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Fulltext Role of the CYP1A2 Gene Polymorphism on Early Ageing from Occupational Exposure

Eshkoor S, Ismail P, Rahman S, Moin S, Adon M

Balkan J Med Genet, 2013 Dec;16(2):45-52.
PMID: 24778563 DOI: 10.2478/bjmg-2013-0031

The ageing process is influenced by many internal and external factors. The toxic substances in the environment can cause genomic damages to cells, which increase the risk of early ageing. Furthermore, the cytochrome P450 1A2 (CYP1A2) gene polymorphism is a susceptibility factor and may enhance the risk of DNA damage in cells. The current study was carried out to show whether occupational exposure could cause genotoxicity in cells carrying the CYP1A2 gene polymorphism, thus enhancing the likelihood of early ageing. This study was conducted on mechanical workshop workers and a control group by collecting buccal cells from their mouths. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to identify the CYP1A2 gene polymorphism in the cells. In addition, three extra methods including micronuclei (MN) test, comet assay and real-time PCR (RT-PCR) were applied to determine the effects of gene polymorphisms on DNA damage and ageing from occupational exposure. The results showed that DNA damage in the cells carrying the mutated genotype was higher than the wild genotype. In addition, the difference in MN frequency (p = 0.001) and relative telomere length (p = 0.002) between workers and controls was significant (p <0.05) in the mutated genotype. The findings indicated a possible protective effect of gene polymorphism against early ageing, which was characterized by lack of a significant influence of CYP1A2 gene polymorphism on genetic material in the subjects (p >0.05). It was concluded that the CYP1A2 gene could be a contributing factor to prevent early ageing from occupational exposure.
Fulltext A research on functional status, environmental conditions, and risk of falls in dementia

Eshkoor SA, Hamid TA, Nudin SS, Mun CY

Int J Alzheimers Dis, 2014;2014:769062.
PMID: 24963440 DOI: 10.1155/2014/769062

This study aimed to determine the effects of disability, physical activity, and functional status as well as environmental conditions on the risk of falls among the elderly with dementia after adjusting for sociodemographic factors. Data were derived from a group including 1210 Malaysian elderly who were demented and noninstitutionalized. The study was a national cross-sectional survey that was entitled "Determinants of Health Status among Older Malaysians." Approximately 17% of subjects experienced falls. The results showed that ethnic non-Malay (OR = 1.73) and functional decline (OR = 1.67) significantly increased the risk of falls in samples (P < 0.05). The findings indicated that increased environmental quality (OR = 0.64) significantly decreased the risk of falls (P < 0.05). Disability, age, marital status, educational level, sex differences, and physical activity were found irrelevant to the likelihood of falls in subjects (P > 0.05). It was concluded that functional decline and ethnic non-Malay increased the risk of falls but the increased environmental quality reduced falls.
Fulltext Association between dentures and the rate of falls in dementia

Eshkoor SA, Hamid TA, Nudin SS, Mun CY

Med Devices (Auckl), 2014;7:225-30.
PMID: 25018658 DOI: 10.2147/MDER.S63220

BACKGROUND: Poor oral health, chronic diseases, functional decline, and low cognitive ability can increase the risk of falls in the elderly.
OBJECTIVES: The current study aimed to show the effects of oral health, diabetes mellitus (DM), hypertension (HT), heart disease, functional status, and sociodemographic factors on the risk of falls in elderly with dementia.
MATERIALS AND METHODS: The sample comprised 1,210 Malaysian elderly who were demented and noninstitutionalized. This study was a national cross-sectional survey entitled "Determinants of Health Status among Older Malaysians". The effects of age, ethnicity, sex differences, marital status, educational level, oral health, DM, HT, heart disease, and functional status on the risk of falls were evaluated. The multiple logistic regression model was used to estimate the effects of contributing variables on the risk of falls in samples.
RESULTS: The prevalence of falls was approximately 17% in subjects. It was found that age (odds ratio [OR] 1.02), non-Malay ethnicity (OR 1.66), heart disease (OR 1.92), and functional decline (OR 1.58) significantly increased the risk of falls in respondents (P<0.05). Furthermore, having teeth (OR 0.59) and dentures (OR 0.66) significantly decreased the rate of falls (P<0.05).
CONCLUSION: It was concluded that age, non-Malay ethnicity, functional decline, heart disease, and oral health significantly affected falls in dementia.
KEYWORDS: chronic diseases; dementia; fall; functional decline; oral health
Fulltext The centella asiatica juice effects on DNA damage, apoptosis and gene expression in hepatocellular carcinoma (HCC)

Hussin F, Eshkoor SA, Rahmat A, Othman F, Akim A

BMC Complement Altern Med, 2014 Jan 20;14:32.
PMID: 24444147 DOI: 10.1186/1472-6882-14-32

BACKGROUND: This paper is to investigate the effects of Centella asiatica on HepG2 (human hepatocellular liver carcinoma cell line). Centella asiatica is native to the Southeast Asia that is used as a traditional medicine. This study aims to determine the chemopreventive effects of the Centella asiatica juice on human HepG2 cell line.
METHODS: Different methods including flow cytometry, comet assay and reverse transcription-polymerase chain reaction (RT-PCR) were used to show the effects of juice exposure on the level of DNA damage and the reduction of cancerous cells. MTT assay is a colorimetric method applied to measure the toxic effects of juice on cells.
RESULTS: The Centella asiatica juice was not toxic to normal cells. It showed cytotoxic effects on tumor cells in a dose dependent manner. Apoptosis in cells was started after being exposed for 72 hr of dose dependent. It was found that the higher percentage of apoptotic cell death and DNA damage was at the concentration above 0.1%. In addition, the juice exposure caused the reduction of c-myc gene expression and the enhancement of c-fos and c-erbB2 gene expressions in tumor cells.
CONCLUSIONS: It was concluded that the Centella asiatica juice reduced liver tumor cells. Thus, it has the potential to be used as a chemopreventive agent to prevent and treat liver cancer.
Does substance abuse contribute to further risk of falls in dementia

Eshkoor SA, Hamid TA, Nudin SS, Mun CY

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn, 2014;21(3):317-24.
PMID: 23883099 DOI: 10.1080/13825585.2013.819067

This study aimed to predict the risk of falls by focusing on substance abuse in the elderly with dementia. Our national cross-sectional survey included 1210 elderly Malaysian demented subjects. The study identified the effects of age, ethnicity, sex differences, marital status, educational level, and substance abuse on the likelihood of falls in the elderly with dementia. The multivariate logistic regression model was used to analyze data collected from samples. The prevalence of falls was about 17% among subjects and significantly increased with age (p = .006). Furthermore, the results showed that age (OR = 1.03), ethnicity (OR = 1.69), substance abuse (OR = 1.68), and female sex (OR = 1.45) significantly enhanced the risk of falls in respondents (p < .05). Educational level and marital status had no significant effects on the likelihood of falls (p > .05). However, the findings provided evidence of an additional effect of substance abuse on further risk of falls in older adults with dementia.
Does GSTP1 polymorphism contribute to genetic damage caused by ageing and occupational exposure?

Eshkoor SA, Ismail P, Rahman SA, Moin S

Arh Hig Rada Toksikol, 2011 Dec;62(4):291-8.
PMID: 22202462 DOI: 10.2478/10004-1254-62-2011-2088

The aim of our study was to see the effects of GSTP1 polymorphism on biomarkers of ageing, including micronuclei (MN), comet tail length, and relative telomere length in automobile repair workers, who are exposed to a broad spectrum of potential mutagens. The analysis was performed on buccal cells collected from occupationally exposed and non-exposed (control) subjects. Samples were analysed using cytogenetic and molecular methods, including restriction fragment length polymorphism (RFLP), MN test, comet assay, and real-time PCR. The results confirmed the DNA damaging effects of substances used in the mechanical workshops, but did not confirm the influence of GSTP1 gene polymorphism on DNA damage. However, further studies on both occupationally exposed and control populations are needed to understand the relationship between GSTP1 polymorphism and genome damage.
Fulltext Mild cognitive impairment and its management in older people

Eshkoor SA, Hamid TA, Mun CY, Ng CK

Clin Interv Aging, 2015;10:687-93.
PMID: 25914527 DOI: 10.2147/CIA.S73922

Mild cognitive impairment (MCI) is a common condition in the elderly. It is characterized by deterioration of memory, attention, and cognitive function that is beyond what is expected based on age and educational level. MCI does not interfere significantly with individuals' daily activities. It can act as a transitional level of evolving dementia with a range of conversion of 10%-15% per year. Thus, it is crucial to protect older people against MCI and developing dementia. The preventive interventions and appropriate treatments should improve cognitive performance, and retard or prevent progressive deficits. The avoidance of toxins, reduction of stress, prevention of somatic diseases, implementation of mental and physical exercises, as well as the use of dietary compounds like antioxidants and supplements can be protective against MCI. The modification of risk factors such as stopping smoking, as well as the treatment of deficiency in vitamins and hormones by correcting behaviors and lifestyle, can prevent cognitive decline in the elderly. The progressive increase in the growth rate of the elderly population can enhance the rate of MCI all over the world. There is no exact cure for MCI and dementia; therefore, further studies are needed in the future to determine causes of MCI and risk factors of progression from MCI to dementia. This will help to find better ways for prevention and treatment of cognitive impairment worldwide.
p16 gene expression in basal cell carcinoma

Eshkoor SA, Ismail P, Rahman SA, Oshkour SA

Arch Med Res, 2008 Oct;39(7):668-73.
PMID: 18760195 DOI: 10.1016/j.arcmed.2008.06.003

Basal cell carcinoma (BCC) develops predominantly in sun-exposed skin in fair-skinned individuals prone to sunburn. BCC typically occurs in adults. High exposure to ultraviolet (UV) radiation increases rate of developing BCC, a slowly growing tumor that occurs in hair-growing squamous epithelium and rarely metastasizes. In genetic studies, BCC patients have cell-cycle abnormalities of different parts of the signaling pathway. Retinoblastoma regulatory pathway is important in cell cycle arrest. In this pathway, p16INK4a, an inhibitor of Rb pathway, binds to CDK4 and CDK6 competitively with cyclin D1 to prevent phosphorylation of tumor suppressor pRB gene. Alteration of this pathway contributes to development of human cancers and also is effective in skin cancers. In this study, we analyzed mRNA expression using in situ RT-PCR and the role of immunohistochemical expression of p16INK4a in BCC.
Increased protein expression of p16 and cyclin D1 in squamous cell carcinoma tissues

Eshkoor SA, Ismail P, Rahman SA, Mirinargesi M, Oshkour SA

Biosci Trends, 2009 Jun;3(3):105-9.
PMID: 20103831

Abnormalities of Rb-pathway components are common in the formation of cancer. The immunostaining for cyclin D1 and p16 protein was applied on 1 mm serial tissue microarray (TMA) paraffin sections. Tissue microarray (TMAs) is potentially a good method to find the molecular features of the genes and expressions of them. The aim of this study was to evaluate the protein expressions of cyclin D1 and p16 genes in squamous cell carcinomas (SCCs) of skin and compare with the normal skin tissue. Twenty-five cases of cutaneous SCCs expressed cyclin D1 and p16 proteins. All SCCs samples on the slides showed positive protein expressions of cyclin D1 and p16 genes. Our findings suggested that the increased protein expressions of cyclin D1 and p16 genes might lead to aberrant expressions of these proteins in the affected tumor cells. This study demonstrated that cell cycle controlled deregulation and uncontrolled cell cycle progression might result in the carcinogenesis.
Fulltext The effects of sleep quality, physical activity, and environmental quality on the risk of falls in dementia

Eshkoor SA, Hamid TA, Nudin SS, Mun CY

Am J Alzheimers Dis Other Demen, 2013 Jun;28(4):403-7.
PMID: 23698600 DOI: 10.1177/1533317513488921

OBJECTIVES: This study aimed to identify the effects of sleep quality, physical activity, environmental quality, age, ethnicity, sex differences, marital status, and educational level on the risk of falls in the elderly individuals with dementia.
METHODOLOGY: Data were derived from a group of 1210 Malaysian elderly individuals who were noninstitutionalized and demented. The multiple logistic regression model was applied to estimate the risk of falls in respondents.
RESULTS: Approximately the prevalence of falls was 17% among the individuals. The results of multiple logistic regression analysis revealed that age (odds ratio [OR] = 1.03), ethnicity (OR = 1.76), sleep quality (OR = 1.46), and environmental quality (OR = 0.62) significantly affected the risk of falls in individuals (P < .05). Furthermore, sex differences, marital status, educational level, and physical activity were not significant predictors of falls in samples (P > .05).
CONCLUSION: It was found that age, ethnic non-Malay, and sleep disruption increased the risk of falls in respondents, but high environmental quality reduced the risk of falls.
Fulltext The effects of social support and having a partner on sleep quality in dementia

Eshkoor SA, Hamid TA, Nudin SS, Mun CY

Am J Alzheimers Dis Other Demen, 2013 May;28(3):253-7.
PMID: 23612908 DOI: 10.1177/1533317513481098

OBJECTIVES: This study aimed to determine the effects of social support and having a partner on sleep quality in the elderly patients with dementia.
METHODOLOGY: This research was conducted on 1210 noninstitutionalized elderly Malaysian individuals with dementia. The effects of age, ethnicity, educational level, marital status, sex differences, social support, and having a partner on sleep quality were evaluated in the respondents. The multiple logistic regression analysis was used to predict the risk of sleep disturbances among the participants.
RESULTS: Approximately, 41% of the participants experienced sleep disruption. Further findings showed that ethnicity (odds ratio [OR] = 0.62), social support (OR = 1.35), marital status (OR = 2.21), educational level (OR = 0.65), and having a partner (OR = 0.45) significantly affected sleep quality (P < .05). Sex differences and age were unrelated predictors of sleep disturbances (P > .05).
CONCLUSION: It was concluded that social isolation and being single increased sleep disruption among respondents, but having a partner and ethnic non-Malay decreased the rate of sleep problems.
Factors Related to Urinary Incontinence among the Malaysian Elderly

Eshkoor SA, Hamid TA, Shahar S, Mun CY

J Nutr Health Aging, 2017;21(2):220-226.
PMID: 28112780 DOI: 10.1007/s12603-016-0779-x

BACKGROUND: Urinary incontinence is a prevalent condition in the elderly that is the spontaneous leakage of urine. It is an age-related problem and increases especially in people aged above 65 years. It can cause many psychological, behavioral, biological, economic and social effects. The treatment of urinary incontinence can reduce morbidity and mortality. Thus, this study aimed to determine the effects of variables including age, ethnicity, gender, education, marital status, body weight, blood elements and nutritional parameters on urinary incontinence among the Malaysian elderly.
METHODS: The study was on 2322 non-institutionalized Malaysian elderly. The hierarchy logistic regression analysis was applied to estimate the risk of independent variables for urinary incontinence among respondents.
RESULTS: The findings indicated that approximately 3.80% of subjects had urinary incontinence. In addition, constipation was found a significant factor that increased the risk of urinary incontinence in samples (p=0.006; OR=3.77). The increase in dietary monounsaturated fat (p=0.038; OR=0.59) and plasma triglyceride levels (p=0.029; OR=0.56) significantly reduced the risk of incontinence in subjects. Many of suspected variables including socio-demographic factors, diseases, nutritional minerals, blood components and body weight were non-relevant factors to urinary incontinence in respondents.
CONCLUSIONS: Constipation increased the risk of urinary incontinence in subjects, and increase in dietary monounsaturated fat and plasma triglyceride levels decreased the risk.
Fulltext Importance of hypertension and social isolation in causing sleep disruption in dementia

Eshkoor SA, Hamid TA, Nudin SS, Mun CY

Am J Alzheimers Dis Other Demen, 2014 Feb;29(1):61-6.
PMID: 24085252 DOI: 10.1177/1533317513505136

This study aimed to determine the effects of diabetes mellitus (DM), hypertension (HT), heart disease, social isolation, and sociodemographic factors on sleep in the elderly patients with dementia. Samples included 1210 noninstitutionalized, Malaysian elderly patients with dementia. The multiple logistic regression analysis was applied to estimate the risk of sleep disturbances among respondents. Approximately 41% of the patients experienced sleep problems. The results showed that age (odds ratio [OR] = 1.02), social isolation (OR = 1.33), and HT (OR = 1.53) significantly increased sleep disruption in respondents (P .05). It was concluded that age, social isolation, and HT increased sleep disruption but education and ethnic non-Malay reduced the risk of sleep problems. Moreover, HT was the most important variable to increase sleep disturbances in the elderly patients with dementia.
Fulltext Association of GSTM1 and GSTT1 with ageing in auto repair shop workers

Eshkoor SA, Marashi SJ, Ismail P, Rahman SA, Mirinargesi M, Adon MY, et al.

Genet. Mol. Res., 2012;11(2):1486-96.
PMID: 22653598 DOI: 10.4238/2012.May.21.5

We evaluated the possible influence of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) genes on genetic damage due to occupational exposure, which contributes to accelerate ageing. This study was conducted on 120 car auto repair workshop workers exposed to occupational hazards and 120 controls without this kind of exposure. The null and non-null genotypes of GSTM1 and GSTT1 genes were determined by multiplex PCR. Micronucleus frequency, Comet tail length and relative telomere length differences between the null and non-null genotypes of the GSTM1 gene were significantly greater in the exposed group. Lack of GSTT1 did not affect the damage biomarkers significantly (P > 0.05), while lack of GSTM1 was associated with greater susceptibility to genomic damage due to occupational exposure. It was concluded that early ageing is under the influence of these genes and the environmental and socio-demographic factors. Duration of working time was significantly associated with micronucleus frequency, Comet tail length and relative telomere length.
Contribution of CYP2E1 polymorphism to aging in the mechanical workshop workers

Eshkoor SA, Ismail P, Rahman SA, Adon MY, Devan RV

Toxicol. Mech. Methods, 2013 May;23(4):217-22.
PMID: 23193996 DOI: 10.3109/15376516.2012.743637

Aging is attributed to both genetic and environmental factors. Occupational exposure is one of the environmental factors with potential genotoxic effects. Researchers try to determine factors involved in genetic damages at hazards exposure that could accelerate aging. Cytochrome P450 2E1 (CYP2E1) gene contributes in activation and detoxification of the environmental hazards. This polymorphism plays an important role in susceptibility of inter-individuals to DNA damage at the occupational exposure. The current study evaluated the possible influence of this gene polymorphism in aging by genomic damages through the biomarkers alterations of micronuclei (MN), comet tail length and telomere length shortening at the exposure. In this study, buccal cells were collected from the oral cavity of exposed workers and non-exposed controls. The CYP2E1 genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The wild genotype significantly affected MN frequency (p = 0.007) and relative telomere length (p = 0.047) in the older group of workers. It was concluded that the interaction of gene polymorphism and exposure enhances DNA damage and accelerates aging consequently.
Strobilanthes crispus Juice Concentrations and Anticancer Effects on DNA Damage, Apoptosis and Gene Expression in Hepatocellular Carcinoma Cells

Hussin F, Eshkoor SA, Rahmat A, Othman F, Akim A, Eshak Z

Asian Pac J Cancer Prev, 2015;16(14):6047-53.
PMID: 26320494

BACKGROUND: Hepatocellular carcinoma is one of the most common cancers worldwide. Its prevalence is increasing in many countries. Plant products can be used to protect against cancer due to natural anticancer and chemopreventive constituents. Strobilanthes crispus is one of plants with potential chemopreventive ability.
OBJECTIVE: This study aimed to evaluate the anticancer effects of Strobilanthes crispus juice on hepatocellular carcinoma cells.
MATERIALS AND METHODS: MTT assays, flow cytometry, comet assays and the reverse transcription- polymerase chain reaction (RT-PCR) were used to determine the effects of juice on DNA damage and cancer cell numbers.
RESULTS: This juice induced apoptosis after exposure of the HepG2 cell line for 72 h. High percentages of apoptotic cell death and DNA damage were seen at the juice concentrations above 0.1%. It was found that the juice was not toxic for normal cells. In addition, juice exposure increased the expression level of c-myc gene and reduced the expression level of c-fos and c-erbB2 genes in HepG2 cells. The cytotoxic effects of juice on abnormal cells were in dose dependent.
CONCLUSIONS: It was concluded that the Strobilanthes crispus juice may have chemopreventive effects on hepatocellular carcinoma cells.
Fulltext Association of TNF-α G308A gene polymorphism in essential hypertensive patients without type 2 diabetes mellitus

Ghodsian N, Akhlaghi M, Ramachandran V, Heidari F, Haghvirdizadeh P, Eshkoor SA, et al.

Genet. Mol. Res., 2015 Dec 29;14(4):18974-9.
PMID: 26782547 DOI: 10.4238/2015.December.29.4

This study aims to investigate the effects of tumor necrosis factor alpha (TNF-α) G308A gene polymorphism on essential hypertension (EHT) with or without type 2 diabetes mellitus (T2DM). The project was conducted on buccal epithelial and blood cells for case and control patients, respectively. Epithelial cells were obtained from the inner part of the cheeks. Techniques including DNA extraction, polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLP) were utilized to assess biomarkers of DNA damage. Our results demonstrated significant differences between wild and mutated genotypes among EHT patients without T2DM. We also found a significant association between wild and mutated allele frequencies in EHT patients (P < 0.05). Clinical characteristics between the groups (EHT with or without T2DM and controls) showed statistically significant association (P < 0.05). Overall, we show that G308A polymorphism of the TNF-αgene may be a significant genetic risk factor for EHT without T2DM patients in Malaysia.

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