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Displaying publications 61 - 69 of 69 in total

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Fulltext Formononetin: A Review of Its Anticancer Potentials and Mechanisms

Tay KC, Tan LT, Chan CK, Hong SL, Chan KG, Yap WH, et al.

Front Pharmacol, 2019;10:820.
PMID: 31402861 DOI: 10.3389/fphar.2019.00820

Cancer, a complex yet common disease, is caused by uncontrolled cell division and abnormal cell growth due to a variety of gene mutations. Seeking effective treatments for cancer is a major research focus, as the incidence of cancer is on the rise and drug resistance to existing anti-cancer drugs is major concern. Natural products have the potential to yield unique molecules and combinations of substances that may be effective against cancer with relatively low toxicity/better side effect profile compared to standard anticancer therapy. Drug discovery work with natural products has demonstrated that natural compounds display a wide range of biological activities correlating to anticancer effects. In this review, we discuss formononetin (C16H12O4), which originates mainly from red clovers and the Chinese herb Astragalus membranaceus. The compound comes from a class of 7-hydroisoflavones with a substitution of methoxy group at position 4. Formononetin elicits antitumorigenic properties in vitro and in vivo by modulating numerous signaling pathways to induce cell apoptosis (by intrinsic pathway involving Bax, Bcl-2, and caspase-3 proteins) and cell cycle arrest (by regulating mediators like cyclin A, cyclin B1, and cyclin D1), suppress cell proliferation [by signal transducer and activator of transcription (STAT) activation, phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT), and mitogen-activated protein kinase (MAPK) signaling pathway], and inhibit cell invasion [by regulating growth factors vascular endothelial growth factor (VEGF) and Fibroblast growth factor 2 (FGF2), and matrix metalloproteinase (MMP)-2 and MMP-9 proteins]. Co-treatment with other chemotherapy drugs such as bortezomib, LY2940002, U0126, sunitinib, epirubicin, doxorubicin, temozolomide, and metformin enhances the anticancer potential of both formononetin and the respective drugs through synergistic effect. Compiling the evidence thus far highlights the potential of formononetin to be a promising candidate for chemoprevention and chemotherapy.
Fulltext Femoral Neck Non-Union - A Biomechanical Solution with Valgus Sliding Subtrochanteric Osteotomy: A Case Report

Teh KH, Ruben JK, Chan CK, Abbas AA

Malays Orthop J, 2020 Jul;14(2):134-137.
PMID: 32983389 DOI: 10.5704/MOJ.2007.022

Avascular necrosis and non-union are two most dreaded complications of femoral neck fracture fixations. Hip replacement seems to be a simple solution for this complex problem. However, the long-term efficacy of prosthetic replacement in the young population with higher functional demand is still questionable. Femoral head preserving valgus subtrochanteric osteotomies in properly selected cases have strong support from literature. The conventional technique of valgus subtrochanteric osteotomy involves lateral based wedge resection. Alternatively, a simpler sliding oblique subtrochanteric osteotomy without any wedge removal can also be performed. We hereby describe a successful case of sliding subtrochanteric osteotomy with 135° dynamic hip screw (DHS) plate fixation in treating non-union neck of femur fracture in a young gentleman.
DEPDC5 mutations in familial and sporadic focal epilepsy

Tsai MH, Chan CK, Chang YC, Yu YT, Chuang ST, Fan WL, et al.

Clin Genet, 2017 Oct;92(4):397-404.
PMID: 28170089 DOI: 10.1111/cge.12992

BACKGROUND AND AIMS: Mutations in the disheveled, Egl-10 and pleckstrin domain-containing protein 5 (DEPDC5) gene have emerged as an important cause of various familial focal epilepsy syndromes. However, the significance of DEPDC5 mutations in patients with sporadic focal epilepsy has yet to be characterized.
MATERIALS AND METHODS: We studied a kindred of familial focal epilepsy with variable foci using whole-exome sequencing. We subsequently studied a cohort of 293 patients with focal epilepsy and sequenced all exons of DEPDC5 using targeted resequencing.
RESULTS: We reported a Taiwanese family with a novel splice site mutation which affected mRNA splicing and activated the downstream mammalian target of rapamycin (mTOR) pathway. Among patients with focal epilepsies, the majority (220/293) of these patients had sporadic focal epilepsy without malformation of cortical development. Two (0.9%) of these patients had probably pathogenic mutations in the DEPDC5 gene.
DISCUSSION AND CONCLUSIONS: Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy. Since focal epilepsies account for more than 60% of all epilepsies, the effect of mTORC1 inhibitor on patients with focal epilepsy due to DEPDC5 mutations will be an important future direction of research.
Fulltext Molecular Genetic Characterization of Patients With Focal Epilepsy Using a Customized Targeted Resequencing Gene Panel

Tsai MH, Chan CK, Chang YC, Lin CH, Liou CW, Chang WN, et al.

Front Neurol, 2018;9:515.
PMID: 30034362 DOI: 10.3389/fneur.2018.00515

Objective: Focal epilepsy is the most common subtype of epilepsies in which the influence of underlying genetic factors is emerging but remains largely uncharacterized. The purpose of this study is to determine the contribution of currently known disease-causing genes in a large cohort (n = 593) of common focal non-lesional epilepsy patients. Methods: The customized focal epilepsy gene panel (21 genes) was based on multiplex polymerase chain reaction (PCR) and sequenced by Illumina MiSeq platform. Results: Eleven variants (1.85%) were considered as pathogenic or likely pathogenic, including seven novel mutations. There were three SCN1A (p.Leu890Pro, p.Arg1636Ter, and p.Met1714Val), three PRRT2 (two p.Arg217Profs*8 and p.Leu298Pro), two CHRNA4 (p.Ser284Leu, p.Ile321Asn), one DEPDC5 (p.Val516Ter), one PCDH19 (p.Asp233Asn), and one SLC2A1 (p.Ser414Ter) variants. Additionally, 16 other rare variants were classified as unknown significance due to inconsistent phenotype or lack of segregation data. Conclusion: Currently known focal epilepsy genes only explained a very small subset of focal epilepsy patients. This indicates that the underlying genetic architecture of focal epilepsies is very heterogeneous and more novel genes are likely to be discovered. Our study highlights the usefulness, challenges and limitations of using the multi-gene panel as a diagnostic test in routine clinical practice in patients with focal epilepsy.
Fulltext Pathogenic Variants in CEP85L Cause Sporadic and Familial Posterior Predominant Lissencephaly

Tsai MH, Muir AM, Wang WJ, Kang YN, Yang KC, Chao NH, et al.

Neuron, 2020 Apr 22;106(2):237-245.e8.
PMID: 32097630 DOI: 10.1016/j.neuron.2020.01.027

Lissencephaly (LIS), denoting a "smooth brain," is characterized by the absence of normal cerebral convolutions with abnormalities of cortical thickness. Pathogenic variants in over 20 genes are associated with LIS. The majority of posterior predominant LIS is caused by pathogenic variants in LIS1 (also known as PAFAH1B1), although a significant fraction remains without a known genetic etiology. We now implicate CEP85L as an important cause of posterior predominant LIS, identifying 13 individuals with rare, heterozygous CEP85L variants, including 2 families with autosomal dominant inheritance. We show that CEP85L is a centrosome protein localizing to the pericentriolar material, and knockdown of Cep85l causes a neuronal migration defect in mice. LIS1 also localizes to the centrosome, suggesting that this organelle is key to the mechanism of posterior predominant LIS.
Why Women Are Averse to Facility Delivery in Northwest Nigeria: A Qualitative Inquiry

Tukur I, Chan CK, Tinsu T, Muhammed-Baba T, Aderemi Ijaiya M

Iran J Public Health, 2016 May;45(5):586-95.
PMID: 27398331

In many sub-Saharan African countries the rate of antenatal care (ANC) has been increased but skilled birth attendance rate is still low. The objective of this study was to evaluate the reasons why women prefer home delivery when facility based delivery is available at minimal cost.
Fulltext Should I Help? Prosocial Behaviour during the COVID-19 Pandemic

Wider W, Lim MX, Wong LS, Chan CK, Maidin SS

Int J Environ Res Public Health, 2022 Dec 01;19(23).
PMID: 36498158 DOI: 10.3390/ijerph192316084

The Movement Control Order (MCO) enacted during the COVID-19 pandemic has profoundly altered the social life and behaviour of the Malaysian population. Because the society is facing huge social and economic challenges that need individuals to work together to solve, prosocial behaviour is regarded as one of the most important social determinants. Because it is related with individual and societal benefits, participating in prosocial activities may be a major protective factor during times of global crisis. Rather than focusing only on medical and psychiatric paradigms, perhaps all that is necessary to overcome the COVID-19 risks is for individuals to make personal sacrifices for the sake of others. In reality, a large number of initiatives proven to be beneficial in decreasing viral transmission include a trade-off between individual and collective interests. Given its crucial importance, the purpose of this concept paper is to provide some insight into prosocial behaviour during the COVID-19 period. Understanding prosocial behaviour during the COVID-19 pandemic is crucial because it may assist in the establishment of a post-COVID society and provide useful strategies for coping with future crises.
Fulltext Contextualizing chronicity: a perspective from Malaysia

Yasin S, Chan CK, Reidpath DD, Allotey P

Global Health, 2012 Mar 08;8:4.
PMID: 22397462 DOI: 10.1186/1744-8603-8-4
Fulltext Test-retest reliability of the single leg stance on a Lafayette stability platform

Zaghlul N, Goh SL, Razman R, Danaee M, Chan CK

PLoS One, 2023;18(1):e0280361.
PMID: 36649257 DOI: 10.1371/journal.pone.0280361

The validity and reliability of the Lafayette stability platform are well-established for double leg testing. However, no evaluation of single leg (SL) stance on the platform was discovered yet. Therefore, this study aimed to investigate the reliability of conducting the SL stance on the Lafayette platform. Thirty-six healthy and active university students (age 23.2 ± 3.2 years; BMI 21.1 ± 3.1 kg/m2) were tested twice, one week apart (week 1; W1, week 2; W2). They stood on their dominant leg with eyes-open (EO) and eyes-closed (EC) in random order. Three successful trials of 20 seconds each were recorded. The duration during which the platform was maintained within 0° of tilt was referred to as time in balance (TIB). At all-time points, TIB was consistently longer in EO (EOW1: 17.02 ± 1.04s; EOW2: 17.32 ± 1.03s) compared to EC (ECW1: 11.55 ± 1.73s; ECW2: 13.08 ± 1.82s). A ±10 seconds difference was demonstrated in the Bland-Altman analysis in both EO and EC. Lower standard error of measurement (SEM) and coefficient of variation (CV) indicated consistent output. High intraclass correlation coefficient (ICC) values were seen between weeks (EO = 0.74; EC = 0.76) and within weeks (EOW1 = 0.79; EOW2 = 0.86; ECW1 = 0.71; ECW2 = 0.71). Although statistical measures (i.e., SEM, CV, and ICC) indicated good reliability of Lafayette for SL tasks, the wide agreement interval is yet to be clinically meaningful. Factors underlying the wide variation need to be identified before Lafayette is used for TIB assessment.