Publications by authors named "Gaoyun Chen"

11 Publications

  • Page 1 of 1

Impact of dietary aflatoxin on immune development in Gambian infants: a cohort study.

BMJ Open 2021 07 20;11(7):e048688. Epub 2021 Jul 20.

School of Medicine, University of Leeds, Leeds, UK

Background: Chronic aflatoxin (AF) exposure has been shown to occur at high levels in children from sub-Saharan Africa (SSA), and has been associated with growth retardation and immune dysfunction. Our objective was to investigate the impact of AF exposure on immune development in early infancy using thymic size and antibody (Ab) response to vaccination as indicators of immune function.

Methods: A total of 374 infants born between May 2011 and December 2012 were enrolled into the current study. These infants were recruited from a larger, randomised trial examining the impact of nutritional supplementation of mothers and infants on infant immune development (the Early Nutrition and Immune Development Trial). Thymic size (Thymic Index, TI) was measured by sonography at 1 week, 8 weeks, 24 weeks and 52 weeks of infant age. Infants were given the diphtheria-tetanus-pertussis (DTP) vaccine at 8 weeks, 12 weeks and 16 weeks of age, and Ab responses to each vaccine measured at 12 weeks and 24 weeks of age. AF-albumin (AF-alb) adduct levels in infant blood were measured by ELISA as the biomarker of AF exposure.

Results: The geometric mean (GM) level of AF-alb increased with age. Only half of infants had detectable AF-alb with a GM of 3.52 pg/mg at 24 weeks, increasing to 25.39 pg/mg at 52 weeks, when 98% of infants had AF-alb >limit of detection. Significant negative association of AF-alb level with TI was seen in infants during the first 24 weeks, especially at 8 weeks of age (p<0.001), which is the time point of fastest thymus growth. There were no associations between AF exposure level and Ab response to pertussis and tetanus, but a significant positive correlation was observed between AF-alb level and Ab titre to diphtheria (p<0.005).

Conclusions: High levels of AF exposure during early infancy may impact on infant immune development.

Trial Registration Number: ISRCTN49285450.
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http://dx.doi.org/10.1136/bmjopen-2021-048688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292809PMC
July 2021

Development and characterisation of novel poly (vinyl alcohol)/poly (vinyl pyrrolidone)-based hydrogel-forming microneedle arrays for enhanced and sustained transdermal delivery of methotrexate.

Int J Pharm 2020 Aug 25;586:119580. Epub 2020 Jun 25.

School of Pharmacy, Medical Biology Centre, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom. Electronic address:

Methotrexate (MTX) is one of the mainstays of treatment for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) and it is mainly administered either orally or by subcutaneous (SC) injection, which are not so satisfactory. While orally administered MTX is associated with variable bioavailability and causes gastrointestinal side effects, including nausea and vomiting, SC injection is painful and produces high peak blood levels of MTX. Transdermal delivery presents an attractive alternative administration route. However, MTX passive permeation through the skin is hindered by the skin barrier and MTX physicochemical properties. To address these issues, hydrogel-forming microneedle arrays (HFMN) and a patch-like reservoir loaded with MTX (MTX-RV) were developed and combined to form a minimally invasive patch to deliver MTX transdermally in a sustained manner. HFMN were prepared from an aqueous blend of poly (vinyl alcohol) (PVA) and poly (vinyl pyrrolidone) (PVP) which was crosslinked chemically with citric acid (CA) at 130˚C. MTX-RV was prepared from hydroxypropyl methylcellulose (HPMC) and glycerol. Both the HFMN and MTX-RV were fully characterised and then combined to form an integrated patch, which was evaluated ex vivo and in preclinical studies. The HFMN demonstrated a satisfactory mechanical strength and insertion capability into excised neonatal porcine skin, as well as moderate swelling properties. The MTX-RV incorporated a high dose of MTX (150.3 ± 5.3 µg/mg) without precipitation. The integrated patch delivered MTX at a steady-state flux of 506.8 ± 136.9 µg.cm/h in an ex vivo setup. Furthermore, in preclinical studies performed in Sprague Dawley rats, MTX appeared in blood after 1 h from patch application at a concentration of 7.6 ± 2.0 nM. MTX blood level increased gradually to reach its peak, C = 35.1 ± 5.1 nM, at 24 h. Importantly, the HFMN were removed intact from the skin with only mild erythema, despite the cytotoxic nature of MTX. Accordingly, the integrated patch produced in this work represents a promising minimally invasive transdermal drug delivery system that can overcome the skin barrier and deliver MTX in a sustained manner. This may help in minimising or even avoiding the nausea and vomiting, associated with the conventional administration routes.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119580DOI Listing
August 2020

Impaired growth in rural Gambian infants exposed to aflatoxin: a prospective cohort study.

BMC Public Health 2018 Nov 9;18(1):1247. Epub 2018 Nov 9.

School of Food Science and Nutrition, University of Leeds, Leeds, UK.

Background: Exposure to aflatoxin, a mycotoxin produced by fungi that commonly contaminates cereal crops across sub-Saharan Africa, has been associated with impaired child growth. We investigated the impact of aflatoxin exposure on the growth of Gambian infants from birth to two years of age, and the impact on insulin-like growth factor (IGF)-axis proteins.

Methods: A subsample (N = 374) of infants from the Early Nutrition and Immune Development (ENID) trial (ISRCTN49285450) were included in this study. Aflatoxin-albumin adducts (AF-alb) were measured in blood collected from infants at 6, 12 and 18 months of age. IGF-1 and IGFBP-3 were measured in blood collected at 12 and 18 months. Anthropometric measurements taken at 6, 12, 18 and 24 months of age were converted to z-scores against the WHO reference. The relationship between aflatoxin exposure and growth was analysed using multi-level modelling.

Results: Inverse relationships were observed between lnAF-alb and length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) z-scores from 6 to 18 months of age (β = - 0·04, P = 0·015; β = - 0·05, P = 0.003; β = - 0·06, P = 0·007; respectively). There was an inverse relationship between lnAF-alb at 6 months and change in WLZ between 6 and 12 months (β = - 0·01; P = 0·013). LnAF-alb at 12 months was associated with changes in LAZ and infant length between 12 and 18 months of age (β = - 0·01, P = 0·003; β = - 0·003, P = 0·02; respectively). LnAF-alb at 6 months was associated with IGFBP-3 at 12 months (r = - 0·12; P = 0·043).

Conclusions: This study found a small but significant effect of aflatoxin exposure on the growth of Gambian infants. This relationship is not apparently explained by aflatoxin induced changes in the IGF-axis.
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http://dx.doi.org/10.1186/s12889-018-6164-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234772PMC
November 2018

Quantification of amlodipine in dried blood spot samples by high performance liquid chromatography tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2018 Jan 16;1072:252-258. Epub 2017 Nov 16.

Clinical and Practice Research Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address:

A sensitive and specific method, utilising high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was developed for the quantitative determination of amlodipine in dried blood spot (DBS) samples. Chromatographic separation was achieved using a Waters XBridge C18 column with gradient elution of a mixture of water and acetonitrile containing 0.1% formic acid (v/v). Amlodipine was quantified using a Waters Quattro Premier mass spectrometer coupled with an electro-spray ionization (ESI) source in positive ion mode. The MRM transitions of 408.9 m/z→238.1m/z and 408.9→294.0 m/z were used to quantify and qualify amlodipine, respectively. The method was validated across the concentration range of 0.5-30ng/mL by assessing specificity, sensitivity, linearity, precision, accuracy, recovery and matrix effect according to the Food and Drug Administration (FDA) guidelines. This method was also validated clinically within a large pharmacoepidemiological study in which amlodipine blood concentration was determined in patients who had been prescribed this medication.
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http://dx.doi.org/10.1016/j.jchromb.2017.11.018DOI Listing
January 2018

Comparison of urinary aflatoxin M1 and aflatoxin albumin adducts as biomarkers for assessing aflatoxin exposure in Tanzanian children.

Biomarkers 2018 Mar 20;23(2):131-136. Epub 2017 Feb 20.

e LICAMM , School of Medicine, University of Leeds , Leeds, United Kingdom.

Purpose: To determine levels of urinary aflatoxin M1 (AFM1) in children and correlate the concentrations with previously reported aflatoxin albumin adduct (AF-alb) levels in these children.

Materials And Methods: Matched urine and blood samples were collected from 84 Tanzanian children aged 6-14 months old. From 31 children in one village (Kigwa), samples were collected at three time points six months apart. Samples were collected from 31 and 22 children from two different regions at the second time point only. Urinary AFM1 was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit with a modified protocol to improve sensitivity. AF-alb was measured using an established ELISA method.

Results: The relative ranking of the three villages for exposure to aflatoxin based on either AFM or AF-alb biomarker measurements was the same. In Kigwa village, both AFM1 and AF-alb levels were higher at six months post-harvest compared to baseline. However, at the next visit, the AFM1 levels dropped from a GM (interquartile range) of 71.0 (44.7, 112.6) at visit two to 49.3 (31.5, 77.3) pg/ml urine, whereas AF-alb levels increased from 47.3 (29.7, 75.2) to 52.7 (35.4, 78.3) pg/mg albumin between these two visits, reflecting the fact that AFM1 measures short-term exposure, whereas AF-alb measures longer term exposure. There was a correlation between AFB1 intake and AFM1 excretion (r= 0.442, p ≤ 0.001).

Conclusions: Urinary AFM1 is a good biomarker for AFB1 exposure in Tanzanian children, reflecting geographical and temporal variations in exposure to this foodborne toxin.
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http://dx.doi.org/10.1080/1354750X.2017.1285960DOI Listing
March 2018

Dietary exposure to aflatoxin and micronutrient status among young children from Guinea.

Mol Nutr Food Res 2016 Mar 18;60(3):511-8. Epub 2015 Dec 18.

Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, UK.

Scope: Aflatoxin exposure coincides with micronutrient deficiencies in developing countries. Animal feeding studies have postulated that aflatoxin exposure may be exacerbating micronutrient deficiencies. Evidence available in human subjects is limited and inconsistent. The aim of the study was to investigate the relationship between aflatoxin exposure and micronutrient status among young Guinean children.

Methods And Results: A total of 305 children (28.8 ± 8.4 months) were recruited at groundnut harvest (rainy season), of which 288 were followed up 6 months later postharvest (dry season). Blood samples were collected at each visit. Aflatoxin-albumin adduct levels were measured by ELISA. Vitamin A, vitamin E and β-carotene concentrations were measured using HPLC methods. Zinc was measured by atomic absorption spectroscopy. Aflatoxin exposure and micronutrient deficiencies were prevalent in this population and were influenced by season, with levels increasing between harvest and postharvest. At harvest, children in the highest aflatoxin exposure group, compared to the lowest, were 1.98 (95%CI: 1.00, 3.92) and 3.56 (95%CI: 1.13, 11.15) times more likely to be zinc and vitamin A deficient.

Conclusion: Although children with high aflatoxin exposure levels were more likely to be zinc and vitamin A deficient, further research is necessary to determine a cause and effect relationship.
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http://dx.doi.org/10.1002/mnfr.201500382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915736PMC
March 2016

Structure-tunable Janus fibers fabricated using spinnerets with varying port angles.

Chem Commun (Camb) 2015 Mar;51(22):4623-6

School of Human Sciences, Faculty of Life Sciences and Computing, London Metropolitan University, 166-220 Holloway Road, London N7 8DB, UK.

The preparation of Janus fibers using a new side-by-side electrospinning process is reported. By manipulating the angle between the two ports of the spinneret emitting the working fluids, Janus nanofibers with tunable structures in terms of width, interfacial area and also volume of each side can be easily fabricated.
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http://dx.doi.org/10.1039/c5cc00378dDOI Listing
March 2015

MicroRNAs: potential biomarkers for disease diagnosis.

Biomed Mater Eng 2014 ;24(6):3917-25

Institute of Chemical Defence, Changping District, Beijing 102205, PR China.

MicroRNAs (miRNAs) are a group of endogenous noncoding small RNAs characterized by high conservation; furthermore, various studies have shown the capability of miRNAs to impact diseases. For example, a study shows that cell-free miRNAs are stable in bodily fluids, which gives circulating miRNAs the ability to be potential biomarkers for noninvasive diagnosis. Additionally, accumulating studies have supported that miRNAs can function as suppressor genes, again demonstrating their effect on disease. This review introduces this particular role of miRNAs as well as analyzes the prospect of miRNAs as biomarkers and the capacity for using miRNA-based resources to benefit mankind.
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http://dx.doi.org/10.3233/BME-141223DOI Listing
June 2015

Sensitized terbium(III) macrocyclic-phthalimide complexes as luminescent pH switches.

Dalton Trans 2013 Oct;42(39):14115-24

School of Human Sciences, Faculty of Life Sciences and Computing, London Metropolitan University, 166-220 Holloway Road, London N7 8DB, UK.

Four new macrocyclic-phthalimide ligands were synthesised via the coupling of N-(3-bromopropyl)phthalimide either to cyclen (1,4,7,10-tetraazacyclododecane) itself or its carboxylate-functionalized analogues, and photophysical studies were carried out on their corresponding Tb(III) complexes in aqueous media as a function of pH. Luminescence intensities of Tb·L1a–Tb·L3a were in ‘switched off’ mode under acidic conditions (pH < 4), and were activated on progression to basic conditions as the phthalimido functions therein were hydrolysed to their corresponding phthalamates Tb·L1b–Tb·L3b. Emission of phthalamate-based macrocyclic Tb(III) complexes Tb·L1b–Tb·L3b was in ‘switched on’ mode between pH 4 and 11, exhibiting high quantum yields (Φ) and long lifetimes (τ) of the order of milliseconds at pH ~ 6. Tb(III) emissions were found to decline with increasing number of chromophores. The values of Φ and τ were 46% and 2.4 ms respectively for Tb·L1b at pH ~ 6 when activated. This is the best pH-dependent sensor based on a Tb(III) complex reported to date, benefiting from the macrocyclic architecture of the ligand.
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http://dx.doi.org/10.1039/c3dt51236cDOI Listing
October 2013

A chemically unlocked binary molecular switch.

Chem Commun (Camb) 2012 Sep 31;48(72):9026-8. Epub 2012 Jul 31.

School of Human Sciences, Faculty of Life Sciences, London Metropolitan University, 166-220 Holloway Road, London, UK N7 8DB.

A highly luminescent and sensitive terbium complex of a ligand comprising of a phthalimide group appended to a DO3A moiety is an active pH sensor that is conditional on its previous pH.
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http://dx.doi.org/10.1039/c2cc34425dDOI Listing
September 2012

[Cloning, expression and evaluation of Saccharomyces cerevisiae ADH2].

Sheng Wu Gong Cheng Xue Bao 2010 Feb;26(2):165-9

Laboratory of Biology Defense, Command and Engineering College of Chemical Defense, Beijing, China.

In order to clone and express alcohol dehydrogenase II (ADH2) gene from Saccharomyces cerevisiae in E. coli BL21 (DE3) efficiently, we extracted the total RNA as template and obtained ADH2 gene by RT-PCR and connected ADH2 gene to pTAT plasmids to gain recombinant expression plasmid pTAT-ADH2, then transformed this recombinant expression plasmid pTAT-ADH2 into E. coli BL21 (DE3). The recombinant was induced by IPTG to express ADH2. After purification, ADH2 activity was tested in vitro and toxicologic test was done in mouse. Sequence test showed that the acquired fragments exhibited 90% homology to ADH2 gene sequence from GenBank report. The target gene expressed efficiently and took up to approximant 50% of total protein by SDS-PAGE and band scanning analysis. The purified protein exhibited the identified activity through biochemical test and mouse toxicological test. As a result, the acquired ADH2 gene was highly homology to the published sequence and expressed at a high level in E. coli BL21 (DE3), more importantly, ADH2 proved to have ethanol dehydrogenase activity.
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February 2010
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