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Fulltext The Photocatalytic Effects of Modified Hydrothermal Nanotitania Extraction on the Skin and Behavior of Sprague-Dawley Rats

Harun AM, Awang H, Noor NFM, Makhatar NM, Yusoff ME, Affandi NDN, et al.

Biomed Res Int, 2021;2021:6173143.
PMID: 34859102 DOI: 10.1155/2021/6173143

BACKGROUND: Potential antibacterial substances, such as titanium dioxide (TiO2), are being extensively studied throughout the research world. A modified hydrothermal nanotitania extraction was shown to inhibit Staphylococcus aureus growth in the laboratory. However, the toxicity effect of the extract on rats is unknown. In this study, we observed the effects of a modified hydrothermal nanotitania extraction on the skin and behavior of Sprague-Dawley rats.
METHODS: Sprague-Dawley (Rattus norvegicus) rats were used as the experimental animals. The skin around the dorsum of the tested animals was shaved and pasted with 0.1 mg and 0.5 mg of the nanotitania extraction. The color and condition of the pasted area and the behavior of the animals were observed.
RESULTS: 0.1 mg nanotitania extraction application on the dorsum of the rat produced no skin color changes at day 1, day 3, day 5, or day 7 postapplication. There were no changes in their behavior up to day 7 with no skin rashes or skin scratches seen or fur changes. However, 0.5 mg of nanotitania extraction resulted in redness and less fur regrowth at day 7.
CONCLUSIONS: A 0.1 mg modified nanotitania extraction was observed to have no effect on the skin of Sprague-Dawley rats.
Fulltext Teledentistry as a Supportive Tool for Dentists in Pakistan

Subhan R, Ismail WA, Musharraf S, Khan M, Hafeez R, Alam MK

Biomed Res Int, 2021;2021:8757859.
PMID: 34540998 DOI: 10.1155/2021/8757859

The current scenario of the COVID-19 pandemic has forced dentists to seek different options for delivering healthcare services other than the in-person direct examination in clinical practice. Teledentistry is one of the options for remote patient care and monitoring. Objective. The present survey was conducted to assess the knowledge and perception of the dentists in Pakistan regarding teledentistry as an emergent supportive tool. Materials and Methods. A self-administered, close-ended, and prevalidated survey questionnaire was used, comprising 21 questions, and distributed electronically via e-mail, WhatsApp, and Facebook Messenger to evaluate the knowledge and perception of dentists regarding teledentistry. The data collected was compiled in a systematic manner and analyzed in terms of frequency (yes/no). Results. Out of a total of 350 dentists, 325 responded to the questionnaire, and it was seen that 62.5% of them did not have knowledge about teledentistry prior to COVID-19. 65.8% of dentists considered the practice of teledentistry in nonpandemic situations in the future. Conclusion. In the present study, it was observed that most of the dental professionals had inadequate knowledge about teledentistry before COVID-19, but the awareness and perception regarding teledentistry were currently satisfactory among the dental professionals in Pakistan. This emerging trend gives a positive hope for the implementation of teledentistry in the healthcare setup of Pakistan in the near future, as it will prove to be beneficial for safe dental practice during times of pandemic and even after.
Fulltext Amelioration of Isoproterenol-Induced Oxidative Damage in Rat Myocardium by Withania somnifera Leaf Extract

Khalil MI, Ahmmed I, Ahmed R, Tanvir EM, Afroz R, Paul S, et al.

Biomed Res Int, 2015;2015:624159.
PMID: 26539517 DOI: 10.1155/2015/624159

We investigated the protective role of Withania somnifera leaf extract (WSLEt) on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg body weight (b.w.)) administered to rats for two consecutive days caused a significant increase in cardiac troponin I (cTnI) levels and serum lipid profiles, as well as the activities of some marker enzymes. In addition to these diagnostic markers, there were increased levels of lipid peroxidation (LPO) and decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), and glutathione-S-transferase (GST)) in the myocardium. However, oral pretreatment (100 mg/kg b.w.) with WSLEt for 4 weeks elicited a significant cardioprotective activity by lowering the levels of cTnI, lipid profiles, and marker enzymes. The levels of LPO products were also significantly decreased. Elevated activities of antioxidant enzymes were also observed in rats pretreated with WSLEt. As further confirmed histopathologically, our findings strongly suggest that the cardioprotective effect of WSLEt on myocardium experiencing ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidant system and an inhibition of LPO in the myocardial membrane. We conclude that WSLEt confers some protection against oxidative damage in ISO-induced MI in rats.
Fulltext Wireless Networking-Driven Healthcare Approaches in Combating COVID-19

BasheeruddinAsdaq SM, Naveen NR, Gunturu LN, Pamayyagari K, Abdullah I, Sreeharsha N, et al.

Biomed Res Int, 2021;2021:9195965.
PMID: 34977249 DOI: 10.1155/2021/9195965

Since its outbreak, the coronavirus (COVID-19) pandemic has caused havoc on people's lives. All activities were paused due to the virus's spread across the continents. Researchers have been working hard to find new medication treatments for the COVID-19 pandemic. The World Health Organization (WHO) recommends that safety and self-measures play a major role in preventing the virus from spreading from one person to another. Wireless technology is playing a critical role in avoiding viral propagation. This technology mainly comprises of portable devices that assist self-isolated patients in adhering to safe precautionary measures. Government officials are currently using wireless technologies to identify infected people at large gatherings. In this research, we gave an overview of wireless technologies that assisted the general public and healthcare professionals in maintaining effective healthcare services during COVID-19. We also discussed the possible challenges faced by them for effective implementation in day-to-day life. In conclusion, wireless technologies are one of the best techniques in today's age to effectively combat the pandemic.
Fulltext Organogenesis and Ultrastructural Features of In Vitro Grown Canna indica L

Wafa SN, Mat Taha R, Mohajer S, Mahmad N, Ali Ahmed Abdul B

Biomed Res Int, 2016;2016:2820454.
PMID: 26885503 DOI: 10.1155/2016/2820454

An efficient protocol for micropropagation of Canna indica L., an economically and pharmaceutically important plant, was standardized using rhizome explants, excised from two-month-old aseptic seedlings. Complete plant regeneration was induced on MS medium supplemented with 3.0 mg/L BAP plus 1.5 mg/L NAA, which produced the highest number of shoots (73.3 ± 0.5%) and roots (86.7 ± 0.4%) after 2 weeks. Furthermore, the optimum media for multiple shoots regeneration were recorded on MS enriched with 7.0 mg/L BAP (33.0 ± 0.5%). Plantlets obtained were transplanted to pots after two months and acclimatized in the greenhouse, with 75% survival. In addition, ultrastructural studies showed that rhizomes of in vitro grown specimens were underdeveloped compared to the in vivo specimens, possibly due to the presence of wide spaces. Meanwhile, the leaves of in vivo specimens had more open stomata compared to in vitro specimens, yet their paracytic stomata structures were similar. Hence, there were no abnormalities or major differences between in vitro regenerants and mother plants.
Fulltext An expedient synthesis, acetylcholinesterase inhibitory activity, and molecular modeling study of highly functionalized hexahydro-1,6-naphthyridines

Almansour AI, Kumar RS, Arumugam N, Basiri A, Kia Y, Ali MA

Biomed Res Int, 2015;2015:965987.
PMID: 25710037 DOI: 10.1155/2015/965987

A series of hexahydro-1,6-naphthyridines were synthesized in good yields by the reaction of 3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones with cyanoacetamide in the presence of sodium ethoxide under simple mixing at ambient temperature for 6-10 minutes and were assayed for their acetylcholinesterase (AChE) inhibitory activity using colorimetric Ellman's method. Compound 4e with methoxy substituent at ortho-position of the phenyl rings displayed the maximum inhibitory activity with IC50 value of 2.12 μM. Molecular modeling simulation of 4e was performed using three-dimensional structure of Torpedo californica AChE (TcAChE) enzyme to disclose binding interaction and orientation of this molecule into the active site gorge of the receptor.
Fulltext Sharp turning and corner turning: comparison of energy expenditure, gait parameters, and level of fatigue among community-dwelling elderly

Justine M, Manaf H, Sulaiman A, Razi S, Alias HA

Biomed Res Int, 2014;2014:640321.
PMID: 24977154 DOI: 10.1155/2014/640321

This study compares energy expenditure (EE), gait parameters (GP), and level of fatigue (LOF) between 5-minute walking with sharp turning (ST) and corner turning (CT). Data were obtained from 29 community-dwelling elderly (mean age, 62.7 ± 3.54 years). For 5 minutes, in ST task, participants walked on a 3-meter pathway with 2 cones placed at each end (180° turning), while in CT task, participants walked on a 6-meter pathway with 4 cones placed at 4 corners (90° turning). The physiological cost index, pedometer, and 10-point Modified Borg Dyspnoea Scale were used to measure EE (beats/min), GP (no of steps), and LOF, respectively. Data were analyzed by using independent t-tests. EE during ST (0.62 ± 0.21 beats/min) was significantly higher than CT (0.48 ± 0.17 beats/min) (P < 0.05). GP (434 ± 92.93 steps) and LOF (1.40 ± 1.11) in ST were found to be lower compared to GP (463 ± 92.18 steps) and LOF (1.54 ± 1.34) in CT (All, P > 0.05). Higher EE in ST could be due to the difficulty in changing to a 180° direction, which may involve agility and different turning strategies (step-turn or pivot-turn) to adjust the posture carefully. In CT, participants could choose a step-turn strategy to change to a 90° direction, which was less challenging to postural control.
Fulltext Antioxidant and hepatoprotective effect of aqueous extract of germinated and fermented mung bean on ethanol-mediated liver damage

Mohd Ali N, Mohd Yusof H, Long K, Yeap SK, Ho WY, Beh BK, et al.

Biomed Res Int, 2013;2013:693613.
PMID: 23484140 DOI: 10.1155/2013/693613

Mung bean is a hepatoprotective agent in dietary supplements. Fermentation and germination processes are well recognized to enhance the nutritional values especially the concentration of active compounds such as amino acids and GABA of various foods. In this study, antioxidant and hepatoprotective effects of freeze-dried mung bean and amino-acid- and GABA-enriched germinated and fermented mung bean aqueous extracts were compared. Liver superoxide dismutase (SOD), malondialdehyde (MDA), ferric reducing antioxidant power (FRAP), nitric oxide (NO) levels, and serum biochemical profile such as aspartate transaminase (AST), alanine transaminase (ALT), triglycerides (TG), and cholesterol and histopathological changes were examined for the antioxidant and hepatoprotective effects of these treatments. Germinated and fermented mung bean have recorded an increase of 27.9 and 7.3 times of GABA and 8.7 and 13.2 times of amino acid improvement, respectively, as compared to normal mung bean. Besides, improvement of antioxidant levels, serum markers, and NO level associated with better histopathological evaluation indicated that these extracts could promote effective recovery from hepatocyte damage. These results suggested that freeze-dried, germinated, and fermented mung bean aqueous extracts enriched with amino acids and GABA possessed better hepatoprotective effect as compared to normal mung bean.
Fulltext Corrigendum to "Safety and Clinical Usage of Newcastle Disease Virus in Cancer Therapy"

Lam HY, Yeap SK, Pirozyan MR, Omar AR, Yusoff K, Abd-Aziz S, et al.

Biomed Res Int, 2017;2017:4529437.
PMID: 29333441 DOI: 10.1155/2017/4529437

[This corrects the article DOI: 10.1155/2011/718710.].
Fulltext An Overview of In Vitro, In Vivo, and Computational Techniques for Cancer-Associated Angiogenesis Studies

Rahman HS, Tan BL, Othman HH, Chartrand MS, Pathak Y, Mohan S, et al.

Biomed Res Int, 2020;2020:8857428.
PMID: 33381591 DOI: 10.1155/2020/8857428

Angiogenesis is a crucial area in scientific research because it involves many important physiological and pathological processes. Indeed, angiogenesis is critical for normal physiological processes, including wound healing and embryonic development, as well as being a component of many disorders, such as rheumatoid arthritis, obesity, and diabetic retinopathies. Investigations of angiogenic mechanisms require assays that can activate the critical steps of angiogenesis as well as provide a tool for assessing the efficacy of therapeutic agents. Thus, angiogenesis assays are key tools for studying the mechanisms of angiogenesis and identifying the potential therapeutic strategies to modulate neovascularization. However, the regulation of angiogenesis is highly complex and not fully understood. Difficulties in assessing the regulators of angiogenic response have necessitated the development of an alternative approach. In this paper, we review the standard models for the study of tumor angiogenesis on the macroscopic scale that include in vitro, in vivo, and computational models. We also highlight the differences in several modeling approaches and describe key advances in understanding the computational models that contributed to the knowledge base of the field.
Fulltext Family context and Khat chewing among adult Yemeni women: a cross-sectional study

Al-Abed AA, Sutan R, Al-Dubai SA, Aljunid SM

Biomed Res Int, 2014;2014:505474.
PMID: 24982886 DOI: 10.1155/2014/505474

Khat chewing is associated with unfavourable health outcomes and family dysfunction. Few studies have addressed the factors associated with khat chewing among Yemeni women. However, the family and husband effects on chewing khat by women have not been addressed. This study aimed to determine the prevalence of khat chewing among Yemeni women and its associated factors, particularly husbands and family factors. A cross-sectional study was conducted among 692 adult Yemeni women in the city of Sana'a in Yemen using structured "face to face" interviews. Mean (±SD) age of women was 27.3 years (±6.10). The prevalence of chewing khat by women was 29.6%. Factors associated with chewing khat among women were chewing khat by husbands (OR = 1.8; 95% CI: 1.26, 2.53), being married (OR = 2.0; 95% CI: 1.20, 3.37), frequent family social gatherings (OR = 1.5; 95% CI: 1.06, 2.10), high family income (OR = 1.57; 95% CI: 1.12, 2.21), larger house (OR = 1.63; 95% CI: 1.16, 2.31), and age of women (OR = 0.64; 95% CI: 0.44, 0.92). It is concluded that khat chewing by women in this study was significantly associated with family factors and with khat chewing by their husbands. Urgent action is needed to control khat chewing particularly among women.
Fulltext Behaviour Change in Public Health: Evidence and Implications

Pokhrel S, Anokye NK, Reidpath DD, Allotey P

Biomed Res Int, 2015;2015:598672.
PMID: 26380284 DOI: 10.1155/2015/598672
Fulltext Central Composite Designed Fast Dissolving Tablets for Improved Solubility of the Loaded Drug Ondansetron Hydrochloride

Thalluri C, Amin R, Mandhadi JR, Gacem A, Emran TB, Dey BK, et al.

Biomed Res Int, 2022;2022:2467574.
PMID: 36046453 DOI: 10.1155/2022/2467574

Ondansetron tablets that are directly compressed using crospovidone and croscarmellose as a synthetic super disintegrant are the subject of this investigation. A central composite, response surface, randomly quadratic, nonblock (version 13.0.9.0) 32 factorial design is used to optimize the formulation (two-factor three-level). To make things even more complicated, nine different formulation batches (designated as F1-F9) were created. There were three levels of crospovidone and croscarmellose (+1, 0, -1). In addition to that, pre- and postcompressional parameters were evaluated, and all evaluated parameters were found to be within acceptable range. Among all postcompressional parameter dispersion and disintegration time, in vitro drug release experiments (to quantify the amount of medication released from the tablet) and their percentage prediction error were shown to have a significant influence on three dependent variables. Various pre- and postcompression characteristics of each active component were tested in vitro. Bulk density, tap density, angle of repose, Carr's index, and the Hausner ratio were all included in this analysis, as were many others. This tablet's hardness and friability were also assessed along with its dimension and weight variations. Additional stability studies may be conducted using the best batch of the product. For this study, we utilised the Design-Expert software to select the formulation F6, which had dispersion times of 17.67 ± 0.03 seconds, disintegration times of 120.12 ± 0.55 seconds, and percentage drug release measurements of 99.25 ± 0.36 within 30 minutes. Predicted values and experimental data had a strong correlation. Fast dissolving pills of ondansetron hydrochloride may be created by compressing the tablets directly.
Fulltext Effect of High Protein Diet and Probiotic Lactobacillus casei Shirota Supplementation in Aflatoxin B1-Induced Rats

Nurul Adilah Z, Liew WP, Mohd Redzwan S, Amin I

Biomed Res Int, 2018;2018:9568351.
PMID: 29951550 DOI: 10.1155/2018/9568351

Probiotic Lactobacillus casei Shirota (LcS) is a potential decontaminating agent of aflatoxin B1 (AFB1). However, few studies have investigated the influence of diet, especially a high protein (HP) diet, on the binding of AFB1 by probiotics. This research was conducted to determine the effect of HP diet on the ability of LcS to bind AFB1 and reduce aflatoxin M1 (AFM1) in AFB1-induced rats. Sprague Dawley rats were randomly divided into three groups: A (HP only), B (HP + 108 CFU LcS + 25 μg AFB1/kg BW), and C (HP + 25 μg AFB1/kg BW). Levels of AST and ALP were higher in all groups but other liver function's biomarkers were in the normal range, and the liver's histology showed no structural changes. The urea level of rats in group B (10.02 ± 0.73 mmol/l) was significantly lower (p < 0.05) than that of rats in group A (10.82 ± 0.26 mmol/l). The presence of carcinoma in the small intestine and colon was more obvious in group C than in group B. Moreover, rats in group B had significantly (p < 0.05) lower AFM1 concentration (0.39 ± 0.01 ng/ml) than rats in group C (5.22 ± 0.28 ng/ml). Through these findings, LcS supplementation with HP diet alleviated the adverse effects of AFB1 by preventing AFB1 absorption in the small intestine and reducing urinary AFM1.
Fulltext Numerical Solution of Blood Flow and Mass Transport in an Elastic Tube with Multiple Stenoses

Alsemiry RD, Sarifuddin, Mandal PK, Sayed HM, Amin N

Biomed Res Int, 2020;2020:7609562.
PMID: 32090110 DOI: 10.1155/2020/7609562

The simultaneous effect of flexible wall and multiple stenoses on the flow and mass transfer of blood is investigated through numerical computation and simulations. The solution is obtained using the Marker and Cell technique on an axisymmetric model of Newtonian blood flow. The results compare favorably with physical observations where the pulsatile boundary condition and double stenoses result in a higher pressure drop across the stenoses. The streamlines, the iso-concentration lines, the Sherwood number, and the mass concentration variations along the entire wall segment provide a comprehensive analysis of the mass transport characteristics. The double stenoses and pulsatile inlet conditions increase the number of recirculation regions and effect a higher mass transfer rate at the throat, whereby more mass is expected to accumulate and cause further stenosis.
Fulltext Characterisation of potential antidiabetic-related proteins from Pleurotus pulmonarius (Fr.) Quél. (grey oyster mushroom) by MALDI-TOF/TOF mass spectrometry

Wahab NA, Abdullah N, Aminudin N

Biomed Res Int, 2014;2014:131607.
PMID: 25243114 DOI: 10.1155/2014/131607

Pleurotus pulmonarius has been reported to have a potent remedial effect on diabetic property and considered to be an alternative for type 2 diabetes mellitus treatment. This study aimed to investigate the antidiabetic properties of ammonium sulphate precipitated protein fractions from P. pulmonarius basidiocarps. Preliminary results demonstrated that 30% (NH4)2SO4 precipitated fraction (F30) inhibited Saccharomyces cerevisiae α-glucosidase activity (24.18%), and 100% (NH4)2SO4 precipitated fraction (F100) inhibited porcine pancreatic α-amylase activity (41.80%). Following RP-HPLC purification, peak 3 from F30 fraction demonstrated inhibition towards α-glucosidase at the same time with meagre inhibition towards α-amylase activity. Characterisation of proteins using MALDI-TOF/TOF MS demonstrated the presence of four different proteins, which could be implicated in the regulation of blood glucose level via various mechanisms. Therefore, this study revealed the presence of four antidiabetic-related proteins which are profilin-like protein, glyceraldehyde-3-phosphate dehydrogenase-like protein, trehalose phosphorylase-like (TP-like) protein, and catalase-like protein. Hence, P. pulmonarius basidiocarps have high potential in lowering blood glucose level, reducing insulin resistance and vascular complications.
Fulltext Inhibitory effect on in vitro LDL oxidation and HMG Co-A reductase activity of the liquid-liquid partitioned fractions of Hericium erinaceus (Bull.) Persoon (lion's mane mushroom)

Rahman MA, Abdullah N, Aminudin N

Biomed Res Int, 2014;2014:828149.
PMID: 24959591 DOI: 10.1155/2014/828149

Oxidation of low-density lipoprotein (LDL) has been strongly suggested as the key factor in the pathogenesis of atherosclerosis. Mushrooms have been implicated in having preventive effects against chronic diseases due especially to their antioxidant properties. In this study, in vitro inhibitory effect of Hericium erinaceus on LDL oxidation and the activity of the cholesterol biosynthetic key enzyme, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG Co-A) reductase, was evaluated using five liquid-liquid solvent fractions consisting of methanol : dichloromethane (M : DCM), hexane (HEX), dichloromethane (DCM), ethyl acetate (EA), and aqueous residue (AQ). The hexane fraction showed the highest inhibition of oxidation of human LDL as reflected by the increased lag time (100 mins) for the formation of conjugated diene (CD) at 1 µg/mL and decreased production (68.28%, IC50 0.73 mg/mL) of thiobarbituric acid reactive substances (TBARS) at 1 mg/mL. It also mostly inhibited (59.91%) the activity of the HMG Co-A reductase at 10 mg/mL. The GC-MS profiling of the hexane fraction identified the presence of myconutrients: inter alia, ergosterol and linoleic acid. Thus, hexane fraction of Hericium erinaceus was found to be the most potent in vitro inhibitor of both LDL oxidation and HMG Co-A reductase activity having therapeutic potential for the prevention of oxidative stress-mediated vascular diseases.
Fulltext Genetic Diversity Assessment of MPOB-Senegal Oil Palm Germplasm Using Microsatellite Markers

Myint KA, Yaakub Z, Rafii MY, Oladosu Y, Samad MYA, Ramlee SI, et al.

Biomed Res Int, 2021;2021:6620645.
PMID: 33997027 DOI: 10.1155/2021/6620645

Molecular characterization of oil palm germplasm is crucial in utilizing and conserving germplasm with promising traits. This study was conducted to evaluate the genetic diversity structures and relationships among 26 families of MPOB-Senegal oil palm germplasm using thirty-five microsatellite markers. High level of polymorphism (P = 96.26%), number of effective allele (N e = 2.653), observed heterozygosity (H o = 0.584), expected heterozygosity (H e = 0.550), total heterozygosity (H T = 0.666), and rare alleles (54) were observed which indicates that MPOB-Senegal germplasm has a broad genetic variation. Among the SSR markers, sMo00053 and sMg00133 were the most informative markers for discrimination among the MPOB-Senegal oil palm germplasm for having the highest private alleles and the rare alleles. For selection and conservation, oil palm populations with high rare alleles and Nei's gene diversity index should be considered as these populations may possess unique genes for further exploitation.
Fulltext Recombinant dense granular protein (GRA5) for detection of human toxoplasmosis by Western blot

Ching XT, Lau YL, Fong MY, Nissapatorn V, Andiappan H

Biomed Res Int, 2014;2014:690529.
PMID: 24987700 DOI: 10.1155/2014/690529

Toxoplasma gondii infects all warm-blooded animals, including humans, causing serious public health problems and great economic loss for the food industry. Commonly used serological tests require costly and hazardous preparation of whole Toxoplasma lysate antigens from tachyzoites. Here, we have evaluated an alternative method for antigen production, which involved a prokaryotic expression system. Specifically, we expressed T. gondii dense granular protein-5 (GRA5) in Escherichia coli and isolated it by affinity purification. The serodiagnostic potential of the purified recombinant GRA5 (rGRA5) was tested through Western blot analysis against 212 human patient serum samples. We found that rGRA5 protein was 100% specific for analysis of toxoplasmosis-negative human sera. Also, rGRA5 was able to detect acute and chronic T. gondii infections (sensitivities of 46.8% and 61.2%, resp.).
Fulltext HOXA4 gene promoter hypermethylation as an epigenetic mechanism mediating resistance to imatinib mesylate in chronic myeloid leukemia patients

Elias MH, Baba AA, Husin A, Sulong S, Hassan R, Sim GA, et al.

Biomed Res Int, 2013;2013:129715.
PMID: 23484077 DOI: 10.1155/2013/129715

Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients has emerged as a significant clinical problem. The observation that increased epigenetic silencing of potential tumor suppressor genes correlates with disease progression in some CML patients treated with IM suggests a relationship between epigenetic silencing and resistance development. We hypothesize that promoter hypermethylation of HOXA4 could be an epigenetic mechanism mediating IM resistance in CML patients. Thus a study was undertaken to investigate the promoter hypermethylation status of HOXA4 in CML patients on IM treatment and to determine its role in mediating resistance to IM. Genomic DNA was extracted from peripheral blood samples of 95 CML patients (38 good responders and 57 resistant) and 12 normal controls. All samples were bisulfite treated and analysed by methylation-specific high-resolution melt analysis. Compared to the good responders, the HOXA4 hypermethylation level was significantly higher (P = 0.002) in IM-resistant CML patients. On comparing the risk, HOXA4 hypermethylation was associated with a higher risk for IM resistance (OR 4.658; 95% CI, 1.673-12.971; P = 0.003). Thus, it is reasonable to suggest that promoter hypermethylation of HOXA4 gene could be an epigenetic mechanism mediating IM resistance in CML patients.

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