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Background: The techniques for detecting single nucleotide polymorphisms (SNP) require lengthy and complex experimental procedures and expensive instruments that may only be available in some laboratories. Thus, a deoxyribonucleic acid (DNA)-based lateral flow assay (LFA) was developed as a point-of-care test (POCT) diagnostic tool for genotyping. In this study, single nucleotide variation (E101K) in the low-density lipoprotein receptor (LDLR) gene leading to familial hypercholesterolemia (FH) was chosen as a model. Methods: Hypercholesterolemic individuals (n = 103) were selected from the Malaysian Cohort project (UKM Medical Molecular Biology Institute) while the control samples were selected from the Biobank (UKM Medical Molecular Biology Institute). The DNA samples were isolated from whole blood. Polymerase chain reaction (PCR) amplification process was performed using bifunctional labelled primers specifically designed to correspond to the variant that differentiates wild-type and mutant DNA for visual detection on LFA. The variant was confirmed using Sanger sequencing, and the sensitivity and specificity of the LFA detection method were validated using the Agena MassARRAY® technique. Results: Out of 103 hypercholesterolemic individuals, 5 individuals (4.8%) tested positive for E101K, LDLR mutation and the rest, including healthy control individuals, tested negative. This result was concordant with Sanger sequencing and Agena MassARRAY®. These five individuals could be classified as Definite FH, as the DNA diagnosis was confirmed. The sensitivity and specificity of the variant detection by LFA is 100% compared to results using the genotyping method using Agena MassARRAY®. Conclusion: The developed LFA can potentially be used in the POC setting for detecting the E101K variant in the LDLR gene. This LFA can also be used to screen family members with E101K variant in the LDLR gene and is applicable for other SNP's detection.
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Prediction model has been the focus of studies since the last century in the diagnosis and prognosis of various diseases. With the advancement in computational technology, machine learning (ML) has become the widely used tool to develop a prediction model. This review is to investigate the current development of prediction model for the risk of cardiovascular disease (CVD) among type 2 diabetes (T2DM) patients using machine learning. A systematic search on Scopus and Web of Science (WoS) was conducted to look for relevant articles based on the research question. The risk of bias (ROB) for all articles were assessed based on the Prediction model Risk of Bias Assessment Tool (PROBAST) statement. Neural network with 76.6% precision, 88.06% sensitivity, and area under the curve (AUC) of 0.91 was found to be the most reliable algorithm in developing prediction model for cardiovascular disease among type 2 diabetes patients. The overall concern of applicability of all included studies is low. While two out of 10 studies were shown to have high ROB, another studies ROB are unknown due to the lack of information. The adherence to reporting standards was conducted based on the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) standard where the overall score is 53.75%. It is highly recommended that future model development should adhere to the PROBAST and TRIPOD assessment to reduce the risk of bias and ensure its applicability in clinical settings. Potential lipid peroxidation marker is also recommended in future cardiovascular disease prediction model to improve overall model applicability.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Prognóstico , Aprendizado de MáquinaRESUMO
Despite the advancements in primary brain tumour diagnoses and treatments, the mortality rate remains high, particularly in glioblastoma (GBM). Chemoresistance, predominantly in recurrent cases, results in decreased mean survival of patients with GBM. We aimed to determine the chemosensitisation and oncogenic characteristics of zinc finger protein 36-like 2 (ZFP36L2) in LN18 GBM cells via RNA interference (RNAi) delivery. We conducted a meta-analysis of microarray datasets and RNAi screening using pooled small interference RNA (siRNA) to identify the druggable genes responsive to GBM chemosensitivity. Temozolomide-resistant LN18 cells were used to evaluate the effects of gene silencing on chemosensitisation to the sub-lethal dose (1/10 of the median inhibitory concentration [IC50]) of temozolomide. ZFP36L2 protein expression was detected by western blotting. Cell viability, proliferation, cell cycle and apoptosis assays were carried out using commercial kits. A human apoptosis array kit was used to determine the apoptosis pathway underlying chemosensitisation by siRNA against ZFP36L2 (siZFP36L2). Statistical analyses were performed using one-way analysis of variance; p > 0.05 was considered significant. The meta-analysis and RNAi screening identified ZFP36L2 as a potential marker of GBM. ZFP36L2 knockdown significantly induced apoptosis (p < 0.05). Moreover, ZFP36L2 inhibition led to increased cell cycle arrest and decreased cell proliferation. Downstream analysis showed that the sub-lethal dose of temozolomide and siZFP26L2 caused major upregulation of BCL2-associated X, apoptosis regulator (BAX). ZFP36L2 has oncogenic and chemosensitive characteristics and may play an important role in gliomagenesis through cell proliferation, cell cycle arrest and apoptosis. This suggests that RNAi combined with chemotherapy treatment such as temozolomide may be a potential GBM therapeutic intervention in the future.
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Glioblastoma/tratamento farmacológico , Temozolomida/farmacologia , Fatores de Transcrição/genética , Proteína X Associada a bcl-2/genética , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Camundongos , RNA Interferente Pequeno/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
circRNAs have emerged as one of the key regulators in many cellular mechanisms and pathogenesis of diseases. However, with the limited knowledge and current technologies for circRNA investigations, there are several challenges that need to be addressed for. These include challenges in understanding the regulation of circRNA biogenesis, experimental designs, and sample preparations to characterize the circRNAs in diseases as well as the bioinformatics pipelines and algorithms. In this chapter, we discussed the above challenges and possible strategies to overcome those limitations. We also addressed the differences between the existing applications and technologies to study the circRNAs in diseases. By addressing these challenges, further understanding of circRNAs roles and regulations as well as the discovery of novel circRNAs could be achieved.
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RNA/genética , Pesquisa/tendências , Agricultura/métodos , Biomarcadores , Biologia Computacional , Bases de Dados Genéticas , Previsões , Regulação da Expressão Gênica/genética , Terapia Genética , Humanos , RNA/análise , RNA CircularRESUMO
This study investigated the potential of chitosan-coated mixed micellar nanocarriers (polyplexes) for codelivery of siRNA and doxorubicin (DOX). DOX-loaded mixed micelles (serving as cores) were prepared by thin film hydration method and coated with chitosan (CS, serving as outer shell), and complexed with multidrug resistance (MDR) inhibiting siRNA. Selective targeting was achieved by folic acid conjugation. The polyplexes showed pH-responsive enhanced DOX release in acidic tumor pH, resulting in higher intracellular accumulation, which was further augmented by downregulation of mdr-1 gene after treatment with siRNA-complexed polyplexes. In vitro cytotoxicity assay demonstrated an enhanced cytotoxicity in native 4T1 and multidrug-resistant 4T1-mdr cell lines, compared to free DOX. Furthermore, in vivo, polyplexes codelivery resulted in highest DOX accumulation and significantly reduced the tumor volume in mice with 4T1 and 4T1-mdr tumors as compared to the free DOX groups, leading to improved survival times in mice. In conclusion, codelivery of siRNA and DOX via polyplexes has excellent potential as targeted drug nanocarriers for treatment of MDR cancers.
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Neoplasias da Mama/terapia , Quitosana/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Resistência a Múltiplos Medicamentos , Nanopartículas/administração & dosagem , Polímeros/administração & dosagem , RNA Interferente Pequeno/genética , Animais , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Polietilenoglicóis , Polímeros/químicaRESUMO
BACKGROUND: Impulse control disorder (ICD) and behaviours (ICB) represent a group of behavioural disorders that have become increasingly recognised in Parkinson's disease (PD) patients who previously used dopaminergic medications, particularly dopamine agonists and levodopa. It has been suggested that these medications can lead to the development of ICB through the abnormal modulation of dopaminergic transmission and signalling in the mesocorticolimbic dopaminergic system. Several studies have reported an association between polymorphisms in the dopamine receptor (DRD) and N-methyl-D-aspartate 2B (GRIN2B) genes with the development of ICB in PD (PD-ICB) patients. Thus, this study aimed to investigate the association of selected polymorphisms within the DRD and GRIN2B genes with the development of ICB among PD patients using high resolution melt (HRM) analysis. METHOD: We used high resolution melt (HRM) analysis to genotype 11 polymorphisms in 5 DRD genes [DRD1 (rs4532, rs4867798 and rs265981), DRD2 (ANKK1 rs1800497, rs104894220 and rs144999500), DRD3 (rs3732783 and rs6280), DRD4 (rs1800443), and DRD5 (rs144132215)] and 1 polymorphism in GRIN2B (rs7301328) in PD patients with (cases, n = 52) and without (controls, n = 39) ICB. Cases were obtained from two tertiary movement disorder centres [UKMMC (n = 9) and UMMC (n = 43)]. At both centres, the diagnosis of ICB was made using the QUIP questionnaire. Controls were recruited from PD patients who attended UKMMC and were found to be negative for ICB using the QUIP questionnaire. RESULTS: The HRM analysis showed that 7 of 11 polymorphisms [DRD1 (rs4532, rs4867798, and rs265981), DRD2 (ANKK1 rs1800497), DRD3 (rs3732783 and rs6280), and GRIN2B (rs7301328)] exhibited a clear distinction between wild-type and variant alleles. Variants of DRD2/ANKK1 rs1800497 (OR = 3.77; 95% CI, 1.38-10.30; p = 0.0044), DRD1 rs4867798 (OR = 24.53; 95% CI, 1.68-357.28; p = 0.0054), DRD1 rs4532 (OR = 21.33; 95% CI, 1.97-230.64; p = 0.0024), and GRIN2B rs7301328 (OR = 25.07; 95% CI, 1.30-483.41; p = 0.0097) were found to be associated with an increased risk of developing ICB among PD patients. CONCLUSION: Our findings suggest that polymorphisms in dopamine [DRD1 (rs4532 and rs4867798) and DRD2/ANKK1 rs1800497] and glutamate (GRIN2B rs7301328) receptor genes confer increased risk of ICB development among PD patients.
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Transtornos Disruptivos, de Controle do Impulso e da Conduta/genética , Doença de Parkinson/genética , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Receptores de N-Metil-D-Aspartato/genética , Adulto , Idoso , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Feminino , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Polimorfismo Genético , Proteínas Serina-Treonina Quinases/genéticaRESUMO
Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δß-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/ß-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.
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Hemoglobinas Anormais/genética , Talassemia alfa/genética , Talassemia beta/genética , Sequência de Bases , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Malásia , Masculino , Dados de Sequência Molecular , Linhagem , Fenótipo , Irmãos , Talassemia alfa/sangue , Talassemia beta/sangueRESUMO
In this study of postmenopausal women in Malaysia, total adiposity was inversely associated with total BMD, while regional associations varied. No differences were detected across Malay, Chinese, and Indian ethnicities. Low BMD contributes substantially to morbidity and mortality, and increasing adiposity levels globally may be contributing to this. PURPOSE: To investigate associations of total and regional adiposity with bone mineral density (BMD) among a multi-ethnic cohort of postmenopausal women. METHODS: Dual X-ray absorptiometry (DXA) imaging was undertaken for 1990 postmenopausal women without prior chronic diseases (30% Malay, 53% Chinese, and 17% Indian) from The Malaysian Cohort (TMC). The strength of the associations between standardized total and regional body fat percentages with total and regional BMD was examined using linear regression models adjusted for age, height, lean mass, ethnicity, education, and diabetes. Effect modification was assessed for ethnicity. RESULTS: Women with a higher total body fat percentage were more likely to be Indian or Malay. Mean (SD) BMD for the whole-body total, lumbar spine, leg, and arm were 1.08 (0.11), 0.96 (0.15), 2.21 (0.22), and 1.36 (0.12) g/cm2, respectively. Total body and visceral fat percentage were inversely associated with total BMD (- 0.02 [95% CI - 0.03, - 0.01] and - 0.01 [- 0.02, - 0.006] g/cm2 per 1 SD, respectively). In contrast, subcutaneous and gynoid fat percentages were positively associated with BMD (0.007 [0.002, 0.01] and 0.01 [0.006, 0.02] g/cm2, respectively). Total body fat percentage showed a weak positive association with lumbar BMD (0.01 [0.004, 0.02]) and inverse associations with leg (- 0.04 [- 0.06, - 0.03]) and arm (- 0.02 [- 0.03, - 0.02]) BMD in the highest four quintiles. There was no effect modification by ethnicity (phetero > 0.05). CONCLUSION: Total adiposity was inversely associated with total BMD, although regional associations varied. There was no heterogeneity across ethnic groups suggesting adiposity may be a risk factor for low BMD across diverse populations.
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Absorciometria de Fóton , Densidade Óssea , Pós-Menopausa , Humanos , Feminino , Malásia/etnologia , Malásia/epidemiologia , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Pós-Menopausa/etnologia , Idoso , Estudos de Coortes , Distribuição da Gordura Corporal/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Vértebras Lombares/diagnóstico por imagem , Adiposidade/etnologia , Adiposidade/fisiologiaRESUMO
The performance of the graphene-based field-effect transistor (FET) as a biosensor is based on the output drain current (Id). In this work, the signal-to-noise ratio (SNR) was investigated to obtain a high-performance device that produces a higher Id value. Using the finite element method, a novel top-gate FET was developed in a three-dimensional (3D) simulation model with the titanium dioxide-reduced graphene oxide (TiO2-rGO) nanocomposite as the transducer material, which acts as a platform for biosensing application. Using the Taguchi mixed-level method in Minitab software (Version 16.1.1), eighteen 3D models were designed based on an orthogonal array L18 (6134), with five factors, and three and six levels. The parameters considered were the channel length, electrode length, electrode width, electrode thickness and electrode type. The device was fabricated using the conventional photolithography patterning technique and the metal lift-off method. The material was synthesised using the modified sol-gel method and spin-coated on top of the device. According to the results of the ANOVA, the channel length contributed the most, with 63.11%, indicating that it was the most significant factor in producing a higher Id value. The optimum condition for the highest Id value was at a channel length of 3 µm and an electrode size of 3 µm × 20 µm, with a thickness of 50 nm for the Ag electrode. The electrical measurement in both the simulation and experiment under optimal conditions showed a similar trend, and the difference between the curves was calculated to be 28.7%. Raman analyses were performed to validate the quality of TiO2-rGO.
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Hypercholesterolemia was prevalent in 44.9% of The Malaysian Cohort participants, of which 51% were Malay. This study aimed to identify the variants involved in hypercholesterolemia among Malays and to determine the association between genetic and non-genetic risk factors. This nested case-control study included 25 Malay participants with the highest low-density lipoprotein cholesterol (LDL-C, >4.9 mmol/L) and total cholesterol (TC, >7.5 mmol/L) and 25 participants with the lowest LDL-C/TC. Genomic DNA was extracted, and whole-exome sequencing was performed using the Ion ProtonTM system. All variants were annotated, filtered, and cross-referenced against publicly available databases. Forty-five selected variants were genotyped in 677 TMC Malay participants using the MassARRAY® System. The association between genetic and non-genetic risk factors was determined using logistic regression analysis. Age, fasting blood glucose, tobacco use, and family history of hyperlipidemia were significantly associated with hypercholesterolemia. Participants with the novel OSBPL7 (oxysterol-binding protein-like 7) c.651_652del variant had 17 times higher odds for hypercholesterolemia. Type 2 diabetes patients on medication and those with PCSK9 (proprotein convertase subtilisin/kexin type 9) rs151193009 had low odds for hypercholesterolemia. Genetic predisposition can interact with non-genetic factors to increase hypercholesterolemia risk in Malaysian Malays.
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Diabetes Mellitus Tipo 2 , Hipercolesterolemia , Humanos , Pró-Proteína Convertase 9/genética , Hipercolesterolemia/epidemiologia , Hipercolesterolemia/genética , LDL-Colesterol/uso terapêutico , Estudos de Casos e Controles , Pró-Proteína Convertases/genética , Pró-Proteína Convertases/uso terapêutico , Serina Endopeptidases/genética , Fatores de RiscoRESUMO
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 1 million cases diagnosed annually. In Malaysia, CRC is the second most common cancer in women and ranked first in men. The underlying cause of CRC remains unknown. AIMS: The aim of this study was to analyze the mutations in genes involved in CRC including MLH1, MSH2, KRAS, and APC genes. METHODS: A total of 76 patients were recruited. We used the polymerase chain reaction-denaturing high-performance liquid chromatography for the detection of mutations in the mismatch repair (MMR) and APC genes and the PCR single-strand conformation polymorphism for screening of the KRAS gene mutations. RESULTS: We identified 17 types of missense mutations in 38 out of 76 patients in our patients. Nine mutations were identified in the APC gene, five mutations were detected in the KRAS gene, and two mutations were identified in the MSH2 gene. Only one mutation was identified in MLH1. Out of these 17 mutations, eight mutations (47 %) were predicted to be pathogenic. Seven patients were identified with multiple mutations (3: MSH2 and KRAS, 1: KRAS and APC, 1: MLH1 and APC, 2: APC and APC). CONCLUSIONS: We have established the PCR-DHPLC and PCR-SSCP for screening of mutations in CRC patients. This study has given a snapshot of the spectrum of mutations in the four genes that were analyzed. Mutation screening in patients and their family members will help in the early detection of CRC and hence will reduce mortality due to CRC.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais/genética , Genes APC , Mutação de Sentido Incorreto , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas ras/metabolismo , Idoso , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Perda de Heterozigosidade , Malásia , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas p21(ras)RESUMO
Asians are more susceptible to type 2 diabetes mellitus (T2D) and its coronary heart disease (CHD) complications than the Western populations, possibly due to genetic factors, higher degrees of obesity, insulin resistance, and endothelial dysfunction that could occur even in healthy individuals. The genetic factors and their mechanisms, along with gene-gene and gene-environment interactions associated with CHD in T2D Asians, are yet to be explored. Therefore, the objectives of this paper were to review the current evidence of genetic factors for CHD, summarize the proposed mechanisms of these genes and how they may associate with CHD risk, and review the gene-gene and gene-environment interactions in T2D Asians with CHD. The genetic factors can be grouped according to their involvement in the energy and lipoprotein metabolism, vascular and endothelial pathology, antioxidation, cell cycle regulation, DNA damage repair, hormonal regulation of glucose metabolism, as well as cytoskeletal function and intracellular transport. Meanwhile, interactions between single nucleotide polymorphisms (SNPs) from different genes, SNPs within a single gene, and genetic interaction with environmental factors including obesity, smoking habit, and hyperlipidemia could modify the gene's effect on the disease risk. Collectively, these factors illustrate the complexities of CHD in T2D, specifically among Asians.
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Doença das Coronárias , Diabetes Mellitus Tipo 2 , Povo Asiático/genética , Doença das Coronárias/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Genome-wide association studies (GWAS) have discovered 163 loci related to coronary heart disease (CHD). Most GWAS have emphasized pathways related to single-nucleotide polymorphisms (SNPs) that reached genome-wide significance in their reports, while identification of CHD pathways based on the combination of all published GWAS involving various ethnicities has yet to be performed. We conducted a systematic search for articles with comprehensive GWAS data in the GWAS Catalog and PubMed, followed by a meta-analysis of the top recurring SNPs from ≥2 different articles using random or fixed-effect models according to Cochran Q and I2 statistics, and pathway enrichment analysis. Meta-analyses showed significance for 265 of 309 recurring SNPs. Enrichment analysis returned 107 significant pathways, including lipoprotein and lipid metabolisms (rs7412, rs6511720, rs11591147, rs1412444, rs11172113, rs11057830, rs4299376), atherogenesis (rs7500448, rs6504218, rs3918226, rs7623687), shared cardiovascular pathways (rs72689147, rs1800449, rs7568458), diabetes-related pathways (rs200787930, rs12146487, rs6129767), hepatitis C virus infection/hepatocellular carcinoma (rs73045269/rs8108632, rs56062135, rs188378669, rs4845625, rs11838776), and miR-29b-3p pathways (rs116843064, rs11617955, rs146092501, rs11838776, rs73045269/rs8108632). In this meta-analysis, the identification of various genetic factors and their associated pathways associated with CHD denotes the complexity of the disease. This provides an opportunity for the future development of novel CHD genetic risk scores relevant to personalized and precision medicine.
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Aim: Mitochondrial DNA (mtDNA) alterations play an important role in the multistep processes of cancer development. Gliomas are among the most diagnosed brain cancer. The relationship between mtDNA alterations and different grades of gliomas are still elusive. This study aimed to elucidate the profile of somatic mtDNA mutations in different grades of gliomas and correlate it with clinical phenotype. Materials & methods: Forty histopathologically confirmed glioma tissue samples and their matched blood were collected and subjected for mtDNA sequencing. Results & conclusion: About 75% of the gliomas harbored at least one somatic mutation in the mtDNA gene, and 45% of these mutations were pathogenic. Mutations were scattered across the mtDNA genome, and the commonest nonsynonymous mutations were located at complex I and IV of the mitochondrial respiratory chain. These findings may have implication for future research to determine the mitochondrial energetics and its downstream metabolomics on gliomas.
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Genoma Mitocondrial , Glioma , DNA Mitocondrial/genética , Glioma/genética , Humanos , Mitocôndrias/genética , Mutação/genéticaRESUMO
The global prevalence of nonalcoholic fatty liver disease (NAFLD) or metabolic associated fatty liver disease (MAFLD), as it is now known, has gradually increased. NAFLD is a disease with a spectrum of stages ranging from simple fatty liver (steatosis) to a severe form of steatosis, nonalcoholic steatohepatitis (NASH), which could progress to irreversible liver injury (fibrosis) and organ failure, and in some cases hepatocellular carcinoma (HCC). Although a liver biopsy remains the gold standard for accurate detection of this condition, it is unsuitable for clinical screening due to a higher risk of death. There is thus an increased need to find alternative techniques or tools for accurate diagnosis. Early detection for NASH matters for patients because NASH is the marker for severe disease progression. This review summarizes the current noninvasive tools for NAFLD diagnosis and their performance. We also discussed potential and newer alternative tools for diagnosing NAFLD.
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The discovery of non-coding RNAs (ncRNAs) has opened a new paradigm to use ncRNAs as biomarkers to detect disease progression. Long non-coding RNAs (lncRNA) have garnered the most attention due to their specific cell-origin and their existence in biological fluids. Type 2 diabetes patients will develop cardiovascular disease (CVD) complications, and CVD remains the top risk factor for mortality. Understanding the lncRNA roles in T2D and CVD conditions will allow the future use of lncRNAs to detect CVD complications before the symptoms appear. This review aimed to discuss the roles of lncRNAs in T2D and CVD conditions and their diagnostic potential as molecular biomarkers for CVD complications in T2D.
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OBJECTIVE: In this present study, we aim to evaluate the accuracy of the HbA1c relative to fasting plasma glucose (FPG) in the diagnosis of diabetes and pre-diabetes among The Malaysian Cohort (TMC) participants. METHODOLOGY: FPG and HbA1c were taken from 40,667 eligible TMC participants that have no previous history of diabetes, aged between 35-70 years and were recruited from 2006 - 2012. Participants were classified as normal, diabetes and pre-diabetes based on the 2006 World Health Organization (WHO) criteria. Statistical analyses were performed using ANOVA and Chi-square test, while Pearson correlation and Cohen's kappa were used to examine the concordance rate between FPG and HbA1c. RESULTS: The study samples consisted of 16,224 men and 24,443 women. The prevalence of diabetes among the participants was 5.7% and 7.5% according to the FPG and HbA1c level, respectively. Based on FPG, 10.6% of the participants had pre-diabetes but this increased to 14.2% based on HbA1c (r=0.86; P<0.001). HbA1c had a sensitivity of 58.20 (95% CI: 56.43, 59.96) and a specificity of 98.59 (95% CI: 98.46, 98.70). CONCLUSION: A higher prevalence of pre-diabetes and diabetes was observed when using HbA1c as a diagnosis tool, suggesting that it could possibly be more useful for early detection. However, given that HbA1c may also have lower sensitivity and higher false positive rate, several diagnostic criteria should be used to diagnose diabetes accurately.
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INTRODUCTION: During the second wave of the coronavirus disease 19 (COVID-19) pandemic, Malaysia reported several COVID-19 clusters related to healthcare workers. Thus, addressing and understanding the risk of exposure in healthcare workers is important to prevent future infection and reduce secondary COVID-19 transmission within the healthcare settings. In this study, we aim to assess exposure and prevention practices against COVID-19 among healthcare workers at the Hospital Canselor Tuanku Muhriz, a university teaching hospital based in Kuala Lumpur, Malaysia. METHODOLOGY: A total of 571 healthcare workers at COVID-19 and non-COVID-19 wards as well as the emergency department and laboratory staff at COVID-19 testing labs were recruited. The presence of novel human coronavirus (SARS-CoV-2) and IgM/IgG antibodies were confirmed in all healthcare workers. The healthcare workers responded to an online Google Forms questionnaire that evaluates demographic information and comorbidities, exposure and adherence to infection prevention and control measures against COVID-19. Descriptive analysis was performed using Statistical Package for the Social Sciences 24.0. RESULTS: Three healthcare workers (0.5%) tested positive for SARS-CoV-2, while the remaining 568 (99.5%) were negative. All were negative for IgM and IgG antibodies during recruitment (day 1) and follow-up (day 15). More than 90% of the healthcare workers followed infection prevention and control practices recommendations regardless of whether they have been exposed to occupational risk for COVID-19. CONCLUSIONS: The healthcare workers' high level of adherence to infection prevention practices at this hospital helped reduce and minimize their occupational exposure to COVID-19.
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COVID-19/epidemiologia , Controle de Doenças Transmissíveis/normas , Pessoal de Saúde/estatística & dados numéricos , Exposição Ocupacional/prevenção & controle , Adulto , COVID-19/transmissão , Teste para COVID-19/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Malásia/epidemiologia , Masculino , Exposição Ocupacional/estatística & dados numéricos , Pandemias , Equipamento de Proteção Individual/estatística & dados numéricos , Medição de Risco , SARS-CoV-2RESUMO
Background: Oxidative stress markers are found to be linked with depression and suicide attempts in bipolar disorder (BD), although the role of DNA damage as a marker of suicidal ideation and attempt has yet to be determined. We aim to investigate the association between DNA damage and suicidal behaviour, i.e., suicidal ideation and suicide attempt, among suicidal ideators in BD patients while accounting for clinical and psychosocial risk factors. Methods: A cross-sectional study was conducted in the Universiti Kebangsaan Malaysia Medical Centre on 62 consecutive BD patients diagnosed using the M.I.N.I. Neuropsychiatric Interview and 26 healthy control participants. Socio-demographic and clinical assessments were performed using the Columbia Suicide Severity Rating Scale (C-SSRS) for lifetime suicidal ideation and attempt, Quick Inventory of Depressive Symptomatology (QIDS) for depression severity, Clinical Global Impression for Bipolar Disorder (CGI-BD) for illness severity [both mania (CGI-Mania) and major depressive episode (CGI-MDE)], Social Readjustment Rating Scale (SRRS) for change in life events, and Barratt Impulsiveness Scale (BIS) for behavioural impulsivity. The degree of DNA damage in peripheral blood samples was determined using a standard protocol of comet assay. Results: Multivariable logistic regression revealed higher scores of CGI-MDE as the sole significant factor for lifetime suicidal ideation (OR = 1.937, 95% CI = 1.799-2.076). Although initial bivariate analysis showed a significant association between DNA damage, malondialdehyde (MDA), catalase (CAT), and suicidal behaviour, the findings were not seen in multivariable logistic regression. Bivariate subgroup analysis showed that moderate and severe DNA damage (p = 0.032 and p = 0.047, respectively) was significantly associated with lifetime suicide attempts among lifetime suicidal ideators. The study is the first to look at the connexion between DNA damage and suicidal risk in bipolar patients. It is limited by the small sample size and lack of information on illicit substance use. Conclusions: More severe DNA damage was significantly associated with lifetime suicide attempts among lifetime suicidal ideators in BD. However, the severity of depression was found to be independently associated with lifetime suicidal ideation per se rather than DNA damage in BD. Larger prospective studies are required to ascertain the potential of DNA damage as a biomarker for the transition from suicidal ideation to a suicide attempt.
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Glioblastoma multiforme (GBM) is an aggressive type of brain tumour that commonly exhibits resistance to treatment. The tumour is highly heterogenous and complex kinomic alterations have been reported leading to dysregulation of signalling pathways. The present study aimed to investigate the novel kinome pathways and to identify potential therapeutic targets in GBM. Metaanalysis using Oncomine identified 113 upregulated kinases in GBM. RNAi screening was performed on identified kinases using ONTARGETplus siRNA library on LN18 and U87MG. Tousledlike kinase 1 (TLK1), which is a serine/threonine kinase was identified as a potential hit. In vitro functional validation was performed as the role of TLK1 in GBM is unknown. TLK1 knockdown in GBM cells significantly decreased cell viability, clonogenicity, proliferation and induced apoptosis. TLK1 knockdown also chemosensitised the GBM cells to the sublethal dose of temozolomide. The downstream pathways of TLK1 were examined using microarray analysis, which identified the involvement of DNA replication, cell cycle and focal adhesion signalling pathways. In vivo validation of the subcutaneous xenografts of stably transfected shTLK1 U87MG cells demonstrated significantly decreased tumour growth in female BALB/c nude mice. Together, these results suggested that TLK1 may serve a role in GBM survival and may serve as a potential target for glioma.