Displaying publications 61 - 80 of 86 in total

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  1. Azlan A, Khor KZ, Rajasegaran Y, Rosli AA, Said MSM, Yusoff NM, et al.
    Med Oncol, 2023 Jun 21;40(7):208.
    PMID: 37341821 DOI: 10.1007/s12032-023-02075-w
    Reactive oxygen species (ROS) homeostasis is crucial for leukaemogenesisand deregulation would hamper leukaemic progression. Although the regulatory effects of RUNX1/ETO has been extensively studied, its underlying molecular mechanims in ROS production in t(8,21) AML is yet to be fully elucidated. Here, we report that RUNX1/ETO could directly control FLT3 by occupying several DNA elements on FLT3 locus. The possible hijacking mechanism by RUNX1/ETO over FLT3 mediated ROS modulation in AML t(8;21) was made apparent when suppression of RUNX1/ETO led to decrement in ROS levels and the direct oxidative marker FOXO3 but not in FLT3 and RAC1 suppressed t(8,21) AML cell line Furthermore, nuclear import of RUNX1/ETO was aberrated following RUNX1/ETO and RAC1 suppression suggesting association in ROS control. A different picture was depicted in non t(8;21) cells where suppression of RAC1 and FLT3 led to decreased levels of FOXO3a and ROS. Results alltogether indicate a possible dysregulation of ROS levels by RUNX1/ETO in t(8,21) AML.
  2. Sultana S, Azlan A, Mohd Desa MN, Mahyudin NA, Anburaj A
    PMID: 38284970 DOI: 10.1080/19440049.2024.2304577
    Regular testing and systematic investigation play a vital role to ensure product safety. Until now, the existing food authentication techniques have been based on proteins, lipids, and nucleic acid-based assays. Among various deoxyribonucleic acid (DNA)-based methods, the recently developed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) based bio-sensing is an innovative and fast-expanding technology. The CRISPR/Cas-9 is known as Clustered Regularly Interspaced Short Palindromic Repeats due to the flexibility and simplicity of the CRISPR/Cas9 site-specific editing tool has been applied in many biological research areas such as Gene therapy, cell line development, discovering mechanisms of disease, and drug discovery. Nowadays, the CRISPR-Cas system has also been introduced into food authentication via detecting DNA barcodes of poultry and livestock both in processed and unprocessed food samples. This review documents various DNA based approaches, in an accessible format. Future CRISPR technologies are forecast while challenges are outlined.
  3. Sultana S, Hossain MAM, Azlan A, Johan MR, Chowdhury ZZ, Ali ME
    Food Chem, 2020 Apr 07;325:126756.
    PMID: 32413685 DOI: 10.1016/j.foodchem.2020.126756
    Detection of animal materials in gelatin-based products is required to address religious and cultural concerns, because porcine and bovine gelatins are prohibited in Halal, Kosher and Hindus consumer goods. In this paper, multiplex quantitative polymerase chain reaction (qPCR) assay using TaqMan probe was developed to discriminate bovine, porcine and fish gelatin species in a single assay platform. The assay was specific to cattle, pigs and fish, having been tested against 14 non-target species. The limit of detection, under gelatin admixed conditions, was 0.005 ng/µL. Finally, a pilot survey was undertaken testing 35 Halal branded processed food and dietary items. Out of 35 samples, only two were found to be positive for porcine species. The authenticity of these two qPCR products was confirmed by DNA sequencing analysis, which showed 99-100% similarity with Sus scrofa (Wild boar) species.
  4. S M N Mydin RB, Azlan A, Okekpa SI, Gooderham NJ
    Cell Biochem Funct, 2024 Mar;42(2):e3945.
    PMID: 38362935 DOI: 10.1002/cbf.3945
    MicroRNAs (miRNA) are small and conserved noncoding RNA molecules that regulate gene expression at the posttranscriptional level. These groups of RNAs are crucial in various cellular processes, especially in mediating disease pathogenesis, particularly cancer. The dysregulation of miRNAs was reported in many cancer types, including nasopharyngeal cancer (NPC), which is a malignant tumor of the nasopharynx. In this review, miRNAs involvement in crucial signaling pathways associated with NPC such as PTEN/PI3K/AKT, TGFβ/SMAD, RAS/MAPK, Wnt/β-catenin and pRB-E2F was investigated. miRNAs could function as tumor suppressor-miR or onco-miR in NPC profoundly influenced cell cycle, apoptosis, proliferation, migration, and metastasis. This comprehensive review of current literature provided a thorough profile of miRNAs and their interplay with the aforementioned signaling pathways in NPC. Understanding these molecular interactions could remarkably impact the diagnosis, prognosis, and therapeutic strategies for NPC.
  5. Karim AA, Azlan A, Ismail A, Hashim P, Abd Gani SS, Zainudin BH, et al.
    BMC Complement Altern Med, 2014 Oct 07;14:381.
    PMID: 25292439 DOI: 10.1186/1472-6882-14-381
    BACKGROUND: Cocoa pod is an outer part of cocoa fruits being discarded during cocoa bean processing. Authors found out that data on its usage in literature as cosmetic materials was not recorded in vast. In this study, cocoa pod extract was investigated for its potential as a cosmetic ingredient.

    METHODS: Cocoa pod extract (CPE) composition was accomplished using UHPLC. The antioxidant capacity were measured using scavenging assay of 1,2-diphenyl-2-picrylhydrazyl (DPPH), β-carotene bleaching assay (BCB) and ferric reducing antioxidant power (FRAP). Inhibiting effect on skin degradation enzymes was carried out using elastase and collagenase assays. The skin whitening effect of CPE was determined based on mushroom tyrosinase assay and sun screening effect (UV-absorbance at 200-400 nm wavelength).

    RESULTS: LC-MS/MS data showed the presence of carboxylic acid, phenolic acid, fatty acid, flavonoids (flavonol and flavones), stilbenoids and terpenoids in CPE. Results for antioxidant activity exhibited that CPE possessed good antioxidant activity, based on the mechanism of the assays compared with ascorbic acid (AA) and standardized pine bark extract (PBE); DPPH: AA > CPE > PBE; FRAP: PBE > CPE > AA; and BCB: BHT > CPE > PBE. Cocoa pod extract showed better action against elastase and collagenase enzymes in comparison with PBE and AA. Higher inhibition towards tyrosinase enzyme was exhibited by CPE than kojic acid and AA, although lower than PBE. CPE induced proliferation when tested on human fibroblast cell at low concentration. CPE also exhibited a potential as UVB sunscreen despite its low performance as a UVA sunscreen agent.

    CONCLUSIONS: Therefore, the CPE has high potential as a cosmetic ingredient due to its anti-wrinkle, skin whitening, and sunscreen effects.

  6. Prasad KN, Chew LY, Khoo HE, Kong KW, Azlan A, Ismail A
    PMID: 20936182 DOI: 10.1155/2010/871379
    Antioxidant capacities of ethylacetate, butanol, and water fractions of peel, pulp, and seeds of Canarium odontophyllum Miq. (CO) were determined using various in vitro antioxidant models. Ethylacetate fraction of peel (EAFPE) exhibited the highest total phenolic (TPC), total flavonoid content (TFC), and antioxidant activities compared to pulp, seeds, and other solvent fractions. Antioxidant capacities were assayed by total antioxidant capability, 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical activity, ferric reducing antioxidant power (FRAP), and hemoglobin oxidation assay. Total phenolic content of ethylacetate fractions was positively correlated with the antioxidant activity. This is the first report on the antioxidant activities from CO fruit fractions. Thus, EAFPE can be used potentially as a readily accessible source of natural antioxidants and as a possible pharmaceutical supplement.
  7. Baskaran G, Salvamani S, Azlan A, Ahmad SA, Yeap SK, Shukor MY
    PMID: 26697097 DOI: 10.1155/2015/751714
    Hypercholesterolemia is the major risk factor that leads to atherosclerosis. Nowadays, alternative treatment using medicinal plants gained much attention since the usage of statins leads to adverse health effects, especially liver and muscle toxicity. This study was designed to investigate the hypocholesterolemic and antiatherosclerotic effects of Basella alba (B. alba) using hypercholesterolemia-induced rabbits. Twenty New Zealand white rabbits were divided into 5 groups and fed with varying diets: normal diet, 2% high cholesterol diet (HCD), 2% HCD + 10 mg/kg simvastatin, 2% HCD + 100 mg/kg B. alba extract, and 2% HCD + 200 mg/kg B. alba extract, respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol, LDL, and triglycerides and increased HDL and antioxidant enzymes (SOD and GPx) levels. The elevated levels of liver enzymes (AST and ALT) and creatine kinase were noted in hypercholesterolemic and statin treated groups indicating liver and muscle injuries. Treatment with B. alba extract also significantly suppressed the aortic plaque formation and reduced the intima: media ratio as observed in simvastatin-treated group. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and atherosclerosis.
  8. Khoo HE, Azlan A, Nurulhuda MH, Ismail A, Abas F, Hamid M, et al.
    PMID: 24368926 DOI: 10.1155/2013/434057
    This study aimed to determine anthocyanins and their antioxidative and cardioprotective properties in defatted dabai parts. Anthocyanins in crude extracts and extract fractions of defatted dabai peel and pericarp were quantified using UHPLC, while their antioxidant capacity and oxidative stress inhibition ability were evaluated by using DPPH and CUPRAC assays as well as linoleic acid oxidation system, hemoglobin oxidation, and PARP-1 inhibition ELISA. Cardioprotective effect of the defatted dabai peel extract was evaluated using hypercholesterolemic-induced New Zealand white rabbits. Six anthocyanins were detected in the defatted dabai peel, with the highest antioxidant capacities and oxidative stress inhibition effect compared to the other part. The defatted dabai peel extract has also inhibited lipid peroxidation (plasma MDA) and elevated cellular antioxidant enzymes (SOD and GPx) in the tested animal model. Major anthocyanin (cyanidin-3-glucoside) and other anthocyanins (pelargonidin-3-glucoside, malvidin-3-glucoside, cyanidin-3-galactoside, cyanidin-3-arabinoside, and peonidin-3-glucoside) detected in the defatted dabai peel are potential future nutraceuticals with promising medicinal properties.
  9. Prasad N, Yang B, Kong KW, Khoo HE, Sun J, Azlan A, et al.
    PMID: 23710209 DOI: 10.1155/2013/154606
    Nypa fruticans Wurmb. is one of the important underutilized fruit of Malaysia, which lacks scientific attention. Total phenolics, flavonoid content, and antioxidant capacities from endosperm extracts of Nypa fruticans (unripe and ripe fruits) were evaluated. Endosperm extract of unripe fruits (EEU) exhibited the highest phenolics (135.6 ± 4.5 mg GAE/g), flavonoid content (68.6 ± 3.1 RE/g), and antioxidant capacity. Free radical scavenging capacity of EEU as assessed by 2-2'-azino-bis (3-ethylbenz-thiazoline-6-sulfonic acid (ABTS) and 1,1-diphenyl-2-picryl hydrazyl (DPPH) radicals showed inhibitory activity of 78 ± 1.2% and 85 ± 2.6%, respectively. Beta carotene bleaching coefficient of EEU was higher (2550 ± 123), when compared to endosperm extract of ripe fruits (1729 ± 172). Additionally, EEU exhibited high antioxidant capacity by phosphomolybdenum method and ferric reducing antioxidant power values. Eight phenolic compounds from Nypa fruticans endosperm extracts were identified and quantified by ultra-high-performance liquid chromatography. Chlorogenic acid, protocatechuic acid, and kaempferol were the major phenolic compounds. Thus this fruit could be used as a potential source of natural antioxidant.
  10. Zolkeflee NKZ, Wong PL, Maulidiani M, Ramli NS, Azlan A, Mediani A, et al.
    Biochem Biophys Res Commun, 2024 May 14;708:149778.
    PMID: 38507867 DOI: 10.1016/j.bbrc.2024.149778
    The increasing prevalence of lean diabetes has prompted the generation of animal models that mimic metabolic disease in humans. This study aimed to determine the optimum streptozotocin-nicotinamide (STZ-NA) dosage ratio to elicit lean diabetic features in a rat model. It also used a proton nuclear magnetic resonance (1H NMR) urinary metabolomics approach to identify the metabolic effect of metformin treatment on this novel rat model. Three different STZ-NA dosage regimens (by body weight: Group A: 110 mg/kg NA and 45 mg/kg STZ; Group B: 180 mg/kg NA and 65 mg/kg STZ and Group C: 120 mg/kg NA and 60 mg/kg STZ) were administered to Sprague-Dawley rats along with oral metformin. Group A diabetic rats (A-DC) showed favorable serum biochemical analyses and a more positive response toward oral metformin administration relative to the other STZ-NA dosage ratio groups. Orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed that glucose, citrate, pyruvate, hippurate, and methylnicotinamide differentiating the OPLS-DA of A-MTF rats (Group A diabetic rats treated with metformin) and A-DC model rats. Subsequent metabolic pathway analyses revealed that metformin treatment was associated with improvement in dysfunctions caused by STZ-NA induction, including carbohydrate metabolism, cofactor metabolism, and vitamin and amino acid metabolism. In conclusion, our results identify the best STZ-NA dosage ratio for a rat model to exhibit lean type 2 diabetic features with optimum sensitivity to metformin treatment. The data presented here could be informative to improve our understanding of non-obese diabetes in humans through the identification of possible activated metabolic pathways in the STZ-NA-induced diabetic rats model.
  11. Halim MA, Tan FHP, Azlan A, Rasyid II, Rosli N, Shamsuddin S, et al.
    Malays J Med Sci, 2020 May;27(3):7-19.
    PMID: 32684802 MyJurnal DOI: 10.21315/mjms2020.27.3.2
    Ageing is a phenomenon where the accumulation of all the stresses that alter the functions of living organisms, halter them from maintaining their physiological balance and eventually lead to death. The emergence of epigenetic tremendously contributed to the knowledge of ageing. Epigenetic changes in cells or tissues like deoxyribonucleic acid (DNA) methylation, modification of histone proteins, transcriptional modification and also the involvement of non-coding DNA has been documented to be associated with ageing. In order to study ageing, scientists have taken advantage of several potential organisms to aid them in their study. Drosophila melanogaster has been an essential model in establishing current understanding of the mechanism of ageing as they possess several advantages over other competitors like having homologues to more than 75% of human disease genes, having 50% of Drosophila genes are homologues to human genes and most importantly they are genetically amenable. Here, we would like to summarise the extant knowledge about ageing and epigenetic process and the role of Drosophila as an ideal model to study epigenetics in association with ageing process.
  12. Wong PL, Zolkeflee NKZ, Ramli NS, Tan CP, Azlan A, Abas F
    J Tradit Complement Med, 2024 Jul;14(4):456-466.
    PMID: 39035686 DOI: 10.1016/j.jtcme.2024.02.001
    BACKGROUND AND AIM: Interest in the safety of herbal medicine is growing rapidly regarding knowledge and challenges in natural products. Hence, this study aimed to reveal the toxicological profile of Ardisia elliptica, a traditional medicinal plant used in the treatment of various illnesses.

    EXPERIMENTAL PROCEDURE: Acute toxicity study was performed on female and male Sprague Dawley rats with a single oral administration of 2000 mg/kg BW of 70% ethanolic A. elliptica leaf extract, using a combination of conventional investigations and 1H-NMR-based metabolomics approaches.

    RESULTS: Physical, hematological, biochemical, and histopathological assessments demonstrated the usual rat profile, with no mortality and delayed toxicity 14 days after administration. 1H NMR serum metabolomics depicted similar metabolites between normal and treated groups. Nevertheless, 1H NMR of urinary metabolomics revealed perturbation in carbohydrate, amino acid, and energy metabolism within 24h after extract administration, while no accumulation of toxic biomarkers in the collected biological fluids on Day 14. A minor gender-based difference revealed the influence of sex hormones and different energy expenditure on response to extract treatment.

    CONCLUSION: This study suggested that 2000 mg/kg BW of 70% ethanolic A. elliptica leaf extract is considered as safe for consumption and offered a comprehensive overview of the response of physiological and metabolic aspects applicable to food and herbal product development.

  13. Solayappan M, Azlan A, Khor KZ, Yik MY, Khan M, Yusoff NM, et al.
    Front Genet, 2021;12:767298.
    PMID: 35154242 DOI: 10.3389/fgene.2021.767298
    Hematological malignancies (HM) are a group of neoplastic diseases that are usually heterogenous in nature due to the complex underlying genetic aberrations in which collaborating mutations enable cells to evade checkpoints that normally safeguard it against DNA damage and other disruptions of healthy cell growth. Research regarding chromosomal structural rearrangements and alterations, gene mutations, and functionality are currently being carried out to understand the genomics of these abnormalities. It is also becoming more evident that cross talk between the functional changes in transcription and proteins gives the characteristics of the disease although specific mutations may induce unique phenotypes. Functional genomics is vital in this aspect as it measures the complete genetic change in cancerous cells and seeks to integrate the dynamic changes in these networks to elucidate various cancer phenotypes. The advent of CRISPR technology has indeed provided a superfluity of benefits to mankind, as this versatile technology enables DNA editing in the genome. The CRISPR-Cas9 system is a precise genome editing tool, and it has revolutionized methodologies in the field of hematology. Currently, there are various CRISPR systems that are used to perform robust site-specific gene editing to study HM. Furthermore, experimental approaches that are based on CRISPR technology have created promising tools for developing effective hematological therapeutics. Therefore, this review will focus on diverse applications of CRISPR-based gene-editing tools in HM and its potential future trajectory. Collectively, this review will demonstrate the key roles of different CRISPR systems that are being used in HM, and the literature will be a representation of a critical step toward further understanding the biology of HM and the development of potential therapeutic approaches.
  14. Amom Z, Zakaria Z, Mohamed J, Azlan A, Bahari H, Taufik Hidayat Baharuldin M, et al.
    J Clin Biochem Nutr, 2008 Sep;43(2):88-94.
    PMID: 18818758 DOI: 10.3164/jcbn.2008051
    Accumulating data demonstrated that hypercholesterolemia and oxidative stress play an important role in the development of atherosclerosis. In the present study, a protective activity of alpha-lipoic acid; a metabolic antioxidant in hypercholesterolemic-induced animals was investigated. Eighteen adult male New Zealand White (NZW) rabbit were segregated into three groups labelled as group N, HCD and ALA (n = 6). Group N (normal control) was fed with normal chow, the rest (HCD and ALA) were fed with 100 g/head/day of 1% cholesterol rich diet to induce hypercholesterolemia. Four point two mg/body weight of alpha lipoic acid was concomintantly supplemented to the ALA group. Drinking water was given ad-libitum. The study was designed for 10 weeks. Blood sampling was taken from the ear lobe vein at the beginning, week 5 and week 10. Plasma was prepared for lipid profile estimation and microsomal lipid peroxidation index indicated with malondialdehyde (MDA) formation. At the end of the experiment, the animals were sacrificed and the aorta were excised for intimal lesion analysis. The plasma total cholesterol (TC) and low density lipoprotein (LDL) levels were found to be significantly low in ALA group compared to that of the HCD group (p<0.05). Similarly, low level of MDA (p<0.05) in ALA group was observed compared to that of the HCD group showing a significant reduction of lipid peroxidation activity. Histomorphometric intimal lesion analysis of the aorta showing less of atheromatous plaque formation in alpha lipoic acid supplemented group (p<0.05) compared to HCD group. These findings suggested that alpha lipoic acid posses a dual lipid lowering and anti-atherosclerotic properties indicated with low plasma TC and LDL levels and reduction of athero-lesion formation in hypercholesterolemic-induced rabbits.
  15. Mohd Yusof BN, Yahya NF, Hasbullah FY, Wan Zukiman WZHH, Azlan A, Yi RLX, et al.
    Diabetes Res Clin Pract, 2021 Feb;172:108530.
    PMID: 33157118 DOI: 10.1016/j.diabres.2020.108530
    AIMS: This narrative review aimed to synthesize the evidence on the effects of Ramadan-focused nutrition therapy for people with diabetes.

    METHODS: We searched MEDLINE (via PubMed) and Science Direct databases for articles that included the component of nutrition for adult patients with type 2 diabetes (T2D), published in English between 2010 and 2020.

    RESULTS: Fourteen studies met the criteria. Eight of 14 studies had an intervention with a control arm. In comparison to the control group, all studies (n = 8) showed a reduction in hypoglycemic events. However, only half of these studies (n = 4) had shown at least one positive clinical outcome. Features of nutrition therapy that appeared to have favorable clinical outcomes include individualized caloric prescription; distributing carbohydrates equally between Suhoor, Iftar and snacks; providing meal plans; adjusting food intake to suit Ramadan; and incorporating diabetes-specific formula as part of Suhoor or snack.

    CONCLUSIONS: The review provides evidence for the effectiveness of Ramadan-focused nutrition therapy among people with T2D and identifies key features of nutrition therapy that may provide favourable clinical outcomes. Additional data on dietary quality and adequacy during Ramadan fasting warrants further studies.

  16. Hor YY, Ooi CH, Lew LC, Jaafar MH, Lau AS, Lee BK, et al.
    J Appl Microbiol, 2021 Apr;130(4):1307-1322.
    PMID: 32638482 DOI: 10.1111/jam.14776
    AIM: The aim of this study was to evaluate the molecular mechanisms of Lactobacillus strains in improving ageing of the musculoskeletal system.

    METHODS AND RESULTS: The anti-ageing mechanism of three probiotics strains Lactobacillus fermentum DR9, Lactobacillus paracasei OFS 0291 and L. helveticus OFS 1515 were evaluated on gastrocnemius muscle and tibia of d-galactose-induced ageing rats. Upon senescence induction, aged rats demonstrated reduced antioxidative genes CAT and SOD expression in both bone and muscle compared to the young rats (P 

  17. Zaydi AI, Lew LC, Hor YY, Jaafar MH, Chuah LO, Yap KP, et al.
    Benef Microbes, 2020 Dec 02;11(8):753-766.
    PMID: 33245015 DOI: 10.3920/BM2019.0200
    Aging processes affect the brain in many ways, ranging from cellular to functional levels which lead to cognitive decline and increased oxidative stress. The aim of this study was to investigate the potentials of Lactobacillus plantarum DR7 on brain health including cognitive and memory functions during aging and the impacts of high fat diet during a 12-week period. Male Sprague-Dawley rats were separated into six groups: (1) young animals on normal diet (ND, (2) young animals on a high fat diet (HFD), (3) aged animals on ND, (4) aged animals on HFD, (5) aged animals on HFD and L. plantarum DR7 (109 cfu/day) and (6) aged animals receiving HFD and lovastatin. To induce ageing, all rats in group 3 to 6 were injected sub-cutaneously at 600 mg/kg/day of D-galactose daily. The administration of DR7 has reduced anxiety accompanied by enhanced memory during behavioural assessments in aged-HFD rats (P<0.05). Hippocampal concentration of all three pro-inflammatory cytokines were increased during aging but reduced upon administration of both statin and DR7. Expressions of hippocampal neurotransmitters and apoptosis genes showed reduced expressions of indoleamine dioxygenase and P53 accompanied by increased expression of TPH1 in aged- HFD rats administered with DR7, indicating potential effects of DR7 along the pathways of serotonin and oxidative senescence. This study provided an insight into potentials of L. plantarum DR7 as a prospective dietary strategy to improve cognitive functions during aging. This study provided an insight into potentials of L. plantarum DR7 as a prospective dietary strategy to improve cognitive functions during aging.
  18. Lew LC, Hor YY, Jaafar MH, Lau ASY, Ong JS, Chuah LO, et al.
    Benef Microbes, 2019 Dec 09;10(8):883-892.
    PMID: 31965837 DOI: 10.3920/BM2019.0058
    This study aimed to evaluate the anti-ageing effects of different strains of lactobacilli putative probiotics on an ageing rat model as induced by D-galactose and a high fat diet. Male Sprague-Dawley rats were fed with high fat diet (54% kcal fat) and injected with D-galactose daily for 12 weeks to induce ageing. The effects of putative probiotic strains on age-related impairment such as telomere length, plasma lipid peroxidation, hepatic 5'adenosine monophosphate-activated protein kinase (AMPK) expression, as well as endurance performance were evaluated. Administration of statin, Lactobacillus plantarum DR7 (LP-DR7), Lactobacillus fermentum DR9 (LF-DR9), and Lactobacillus reuteri 8513d (LR-8513d) significantly reduced the shortening of telomere and increased the expression of AMPK subunit-α1 (P<0.05). Plasma lipid peroxidation was lower (P<0.05) in groups administered with statin and LF-DR9 as compared to the control. AMPK subunit-α2 was elevated in rats administered with LP-DR7 as compared to the control (P<0.05). Using an in vivo ageing rat model, the current study has illustrated the potentials of lactobacilli putative probiotics in alleviation of age-related impairment in a strain-dependent manner.
  19. Moses EJ, Azlan A, Khor KZ, Mot YY, Mohamed S, Seeni A, et al.
    Cell Mol Life Sci, 2023 Feb 23;80(3):70.
    PMID: 36820913 DOI: 10.1007/s00018-023-04713-y
    The fusion oncoprotein RUNX1/ETO which results from the chromosomal translocation t (8;21) in acute myeloid leukemia (AML) is an essential driver of leukemic maintenance. We have previously shown that RUNX1/ETO knockdown impairs expression of the protein component of telomerase, TERT. However, the underlying molecular mechanism of how RUNX1/ETO controls TERT expression has not been fully elucidated. Here we show that RUNX1/ETO binds to an intergenic region 18 kb upstream of the TERT transcriptional start site and to a site located in intron 6 of TERT. Loss of RUNX1/ETO binding precedes inhibition of TERT expression. Repression of TERT expression is also dependent on the destabilization of the E3 ubiquitin ligase SKP2 and the resultant accumulation of the cell cycle inhibitor CDKN1B, that are both associated with RUNX1/ETO knockdown. Increased CDKN1B protein levels ultimately diminished TERT transcription with E2F1/Rb involvement. Collectively, our results show that RUNX1/ETO controls TERT expression directly by binding to its locus and indirectly via a SKP2-CDKN1B-E2F1/Rb axis.
  20. Wong PL, Zolkeflee NKZ, Ramli NS, Tan CP, Azlan A, Tham CL, et al.
    J Ethnopharmacol, 2024 Jan 10;318(Pt B):117015.
    PMID: 37572932 DOI: 10.1016/j.jep.2023.117015
    ETHNOPHARMACOLOGICAL RELEVANCE: Ardisia elliptica Thunb. (AE) (Primulaceae) is a medicinal plant found in the Malay Peninsula and has been traditionally used to treat diabetes. However, limited studies to date in providing scientific evidence to support the antidiabetic efficacy of this plant by in-vitro and in-vivo models.

    AIM OF THE STUDY: To investigate the anti-hyperglycemic potential of AE through in-vitro enzymatic activities and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat models using proton-nuclear magnetic resonance (1H-NMR)-based metabolomics approach.

    MATERIALS AND METHODS: Anti-α-amylase and anti-α-glucosidase activities of the hydroethanolic extracts of AE were evaluated. The absolute quantification of bioactive constituents, using ultra-high performance liquid chromatography (UHPLC) was performed for the most active extract. Three different dosage levels of the AE extract were orally administered for 4 weeks consecutively in STZ-NA induced diabetic rats. Physical assessments, biochemical analysis, and an untargeted 1H-NMR-based metabolomics analysis of the urine and serum were carried out on the animal model.

    RESULTS: Type 2 diabetes mellitus (T2DM) rat model was successfully developed based on the clear separation observed between the STZ-NA induced diabetic and normal non-diabetic groups. Discriminating biomarkers included glucose, citrate, succinate, allantoin, hippurate, 2-oxoglutarate, and 3-hydroxybutyrate, as determined through an orthogonal partial least squares-discriminant analysis (OPLS-DA) model. A treatment dosage of 250 mg/kg body weight (BW) of standardized 70% ethanolic AE extract mitigated increase in serum glucose, creatinine, and urea levels, providing treatment levels comparable to that obtained using metformin, with flavonoids primarily contribute to the anti-hyperglycemic activities. Urinary metabolomics disclosed that the following disturbed metabolism pathways: the citrate cycle (TCA cycle), butanoate metabolism, glycolysis and gluconeogenesis, pyruvate metabolism, and synthesis and degradation of ketone bodies, were ameliorated after treatment with the standardized AE extract.

    CONCLUSIONS: This study demonstrated the first attempt at revealing the therapeutic effect of oral treatment with 250 mg/kg BW of standardized AE extract on chemically induced T2DM rats. The present study provides scientific evidence supporting the ethnomedicinal use of Ardisia elliptica and further advances the understanding of the fundamental molecular mechanisms affected by this herbal antidote.

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