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  1. Detecting adulteration of stingless bee honey using untargeted 1H NMR metabolomics with chemometrics
    Yong CH, Muhammad SA, Aziz FA, Nasir FI, Mustafa MZ, Ibrahim B, et al.
    Food Chem, 2021 Aug 09;368:130808.
    PMID: 34419793 DOI: 10.1016/j.foodchem.2021.130808
    As stingless bee honey (SBH) is gaining in popularity in the Malaysian market, it is now prone to adulteration. The higher price of SBH compared to floral honey has led to the use of unusual adulterants such as vinegar and even floral honey to mimic the unique taste and appearance of SBH. Since the current AOAC 998.12 method fails to detect these adulterants as their δ13C values are in the range for C3 plants, untargeted 1H NMR metabolomics was proposed. Principal component analysis of SBH 1H NMR fingerprints was able to distinguish authentic SBHs from adulterated ones down to 1% adulteration level for selected adulterants. Discriminant analysis showed promising results in distinguishing the preliminary datasets of authentic SBHs from the adulterated ones, including discriminating SBHs adulterated with different adulterants derived from C3 and C4 plants. Hence, to assure any emerging adulterant can be detected, all 1H NMR regions should be considered.
  2. Fulltext Insights into Alexandrium minutum Nutrient Acquisition, Metabolism and Saxitoxin Biosynthesis through Comprehensive Transcriptome Survey
    Akbar MA, Yusof NYM, Sahrani FK, Usup G, Ahmad A, Baharum SN, et al.
    Biology (Basel), 2021 Aug 25;10(9).
    PMID: 34571703 DOI: 10.3390/biology10090826
    The toxin-producing dinoflagellate Alexandrium minutum is responsible for the outbreaks of harmful algae bloom (HABs). It is a widely distributed species and is responsible for producing paralytic shellfish poisoning toxins. However, the information associated with the environmental adaptation pathway and toxin biosynthesis in this species is still lacking. Therefore, this study focuses on the functional characterization of A. minutum unigenes obtained from transcriptome sequencing using the Illumina Hiseq 4000 sequencing platform. A total of 58,802 (47.05%) unigenes were successfully annotated using public databases such as NCBI-Nr, UniprotKB, EggNOG, KEGG, InterPRO and Gene Ontology (GO). This study has successfully identified key features that enable A. minutum to adapt to the marine environment, including several carbon metabolic pathways, assimilation of various sources of nitrogen and phosphorus. A. minutum was found to encode homologues for several proteins involved in saxitoxin biosynthesis, including the first three proteins in the pathway of saxitoxin biosynthesis, namely sxtA, sxtG and sxtB. The comprehensive transcriptome analysis presented in this study represents a valuable resource for understanding the dinoflagellates molecular metabolic model regarding nutrient acquisition and biosynthesis of saxitoxin.
  3. Fulltext Optical pH Sensor Based on Immobilization Anthocyanin from Dioscorea alata L. onto Polyelectrolyte Complex Pectin-Chitosan Membrane for a Determination Method of Salivary pH
    Safitri E, Humaira H, Murniana M, Nazaruddin N, Iqhrammullah M, Md Sani ND, et al.
    Polymers (Basel), 2021 Apr 14;13(8).
    PMID: 33919956 DOI: 10.3390/polym13081276
    A simple optical pH sensor based on immobilization, Dioscorea alata L. anthocyanin methanol extract, onto a pectin-chitosan polyelectrolyte complex (pectin-chitosan PEC), has been successfully fabricated. The optical pH sensor was manufactured as a membrane made of pectin-chitosan PEC and the extracted anthocyanin. This sensor has the highest sensitivity of anthocyanin content at 0.025 mg/L in phosphate buffer and 0.0375 mg/L in citrate buffer. It also has good reproducibility with a relative standard deviation (%RSD) of 7.7%, and gives a stable response at time values greater than 5 min from exposure in a buffer solution, and the sensor can be utilized within five days from its synthesis. This optical pH sensor has been employed to determine saliva pH of people of different ages and showed no significant difference when compared to a potentiometric method.
  4. Genome-wide screening of vaccine targets prioritization and reverse vaccinology aided design of peptides vaccine to enforce humoral immune response against Campylobacter jejuni
    Zeb A, Ali SS, Azad AK, Safdar M, Anwar Z, Suleman M, et al.
    Comput Biol Med, 2021 06;133:104412.
    PMID: 33934066 DOI: 10.1016/j.compbiomed.2021.104412
    Campylobacter jejuni, gram-negative bacteria, is an infectious agent of foodborne disease-causing bloody diarrhea, abdominal pain, fever, Guillain-Barré syndrome (GBS) and Miller Fisher syndrome in humans. Campylobacter spp. with multidrug resistance to fluoroquinolones, tetracycline, and erythromycin are reported. Hence, an effective vaccine candidate would provide long-term immunity against C. jejuni infections. Thus, we used a subtractive proteomics pipeline to prioritize essential proteins, which impart a critical role in virulence, replication and survival. Five proteins, i.e. Single-stranded DNA-binding protein, UPF0324 membrane protein Cj0999c, DNA translocase FtsK, 50S ribosomal protein L22, and 50S ribosomal protein L1 were identified as virulent proteins and selected for vaccine designing. We reported that the multi-epitopes subunit vaccine based on CTL, HTL and B-cell epitopes combination possess strong antigenic properties and associates no allergenic reaction. Further investigation revealed that the vaccine interacts with the immune receptor (TLR-4) and triggered the release of primary and secondary immune factors. Moreover, the CAI and GC contents obtained through codon optimization were reported to be 0.93 and 53% that confirmed a high expression in the selected vector. The vaccine designed in this study needs further scientific consensus and will aid in managing C. jejuni infections.
  5. Fulltext Synergistic effects of Cu-doped ZnO nanoantibiotic against Gram-positive bacterial strains
    Khalid A, Ahmad P, Alharthi AI, Muhammad S, Khandaker MU, Faruque MRI, et al.
    PLoS One, 2021;16(5):e0251082.
    PMID: 33989295 DOI: 10.1371/journal.pone.0251082
    A viable hydrothermal technique has been explored for the synthesis of copper doped Zinc oxide nanoparticles (Cu-doped ZnO-NPs) based on the precursor's mixture of Copper-II chloride dihydrate (CuCl2.2H2O), Zinc chloride (ZnCl2), and potassium hydroxide (KOH). X-ray diffraction (XRD) reported the hexagonal wurtzite structure of the synthesized Cu-doped ZnO-NPs. The surface morphology is checked via field emission scanning electron microscopy (FE-SEM), whereas, the elemental compositions of the samples were confirmed by Raman, and X-ray photoelectron spectroscopy (XPS), respectively. The as-obtained ZnO-NPs and Cu-doped ZnO-NPs were then tested for their antibacterial activity against clinical isolates of Gram-positive (Staphylococcus aureus, Streptococcus pyogenes) and Gram-negative (Escherichia coli, Klebsiella pneumonia) bacteria via agar well diffusion method. The zone of inhibition (ZOI) for Cu-doped ZnO-NPs was found to be 24 and 19 mm against S. Aureus and S. pyogenes, and 18 and 11 mm against E. coli and K. pneumoniae, respectively. The synthesized Cu-doped ZnO-NPs can thus be found as a potential nano antibiotic against Gram-positive multi-drug resistant bacterial strains.
  6. N-([1,1'-biaryl]-4-yl)-1-naphthamide-based scaffolds synthesis, their cheminformatics analyses, and screening as bacterial biofilm inhibitor
    Ejaz S, Zubair M, Rasool N, Ahmed F, Bilal M, Ahmad G, et al.
    J Basic Microbiol, 2021 Nov 01.
    PMID: 34724237 DOI: 10.1002/jobm.202100288
    Naphthamides have pharmacological potential as they express strong activities against microorganisms. The commercially available naphthoyl chloride and 4-bromoaniline were condensed in dry dichloromethane (DCM) in the presence of Et3 N to form N-(4-bromophenyl)-1-naphthamide (86%) (3). Using a Pd(0) catalyzed Suzuki-Miyaura Cross-Coupling reaction of (3) and various boronic acids, a series of N-([1,1'-biaryl]-4-yl)-1-naphthamide derivatives (4a-h) were synthesized in moderate to good yields. The synthesized derivatives were evaluated for cytotoxicity haemolytic assay and biofilm inhibition activity through in silico and in vitro studies. Molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity risk, and other cheminformatics predict synthesized molecules as biologically active moieties, further validated through in vitro studies in which compounds (4c) and (4f) showed significant haemolytic activity whereas (4e) exhibited an efficient biofilm inhibition activity against Gram-negative bacteria Escherichia coli and Gram-positive bacteria Bacillus subtilis. When forming biofilms, bacteria become resistant to various antimicrobial treatments. Currently, research is focused on the development of agents that inhibit biofilm formation, thus the present work is valuable for preventing future drug resistance.
  7. Fulltext Degradation of Perovskite Thin Films and Solar Cells with Candle Soot C/Ag Electrode Exposed in a Control Ambient
    Islam MA, Mohafez H, Sobayel K, Wan Muhamad Hatta SF, Hasan AKM, Khandaker MU, et al.
    Nanomaterials (Basel), 2021 Dec 20;11(12).
    PMID: 34947812 DOI: 10.3390/nano11123463
    Perovskite solar cells (PSCs) have already achieved efficiencies of over 25%; however, their instability and degradation in the operational environment have prevented them from becoming commercially viable. Understanding the degradation mechanism, as well as improving the fabrication technique for achieving high-quality perovskite films, is crucial to overcoming these shortcomings. In this study, we investigated details in the changes of physical properties associated with the degradation and/or decomposition of perovskite films and solar cells using XRD, FESEM, EDX, UV-Vis, Hall-effect, and current-voltage (I-V) measurement techniques. The dissociation, as well as the intensity of perovskite peaks, have been observed as an impact of film degradation by humidity. The decomposition rate of perovskite film has been estimated from the structural and optical changes. The performance degradation of novel planner structure PSCs has been investigated in detail. The PSCs were fabricated in-room ambient using candle soot carbon and screen-printed Ag electrode. It was found that until the perovskite film decomposed by 30%, the film properties and cell efficiency remained stable.
  8. Fulltext Development of Nonlaboratory-Based Risk Prediction Models for Cardiovascular Diseases Using Conventional and Machine Learning Approaches
    Sajid MR, Almehmadi BA, Sami W, Alzahrani MK, Muhammad N, Chesneau C, et al.
    Int J Environ Res Public Health, 2021 11 29;18(23).
    PMID: 34886312 DOI: 10.3390/ijerph182312586
    Criticism of the implementation of existing risk prediction models (RPMs) for cardiovascular diseases (CVDs) in new populations motivates researchers to develop regional models. The predominant usage of laboratory features in these RPMs is also causing reproducibility issues in low-middle-income countries (LMICs). Further, conventional logistic regression analysis (LRA) does not consider non-linear associations and interaction terms in developing these RPMs, which might oversimplify the phenomenon. This study aims to develop alternative machine learning (ML)-based RPMs that may perform better at predicting CVD status using nonlaboratory features in comparison to conventional RPMs. The data was based on a case-control study conducted at the Punjab Institute of Cardiology, Pakistan. Data from 460 subjects, aged between 30 and 76 years, with (1:1) gender-based matching, was collected. We tested various ML models to identify the best model/models considering LRA as a baseline RPM. An artificial neural network and a linear support vector machine outperformed the conventional RPM in the majority of performance matrices. The predictive accuracies of the best performed ML-based RPMs were between 80.86 and 81.09% and were found to be higher than 79.56% for the baseline RPM. The discriminating capabilities of the ML-based RPMs were also comparable to baseline RPMs. Further, ML-based RPMs identified substantially different orders of features as compared to baseline RPM. This study concludes that nonlaboratory feature-based RPMs can be a good choice for early risk assessment of CVDs in LMICs. ML-based RPMs can identify better order of features as compared to the conventional approach, which subsequently provided models with improved prognostic capabilities.
  9. Malignant Transformation of Juvenile Recurrent Respiratory Papillomatosis
    Muhammad Fauzi HG, Mohan Singh AS, Abdul Rahim S, Chooi LL, Ramasamy V, Mohamad Pakarul Razy NH, et al.
    Gulf J Oncolog, 2021 May;1(36):79-81.
    PMID: 35017141
    Malignant transformation of recurrent respiratory papillomatosis (RRP) is a rare entity occurring in only less than 5% of patients with RRP. The risk of transformation can arise even in the absence of risk factors such as smoking and radiation. We describe a patient with juvenile RRP diagnosed since childhood, who suffered malignant transformation into a squamous cell carcinoma after 29 years. Keywords: Recurrent respiratory papillomatosis; laryngeal neoplasms; squamous cell carcinoma; human papilloma-virus.
  10. Fulltext Quality of life of women with breast cancer in a tertiary referral university hospital
    Yusoff J, Ismail A, Abd Manaf MR, Ismail F, Abdullah N, Muhammad R, et al.
    Health Qual Life Outcomes, 2022 Jan 29;20(1):15.
    PMID: 35093066 DOI: 10.1186/s12955-022-01921-1
    BACKGROUND: Quality of life (QoL) is one of the treatment outcome measures in patients with breast cancer. In this study, we measured the QoL of women with breast cancer at Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and identified the associated factors.

    METHODOLOGY: This cross-sectional study was conducted from October 2017 to December 2017 and involved female patients with breast cancer. The QoL scores and domains were determined using the EuroQol EQ-5D-5L, and were presented as the utility value and visual analog scores, respectively.

    RESULTS: We recruited a total of 173 women, aged 33-87 years. The median VA score was 80.00 (interquartile range [IQR] 70.00-90.00); the median utility value was 0.78 (interquartile range [IQR] 0.65-1.00. Women who did not take traditional medicine had a higher utility index score of 0.092 (95% CI 0.014-0.171), and women with household income of RM3000-5000 had a higher utility index score of 0.096 (95% CI 0.011-0.180).

    CONCLUSION: Traditional medicine consumption and household income were significantly associated with lower QoL. The pain/discomfort domain was the worst affected QoL domain and was related to traditional medicine use and household income. Addressing pain management in patients with breast cancer and the other factors contributing to lower QoL may improve the QoL of breast cancer survivors in the future.

  11. Fulltext Urology services in a tertiary hospital: continuing work during the COVID-19 Movement Control Order in Malaysia
    Khor V, Sidhu S, Muhammad Afiq MFO, Pushpanathan M, Fahmy O, Khairul Asri MG, et al.
    Singapore Med J, 2024 Mar 01;65(Suppl 1):S35-S40.
    PMID: 35139632 DOI: 10.11622/smedj.2022008
  12. Fulltext Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats
    Afzan A, Abdullah NR, Halim SZ, Rashid BA, Semail RH, Abdullah N, et al.
    Molecules, 2012 Apr 10;17(4):4326-42.
    PMID: 22491681 DOI: 10.3390/molecules17044326
    Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.
  13. The effects of alpha-tocopherol supplementation on fracture healing in a postmenopausal osteoporotic rat model
    Mohamad S, Shuid AN, Mohamed N, Fadzilah FM, Mokhtar SA, Abdullah S, et al.
    Clinics (Sao Paulo), 2012 Sep;67(9):1077-85.
    PMID: 23018307
    OBJECTIVE: Osteoporosis increases the risk of bone fractures and may impair fracture healing. The aim of this study was to investigate whether alpha-tocopherol can improve the late-phase fracture healing of osteoporotic bones in ovariectomized rats.

    METHOD: In total, 24 female Sprague-Dawley rats were divided into three groups. The first group was sham-operated, and the other two groups were ovariectomized. After two months, the right femora of the rats were fractured under anesthesia and internally repaired with K-wires. The sham-operated and ovariectomized control rat groups were administered olive oil (a vehicle), whereas 60 mg/kg of alpha-tocopherol was administered via oral gavage to the alpha-tocopherol group for six days per week over the course of 8 weeks. The rats were sacrificed, and the femora were dissected out. Computed tomography scans and X-rays were performed to assess fracture healing and callus staging, followed by the assessment of callus strengths through the biomechanical testing of the bones.

    RESULTS: Significantly higher callus volume and callus staging were observed in the ovariectomized control group compared with the sham-operated and alpha-tocopherol groups. The ovariectomized control group also had significantly lower fracture healing scores than the sham-operated group. There were no differences between the alpha-tocopherol and sham-operated groups with respect to the above parameters. The healed femora of the ovariectomized control group demonstrated significantly lower load and strain parameters than the healed femora of the sham-operated group. Alpha-tocopherol supplementation was not able to restore these biomechanical properties.

    CONCLUSION: Alpha-tocopherol supplementation appeared to promote bone fracture healing in osteoporotic rats but failed to restore the strength of the fractured bone.

  14. Fulltext The Effects of Cosmos caudatus on Structural Bone Histomorphometry in Ovariectomized Rats
    Mohamed N, Gwee Sian Khee S, Shuid AN, Muhammad N, Suhaimi F, Othman F, et al.
    Evid Based Complement Alternat Med, 2012;2012:817814.
    PMID: 22924056 DOI: 10.1155/2012/817814
    Osteoporosis is considered a serious debilitating disease. Cosmos caudatus (ulam raja), a plant containing antioxidant compounds and minerals, may be used to treat and prevent osteoporosis. This study determines the effectiveness of C. caudatus as bone protective agent in postmenopausal osteoporosis rat model. Thirty-two female rats, aged 3 months old, were divided into 4 groups. Group one was sham operated (sham) while group two was ovariectomized. These two groups were given ionized water by forced feeding. Groups three and four were ovariectomized and given calcium 1% ad libitum and force-fed with C. caudatus at the dose of 500 mg/kg, respectively. Treatments were given six days per week for a period of eight weeks. Body weight was monitored every week and structural bone histomorphometry analyses of the femur bones were performed. Ovariectomy decreased trabecular bone volume (BV/TV), decreased trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Both calcium 1% and 500 mg/kg C. caudatus reversed the above structural bone histomorphometric parameters to normal level. C. caudatus shows better effect compared to calcium 1% on trabecular number (Tb.N) and trabecular separation (Tb.Sp). Therefore, Cosmos caudatus 500 mg/kg has the potential to act as the therapeutic agent to restore bone damage in postmenopausal women.
  15. Synthesis and structure-activity relationship of thiobarbituric acid derivatives as potent inhibitors of urease
    Khan KM, Rahim F, Khan A, Shabeer M, Hussain S, Rehman W, et al.
    Bioorg Med Chem, 2014 Aug 1;22(15):4119-23.
    PMID: 24986232 DOI: 10.1016/j.bmc.2014.05.057
    A series of thiobarbituric acid derivatives 1-27 were synthesized and evaluated for their urease inhibitory potential. Exciting results were obtained from the screening of these compounds 1-27. Compounds 5, 7, 8, 11, 16, 17, 22, 23 and 24 showed excellent urease inhibition with IC50 values 18.1 ± 0.52, 16.0 ± 0.45, 16.0 ± 0.22, 14.3 ± 0.27, 6.7 ± 0.27, 10.6 ± 0.17, 19.2 ± 0.29, 18.2 ± 0.76 and 1.61 ± 0.18 μM, respectively, much better than the standard urease inhibitor thiourea (IC₅₀=21 ± 0.11 μM). Compound 3, 4, 10, and 26 exhibited comparable activities to the standard with IC₅₀ values 21.4 ± 1.04 and 21.5 ± 0.61 μM, 22.8 ± 0.32, 25.2 ± 0.63, respectively. However the remaining compounds also showed prominent inhibitory potential The structure-activity relationship was established for these compounds. This study identified a novel class of urease inhibitors. The structures of all compounds were confirmed through spectroscopic techniques such as EI-MS and (1)H NMR.
  16. Fulltext Comparison of reduced-intensity and myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia and acute lymphoblastic leukemia: a meta-analysis
    Abdul Wahid SF, Ismail NA, Mohd-Idris MR, Jamaluddin FW, Tumian N, Sze-Wei EY, et al.
    Stem Cells Dev, 2014 Nov 1;23(21):2535-52.
    PMID: 25072307 DOI: 10.1089/scd.2014.0123
    Currently, the indications to perform reduced-intensity conditioning allogeneic hematopoietic stem cell transplant (RIC-HCT) are based on data derived mainly from large registry and single-centre retrospective studies. Thus, at the present time, there is limited direct evidence supporting the current practice in selecting patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) for RIC versus myeloablative conditioning (MAC) transplants. To determine the relationship between dose intensity of conditioning regimen and survival outcomes after allografting in AML/ALL patients, we performed a meta-analysis of 23 clinical trials reported between 1990 and 2013 involving 15,258 adult patients that compare survival outcomes after RIC-HCT versus MAC-HCT. RIC-HCT resulted in comparable <2-year and 2-6 year overall survival (OS) rates post-transplantation even though the RIC-HCT recipients were older and had more active disease than MAC-HCT recipients. The 2-6 year progression-free survival (PFS), nonrelapse mortality, acute graft-versus-host disease (GvHD) and chronic GvHD rates were reduced after RIC-HCT, but relapse rate was increased. Similar outcomes were observed regardless of disease type and status at transplantation. Odds ratio for all outcomes remained comparable with or without performing separate analyses for the year of HCT and for retrospective versus prospective studies. Among RIC-HCT recipients, survival rates were superior if patients were in CR at transplantation. Significant inter-study heterogeneity for aGvHD data and publication bias for PFS data were observed. This meta-analysis showed no OS benefit of MAC-HCT over RIC-HCT across the entire cohort of patients suggesting that RIC-HCT could be an effective therapeutic option for AML/ALL patients who are ineligible for MAC-HCT and CR status is preferred before RIC-HCT.
  17. Fulltext New cholinesterase inhibitory constituents from Lonicera quinquelocularis
    Khan D, Khan HU, Khan F, Khan S, Badshah S, Khan AS, et al.
    PLoS One, 2014;9(4):e94952.
    PMID: 24733024 DOI: 10.1371/journal.pone.0094952
    A phytochemical investigation on the ethyl acetate soluble fraction of Lonicera quinquelocularis (whole plant) led to the first time isolation of one new phthalate; bis(7-acetoxy-2-ethyl-5-methylheptyl) phthalate (3) and two new benzoates; neopentyl-4-ethoxy-3, 5-bis (3-methyl-2-butenyl benzoate (4) and neopentyl-4-hydroxy-3, 5-bis (3-methyl-2-butenyl benzoate (5) along with two known compounds bis (2-ethylhexyl phthalate (1) and dioctyl phthalate (2). Their structures were established on the basis of spectroscopic analysis and by comparison with available data in the literature. All the compounds (1-5) were tested for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in dose dependent manner. The IC50 (50% inhibitory effect) values of compounds 3 and 5 against AChE were 1.65 and 3.43 µM while the values obtained against BChE were 5.98 and 9.84 µM respectively. Compounds 2 and 4 showed weak inhibition profile.
  18. Tumour necrosis factor alpha down-regulates the expression of peroxisome proliferator activated receptor alpha (PPARα) in human hepatocarcinoma HepG2 cells by activation of NF-κB pathway
    Lim WS, Ng DL, Kor SB, Wong HK, Tengku-Muhammad TS, Choo QC, et al.
    Cytokine, 2013 Jan;61(1):266-74.
    PMID: 23141142 DOI: 10.1016/j.cyto.2012.10.007
    Peroxisome proliferator activated receptor-alpha (PPARα) plays a major role in the regulation of lipid and glucose homeostasis, and inflammatory responses. The objectives of the study were to systematically investigate the effects of TNF-α and its regulatory pathway on PPARα expression in HepG2 cells using Real-Time RT-PCR and western blot analysis. Here, TNF-α suppressed PPARα mRNA expression in a dose- and time-dependent manner at the level of gene transcription. Pre-treatment of cells with 10μM of Wedelolactone for 2h was sufficient to restore PPARα expression to basal levels and also affected the expression of PPARα-regulated genes. This study also demonstrated that TNF-α represses PPARα expression by augmenting the activity of canonical NF-κB signalling pathway. This was shown by the abrogation of TNF-α-mediated PPARα down-regulation, after both p65 and p50 were knocked down via siRNA. The IKK contributes to IκBα degradation and mediates inducible phosphorylation of p105 at Ser933. Surprisingly, phosphorylation of p65 at Ser468 and Ser536 were severely abrogated with Wedelolactone inhibition, suggesting that Ser468 and Ser536, but not Ser276, may mediate the TNF-α inhibitory action on PPARα gene expression. These results suggest that TNF-α might, at least in part, suppress PPARα expression through activation of IKK/p50/p105/p65 pathway. Furthermore, phosphorylation of p65 at Ser468 and Ser536 may play a crucial role in the mechanism that limits PPARα production in the human HepG2 cells.
  19. Fulltext Palm tocotrienol supplementation enhanced bone formation in oestrogen-deficient rats
    Soelaiman IN, Ming W, Abu Bakar R, Hashnan NA, Mohd Ali H, Mohamed N, et al.
    Int J Endocrinol, 2012;2012:532862.
    PMID: 23150728 DOI: 10.1155/2012/532862
    Postmenopausal osteoporosis is the commonest cause of osteoporosis. It is associated with increased free radical activity induced by the oestrogen-deficient state. Therefore, supplementation with palm-oil-derived tocotrienols, a potent antioxidant, should be able to prevent this bone loss. Our earlier studies have shown that tocotrienol was able to prevent and even reverse osteoporosis due to various factors, including oestrogen deficiency. In this study we compared the effects of supplementation with palm tocotrienol mixture or calcium on bone biomarkers and bone formation rate in ovariectomised (oestrogen-deficient) female rats. Our results showed that palm tocotrienols significantly increased bone formation in oestrogen-deficient rats, seen by increased double-labeled surface (dLS/Bs), reduced single-labeled surface (sLS/BS), increased mineralizing surface (MS/BS), increased mineral apposition rate (MAR), and an overall increase in bone formation rate (BFR/BS). These effects were not seen in the group supplemented with calcium. However, no significant changes were seen in the serum levels of the bone biomarkers, osteocalcin, and cross-linked C-telopeptide of type I collagen, CTX. In conclusion, palm tocotrienol is more effective than calcium in preventing oestrogen-deficient bone loss. Further studies are needed to determine the potential of tocotrienol as an antiosteoporotic agent.
  20. The effects of piper sarmentosum water extract on the expression and activity of 11β-hydroxysteroid dehydrogenase type 1 in the bones with excessive glucocorticoids
    Suhana Mohd Ramli E, Nirwana Soelaiman I, Othman F, Ahmad F, Nazrun Shuib A, Mohamed N, et al.
    Iran J Med Sci, 2012 Mar;37(1):39-46.
    PMID: 23115429
    BACKGROUND: Long-term glucocorticoid therapy causes secondary osteoporosis leading to pathological fractures. Glucocorticoid action in bone is dependant upon the activity of 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). Piper sarmentosum is a local herb that possesses the ability to inhibit 11-βHSD1 enzyme activity. We aimed to determine the effects of Piper sarmentosum water extract on 11-βHSD1 expressions and activity in the bones of glucocorticoid-treated adrenalectomized rats.

    METHODS: Forty male Sprague-Dawley rats (200-250 g) were used. Twenty-four animals were adrenalectomized and received intramuscular injection of dexamethasone (120 μg/kg/day). They were simultaneously administered with either Piper sarmentosum water extract (125 mg/kg/day), GCA (120 mg/kg/day) or distilled water as vehicle by oral gavage for two months. Eight animals were sham-operated and given vehicle daily, i.e. intramuscular olive oil and oral distilled water.

    RESULTS: Following two months treatment, dexamethasone-treated adrenalectomized rats had significantly lower 11β-HSD1 dehydrogenase activity and higher 11β-HSD1 expression in the femoral bones compared to the sham-operated and baseline group. The rats supplemented with Piper sarmentosum water extract had significantly higher 11β-HSD1 dehydrogenase activity and lower 11β-HSD1 expression in the bones.

    CONCLUSION: The results showed that Piper sarmentosum water extract had the ability to prevent glucocorcoticoid excess in the bones of glucocorticoid-treated adrenalectomized rats through the local modulation of 11β-HSD1 expression and activity, and may be used as prophylaxis for osteoporosis in patients on long-term glucocorticoid treatment.

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