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Fulltext An In Vitro Anticancer Activity Evaluation of Neolamarckia cadamba (Roxb.) Bosser Leaves' Extract and its Metabolite Profile

Razali S, Firus Khan AY, Khatib A, Ahmed QU, Abdul Wahab R, Zakaria ZA

Front Pharmacol, 2021;12:741683.
PMID: 34721030 DOI: 10.3389/fphar.2021.741683

The leaves of Neolamarckia cadamba (NC) (Roxb.) Bosser (family: Rubiaceae) are traditionally used to treat breast cancer in Malaysia; however, this traditional claim is yet to be scientifically verified. Hence, this study was aimed to evaluate the anticancer effect of NC leaves' ethanol extract against breast cancer cell line (MCF-7 cells) using an in vitro cell viability, cytotoxicity, and gene expression assays followed by the gas chromatography analysis to further confirm active principles. Results revealed 0.2 mg/ml as the half maximal inhibitory concentration (IC50) against MCF-7. The extract exerted anticancer effect against MCF-7 cells in a dose- and time-dependent manner. The cell cycle assay showed that the extract arrested MCF-7 cells in the G0/G1 phase, and apoptosis was observed after 72 h by the Annexin-V assay. The gene expression assay revealed that the cell cycle arrest was associated with the downregulation of CDK2 and subsequent upregulation of p21 and cyclin E. The extract induced apoptosis via the mediation of the mitochondrial cell death pathways. A chromatography analysis revealed the contribution of D-pinitol and myo-inositol as the two major bioactive compounds to the activity observed. Overall, the study demonstrated that NC leaves' ethanol extract exerts anticancer effect against MCF-7 human breast cancer cells through the induction of apoptosis and cell cycle arrest, thereby justifying its traditional use for the treatment of breast cancer in Malaysia.
Fulltext A Systematic Review on Attenuation of PCSK9 in Relation to Atherogenesis Biomarkers Associated with Natural Products or Plant Bioactive Compounds in In Vitro Studies: A Critique on the Quality and Imprecision of Studies

Zulkapli R, Yusof MYPM, Abd Muid S, Wang SM, Firus Khan AY, Nawawi H

Int J Environ Res Public Health, 2022 Oct 08;19(19).
PMID: 36232177 DOI: 10.3390/ijerph191912878

A systematic review was performed to identify all the related publications describing PCSK9 and atherogenesis biomarkers attenuation associated with a natural product and plant bioactive compounds in in vitro studies. This review emphasized the imprecision and quality of the included research rather than the detailed reporting of the results. Literature searches were conducted in Scopus, PubMed, and Science Direct from 2003 until 2021, following the Cochrane handbook. The screening of titles, abstracts, and full papers was performed by two independent reviewers, followed by data extraction and validity. Study quality and validity were assessed using the Imprecision Tool, Model, and Marker Validity Assessment that has been developed for basic science studies. A total of 403 articles were identified and 31 of those that met the inclusion criteria were selected. 13 different atherogenesis biomarkers in relation to PCSK9 were found, and the most studied biomarkers are LDLR, SREBP, and HNF1α. In terms of quality, our review suggests that the basic science study in investigating atherogenesis biomarkers is deficient in terms of imprecision and validity.
Fulltext Skin cancer detection using non-invasive techniques

Narayanamurthy V, Padmapriya P, Noorasafrin A, Pooja B, Hema K, Firus Khan AY, et al.

RSC Adv, 2018 Aug 02;8(49):28095-28130.
PMID: 35542700 DOI: 10.1039/c8ra04164d

Skin cancer is the most common form of cancer and is globally rising. Historically, the diagnosis of skin cancers has depended on various conventional techniques which are of an invasive manner. A variety of commercial diagnostic tools and auxiliary techniques are available to detect skin cancer. This article explains in detail the principles and approaches involved for non-invasive skin cancer diagnostic methods such as photography, dermoscopy, sonography, confocal microscopy, Raman spectroscopy, fluorescence spectroscopy, terahertz spectroscopy, optical coherence tomography, the multispectral imaging technique, thermography, electrical bio-impedance, tape stripping and computer-aided analysis. The characteristics of an ideal screening test are outlined, and the authors pose several points for clinicians and scientists to consider in the evaluation of current and future studies of skin cancer detection and diagnosis. This comprehensive review critically analyses the literature associated with the field and summarises the recent updates along with their merits and demerits.
Direct cell imprint lithography in superconductive carbon black polymer composites: process optimization, characterization and in vitro toxicity analysis

Narayanamurthy V, Samsuri F, Firus Khan AY, Hamzah HA, Baharom MB, Kumary TV, et al.

Bioinspir Biomim, 2019 11 06;15(1):016002.
PMID: 30897554 DOI: 10.1088/1748-3190/ab1243

Cell imprint lithography (CIL) or cell replication plays a vital role in fields like biomimetic smart culture substrates, bone tissue engineering, cell guiding, cell adhesion, tissue engineering, cell microenvironments, tissue microenvironments, cell research, drug delivery, diagnostics, therapeutics and many other applications. Herein we report a new formulation of superconductive carbon black photopolymer composite and its characterization towards a CIL process technique. In this article, we demonstrated an approach of using a carbon nanoparticle-polymer composite (CPC) for patterning cells. It is observed that a 0.3 wt % load of carbon nanoparticles (CNPs) in a carbon polymer mixture (CPM) was optimal for cell-imprint replica fabrication. The electrical resistance of the 3-CPC (0.3 wt %) was reduced by 68% when compared to N-CPC (0 wt %). This method successfully replicated the single cell with sub-organelle scale. The shape of microvesicles, grooves, pores, blebs or microvilli on the cellular surface was patterned clearly. This technique delivers a free-standing cell feature substrate. In vitro evaluation of the polymer demonstrated it as an ideal candidate for biomimetic biomaterial applications. This approach also finds its application in study based on morphology, especially for drug delivery applications and for investigations based on molecular pathways.
Fulltext The Malaysian HEalth and WellBeing AssessmenT (MyHEBAT) Study Protocol: An Initiation of a National Registry for Extended Cardiovascular Risk Evaluation in the Community

Firus Khan AY, Ramli AS, Abdul Razak S, Mohd Kasim NA, Chua YA, Ul-Saufie AZ, et al.

Int J Environ Res Public Health, 2022 Sep 19;19(18).
PMID: 36142062 DOI: 10.3390/ijerph191811789

Cardiovascular disease (CVD) has been a burden to many developing countries for decades, including Malaysia. Although various steps have been taken to prevent and manage CVD, it remains the leading cause of morbidity and mortality. The rising prevalence of CVD risk factors such as hypertension, hypercholesterolaemia, diabetes, overweight and obesity is the main driving force behind the CVD epidemic. Therefore, a nationwide health study coined as the Malaysian Health and Wellbeing Assessment (MyHEBAT) was designed. It aimed to investigate the prevalence of CVD and the associated risk factors in the community across Malaysia. The MyHEBAT study recruited participants (18-75 years old) through community health screening programmes from 11 states in Malaysia. The MyHEBAT study was further divided into two sub-studies, namely, the Cardiovascular Risk Epidemiological Study (MyHEBAT-CRES) and the MyHEBAT Familial Hypercholesterolaemia Study (MyHEBAT-FH). These studies assessed the prevalence of CVD risk factors and the prevalence of FH in the community, respectively. The data garnered from the MyHEBAT study will provide information for healthcare providers to devise better prevention and clinical practice guidelines for managing CVD in Malaysia.
Determination toxic effects of Hystrix Brachyura Bezoar extracts using cancer cell lines and embryo zebrafish (Danio rerio) models and identification of active principles through GC-MS analysis

Firus Khan AY, Ahmed QU, Nippun TS, Hilles A, Jalal TK, Teh LK, et al.

J Ethnopharmacol, 2020 Nov 15;262:113138.
PMID: 32726681 DOI: 10.1016/j.jep.2020.113138

ETHNOPHARMACOLOGICAL RELEVANCE: Porcupine bezoar (PB) is used as folk medicine for various medical conditions including cancer treatment in Malaysia. However, its toxicity profile has never been thoroughly ascertained to confirm its safe nature as an efficacious traditional medicine in the treatment of cancer as well as other ailments.
AIM OF THE STUDY: This study was aimed to reveal three different PBs' aqueous extracts(viz. PB-A, PB-B, PB-C) chemical constituent's profile using GC-MS analysis, anticancer property on A375, HeLa and MCF7 cancer cells, toxicity profile on zebrafish embryo morphology, EC50, LC50 and teratogenicity index.
MATERIALS AND METHODS: PBs' extracts characterization was performed through GC-MS analysis, in vitro anticancer effect was carried out on A375, HeLa and MCF7 cancer cell lines and finally and toxicity properties on three different PBs aqueous extracts (viz. PB-A, PB-B, PB-C) were determined using zebrafish embryo model.
RESULTS: The GC-MS analysis revealed 10 similar compounds in all PBs' extracts. Dilauryl thiodipropionate was found to be a major compound in all PBs' extracts followed by tetradecanoic acid. An in vitro anticancer study revealed PB extracts exerted median inhibition concentration (IC50) <50 μg/mL, on cancer cells viz. A375, HeLa and MCF7 with no significant toxicity on normal cells viz. NHDF cells. In vivo toxicity of PBs extracts found affecting tail detachment, hatching, craniofacial, brain morphology, soft tissues, edema, spinal, somites, notochord and cardiovascular system (brachycardia, disruption of blood circulation) deformities. The LC50 and EC50 demonstrated PB extracts effect as dose and time dependent with median concentration <150.0 μg/mL. Additionally, teratogenicity index (TI) viz. >1.0 revealed teratogenic property for PB extracts.
CONCLUSIONS: The findings revealed that all three PBs aqueous extracts possessed anticancer activity and exhibited significant toxicological effects on zebrafish embryos with high teratogenicity index. Hence, its use as an anticancer agent requires further investigation and medical attentions to determine its safe dose.