Displaying publications 1 - 20 of 27 in total

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  1. Karim Z, Zulkifli NA, Sheikh Abdul Kadir SH, Abd Khalil K, Musa M
    Ann Oncol, 2018 Nov;29 Suppl 9:ix55.
    PMID: 32178067 DOI: 10.1093/annonc/mdy432.026
  2. See WYN, Ismail F, Sheikh Abdul Kadir SH, Subrayan V
    Curr Eye Res, 2021 Dec 29.
    PMID: 34963422 DOI: 10.1080/02713683.2021.2011326
    PURPOSE/ AIM: The main purpose of this work is to study the cellular viability effect of irradiated riboflavin in cultured human tenon fibroblasts.

    MATERIALS AND METHODS: The tenon tissue was harvested from a patient undergoing strabismus surgery. The human tenon fibroblast cell culture and isolation were performed according to the standard laboratory cell culturing protocol. The cells were divided into three groups: control, treatment with irradiated and non-irradiated riboflavin. There were five different concentrations (0.00156%, 0.003125%, 0.00625%, 0.0125%, 0.025%) in each group of riboflavin. The fibroblasts were treated with riboflavin and the cellular viability was assessed at 24-hour and 48-hour post treatment with MTT 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyl tetrazolium bromide colorimetric assay. The absorbance values were analysed using Magellan microplate reader data analysis. A triplicate of readings was taken. The data were presented as mean ± standard deviation of the triplicates. Statistical analysis was performed with Statistical Package for Social Sciences (SPSS) analysis version 23.

    RESULTS: Irradiated riboflavin caused a concentration-dependent cell death in human tenon fibroblast cell culture (p

  3. Mohamad NA, Rahman AA, Sheikh Abdul Kadir SH
    Oncol Lett, 2023 Jan;25(1):34.
    PMID: 36589673 DOI: 10.3892/ol.2022.13620
    Piper betle leaves are widely cultivated in Malaysia, India, Indonesia and Thailand. They have been used as a traditional medicine for centuries due to their medicinal properties, including antioxidant, antiproliferative, antibacterial, antifungal and anti-inflammatory properties, which are attributable to their high phenolic contents. Hydroxychavicol (HC), a primary constituent of P. betle leaves, is known to possess antiproliferative activity at micromolar doses on various cancer cell lines of different origins while leaving normal cells unharmed. The present review summarises the mechanisms of action of HC reported in the literature, reviews the scope of work done thus far and outlines the direction of future research on the potential of HC as an anticancer agent. PubMed, Scopus and Web of Science were searched using the keywords (hydroxychavicol OR 4-allylpyrocatechol OR 4-allylcatechol) AND (cancer OR carcinogenesis OR tumour OR carcinoma) to acquire research articles. In vitro studies reported several possible mechanisms for the chemopreventive effects of HC against cancer cell lines, including chronic myelogenous leukaemia (CML), prostate, glioma, breast and colorectal cancers, while in vivo studies encompassed investigations on Ehrlich ascites carcinoma cells in Swiss albino mice and a CML mouse model. These studies suggest that HC exerts its anticancer effect via the modulation of mitochondrial membrane potential and the c-Jun N-terminal kinase, mitogen-activated protein kinase and endoplasmic reticulum-unfolded protein responses pathways and the generation of reactive oxygen species. In summary, future research should focus on combinations of HC with other anticancer drugs and testing in animal models to evaluate its bioavailability, potency and tissue and dose selectivity.
  4. Efendy Goon D, Sheikh Abdul Kadir SH, Latip NA, Ab Rahim S, Mazlan M
    Biomolecules, 2019 02 13;9(2).
    PMID: 30781901 DOI: 10.3390/biom9020064
    Palm oil is natural oil packed with important compounds and fatty acids ready to be exploited in lipid-based formulations and drug delivery. Palm oil and palm kernel oil contain long-chain and medium-chain triglycerides, respectively, including phytonutrients such as tocotrienol, tocopherol and carotenes. The exploitation of these compounds in a lipid-based formulation would be able to address hydrophobicity, lipophilicity, poor bioavailability and low water-solubility of many current drugs. The utilisation of palm oil as part of the drug delivery system seemed to improve the bioavailability and solubility of the drug, stabilising emulsification of formulation between emulsifier and surfactant, promoting enhanced drug permeability and performance, as well as extending the shelf-life of the drug. Despite the complexity in designing lipid-based formulations, palm oil has proven to offer dynamic behaviour in providing versatility in drug design, form and delivery. However, the knowledge and application of palm oil and its fractions in lipid-based formulation are scarce and interspersed. Therefore, this study aims to focus on the research and outcomes of using palm oil in lipid-based formulations and drug delivery systems, due to the importance of establishing its capabilities and benefits.
  5. Mohd Nasir NA, Agarwal R, Krasilnikova A, Sheikh Abdul Kadir SH, Iezhitsa I
    Eur J Pharmacol, 2020 Nov 15;887:173431.
    PMID: 32758568 DOI: 10.1016/j.ejphar.2020.173431
    Intraocular pressure (IOP) lowering in glaucomatous eyes is currently achieved mainly by improved aqueous outflow via alternate drainage pathways. However, the focus is now shifting to trabecular meshwork (TM), the site or major pathological changes including increased extracellular matrix (ECM) deposition and reduced matrix metalloproteinases (MMPs) secretion by TM cells. Trans-resveratrol was previously shown to lower IOP and reduce ECM deposition; however, the mechanisms of action remain unclear. Therefore, we determined the effect of trans-resveratrol on MMP-2 and -9 expression by human TM cells (HTMCs) in the presence of dexamethasone and whether it also affects adenosine A1 receptors (A1AR) expression and nuclear factor kappa B (NFkB) activation. We observed that trans-resveratrol, 12.5 μM, increased MMP-2 and -9 protein expression by HTMCs despite exposure to dexamethasone (1.89- and 1.53-fold, respectively; P 
  6. Mohd Nasir NA, Agarwal R, Krasilnikova A, Sheikh Abdul Kadir SH, Iezhitsa I
    J Basic Clin Physiol Pharmacol, 2020 Jul 22;31(6).
    PMID: 32697755 DOI: 10.1515/jbcpp-2019-0373
    Objectives Steroid-induced ocular hypertension and glaucoma are associated with extracellular matrix remodeling at the trabecular meshwork (TM) of the eye due to reduced secretion of matrix metalloproteinases (MMPs), a family of enzymes regulating extracellular matrix proteolysis. Several biological functions of steroids are known to involve regulation of adenosine A1 receptors (A1AR) and nuclear factor kappa B (NFKB). Since MMPs expression in TM has been shown to be regulated by A1AR as well as transcription factors, it is likely that dexamethasone-induced changes in aqueous humor dynamics involve reduced MMP and A1AR expression and reduced NFKB activation. Hence, the current study investigated the association of dexamethasone-induced reduction in MMP secretion with reduced NFKB activation and A1AR expression. Methods Human trabecular meshwork cells (HTMCs) were characterized by estimating myocilin and alpha smooth muscle actin expression and then were treated with dexamethasone 100 nM for 2, 5 and 7 days. The MMP secretion was estimated in culture media using Western blot. Immunocytochemistry (ICC) and ELISA were done to investigate the effect of dexamethasone on NFKB phosphorylation. A1AR expression in HTMCs was determined using Western blot and ELISA. Results Dexamethasone caused a significant reduction in both MMP-2 and -9 expression compared to untreated group after five and seven days but not after two days of culture. Significantly reduced phosphorylated NFKB and A1AR protein levels were detected in dexamethasone treated compared to vehicle treated HTMCs after five days of culture. Conclusions Dexamethasone reduces MMP-2 and -9 secretion by HTMCs and this effect of dexamethasone is associated with reduced NFKB phosphorylation and A1AR expression.
  7. Abdullah Soheimi SS, Abdul Rahman A, Abd Latip N, Ibrahim E, Sheikh Abdul Kadir SH
    PMID: 34444092 DOI: 10.3390/ijerph18168345
    Perfluorinated compounds (PFCs) are non-biodegradable synthetic chemical compounds that are widely used in manufacturing many household products. Many studies have reported the association between PFCs exposure with the risk of developing cardiovascular diseases (CVDs). However, those reports are still debatable, due to their findings. Thus, this review paper aimed to analyse the association of PFCs compound with CVDs and their risk factors in humans by systematic review and meta-analysis. Google Scholar, PubMed and ScienceDirect were searched for PFCs studies on CVDs and their risk from 2009 until present. The association of PFCs exposure with the prevalence of CVDs and their risk factors were assessed by calculating the quality criteria, odds ratios (ORs), and 95% confidence intervals (CIs). CVDs risk factors were divided into serum lipid profile (main risk factor) and other known risk factors. The meta-analysis was then used to derive a combined OR test for heterogeneity in findings between studies. Twenty-nine articles were included. Our meta-analysis indicated that PFCs exposure could be associated with CVDs (Test for overall effect: z = 2.2, p = 0.02; Test for heterogeneity: I2 = 91.6%, CI = 0.92-1.58, p < 0.0001) and their risk factors (Test for overall effect: z = 4.03, p < 0.0001; Test for heterogeneity: I2 = 85.8%, CI = 1.00-1.14, p < 0.0001). In serum lipids, total cholesterol levels are frequently reported associated with the exposure of PFCs. Among PFCs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) exposure increased the risk of CVDs than other types of PFCs. Although the risk of PFOA and PFOS were positively associated with CVDs and their risk factors, more observational studies shall be carried out to identify the long-term effects of these contaminants in premature CVDs development in patients.
  8. Abulehia H, Mohd Nor NS, Sheikh Abdul Kadir SH, Abdul Aziz M, Zulkifli S
    Sci Rep, 2023 Jun 08;13(1):9322.
    PMID: 37291156 DOI: 10.1038/s41598-023-36043-1
    Bisphenol A (BPA) is a plasticiser used in the manufacturing of many products and its effects on human health remain controversial. Up till now, BPA involvement in metabolic syndrome risk and development is still not fully understood. In this study, we aimed to investigate the effect of prenatal BPA exposure with postnatal trans-fat diet intake on metabolic parameters and pancreatic tissue histology. Eighteen pregnant rats were divided into control (CTL), vehicle tween 80 (VHC), and BPA (5 mg/kg/day) from gestational day (GD) 2 until GD 21, then their weaning rat's offspring were fed with normal diet (ND) or trans-fat diet (TFD) from postnatal week (PNW) 3 until PNW 14. The rats were then sacrificed and the blood (biochemical analysis) and pancreatic tissues (histological analysis) were collected. Glucose, insulin, and lipid profile were measured. The study has shown that there was no significant difference between groups with regard to glucose, insulin, and lipid profiles (p > 0.05). All pancreatic tissues showed normal architecture with irregular islets of Langerhans in TFD intake groups compared to offspring that consumed ND. Furthermore, the pancreatic histomorphometry was also affected whereby the study findings revealed that there was a significant increase in the mean number of pancreatic islets in rats from BPA-TFD group (5.987 ± 0.3159 islets/field, p = 0.0022) compared to those fed with ND and BPA non-exposed. In addition, the results have found that prenatal BPA exposure resulted in a significant decrease in the pancreatic islets diameter of the BPA-ND group (183.3 ± 23.28 µm, p = 0.0022) compared to all other groups. In conclusion, prenatal BPA exposure with postnatal TFD in the offspring may affect glucose homeostasis and pancreatic islets in adulthood, and the effect may be more aggravated in late adulthood.
  9. Mohd Kasim NA, Mohd Nor NS, Wen MT, Syed Kamaruddin SKA, Sheikh Abdul Kadir SH
    Malays J Pathol, 2023 Aug;45(2):293-296.
    PMID: 37658539
    INTRODUCTION: A 1-year-old Malay girl presented with pallor, failure to thrive and hepatosplenomegaly. Her blood was sent for thalassaemia screening and it was incidentally found that her blood appeared lipaemic.

    CASE REPORT: Primary and secondary causes of hyperlipidaemia were investigated. Her blood was sent for fasting lipid profile, thyroid function test (TFT), fasting plasma glucose (FPG), liver function test (LFT), renal profile (RP) and HIV screening. Lipaemic interference was removed by high-speed centrifugation. She is a product of non-consanguineous marriage. She is staying together with her stepfather who is HIV positive. Her mother's infective status was negative with no dyslipidaemic features and a normal lipid profile. Lipid profile of her biological father was not known. No other lipid stigmata such as eruptive xanthoma or lipaemia retinalis was seen in the patient. Haemoglobin analysis showed Hb E-Beta thalassaemia major. Her triglycerides was 9.05 mmol/L with normal total cholesterol, 2.85 mmol/L and high-density lipoprotein cholesterol (HDL-c), 0.26 mmol/L. Calculated low-density lipoprotein cholesterol (LDL-c) was invalid as triglycerides was >4.5 mmol/L. TFT, RP, FPG, LFT were normal and HIV status was negative. She was transfused with 10 ml/kg packed cell and her blood post transfusion appeared non lipaemic.

    CONCLUSION: Primary hypertriglyceridaemia was excluded based on insignificant family history of dyslipidaemia. Secondary causes of hypertriglyceridaemia were ruled out based on unremarkable laboratory investigations. Thus, we conclude that this patient is having hypertriglyceridaemia thalassaemia syndrome (HTS) which is a rare disorder with unknown pathogenesis. Further research may be required to explore this unknown association.

  10. Sherzay N, Azimi Z, Sheikh Abdul Kadir SH, Mohd Nor NS
    J Blood Med, 2024;15:69-75.
    PMID: 38375064 DOI: 10.2147/JBM.S437594
    PURPOSE: This study was designed and conducted to validate the reference values of hematological parameters for healthy adult male and female residents of Kabul city, Afghanistan.

    METHODOLOGY: In this cross-sectional study, the samples were collected according to a non-random sampling method. Blood samples were collected from students and employees of Kabul University. The study included 166 males and 125 females, aged 18-45 years. The selection and exclusion of participants were carried out according to a questionnaire and the assessment of serum ferritin and vitamin B12 levels. Candidates with lower serum ferritin and vitamin B12, a history of chronic disease, females with menstruation or pregnancy, and those with chronic abdominal pain were excluded.

    RESULTS: Reference ranges for all blood parameters were determined by a non-parametric method. The determined reference values were compared between males and females by the Z-test. Reference intervals for hemoglobin (4.5-6.3 g/dL for males and 3.66-5.67 g/dL for females) and hematocrit (36.23-55.93% for males and 30.20-53.86% for females) were significantly (p<0.05) higher in males. No significant (p<0.05) differences were observed between the reference intervals for the red blood cell count.

    CONCLUSION: Therefore, we conclude that the commonly used reference intervals should be revised for the Afghan population, as our findings indicated higher reference values for the hemoglobin and hematocrit indices.

  11. Zulkifli S, Mohd Nor NS, Sheikh Abdul Kadir SH, Mohd Ranai N, Abdul Khalil K
    PLoS One, 2024;19(7):e0306741.
    PMID: 38980850 DOI: 10.1371/journal.pone.0306741
    There has been much evidence showing the repercussions of prenatal bisphenol A (BPA) exposure with a postnatal high fat-diet (HFD) on offspring's health. However, the information on how the interaction between these two variables affects the gut microbiome is rather limited. Hence, we investigated the impact of a postnatal trans fat diet (TFD) on the gut microbiome of offspring exposed to BPA during the prenatal period in an animal model. Pregnant rats were divided into 5 mg/kg/day BPA, vehicle Tween80 (P80) or control (CTL) drinking water until delivery (N = 6 per group). Then, weaned male pups were further subdivided into three normal diet (ND) groups (CTLND, P80ND, and BPAND) and three TFD groups (CTLTFD, P80TFD, and BPATFD) (n = 6 per group). 180-250 g of faecal samples were collected on days 50 and 100 to assess the composition of the offspring's intestinal flora using next-generation sequencing. The alpha diversity indices of TFD offspring with and without BPA were markedly lower than their ND counterparts (p<0.001-p<0.05). The beta diversity, hierarchical cluster and network analyses of the offspring's microbiome demonstrated that the microbiome species of the TFD group with and without BPA were distinctly different compared to the ND group. Consistently, TFD and ND offspring pairings exhibited a higher number of significantly different species (p<0.0001-p<0.05) compared to those exposed to prenatal BPA exposure and different life stages comparisons, as shown by the multivariate parametric analysis DESeq2. Predictive functional profiling of the offspring's intestinal flora demonstrated altered expressions of genes involved in metabolic pathways. In summary, the gut flora composition of the rat offspring may be influenced by postnatal diet instead of prenatal exposure to BPA. Our data indicate the possibility of perturbed metabolic functions and epigenetic modifications, in offspring that consumed TFD, which may theoretically lead to metabolic diseases in middle or late adulthood. Further investigation is necessary to fully understand these implications.
  12. Othman N, Ismail Z, Selamat MI, Sheikh Abdul Kadir SH, Shibraumalisi NA
    Int J Environ Res Public Health, 2022 Oct 26;19(21).
    PMID: 36360801 DOI: 10.3390/ijerph192113923
    Polychlorinated biphenyls (PCBs) were widely used in industrial and commercial applications, until they were banned in the late 1970s as a result of their significant environmental pollution. PCBs in the environment gained scientific interest because of their persistence and the potential threats they pose to humans. Traditionally, human exposure to PCBs was linked to dietary ingestion. Inhalational exposure to these contaminants is often overlooked. This review discusses the occurrence and distribution of PCBs in environmental matrices and their associated health impacts. Severe PCB contamination levels have been reported in e-waste recycling areas. The occurrence of high PCB levels, notably in urban and industrial areas, might result from extensive PCB use and intensive human activity. Furthermore, PCB contamination in the indoor environment is ten-fold higher than outdoors, which may present expose risk for humans through the inhalation of contaminated air or through the ingestion of dust. In such settings, the inhalation route may contribute significantly to PCB exposure. The data on human health effects due to PCB inhalation are scarce. More epidemiological studies should be performed to investigate the inhalation dose and response mechanism and to evaluate the health risks. Further studies should also evaluate the health impact of prolonged low-concentration PCB exposure.
  13. Rosli NFH, Mohd Nor NS, Adnan RA, Sheikh Abdul Kadir SH
    Clin Exp Pediatr, 2024 Nov 06.
    PMID: 39533737 DOI: 10.3345/cep.2024.00227
    The endocrine system is a complex network of glands that produce and release hormones that regulate various physiological processes. In the past few decades, the human skin has been identified as an important peripheral endocrine organ that is the main site for the synthesis of vitamin D through exposure to sunlight. Mutations in downstream vitamin D-related gene pathways are associated with disease development. The vitamin D receptor (VDR) gene, which regulates the pleiotropic effects of vitamin D, has been extensively studied in adult populations. Several studies have reported the prevalence of vitamin D deficiency in children and adolescents. With changes in socioeconomic status and lifestyle, vitamin D-deficient individuals are prone to developing the disease at a young age. However, geographical and racial differences affect the association between VDR gene polymorphisms and vitamin D endocrine disorders, explaining the non-consensus effects of polymorphisms and their association with disease development across populations. In this review, we discuss the connection between the vitamin D endocrine system and polymorphisms in the gene encoding VDR in children and adolescents, focusing on its effects on growth, puberty, insulin resistance, and the immune system.
  14. Hanafi NI, Mohamed AS, Md Noor J, Abdu N, Hasani H, Siran R, et al.
    Genet. Mol. Res., 2016 Jun 17;15(2).
    PMID: 27323195 DOI: 10.4238/gmr.15028150
    Ursodeoxycholic acid (UDCA) is used to treat liver diseases and demonstrates cardioprotective effects. Accumulation of the plasma membrane sphingolipid sphingomyelin in the heart can lead to atherosclerosis and coronary artery disease. Sphingomyelinases (SMases) break down sphingomyelin, producing ceramide, and inhibition of SMases activity can promote cell survival. We hypothesized that UDCA regulates activation of ERK and Akt survival signaling pathways and SMases in protecting cardiac cells against hypoxia. Neonatal cardiomyocytes were isolated from 0- to 2-day-old Sprague Dawley rats, and given 100 μM CoCl2, 150 μM H2O2, or placed in a hypoxia chamber for 24 h. The ameliorative effects of 100-μM UDCA treatment for 12 h were then assessed using MTS, QuantiGene Plex (for Smpd1 and Smpd2), and SMase assays, beating rate assessment, and western blotting (for ERK and Akt). Data were analyzed by the paired Student t-tests and one-way analyses of variance. Cell viability decreased significantly after H2O2 (85%), CoCl2 (50%), and hypoxia chamber (52%) treatments compared to the untreated control (100%). UDCA significantly counteracted the effects of chamber- and CoCl2- induced hypoxia on viability and beating rate. However, no significant differences were observed in acid SMase gene and protein expression between the untreated, CoCl2, and UDCA-CoCl2 groups. In contrast, neutral SMase gene and protein expression did significantly differ between the latter two groups. ERK and Akt phosphorylation was higher in hypoxic cardiomyocytes treated with UDCA than those given CoCl2 alone. In conclusion, UDCA regulates the activation of survival signaling proteins and SMases in neonatal rat cardiomyocytes during hypoxia.
  15. Norhazlin J, Nor-Ashikin MN, Hoh BP, Sheikh Abdul Kadir SH, Norita S, Mohd-Fazirul M, et al.
    Genet. Mol. Res., 2015;14(3):10172-84.
    PMID: 26345954 DOI: 10.4238/2015.August.28.1
    The quality of RNA is crucial when performing microarray experiments. This is particularly important when dealing with preimplantation embryos, from which a minimum yield of RNA of good quality can be produced. We report the optimization of several RNA extraction methods applied to preimplantation embryos at different stages of development. The quality of the samples was confirmed using a microarray and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis. A total of 30 cultured two-cell stage embryos of ICR mice were pooled at the 8-cell, morula, and blastocyst stages. The embryos were divided into two groups comprising DNase-treated and non-DNase-treated RNA samples. Total RNA was extracted using a Pico Pure RNA Isolation Kit following the manufacturer protocol, with some modifications. Lysed samples were bound to a silica-based filter, treated with deoxyribonuclease I (DNase I), and washed several times before elution. RNA concentration and integrity were evaluated using an Agilent 2100 Bioanalyzer and an RNA 6000 Pico Assay kit. Although concentrations of non-DNase-treated RNAs were higher than DNase-treated RNA, DNase-treated RNA gave a higher RNA integrity number compared with non-DNase-treated RNA. Inclusion of DNase treatment in the RNA extraction procedure gave the best quality RNA samples from preimplantation embryos, as validated by microarray and RT-qPCR quality control.
  16. Mohamed AS, Hanafi NI, Sheikh Abdul Kadir SH, Md Noor J, Abdul Hamid Hasani N, Ab Rahim S, et al.
    Cell Biochem Funct, 2017 Oct;35(7):453-463.
    PMID: 29027248 DOI: 10.1002/cbf.3303
    In hepatocytes, ursodeoxycholic acid (UDCA) activates cell signalling pathways such as p53, intracellular calcium ([Ca2+ ]i ), and sphingosine-1-phosphate (S1P)-receptor via Gαi -coupled-receptor. Recently, UDCA has been shown to protect the heart against hypoxia-reoxygenation injury. However, it is not clear whether UDCA cardioprotection against hypoxia acts through a transcriptional mediator of cells stress, HIF-1α and p53. Therefore, in here, we aimed to investigate whether UDCA could protect cardiomyocytes (CMs) against hypoxia by regulating expression of HIF-1α, p53, [Ca2+ ]i , and S1P-Gαi -coupled-receptor. Cardiomyocytes were isolated from newborn rats (0-2 days), and hypoxia was induced by using cobalt chloride (CoCl2 ). Cardiomyocytes were treated with UDCA and cotreated with either FTY720 (S1P-receptor agonist) or pertussis toxin (PTX; Gαi inhibitor). Cells were subjected for proliferation assay, beating frequency, QuantiGene Plex assay, western blot, immunofluorescence, and calcium imaging. Our findings showed that UDCA counteracted the effects of CoCl2 on cell viability, beating frequency, HIF-1α, and p53 protein expression. We found that these cardioprotection effects of UDCA were similar to FTY720, S1P agonist. Furthermore, we observed that UDCA protects CMs against CoCl2 -induced [Ca2+ ]i dynamic alteration. Pharmacological inhibition of the Gαi -sensitive receptor did not abolish the cardioprotection of UDCA against CoCl2 detrimental effects, except for cell viability and [Ca2+ ]i . Pertussis toxin is partially effective in inhibiting UDCA protection against CoCl2 effects on CM cell viability. Interestingly, PTX fully inhibits UDCA cardioprotection on CoCl2 -induced [Ca2+ ]i dynamic changes. We conclude that UDCA cardioprotection against CoCl2 -induced hypoxia is similar to FTY720, and its actions are not fully mediated by the Gαi -coupled protein sensitive pathways. Ursodeoxycholic acid is the most hydrophilic bile acid and is currently used to treat liver diseases. Recently, UDCA is shown to have a cardioprotection effects; however, the mechanism of UDCA cardioprotection is still poorly understood. The current data generated were the first to show that UDCA is able to inhibit the activation of HIF-1α and p53 protein during CoCl2 -induced hypoxia in cardiomyocytes. This study provides an insight of UDCA mechanism in protecting cardiomyocytes against hypoxia.
  17. Razman AZ, Chua YA, Mohd Kasim NA, Al-Khateeb A, Sheikh Abdul Kadir SH, Jusoh SA, et al.
    Int J Mol Sci, 2022 Nov 29;23(23).
    PMID: 36499307 DOI: 10.3390/ijms232314971
    Familial hypercholesterolaemia (FH) is caused by mutations in lipid metabolism genes, predominantly in low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin-type 9 (PCSK9) and LDL receptor adaptor protein 1 (LDLRAP1). The prevalence of genetically confirmed FH and the detection rate of pathogenic variants (PV) amongst clinically diagnosed patients is not well established. Targeted next-generation sequencing of LDLR, APOB, PCSK9 and LDLRAP1 was performed on 372 clinically diagnosed Malaysian FH subjects. Out of 361 variants identified, 40 of them were PV (18 = LDLR, 15 = APOB, 5 = PCSK9 and 2 = LDLRAP1). The majority of the PV were LDLR and APOB, where the frequency of both PV were almost similar. About 39% of clinically diagnosed FH have PV in PCSK9 alone and two novel variants of PCSK9 were identified in this study, which have not been described in Malaysia and globally. The prevalence of genetically confirmed potential FH in the community was 1:427, with a detection rate of PV at 0.2% (12/5130). About one-fourth of clinically diagnosed FH in the Malaysian community can be genetically confirmed. The detection rate of genetic confirmation is similar between potential and possible FH groups, suggesting a need for genetic confirmation in index cases from both groups. Clinical and genetic confirmation of FH index cases in the community may enhance the early detection of affected family members through family cascade screening.
  18. Md Shahrulnizam NAN, Mohd Efendy Goon MD, Ab Rahim S, Lew SW, Sheikh Abdul Kadir SH, Ibrahim E
    Genes Nutr, 2024 Feb 27;19(1):3.
    PMID: 38413846 DOI: 10.1186/s12263-024-00742-9
    Tocotrienol-rich fraction (TRF) has been reported to protect the heart from oxidative stress-induced inflammation. It is, however, unclear whether the protective effects of TRF against oxidative stress involve the activation of farnesoid X receptor (fxr), a bile acid receptor, and the regulation of bile acid metabolites. In the current study, we investigated the effects of TRF supplementation on antioxidant activities, expression of fxr and its target genes in cardiac tissue, and serum untargeted metabolomics of high-fat diet-fed mice. Mice were divided into high-fat diet (HFD) with or without TRF supplementation (control) for 6 weeks. At the end of the intervention, body weight (BW), waist circumference (WC), and random blood glucose were measured. Heart tissues were collected, and the gene expression of sod1, sod2, gpx, and fxr and its target genes shp and stat3 was determined. Serum was subjected to untargeted metabolomic analysis using UHPLC-Orbitrap. In comparison to the control, the WC of the TRF-treated group was higher (p >0.05) than that of the HFD-only group, in addition there was no significant difference in weight or random blood glucose level. Downregulation of sod1, sod2, and gpx expression was observed in TRF-treated mice; however, only sod1 was significant when compared to the HFD only group. The expression of cardiac shp (fxr target gene) was significantly upregulated, but stat3 was significantly downregulated in the TRF-treated group compared to the HFD-only group. Biochemical pathways found to be influenced by TRF supplementation include bile acid secretion, primary bile acid biosynthesis, and biotin and cholesterol metabolism. In conclusion, TRF supplementation in HFD-fed mice affects antioxidant activities, and more interestingly, TRF also acts as a signaling molecule that is possibly involved in several bile acid-related biochemical pathways accompanied by an increase in cardiac fxr shp expression. This study provides new insight into TRF in deregulating bile acid receptors and metabolites in high-fat diet-fed mice.
  19. Md Noh SM, Sheikh Abdul Kadir SH, Bannur ZM, Froemming GA, Abdul Hamid Hasani N, Mohd Nawawi H, et al.
    Exp Eye Res, 2014 Oct;127:236-42.
    PMID: 25139730 DOI: 10.1016/j.exer.2014.08.005
    Anti-Vascular Endothelial Growth Factors (Anti-VEGF) agents have received recent interest as potential anti-fibrotic agents for their concurrent use with trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology following trabeculectomy augmented with ranibizumab. The effects of this humanized monoclonal antibody on human Tenon's fibroblast (HTF), the key player of post trabeculectomy scar formation, are not fully understood. This study was conducted to understand the effects of ranibizumab on extracellular matrix production by HTF. The effect of ranibizumab on HTF proliferation and cell viability was determined using MTT assay (3-(4,5-dimethylthiazone-2-yl)-2,5-diphenyl tetrazolium). Ranibizumab at concentrations ranging from 0.01 to 0.5 mg/mL were administered for 24, 48 and 72 h in serum and serum free conditions. Supernatants and cell lysates from samples were assessed for collagen type 1 alpha 1 and fibronectin mRNA and protein level using quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). After 48-h, ranibizumab at 0.5 mg/mL, significantly induced cell death under serum-free culture conditions (p 
  20. Zainol Abidin MN, Goh PS, Said N, Ismail AF, Othman MHD, Hasbullah H, et al.
    ACS Appl Mater Interfaces, 2020 Jul 22;12(29):33276-33287.
    PMID: 32589391 DOI: 10.1021/acsami.0c08947
    The development of wearable artificial kidney demands an efficient dialysate recovery, which relies upon the adsorption process. This study proposes a solution to solve the problem of competitive adsorption between the uremic toxins by employing two adsorptive components in a membrane separation process. Dual-layer hollow fiber (DLHF) membranes, which are composed of a polysulfone (PSf)/activated carbon (AC) inner layer and a PSf/poly(methyl methacrylate) (PMMA) outer layer, were prepared for co-adsorptive removal of creatinine and urea from aqueous solution. The DLHF membranes were characterized in terms of morphological, physicochemical, water transport, and creatinine adsorption properties. The membrane was then subjected to an ultrafiltration adsorption study for performance evaluation. The incorporation of AC in membrane, as confirmed by microscopic and surface analyses, has improved the pure water flux up to 25.2 L/(m2 h). A membrane with optimum AC loading (9 wt %) demonstrated the highest maximum creatinine adsorption capacity (86.2 mg/g) based on the Langmuir adsorption isotherm model. In the ultrafiltration adsorption experiment, the membrane removed creatinine and urea with a combined average percent removal of 29.3%. Moreover, the membrane exhibited creatinine and urea uptake recoveries of 98.8 and 81.2%, respectively. The combined action of PMMA and AC in the PSf DLHF membrane has made the adsorption of multiple uremic toxins possible during dialysate recovery.
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