ORCID Profile
0000-0002-8888-3789
Current Organisations
The University of Newcastle
,
Nutrition Research Australia
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Genomics | Neural, Evolutionary and Fuzzy Computation | Pattern Recognition and Data Mining | Biochemistry and Cell Biology | Information and Computing Sciences not elsewhere classified | Synthetic Biology | Artificial Intelligence and Image Processing
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Publisher: Elsevier BV
Date: 07-2013
Publisher: SAGE Publications
Date: 15-04-2015
Abstract: Interest in vitamin D and the VDR gene is increasing as putative roles in human health and evolutionary processes are explored. This review looks beyond the classic biochemistry that links vitamin D to calcium homeostasis it explores how vitamin D interacts with light in a broader perspective than simple skin photosynthesis. It examines how the vitamin influences circadian rhythm, and how it may have helped drive the evolution of skin pigmentation. To this end, the nutrient–nutrient relationship with folate is also explored. The VDR gene is additionally examined as a factor in the evolutionary selection of skin depigmentation at higher latitudes to allow vitamin D synthesis. Evidence is given to show that VDR polymorphisms exhibit a latitudinal gradient in allele prevalence consistent with such a paradigm. Overall, the review examines new evo-devo ideas that link light-sensitive vitamins to human health henotype, both within and across the lifecycle.
Publisher: MDPI AG
Date: 20-09-2018
DOI: 10.3390/NU10101336
Abstract: The type 2 family of taste receptors (T2Rs) detect and respond to bitter tastants. These receptors are expressed throughout the gastrointestinal (GI) tract, with location dependant roles. In the oral cavity, T2Rs are involved in the conscious perception of bitter tastants, while in the lower GI tract they have roles in chemoreception and regulation of GI function. Through these erse roles, these receptors may be involved in modulating appetite and diet, with consequences for weight regulation and obesity. Interestingly, the concentration of T2Rs in the GI tract is greatest in the large intestine, the organ with the densest colonisation of bacteria. The gut microbiome has been the subject of intense research, as a plethora of roles linking microbiota to human health continue to be uncovered. Of particular interest is the microbial signature associated with obesity. Obesity is a leading health concern, and advances in our understanding of this disease are needed. Diet is a known modifiable factor in the development of obesity. However, diet only partially explains disease risk. Changes in microbial energy harvesting by the microbiota plays a role in obesity, and the composition of these energy harvesting populations may be controlled by taste receptors. This review explores T2Rs as a potential link between obesity and the human GI microbiome.
Publisher: Wiley
Date: 22-04-2017
DOI: 10.1002/AJHB.23010
Abstract: The vitamin D receptor (VDR) is a member of the nuclear receptor family of transcription factors. We examined whether degree of VDR gene methylation acts as a molecular adaptation to light exposure. We explored this in the context of photoperiod at conception, recent UV irradiance at 305 nm, and gene-latitude effects. Eighty subjects were examined for VDR gene-CpG island methylation density. VDR gene variants were also examined by PCR-RFLP. Photoperiod at conception was significantly positively related to VDR methylation density, explaining 17% of the variance in methylation (r Duration of early-life light exposure and strength of recent irradiance, along with latitudinal genetic factors, influence degree of VDR gene methylation consistent with this epigenetic phenomenon being a molecular adaptation to variation in ambient light exposure. Findings contribute to our understanding of human biology.
Publisher: Bioscientifica
Date: 2020
DOI: 10.1530/REP-19-0201
Abstract: In women, the non-growing population of follicles that comprise the ovarian reserve is determined at birth and serves as the reservoir for future fertility. This reserve of dormant, primordial follicles and the mechanisms controlling their selective activation which constitute the committing step into folliculogenesis are essential for determining fertility outcomes in women. Much of the available data on the mechanisms responsible for primordial follicle activation focuses on a selection of key molecular pathways, studied primarily in animal models, with findings often not synonymous in humans. The excessive induction of primordial follicle activation may cause the development of premature ovarian insufficiency (POI), a condition characterised by menopause before age 40 years. POI affects 1–2% of all women and is accompanied by additional health risks. Therefore, it is critical to further our understanding of primordial follicle activation in order to diagnose, treat and prevent premature infertility. Research in primordial follicle activation has focused on connecting new molecules to already established key signalling pathways, such as phosphatidylinositol 3-Kinase (PI3K) and mammalian target of rapamycin (mTOR). Additionally, other aspects of the ovarian environment, such as the function of the extracellular matrix, in contributing to primordial follicle activation have gained traction. Clinical applications are examining replication of this extracellular environment through the construction of biological matrices mimicking the 3D ovary, to support follicular growth through to ovulation. This review outlines the importance of the events leading to the establishment of the ovarian reserve and highlights the fundamental factors known to influence primordial follicle activation in humans presenting new horizons for female infertility treatment.
Publisher: American Thoracic Society
Date: 05-2012
DOI: 10.1164/AJRCCM-CONFERENCE.2012.185.1_MEETINGABSTRACTS.A2863
Publisher: MDPI AG
Date: 10-01-2023
DOI: 10.3390/NU15020349
Abstract: As food choices are usually processed subconsciously, both situational and food environment cues influence choice. This study developed and tested a mobile app to investigate the association between physical and digital environments on snack choices. SnackTrack was designed and used to collect data on the snack choices of 188 users in real-life settings during an 8-week feasibility trial. The app asks users to take a photo of the food they are planning to consume and to provide additional information regarding the physical environment and context in which this food was eaten. The app also displayed various user interface designs (i.e., different background images) to investigate the potential effects of images on snack choice. Preliminary results suggest that the time of snack obtainment did not have a significant effect on the healthfulness of the snacks chosen. Conversely, it was found that unhealthy background images appeared to encourage healthier snack choices. In conclusion, despite consumers having the knowledge to make healthy choices, environmental cues can alter food choices. SnackTrack, a novel tool to investigate the influence of physical and digital environments on consumers’ food choices, provides possibilities for exploring what encourages (un)healthy eating behaviours.
Publisher: Frontiers Media SA
Date: 17-08-2021
Abstract: Single nucleotide polymorphisms (SNPs) in taste receptors influence dietary choices that contribute to health and quality of life. In idual 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.
Publisher: Elsevier BV
Date: 2023
Publisher: S. Karger AG
Date: 2015
DOI: 10.1159/000381676
Abstract: b i Background and Aims: /i /b Circulating microRNAs (miRNAs) are linked to disease and are potential biomarkers. Vitamin D may modulate miRNA profiles, and vitamin D status has been linked to risk of disease, including cardiovascular disease and cancers. We hypothesise that genotypic variance influences these relationships. We examined the correlations between vitamin D intake and circulating levels of the miRNAs let-7a/b, and the involvement of two common vitamin D receptor i (VDR) /i polymorphisms, i Bsm /i I and i Apa /i I. b i Methods: /i /b Two hundred participants completed food frequency and supplement questionnaires, and were assayed for circulating let-7b expression by qPCR. Polymorphisms were detected using restriction fragment length polymorphism-PCR. b i Results: /i /b let-7b expression negatively correlated with vitamin D intake (r sub s /sub = -0.20, p = 0.005). The magnitude and direction of correlation were maintained in the presence of the i Bsm /i I restriction site (r sub s /sub = -0.27, p = 0.0005). However, in the absence of i Bsm /i I restriction site, the direction of the correlation was reversed (r sub s /sub = +0.319, p = 0.0497). These correlations were significantly different (z-score = 2.64, p = 0.0085). The correlation between vitamin D intake and let-7a was only significant in those without the i Apa /i I restriction site. b i Conclusions: /i /b The correlation between vitamin D intake and let-7a/b expression in this cohort varies with i VDR /i genotype. This study highlights the importance of considering underlying genotypic variance in miRNA expression studies and in nutritional epigenetics generally.
Publisher: MDPI AG
Date: 08-06-2020
Abstract: 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 erse 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.
Publisher: Springer Science and Business Media LLC
Date: 12-08-2022
DOI: 10.1007/S00280-022-04463-X
Abstract: Gastrointestinal mucositis (GIM) is a side effect of high-dose irinotecan (CPT-11), causing debilitating symptoms that are often poorly managed. The role of TLR4 in the development of GIM has been clearly demonstrated. We, therefore, aimed to investigate the potential of the TLR4 antagonist, IAXO-102, to attenuate gastrointestinal inflammation as well as supress tumour activity in a colorectal-tumour-bearing mouse model of GIM induced by CPT-11. 24 C57BL/6 mice received a vehicle, daily i.p. IAXO-102 (3 mg/kg), i.p. CPT-11 (270 mg/kg) or a combination of CPT-11 and IAXO-102. GIM was assessed using validated toxicity markers. At 72 h, colon and tumour tissue were collected and examined for histopathological changes and RT-PCR for genes of interest TLR4, MD-2, CD-14, MyD88, IL-6, IL-6R, CXCL2, CXCR1, and CXCR2. IAXO-102 prevented diarrhoea in mice treated with CPT-11. Tumour volume in IAXO-102-treated mice was lower compared to vehicle at 48 h ( P 0.05). There were no differences observed in colon and tumour weights between the treatment groups. Mice who received the combination treatment had improved tissue injury score ( P 0.05) in the colon but did not show any improvements in cell proliferation or apoptotic rate. Expression of all genes was similar across all treatment groups in the tumour ( P 0.05). In the colon, there was a difference in transcript expression in vehicle vs. IAXO-102 ( P 0.05) and CPT-11 vs. combination ( P 0.01) in MD-2 and IL-6R, respectively. IAXO-102 was able to attenuate symptomatic parameters of GIM induced by CPT-11 as well as reduce tissue injury in the colon. However, there was no effect on cell proliferation and apoptosis. As such, TLR4 activation plays a partial role in GIM development but further research is required to understand the specific inflammatory signals underpinning tissue-level changes.
Publisher: Wiley
Date: 22-10-2017
DOI: 10.1002/AJHB.22929
Abstract: The purpose of this study was to examine whether UV exposure alters folate status according to C677T-MTHFR genotype, and to consider the relevance of this to human health and the evolutionary model of skin pigmentation. Total Ozone Mapping Spectrometer (TOMS) satellite data were used to examine surface UV-irradiance, as a marker of UV exposure, in a large (n = 649) Australian cross-sectional study population. PCR/RFLP analysis was used to genotype C677T-MTHFR. Overall, cumulative UV-irradiance (42 and 120 days pre-clinic) was significantly negatively related to red cell folate (RCF) levels. When the cohort was stratified by MTHFR-C677T genotype, the relationship between UV-irradiance (42 days pre-clinic) and RCF remained significant only in the cohorts containing carriers of the T allele. Statistically significant z-score statistics and interaction terms from genotype and UV-irradiance (p-interaction) demonstrated that genotype did modify the effect of UV-irradiance on RCF, with the largest effect of UV being demonstrated in the 677TT-MTHFR subjects. Data provide strong evidence that surface UV-irradiance reduces long-term systemic folate levels, and that this is influenced by the C677T-MTHFR gene variant. We speculate this effect may be due to 677TT-MTHFR in iduals containing more 5,10CH
Publisher: Oxford University Press (OUP)
Date: 02-2016
DOI: 10.1095/BIOLREPROD.115.135848
Abstract: The theory of fetal origins of adult disease was first proposed in 1989, and in the decades since, a wide range of other diseases from obesity to asthma have been found to originate in early development. Because mammalian oocyte development begins in fetal life it has been suggested that environmental and lifestyle factors of the mother could directly impact the fertility of subsequent generations. Cigarette smoke is a known ovotoxicant in active smokers, yet disturbingly 13% of Australian and 12% of US women continue to smoke throughout pregnancy. The focus of our investigation was to characterize the adverse effects of smoking on ovary and oocyte quality in female offspring exposed in utero. Pregnant mice were nasally exposed to cigarette smoke for 12 wk throughout pregnancy/lactation, and ovary and oocyte quality of the F1 (maternal smoke exposed) generation was examined. Neonatal ovaries displayed abnormal somatic cell proliferation and increased apoptosis, leading to a reduction in follicle numbers. Further investigation found that altered somatic cell proliferation and reduced follicle number continued into adulthood however, apoptosis did not. This reduction in follicles resulted in decreased oocyte numbers, with these oocytes found to have elevated levels of oxidative stress, altered metaphase II spindle, and reduced sperm-egg interaction. These ovarian and oocyte changes ultimately lead to subfertility, with maternal smoke-exposed animals having smaller litters and also taking longer to conceive. In conclusion, our results demonstrate that in utero and lactational exposure to cigarette smoke can have long-lasting effects on the fertility of the next generation of females.
Publisher: MDPI AG
Date: 10-04-2020
DOI: 10.3390/NU12041056
Abstract: A small amount of emerging research has observed variations between in idual sensitivity, preference and intake of salt in the presence of single nucleotide polymorphisms (SNP) on the genes encoding salt taste receptors. Sodium intake is a significant risk factor for common diseases in elderly populations such as hypertension and cardiovascular disease however, this does not fully explain the risk. Research into the influence of salt taste genetics on diet quality is yet to be undertaken and current research on indicators of health is limited and mixed in the direction of associations. Therefore, a secondary analysis of data from a well-characterised elderly cohort (the cross-sectional Retirement Health and Lifestyle Study, n = 536) was conducted to explore relationships between the salt taste-related SNP TRPV1-rs8065080 (assessed by Taqman genotyping assay), dietary habits and biomarkers of health. Data were analysed with standard least squares regression modelling and Tukey’s HSD post hoc tests. No association was found between the TRPV1-rs8065080 genotype, sodium intake or multiple diet quality indices (assessed by food frequency questionnaire). Sodium-related markers of health including blood pressure and markers of kidney function (urinary creatinine and albumin/creatinine ratio) and general health markers, such as Body Mass Index (BMI), were also not related to TRPV1-rs8065080 genotype. To date, this study is the most comprehensive investigation conducted to determine if the TRPV1-rs8065080 genotype relates to sodium intake and health markers influenced by sodium intake. Although no significant relationships were found, these findings are an important contribution to the limited body of knowledge surround this SNP. In addition to further research across other ages and cultures, the TRPV1-rs8065080 genotype may interact with other ion channels, and so further studies are required to determine if polymorphic variations influence sodium intake, diet and health.
Publisher: MDPI AG
Date: 18-05-2020
DOI: 10.3390/NU12051455
Abstract: 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 (pinteraction = 0.002), and 4M-EDR and MTHFD1-rs2236225 (pinteraction = 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 ( .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.
Publisher: Public Library of Science (PLoS)
Date: 08-2012
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.CCA.2017.09.001
Abstract: Low folate status is linked to increased risk of a number of conditions, including developmental disorders, some cancers, neurodegenerative and cardiovascular diseases. Some of the mechanisms of these associations are known, but much remains to be elucidated. Aberrant microRNA (miRNA) profiles are also signatures of these conditions, and as such, the association between folate status and miRNA are now being investigated. Potential associations are bidirectional, with miRNA linked to regulation of folate-mediated pathways, and folate linked to modulation of miRNA expression. miRNA are short non-coding RNA, involved in post-transcriptional regulation of gene expression via complementary binding to mRNA. Evidence is emerging that links folate levels to the regulation of miRNA levels, and miRNA to the regulation of the expression of enzymes involved in folate mediated one carbon metabolism. One carbon metabolism is the source of methyl groups for methylation reactions, including DNA methylation and is important in DNA synthesis and repair. miRNA may be modulated by DNA methylation and other epigenetic mechanisms directly, or indirectly via modulation of upstream signalling pathways. As such, there may be bi-directional associations between folate status and miRNA profiles. miRNA may also act as biomarkers for diagnosis or prognosis of conditions associated with folate status.
Publisher: BMJ
Date: 06-03-2015
DOI: 10.1136/THORAXJNL-2014-206067
Abstract: Steroid-insensitive endotypes of asthma are an important clinical problem and effective therapies are required. They are associated with bacterial infection and non-eosinophilic inflammatory responses in the asthmatic lung. Macrolide therapy is effective in steroid-insensitive endotypes, such as non-eosinophilic asthma. However, whether the effects of macrolides are due to antimicrobial or anti-inflammatory mechanisms is not known. To determine and assess the efficacy of macrolide (ie, clarithromycin) and non-macrolide (ie, amoxicillin) antibiotic treatments in experimental models of infection-induced, severe, steroid-insensitive neutrophilic allergic airways disease (SSIAAD), compared with steroid-sensitive AAD and to delineate the antimicrobial and anti-inflammatory effects of macrolide therapy. We developed and used novel mouse models of Chlamydia and Haemophilus lung infection-induced SSIAAD. We used these models to investigate the effects of clarithromycin and amoxicillin treatment on immune responses and airways hyper-responsiveness (AHR) in Ova-induced, T helper lymphocyte (Th) 2 -associated steroid-sensitive AAD and infection-induced Th1/Th17-associated SSIAAD compared with dexamethasone treatment. Clarithromycin and amoxicillin had similar antimicrobial effects on infection. Amoxicillin did attenuate some features, but did not broadly suppress either form of AAD. It did restore steroid sensitivity in SSIAAD by reducing infection. In contrast, clarithromycin alone widely suppressed inflammation and AHR in both steroid-sensitive AAD and SSIAAD. This occurred through reductions in Th2 responses that drive steroid-sensitive eosinophilic AAD and tumour necrosis factor α and interleukin 17 responses that induce SSIAAD. Macrolides have broad anti-inflammatory effects in AAD that are likely independent of their antimicrobial effects. The specific responses that are suppressed are dependent upon the responses that dominate during AAD.
Publisher: MDPI AG
Date: 24-02-2021
DOI: 10.3390/NU13030719
Abstract: Differences in sour-taste thresholds have been identified in cognition-related diseases. Diet is a modulator of cognitive health, and taste perception influences dietary preferences and habits. Heritable genetics and polymorphisms in the KCNJ2 gene involved in the transduction of sour taste have been linked to variations in sour taste and non-gustatory functions. However, relationships between sour taste genetics, mild cognitive impairment, and diet quality are yet to be elucidated. This study investigated the associations between the presence of the KCNJ2-rs236514 variant (A) allele, diet quality indices, and mild cognitive impairment evaluated by the Mini-Mental State Examination (MMSE), in a secondary cross-sectional analysis of data from the Retirement Health & Lifestyle Study. Data from 524 elderly Australians (≥65y) were analyzed, using standard least squares regression and nominal logistic regression modeling, with demographic adjustments applied. Results showed that the presence of the KCNJ2-A allele is associated with increased proportions of participants scoring in the range indicative of mild or more severe cognitive impairment (MMSE score of ≤26) in the total cohort, and males. These associations remained statistically significant after adjusting for age, sex, and diet quality indices. The absence of association between the KCNJ2-A allele and cognitive impairment in women may be related to their higher diet quality scores in all indices. The potential link between sour taste genotype and cognitive impairment scores may be due to both oral and extra-oral functions of sour taste receptors. Further studies are required on the role and relationship of neurotransmitters, sour taste genotypes and sour taste receptors in the brain, and dietary implications, to identify potential risk groups or avenues for therapeutic or prophylactic interventions.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.TAAP.2013.05.009
Abstract: Cigarette smoke is a reproductive hazard associated with pre-mature reproductive senescence and reduced clinical pregnancy rates in female smokers. Despite an increased awareness of the adverse effects of cigarette smoke exposure on systemic health, many women remain unaware of the adverse effects of cigarette smoke on female fertility. This issue is compounded by our limited understanding of the molecular mechanisms behind cigarette smoke induced infertility. In this study we used a direct nasal exposure mouse model of cigarette smoke-induced chronic obstructive pulmonary disease to characterise mechanisms of cigarette-smoke induced ovotoxicity. Cigarette smoke exposure caused increased levels of primordial follicle depletion, antral follicle oocyte apoptosis and oxidative stress in exposed ovaries, resulting in fewer follicles available for ovulation. Evidence of oxidative stress also persisted in ovulated oocytes which escaped destruction, with increased levels of mitochondrial ROS and lipid peroxidation resulting in reduced fertilisation potential. Microarray analysis of ovarian tissue correlated these insults with a complex mechanism of ovotoxicity involving genes associated with detoxification, inflammation, follicular activation, immune cell mediated apoptosis and membrane organisation. In particular, the phase I detoxifying enzyme cyp2e1 was found to be significantly up-regulated in developing oocytes an enzyme known to cause molecular bioactivation resulting in oxidative stress. Our results provide a preliminary model of cigarette smoke induced sub-fertility through cyp2e1 bioactivation and oxidative stress, resulting in developing follicle depletion and oocyte dysfunction.
Publisher: Informa UK Limited
Date: 30-03-2021
DOI: 10.1080/14647273.2021.1871784
Abstract: The growth of smartphone application use across areas of female reproductive health has led to increased interest into their functions and benefits. This scoping review aims to determine the nature and extent of the peer-reviewed literature presented on fertility-based apps, to identify the reliability of the information within the apps, and to determine the ability of this information to educate users. A systematic search of six databases was conducted in April 2020, returning a total of 21,158 records. After duplicate removal, title and abstract screening exclusionary steps, 27 records were reviewed and charted. Records covered a variety of reproductive health themes including contraception, sexual health, and family planning, and used a range of methodologies. The accuracy of fertility information within the apps reported in these studies was variable, but overall there was a lack of depth in the coverage of content in apps. It was common for studies in this review to base fertile window algorithms on stringent cycle length and variability requirements, limiting the applicability of information delivered to users. Furthermore, studies from app affiliates often lacked collaborations with researchers, minimising the potential for fertility knowledge improvements integrated across the suite of female reproductive health apps.
Publisher: Elsevier BV
Date: 06-2016
Publisher: MDPI AG
Date: 28-02-2020
Abstract: 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.
Publisher: American Physiological Society
Date: 06-2019
DOI: 10.1152/AJPRENAL.00082.2019
Abstract: Maternal undernutrition during pregnancy is prevalent across the globe, and the origins of many chronic diseases can be traced back to in utero conditions. This systematic review considers the current evidence in animal models regarding the relationship between maternal global nutrient restriction during pregnancy and offspring kidney structure and function. CINAHL, Cochrane, EMBASE, MEDLINE, and Scopus were searched to November 2017. Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed, and articles were screened by two independent reviewers. Twenty-eight studies met the inclusion criteria: 16 studies were on rats, 9 on sheep, 2 on baboons, and 1 on goats. The majority of the rat studies had maternal global nutrient restriction during pregnancy at 50% of ad libitum while restriction for sheep and baboon studies ranged from 50% to 75%. Because of the heterogeneity of outcome measures and the large variation in the age of offspring at followup, no meta-analysis was possible. Common outcome measures included kidney weight, nephron number, glomerular size, glomerular filtration rate, and creatinine clearance. To date, there have been no studies assessing kidney function in large animal models. Most studies were rated as having a high or unknown risk of bias. The current body of evidence in animals suggests that exposure to maternal global nutrient restriction during pregnancy has detrimental effects on offspring kidney structure and function, such as lower kidney weight, lower nephron endowment, larger glomerular size, and lower glomerular filtration rate. Further long-term followup of studies in large animal models investigating kidney function through to adulthood are warranted.
Publisher: MDPI AG
Date: 18-05-2021
DOI: 10.3390/ORAL1020013
Abstract: (1) Background: The aetiology of oral disease is multifactorial, involving genetic and environmental factors, including dietary ones. Bitter taste genetics may be related to oral health through dietary modulation or non-gustatory roles, including modulation of inflammation. Investigations of bitter taste and oral health associations to date have been restricted to specific polymorphisms, limited outcomes (caries), and age-groups (children), and links to inflammation remain to be elucidated. (2) Methods: A cross-sectional study (n = 65) investigated the correlations between bitter taste genotypes, oral health outcomes, and oral inflammation markers. Oral examinations were conducted, including saliva testing with evaluation of flow rate, pH, and buffering and antioxidant capacity (FRAP) and IL-1β, TNF-α, IL-6 levels. DNA was collected via buccal swabs and used to evaluate the presence of multiple bitter-taste receptor gene polymorphisms. (3) Results: The major allele for TAS2R4-rs2233998, TAS2R5-rs2227264, TAS2R50-rs1376251, and TAS2R9-rs3741845 was associated with a higher mean of unstimulated salivary flow rate, FRAP, TNF-α, IL-1β, and likelihood of filled teeth. Presence of the major allele for TAS2R4-rs2234001 and TAS2R9-rs3741845 was associated with lower means FRAP, TNF-α, IL-1β, DMFT index, and likelihood of missing teeth. (4) Conclusions: These findings suggest relationships between bitter-taste genotypes, oral health outcomes, and inflammatory markers. These findings justify the need for further studies that could help identify risk groups and develop novel agents for maintaining oral health.
Publisher: Public Library of Science (PLoS)
Date: 19-06-2012
Publisher: Elsevier
Date: 2019
Publisher: Wiley
Date: 21-08-2021
DOI: 10.1002/AJHB.23667
Abstract: To test the “vitamin D‐folate hypothesis for the evolution of human skin pigmentation.” 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. 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 . New biophysical evidence supports the vitamin D‐folate hypothesis for evolution of skin pigmentation.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6FO01759B
Abstract: Sex-specific interactions between bitter taste phenotype, TAS2R38 genotype and alcohol intake may explain variance is previous studies, and may have implications for disease risk.
Publisher: MDPI AG
Date: 17-02-2022
DOI: 10.3390/NU14040848
Abstract: Australians’ vegetable intakes are low, and strategies are needed for improvement. Popular convenience cooking products (meal bases and recipe bases, ready-made marinades, and convenience cooking sauces) address common cooking and vegetable consumption barriers (cost, time, and cooking skills). However, relationships between their usage and vegetable intakes have not been established. Therefore, Australian adults were surveyed on convenience cooking product use, vegetable intake and variety, behaviours when barriers to vegetable inclusion arise, and vegetable choice factors. Of 842 participants, 36.7% used meal and recipe bases, 28.1% marinades, and 47.2% cooking sauces, with most following the back-of-pack recipes at least sometimes. A total of 12.5% of participants used products from all three categories. Factors associated with lower vegetable intakes were meal and recipe base and cooking sauce use, using a higher number of product categories, and always following back-of-pack recipes. Factors associated with lower vegetable variety were the use of meal and recipe bases and cooking sauces. Factors in vegetable choice, and behaviours when not including a listed vegetable (due to not having or liking the vegetable, or an inability to eat it) did not vary by usage habits. These results provide insights into current vegetable intakes of those using convenience products, providing a baseline for future changes in the product design and recommendations.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2020
DOI: 10.1186/S12905-020-00912-Y
Abstract: Previous studies have identified that women living in developed countries have insufficient knowledge of factors which may be contributing to the increasingly high global infertility rates such as maternal age and assisted reproductive technologies. There is a large market of reproductive health smartphone applications, yet little is known about the advantages these apps may confer to users in regards to reproductive health knowledge. An anonymous, online survey of women living in Australia aged 18 and above was open March–June 2018, until ≥200 responses were acquired for statistical power. Respondents answered questions regarding knowledge about general fertility and related factors (age, cyclic fertility, smoking, obesity, miscarriage rate, and success of assisted reproductive technologies). Fertility knowledge was compared in respondents who did or did not use apps relating to female reproductive health. Additionally the functions preferred in reproductive health apps was described by app using respondents. Sociodemographic information was also collected, and relevant data within the dataset was subject to multivariable modelling for the outcome of the fertility knowledge questions. Of the 673 respondents that completed the survey, 43.09% reported using mobile phone applications relating to female reproductive health. On average, respondents answered only three of the six fertility knowledge questions correctly. App using respondents were more likely to score better on one question, related to fertility during the menstrual cycle ( p 0.001). App users most commonly reported using the menstrual tracking function in apps (82.4%), which may account for the increased knowledge of cyclic fertility. This data provides preliminary evidence toward the usefulness of smartphone applications as a medium for providing information about fertility to women. A limited understanding of one’s own fertility was demonstrated despite being essential for the decision-making of women throughout their reproductive years.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 12-2010
Publisher: Elsevier BV
Date: 12-2016
Publisher: Oxford University Press (OUP)
Date: 28-04-2018
Abstract: This review explores contemporary ideas about the relationship between light exposure and vitamin biology. Nutritional biochemistry has long recognized the relationship between vitamins A and D and light exposure, but in recent years other vitamins have also been implicated in photoresponsive biological mechanisms that influence health, well-being, and even evolutionary processes. Interactions between light and vitamins can modify genotype-phenotype relationships across the life cycle, providing a basis for interesting new explanations relevant to wide aspects of human biology. This review examines both well-established and emerging ideas about vitamin photobiology in the context of the following: (1) light responsiveness of vitamin D (photosynthesized in skin), vitamin A (linked to vision), and vitamin B3 (needed to repair genomic damage) (2) vulnerability of folate and vitamins B1, B2, B12, and D to ultraviolet (UV) light (all potentially degraded) (3) protective/filtering actions of carotenoids and vitamins C and E, which act as antioxidants and/or natural sunscreens, against UV light (4) role of folate, carotenoids, and vitamins A, B3, C, D, and E in UV-related genomic regulation, maintenance, and repair (5) role of folate and vitamins A, B2, B12, and D in a range of light-signaling and light-transduction pathways and (6) links between folate and vitamin D and the evolution of UV light-adaptive phenotypes.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-11-2021
DOI: 10.1126/SCITRANSLMED.AAV7223
Abstract: Inhibition of cigarette smoke–induced microRNA-21 suppresses chronic obstructive pulmonary disease through effects on a SATB1/S100A9/NF-κB axis.
Publisher: Elsevier BV
Date: 04-2015
Publisher: Informa UK Limited
Date: 27-07-2023
Publisher: Wiley
Date: 17-01-2014
DOI: 10.1002/AR.22867
Abstract: Preterm infants who receive supplemental oxygen for prolonged periods are at increased risk of impaired lung function later in life. This suggests that neonatal hyperoxia induces persistent changes in small conducting airways (bronchioles). Although the effects of neonatal hyperoxia on alveolarization are well documented, little is known about its effects on developing bronchioles. We hypothesized that neonatal hyperoxia would remodel the bronchiolar walls, contributing to altered lung function in adulthood. We studied three groups of mice (C57BL/6J) to postnatal day 56 (P56 adulthood) when they either underwent lung function testing or necropsy for histological analysis of the bronchiolar wall. One group inhaled 65% O2 from birth until P7, after which they breathed room air this group experienced growth restriction (HE+GR group). We also used a group in which hyperoxia-induced GR was prevented by dam rotation (HE group). A control group inhaled room air from birth. At P56, the bronchiolar epithelium of HE mice contained fewer Clara cells and more ciliated cells, and the bronchiolar wall contained ∼25% less collagen than controls in HE+GR mice the bronchiolar walls had ∼13% more collagen than controls. Male HE and HE+GR mice had significantly thicker bronchiolar epithelium than control males and altered lung function (HE males: greater dynamic compliance HE+GR males: lower dynamic compliance). We conclude that neonatal hyperoxia remodels the bronchiolar wall and, in adult males, affects lung function, but effects are altered by concomitant growth restriction. Our findings may partly explain the reports of poor lung function in ex-preterm children and adults.
Publisher: Wiley
Date: 21-11-2018
DOI: 10.1002/AJHB.23079
Abstract: Folate-mediated 1-carbon transfer processes are vital in human health but are susceptible to independent and interactive influences of genetic variance and environmental exposures. Evidence suggests folate levels may be impacted by genetic variance and environmental UVR, with the effect of UVR levels influenced in part by degree of skin pigmentation. Folate-related genes are also influenced by UVR levels however, the potential relationship between key folate-related genes and skin pigmentation has not yet been explored. The purpose of this study was to examine potential associations between frequencies of key folate variants and degree of skin pigmentation. Association between population prevalence of 17 variants in 9 folate-related genes (MTRR, MTR, MTHFR, CBS, SHMT1, MTHFD1, RFC1, BHMT, TYMS) and the Fitzpatrick skin phototype of populations was assessed via collation of genotypic data from ALFRED (Allele Frequency Database) and 1000 Genomes databases. A significant association between variant frequency and Fitzpatrick phototype was observed for 16 of 17 examined variants (P < .0029 Bonferroni corrected significance threshold in all cases). These findings demonstrate novel relationships between skin color and folate-related genes, with trends suggesting folate genotypes are selected to maintain homeostasis in the folate system under differing UVR conditions.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4FO00539B
Abstract: Bitter is the most complex, and arguably the most important of human tastes however the complex relationships to health and disease are yet to be fully elucidated.
Publisher: Wiley
Date: 11-06-2019
DOI: 10.1002/AJHB.23272
Abstract: Within the Developmental Origins of Adult Disease (DOHaD) model, early life environmental exposures can confer a long-term legacy on human health. This mechanism may be adaptive or maladaptive depending on lifestyle circumstances. This article examines the role of first trimester UV-exposure on late-life vitamin D levels, and potentially related adaptive and maladaptive phenotypes (height and osteoporosis respectively). Six hundred and forty nine subjects were examined for vitamin D Solar irradiance over the first 90 days postconception correlated positively with late-life vitamin D Increased solar irradiance/UV exposure during the first trimester of pregnancy calibrates adult vitamin D metabolism, which is an important hormone in maintaining calcium balance. This may explain how very early lifecycle UV exposure can influence skeletal development (adult height) and modify risk for the skeletal degenerative disorder osteoporosis. The data demonstrate humans are tuned to the world (exposome) in ways we have not yet fully considered, and which are entrained at the earliest phase of the lifecycle.
Publisher: Elsevier BV
Date: 06-2015
Publisher: MDPI AG
Date: 14-11-2018
DOI: 10.3390/NU10111759
Abstract: We thank Elias and Williams for their interest in our review [...]
Publisher: Informa UK Limited
Date: 08-09-2021
DOI: 10.1080/09637486.2021.1975659
Abstract: ABSTARCTMeal/recipe bases are low-cost and popular convenience cooking products, requiring limited preparation time and cooking skills. Back-of-pack recipes provided on these products could help encourage vegetable consumption however, the vegetable content of these recipes has not been examined. Therefore, an audit was conducted of recipes provided on recipe/meal bases (
Publisher: Oxford University Press (OUP)
Date: 30-09-2014
Abstract: What are the effects on fertility of cigarette smoke-induced toxicity on male offspring exposed during the gestational/weaning period? Maternal cigarette smoke exposure during the gestational/weaning period causes long-term defects in male offspring fertility. Cigarette smoke is a well-known reproductive toxicant which is particularly harmful to both fetal and neonatal germ cells. However, recent studies suggest a significant portion of young mothers in the developed world still smoke during pregnancy. In the context of male reproductive health, our understanding of the effects of in utero exposure on offspring fertility is limited. In this study, 27 C57BL/6 5-week-old female mice were exposed via the nose-only to cigarette smoke (treatment) or 27 were exposed to room air (control) for 6 weeks before being housed with stud males to produce litters. In the treatment group, smoke exposure continued throughout mating, pregnancy and lactation until weaning of pups at 21 days post birth. Male offspring were examined at post-natal days 3, 6, 12, 21 and 98 (adult). Approximately 108 maternal smoke-exposed C57BL/6 offspring and controls were examined. Spermatogenesis was examined using testicular histology and apoptosis/DNA damage was assessed using caspase immunohistochemistry and TUNEL. Sertoli cell morphology and fluctuations in the spermatogonial stem cell population were also examined using immunohistochemistry. Microarray and QPCR analysis were performed on adult testes to examine specific long-term transcriptomic alteration as a consequence of maternal smoke exposure. Sperm counts and motility, zona/oolemma binding assays, COMET analysis and mitochondrial genomic sequencing were also performed on spermatozoa obtained from adult treated and control mice. Fertility trials using exposed adult male offspring were also performed. Maternal cigarette smoke exposure caused increased gonocyte and meiotic spermatocyte apoptosis (P < 0.01) as well as germ cell depletion in the seminiferous tubules of neonatal and juvenile offspring. Aberrant testicular development characterized by abnormal Sertoli and germ cell organization, a depleted spermatogonial stem cell population (P < 0.01), atrophic seminiferous tubules and increased germ cell DNA damage (P < 0.01) persisted in adult offspring 11 weeks after exposure. Microarray analysis of adult offspring testes associated these defects with meiotic germ cell development, sex hormone metabolism, oxidative stress and Sertoli cell signalling. Next generation sequencing also revealed a high mitochondrial DNA mutational load in the testes of adult offspring (P < 0.01). Adult maternal smoke-exposed offspring also had reduced sperm counts with spermatozoa exhibiting morphological abnormalities (P < 0.01), affecting motility and fertilization potential. Odf2, a spermatozoa flagellum component required for coordinated ciliary beating, was also significantly down-regulated (P < 0.01) in maternal smoke-exposed adult offspring, with aberrant localization along the spermatozoa flagellum. Adult maternal smoke-exposed offspring took significantly longer to impregnate control females and had a slight but significant (P < 0.01) reduction in litter size. This study examined only one species (mouse) using a smoking model which only simulates human cigarette smoke exposure. This study represents the first comprehensive animal model of maternal smoking on male offspring reproductive function, suggesting that exposure during the gestational/weaning period causes long-term defects in male offspring fertility. This is due to a compromised spermatogonial stem cell population resulting from gonocyte apoptosis and impaired spermatogenic development. This results in significant germ cell damage and Sertoli cell dysfunction, impacting germ cell number, tubule organization, DNA damage and spermatozoa in adult offspring. This study strengthens the current literature suggesting that maternal exposure impairs male offspring fertility, which is currently debated due to conflicting studies. This study was funded by the Australian Research Council, Hunter Medical Research Institute, National Health and Medical Research Council of Australia and the Newcastle Permanent Building Society Charitable Trust. The authors declare no conflict of interest.
Publisher: Springer Science and Business Media LLC
Date: 17-02-2020
Publisher: Oxford University Press (OUP)
Date: 12-01-2011
Abstract: BACKGROUND The precise effects of cigarette smoking on female fertility have not yet been clearly defined. We have used a mouse model that mimics human smoking and is able to control for variables that may confound clinical studies to assess the impact of chronic smoking on the quality of mouse oocytes. METHODS Mice received cigarette smoke directly to their lungs for 12 weeks. Lung tissue was analyzed for emphysematous changes and cumulus enclosed oocytes (CEOs) were recovered to study their quality. CEOs were in vitro matured, fixed and stained for chromatin and tubulin. Meiotic spindles, chromatin and the zona pellucida were all examined using confocal microscopy. RESULTS After 12 weeks of cigarette smoking, mice developed alveolar tissue damage that was determined by an increase in destructive index of the lung parenchyma. The numbers of oocytes recovered and the rates of oocyte maturation were not significantly different from non-smoking mice. However, oocytes from smoking mice had a significantly thicker zona pellucida along with shorter and wider meiotic spindles. Furthermore in total, almost a quarter of oocytes from smoking mice were abnormal as assessed by either errors in chromosomal congression or spindle shape. CONCLUSIONS We have used a novel model of inhalational cigarette smoking to show that chronic smoking has a detrimental effect on oocyte quality, and this can be observed even though oocytes are removed from the ovary and cultured in vitro.
Publisher: Springer International Publishing
Date: 2019
Publisher: Springer International Publishing
Date: 2019
Publisher: MDPI AG
Date: 19-05-2021
DOI: 10.3390/NU13051724
Abstract: Background: Most Australians do not meet vegetable intake recommendations. Vegetables are most often consumed in evening meals. However, they often require preparation and therefore cooking skills. Convenience cooking products such as meal bases/concentrates and ready-made sauces are increasingly common and popular and may help address the barriers to vegetable consumption in terms of cost and time. These products also typically provide recipes, which include vegetables, and as such, may help address the barriers of cooking skills, confidence, and creativity. However, the relationships between the use of these products, cooking confidence, and cooking creativity remain unknown. Methods: Australian adults were surveyed (snowball recruitment, n = 842) on their use of convenience cooking products (meal bases/recipe concentrates, simmer sauces, marinades, and other cooking sauces), cooking confidence (7 item scale) and creativity (6 item scale), and demographic information. Results: Overall, 63.2% of participants reported using convenience cooking products. Those using these products had lower mean cooking skills confidence and creativity scores than those who did not, in all product categories assessed. Among users, those who reported "always" following the recipes provided had lower mean cooking confidence and creativity scores than those who followed the recipes less regularly. Conclusions: Therefore, improving the vegetable content of recipes provided with these products may be a tool to increase vegetable intake by users with lower cooking skills (confidence and creativity). This may complement traditional approaches such as education in improving vegetable intake.
Publisher: Public Library of Science (PLoS)
Date: 13-10-2010
Publisher: MDPI AG
Date: 15-02-2023
DOI: 10.3390/NU15040966
Abstract: Low levels of cooking skills, confidence and home cooking are related to poorer dietary outcomes and are a common barrier to adequate vegetable consumption. Convenience cooking products may play a role in lowering the levels of confidence and creativity required to prepare home-cooked meals. It has previously been reported that those who use convenience cooking products have lower levels of cooking confidence and creativity and lower vegetable intakes compared to those who do not use these products. However, the relationship between these outcomes and the frequency of use of convenience cooking products has not been assessed. Therefore, a balanced demographic panel of Australian adults (n = 1034) was surveyed on the frequency of convenience cooking product use, vegetable intake and variety, and opinions and habits regarding vegetable intake. Those who used the products more regularly had higher cooking confidence and creativity, and higher vegetable variety scores, compared to less regular users (p 0.05). However, the frequency of use of convenience cooking products was not associated with higher vegetable intake and did not influence views around the ease of eating vegetables. Therefore, these products may be a tool for assisting those with lower levels of cooking skills in accessing a higher variety of vegetables, but vegetable quantity in these products may need to be revised to assist consumers in better meeting intake recommendations.
Publisher: Elsevier BV
Date: 06-2017
Publisher: Elsevier BV
Date: 12-2014
Publisher: Oxford University Press (OUP)
Date: 20-09-2023
Publisher: Proceedings of the National Academy of Sciences
Date: 08-05-2017
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.JCONREL.2021.12.003
Abstract: Challenges to effective delivery of drugs following oral administration has attracted growing interest over recent decades. Small molecule drugs ( 5) and high long-chain triglyceride solubility (> 50 mg/g), properties required to enable drug association with the lipoprotein transport pathway. The majority of small molecule drugs, however, are not this lipophilic and therefore not substantially transported via the intestinal lymph. This has contributed to a growing body of investigation into prodrug approaches to deliver drugs to the lymphatic system by chemical manipulation. Optimised lipophilic prodrugs have the potential to increase lymphatic transport thereby improving oral pharmacokinetics via a reduction in first pass metabolism and may also target of disease-specific reservoirs within the lymphatics. This may provide advantages for current pharmacotherapy approaches for a wide array of pathological conditions, e.g. immune disease, cancer and metabolic disease, and also presents a promising approach for advanced vaccination strategies. In this review, specific emphasis is placed on medicinal chemistry strategies that have been successfully employed to design lipophilic prodrugs to deliberately enable lymphatic transport. Recent progress and opportunities in medicinal chemistry and drug delivery that enable new platforms for efficacious and safe delivery of drugs are critically evaluated.
Publisher: Springer Science and Business Media LLC
Date: 13-03-2020
DOI: 10.1186/S12263-020-00663-3
Abstract: The frequency of vitamin D-associated gene variants appear to reflect changes in long-term ultraviolet B radiation (UVB) environment, indicating interactions exist between the primary determinant of vitamin D status, UVB exposure and genetic disposition. Such interactions could have health implications, where UVB could modulate the impact of vitamin D genetic variants identified as disease risk factors. However, the current understanding of how vitamin D variants differ between populations from disparate UVB environments is limited, with previous work examining a small pool of variants and restricted populations only. Genotypic data for 46 variants within multiple vitamin D-related loci ( DHCR7/NADSYN1 , GC , CYP2R1 , CYP11A1 , CYP27A1 , CYP24A1 , VDR , RXRα and RXRγ ) was collated from 60 s le sets (2633 subjects) with European, East Asian and Sub-Saharan African origin via the NCBI 1000 Genomes Browser and ALFRED (Allele Frequency Database), with the aim to examine for patterns in the distribution of vitamin D-associated variants across these geographic areas. The frequency of all examined genetic variants differed between populations of European, East Asian and Sub-Saharan African ancestry. Changes in the distribution of variants in CYP2R1 , CYP11A1 , CYP24A1 , RXRα and RXRγ genes between these populations are novel findings which have not been previously reported. The distribution of several variants reflected changes in the UVB environment of the population’s ancestry. However, multiple variants displayed population-specific patterns in frequency that appears not to relate to UVB changes. The reported population differences in vitamin D-related variants provides insight into the extent by which activity of the vitamin D system can differ between cohorts due to genetic variance, with potential consequences for future dietary recommendations and disease outcomes.
Publisher: Wiley
Date: 09-2018
DOI: 10.1002/AJHB.23166
Abstract: The purpose of this study was (1) to elucidate any reciprocal seasonal relationship that might exist between red cell folate (RCF) and serum vitamin D A large (n = 649) Australian cross-sectional study population was examined. Polymerase chain reaction (PCR)/Restriction fragment length polymorphism (RFLP) analysis was used to genotype C677T-MTHFR, C1420T-SHMT, T401C-MTHFD and 2R > 3R-TS. RCF was measured by chemiluminescent immunoassay and vitamin D RCF and photosynthesized vitamin D Findings are consistent with what might be required for the "folate-vitamin D-UV hypothesis of skin pigmentation" model. It suggests genetic influence in provision of one-carbon units by 5,10-methylene-H
Publisher: Informa UK Limited
Date: 17-02-2016
DOI: 10.1080/01635581.2016.1142584
Abstract: Vitamin D receptor (VDR) gene polymorphisms may influence risk for adenomatous polyps (AP), a benign precursor to colon cancer, via modulation of vitamin D sensitive pathways, including cell proliferation and differentiation. However, results have been mixed and any association remains contentious. Failure to clinically exclude the presence of (AP in control cohorts may contribute to the lack of consensus. Therefore, we assessed the role of the FokI, BsmI, ApaI, and TaqI VDR polymorphisms in modifying risk for AP, adjusting for a range of dietary and lifestyle variables. Blood was collected from colonoscopy patients (n = 258) and VDR polymorphisms assessed by restriction fragment length polymorphism. Dietary habits were estimated from food frequency questionnaires. Odds ratios for AP were calculated by genotype, stratified by sex, and adjusted for age, lifestyle, and dietary factors. FokI was associated with modified risk for AP in males, whereas the BsmI/ApaI/TaqI haplotype was associated with modified risk in females. No interaction was found between VDR variants and vitamin D intake. This study offers novel insight into the potential for VDR genetics to contribute to risk for AP and is the first to demonstrate a sex-specific relationship between these polymorphisms and risk for AP.
Publisher: MDPI AG
Date: 10-08-2020
DOI: 10.3390/NU12082388
Abstract: Vitamin D is well known for its important roles in maintaining calcium homeostasis and bone mineralization via the regulation of calcium mobilization and renal reabsorption, and the intestinal absorption of both calcium and phosphorus [...]
Publisher: Cambridge University Press (CUP)
Date: 09-05-2014
DOI: 10.1017/S0954422414000043
Abstract: A growing number of studies in recent years have highlighted the importance of molecular nutrition as a potential determinant of health and disease. In particular, the ability of micronutrients to regulate the final expression of gene products via modulation of transcription and translation is now being recognised. Modulation of microRNA (miRNA) by nutrients is one pathway by which nutrition may mediate gene expression. miRNA, a class of non-coding RNA, can directly regulate gene expression post-transcriptionally. In addition, miRNA are able to indirectly influence gene expression potential at the transcriptional level via modulation of the function of components of the epigenetic machinery (DNA methylation and histone modifications). These mechanisms interact to form a complex, bi-directional regulatory circuit modulating gene expression. Disease-specific miRNA profiles have been identified in multiple disease states, including those with known dietary risk factors. Therefore, the role that nutritional components, in particular, vitamins and minerals, play in the modulation of miRNA profiles, and consequently health and disease, is increasingly being investigated, and as such is a timely subject for review. The recently posited potential for viable exogenous miRNA to enter human blood circulation from food sources adds another interesting dimension to the potential for dietary miRNA to contribute to gene modulation.
Publisher: European Respiratory Society (ERS)
Date: 04-06-2010
DOI: 10.1183/09031936.00049510
Abstract: An inverse association exists between some bacterial infections and the prevalence of asthma. We investigated whether Streptococcus pneumoniae infection protects against asthma using mouse models of ovalbumin (OVA)-induced allergic airway disease (AAD). Mice were intratracheally infected or treated with killed S. pneumoniae before, during or after OVA sensitisation and subsequent challenge. The effects of S. pneumoniae on AAD were assessed. Infection or treatment with killed S. pneumoniae suppressed hallmark features of AAD, including antigen-specific T-helper cell (Th) type 2 cytokine and antibody responses, peripheral and pulmonary eosinophil accumulation, goblet cell hyperplasia, and airway hyperresponsiveness. The effect of infection on the development of specific features of AAD depended on the timing of infection relative to allergic sensitisation and challenge. Infection induced significant increases in regulatory T-cell (Treg) numbers in lymph nodes, which correlated with the degree of suppression of AAD. Tregs reduced T-cell proliferation and Th2 cytokine release. The suppressive effects of infection were reversed by anti-CD25 treatment. Respiratory infection or treatment with S. pneumoniae attenuates allergic immune responses and suppresses AAD. These effects may be mediated by S. pneumoniae-induced Tregs. This identifies the potential for the development of therapeutic agents for asthma from S. pneumoniae.
Publisher: Xia & He Publishing
Date: 17-09-2016
Publisher: Elsevier BV
Date: 12-2019
Publisher: Oxford University Press (OUP)
Date: 10-05-2021
Abstract: Many modern techniques employed to uncover the molecular fundamentals underlying biological processes require dissociated cells as their starting point/substrate. Investigations into ovarian endocrinology or folliculogenesis, therefore, necessitate robust protocols for dissociating the ovary into its constituent cell populations. While in the mouse, methods to obtain in idual, mature follicles are well-established, the separation and isolation of single cells of all types from early mouse follicles, including somatic cells, has been more challenging. Herein we present two methods for the isolation of somatic cells in the ovary. These methods are suitable for a range of applications relating to the study of folliculogenesis and mouse ovarian development. First, an enzymatic dissociation utilising collagenase and a temporary, primary cell culture step using neonatal mouse ovaries which yields large quantities of granulosa cells from primordial, activating, and primary follicles. Second, a rapid papain dissociation resulting in a high viability single cell suspension of ovarian somatic cells in less than an hour, which can be applied from embryonic to adult ovarian s les. Collectively these protocols can be applied to a broad array of investigations with unique advantages and benefits pertaining to both.
Publisher: Elsevier BV
Date: 12-2019
Publisher: Elsevier BV
Date: 12-2019
Publisher: MDPI AG
Date: 30-04-2018
DOI: 10.3390/NU10050554
Publisher: MDPI AG
Date: 09-02-2021
DOI: 10.3390/NU13020571
Abstract: 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 in iduals. 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 s les (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.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.INJURY.2017.04.014
Abstract: Healthcare use by traumatically injured in iduals prior to and subsequent to their injury are not often explored for different types of injuries. This study aims to describe health care use 12 months preceding and 12 months following a traumatic injury by injury type and injury severity. Hospital and mortality data from three Australian states were linked in a population-based matched cohort study. In iduals ≥18 years who had an injury-related hospital admission in 2009 were identified as the injured cohort. A comparison cohort of non-injured people, matched 1:1 on age, gender and postcode of residence, was randomly selected from the electoral roll. Twelve-month pre- and post-index injury health service use was examined. Rates, adjusted rate ratios and attributable risk proportions were calculated by injury type and severity. The injury cohort experienced higher 12-month pre- and post-injury hospital admissions than the non-injured group. By 6 to 7 months post-injury, the injury cohort had largely returned to their pre-injury health service use levels, except for injuries involving dislocations, sprains and strains and injury to nerves and spinal cord. Hip fracture (17.69 per 100 person-months) and poisoning (16.09 per 100 person-months) had the highest rates of post-injury hospitalisation in the injured cohort. The adjusted rate ratios (ARR) for post-injury hospitalisation were highest for poisoning (ARR: 3.77 95% CI: 3.38-4.21) and injury to nerves and spinal cord (ARR: 2.73 95% CI: 2.27-3.28). Poisoning also had the highest ARR for post-injury LOS (ARR: 5.31 95% CI: 4.51-6.27). After sustaining a traumatic injury, many in iduals are readmitted to hospital and require ongoing care up to 12 months post-injury. That injured in iduals post-injury largely return to their pre-index injury hospital use by 6 to 7 months could imply a return to pre-injury function and/or that other measures of health service use should be explored. Trauma services should consider long-term follow-up and support services for seriously injured patients post-hospital discharge.
Publisher: Wiley
Date: 06-10-2023
DOI: 10.1002/OSP4.712
Publisher: Elsevier BV
Date: 12-2015
Publisher: Elsevier BV
Date: 03-2013
Start Date: 07-2020
End Date: 07-2024
Amount: $390,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 06-2020
End Date: 06-2021
Amount: $400,000.00
Funder: Australian Research Council
View Funded Activity