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Activation of autophagy by stress-activated signals as a cellular self-defense mechanism against the cytotoxic effects of MBIC in human breast cancer cells in vitro

Hasanpourghadi M, Majid NA, Mustafa MR

Biochem Pharmacol, 2018 06;152:174-186.
PMID: 29608909 DOI: 10.1016/j.bcp.2018.03.030

We recently reported that methyl 2-(-5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) is a microtubule targeting agent (MTA) with multiple mechanisms of action including apoptosis in two human breast cancer cell-lines MCF-7 and MDA-MB-231. In the present study, investigation of early molecular events following MBIC treatment demonstrated the induction of autophagy. This early (<24 h) response to MBIC was characterized by accumulation of autophagy markers; LC3-II, Beclin1, autophagic proteins (ATGs) and collection of autophagosomes but with different variations in the two cell-lines. MBIC-induced autophagy was associated with generation of reactive oxygen species (ROS). In parallel, an increased activation of SAPK/JNK pathway was detected, as an intersection of ROS production and induction of autophagy. The cytotoxic effect of MBIC was enhanced by inhibition of autophagy through blockage of SAPK/JNK signaling, suggesting that MBIC-induced autophagy, is a possible cellular self-defense mechanism against toxicity of this agent in both breast cancer cell-lines. The present findings suggest that inhibition of autophagy eliminates the cytoprotective activity of MDA-MB-231 and MCF-7 cells, and sensitizes both the aggressive and non-aggressive human breast cancer cell-lines to the cytotoxic effects of MBIC.
Fulltext Transient cortical blindness secondary to hepatic encephalopathy in a pediatric patient: A case report and literature review

Ain-Nasyrah AS, Majid NA, Shatriah I

Taiwan J Ophthalmol, 2020 10 21;11(4):413-416.
PMID: 35070675 DOI: 10.4103/tjo.tjo_43_20

Cortical blindness, also known as cerebral visual impairment, may occur in pediatric patients. Hepatic encephalopathy is a rare cause of cortical blindness in children. This report describes a girl with underlying type 1 autoimmune hepatitis, who complained of sudden-onset, painless visual loss in both eyes, which was associated with generalized headache and altered mental status. She was treated with intravenous antibiotics and syrup lactulose. The patient regained full visual recovery after 1 week. Prompt diagnosis and treatment are mandatory in such uncommon instances.
Characteristics of Pelargonium radula as a mercury bioindicator for safety assessment of drinking water

Majid NA, Phang IC, Darnis DS

Environ Sci Pollut Res Int, 2017 Oct;24(29):22827-22838.
PMID: 28150147 DOI: 10.1007/s11356-017-8484-9

Identification of Pelargonium radula as bioindicator for mercury (Hg) detection confers a new hope for monitoring the safety of drinking water consumption. Hg, like other non-essential metals, inflicts the deterioration of biological functions in human and other creatures. In the present study, effects of Hg on the physiology and biochemical content of P. radula were undertaken to understand the occurrence of the morphological changes observed. Young leaves of P. radula were treated with different concentrations of Hg-containing solution (0.5, 1.0 and 2.0 ppb) along with controls for 4 h, prior to further analysis. Elevated Hg concentration in treatment solution significantly prompted an increased accumulation of Hg in the leaf tissues. Meanwhile, total protein, chlorophyll and low molecular mass thiol contents (cysteine, glutathione and oxidized glutathione) decreased as Hg accumulation increased. However, phytochelatin 2 productions were induced in the treated leaves, in comparison to the control. Based on these findings, it is postulated that as low as 0.5 ppb of Hg interferes with the metabolic processes of plant cells, which was reflected from the morphological changes exhibited on P. radula leaves-the colour of the Hg-treated leaves changed from green to yellowish-brown, became chlorosis and wilted. Changes in the tested characteristics of plant are closely related to the Hg-induced morphological changes on P. radula leaves, a potential bioindicator for detecting Hg in drinking water.
Fulltext Dataset of exceptional women directors and carbon information disclosures of global energy companies

Majid NA, Jaaffar AH, Kimpah J

Data Brief, 2023 Dec;51:109650.
PMID: 37869621 DOI: 10.1016/j.dib.2023.109650

Dataset in this article contains solid information on the novel dataset of exceptional women directors (EWDs) and carbon information disclosures (CID) of global energy leading companies. The data presented is related to the research article entitled "The Effect of Women's Leadership on Carbon Disclosure by the Top 100 Global Energy Leaders" [1]. In exploring the degree of EWDs' and the level of CID, the content analysis technique based on the enhanced scoring indicators were deployed to obtain the data of the 97 companies based on accessible materials from companies' websites or any associated reports such as sustainability, environmental, annual, or integrated reports within three-year periods (2018 - 2020) for the global energy leading companies which listed in Thomson Reuters Database 2017. Data on EWDs' engagement and CID are extracted from the available information, reports, and materials. The data are collected based on the enhanced version of the EWD's indicators adapted from Ramon Llorens, García-Meca and Pucheta-Martínez [2], Hillman, Cannella and Paetzold [3], and Jaaffar and Amran [4]. Meanwhile, data collected for CID by using Carbon Disclosures Index (CDI) comprising 90 scores within nine aspects; Strategy and Policy; Climate Change Risks and Opportunities; Corporate GHG Emissions Targets; Company Wide Carbon Footprint; GHG Emissions Change Over Time; Energy-Related Reporting; Emission Reduction Initiatives Implementation; Carbon Emission Accountability; and Quality of Disclosure as suggested by the prior scholars [5], [6], [7]. This dataset shed light as an indicator to measure exceptional women director in the energy companies in promoting transparent carbon disclosure performance as well as boosting women leadership involvement and participation in the most polluting sector which aligned with the United Nations Sustainable Development Goals; SDG 5 gender equality, SDG 10 reduced inequality, and SDG 13 climate action.
Fulltext Unlocking the potential of LSTM for accurate salary prediction with MLE, Jeffreys prior, and advanced risk functions

Li F, Majid NA, Ding S

PeerJ Comput Sci, 2024;10:e1875.
PMID: 38435555 DOI: 10.7717/peerj-cs.1875

This article aims to address the challenge of predicting the salaries of college graduates, a subject of significant practical value in the fields of human resources and career planning. Traditional prediction models often overlook diverse influencing factors and complex data distributions, limiting the accuracy and reliability of their predictions. Against this backdrop, we propose a novel prediction model that integrates maximum likelihood estimation (MLE), Jeffreys priors, Kullback-Leibler risk function, and Gaussian mixture models to optimize LSTM models in deep learning. Compared to existing research, our approach has multiple innovations: First, we successfully improve the model's predictive accuracy through the use of MLE. Second, we reduce the model's complexity and enhance its interpretability by applying Jeffreys priors. Lastly, we employ the Kullback-Leibler risk function for model selection and optimization, while the Gaussian mixture models further refine the capture of complex characteristics of salary distribution. To validate the effectiveness and robustness of our model, we conducted experiments on two different datasets. The results show significant improvements in prediction accuracy, model complexity, and risk performance. This study not only provides an efficient and reliable tool for predicting the salaries of college graduates but also offers robust theoretical and empirical foundations for future research in this field.
Fulltext Comparison of the Clinical and Biochemical Profile of Metabolic Syndrome Between Obese Children Below and Above 10-Years Old Attending Paediatric Clinic Hospital Universiti Sains Malaysia from 2006 to 2015

Hussain S, Men KK, Majid NA

J ASEAN Fed Endocr Soc, 2017;32(2):132-138.
PMID: 33442096 DOI: 10.15605/jafes.032.02.06

Objectives: We aim to compare the clinical and biochemical profile of metabolic syndrome between obese children below and above 10 years attending Paediatric clinic Hospital Universiti Sains Malaysia (HUSM) from 2006 to 2015. This is to determine if age, particularly the transition to puberty, modifies the prevalence of components of metabolic syndrome in obese children.
Methodology: The medical records of 84 obese children under 18 years of age seen at Paediatric clinic HUSM from 2006 to 2015 were reviewed. Demographic (age, gender, ethnicity), anthropometric (weight and height), clinical [body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP)] and biochemical [serum total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), fasting plasma glucose (FPG)] parameters were recorded, analyzed and compared.
Results: Majority of subjects in both age groups were boys, with 68.2% <10 years old. Mean age was 9.69 years (±3.36). The clinical and biochemical parameters of metabolic syndrome were similar between those <10 years old and >10 years, with the exception of BMI, waist circumference, SBP and TG level. Multivariate regression analysis showed that the parameters of metabolic syndrome significantly associated with age ≥10 years were systolic hypertension (adjusted OR 7.17, 95% CI, 1.48 to 34.8) and BMI >30 kg/m2 (adjusted OR 3.02, 95% CI, 1.16 to 7.86).
Conclusion: There were similar clinical and biochemical parameters of metabolic syndrome in both age groups. The proportions of children with metabolic syndrome were similar regardless of age group. The overall prevalence rate of metabolic syndrome was 27.3%. In view of the alarming presence of components of metabolic syndrome even in children less than 10 years of age, efforts aimed at the prevention of childhood obesity in the community should be intensified.
Fulltext Food Allergy and Helicobacter pylori Infection: A Systematic Review

Ma ZF, Majid NA, Yamaoka Y, Lee YY

Front Microbiol, 2016;7:368.
PMID: 27047479 DOI: 10.3389/fmicb.2016.00368

Based on the hygiene hypothesis, a low prevalence of Helicobacter pylori (H. pylori) infection may explain the recent high prevalence of allergic diseases including food allergy. However, there are very few studies that investigate the relationship between H. pylori and food allergy.
Fulltext In vivo acute toxicity and anti-gastric evaluation of a novel dichloro Schiff base: Bax and HSP70 alteration

Saremi K, Rad SK, Khalilzadeh M, Hussaini J, Majid NA

Acta Biochim Biophys Sin (Shanghai), 2020 Jan 02;52(1):26-37.
PMID: 31889181 DOI: 10.1093/abbs/gmz140

Chlorine is shown to possess anti-gastric ulcer activity, since it can inactivate Helicobacter pylori, which is regarded as one of the most common risk factors for causing gastric problems. In the current study, the gastroprotective property of a novel dichloro-substituted Schiff base complex, 2, 2'- [-1, 2-cyclohexanediylbis(nitriloethylidyne)] bis(4-chlorophenol) (CNCP), against alcohol-induced gastric lesion in SD rats was assessed. SD rats were divided into four groups, i.e. normal, ulcer control, testing, and reference groups. Ulcer area, gastric wall mucus, and also gastric acidity of the animal stomachs were measured. In addition, antioxidant activity of CNCP was evaluated and its safe dose was identified. Immunohistochemistry staining was also carried to evaluate two important proteins, i.e. Bcl2-associated X protein (Bax) and heat shock protein 70 (HSP70). Moreover, the activities of super oxide dismutase and catalase, as well as the levels of prostaglandin E2 (PGE2) and malondialdehyde (MDA) were also measured. Antioxidant activity of CNCP was approved via the aforementioned experiments. Histological evaluations showed that the compound possesses stomach epithelial defense activity. Additionally, periodic acid-Schiff staining exhibited over-expression of HSP70 and down-expression of Bax protein in the CNCP-treated rats. Moreover, CNCP caused deceased MDA level and elevated PGE2 level, and at the same time increased the activities of the two enzymes.
Non-attendance to the paediatric clinics in a Malaysian tertiary hospital: a sizeable problem and identification of an efficacious intervention

Jamil MT, Ismail NZ, Zulkifli AB, Majid NA, Van Rostenberghe H

J Paediatr Child Health, 2011 Jun;47(6):346-9.
PMID: 21309884 DOI: 10.1111/j.1440-1754.2010.01989.x

AIM: To determine the rate, causes and risk factors of non-attendance to the paediatric clinic in a tertiary hospital in Malaysia and to determine the efficacy of one telephone call to confirm a new appointment.
METHODS: For all non-attending patients, during a 2-month period, a pro forma was filled up based on patients' records. During a phone call, additional questions were asked, and a new appointment was offered.
RESULTS: Of 1563 patients who had an appointment, 497 (31.8%) were non-attendees. Weather conditions, the sub-specialty and timing (morning or afternoon) had a significant effect on non-attendance. Forgetfulness was the main cause. Only 160 patients could be successfully contacted. Among the contactable patients, 55 already had an appointment, and 10 had reasons not to get a new appointment. Of the 95 remaining patients, 73 (76.8%) attended the new appointment.
CONCLUSION: The non-attendance rate was high. One telephone call had a reasonable efficacy for the contactable patients, but because a high number of patients were not contactable, overall effectiveness was poor.
Study site: Paediatric clinic, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia,
Fulltext Helicobacter pylori infection among Aborigines (the Orang Asli) in the northeastern region of Peninsular Malaysia

Rahim AA, Lee YY, Majid NA, Choo KE, Raj SM, Derakhshan MH, et al.

Am J Trop Med Hyg, 2010 Nov;83(5):1119-22.
PMID: 21036849 DOI: 10.4269/ajtmh.2010.10-0226

Whether the exceptionally low prevalence of Helicobacter pylori (HP) infection reported among Malays is also present among aborigines (the Orang Asli) living in northeastern Peninsular Malaysia is unknown. We studied asymptomatic Orang Asli from settlements situated 210 km from the city of Kota Bharu. The HP infection status was confirmed by a validated serology test. Nineteen percent of 480 Orang Asli tested positive for HP infection. The prevalence was 40.6% in the birth cohort of the 1940s and declined steadily in later cohorts to under 10% among 12-30 year olds. This may be related to the phases of relocation from the jungles into resettlement camps and ultimately into designated villages near rivers. The low prevalence pattern after the 1970s was probably partly a result of improvement in sanitation and hygiene practice in these villages but other unidentified factors may also be operating.
Cleistopholine isolated from Enicosanthellum pulchrum exhibits apoptogenic properties in human ovarian cancer cells

Nordin N, Majid NA, Mohan S, Dehghan F, Karimian H, Rahman MA, et al.

Phytomedicine, 2016 Apr 15;23(4):406-16.
PMID: 27002411 DOI: 10.1016/j.phymed.2016.02.016

Cleistopholine is a natural alkaloid present in plants with numerous biological activities. However, cleistopholine has yet to be isolated using modern techniques and the mechanism by which this alkaloid induces apoptosis in cancer cells remains to be elucidated.
Fulltext Liriodenine, an aporphine alkaloid from Enicosanthellum pulchrum, inhibits proliferation of human ovarian cancer cells through induction of apoptosis via the mitochondrial signaling pathway and blocking cell cycle progression

Nordin N, Majid NA, Hashim NM, Rahman MA, Hassan Z, Ali HM

Drug Des Devel Ther, 2015;9:1437-48.
PMID: 25792804 DOI: 10.2147/DDDT.S77727

Enicosanthellum pulchrum is a tropical plant from Malaysia and belongs to the Annonaceae family. This plant is rich in isoquinoline alkaloids. In the present study, liriodenine, an isoquinoline alkaloid, was examined as a potential anticancer agent, particularly in ovarian cancer. Liriodenine was isolated by preparative high-performance liquid chromatography. Cell viability was performed to determine the cytotoxicity, whilst the detection of morphological changes was carried out by acridine orange/propidium iodide assay. Initial and late apoptosis was examined by Annexin V-fluorescein isothiocyanate and DNA laddering assays, respectively. The involvement of pathways was detected via caspase-3, caspase-8, and caspase-9 analyses. Confirmation of pathways was further performed in mitochondria using a cytotoxicity 3 assay. Apoptosis was confirmed at the protein level, including Bax, Bcl-2, and survivin, while interruption of the cell cycle was used for final validation of apoptosis. The result showed that liriodenine inhibits proliferation of CAOV-3 cells at 37.3 μM after 24 hours of exposure. Changes in cell morphology were detected by the presence of cell membrane blebbing, chromatin condensation, and formation of apoptotic bodies. Early apoptosis was observed by Annexin V-fluorescein isothiocyanate bound to the cell membrane as early as 24 hours. Liriodenine activated the intrinsic pathway by induction of caspase-3 and caspase-9. Involvement of the intrinsic pathway in the mitochondria could be seen, with a significant increase in mitochondrial permeability and cytochrome c release, whereas the mitochondrial membrane potential was decreased. DNA fragmentation occurred at 72 hours upon exposure to liriodenine. The presence of DNA fragmentation indicates the CAOV-3 cells undergo late apoptosis or final stage of apoptosis. Confirmation of apoptosis at the protein level showed overexpression of Bax and suppression of Bcl-2 and survivin. Liriodenine inhibits progression of the CAOV-3 cell cycle in S phase. These findings indicate that liriodenine could be considered as a promising anticancer agent.
Optimization of Protein Extraction and Two-Dimensional Electrophoresis Protocols for Oil Palm Leaf

Daim LD, Ooi TE, Yusof HM, Majid NA, Karsani SA

Protein J, 2015 Aug;34(4):304-12.
PMID: 26263918 DOI: 10.1007/s10930-015-9626-x

Oil palm (Elaeis guineensis) is an important economic crop cultivated for its nutritional palm oil. A significant amount of effort has been undertaken to understand oil palm growth and physiology at the molecular level, particularly in genomics and transcriptomics. Recently, proteomics studies have begun to garner interest. However, this effort is impeded by technical challenges. Plant sample preparation for proteomics analysis is plagued with technical challenges due to the presence of polysaccharides, secondary metabolites and other interfering compounds. Although protein extraction methods for plant tissues exist, none work universally on all sample types. Therefore, this study aims to compare and optimize different protein extraction protocols for use with two-dimensional gel electrophoresis of young and mature leaves from the oil palm. Four protein extraction methods were evaluated: phenol-guanidine isothiocyanate, trichloroacetic acid-acetone precipitation, sucrose and trichloroacetic acid-acetone-phenol. Of these four protocols, the trichloroacetic acid-acetone-phenol method was found to give the highest resolution and most reproducible gel. The results from this study can be used in sample preparations of oil palm tissue for proteomics work.
Fulltext Gastroprotective activity of a novel Schiff base derived dibromo substituted compound against ethanol-induced acute gastric lesions in rats

Saremi K, Rad SK, Tayeby F, Abdulla MA, Karimian H, Majid NA

BMC Pharmacol Toxicol, 2019 Feb 15;20(1):13.
PMID: 30770761 DOI: 10.1186/s40360-019-0292-z

BACKGROUND: Basic function of bromine in body is to activate pepsin production in gastritis with low acidity. The present study encompasses a broad in vivo study to evaluate gastroprotective activity of a novel dibromo substituted Schiff base complex against Sprague Dawley (SD) rats.
METHODS: 2, 2'-[1, 2-cyclohexanediylbis (nitriloethylidyne)]bis(4-bromophenol) (CNBP) is synthesized via a Schiff base reaction, using the related ketone and diamine as the starting materials. SD rats are divided as normal, ulcer control (5 ml/kg of 10% Tween 20), testing (10 and 20 mg/kg of CNBP) and reference groups (omeprazole 20 mg/kg). Except for the normal group, the rest of the groups are induced gastric ulcer by ethanol 1 h after the pre-treatment. Ulcer area, gastric wall mucus, and acidity of gastric content of the animal stomachs are measured after euthanization. Antioxidant activity of the compound is tested by Ferric reducing antioxidant power (FRAP) test and safety of the compound is identified through acute toxicity by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, activities of superoxide dismutase (SOD), catalase (CAT), levels of prostaglandins E2 (PGE2) and also malondialdehyde (MDA) are determined.
RESULTS: Antioxidant activity of CNBP was approved via FRAP assay. Vast shallow hemorrhagic injury of gastric glandular mucosa was observed in the ulcer group compared to the CNBP-treated animals. Histological evaluations confirmed stomach epithelial defense effect of CNBP with drastic decrease of gastric ulceration, edema and leucocytes penetration of submucosal stratum. Immunostaining exhibited over-expression in HSP70 protein in CNBP-treated groups compared to that of the ulcer group. Also, gastric protein analysis showed low levels of MDA, PGE2 and high activity of SOD and CAT.
CONCLUSIONS: CNBP with noticeable antioxidant property showed gastroprotective activity in the testing rodents via alteration of HSP70 protein expression. Also, antioxidant enzyme activities which were changed after treatment with CNBP in the animals could be elucidated as its gastroprotective properties.
Hot water extract of Pleurotus pulmonarius stalk waste enhances innate immune response and immune-related gene expression in red hybrid tilapia Oreochromis sp. following challenge with pathogen-associated molecular patterns

Ching JJ, Shuib AS, Abdullah N, Majid NA, Taufek NM, Sutra J, et al.

Fish Shellfish Immunol, 2021 Sep;116:61-73.
PMID: 34157396 DOI: 10.1016/j.fsi.2021.06.005

In aquaculture, commercial fish such as red hybrid tilapia are usually raised at high density to boost the production within a short period of time. This overcrowded environment, however, may cause stress to the cultured fish and increase susceptibility to infectious diseases. Antibiotics and chemotherapeutics are used by fish farmers to overcome these challenges, but this may increase the production cost. Studies have reported on the potential of mushroom polysaccharides that can act as immunostimulants to enhance the immune response and disease resistance in fish. In the current study, hot water extract (HWE) from mushroom stalk waste (MSW) was used to formulate fish feed and hence administered to red hybrid tilapia to observe the activation of immune system. Upon 30 days of feeding, the fish were challenged with pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides (LPS) and polyinosinic:polycytidylic acid (poly (I:C)) to mimic bacterial and viral infection, respectively. HWE supplementation promoted better feed utilisation in red hybrid tilapia although it did not increase the body weight gain and specific growth rate compared to the control diet. The innate immunological parameters such as phagocytic activity and respiratory burst activity were significantly higher in HWE-supplemented group than that of the control group following PAMPs challenges. HWE-supplemented diet also resulted in higher mRNA transcription of il1b and tnfa in midgut, spleen and head kidney at 1-day post PAMPs injection. Tlr3 exhibited the highest upregulation in the HWE fed fish injected with poly (I:C). At 3-days post PAMPs injection, both ighm and tcrb expression were upregulated significantly in the spleen and head kidney. Results showed that HWE supplementation enhances the immune responses of red hybrid tilapia and induced a higher serum bactericidal activity against S. agalactiae.
Transgenic oil palm: production and projection

Parveez GK, Masri MM, Zainal A, Majid NA, Yunus AM, Fadilah HH, et al.

Biochem Soc Trans, 2000 Dec;28(6):969-72.
PMID: 11171275

Oil palm is an important economic crop for Malaysia. Genetic engineering could be applied to produce transgenic oil palms with high value-added fatty acids and novel products to ensure the sustainability of the palm oil industry. Establishment of a reliable transformation and regeneration system is essential for genetic engineering. Biolistic was initially chosen as the method for oil palm transformation as it has been the most successful method for monocotyledons to date. Optimization of physical and biological parameters, including testing of promoters and selective agents, was carried out as a prerequisite for stable transformation. This has resulted in the successful transfer of reporter genes into oil palm and the regeneration of transgenic oil palm, thus making it possible to improve the oil palm through genetic engineering. Besides application of the Biolistics method, studies on transformation mediated by Agrobacterium and utilization of the green fluorescent protein gene as a selectable marker gene have been initiated. Upon the development of a reliable transformation system, a number of useful targets are being projected for oil palm improvement. Among these targets are high-oleate and high-stearate oils, and the production of industrial feedstock such as biodegradable plastics. The efforts in oil palm genetic engineering are thus not targeted as commodity palm oil. Due to the long life cycle of the palm and the time taken to regenerate plants in tissue culture, it is envisaged that commercial planting of transgenic palms will not occur any earlier than the year 2020.
Synthesis and Characterization of a New Benzoindole Derivative with Apoptotic Activity Against Colon Cancer Cells

Hajiaghaalipour F, Faraj FL, Bagheri E, Ali HM, Abdulla MA, Majid NA

Curr Pharm Des, 2017;23(41):6358-6365.
PMID: 28325143 DOI: 10.2174/1381612823666170321093345

BACKGROUND: Colorectal cancer is the third most common form of cancer in both men and women around the world. The chemistry and biological study of heterocyclic compounds have been an interesting area for a long time in pharmaceutical and medicinal chemistry.
METHODS: A new synthetic compound, 2-(1,1-dimethyl-1H-benzo[e]indol-2-yl)-3-((2-hydroxyphenyl)amino) acrylaldehyde, abbreviated as DBID, was prepared through the reaction of 2-(diformylmethylidene)-1,1- dimethylbenzo[e]indole with 2-aminophenol. The chemical structure of the synthesized compound was characterized by 1H NMR, 13C NMR and APT-NMR spectroscopy and confirmed by elemental analysis (CHN). The compound was screened for the antiproliferation effect against colorectal cancer cell line, HCT 116 and its possible mechanism of action was elucidated. To determine the IC50 value, the MTT assay was used and its apoptosisinducing effect was investigated.
RESULTS: DBID inhibited the proliferation of HCT 116 cells with an IC50 of 9.32 µg/ml and significantly increased the levels of caspase -8, -9 and -3/7 in the treated cells compared to untreated cells. Apoptosis features in HCT 116 cell was detected in treated cells by using the AO/PI staining that confirmed that the cells had undergone remarkable morphological changes in apoptotic bodies. Furthermore, this changes in expression of caspase -8, -9 and -3 were confirmed by gene and protein quantification using RT-PCR and western blot analysis, respectively.
CONCLUSION: The current study showed that the DBID compound has demonstrated chemotherapeutic activity which was evidenced by significant increases in the expression and activation of caspase and exploit the apoptotic signaling pathways to trigger cancer cell death.
Parent-report instruments for assessing feeding difficulties in children with neurological impairments: a systematic review

Jaafar NH, Othman A, Majid NA, Harith S, Zabidi-Hussin Z

Dev Med Child Neurol, 2019 02;61(2):135-144.
PMID: 30079517 DOI: 10.1111/dmcn.13986

AIM: This study aimed to review the psychometric properties and clinical application of parent-report instruments that assess feeding difficulties in children with neurological impairments.
METHOD: Papers were identified through five electronic databases based on 15 keywords and were included if they met the following criteria: published in English, described the implementation of parent-report instruments, and included children with neurological impairments (either in the report or a related study population).
RESULTS: In total, 1220 relevant abstracts were screened and 22 full-text articles were evaluated. The following six parent-report instruments met the inclusion criteria: (1) Screening Tool of Feeding Problems applied to children, (2) Paediatric Eating Assessment Tool, (3) Paediatric Assessment Scale for Severe Feeding Problems, (4) Montreal Children's Hospital Feeding Scale, (5) Children's Eating Behaviour Inventory, and (6) Behavioural Paediatric Feeding Assessment Scale (BPFAS). Based on comprehensive psychometric testing and consistently good results, the BPFAS was considered the most valid and reliable instrument. The BPFAS also showed good clinical applicability because it was readily available, required a short administration time, and used a simple scoring system.
INTERPRETATION: We reviewed the available parent-report instruments for assessing feeding difficulties in children with neurological impairments. The BPFAS had the best psychometric properties and clinical applicability.
WHAT THIS PAPER ADDS: Six parent-report instruments were suitable for assessing feeding in children with neurological impairments. The Behavioural Paediatric Feeding Assessment Scale (BPFAS) has the strongest psychometric properties. The BPFAS also has good clinical applicability.
Plagioneurin B, a potent isolated compound induces apoptotic signalling pathways and cell cycle arrest in ovarian cancer cells

Nordin N, Majid NA, Othman R, Omer FAA, Nasharuddin MNA, Hashim NM

Apoptosis, 2018 02;23(2):152-169.
PMID: 29430581 DOI: 10.1007/s10495-018-1447-x

Plagioneurin B belongs to acetogenin group has well-established class of compounds. Acetogenin group has attracted worldwide attention in the past few years due their biological abilities as inhibitors for several types of tumour cells. Plagioneurin B was isolated via conventional chromatography and tested for thorough mechanistic apoptosis activity on human ovarian cancer cells (CAOV-3). Its structure was also docked at several possible targets using Autodock tools software. Our findings showed that plagioneurin B successfully inhibits the growth of CAOV-3 cells at IC50 of 0.62 µM. The existence of apoptotic bodies, cell membrane blebbing and chromatin condensation indicated the hallmark of apoptosis. Increase of Annexin V-FITC bound to phosphatidylserine confirmed the apoptosis induction in the cells. The apoptosis event was triggered through the extrinsic and intrinsic pathways via activation of caspases 8 and 9, respectively. Stimulation of caspase 3 and the presence of DNA ladder suggested downstream apoptotic signalling were initiated. Further confirmation of apoptosis was conducted at the molecular levels where up-regulation in Bax, as well as down-regulation of Bcl-2, Hsp-70 and survivin were observed. Plagioneurin B was also seen to arrest CAOV-3 cells cycle at the G2/M phase. Docking simulation of plagioneurin B with CD95 demonstrated that the high binding affinity and hydrogen bonds formation may explain the capability of plagioneurin B to trigger apoptosis. This study is therefore importance in finding the effective compound that may offer an alternative drug for ovarian cancer treatment.
A study of the antioxidant effect of alpha lipoic acids on sperm quality

Ibrahim SF, Osman K, Das S, Othman AM, Majid NA, Rahman MP

Clinics (Sao Paulo), 2008 Aug;63(4):545-50.
PMID: 18719769

OBJECTIVE: Assisted reproductive techniques are useful in helping infertile couples achieve successful conception. Initial studies have shown that sperm cryopreservation, one step in assisted reproduction, causes a dramatic reduction in sperm quality. This has been attributed to, among other things, free radical activities. The aim of the present study was to minimize this oxidative attack by adding an antioxidant into the sperm microenvironment. Alpha lipoic acids were selected for this purpose for their efficient free radical scavenging properties and solubility in lipid and aqueous phases.
METHODS: For this investigation, semen from six Boer bucks was pooled. Seminal analysis of the baseline prior to incubation of samples with different concentrations of Alpha lipoic acids (0.00625, 0.0125, 0.025, 0.05, 0.1 mmol/ml) was performed, and post-seminal analysis was conducted after a one-hour incubation. The comet assay was used to observe the effect of Alpha lipoic acids on sperm DNA integrity. Statistical analysis using an unpaired t-test with a significance level of p<0.05 was then performed.
RESULTS: Our results indicate that the sperm motility rate was improved after incubation with Alpha lipoic acids at a concentration of 0.02 mmol/ml. This concentration was also capable of reducing DNA damage.
CONCLUSION: In conclusion, Alpha lipoic acids renders cryoprotection to sperm, thereby improving sperm quality.

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