of human skin pigmentation.", Methods: Total ozone mapping spectrometer (TOMS) satellite data were used to examine surface UV-irradiance in a large (n = 649) Australian cross-sectional study population. Genetic analysis was used to score vitamin D- and folate-related gene polymorphisms (n = 22), along with two pigmentation gene variants (IRF4-rs12203592/HERC2-rs12913832). Red cell folate and vitamin D 3 were measured by immunoassay and HPLC, respectively., Results: Ultraviolet radiation (UVR) and pigmentation genes interact to modify blood vitamin levels; Light skin IRF4-TT genotype has greatest folate loss while light skin HERC2-GG genotype has greatest vitamin D 3 synthesis (reflected in both TOMS and seasonal data). UV-wavelength exhibits a dose-response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D 3 photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm. Three dietary antioxidants (vitamins C, E, and β-carotene) interact with UVR and pigmentation genes preventing oxidative loss of labile reduced folate vitamers, with greatest benefit in light skin IRF4-TT subjects. The putative photosensitiser, riboflavin, did not sensitize red cell folate to UVR and actually afforded protection. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D 3 synthesis) has 0% occurrence. The opposing, commonest (39%) compound genotype (darkest IRF4-CC/lightest HERC2-GG) permits least folate loss and greatest synthesis of vitamin D 3 ., Conclusion: New biophysical evidence supports the vitamin D-folate hypothesis for evolution of skin pigmentation., (© 2021 Wiley Periodicals LLC.)

In silico approaches identified 1, N-(6-((4-bromo- benzyl)amino)hexyl)-3,5-bis(trifluoromethyl)benzene sulfonamide, as a potential inhibitor of the S100A2-p53 protein-protein interaction, a validated pancreatic cancer drug target. Subsequent cytotoxicity screening revealed it to be a 2.97 μM cell growth inhibitor of the MiaPaCa-2 pancreatic cell line. This is in keeping with our hypothesis that inhibiting this interaction would have an anti-pancreatic cancer effect with S100A2, the validated PC drug target. A combination of focused library synthesis (three libraries, 24 compounds total) and cytotoxicity screening identified a propyl alkyl diamine spacer as optimal; the nature of the terminal phenyl substituent had limited impact on observed cytotoxicity, whereas N-methylation was detrimental to activity. In total 15 human cancer cell lines were examined, with most analogues showing broad-spectrum activity. Near uniform activity was observed against a panel of six pancreatic cancer cell lines: MiaPaCa-2, BxPC-3, AsPC-1, Capan-2, HPAC and PANC-1. In all cases there was good to excellent correlation between the predicted docking pose in the S100A2-p53 binding groove and the observed cytotoxicity, especially in the pancreatic cancer cell line with high endogenous S100A2 expression. This supports S100A2 as a pancreatic cancer drug target., (© 2021 Wiley-VCH GmbH.)

In silico screening predicted 1 (N-(4-((4-(3-(4-(3-methoxyphenyl)-1H-1,2,3-triazol-1-yl)propyl)piperazin-1-yl) sulfonyl)-phenyl)acetamide) as an inhibitor of the S100A2-p53 protein-protein interaction. S100A2 is a validated pancreatic cancer drug target. In the MiaPaCa-2 pancreatic cell line, 1 was a ∼50 μM growth inhibitor. Synthesis of five focused compound libraries and cytotoxicity screening revealed increased activity from the presence of electron withdrawing moieties on the sulfonamide aromatic ring, with the 3,5-bis-CF 3 Library 3 analogues the most active, with GI 50 values of 0.91 (3-ClPh; 13 i; BxPC-3, Pancreas) to 9.0 μM (4-CH 3 ; 13 d; PANC-1, Pancreas). Activity was retained against an expanded pancreatic cancer cell line panel (MiaPaCa-2, BxPC-3, AsPC-1, Capan-2, PANC-1 and HPAC) and the normal cell line MCF10A (breast). Bulky 4-disposed substituents on the terminal phenyl ring enhanced broad spectrum activity with growth inhibition values spanning 1.1 to 3.1 μM (4-C(CH 3 ) 3 ; 13 e; BxPC-3 and AsPC-1 (pancreas), respectively). Central alkyl spacer contraction from propyl to ethyl proved detrimental to activity with Library 4 and 5.5- to 10-fold less cytotoxic than the propyl linked Library 2 and Library 3. The data herein was consistent with the predicted binding poses of the compounds evaluated. The highest levels of cytotoxicity were observed with those analogues best capable of adopting a near identical pose to the p53-peptide in the S100A2-p53 binding groove., (© 2021 Wiley-VCH GmbH.)

Single nucleotide polymorphisms (SNPs) in taste receptors influence dietary choices that contribute to health and quality of life. Individual differences in sour taste perception and preference have been linked to heritable genetics, yet the impact of sour taste receptor SNPs on sour taste is under-researched, and studies on sour taste SNP associations to diet and health are lacking. Therefore, this study explored the relationships between the sour taste SNP KCNJ2 -rs236514 and estimated macronutrient, vitamin and mineral intakes, and markers of metabolic health. Associations were explored in 523 participants aged 65 years and older with data analysed using standard least squares and nominal logistic regression modelling with post hoc student's t -tests and Tukey's HSD. Associations were found between the presence of the KCNJ2 -rs236514 variant allele (A) and lower intakes of energy, total fat, monounsaturated fat and saturated fat. The lower fat intakes were significant in female carriers of the variant allele (A), along with lower water intake. Lower retinol, riboflavin, folate, calcium and sodium intakes were found in the KCNJ2 -A allele carriers. In females, the variant allele was associated with lower sodium intake before and after Bonferroni adjustment. Higher body mass index, waist and waist-to-hip ratio measures were found in males carrying the variant allele. Lower levels of liver function biomarkers were associated with the presence of the KCNJ2 -A allele. Overall and in males, the variant's association to lower gamma-glutamyl transferase (GGT) levels remained significant after Bonferroni adjustments. These novel findings suggest the sour taste SNP, KCNJ2 -rs236514, may be modifying macronutrient, vitamin and mineral intakes, and markers of metabolic health. Research on the extra-oral functions of this SNP may improve health outcomes for those with overweight, obesity and liver disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ferraris, Turner, Scarlett, Veysey, Lucock, Bucher and Beckett.)

Scaevola spinescens is endemic to Australia and has traditionally been used by Aboriginal and Torres Strait Islander communities to treat a variety of conditions including colds, flu, fever, stomach pain, urinary disorders, sores, tinea, leprosy, and cancer. Extracts prepared from S. spinescens are non-toxic and have been linked with various medicinal properties including antiviral, antibacterial, anti-inflammatory, and anticancer activities. These studies support the ethnopharmacological use of S. spinescens by Indigenous peoples of Australia and highlight the need for further investigations on the plant for potential use in pharmaceutical and food applications. This review provides a comprehensive, up-to-date review of the literature on S. spinescens focusing on the traditional use, medicinal properties, phytochemicals, and factors that affect their composition during pre-treatment and extraction, as well as providing a framework for future studies of the plant., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Scaevola spinescens is endemic to Australia and traditionally used as a medicinal plant. While its bioactive compounds have been studied, their concentrations in different parts of the plant have not been reported. This study compared total phenolic content (TPC), flavonoids, saponins and antioxidant properties, as well as major individual phytochemical compounds in the whole root, root bark, root wood, whole stem, stem bark, stem wood, and leaf of S. spinescens . The results showed the leaf had significantly highest concentrations of TPC followed by the root bark and stem bark (47.34, 12.24 and 10.20 mg GAE/g, respectively). Flavonoids concentrations were also significantly higher in the leaf compared to the root bark and stem bark (20.95, 6.22 and 4.19 mg CE/g, respectively). For saponins, the root bark contained significantly highest concentrations (112.58 mg EE/g). Luteolin 7-glucoside was isolated and identified in the leaf of S. spinescens. Eight major compounds were identified with the leaf displaying the highest diversity of major compounds, and in higher concentrations, compared to the other plant constituents. As the leaf and root bark contained the highest concentrations of phytochemicals, these plant parts are recommended as starting material for future studies, to further isolate and identify the major compounds from S. spinescens and investigate their biological properties for use in pharmaceutical and food applications., Competing Interests: The authors declare the following conflict of interests: Quan V. Vuong; [is an advisory board member for Heliyon Food Science and Nutrition]., (© 2021 Published by Elsevier Ltd.)

Globally, more than one-third of adults are overweight. Overweight and obesity are complex and multifaceted conditions, associated with an increased risk of chronic illness and early mortality. While there are known risk factors, these alone do not fully explain the varying outcomes between individuals. Recently, taste receptors have been proposed to have a role in the risk for obesity. These receptors are expressed throughout the gastrointestinal tract. In this system, they may be involved in modulating dietary intake and metabolic processes. The taste 2 family of receptors (T2Rs) detects bitter compounds. Receptors T2R4 and T2R5 detect (-)-epicatechin (epicatechin), an antioxidant polyphenol, which may have protective effects against obesity. However, the potential role for taste receptors in this association has not been explored. This study assessed whether polymorphisms in TAS2R4 (rs2233998 and rs2234001) and TAS2R5 (rs2227264) were associated with body mass index (BMI). Genotyping (Taqman qPCR assays) was performed on DNA extracted from blood samples ( n = 563) from an elderly cohort. Homozygosity for the minor allele of all polymorphisms was significantly associated with a lower BMI in males. The TAS2R4 -rs2233998 CC genotype, the TAS2R4 -rs2234001 CC genotype and the TAS2R5 -rs2227264 TT genotype were associated with lower BMI (2.1, 2.1 and 2.2 units; p = 0.002, 0.003 and 0.001, respectively). Epicatechin intake was not associated with BMI and genotype was not associated with epicatechin intake. This suggests that the association between TAS2R genotype and elevated BMI risk occurs through altered extra-oral responses and not directly via altered epicatechin intake.

Objective: We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection., Background: Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease., Method: In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram., Results: High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables., Conclusions: Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.

Intense sweeteners (IS) are often marketed as a healthier alternative to sugars, with the potential to aid in combating the worldwide rise of diabetes and obesity. However, their use has been counterintuitively associated with impaired glucose homeostasis, weight gain and altered gut microbiota. The nature of these associations, and the mechanisms responsible, are yet to be fully elucidated. Differences in their interaction with taste receptors may be a potential explanatory factor. Like sugars, IS stimulate sweet taste receptors, but due to their diverse structures, some are also able to stimulate bitter taste receptors. These receptors are expressed in the oral cavity and extra-orally, including throughout the gastrointestinal tract. They are involved in the modulation of appetite, glucose homeostasis and gut motility. Therefore, taste genotypes resulting in functional receptor changes and altered receptor expression levels may be associated with metabolic conditions. IS and taste receptors may both interact with the gastrointestinal microbiome, and their interactions may potentially explain the relationship between IS use, obesity and metabolic outcomes. While these elements are often studied in isolation, the potential interactions remain unexplored. Here, the current evidence of the relationship between IS use, obesity and metabolic outcomes is presented, and the potential roles for interactions with taste receptors and the gastrointestinal microbiota in modulating these relationships are explored., Competing Interests: The authors declare no conflict of interest.

Banana peel, a by-product rich in phenolics and other bioactive compounds, has great potentials as a natural preservative or healthy food ingredient. However, the instability of bioactive compounds derived from banana peel limits their applications, and as such encapsulation is necessary to improve their stability and widen their applications. This study investigated the impact of spray drying conditions and coating materials on the physical, phytochemical, and antioxidant properties of the peel extract to identify the most suitable encapsulation process. The results showed that inlet temperature (ranging from 140 to 180 °C) and feeding rate (3-15 mL/min) did not significantly affect the total phenolic content (TPC) and antioxidant capacity but influenced the moisture content and recovery yield of the powder. The ratio of dry matter in fresh extract-to-coating material (DM-to-CM) (1:1-1:7 (w/w)) did not affect the moisture content. However, it affected the TPC, antioxidant properties, and recovery yield of the powder. Finally, the type of coating materials did not significantly affect TPC and antioxidant properties, but other physical properties, dopamine levels and recovery yield. The most suitable encapsulation conditions were identified as an inlet drying temperature of 150 °C, a feeding rate of 9 mL/min, a ratio of DM-to-CM of 1:1 (w/w), and coating with a combination of maltodextrin M100 and gum acacia. Powder prepared under the most suitable conditions had a spherical shape with a rough surface and had stable TPC under storage conditions of 40 °C for 4 weeks. It also has ideal physical, phytochemical and antioxidant properties and is suitable for further applications., (© Association of Food Scientists & Technologists (India) 2020.)

Elevated homocysteine (Hcy) levels are a risk factor for vascular diseases. Recently, increases in ultraviolet radiation (UVR) have been linked to decreased Hcy levels. This relationship may be mediated by the status of UVR-responsive vitamins, vitamin D and folate, and/or genetic variants influencing their levels; however, this has yet to be examined. Therefore, the independent and interactive influences of environmental UVR, vitamin D and folate levels and related genetic variants on Hcy levels were examined in an elderly Australian cohort ( n = 619). Red blood cell folate, 25-hydroxyvitamin D (25(OH)D), and plasma Hcy levels were determined, and genotyping for 21 folate and vitamin D-related variants was performed. Erythemal dose rate accumulated over six-weeks (6W-EDR) and four-months (4M-EDR) prior to clinics were calculated as a measure of environmental UVR. Multivariate analyses found interactions between 6W-EDR and 25(OH)D levels (p interaction = 0.002), and 4M-EDR and MTHFD1 -rs2236225 (p interaction = 0.006) in predicting Hcy levels. The association between 6W-EDR and Hcy levels was found only in subjects within lower 25(OH)D quartiles (<33.26 ng/mL), with the association between 4M-EDR and Hcy occurring only in subjects carrying the MTHFD1 -rs2236225 variant. 4M-EDR, 6W-EDR, and MTHFD1 -rs2236225 were also independent predictors of Hcy. Findings highlight nutrient-environment and gene-environment interactions that could influence the risk of Hcy-related outcomes.

Breast cancer is the most commonly diagnosed and the second leading cause of cancer-related mortality among women worldwide. miR-518f-5p has been shown to modulate the expression of the metastasis suppressor CD9 in prostate cancer. However, the role of miR-518f-5p and CD9 in breast cancer is unknown. Therefore, this study aimed to elucidate the role of miR-518f-5p and the mechanisms responsible for decreased CD9 expression in breast cancer, as well as the role of CD9 in de novo tumor formation and metastasis. miR-518f-5p function was assessed using migration, adhesion, and proliferation assays. miR-518f-5p was overexpressed in breast cancer cell lines that displayed significantly lower CD9 expression as well as less endogenous CD9 3'UTR activity, as assessed using qPCR and dual luciferase assays. Transfection of miR-518f-5p significantly decreased CD9 protein expression and increased breast cell migration in vitro. Cd9 deletion in the MMTV/PyMT mouse model impaired tumor growth, but had no effect on tumor initiation or metastasis. Therefore, inhibition of miR-518f-5p may restore CD9 expression and aid in the treatment of breast cancer metastasis.

Treatment options for pancreatic cancer (PC) are severely limited due to late diagnosis, early metastasis and the inadequacy of chemotherapy and radiotherapy to combat the aggressive biology of the disease. In recent years, plant-derived bioactive compounds have emerged as a source of novel, anti-cancer agents. Used in traditional medicine worldwide, Elaeocarpus species have reported anti-inflammatory, antioxidant and anti-cancer properties. This study aimed to isolate and identify potential anti-PC compounds in the fruit of Elaeocarpus reticulatus Sm. A 50% acetone crude extract significantly decreased the viability of four pancreatic cell lines (≥ 10 µg/mL for BxPC-3 cells) and induced apoptosis in BxPC-3 and HPDE cells. Analysis by HPLC identified the triterpenoid Cucurbitacin I as a likely component of the extract. Furthermore, treatment with Cucurbitacin I significantly reduced the viability of HPDE and BxPC-3 cells, with results comparable to the same concentration of gemcitabine. Interestingly, attempts to isolate bioactive compounds revealed that the crude extract was more effective at reducing PC-cell viability than the fractionated extracts. This study provides initial insight into the bioactive constituents of E. reticulatus fruits.

Ultraviolet radiation (UVR) is a ubiquitous exposure which may contribute to decreased folate levels. Skin pigmentation mediates the biological effect of UVR exposure, but its relationship to folate levels is unexamined. Interactions may exist between UVR and pigmentation genes in determining folate status, which may, in turn, impact homocysteine levels, a potential risk factor for multiple chronic diseases. Therefore, independent and interactive influences of environmental UVR and genetic variants related to skin pigmentation (MC1R-rs1805007, IRF4-rs12203592 and HERC2-rs12913832) on folate (red blood cell (RBC) and serum) and homocysteine levels were examined in an elderly Australian cohort (n = 599). Genotypes were assessed by RT/RFLP-PCR, and UVR exposures were assessed as the accumulated erythemal dose rate accumulated over 4 months (4M-EDR). Multivariate analysis found significant negative associations between 4M-EDR and RBC folate (p < 0.001, β = -0.19), serum folate (p = 0.045, β = -0.08) and homocysteine levels (p < 0.001, β = -0.28). Significant associations between MC1R -rs1805007 and serum folate levels ( p = 0.020), and IRF4 -rs12203592 and homocysteine levels ( p = 0.026) occurred but did not remain significant following corrections with confounders. No interactions between 4M-EDR and pigmentation variants in predicting folate/homocysteine levels were found. UVR levels and skin pigmentation-related variants are potential determinants of folate and homocysteine status, although, associations are mixed and complex, with further studies warranted., Competing Interests: The authors declare no conflict of interest

Pancreatic cancer (PC) is one of the leading causes of cancer death in Western societies. The absence of specific symptoms, late diagnosis and the resistance towards chemotherapy result in significant treatment difficulties. As such, it is important to find more effective therapeutic agents for the treatment of PC. Helicteres hirsuta Lour. (H. hirsuta) has been traditionally used in many countries for the treatment of various ailments, indicating that it contains potential therapeutic agents. This study aimed to derive different fractions from the saponin-enriched extract of H. hirsuta stem using RP-HPLC and examine the in vitro anti-pancreatic cancer activity of the derived fractions (F0-F5). With the exception of F0, the five fractions (F1-F5) possessed strong inhibitory activity against PC cells at IC 50 values of 3.11-17.12 μg/mL. The flow cytometry assays revealed the active fractions caused cell cycle arrest at S phase and promoted apoptosis in MIAPaCa-2 PC cells. The LC/MS analysis revealed that the isolated fractions contained bioactive compounds, such as caffeic acid, rosmarinic acid, sagerinic acid, usnic acid, cucurbitacins and absinthin. It can be concluded that the fractions isolated from H. hirsuta stem exhibit potent in vitro anti-pancreatic cancer activity and thus warrant further in vivo studies to assess their activity against PC followed by isolation of individual bioactive compounds and the evaluation of their anti-pancreatic cancer activity.

Pancreatic cancer (PC), with a 5 year survival of <7%, is one of the most fatal of all human cancers. The highly aggressive and metastatic character of this disease poses a challenge that current therapies are failing, despite significant efforts, to meet. This review examines the current status of the 35 small molecule inhibitors targeting pancreatic cancer in clinical trials and the >50 currently under investigation. These compounds inhibit biological targets spanning protein kinases, STAT3, BET, HDACs and Bcl-2 family proteins. Unsurprisingly, protein kinase inhibitors are overrepresented. Some trials show promise; a phase I combination trial of vorinostat 11 and capecitabine 17 gave a median overall survival (MoS) of 13 months and a phase II study of pazopanib 15 showed a MoS of 25 months. The current standard of care for metastatic pancreatic ductal adenocarcinoma, fluorouracil/folic acid (5-FU, Adrucil®), and gemcitabine (GEMZAR®) afforded a MoS of 23 and 23.6 months (EPAC-3 study), respectively. In patients who can tolerate the FOLFIRINOX regime, this is becoming the standard of treatment with a MoS of 11.1 months. Clinical study progress has been slow with limited improvement in patient survival relative to gemcitabine 1 monotherapy. A major cause of low PC survival is the late stage of diagnosis, occurring in patients who consider typical early stage warning signs of aches and pains normal. The selection of patients with specific disease phenotypes, the use of improved efficient drug combinations, the identification of biomarkers to specific cancer subtypes and more effective designs of investigation have improved outcomes. To move beyond the current dire condition and paucity of PC treatment options, determination of the best regimes and new treatment options is a challenge that must be met. The reasons for poor PC prognosis have remained largely unchanged for 20 years. This is arguably a consequence of significant changes in the drug discovery landscape, and the increasing pressure on academia to deliver short term 'media' friendly short-term news 'bites'. PC research sits at a pivotal point. Perhaps the greatest challenge is enacting a culture change that recognises that major breakthroughs are a result of blue sky, truly innovative and curiosity driven research., (This journal is © The Royal Society of Chemistry 2020.)

Starch is the most popular plant polysaccharides, which has been widely used for the development of edible coating films because of its abundance, cost-effectiveness, and excellent film-forming abilities. Starch-based films have good optical, organoleptic and gas barrier properties, however, they have poor mechanical properties. Many attempts have been made to overcome these limitations, such as the addition of co-biopolymers or other secondary additives to improve the mechanical and tensile properties of the films. Properties of the starch-based films can be influenced by many factors, including types of starches, temperature and time during film formation, plasticizers, co-biopolymers, and storage conditions. Understanding the mechanisms of these factors is very important for future studies on the development of starch-based films. This review focuses on starch as a film/coating material and comprehensively discusses the effects of major factors on properties of starch-based films., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Catharanthus roseus (L.) G. Don (C. roseus) is a well-known medicinal plant for its source of alkaloids solely found in the leaves. Other parts including the root are usually discarded after the alkaloid extraction. This study sought to investigate phytochemical profiles, antioxidant, antimicrobial and cytotoxic properties of the C. roseus root extract (RE) and its two sub-fractions including saponin-enriched (SE) and aqueous (AQ) fractions. The results showed that the RE was a rich source of saponins (1744.44 mg ESE/g) and phenolics (51.27 mg GAE/g), which comprised of gallic acid (25.74 mg/g), apigenin (1.45 mg/g) and kaempferol (1.58 mg/g). The SE fraction was enriched with 31% of saponins and 63% of phenolics higher than those of the RE; whereas the concentrations of saponins and phenolics of the AQ fraction were lower than those of the RE by 40% and 74%, respectively. The content of gallic acid in the SE fraction was 1.4-fold and 1.5-fold higher than those of the RE or AQ fraction, respectively. The SE fraction demonstrated potent antioxidant capacity, which was significantly higher than the RE or AQ fraction, and also exhibited strong anti-proliferative activity against 11 cancer cell lines including A2780 (ovarian), H460 (lung), A431 (skin), MIA PaCa-2 (pancreas), Du145 (prostate), HT29 (colon), MCF-7 (breast), BE2-C (neuroblastoma), SJ-G2, U87 and SMA (glioblastoma) with low GI 50 values (≤ 2.00 µg/mL). The SE fraction was also shown to effectively inhibit the growth of both bacteria (Escherichia coli, Enterobacter aerogenes and Staphylococccus lugdunensis) and fungi (Candida albicans and Aspergillus niger). These findings warrant further investigation to isolate major compounds from the SE fraction and further test their antioxidant, anticancer and antimicrobial activities.

UV-C (180-280 nm) has been shown to extend the postharvest shelf-life of many horticulture crops. In this study, Tahitian limes ( Citrus latifolia ) were exposed to 0, 3.4, 7.2 and 10.5 kJ m -2  UV-C then stored for 28 days in air at 10 °C and 80% RH. Weight loss, peel colour, calyx abscission, ethylene production, respiration rate, total soluble solids (TSS), titratable acidity (TA) and acceptability index were assessed. The results showed that UV-C treatment maintained lime peel green colour and retained calyx attachment after 28 days storage. UV-C treatment also affected endogenous ethylene production and respiration rate, where the highest UV-C treatment (10.5 kJ m -2 ) maintained low ethylene production and low respiration rates after 28 days storage with no differences between the different UV-C intensities. In terms of fruit acceptability, limes were exposed to 10.5 kJ m -2  UV-C had a 60% acceptability index after 28 days storage, while untreated control fruit retained acceptability of 39%. In general, the pre-storage UV-C treatments did not affect fruit weight loss, TSS or TA contents during storage.

Banana peel is rich in phenolic compounds and is generally considered as waste. This study aimed to maximise recovery of phenolics from banana peel using water via microwave assisted extraction. The impact of various parameters including pH of solvent, sample to solvent ratio, irradiation time with/without cooling periods, and irradiation power were investigated individually. Following this, extraction conditions were further optimised using Response Surface Methodology. The results revealed that the extraction efficiency can be significantly improved by reducing the pH of water, increasing microwave power and time. However, cooling time during irradiation did not affect the extraction efficiency. Optimal conditions were identified at pH of 1, ratio of 2:100 g/mL, 6 min irradiation, and microwave power of 960 W. Under these optimal conditions, approximately 50.55 mg phenolics could be recovered from 1 g dried peel. These conditions are recommended for recovery of phenolic compounds from banana peel for further utilisation.

Pancreatic cancer (PC) is a complex, heterogeneous disease with a dismal prognosis. Current therapies have failed to improve survival outcomes, urging the need for discovery of novel targeted treatments. Bispidinone derivatives have yet to be investigated as cytotoxic agents against PC cells. The cytotoxic effect of four bispidinone derivatives ( BisP1 : 1,5-diphenyl-3,7-bis(2-hydroxyethyl)-3,7-diazabicyclo[3.3.1]nonan-9-one; BisP2 : 3,7-bis-(2-(S)-amino-4-methylsulfanylbutyryl)-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one dihydrochloride; BisP3: [2-{7-[2-( S )- tert -butoxycarbonylamino-3-(1 H -indol-3-yl)-propionyl]-9-oxo-1,5-diphenyl-3,7-diazabicyclo[3.3.1]non-3-yl}-1-( S )-(1 H -indol-3-ylmethyl)-2-oxoethyl]-carbamic acid tertbutyl ester; BisP4 : 3,7-bis-[2-( S )-amino-3-(1 H -indol-3-yl)-propionyl]-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one dihydrochloride) was assessed against PC cell lines (MiaPaca-2, CFPAC-1 and BxPC-3). Cell viability was assessed using a Cell Counting Kit-8 (CCK-8) colorimetric assay, while apoptotic cell death was confirmed using fluorescence microscopy and flow cytometry. Initial viability screening revealed significant cytotoxic activity from BisP4 treatment (1 µM⁻100 µM) on all three cell lines, with IC 50 values for MiaPaca-2, BxPC-3, and CFPAC-1 16.9 µM, 23.7 µM, and 36.3 µM, respectively. Cytotoxic treatment time-response (4 h, 24 h, and 48 h) revealed a 24 h treatment time was sufficient to produce a cytotoxic effect on all cell lines. Light microscopy evaluation (DAPI staining) of BisP4 treated MiaPaca-2 PC cells revealed dose-dependent characteristic apoptotic morphological changes. In addition, flow cytometry confirmed BisP4 induced apoptotic cell death induction of activated caspase-3/-7. The bispidinone derivative BisP4 induced an apoptosis-mediated cytotoxic effect on MiaPaca-2 cell lines and significant cytotoxicity on CFPAC-1 and BxPC-3 cell lines. Further investigations into the precise cellular mechanisms of action of this class of compounds are necessary for potential development into pre-clinical trials.

Objective: The aim of this study was to assess cytotoxic activity of extracts and fractions from the Paramignya trimera root (PTR) and Phyllanthus amarus (PA) against two pancreatic cancer cell lines (primary: BxPc3 and secondary: CFPAC1)., Materials and Methods: The root of PT and whole plant of PA were used in this study. The extracts and fractions from the PTR and PA were prepared using microwave-assisted extraction and high-performance liquid chromatography, respectively. The cytotoxic activity was assessed using the Dojindo Cell Counting Kit-8 assay., Results: The findings showed impressive cytotoxic capacity of the PTR extract against both pancreatic cancer cells of BxPc3 and CFPAC1 in a range of concentrations from 50 to 200 μg/mL, which was higher than those of ostruthin (67 μM), gemcitabine (50 nM), and four its fractions (50 μg/mL), and to be comparable to a saponin-enriched extract from Quillaja bark at 200 μg/mL. In contrast, the cytotoxic capacity of the PA extract and nine its fractions against these pancreatic cancer cell lines was significantly lower (P < 0.05) than those of gemcitabine (50 nM) and Quillaja bark extract (200 μg/mL) and being comparable to phyllanthin (4.8 μM). The IC 50 values of the PTR extract against BxPc3 and CFPAC1 cancer cells were 32.12 and 36.65 μg/mL, respectively, which was much lower than that of the PA extract against CFPAC1 cancer cells (128.81 μg/mL)., Conclusion: The outcomes obtained from this study reveal that the PTR extract is a lead source for the potential development of novel antipancreatic cancer drugs and/or functional foods., Competing Interests: None

Helicteres hirsuta Lour. (H. hirsuta) has been considered as a herbal medicine for the treatment of malaria and diabetes but limited studies have been conducted on its anticancer and antibacterial properties. In this study, the in vitro antibacterial and anticancer properties of the leaf and stem extracts and their two sub-fractions (aqueous and saponin-enriched butanol fractions) prepared from H. hirsuta were elucidated. MTT and CCK-8 assays were employed to assess their in vitro anticancer properties against various cancer cell lines. The antibacterial activity was assessed using the disc diffusion method and minimum inhibitory concentration (MIC) values were determined. The results revealed that the saponin-enriched fractions from H. hirsuta leaves and stems showed the highest antibacterial activity against E. coli (MIC values of 2.50 and 5.00 mg/mL, respectively) and S. lugdunensis (MIC values of 0.35 and 0.50 mg/mL, respectively). Importantly, these saponin-enriched fractions possessed strong anticancer activity in vitro towards a range of cancer cell lines including MIA PaCa-2 (pancreas); A2780 (ovarian); H460 (lung); A431 (skin); Du145 (prostate); HT29 (colon); MCF-7 (breast); SJ-G2, U87, SMA (glioblastoma) and BE2-C (neuroblastoma) at low doses (GI 50 values of 0.36-11.17 µg/mL). They especially revealed potent anti-pancreatic cancer activity in vitro against MIA PaCa-2, BxPC-3 and CFPAC-1 cells with IC 50 values of 1.80-6.43 µg/mL. This finding provides scientific evidence of the cytotoxic activity of the extracts prepared from H. hirsuta leaves and stems, and suggests further studies to isolate active compounds for development of new anticancer agents from these plant extracts.

This data article indicates the in vitro cytotoxicity of kaempferol and gallic acid across different cancer cell lines including A2780 (ovarian), H460 (lung), A431 (skin), MIA PaCa-2 (pancreas), Du145 (prostate), HT29 (colon), MCF-7 (breast), BE2-C (neuroblastoma), SJ-G2, U87 and SMA (glioblastoma). The dataset showed that the inhibitory activity of kaempferol was comparatively stronger than gallic acid. Thereby, kaempferol is offered as a potent anticancer agent for further investigation and beneficial as a dietary supplement. The data within this article relates to the research article entitled "Screening phytochemical content, antioxidant, antimicrobial and cytotoxic activities of Catharanthus roseus (L.) G. Don stem extract and its fractions" (Pham et al., 2018).

Background: Extracellular vesicles (EVs) are produced and secreted from most cells of the body and can be recovered in biological fluids. Although there has been extensive characterisation of the protein and nucleic acid component of EVs, their lipidome has received little attention and may represent a unique and untapped source of biomarkers for prostate cancer diagnosis and prognosis., Methods: EVs were isolated from non-tumourigenic (RWPE1), tumourigenic (NB26) and metastatic (PC-3) prostate cell lines. Lipids were extracted and subsequently used for targeted lipidomics analysis for the quantitation of molecular lipid species., Results: A total of 187 molecular lipid species were quantitatively identified in EV samples showing differential abundance between RWPE1, NB26 and PC-3 EV samples. Fatty acids, glycerolipids and prenol lipids were more highly abundant in EVs from non-tumourigenic cells, whereas sterol lipids, sphingolipids and glycerophospholipids were more highly abundant in EVs from tumourigenic or metastatic cells., Conclusions: This study identified differences in the molecular lipid species of prostate cell-derived EVs, increasing our understanding of the changes that occur to the EV lipidome during prostate cancer progression. These differences highlight the importance of characterising the EV lipidome, which may lead to improved diagnostic and prognostic biomarkers for prostate cancer.