Browse publications by year: 2023

  1. Subramanian S, Duraipandian C, Alsayari A, Ramachawolran G, Wong LS, Sekar M, et al.
    Front Pharmacol, 2023;14:1096905.
    PMID: 36817128 DOI: 10.3389/fphar.2023.1096905
    Background: Dodonaea viscosa Jacq. (D. viscosa) belongs to the family of Sapindaceae, commonly known as "Sinatha," and is used as a traditional medicine for treating wounds due to its high flavonoids content. However, to date there is no experimental evidence on its flavonoid-rich fraction of D. viscosa formulation as an agent for healing wounds. Objective: The present study aimed to evaluate the wound healing effect of ethyl acetate fraction of D. viscosa leaves on dermal wounds. Methods: The ethyl acetate fraction was produced from a water-ethanol extract of D. viscosa leaves and was quantitatively evaluated using the HPLC technique. The in-vivo wound healing ability of the ethyl acetate fraction of D. viscosa ointment (DVFO, 2.5%w/w and 5%w/w) was investigated in Sprague-Dawley rats utilizing an incision and excision paradigm with povidone-iodine ointment (5% w/w) as a control. The percentage of wound closure, hydroxyproline and hexosamine concentrations, tensile strength and epithelialization duration were measured. Subsequently, histopathology analysis of skin samples as well as western blots were performed for collagen type 3 (COL3A1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Results: The ethyl acetate fraction of D. viscosa revealed flavonoids with high concentrations of quercetin (6.46% w/w) and kaempferol (0.132% w/w). Compared to the control group, the DVFO (2.5% and 5.0% w/w) significantly accelerated wound healing in both models, as demonstrated by quicker wound contraction, epithelialization, elevated hydroxyproline levels and increased tensile strength. Histopathological investigations also revealed that DVFO treatment improved wound healing by re-epithelialization, collagen formation and vascularization of damaged skin samples. Western blot analysis further demonstrated an up-regulation of COL3A, vascular endothelial growth factor and bFGF protein in wound granulation tissue of the DVFO-treated group (p < 0.01). Conclusion: It is concluded that flavonoid-rich D. viscosa ethyl acetate fraction promotes wound healing by up-regulating the expressions of COL3A, VEGF and bFGF protein in wound granulation tissue. However, extensive clinical and pre-clinical research on the flavonoid-rich fraction of D. viscosa is needed to determine its significant impact in the healing of human wounds.
  2. Shamsuddin SA, Woon CK, Hadie SNH
    J Taibah Univ Med Sci, 2023 Apr;18(2):234-243.
    PMID: 36817220 DOI: 10.1016/j.jtumed.2022.08.007
    OBJECTIVE: The disruption caused by COVID-19 in anatomy education has forced the transition of in-person to online learning. Despite the increasing use of technology-enhanced tools in online classes, anatomy lecturers face significant difficulty in making classes interactive. Hence, this study explored the feasibility of a web-based virtual whiteboard, Google Jamboard (GJ) for two online anatomy practical classes.

    METHODS: This was a qualitative phenomenology study conducted on 116 second-year medical students from two Malaysian public universities via teleconferencing applications that allowed synchronous small-group activities. Each group was given a different link to 10 GJ slides that featured plain anatomy diagrams and instructions for the group task. Upon completion of the tasks, the students presented their tasks to the whole class. An online feedback form was distributed at the end of the practical session to explore the experience of the students when using the tool.

    RESULTS: Thematic analysis of student responses generated seven themes that reflected perceived learning benefits, challenges faced by the students, and suggestions for future improvement.

    CONCLUSIONS: These findings suggest that GJ is a useful tool for promoting collaborative learning in virtual anatomy education. Nevertheless, the impact of this tool on the attainment of learning outcomes remains unknown. Hence, more widescale research is needed to confirm our findings.

  3. Meilianti S, John C, Duggan C, O'campo L, Bates I
    Explor Res Clin Soc Pharm, 2023 Mar;9:100231.
    PMID: 36817332 DOI: 10.1016/j.rcsop.2023.100231
    BACKGROUND: Iron deficiency anaemia (IDA) is the leading cause of anaemia globally, most frequently found in children and pregnant women. With their increasing role in the healthcare system, pharmacists may contribute to the management of anaemia. Through the International Pharmaceutical Federation (FIP) Multinational Needs Assessment Programme, the FIP explored the contribution of pharmacists in anaemia, specifically IDA, focusing on five countries: India, Indonesia, Malaysia, Philippines and Singapore.

    OBJECTIVE: To explore information on pharmacists' roles in a variety of settings related to 1) IDA management; 2) education and training needed to support the roles; and 3) barriers and enablers to expanding or developing the roles.

    METHODS: This study involved a literature review and a focus group discussion with twelve participants selected purposively and nominated by national professional leadership bodies across five countries. A literature search was conducted using PubMed Database. A focus group discussion explored pharmacists' roles, education and training needs, as well as barriers and enablers to support their roles in anaemia management, specifically in IDA. A codebook thematic analysis approach was conducted according to the study objectives.

    RESULTS: Sixteen articles were included in the analysis. The pharmacists' roles in anaemia identified from literature ranged from patient management and monitoring, collaboration with other healthcare professionals and involvement in guideline development, in which the roles vary according to the workplace. Twelve participants attended the focus group discussion. Participants highlighted pharmacists' roles in screening and detection, medication therapeutic management, patient counselling and patient monitoring. Participants emphasised a need for guidelines or toolkits with subsequent training or workshops to support their competency development in anaemia. Monitoring the success of pharmacist delivered anaemia programmes was recommended to support advocating for active pharmacist roles.

    CONCLUSION: Pharmacists have a growing opportunity to contribute to achieving the global targets on anaemia through their involvement in screening and managing anaemia and increasing anaemia awareness among the patients and community.

  4. Zhang L, Wong LR, Wong P, Shen W, Yang S, Huang L, et al.
    Brain Behav Immun Health, 2023 Mar;28:100599.
    PMID: 36817510 DOI: 10.1016/j.bbih.2023.100599
    Baicalein (BE) has both antioxidant and anti-inflammatory effects. It has also been reported able to improve cerebral blood circulation in brain ischemic injury. However, its chronic efficacy and metabolomics in Alzheimer's disease (AD) remain unknown. In this study, BE at 80 mg/kg was administrated through the oral route in J20 AD transgenic mice aged from aged 4 months to aged 10 months. Metabolic- and neurobehavioural phenotyping was done before and after 6 months' treatment to evaluate the drug efficacy and the relevant mechanisms. Meanwhile, molecular docking was used to study the binding affinity of BE and poly (ADP-ribose) polymerase-1 (PARP-1) which is related to neuronal injury. The open field test showed that BE could suppress hyperactivity in J20 mice and increase the frequency of the target quadrant crossing in the Morris Water Maze test. More importantly, BE restored cerebral blood flow back to the normal level after the chronic treatment. A 1H NMR-based metabolomics study showed that BE treatment could restore the tricarboxylic acid cycle in plasma. And such a treatment could suppress oxidative stress, inhibit neuroinflammation, alleviate mitochondrial dysfunction, improve neurotransmission, and restore amino homeostasis via starch and sucrose metabolism and glycolipid metabolism in the cortex and hippocampus, which could affect the behavioural and cerebral blood flow. These findings showed that BE is a potential therapeutic agent for AD.
  5. Bari MW, Ramayah T, Di Virgilio F, Alaverdov E
    Front Public Health, 2023;11:1102736.
    PMID: 36817924 DOI: 10.3389/fpubh.2023.1102736
    MeSH terms: Humans; Occupational Health*; Workplace*
  6. Zhao H, Rafik-Galea S, Fitriana M, Song T
    Front Psychol, 2023;14:1092893.
    PMID: 36818081 DOI: 10.3389/fpsyg.2023.1092893
    BACKGROUND: The fact that female college students are more addicted to smartphones than male college students has raised public concerns. However, previous studies have rarely explored the mechanism of female college students' smartphone addiction. Previous studies have shown that identity may affect the formation process of female college students' smartphone addiction, and the identity of female college students in different grades may be different. Nonetheless, few studies have explored the grade differences in the formation process of female college students' smartphone addiction.

    METHODS: The present study examined the relationship between meaning in life, school adjustment, and smartphone addiction among Chinese female college students using a moderated mediation model in which school adjustment played a mediating role and grade played a moderating role. A total of 1,076 Chinese female college students (Age: 19.83 ± 1.11; 369 freshmen, 379 sophomores, and 328 juniors) completed an online questionnaire regarding meaning in life, school adjustment, and smartphone addiction.

    RESULTS: (1) School adjustment mediated the relationship between meaning in life and smartphone addiction. (2) School adjustment had a partial mediating effect between meaning in life and smartphone addiction for female freshmen and sophomores, but it did not exist among female juniors. (3) The influence of school adjustment on female sophomores' smartphone addiction was significantly stronger than that of female freshmen.

    CONCLUSION: The findings of this study advance our understanding of the potential impacts of meaning in life on smartphone addiction and provide a grade perspective for targeted prevention or intervention with female college students' smartphone addiction.

  7. Jang JH, Gomez RD, Bumbea H, Nogaieva L, Wong LLL, Lim SM, et al.
    EJHaem, 2023 Feb;4(1):26-36.
    PMID: 36819188 DOI: 10.1002/jha2.632
    Treatment of paroxysmal nocturnal haemoglobinuria (PNH) includes the monoclonal antibody eculizumab. This randomised, double-blind, multi-national cross-over Phase III study in PNH patients aimed to demonstrate the equivalence of the proposed eculizumab biosimilar SB12 and reference eculizumab (Soliris, ECU). PNH patients with lactate dehydrogenase (LDH) ≥1·5× upper limit of normal were randomised into treatment sequences SB12-ECU or ECU-SB12. Four weekly infusions of 600 mg eculizumab were followed by fortnightly infusions of 900 mg until week 50 (ECU/SB12 cross-over at week 26). Primary endpoints were LDH at week 26 and the time-adjusted area under the effect curve (AUEC) of LDH over weeks 14‒26 and 40‒52. Among 46 patients (92%) who completed the study, the least squares mean (LSM) difference in LDH at week 26 (34·48; 95% confidence interval [CI] -47·66‒116·62 U/l) and geometric LSM ratio of time-adjusted AUEC of LDH (1·08; 90% CI 0·95‒1·23) were within pre-defined equivalence margins. Mean numbers of transfused red blood cell units, other secondary endpoints, pharmacokinetics, and pharmacodynamics were comparable. No patients developed anti-drug antibodies. Treatment-emergent adverse events were reported in 72% and 68% of patients in the SB12 and ECU treatment groups, respectively. The results demonstrate equivalence of SB12 to ECU and support SB12-use in PNH patients.
  8. Thiagarajan D, Zainal S, Alias R, Bastion MC
    Cureus, 2023 Jan;15(1):e33798.
    PMID: 36819316 DOI: 10.7759/cureus.33798
    PURPOSE: To evaluate the corneal topographical changes in vernal keratoconjunctivitis (VKC) subjects using OCULUS Pentacam.

    DESIGN: This was a cross-sectional study.

    METHODS: VKC patients and normal subjects who fulfilled the inclusion and exclusion criteria were recruited by convenience sampling into the study. Subjects underwent a best-corrected visual acuity measurement with a Snellen chart, retinoscopy, and corneal topography (OCULUS Pentacam®), followed by anterior segment and fundus examination and intraocular pressure measurement. Data were collected and analyzed using SPSS version 26.0 for Windows (SPSS Inc. Chicago, IL, USA). A p-value <0.05 was considered statistically significant.

    RESULTS: A total of 78 eyes of 43 VKC patients and 84 eyes of normal subjects were included in the study. Most of the VKC subjects were Malay males aged 10 years or less. A majority (71.8%) had palpebral VKC of five years duration or less (57.7%) and presented between the ages of six and 10 years (44.9%). Central corneal curvature and astigmatism were significantly higher in VKC subjects compared to the normal population (p < 0.05). The minimal pachymetry was significantly lower with a longer duration of VKC (p < 0.05). Older age of presentation of VKC was associated with higher central corneal curvatures and thinner minimal pachymetry (p < 0.05). There was no association between the type of VKC and corneal topography changes. The prevalence of keratoconus and subclinical keratoconus among VKC subjects was 10.3% and 11.5%, respectively.

    CONCLUSION: Longer duration and older age of presentation of VKC are associated with significant corneal topographical changes, thus exposing them to a higher risk of the future development of keratoconus.

  9. Ag Daud DM, Liau SN, Sudi S, Mohd Noh M, Khin NY
    Cureus, 2023 Jan;15(1):e33918.
    PMID: 36819380 DOI: 10.7759/cureus.33918
    Knee osteoarthritis (OA) is a chronic joint disease that can affect all ages, but it is more common in the elderly. Pharmacological and non-pharmacological treatments have been invented evolutionarily over the years to halt this disease. Exercise is one of the first-line treatments for knee OA as well as for prevention. This case study features a 47-year-old man who has grade IV bilateral knee OA and has never had any surgery and takes fish oil daily as a supplement. His walking pattern was significantly impacted by the chronic knee discomfort he had in both legs. Thus, the walking gait of this patient was analyzed together with core muscle activation before and after two weeks of core resistance exercise intervention. The knee pain score was assessed using the Western Ontario and McMaster Universities Index (WOMAC). The outcomes of this research depict that core resistance training has the potential to be used as an alternative, non-surgical and non-pharmacological treatment for a patient with knee OA.
  10. Sultan Abdul Kader MI, Syafeera N, Md Nor K, Abu Bakar S, Mat Baki M
    Cureus, 2023 Jan;15(1):e33870.
    PMID: 36819404 DOI: 10.7759/cureus.33870
    Foreign body (FB) aspiration in children can result in serious complications that can lead to even death. We present a case of a one-year-old girl child with a history of choking one month prior while she was feeding. A bolus of rice was removed at a local clinic. Consequently, within 24 hours, she developed hoarseness and noisy breathing which was treated as an upper respiratory tract infection at two different clinics. This case report aims to highlight the need for otolaryngology consultation in a child with non-resolving respiratory symptoms following episodes of choking. This will prompt an immediate surgical intervention that could prevent potential morbidity and mortality as a result of a compromised airway.
  11. Juliana N, Teng NIMF, Hairudin KF, Wan Abdul Fatah WA, Das S
    Front Nutr, 2023;10:1079069.
    PMID: 36819675 DOI: 10.3389/fnut.2023.1079069
    INTRODUCTION: Students in colleges are exposed to unhealthy lifestyles and poor dietary choices. They are at risk of being overweight, skipping meals, and developing eating disorders. However, there is a paucity of information on their chrononutrition behavior, which is very important, especially concerning the timing of food consumption across the day. Therefore, the present study aimed to investigate chrononutrition behavior and its potential association with body weight status among college students in Malaysia.

    METHODS: This cross-sectional study was conducted on 409 college students aged above 18 in Malaysia. The chrononutrition behavior was assessed using the validated Chrononutrition Profile Questionnaire (CP-Q). The questionnaire was distributed using an online platform. Participants self-reported their body weight and height, and the Body Mass Index (BMI) was computed. Data were analyzed using the SPSS software.

    RESULTS: A total of 409 participants were recruited, with a mean age of 21.5 ± 2.2 years. The prevalence of underweight, normal, and overweight was 24.7, 49.4, and 25.9%, respectively. The chrononutrition behavior revealed that participants ate breakfast about four times/week (mean 4.27 ± 2.43 days), and only 135 (33.0%) consumed breakfast daily. The largest meal consumed was during lunch (75.8%), and the mean of snacking after the last meal was 3.23 ± 2.01 days. The prevalence of night eating was low, and most participants (70.9) did not wake up at night to eat. The frequency, however, was significantly higher in the underweight group compared to the normal weight group (p < 0.05). We observed a significant association between BMI and eating window, evening latency, evening eating, and night eating. It was found that the underweight had a poor eating window (p < 0.01), poor evening latency (p < 0.01), poor evening eating (p < 0.01), and poor night eating (p < 0.05) compared to those with normal and overweight BMI groups. In contrast to predictions, poor chrononutrition behavior was more likely to predict being underweight compared to normal (p < 0.05).

    CONCLUSION: Underweight young adults are more likely to have poor chrononutrition behavior. The results of the present study suggest that future nutrition education should also focus on the chrononutrition behavior of college students.

  12. Foo CY, Mansor NAN, Ch'ng SS, Mohd Zain M
    J Mark Access Health Policy, 2023;11(1):2173117.
    PMID: 36819892 DOI: 10.1080/20016689.2023.2173117
    INTRODUCTION: To ensure the sustainability of the AT access improvement, it is important that health system stakeholders have timely, analyzed information accessible for reference and decision-making support. In this study, we projected the direct costs required as well as the expected direct medical cost-offset and productivity benefits resulting from improving the disease control.

    METHODS: We implemented a deterministic, prevalence-based mathematical model to project the annual cost of rheumatoid arthritis (RA) management within the public healthcare system in Malaysia. We also calculated the annual productivity loss due to uncontrolled RA in monetary value. Using the projection model, we compared the projected costs of the status quo scenario vs. several scenarios of improved advanced therapy (AT) access over a 5-year period.

    RESULTS: We projected that between 10,765 and 11,024 RA patients in Malaysia over the period of 2020-2024 will need access to AT due to treatment failure with conventional synthetic disease modifying antirheumatic drugs (DMARDs). The projected net total medical cost under the status quo scenario were 163.5 million annually on average (approximately MYR 15,000 per patient per year). Cost related to health service utilization represented the heaviest component, amounting to 71.8% followed by drug cost (24.7%). Under the access improvement scenarios, drug cost constituted a higher proportion of the total medical, ranging from 25.6% to 30.4%. In contrast, the cost of health service utilization shown a reverse pattern (reducing to between 66.3% and 70.1%). Productivity costs were also expected to reduce as AT access improved leading to better outcomes. Treatment shifts to targeted synthetic DMARDs in anticipation of price adjustment appeared to have a cost saving advantage to the health system if all other parameters remain unchanged.

    DISCUSSION: Improving AT access for RA patients towards the aspirational target appeared to be feasible given the current health budget in Malaysia. Broader socio-economic consequences of productivity and income loss should be included as an important part of the policy consideration. The financial implication of different AT utilization mixes and the anticipated price adjustment will likely result in some cost saving to the health system.

  13. Chowdhury K, Ahmad R, Sinha S, Dutta S, Haque M
    Cureus, 2023 Feb;15(2):e35154.
    PMID: 36819973 DOI: 10.7759/cureus.35154
    Drug-resistant tuberculosis (DR-TB) has continued to be a global health cataclysm. It is an arduous condition to tackle but is curable with the proper choice of drug and adherence to the drug therapy. WHO has introduced newer drugs with all-oral shorter regimens, but the COVID-19 pandemic has disrupted the achievements and raised the severity. The COVID-19 controlling mechanism is based on social distancing, using face masks, personal protective equipment, medical glove, head shoe cover, face shield, goggles, hand hygiene, and many more. Around the globe, national and international health authorities impose lockdown and movement control orders to ensure social distancing and prevent transmission of COVID-19 infection. Therefore, WHO proposed a TB control program impaired during a pandemic. Children, the most vulnerable group, suffer more from the drug-resistant form and act as the storehouse of future fatal cases. It has dire effects on physical health and hampers their mental health and academic career. Treatment of drug-resistant cases has more success stories in children than adults, but enrollment for treatment has been persistently low in this age group. Despite that, drug-resistant childhood tuberculosis has been neglected, and proper surveillance has not yet been achieved. Insufficient reporting, lack of appropriate screening tools for children, less accessibility to the treatment facility, inadequate awareness, and reduced funding for TB have worsened the situation. All these have resulted in jeopardizing our dream to terminate this deadly condition. So, it is high time to focus on this issue to achieve our Sustainable Development Goals (SDGs), the goal of ending TB by 2030, as planned by WHO. This review explores childhood TB's current position and areas to improve. This review utilized electronic-based data searched through PubMed, Google Scholar, Google Search Engine, Science Direct, and Embase.
  14. Arliyani I, Tangahu BV, Mangkoedihardjo S, Zulaika E, Kurniawan SB
    Heliyon, 2023 Jan;9(1):e12921.
    PMID: 36820189 DOI: 10.1016/j.heliyon.2023.e12921
    Plant combination and rhizobacterial bioaugmentation are the modification of constructed wetlands (CWs) to promote the detoxification of leachate. In this study, characterization of leachate was carried out to ensure the maximum concentration of leachate that did not affect the plant's growth. Herein, the identification of leachate-resistant rhizobacteria is used to determine the type of bacteria that is resistant and has the potential for leachate processing in the next step. The phytodetoxification test is carried out by comparing the addition of rhizobacteria and without the addition of rhizobacteria to detox leachate parameter Chemical Oxygen Demand (COD), Biological Oxygen Demand (BOD), Total Suspended Solid (TSS), Total Nitrogen (TN), Cadmium (Cd), and Mercury (Hg). Results showed that used plants could still live in the largest leachate concentration of 100%. The rhizobacteria that were identified and bioaugmented in the reactor were Bacillus cereus, Nitrosomonas communis, and Pseudomonas aeruginosa. Phytodetoxification test by a single plant showed the efficiency ranged between 40% and 70%. The addition of rhizobacterial bioaugmentation and plant combination can improve the percentage of COD 80.47%, BOD 84.05%, TSS 80.05%, TN 75.58%, Cd 99.96%, and Hg 90%. These modifications are very influential for leachate detoxification through plant uptake and rhizodegradation processes.
  15. Duong TY, Nguyen NT, Tran DD, Le TH, Nor SAM
    Ecol Evol, 2023 Feb;13(2):e9845.
    PMID: 36820247 DOI: 10.1002/ece3.9845
    Population genetic structure of migratory fishes can reflect ecological and evolutionary processes. Pangasius krempfi is a critically important anadromous catfish in the Mekong River, and its migration pathways and genetic structure have attracted much interest. To investigate, we quantified the genetic diversity of this species using the control region (D-loop) and Cytochrome b (Cytb) of the mitochondrial genome. Fish were sampled (n = 91) along the Mekong tributaries from upstream to estuaries and coastal areas in the Mekong Delta and compared to three samples from Pakse (Laos). The D-loop haplotype (0.941 ± 0.014) and nucleotide diversity (0.0083 ± 0.0005) were high in all populations, but that of Cytb was low (0.331 ± 0.059 and 0.00063 ± 0.00011, respectively). No genetic difference was detected between populations, indicating strong gene flow and confirming a long migration distance for this species. Pangasius krempfi was not genetically structured according to geographical populations but was delineated into three haplogroups, suggesting multiple genetic lineages. The presence of haplogroups in each sampling location implies that migration downstream is random but parallel when the fish enter two river tributaries bifurcating from the main Mekong River. Individuals can also migrate along the coast, far from the estuaries, suggesting a longer migration path than previously reported, which is crucial for maintaining diverse genetic origin and migration pathways for P. krempfi.
  16. Haranal M, Sivalingam S, Borhanuddin BK, Srimurugan B, Latiff HA
    JTCVS Tech, 2023 Feb;17:151-152.
    PMID: 36820341 DOI: 10.1016/j.xjtc.2022.08.023
  17. Jaiswal V, Batra N, Dagar M, Butey S, Huang H, Chia JE, et al.
    Medicine (Baltimore), 2023 Feb 10;102(6):e32775.
    PMID: 36820570 DOI: 10.1097/MD.0000000000032775
    BACKGROUND: There is limited and conflicting data available regarding the cardiovascular disease outcomes associated with inflammatory bowel disease (IBD).

    OBJECTIVE: We aim to perform a systematic review to evaluate the cardiovascular outcomes and mortality associated with IBD patients.

    METHODS: A systematic literature search has been performed on PubMed, Embase, Cochrane, and Scopus from inception till May 2022 without any language restrictions.

    RESULTS: A total of 2,029,941 patients were included in the analysis from 16 studies. The mean age of the patients was 45.6 years. More females were found compared with males (57% vs 43%). The most common risk factors for cardiovascular disease (CVD) included smoking (24.19%) and alcohol (4.60%). The most common comorbidities includes hypertension (30%), diabetes mellitus (14.41%), dyslipidemia (18.42%), previous CVD (22%), and renal disease (10%). Among outcomes, all-cause mortality among IBD patients was 1.66%; ulcerative colitis (UC): 15.92%; and Crohn disease (CD): 0.30%. Myocardial Infarction (MI) among IBD patients were 1.47%, UC: 30.96%; and CD: 34.14%. CVD events among IBD patients were 1.95%. Heart failure events among IBD patients were 5.49%, stroke events among IBD patients were 0.95%, UC: 2.63%, and CD: 2.41%, respectively.

    CONCLUSION: IBD patients are at higher risk for adverse cardiovascular outcomes, especially in women. Although there remains a lack of concrete treatment algorithms and assessment parameters that better characterize IBD risk factors, nutritional modifications and physical activity should be at the forefront of CVD prevention in IBD.

    MeSH terms: Female; Humans; Male; Middle Aged
  18. 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.
    MeSH terms: Humans; Translocation, Genetic; Oncogene Proteins, Fusion/genetics; Cell Line, Tumor; Core Binding Factor Alpha 2 Subunit/genetics; Core Binding Factor Alpha 2 Subunit/metabolism; Cyclin-Dependent Kinase Inhibitor p27/metabolism
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