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Hydrogen peroxide induces acute injury and up-regulates inflammatory gene expression in hepatocytes: an in vitro model

Liau LL, Makpol Suzana, Abdul Ghani Nur Azurah, Chua KH

Sains Malaysiana, 2016;45:451-458.

In the past, many in vitro hepatocyte injury models developed for liver regeneration used carbon tetrachloride as irritant chemical. Recently, carbon tetrachloride usage was prohibited due to serious deleterious effects to human and environment. There is an urgent need to develop a new acute chemical-induced hepatocyte injury model using other chemical compound to replace carbon tetrachloride. In this study, we used hydrogen peroxide (H2O2) to induced hepatocyte injury with HepG2 as the liver cell model. HepG2 injury was established by exposing the cells to CC50 of H2O2 at the concentration of 2.4 mM, predetermined via MTT assay for 2 h exposure. Aspartate aminotransferase (AST) activity was measured to determine the extent of cellular injury and quantitative PCR was carried out to determine the expression of inflammatory genes of the cells 24 h after H2O2 exposure. The results showed that AST activity increased with time and peak at 24 h after H2O2 exposure. Quantitative PCR analysis demonstrated that expression of inflammatory genes (TGF-β1, MMP-3, NF-κβ, IL-8 and IL-6) increased significantly. In addition, the gene expression of GPX, an anti-oxidant enzyme was also increased significantly in response to oxidative stress. In summary, H2O2 demonstrated excellent capability in inducing oxidative injury to HepG2 and together they represent an ideal acute chemical-induced injury model that can be used for liver regeneration study. Our results also provide input for inflammatory gene expression in the hepatocyte injury model.
Retention of Somatic Memory Associated with Cell Identity, Age and Metabolism in Induced Pluripotent Stem (iPS) Cells Reprogramming

Khoo TS, Jamal R, Abdul Ghani NA, Alauddin H, Hussin NH, Abdul Murad NA

Stem Cell Rev Rep, 2020 04;16(2):251-261.
PMID: 32016780 DOI: 10.1007/s12015-020-09956-x

The discovery of induced pluripotent stem (iPS) cells in 2006 marked a major breakthrough in regenerative medicine, enabling reversal of terminally differentiated somatic cells into pluripotent stem cells. The embryonic stem (ES) cells-like pluripotency and unlimited self-renewal capability of iPS cells have granted them enormous potential in many applications, particularly regenerative therapy. Unlike ES cells, however, iPS cells exhibit somatic memories which were carried over from the tissue of origin thus limited its translation in clinical applications. This review provides an updated overview of the retention of various somatic memories associated with the cellular identity, age and metabolism of tissue of origin in iPS cells. The influence of cell types, stage of maturation, age and various other factors on the retention of somatic memory has been discussed. Recent evidence of somatic memory in the form of epigenetic, transcriptomic, metabolic signatures and its functional manifestations in both in vitro and in vivo settings also have been reviewed. The increasing number of studies which had adopted isogenic cell lines for comparisons in recent years had facilitated the identification of genuine somatic memories. These memories functionally affect iPS cells and its derivatives and are potentially tumorigenic thus, raising concerns on their safety in clinical application. Various approaches for memory erasure had since being reported and their efficacies were highlighted in this review.
Prophylactic gonadectomy in 46 XY females; why, where and when?

Basri NI, Soon CH, Ali A, Abdul Ghani NA, Zainuddin AA

Horm Mol Biol Clin Investig, 2021 Mar 08;42(3):325-328.
PMID: 33675193 DOI: 10.1515/hmbci-2021-0001

OBJECTIVES: We compared cases of phenotypic female patients who presented with male karyotype and underwent prophylactic gonadectomy.
CASE PRESENTATION: Five patients with female phenotypes presented in early adulthood with primary amenorrhoea with varying degrees of puberty. One was tall with breast development. Another was very short with clitoromegaly and multiple co-morbidities. The other three had no secondary sexual characteristics. They were examined, after which hormonal profile, karyotyping, ultrasound examination and magnetic resonance imaging were done to assess the site of gonads. Gonadectomy was performed once their 46 XY karyotype was confirmed. Results of histopathological examination of their gonads ranged from dysgenetic gonads to having testicular tissues and malignancy.
CONCLUSION: Female patients with 46 XY karyotypes require prophylactic gonadectomy performed at different timings depending on diagnosis due to the malignancy risk. Pre-operative assessment is essential to locate the gonads prior to surgery.
Fulltext Quality of life of adolescents with menstrual problems in Klang Valley, Malaysia: a school population-based cross-sectional study

Mariappen U, Chew KT, Zainuddin AA, Mahdy ZA, Abdul Ghani NA, Grover S

BMJ Open, 2022 Jan 04;12(1):e051896.
PMID: 34983763 DOI: 10.1136/bmjopen-2021-051896

OBJECTIVE: To describe the prevalence of menstrual problems (heavy menses bleeding, dysmenorrhoea and oligomenorrhoea) and its impact towards quality of life among adolescents in Klang Valley, Malaysia.
DESIGN: Cross-sectional study.
SETTING: Adolescent girls at secondary schools in the Klang Valley, Malaysia.
POPULATION: 729 adolescents aged between 13 and 18 years.
METHOD: A questionnaire survey using Menorrhagia Questionnaire and Paediatric Quality of Life-Teen Report Ages 13-18 (PedsQL).
MAIN OUTCOME MEASURES: Self reports of menstrual bleeding patterns, morbidities and effect on quality of life.
RESULTS: The prevalence of menstrual problems among adolescents was 63.9% in the Klang Valley. Adolescents with menstrual problems had significant lower mean total score of PedsQL (70.23±13.53 vs 76.36±14.93, p=0.001), physical health summary score (74.10±16.83 vs 79.00±15.86, p<0.001) and psychosocial health summary score (68.05±14.27 vs 73.21±13.09, p=0.001) compared with those without menstrual problem. Adolescents experiencing heavy menses bleeding had the lowest physical and emotional function. Those with oligomenorrhoea had the lowest social function, whereas those with dysmenorrhoea had the lowest school function. Cigarette smoking, alcohol and medical illness had lower health-related quality of life, whereas taking oral contraceptive pills for menstrual problems was associated with higher scores in these adolescents.
CONCLUSION: Menstrual problems among adolescents have a significant impact on their quality of life. It is probably wise to screen them at the school level, to identify those with low functional scores and to refer them for proper management at a tertiary adolescent gynaecology centre.
Generation of a novel ex-vivo model to study re-endothelialization

Azman SS, Yazid MD, Abdul Ghani NA, Raja Sabudin RZA, Abdul Rahman MR, Sulaiman N

Artif Cells Nanomed Biotechnol, 2023 Dec;51(1):408-416.
PMID: 37584645 DOI: 10.1080/21691401.2023.2245456

Endothelial dysfunction initiates the pathogenesis of a myriad of cardiovascular diseases, yet the precise underlying mechanisms remain unclear. Current model utilises mechanical denudation of arteries resulting in an arterial-injury model with onset of intimal hyperplasia (IH). Our study shows that 5 min enzymatic denudation of human umbilical artery (hUA) lumen at 37 °C efficiently denudes hUA while maintaining vessel integrity without significantly increase intima-media thickness after 7 days in culture. This ex-vivo model will be a valuable tool in understanding the mechanism of re-endothelialization prior to smooth muscle cells (SMC) activation thus placating IH at an early stage.
Fulltext Health-related quality of life of female patients with congenital adrenal hyperplasia in Malaysia

Zainuddin AA, Grover SR, Abdul Ghani NA, Wu LL, Rasat R, Abdul Manaf MR, et al.

Health Qual Life Outcomes, 2020 Aug 01;18(1):258.
PMID: 32738912 DOI: 10.1186/s12955-020-01515-9

BACKGROUND: This study investigates the health-related quality of life (HRQOL) of female patients with congenital adrenal hyperplasia (CAH) in Malaysia. The objectives were to attain socio-demographic and medical data on these Malaysian females with CAH and establish their health-related quality of life (HRQOL) in comparison to age matched diabetic controls.
METHODS: A cross-sectional study was conducted over 6 months in the two main tertiary centres for CAH patients in Malaysia. Participants including 59 female-raised CAH patients (mean age ± SD = 16.3 ± 4.2 years, range 10-28 years) compared to 57 age-matched female diabetic patients (mean age ± SD = 16.5 ± 3.4 years, range 10-26 years). Socio-demographic and medical profiles was obtained through semi-structured interviews. HRQOL of participants were evaluated utilising validated, Malay translated questionnaires which were age appropriate: Pediatric Quality of Life Inventory (PedsQL v4.0) scales for Child (8-12) and Adolescent (13-18) and Medical Outcome Survey 36-item Short Form version. These were then compared to the diabetic controls.
RESULTS: The CAH participants consisted of children (ages 10-12 years, n = 12), adolescents (ages 13-17 years, n = 29) and adults (≥ 18 years, n = 18). The majority were Malays (64.4%) and had salt-wasting CAH (67.8%). There were no significant differences between the total mean score of the HRQOL of the combined children and adolescents CAH group (total mean score ± SD = 81.6 ± 17.9, 95% CI = 75.6-87.6) when compared to age-matched diabetic patients (total mean score ± SD = 80.8 ± 11.0, 95% CI = 77.0-84.5, P = 0.81, effect size = 0.05); no significant difference between the adult CAH and diabetic controls in the physical [median score (IQR) CAH vs diabetics; 49.3 (11.4) vs. 50.2 (6.1), P = 0.60, effect size = 0.09] and the mental composite scores [median score (IQR) CAH vs. diabetics; 47.8 (14.1) vs. 50.0 (10.8), P = 0.93, effect size = 0.01].
CONCLUSIONS: The HRQOL of the Malaysian CAH cohort were comparable to the diabetic controls.
Reviewing the role of progesterone therapy in endometriosis

Abdul Karim AK, Shafiee MN, Abd Aziz NH, Omar MH, Abdul Ghani NA, Lim PS, et al.

Gynecol Endocrinol, 2019 Jan;35(1):10-16.
PMID: 30044157 DOI: 10.1080/09513590.2018.1490404

Endometriosis is a benign, chronic inflammatory condition characterized by the presence and growth of endometrial implants outside the uterine cavity. The cause of endometriosis is multifactorial. It is due to the diversity of hypothesis and plausibility of hormonal alterations which could play a major role. Evidence has shown that progesterone resistance is a key factor for endometriosis sufferers. Medical therapy can avoid surgical intervention, which may lead to a reduced in ovarian reserve, and its effects of earlier menopause and reduced fecundity. Progesterone receptor isoform has provided new insight as the potential treatment. Progestin, anti-progestin and selective progesterone receptor modulators usage, which target these receptors, could avoid hypo-estrogenic side effects, which can be debilitating. Numerous types of these medications have been used on and off labeled to treat endometriosis with varying success. This review aims to consolidate series of clinical trials using progestins in endometriosis.
Management Options and Outcome of Cerebral Arteriovenous Malformation in Pregnancy: Case Series

Teik CK, Basri NI, Abdul Karim AK, Azrai Abu M, Ahmad MF, Abdul Ghani NA, et al.

Arch Iran Med, 2019 06 01;22(6):340-343.
PMID: 31356101

Cerebral arteriovenous malformation (AVM) is a rare entity with an estimated prevalence of 0.01-0.05% in the general population. We reviewed hospital obstetric records during 2010-2017 and reported a case series of six patients with cerebral AVM in pregnancy, of which five patients had successful pregnancy, and one maternal mortality.