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Optimizing neural network algorithms for submerged membrane bioreactor: A comparative study of OVAT and RSM hyperparameter optimization techniques

Ibrahim S, Abdul Wahab N

Water Sci Technol, 2024 Apr;89(7):1701-1724.
PMID: 38619898 DOI: 10.2166/wst.2024.099

Hyperparameter tuning is an important process to maximize the performance of any neural network model. This present study proposed the factorial design of experiment for screening and response surface methodology to optimize the hyperparameter of two artificial neural network algorithms. Feed-forward neural network (FFNN) and radial basis function neural network (RBFNN) are applied to predict the permeate flux of palm oil mill effluent. Permeate pump and transmembrane pressure of the submerge membrane bioreactor system are the input variables. Six hyperparameters of the FFNN model including four numerical factors (neuron numbers, learning rate, momentum, and epoch numbers) and two categorical factors (training and activation function) are used in hyperparameter optimization. RBFNN includes two numerical factors such as a number of neurons and spreads. The conventional method (one-variable-at-a-time) is compared in terms of optimization processing time and the accuracy of the model. The result indicates that the optimal hyperparameters obtained by the proposed approach produce good accuracy with a smaller generalization error. The simulation results show an improvement of more than 65% of training performance, with less repetition and processing time. This proposed methodology can be utilized for any type of neural network application to find the optimum levels of different parameters.
Fulltext Fetal MRI of thoraco-omphalopagus conjoined twins

Abdullah H, Abdul Wahab N, Abu Bakar K

BMJ Case Rep, 2017 Jun 13;2017.
PMID: 28611167 DOI: 10.1136/bcr-2017-219793
Fulltext Growth inhibition of human gynecologic and colon cancer cells by Phyllanthus watsonii through apoptosis induction

Ramasamy S, Abdul Wahab N, Zainal Abidin N, Manickam S, Zakaria Z

PLoS One, 2012;7(4):e34793.
PMID: 22536331 DOI: 10.1371/journal.pone.0034793

Phyllanthus watsonii Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other Phyllanthus species, published information on the cytotoxicity of P. watsonii are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the P. watsonii extracts and fractions on human gynecologic (SKOV-3 and Ca Ski) and colon (HT-29) cancer cells. P. watsonii extracts exhibited strong cytotoxicity on all the cancer cells studied with IC(50) values of ≤ 20.0 µg/mL. Hexane extract of P. watsonii was further subjected to bioassay-guided fractionation and yielded 10 fractions (PW-1→PW-10). PW-4→PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1→PPWH-8). PPWH-7 possessed greatest cytotoxicity (IC(50) values ranged from 0.66-0.83 µg/mL) and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with P. watsonii especially with PPWH-7. The study also indicated that P. watsonii extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic P. watsonii was investigated for the first time by bioassay-guided approach. These results demonstrated that P. watsonii selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence, P. watsonii has the potential to be further exploited for the discovery and development of new anti cancer drugs.
Effect of extracts from Phyllanthus watsonii Airy Shaw on cell apoptosis in cultured human breast cancer MCF-7 cells

Ramasamy S, Abdul Wahab N, Zainal Abidin N, Manickam S

Exp. Toxicol. Pathol., 2013 Mar;65(3):341-9.
PMID: 22217449 DOI: 10.1016/j.etp.2011.11.005

Species of Phyllanthus have traditionally been used for hundreds of years for treating many ailments including diabetes, anemia, bronchitis and hepatitis. The present study aims to investigate the cytotoxic and apoptotic effects of methanol (PWM), hexane (PWH) and ethyl acetate (PWE) extracts from the leaves of the endemic plant Phyllanthus watsonii Airy Shaw (Phyllanthaceae) on MCF-7 human breast cancer cells. We observed that the PWM, PWH and PWE extracts were cytotoxic and selectively inhibited the growth and proliferation of MCF-7 cells compared to untreated control in a dose dependent manner with an IC(50) of 12.7 ± 4.65, 7.9 ± 0.60 and 7.7 ± 0.29 μg/ml, respectively. However, the extracts were not toxic at these concentrations to normal human lung fibroblast MRC-5 cells. Cell death induced by PWM, PWH and PWE extracts were mainly due to apoptosis which was characterized by apoptotic morphological changes and a nuclear DNA fragmentation. Caspase-3 activation following P. watsonii extracts treatment was also evident for apoptotic cell death which was preceded by an S phase cell cycle perturbation. The results suggested that the cytotoxic activity of P. watsonii extracts was related to an early event of cell cycle perturbation and a later event of apoptosis. Hence, P. watsonii displays potential to be further exploited in the discovery and development of new anticancer agents.
Fulltext Leptospermum flavescens Constituent-LF1 Causes Cell Death through the Induction of Cell Cycle Arrest and Apoptosis in Human Lung Carcinoma Cells

Navanesan S, Abdul Wahab N, Manickam S, Sim KS

PLoS One, 2015;10(8):e0135995.
PMID: 26287817 DOI: 10.1371/journal.pone.0135995

Leptospermum flavescens Sm. (Myrtaceae), locally known as 'Senna makki' is a smallish tree that is widespread and recorded to naturally occur in the montane regions above 900 m a.s.l from Burma to Australia. Although the species is recorded to be used traditionally to treat various ailments, there is limited data on biological and chemical investigations of L. flavescens. The aim of the present study was to investigate and understand the ability of L. flavescens in inducing cell death in lung cancer cells. The cytotoxic potentials of the extraction yields (methanol, hexane, ethyl acetate and water extracts as wells as a semi pure fraction, LF1) were evaluated against two human non-small cell lung carcinoma cell lines (A549 and NCI-H1299) using the MTT assay. LF1 showed the greatest cytotoxic effect against both cell lines with IC50 values of 7.12 ± 0.07 and 9.62 ± 0.50 μg/ml respectively. LF1 treated cells showed a sub-G1 region in the cell cycle analysis and also caused the presence of apoptotic morphologies in cells stained with acridine orange and ethidium bromide. Treatment with LF1 manifested an apoptotic population in cells that were evaluated using the Annexin V/ propidium iodide assay. Increasing dosage of LF1 caused a rise in the presence of activated caspase-3 enzymes in treated cells. Blockage of cell cycle progression was also observed in LF1-treated cells. These findings suggest that LF1 induces apoptosis and cell cycle arrest in treated lung cancer cells. Further studies are being conducted to isolate and identify the active compound as well to better understand the mechanism involved in inducing cell death.
Well-being and needs of Malay carers of people with mental illness in Singapore

Poon AWC, Abdul Wahab N, Salim R, Ow R

Health Soc Care Community, 2021 01;29(1):164-174.
PMID: 32619086 DOI: 10.1111/hsc.13079

Despite the importance of carers supporting the lives of people with mental illness, there are limited studies investigating the well-being and needs of Malay carers in multicultural Singapore. The Malays consist of 13.4% of Singapore's population. A mixed methods qualitative dominant research approach was used to explore the well-being and needs of Malay carers in a voluntary welfare organisation. The Kessler-10, Friendship Scale and Carers' and Users' Expectations of Services-Carer version were used to assess the needs and well-being of 17 Malay carers. Findings show that Malay carers experienced poor well-being and had numerous unmet needs. Four main themes were found: (a) Concerns related to relatives with mental illness, (b) Mental health practices related to carers, (c) Holistic support for carers and (d) Preference for greater spiritual support in mental health. Recovery-oriented mental health practice implications are discussed. Spirituality of Malay carers needs to be given greater consideration in recovery-oriented mental health services.
Fulltext In Vitro Morphological Assessment of Apoptosis Induced by Antiproliferative Constituents from the Rhizomes of Curcuma zedoaria

Syed Abdul Rahman SN, Abdul Wahab N, Abd Malek SN

Evid Based Complement Alternat Med, 2013;2013:257108.
PMID: 23762112 DOI: 10.1155/2013/257108

Bioassay-guided isolation of the active hexane fractions of Curcuma zedoaria led to the identification of five pure compounds, namely, curzerenone (1), neocurdione (2), curdione (3), alismol (4), and zederone (5) and a mixture of sterols, namely, campesterol (6), stigmasterol (7), and β -sitosterol (8). Alismol has never been reported to be present in Curcuma zedoaria. All isolated compounds except (3) were evaluated for their cytotoxic activity against MCF-7, Ca Ski, and HCT-116 cancer cell lines and noncancer human fibroblast cell line (MRC-5) using neutral red cytotoxicity assay. Curzerenone and alismol significantly inhibited cell proliferation in human cancer cell lines MCF-7, Ca Ski, and HCT-116 in a dose-dependent manner. Cytological observations by an inverted phase contrast microscope and Hoechst 33342/PI dual-staining assay showed typical apoptotic morphology of cancer cells upon treatment with curzerenone and alismol. Both compounds induce apoptosis through the activation of caspase-3. It can thus be suggested that curzerenone and alismol are modulated by apoptosis via caspase-3 signalling pathway. The findings of the present study support the use of Curcuma zedoaria rhizomes in traditional medicine for the treatment of cancer-related diseases. Thus, two naturally occurring sesquiterpenoids, curzerenone and alismol, hold great promise for use in chemopreventive and chemotherapeutic strategies.
Phytochemical investigation of Gynura bicolor leaves and cytotoxicity evaluation of the chemical constituents against HCT 116 cells

Teoh WY, Tan HP, Ling SK, Abdul Wahab N, Sim KS

Nat Prod Res, 2016;30(4):448-51.
PMID: 25738869 DOI: 10.1080/14786419.2015.1017726

Gynura bicolor (Compositae) is a popular vegetable in Asia and believed to confer a wide range of benefits including anti-cancer. Our previous findings showed that the ethyl acetate extract of G. bicolor possessed cytotoxicity and induced apoptotic and necrotic cell death in human colon carcinoma cells (HCT 116). A combination of column chromatography had been used to purify chemical constituents from the ethyl acetate and water extract of G. bicolor leaves. Eight chemical constituents 5-p-trans-coumaroylquinic acid (I), 4-hydroxybenzoic acid (II), rutin (III), kampferol-3-O-rutinoside (IV), 3,5-dicaffeoylquinic acid (V), kampferol-3-O-glucoside (VI), guanosine (VII) and chlorogenic acid (VIII) were isolated from G. bicolor grown in Malaysia. To our best knowledge, all chemical constituents were isolated for the first time from G. bicolor leaves except rutin (III). 3,5-dicaffeoylquinic acid (V), guanosine (VII) and chlorogenic acid (VIII) demonstrated selective cytotoxicity (selective index>3) against HCT 116 cancer cells compared to CCD-18Co human normal colon cells.
Nutritional values and bioactive components of under-utilised vegetables consumed by indigenous people in Malaysia

Abdul Wahab N, Ahdan R, Ahmad Aufa Z, Kong KW, Johar MH, Shariff Mohd Z, et al.

J Sci Food Agric, 2015 Oct;95(13):2704-11.
PMID: 25410129 DOI: 10.1002/jsfa.7006

Diverse plants species in the forest remain under-utilised and they are mainly consumed only by local people. However, increasing issues in food security prompted the present study, which explores the nutritional and antioxidant aspects of Malaysian under-utilised vegetables. The studied vegetables were Paku Nyai (Stenochlaena palustris), Cemperai (Champereia manillana), Maman Pasir (Cleome viscose), Dudung (Erechtites valerianifolia) and Semambuk (Ardisia pendula).
Fulltext Corn Starch (Zea mays) Biopolymer Plastic Reaction in Combination with Sorbitol and Glycerol

Hazrol MD, Sapuan SM, Zainudin ES, Zuhri MYM, Abdul Wahab NI

Polymers (Basel), 2021 Jan 12;13(2).
PMID: 33445740 DOI: 10.3390/polym13020242

The research included corn starch (CS) films using sorbitol (S), glycerol (G), and their combination (SG) as plasticizers at 30, 45, and 60 wt %, with a traditional solution casting technique. The introduction of plasticizer to CS film-forming solutions led to solving the fragility and brittleness of CS films. The increased concentration of plasticizers contributed to an improvement in film thickness, weight, and humidity. Conversely, plasticized films reduced their density and water absorption, with increasing plasticizer concentrations. The increase in the amount of the plasticizer from 30 to 60% showed a lower impact on the moisture content and water absorption of S-plasticized films. The S30-plasticized films also showed outstanding mechanical properties with 13.62 MPa and 495.97 MPa, for tensile stress and tensile modulus, respectively. Glycerol and-sorbitol/glycerol plasticizer (G and SG) films showed higher moisture content and water absorption relative to S-plasticized films. This study has shown that the amount and type of plasticizers significantly affect the appearances, physical, morphological, and mechanical properties of the corn starch biopolymer plastic.
Intrinsic capabilities of Leptospermum javanicum in inducing apoptosis and suppressing the metastatic potential of human lung carcinoma cells

Navanesan S, Abdul Wahab N, Manickam S, Cheow YL, Sim KS

Chem Biol Interact, 2017 Aug 01;273:37-47.
PMID: 28578903 DOI: 10.1016/j.cbi.2017.05.022

The active isolate of LF1 in Leptospermum javanicum was further looked into its capabilities in provoking an apoptotic reaction and suppressing the metastasis process in treated non-small lung cancer cells. LF1 underwent isolation and purification to yield a white powder which was identified as Betulinic acid (BA) via NMR, LCMS and IR spectroscopy. The isolate, BA, which produced an encouraging cytotoxic effect against non-small lung cancer cells (A549 and NCI-H1299) through the MTT assay, was further assessed with TUNEL, Sub-G1 population quantification, acridine orange/ethidium bromide staining as well as activated caspase-3 detection. The results pointed towards the induction of apoptosis as a result of increasing doses of BA, regardless of the p53 status in both cell lines. Treatment with BA also prevented an effective attachment of the invasive A549 cells onto a new culture surface in addition to diminishing the migratory potential of treated cells across a porous membrane. Further investigation through the ELISA detection and gelatin zymography showed an adverse effect to production of matrix metalloproteinase-2 (MMP-2) while the levels of matrix metalloproteinase-9 (MMP-9) were not negatively affected. The findings from this study validate the potential of L. javanicum as a potential anti-cancer treatment as stated in our previous study. The isolate, BA not only showed a capacity in inducing apoptotic cell death in non-small lung cancer cells, but managed to distort the ability of the cancer cells in effectively undergoing the metastasis process.
Fulltext Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3'-Untranslated Region of DLC1

Ankasha SJ, Shafiee MN, Abdul Wahab N, Raja Ali RA, Mokhtar NM

Int J Environ Res Public Health, 2021 05 27;18(11).
PMID: 34071861 DOI: 10.3390/ijerph18115741

High-grade serous ovarian cancer (HGSC) is the most common ovarian cancer with highly metastatic properties. A small non-coding RNA, microRNA (miRNA) was discovered to be a major regulator in many types of cancers through binding at the 3'-untranslated region (3'UTR), leading to degradation of the mRNA. In this study, we sought to investigate the underlying mechanisms involved in the dysregulation of miR-200c-3p in HGSC progression and metastasis. We identified the upregulation of miR-200c-3p expression in different stages of HGSC clinical samples and the downregulation of the tumor suppressor gene, Deleted in Liver Cancer 1 (DLC1), expression. Over expression of miR-200c-3p in HGSC cell lines downregulated DLC1 but upregulated the epithelial marker, E-cadherin (CDH1). Based on in silico analysis, two putative binding sites were found within the 3'UTR of DLC1, and we confirmed the direct binding of miR-200c-3p to the target binding motif at position 1488-1495 bp of 3'UTR of DLC1 by luciferase reporter assay in a SKOV3 cell line co-transfected with vectors and miR-200c-3p mimic. These data showed that miR-200c-3p regulated the progression of HGSC by regulating DLC1 expression post-transcription and can be considered as a promising target for therapeutic purposes.
Fulltext Support Vector Regression Modelling of an Aerobic Granular Sludge in Sequential Batch Reactor

Ahmad Yasmin NS, Abdul Wahab N, Ismail FS, Musa MJ, Halim MHA, Anuar AN

Membranes (Basel), 2021 Jul 22;11(8).
PMID: 34436317 DOI: 10.3390/membranes11080554

Support vector regression (SVR) models have been designed to predict the concentration of chemical oxygen demand in sequential batch reactors under high temperatures. The complex internal interaction between the sludge characteristics and their influent were used to develop the models. The prediction becomes harder when dealing with a limited dataset due to the limitation of the experimental works. A radial basis function algorithm with selected kernel parameters of cost and gamma was used to developed SVR models. The kernel parameters were selected by using a grid search method and were further optimized by using particle swarm optimization and genetic algorithm. The SVR models were then compared with an artificial neural network. The prediction results R2 were within >90% for all predicted concentration of COD. The results showed the potential of SVR for simulating the complex aerobic granulation process and providing an excellent tool to help predict the behaviour in aerobic granular reactors of wastewater treatment.
Fulltext Salivary aquaporin-3 as a screening biomarker for xerostomia in patients with periodontal disease and the effects of xerostomia on oral health-related quality of life

Atif S, Abdul Wahab N, Ghafoor S, Azlina A, Tauseef A, Rana S, et al.

PLoS One, 2023;18(4):e0283995.
PMID: 37027451 DOI: 10.1371/journal.pone.0283995

Xerostomia is a subjective condition of dryness of the oral cavity that may lead to several oral problems deteriorating oral health-related quality of life. This study aimed to (1) determine the prevalence of xerostomia, (2) compare the general health status, unstimulated salivary flow rate, and oral health-related quality of life in xerostomics and non-xerostomics, and (3) investigate the potential of salivary aquaporin-3 (AQP-3) as a screening biomarker for xerostomia in patients with periodontal disease. Demographics and systemic health data were collected from 109 healthy participants, 20 to 55 years old, with Community Periodontal Index (CPI) score ≥ 3. For subjective assessment of xerostomia, Shortened Xerostomia Inventory (SXI) was used. For objective assessment of xerostomia, unstimulated salivary flow rate was measured. Shortened Oral Health Impact Profile (S-OHIP) was utilized for oral health-related quality of life assessment. The collected saliva samples were processed and stored at -80°C. Quantification of salivary AQP-3 protein was done with enzyme-linked immunosorbent assay. Xerostomia was reported in 78% of the subjects based on SXI score. Median concentration of AQP-3 was significantly higher in xerostomics compared to non-xerostomics, p = 0.001. Moreover, oral health-related quality of life was significantly poor in xerostomics compared to non-xerostomics, p = 0.002. Furthermore, there were significant correlations between AQP-3 and SXI (r = 0.21, p = 0.025), AQP-3 and S-OHIP (r = 0.2, p = 0.042), S-OHIP and SXI (r = 0.37, p < 0.001), unstimulated salivary flow rate and random blood glucose level (r = 0.32, p = 0.001), and body mass index and mean arterial pressure (r = 0.44, p < 0.001). Regression analysis showed that body mass index, CPI score 3, and salivary AQP-3 were suitable predictors for presence of xerostomia. AQP-3 could be a potential screening biomarker for xerostomia in patients with periodontal disease for its early identification may help improve oral health-related quality of life of the individuals.
A randomized, double-blinded, placebo-controlled clinical trial on Lactobacillus-containing cultured milk drink as adjuvant therapy for depression in irritable bowel syndrome

Sarkawi M, Raja Ali RA, Abdul Wahab N, Abdul Rathi ND, Mokhtar NM

Sci Rep, 2024 Apr 25;14(1):9478.
PMID: 38658619 DOI: 10.1038/s41598-024-60029-2

Irritable bowel syndrome (IBS) is frequently linked with coexisting mental illnesses. Our previous study discovered that 32.1% of IBS patients had subthreshold depression (SD), placing them at higher risk of developing major depression. Gut microbiota modulation through psychobiotics was found to influence depression via the gut-brain axis. However, the efficacy of lessening depression among IBS patients remains ambiguous. The study's aim was to investigate the roles of cultured milk drinks containing 109 cfu Lactobacillus acidophilus LA-5 and Lactobacillus paracasei L. CASEI-01 on depression and related variables among IBS participants with SD. A total of 110 IBS participants with normal mood (NM) and SD, were randomly assigned to one of four intervention groups: IBS-NM with placebo, IBS-NM with probiotic, IBS-SD with placebo, and IBS-SD with probiotic. Each participant was required to consume two bottles of cultured milk every day for a duration of 12 weeks. The following outcomes were assessed: depression risk, quality of life, the severity of IBS, and hormonal changes. The depression scores were significantly reduced in IBS-SD with probiotic and placebo from baseline (p
Fulltext Antioxidant Capacity, Cytotoxicity, and Acute Oral Toxicity of Gynura bicolor

Teoh WY, Sim KS, Moses Richardson JS, Abdul Wahab N, Hoe SZ

Evid Based Complement Alternat Med, 2013;2013:958407.
PMID: 24369485 DOI: 10.1155/2013/958407

Gynura bicolor (Compositae) which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water) of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116), one human breast adenocarcinoma cell line (MCF7), and one human normal colon cell line (CCD-18Co) were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay), possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor.
Fulltext Ethanol-Induced Changes in PKCε: From Cell to Behavior

Pakri Mohamed RM, Mokhtar MH, Yap E, Hanim A, Abdul Wahab N, Jaffar FHF, et al.

Front Neurosci, 2018;12:244.
PMID: 29706864 DOI: 10.3389/fnins.2018.00244

The long-term binge intake of ethanol causes neuroadaptive changes that lead to drinkers requiring higher amounts of ethanol to experience its effects. This neuroadaptation can be partly attributed to the modulation of numerous neurotransmitter receptors by the various protein kinases C (PKCs). PKCs are enzymes that control cellular activities by regulating other proteins via phosphorylation. Among the various isoforms of PKC, PKCε is the most implicated in ethanol-induced biochemical and behavioral changes. Ethanol exposure causes changes to PKCε expression and localization in various brain regions that mediate addiction-favoring plasticity. Ethanol works in conjunction with numerous upstream kinases and second messenger activators to affect cellular PKCε expression. Chauffeur proteins, such as receptors for activated C kinase (RACKs), cause the translocation of PKCε to aberrant sites and mediate ethanol-induced changes. In this article, we aim to review the following: the general structure and function of PKCε, ethanol-induced changes in PKCε expression, the regulation of ethanol-induced PKCε activities in DAG-dependent and DAG-independent environments, the mechanisms underlying PKCε-RACKε translocation in the presence of ethanol, and the existing literature on the role of PKCε in ethanol-induced neurobehavioral changes, with the goal of creating a working model upon which further research can build.
Fulltext Cytotoxic constituents from the rhizomes of Curcuma zedoaria

Ahmed Hamdi OA, Syed Abdul Rahman SN, Awang K, Abdul Wahab N, Looi CY, Thomas NF, et al.

ScientificWorldJournal, 2014;2014:321943.
PMID: 25126594 DOI: 10.1155/2014/321943

Curcuma zedoaria also known as Temu putih is traditionally used in food preparations and treatment of various ailments including cancer. The cytotoxic activity of hexane, dichloromethane, ethyl acetate, methanol, and the methanol-soxhlet extracts of Curcuma zedoaria rhizomes was tested on two human cancer cell lines (Ca Ski and MCF-7) and a noncancer cell line (HUVEC) using MTT assay. Investigation on the chemical components in the hexane and dichloromethane fractions gave 19 compounds, namely, labda-8(17),12 diene-15,16 dial (1), dehydrocurdione (2), curcumenone (3), comosone II (4), curcumenol (5), procurcumenol (6), germacrone (7), zerumbone epoxide (8), zederone (9), 9-isopropylidene-2,6-dimethyl-11-oxatricyclo[6.2.1.0(1,5)]undec-6-en-8-ol (10), furanodiene (11), germacrone-4,5-epoxide (12), calcaratarin A (13), isoprocurcumenol (14), germacrone-1,10-epoxide (15), zerumin A (16), curcumanolide A (17), curcuzedoalide (18), and gweicurculactone (19). Compounds (1-19) were evaluated for their antiproliferative effect using MTT assay against four cancer cell lines (Ca Ski, MCF-7, PC-3, and HT-29). Curcumenone (3) and curcumenol (5) displayed strong antiproliferative activity (IC50 = 8.3 ± 1.0 and 9.3 ± 0.3 μg/mL, resp.) and were found to induce apoptotic cell death on MCF-7 cells using phase contrast and Hoechst 33342/PI double-staining assay. Thus, the present study provides basis for the ethnomedical application of Curcuma zedoaria in the treatment of breast cancer.
Factors associated with ultrasound-guided water enema reduction for pediatric intussusception in resource-limited setting: potential predictive role of thrombocytosis and anemia

Lim RZM, Lee T, Ng JYZ, Quek KF, Abdul Wahab N, Amansah SL, et al.

J Pediatr Surg, 2018 Nov;53(11):2312-2317.
PMID: 29459045 DOI: 10.1016/j.jpedsurg.2018.01.004

BACKGROUND/PURPOSE: Although ultrasound-guided hydrostatic reduction (USGHR) is increasingly used in managing pediatric intussusception, there is limited literature concerning its use in Malaysia. We aim to examine the experience and factors associated with the effectiveness of USGHR using water.
METHODS: This is a single-center retrospective observational study in a Malaysian tertiary referral center. Children with intussusception admitted between year 2012 and 2016 were included and medical records reviewed. Factors associated with success or failure of USGHR were identified using multivariable logistic regression.
RESULTS: Of the 172 cases included, 151 cases (87.8%) underwent USGHR, of whom 129 cases were successfully reduced (success rate of 85.4%). One perforation (0.7%) was reported. Age more than 3years old (aOR=7.16; 95% CI=1.07-47.94; p=0.042), anemia (aOR=10.12; 95% CI=1.12-91.35; p=0.039), thrombocytosis (aOR=11.21; 95% CI=2.06-64.33; p=0.005) and ultrasound findings of free fluid (aOR=9.39; 95% CI=1.62-54.38; p=0.012) and left-sided intussusception (aOR=8.18;95% CI=1.22-54.90, p=0.031) were independently associated with USGHR irreducibility. Symptom duration, blood in stool, vomiting and other clinical presentations, however, showed no association.
CONCLUSIONS: USGHR with water is effective in the non-operative management of pediatric intussusception. Prolonged symptom duration need not necessarily preclude USGHR. The findings of anemia and thrombocytosis as independent predictors of USGHR irreducibility deserve further study.
TYPE OF STUDY: Treatment study LEVEL OF EVIDENCE: III.
Assessing the efficacy of tocotrienol-rich fraction vitamin E in obese children with non-alcoholic fatty liver disease: a single-blind, randomized clinical trial

Al-Baiaty FDR, Ishak S, Mohd Zaki F, Masra F, Abdul Aziz DA, Wan Md Zin WN, et al.

BMC Pediatr, 2024 Aug 20;24(1):529.
PMID: 39160468 DOI: 10.1186/s12887-024-04993-8

BACKGROUND: Childhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD.
METHODS: A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored.
RESULTS: APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045).
CONCLUSION: The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children.
TRIAL REGISTRATION: The study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023).

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