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Fulltext Methylenetetrahydrofolate Reductase CpG Islands: Epigenotyping

Wei LK, Sutherland H, Au A, Camilleri E, Haupt LM, Gan SH, et al.

J Clin Lab Anal, 2016 Jul;30(4):335-44.
PMID: 26109141 DOI: 10.1002/jcla.21860

BACKGROUND: Determination of the differential DNA methylation patterns of methylenetetrahydrofolate reductase (MTHFR) that are associated with differential MTHFR activity is important to understand the pathogenesis of ischemic stroke. However, to date, no data are available on the differential DNA methylation profiles of Kelantanese Malays. Therefore, we developed a rapid and efficient serial pyrosequencing assay to determine differential DNA methylation profiles of MTHFR, which help to further our understanding of the pathogenesis of ischemic stroke. The developed assay also served as the validation platform for our previous computational epigenetic research on MTHFR.
METHODS: Polymerase chain reaction primers were designed and validated to specifically amplify the cytosine that is followed by guanine residues (CpGs) A and B regions. Prior epigenotyping on 110 Kelantanese Malays, the serial pyrosequencing assays for the CpGs A and B regions were validated using five validation controls. The mean values of the DNA methylation profiles of CpGs A and B were calculated.
RESULTS: The mean DNA methylation levels for CpGs A and B were 0.984 ± 0.582 and 2.456 ± 1.406, respectively. The CpGs 8 and 20 showed the highest (5.581 ± 4.497) and the lowest (0.414 ± 2.814) levels of DNA methylation at a single-base resolution.
CONCLUSION: We have successfully developed and validated a pyrosequencing assay that is fast and can yield high-quality pyrograms for DNA methylation analysis and is therefore applicable to high throughput study. Using this newly developed pyrosequencing assay, the MTHFR DNA methylation profiles of 110 Kelantanese Malays were successfully determined. It also validated our computational epigenetic research on MTHFR.
A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats

Tanvir EM, Afroz R, Chowdhury M, Gan SH, Karim N, Islam MN, et al.

Hum Exp Toxicol, 2016 Sep;35(9):991-1004.
PMID: 26519480 DOI: 10.1177/0960327115614384

This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals.
Fulltext Familial primary antiphospholipid syndrome: A report of co-occurrence in three Malaysian family members

Islam MA, Wong KK, Sasongko TH, Gan SH, Wong JS

Eur J Rheumatol, 2016 Sep;3(3):139-141.
PMID: 27733946 DOI: 10.5152/eurjrheum.2015.0068

Here we present a case report of three familial primary antiphospholipid syndrome (PAPS) patients from Malaysia. The three familial patients comprised two females and one male with a mean age of 26.3 years. The first diagnosis was made between 2005 and 2009, and all patients demonstrated deep vein thrombosis, high levels of IgM and IgG anticardiolipin antibodies, and received warfarin treatment international normalized ratio (INR) 2.0-3.0. The patients ceased to show clinical symptoms after treatment. Recently (August 2014), we investigated whether the levels of antiphospholipid antibodies remained elevated, and we found that seronegativity occurred in the patients. We suspect that prolonged anticoagulant treatment might be one of the causes of reduced levels of antiphospholipid antibodies in these familial PAPS patients.
Polyphenols: Potential Future Arsenals in the Treatment of Diabetes

Solayman M, Ali Y, Alam F, Islam MA, Alam N, Khalil MI, et al.

Curr Pharm Des, 2016;22(5):549-65.
PMID: 26601968

Diabetes mellitus (DM) is one of the most common endocrine metabolic disorders. In addition to exercise and diet, oral anti-diabetic drugs have been used as a part of the management strategy worldwide. Unfortunately, none of the conventional anti-diabetic drugs are without side effects, and these drugs pose an economic burden. Therefore, the investigation of novel anti-diabetic regimens is a major challenge for researchers, in which nature has been the primary resource for the discovery of potential therapeutics. Many plants have been shown to act as anti-diabetic agents, in which the main active constituents are believed to be polyphenols. Natural products containing high polyphenol levels can control carbohydrate metabolism by various mechanisms, such as protecting and restoring beta-cell integrity, enhancing insulin releasing activity, and increasing cellular glucose uptake. Blackberries, red grapes, apricots, eggplant and popular drinks such as coffee, cocoa and green tea are all rich in polyphenols, which may dampen insulin resistance and be natural alternatives in the treatment of diabetes. Therefore, the aim of this review is to report on the available anti-diabetic polyphenols (medicinal plants, fruits and vegetables), their mechanisms in the various pathways of DM and their correlations with DM. Additionally, this review emphasizes the types of polyphenols that could be potential future resources in the treatment of DM via either novel regimens or as supplementary agents.
Natural Products Towards the Discovery of Potential Future Antithrombotic Drugs

Islam MA, Alam F, Khalil MI, Sasongko TH, Gan SH

Curr Pharm Des, 2016;22(20):2926-46.
PMID: 26951101

Globally, thrombosis-associated disorders are one of the main contributors to fatalities. Besides genetic influences, there are some acquired and environmental risk factors dominating thrombotic diseases. Although standard regimens have been used for a long time, many side effects still occur which can be life threatening. Therefore, natural products are good alternatives. Although the quest for antithrombotic natural products came to light only since the end of last century, in the last two decades, a considerable number of natural products showing antithrombotic activities (antiplatelet, anticoagulant and fibrinolytic) with no or minimal side effects have been reported. In this review, several natural products used as antithrombotic agents including medicinal plants, vegetables, fruits, spices and edible mushrooms which have been discovered in the last 15 years and their target sites (thrombogenic components, factors and thrombotic pathways) are described. In addition, the side effects, limitations and interactions of standard regimens with natural products are also discussed. The active compounds could serve as potential sources for future research on antithrombotic drug development. As a future direction, more advanced researches (in quest of the target cofactor or component involved in antithrombotic pathways) are warranted for the development of potential natural antithrombotic medications (alone or combined with standard regimens) to ensure maximum safety and efficacy.
Fulltext Impacts of Nonsynonymous Single Nucleotide Polymorphisms of Adiponectin Receptor 1 Gene on Corresponding Protein Stability: A Computational Approach

Saleh MA, Solayman M, Paul S, Saha M, Khalil MI, Gan SH

Biomed Res Int, 2016;2016:9142190.
PMID: 27294143 DOI: 10.1155/2016/9142190

Despite the reported association of adiponectin receptor 1 (ADIPOR1) gene mutations with vulnerability to several human metabolic diseases, there is lack of computational analysis on the functional and structural impacts of single nucleotide polymorphisms (SNPs) of the human ADIPOR1 at protein level. Therefore, sequence- and structure-based computational tools were employed in this study to functionally and structurally characterize the coding nsSNPs of ADIPOR1 gene listed in the dbSNP database. Our in silico analysis by SIFT, nsSNPAnalyzer, PolyPhen-2, Fathmm, I-Mutant 2.0, SNPs&GO, PhD-SNP, PANTHER, and SNPeffect tools identified the nsSNPs with distorting functional impacts, namely, rs765425383 (A348G), rs752071352 (H341Y), rs759555652 (R324L), rs200326086 (L224F), and rs766267373 (L143P) from 74 nsSNPs of ADIPOR1 gene. Finally the aforementioned five deleterious nsSNPs were introduced using Swiss-PDB Viewer package within the X-ray crystal structure of ADIPOR1 protein, and changes in free energy for these mutations were computed. Although increased free energy was observed for all the mutants, the nsSNP H341Y caused the highest energy increase amongst all. RMSD and TM scores predicted that mutants were structurally similar to wild type protein. Our analyses suggested that the aforementioned variants especially H341Y could directly or indirectly destabilize the amino acid interactions and hydrogen bonding networks of ADIPOR1.
Fulltext Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats

Afroz R, Tanvir EM, Karim N, Hossain MS, Alam N, Gan SH, et al.

Biomed Res Int, 2016;2016:6437641.
PMID: 27294126 DOI: 10.1155/2016/6437641

The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium.
Fulltext Phytochemical profiles and inhibitory effects of Tiger Milk mushroom (Lignosus rhinocerus) extract on ovalbumin-induced airway inflammation in a rodent model of asthma

Johnathan M, Gan SH, Ezumi MF, Faezahtul AH, Nurul AA

BMC Complement Altern Med, 2016;16(1):167.
PMID: 27255587 DOI: 10.1186/s12906-016-1141-x

Lignosus rhinocerus (L. rhinocerus), which is known locally as Tiger Milk mushroom, is traditionally used in the treatment of asthma by indigenous communities in Malaysia. However, to date, its efficacy on asthma has not been confirmed by scientific studies and there is also sparse information available on its active constituents. In this study, the volatile constituent of L. rhinocerus hot water extract was investigated using gas chromatography mass spectrometry (GC-MS). The potential effects of L. rhinocerus extract for anti-asthmatic activity was further investigated on ovalbumin (OVA)-sensitized asthmatic Sprague Dawley rats.
Molecular Targets in Advanced Therapeutics of Cancers: The Role of Pharmacogenetics

Abubakar MB, Gan SH

Oncology, 2016;91(1):3-12.
PMID: 27233906 DOI: 10.1159/000446437

The advent of advanced molecular targeted therapy has resulted in improved prognoses for patients with advanced malignancies. However, despite the significant success and specificity of this advocated targeted therapy, significant on- and off-target adverse effects and inter-individual variability in treatment responses have been reported. The interpatient variability in drug response has been suggested to be partly due to variations in patient genomes. Therefore, the identification of genetic biomarkers by conducting pharmacogenetics studies can help predict patient responses to targeted therapy and may serve as a basis for individualized treatment. In this review, both clinically established and potential molecular targets are highlighted. Overall, current literature suggests that individualization of targeted therapy is promising; however, integrating the clinical benefits of identified biomarkers into clinical practice for personalized medicine remains a major challenge, and further studies to validate these markers and identify novel therapeutic approaches are needed.
Antiphospholipid Antibody-Mediated Thrombotic Mechanisms in Antiphospholipid Syndrome: Towards Pathophysiology-Based Treatment

Islam MA, Alam F, Sasongko TH, Gan SH

Curr Pharm Des, 2016;22(28):4451-69.
PMID: 27229722

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by a persistently high titer of antiphospholipid antibodies (aPLs). In addition to pregnancy morbidity, arterial and/or venous thrombosis is another clinical feature of APS. Regardless of the type of APS, the thrombi formed by the induction of aPLs can lead to deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke and gangrene. Although the concept of APS was introduced approximately 32 years ago, its thrombogenic pathophysiology is still unclear. Therefore, patients are treated with anticoagulant and/or antiplatelet regimens just as in other thrombotic disorders even though the thrombotic pathophysiology is mainly aPLs-mediated. In this review, we provided an update of the cellular, auto-immune and genetic factors known to play important roles in the generation of thrombi. Current successful regimens are also outlined along with potential emerging treatment strategies that may lead to the optimum management of thrombotic APS patients.
DNA Methylation: An Epigenetic Insight into Type 2 Diabetes Mellitus

Alam F, Islam MA, Gan SH, Mohamed M, Sasongko TH

Curr Pharm Des, 2016;22(28):4398-419.
PMID: 27229720

DNA methylation, a major regulator of epigenetic modifications has been shown to alter the expression of genes that are involved in aspects of glucose metabolism such as glucose intolerance, insulin resistance, β-cell dysfunction and other conditions, and it ultimately leads to the pathogenesis of type 2 diabetes mellitus (T2DM). Current evidences indicate an association of DNA methylation with T2DM. This review provides an overview of how various factors play crucial roles in T2DM pathogenesis and how DNA methylation interacts with these factors. Additionally, an update on current techniques of DNA methylation analysis with their pros and cons is provided as a basis for the adoption of suitable techniques in future DNA methylation research towards better management of T2DM. To elucidate the mechanistic relationship between vital environmental factors and the development of T2DM, a better understanding of the changes in gene expression associated with DNA methylation at the molecular level is still needed.
Fulltext Determination of heavy metals in the soils of tea plantations and in fresh and processed tea leaves: an evaluation of six digestion methods

Rashid MH, Fardous Z, Chowdhury MA, Alam MK, Bari ML, Moniruzzaman M, et al.

Chem Cent J, 2016;10:7.
PMID: 26900397 DOI: 10.1186/s13065-016-0154-3

BACKGROUND: The aim of this study was to determine the levels of cadmium (Cd), chromium (Cr), lead (Pb), arsenic (As) and selenium (Se) in (1) fresh tea leaves, (2) processed (black) tea leaves and (3) soils from tea plantations originating from Bangladesh.
METHODS: Graphite furnace atomic absorption spectrometry (GF-AAS) was used to evaluate six digestion methods, (1) nitric acid, (2) nitric acid overnight, (3) nitric acid-hydrogen peroxide, (4) nitric-perchloric acid, (5) sulfuric acid, and (6) dry ashing, to determine the most suitable digestion method for the determination of heavy metals in the samples.
RESULTS: The concentration ranges of Cd, Pb, As and Se in fresh tea leaves were from 0.03-0.13, 0.19-2.06 and 0.47-1.31 µg/g, respectively while processed tea contained heavy metals at different concentrations: Cd (0.04-0.16 µg/g), Cr (0.45-10.73 µg/g), Pb (0.07-1.03 µg/g), As (0.89-1.90 µg/g) and Se (0.21-10.79 µg/g). Moreover, the soil samples of tea plantations also showed a wide range of concentrations: Cd (0.11-0.45 µg/g), Pb (2.80-66.54 µg/g), As (0.78-4.49 µg/g), and Se content (0.03-0.99 µg/g). Method no. 2 provided sufficient time to digest the tea matrix and was the most efficient method for recovering Cd, Cr, Pb, As and Se. Methods 1 and 3 were also acceptable and can be relatively inexpensive, easy and fast. The heavy metal transfer factors in the investigated soil/tea samples decreased as follows: Cd > As > Se > Pb.
CONCLUSION: Overall, the present study gives current insights into the heavy metal levels both in soils and teas commonly consumed in Bangladesh.
Fulltext Impact of CYP3A4*18 and CYP3A5*3 Polymorphisms on Imatinib Mesylate Response Among Chronic Myeloid Leukemia Patients in Malaysia

Maddin N, Husin A, Gan SH, Aziz BA, Ankathil R

Oncol Ther, 2016;4(2):303-314.
PMID: 28261657 DOI: 10.1007/s40487-016-0035-x

INTRODUCTION: Imatinib mesylate (IM), a selective inhibitor of the BCR-ABL tyrosine kinase, is a well-established first-line treatment for chronic myeloid leukemia (CML). IM is metabolized mainly by cytochrome P450 (CYP) in the liver, specifically the CYP3A4 and CYP3A5 enzymes. Polymorphisms in these genes can alter the enzyme activity of IM and may affect its response. In this study, the impact of two single-nucleotide polymorphisms (SNPs), CYP3A5*3 (6986A>G) and CYP3A4*18 (878T>C), on IM treatment response in CML patients (n = 270; 139 IM resistant and 131 IM good responders) was investigated.
METHODS: Genotyping of CYP3A4*18 and CYP3A5*3 was performed using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. The association between allelic variants and treatment response was assessed by means of odds ratio (OR) with 95% confidence intervals calculated by logistic regression.
RESULTS: Our results indicated that CML patients carrying the heterozygous (AG) and homozygous variant (GG) genotype of CYP3A5*3 were associated with a significantly lower risk of acquiring resistance with OR 0.171; 95% CI: 0.090-0.324, p
Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases

Islam MA, Alam F, Solayman M, Khalil MI, Kamal MA, Gan SH

Oxid Med Cell Longev, 2016;2016:5137431.
PMID: 27721914

Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described.
Metabolic Control of Type 2 Diabetes by Targeting the GLUT4 Glucose Transporter: Intervention Approaches

Alam F, Islam MA, Khalil MI, Gan SH

Curr Pharm Des, 2016;22(20):3034-49.
PMID: 26951104 DOI: 10.2174/1381612822666160307145801

Type 2 diabetes mellitus (T2DM), the most common form of diabetes, is characterized by insulin resistance in the hepatic and peripheral tissues. Glucose transporter 4 (GLUT4) plays a major role in the pathophysiology of T2DM. Its defective expression or translocation to the peripheral cell plasma membrane in T2DM patients hinders the entrance of glucose into the cell for energy production. In addition to suitable drugs, an appropriate diet and/or exercise can be implemented to target the increase in GLUT4 expression, GLUT4 concentrations and GLUT4 translocation to the cell surface when managing the glucose metabolism of T2DM patients. In this review, we discussed successful intervention strategies that were individually administered or coupled with diet and/or exercise and affected the expression and translocation of GLUT4 in T2DM while reducing the excess glucose load from the blood. Additionally, some potentially good synthetic and natural compounds, which can activate the insulin-independent GLUT4 signaling pathways for the efficient management of T2DM, are highlighted as possible targets or emerging alternative sources for future anti-diabetic drug development.
Type 2 Diabetes Mellitus and Alzheimer's Disease: Bridging the Pathophysiology and Management

Alam F, Islam MA, Sasongko TH, Gan SH

Curr Pharm Des, 2016;22(28):4430-42.
PMID: 27229721 DOI: 10.2174/1381612822666160527160236

Although type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are two independent diseases, evidences from epidemiological, pathophysiological and animal studies have indicated a close pathophysiological relationship between these diseases. Due to the pathophysiological similarity of T2DM and AD, which includes insulin resistance and deficiency, protein aggregation, oxidative stress, inflammation, autophagocytosis and advanced glycation end products; AD is often referred to as "type 3 diabetes". In addition to the targeted regimens usually used for treating T2DM and AD individually, currently, anti-diabetic drugs are successfully used to reduce the cognitive decline in AD patients. Therefore, if a common pathophysiology of T2DM and AD could be clearly determined, both diseases could be managed more efficiently, possibly by shared pharmacotherapy in addition to understanding the broader spectrum of preventive strategies. The aim of this review is to discuss the pathophysiological bridge between T2DM and AD to lay the foundation for the future treatment strategies in the management of both diseases.
'Non-criteria' neurologic manifestations of antiphospholipid syndrome: a hidden kingdom to be discovered

Islam MA, Alam F, Kamal MA, Wong KK, Sasongko TH, Gan SH

CNS Neurol Disord Drug Targets, 2016;15(10):1253-1265.
PMID: 27658514 DOI: 10.2174/1871527315666160920122750

Neurological manifestations or disorders associated with the central nervous system are among the most common and important clinical characteristics of antiphospholipid syndrome (APS). Although in the most recently updated (2006) APS classification criteria, the neurological manifestations encompass only transient ischemic attack and stroke, diverse 'non-criteria' neurological disorders or manifestations (i.e., headache, migraine, bipolar disorder, transverse myelitis, dementia, chorea, epileptic seizures, multiple sclerosis, psychosis, cognitive impairment, Tourette's syndrome, parkinsonism, dystonia, transient global amnesia, obsessive compulsive disorder and leukoencephalopathy) have been observed in APS patients. To date, the underlying mechanisms responsible for these abnormal neurological manifestations in APS remain unclear. In vivo experiments and human observational studies indicate the involvement of thrombotic events and/or high titers of antiphospholipid antibodies in the neuro-pathogenic cascade of APS. Although different types of neurologic manifestations in APS patients have successfully been treated with therapies involving anti-thrombotic regimens (i.e., anticoagulants and/or platelet antiaggregants), antineuralgic drugs (i.e., antidepressants, antipsychotics and antiepileptics) and immunosuppressive drugs alone or in combination, evidence-based guidelines for the management of the neurologic manifestations of APS remain unavailable. Therefore, further experimental, clinical and retrospective studies with larger patient cohorts are warranted to elucidate the pathogenic linkage between APS and the central nervous system in addition to randomized controlled trials to facilitate the discovery of appropriate medications for the 'non-criteria' neurologic manifestations of APS.
Fulltext Anthropometric and reproductive factors among newly- diagnosed breast cancer patients and healthy women: a case-control study

Zunura'in Z, Almardhiyah AR, Gan SH, Arifin WN, Sirajudeen K, Bhavaraju V, et al.

Asian Pac J Cancer Prev, 2016;17(9):4439-4444.
PMID: 27797258

The objective of this case-control study was to determine anthropometric and reproductive factors associated with the development of breast cancer among women. Fifty-six newly diagnosed breast cancer patients were recruited from the Oncology Clinic, Universiti Sains Malaysia (USM), and 56 healthy female hospital employees were recruited as controls. Socio-demographic and reproductive data were obtained using a standard questionnaire. Anthropometric factors (body weight, height, body fat percentage, visceral fat and waist and hip circumference) were assessed. A high waist circumference (adjusted OR= 1.04, [95% CI: 1.00, 1.09]) and being more than 30 years of age at rst full-term pregnancy (adjusted OR=3.77, [95% CI: 1.10, 12.90]) were predictors of breast cancer development. The results of this study indicate that weight and reproductive health management should be emphasized for breast cancer prevention in Malaysia.

Study site: Oncology clinic, Hospital Universiti Sains Malaysia (HUSM)
Management of Patient Care in Hemodialysis While Focusing on Cardiovascular Disease Events and the Atypical Role of Hyper- and/or Hypotension: A Systematic Review

Khan A, Khan AH, Adnan AS, Syed Sulaiman SA, Gan SH, Khan I

Biomed Res Int, 2016;2016:9710965.
PMID: 27833921

Background. Hemodialysis related hemodynamic instability is a major but an underestimated issue. Moreover, cardiovascular events are the leading cause of morbidity and mortality associated with blood pressure in hemodialysis patients. However, there have been many controversies regarding the role and management of hyper- and/or hypotension during hemodialysis that needs to be addressed. Objective. To critically review the available published data on the atypical role of hyper- and/or hypotension in cardiovascular associated morbidity and mortality in patients on hemodialysis and to understand the discrepancies in this context. Methods. A comprehensive search of literature employing electronic as well as manual sources and screening 2783 papers published between Jan 1980 and Oct 2015 was conducted to collect, identify, and analyze relevant information through peer-reviewed research articles, systematic reviews, and other published works. The cardiovascular events, including accelerated atherosclerotic cardiovascular disease (ASCVD), stroke, heart failure, myocardial infarction, myocardial ischemia, and stress induced myocardial dysfunction, leading to death were considered relevant. Results. A total of 23 published articles met the inclusion criteria and were included for in-depth review and analysis to finalize a comprehensive systematic review article. All the studies showed a significant association between the blood pressure and cardiovascular disease events in hemodialysis patients. Conclusions. Both intradialytic hypertension/hypotension episodes are major risk factors for cardiovascular mortality with a high percentage of probable causality; however, clinicians are faced with a dilemma on how to evaluate blood pressure and treat this condition.
Fulltext Phytochemicals and Biogenic Metallic Nanoparticles as Anticancer Agents

Rao PV, Nallappan D, Madhavi K, Rahman S, Jun Wei L, Gan SH

Oxid Med Cell Longev, 2016;2016:3685671.
PMID: 27057273 DOI: 10.1155/2016/3685671

Cancer is a leading cause of death worldwide. Several classes of drugs are available to treat different types of cancer. Currently, researchers are paying significant attention to the development of drugs at the nanoscale level to increase their target specificity and to reduce their concentrations. Nanotechnology is a promising and growing field with multiple subdisciplines, such as nanostructures, nanomaterials, and nanoparticles. These materials have gained prominence in science due to their size, shape, and potential efficacy. Nanomedicine is an important field involving the use of various types of nanoparticles to treat cancer and cancerous cells. Synthesis of nanoparticles targeting biological pathways has become tremendously prominent due to the higher efficacy and fewer side effects of nanodrugs compared to other commercial cancer drugs. In this review, different medicinal plants and their active compounds, as well as green-synthesized metallic nanoparticles from medicinal plants, are discussed in relation to their anticancer activities.

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