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  1. Zulkifli S, Rahman AA, Kadir SHSA, Nor NSM
    Eur J Pediatr, 2021 Oct;180(10):3111-3127.
    PMID: 33893858 DOI: 10.1007/s00431-021-04085-0
    For the past two decades, growing research has been pointing to multiple repercussions of bisphenol A (BPA) exposure to human health. BPA is a synthetic oestrogen which primarily targets the endocrine system; however, the compound also disturbs other systemic organ functions, in which the magnitude of impacts in those other systems is as comparable to those in the endocrine system. To date, the discoveries on the association between BPA and health outcomes mainly came from animal and in vitro studies, with limited human studies which emphasised on children's health. In this comprehensive review, we summarised studies on human, in vivo and in vitro models to understand the consequences of pre-, post- and perinatal BPA exposure on the perinatal, children and adult health, encompassing cardiovascular, neurodevelopmental, endocrine and reproductive effects.Conclusion: Evidence from in vitro and animal studies may provide further support and better understanding on the correlation between environmental BPA exposure and its detrimental effects in humans and child development, despite the difficulties to draw direct causal relations of BPA effects on the pathophysiology of the diseases/syndromes in children, due to differences in body system complexity between children and adults, as well as between animal and in vitro models and humans. What is known: • Very limited reviews are available on how BPA adversely affects children's health. • Previous papers mainly covered two systems in children. What is new: • Comprehensive review on the detrimental effects of BPA on children health outcomes, including expectations on adult health outcomes following perinatal BPA exposure, as well as covering a small part of BPA alternatives. • Essentially, BPA exposure during pregnancy has huge impacts on the foetus in which it may cause changes in foetal epigenetic programming, resulting in disease onsets during childhood as well as adulthood.
  2. Nayan NM, Kadir SHSA, Husin A, Siran R
    Physiol Behav, 2024 Apr 05.
    PMID: 38583549 DOI: 10.1016/j.physbeh.2024.114546
    Maternal bisphenol A (BPA) exposure has been reported to cause learning and memory deficits in born offspring. However, little is known that this impairment is potentially caused by epigenetic modulation on the development of NMDA receptor subunits. This study investigates the effect of prenatal BPA exposure on the hippocampal miR-19a and miR-539, which are responsible for regulating NMDA receptor subunits as well as learning and memory functions. Pregnant Sprague Dawley rats were orally administered with 5 mg/kg/day of BPA from pregnancy day 1 (PD1) until gestation day 21 (GD21), while control mothers received no BPA. The mothers were observed daily until GD21 for either a cesarean section or spontaneous delivery. The male offspring were sacrificed when reaching GD21 (fetus), postnatal days 7, 14, 21 (PND7, 14, 21) and adolescent age 35 (AD35) where their hippocampi were dissected from the brain. The expression of targeted miR-19a, miR-539, GRIN2A, and GRIN2B were determined by qRT-PCR while the level of GluN2A and GluN2B were estimated by western blot. At AD35, the rats were assessed with neurobehavioral tests to evaluate their learning and memory function. The findings showed that prenatal BPA exposure at 5 mg/kg/day significantly reduces the expression of miR-19a, miR-539, GRIN2A, and GRIN2B genes in the male rat hippocampus at all ages. The level of GluN2A and GluN2B proteins is also significantly reduced when reaching adolescent age. Consequently, the rats showed spatial and fear memory impairments when reaching AD35. In conclusion, prenatal BPA exposure disrupts the role of miR-19a and miR-539 in regulating the NMDA receptor subunit in the hippocampus which may be one of the causes of memory and learning impairment in adolescent rats.
  3. Kamaludin R, Othman MHD, Kadir SHSA, Khan J, Ismail AF, Rahman MA, et al.
    Environ Sci Pollut Res Int, 2023 Jan;30(1):259-273.
    PMID: 35902521 DOI: 10.1007/s11356-022-22121-w
    Various treatments of choice are available to overcome contamination of bisphenol A (BPA) in the environment including membrane technologies; however, the treatment still releases contaminants that threaten the human being. Therefore, the present study is conducted to investigate the degradation of BPA by recently developed visible-light-driven photocatalytic nitrogen-doping titanium dioxide (N-doped TiO2) dual-layer hollow fibre (DLHF) membrane and its efficiency in reducing the level of BPA in contaminated water. Fabricated with suitable polymer/photocatalyst (15/7.5 wt.%) via co-extrusion spinning method, the DLHF was characterized morphologically, evaluated for BPA degradation by using submerged photocatalytic membrane reactor under visible light irradiations followed by the investigation of intermediates formed. BPA exposure effects were accessed by immunohistochemistry staining of gastrointestinal sample obtained from animal model. BPA has been successfully degraded up to 72.5% with 2 intermediate products, B1 and B2, being identified followed by total degradation of BPA. BPA exposure leads to the high-intensity IHC staining of Claudin family which indicated the disruption of small intestinal barrier (SIB) integrity. Low IHC staining intensity of Claudin family in treated BPA group demonstrated that reducing the level of BPA by N-doped TiO2 DLHF is capable of protecting the important component of SIB. Altogether, the fabricated photocatalytic DLHF membrane is expected to have an outstanding potential in removing BPA and its health effect for household water treatment to fulfil the public focus on the safety of their household water and their need to consume clean water.
  4. Abidin MNZ, Goh PS, Ismail AF, Othman MHD, Hasbullah H, Said N, et al.
    Mater Sci Eng C Mater Biol Appl, 2016 Nov 01;68:540-550.
    PMID: 27524052 DOI: 10.1016/j.msec.2016.06.039
    Poly (citric acid)-grafted-MWCNT (PCA-g-MWCNT) was incorporated as nanofiller in polyethersulfone (PES) to produce hemodialysis mixed matrix membrane (MMM). Citric acid monohydrate was polymerized onto the surface of MWCNTs by polycondensation. Neat PES membrane and PES/MWCNTs MMMs were fabricated by dry-wet spinning technique. The membranes were characterized in terms of morphology, pure water flux (PWF) and bovine serum albumin (BSA) protein rejection. The grafting yield of PCA onto MWCNTs was calculated as 149.2%. The decrease of contact angle from 77.56° to 56.06° for PES/PCA-g-MWCNTs membrane indicated the increase in surface hydrophilicity, which rendered positive impacts on the PWF and BSA rejection of the membrane. The PWF increased from 15.8Lm(-2)h(-1) to 95.36Lm(-2)h(-1) upon the incorporation of PCA-g-MWCNTs due to the attachment of abundant hydrophilic groups that present on the MWCNTs, which have improved the affinity of membrane towards the water molecules. For protein rejection, the PES/PCA-g-MWCNTs MMM rejected 95.2% of BSA whereas neat PES membrane demonstrated protein rejection of 90.2%. Compared to commercial PES hemodialysis membrane, the PES/PCA-g-MWCNTs MMMs showed less flux decline behavior and better PWF recovery ratio, suggesting that the membrane antifouling performance was improved. The incorporation of PCA-g-MWCNTs enhanced the separation features and antifouling capabilities of the PES membrane for hemodialysis application.
  5. Abidin MNZ, Goh PS, Ismail AF, Othman MHD, Hasbullah H, Said N, et al.
    Mater Sci Eng C Mater Biol Appl, 2017 Aug 01;77:572-582.
    PMID: 28532067 DOI: 10.1016/j.msec.2017.03.273
    A novel approach in the design of a safe, high performance hemodialysis membrane is of great demand. Despite many advantages, the employment of prodigious nanomaterials in hemodialysis membrane is often restricted by their potential threat to health. Hence, this work focusses on designing a biocompatible polyethersulfone (PES) hemodialysis membrane embedded with poly (citric acid)-grafted-multi walled carbon nanotubes (PCA-g-MWCNTs). Two important elements which could assure the safety of the nanocomposite membrane, i.e. (i) dispersion stability and (ii) leaching of MWCNTs were observed. The results showed the improved dispersion stability of MWCNTs in water and organic solvent due to the enriched ratio of oxygen-rich groups which subsequently enhanced membrane separation features. It was revealed that only 0.17% of MWCNTs was leached out during the membrane fabrication process (phase inversion) while no leaching was detected during permeation. In terms of biocompatibility, PES/PCA-g-MWCNT nanocomposite membrane exhibited lesser C3 and C5 activation (189.13 and 5.29ng/mL) and proteins adsorption (bovine serum albumin=4.5μg/cm2, fibrinogen=15.95μg/cm2) as compared to the neat PES membrane, while keeping a normal blood coagulation time. Hence, the PES/PCA-g-MWCNT nanocomposite membrane is proven to have the prospect of becoming a safe and high performance hemodialysis membrane.
  6. Abidin MNZ, Goh PS, Ismail AF, Said N, Othman MHD, Hasbullah H, et al.
    Carbohydr Polym, 2018 Dec 01;201:257-263.
    PMID: 30241818 DOI: 10.1016/j.carbpol.2018.08.069
    Portable dialysis is a need to implement daily and nocturnal hemodialysis. To realize portable dialysis, a dialysate regeneration system comprising superior adsorbents is required to regenerate the used dialysate. This study aims to develop a nano-adsorbent, derived from corn starch for urea removal. Oxidized starch nanoparticles (oxy-SNPs) were prepared via liquid phase oxidation, followed by chemical dissolution and non-solvent precipitation. The oxy-SNPs possessed Z-average size of 177.7 nm with carbonyl and carboxyl contents of 0.068 and 0.048 per 100 glucose units, respectively. The urea adsorption achieved the equilibrium after 4 h with 95% removal. The adsorption mechanism fitted Langmuir isotherm while the adsorption kinetics obeyed pseudo-second-order model. This new material has a maximum adsorption capacity of 185.2 mg/g with a rate constant of 0.04 g/mg.h. Moreover, the oxy-SNPs exhibited the urea uptake recovery of 91.6%. Oxy-SNPs can become a promising adsorbent for dialysate regeneration system to remove urea.
  7. Mansur S, Othman MHD, Ismail AF, Kadir SHSA, Goh PS, Hasbullah H, et al.
    Mater Sci Eng C Mater Biol Appl, 2019 Jun;99:491-504.
    PMID: 30889724 DOI: 10.1016/j.msec.2019.01.092
    Polyurethane (PU) with three different functional groups: carboxyl, hydroxyl and sulphonyl group on its molecular structure were synthesised in this work. The synthesised material suppresses blood clotting and exhibits anticoagulant characteristics due to the presence of the important anionic groups. The synthesised PU was blended with polyethersulphone (PES) and fabricated into flat-sheet membrane to study the physico-chemical and biocompatibility properties of the PES membrane for blood purification application. PES-PU flat-sheet membranes were fabricated via the dry-wet phase separation technique. Different loading of PU (0, 1, 2, 3, 4, and 5%) blended with PES was studied and compared. Based on the in-vitro biocompatibility analysis of the membrane, it can be suggested that the membrane incorporated with PU has better anticoagulant properties compared to the pristine PES membrane. PU incorporation prolonged the clotting time, decreased the formation of thrombin, decreased soluble complement component 3a (C3a) generation and suppressed platelet adhesion and aggregation. The anionic groups on the membrane surface might bind to coagulation factors (antithrombin) and the calcium ions, Ca2+ and thus improve anticoagulant ability. Based on both physico-chemical and in-vitro studied, 4% loading of PU is the optimum loading for incorporation with PES membrane. These results suggested that the blended PES-PU membranes with good haemocompatibility allowed practical application in the field of blood purification.
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