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Differential Gene Expression of Heat Shock Protein 90 (Hsp90) of Candida albicans obtained from Malaysian and Iranian Patients

Khalili V, Shokri H, Md Akim A, Khosravi AR

Malays J Med Sci, 2016 May;23(3):64-71.
PMID: 27418871

Candida albicans (C. albicans) has several virulence factors, in particular heat shock protein 90 (Hsp90), which is expressed by Hsp90 gene. The purposes of this study were to assess the expression of Hsp90 gene in clinical and control isolates of C. albicans obtained from different geographical regions (Malaysia and Iran), different temperatures (25°C, 37°C and 42°C) and mice with candidiasis.
Fulltext Preventive inositol hexaphosphate extracted from rice bran inhibits colorectal cancer through involvement of Wnt/β-catenin and COX-2 pathways

Shafie NH, Mohd Esa N, Ithnin H, Md Akim A, Saad N, Pandurangan AK

Biomed Res Int, 2013;2013:681027.
PMID: 24260743 DOI: 10.1155/2013/681027

Nutritional or dietary factors have drawn attention due to their potential as an effective chemopreventive agent, which is considered a more rational strategy in cancer treatment. This study was designed to evaluate the effect of IP₆ extracted from rice bran on azoxymethane- (AOM-) induced colorectal cancer (CRC) in rats. Initially, male Sprague Dawley rats were divided into 5 groups, with 6 rats in each group. The rats received two intraperitoneal (i.p.) injections of AOM in saline (15 mg/kg body weight) over a 2-week period to induce CRC. IP₆ was given in three concentrations, 0.2% (w/v), 0.5% (w/v), and 1.0% (w/v), via drinking water for 16 weeks. The deregulation of the Wnt/β-catenin signaling pathway and the expression of cyclooxygenase (COX)-2 have been implicated in colorectal tumorigenesis. β-Catenin and COX-2 expressions were analysed using the quantitative RT-PCR and Western blotting. Herein, we reported that the administration of IP₆ markedly suppressed the incidence of tumors when compared to the control. Interestingly, the administration of IP₆ had also markedly decreased β-catenin and COX-2 in colon tumors. Thus, the downregulation of β-catenin and COX-2 could play a role in inhibiting the CRC development induced by IP₆ and thereby act as a potent anticancer agent.
Fulltext In vitro cytotoxicity of Strobilanthes crispus ethanol extract on hormone dependent human breast adenocarcinoma MCF-7 cell

Chong HZ, Rahmat A, Yeap SK, Md Akim A, Alitheen NB, Othman F, et al.

BMC Complement Altern Med, 2012;12:35.
PMID: 22471785 DOI: 10.1186/1472-6882-12-35

Strobilanthes crispus has been traditionally used as antidiabetic, anticancer, diuretic, antilytic and laxative agent. However, cytotoxicity and antiproliferative effect of S. crispus is still unclear.
Role of Honey as a Bifunctional Reducing and Capping/Stabilizing Agent: Application for Silver and Zinc Oxide Nanoparticles

Bahari N, Hashim N, Abdan K, Md Akim A, Maringgal B, Al-Shdifat L

Nanomaterials (Basel), 2023 Mar 31;13(7).
PMID: 37049336 DOI: 10.3390/nano13071244

The use of natural reducing and capping agents has gained importance as a way to synthesize nanoparticles (NPs) in an environmentally sustainable manner. Increasing numbers of studies have been published on the green synthesis of NPs using natural sources such as bacteria, fungi, and plants. In recent years, the use of honey in the synthesis of metal and metal oxide NPs has become a new and promising area of research. Honey acts as both a stabilizing and reducing agent in the NP synthesis process and serves as a precursor. This review focuses on the use of honey in the synthesis of silver NPs (Ag-NPs) and zinc oxide NPs (ZnO-NPs), emphasizing its role as a reducing and capping agent. Additionally, a comprehensive examination of the bio-based reducing and capping/stabilizing agents used in the honey-mediated biosynthesis mechanism is provided. Finally, the review looks forward to environmentally friendly methods for NP synthesis.
Fulltext Approaches for Mitigating Microbial Biofilm-Related Drug Resistance: A Focus on Micro- and Nanotechnologies

Rao H, Choo S, Rajeswari Mahalingam SR, Adisuri DS, Madhavan P, Md Akim A, et al.

Molecules, 2021 Mar 26;26(7).
PMID: 33810292 DOI: 10.3390/molecules26071870

Biofilms play an essential role in chronic and healthcare-associated infections and are more resistant to antimicrobials compared to their planktonic counterparts due to their (1) physiological state, (2) cell density, (3) quorum sensing abilities, (4) presence of extracellular matrix, (5) upregulation of drug efflux pumps, (6) point mutation and overexpression of resistance genes, and (7) presence of persister cells. The genes involved and their implications in antimicrobial resistance are well defined for bacterial biofilms but are understudied in fungal biofilms. Potential therapeutics for biofilm mitigation that have been reported include (1) antimicrobial photodynamic therapy, (2) antimicrobial lock therapy, (3) antimicrobial peptides, (4) electrical methods, and (5) antimicrobial coatings. These approaches exhibit promising characteristics for addressing the impending crisis of antimicrobial resistance (AMR). Recently, advances in the micro- and nanotechnology field have propelled the development of novel biomaterials and approaches to combat biofilms either independently, in combination or as antimicrobial delivery systems. In this review, we will summarize the general principles of clinically important microbial biofilm formation with a focus on fungal biofilms. We will delve into the details of some novel micro- and nanotechnology approaches that have been developed to combat biofilms and the possibility of utilizing them in a clinical setting.
Fulltext Induction of Apoptosis and Modulation of Caspase Activity on MCF-7 Human Breast Cancer Cells by Bioactive Fractionated Cocoa Leaf Extract

Ranneh Y, Abu Bakar MF, Md Akim A, Bin Baharum Z, S Ellulu M, Fadel A

Asian Pac J Cancer Prev, 2023 Jul 01;24(7):2473-2483.
PMID: 37505782 DOI: 10.31557/APJCP.2023.24.7.2473

BACKGROUND: The objective of this study was to investigate the potential anti-proliferative activities of a methanolic extract of cocoa leaves (CL) obtained through sequential partition and fractionation against MCF-7 breast cancer cells. Methods: The methanolic extract of CL was partitioned in three separated solvents (hexane, dichloromethane, and methanol). Hexane partition was the most potent against MCF-7 cells growth with the lowest IC50 value. Then, it was subjected to two fractionation procedures, resulting in the identification of the CL bioactive fraction (II-F7) with potent toxicity against MCF-7 cells.
RESULTS: Further investigation into CL bioactive fraction (II-F7) revealed significant dose-dependent growth inhibitory effects on MCF-7 cells, which were attributed to the induction of apoptosis, as evidenced by the presence of apoptotic bodies, fragmented DNA, and disruption of mitochondrial membrane potential. Additionally, treatment with CL bioactive fraction (II-F7) upregulated the expression of pro-apoptotic genes (DDIT3, GADD45G and HRK) and significantly increased the activities of caspase-8 and caspase-9.
CONCLUSION: Overall, this study suggests that bioactive fraction (II-F7) from CL extract has significant and selective cytotoxicity against MCF-7 cells through inducing apoptosis and has potential as a therapeutic agent for breast cancer treatment.
Fulltext Comments on "Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics"

Ranneh Y, Mahmoud AM, Fadel A, Abu Bakar MF, Md Akim A

Front Pharmacol, 2023;14:1228359.
PMID: 37663246 DOI: 10.3389/fphar.2023.1228359
Fulltext Anti-aging and antioxidant of four traditional malaysian plants using simplex centroid mixture design approach

Ranneh Y, Abu Bakar MF, Ismail NA, Kormin F, Mohamed M, Md Akim A, et al.

Saudi J Biol Sci, 2021 Dec;28(12):6711-6720.
PMID: 34866970 DOI: 10.1016/j.sjbs.2021.07.048

Aging is a naturally biological process with adverse effects. The continuous accumulation of reactive oxygen species (ROS) trigger cellular and tissue damage by activating several aging enzymes. The antioxidant properties of traditional medicinal plants used by Jakun aborigine's community are a promising approach to alleviate aging process and prevent Alzheimer. The aim of the current investigation was to optimize a novel anti-aging formulation from traditional plants (Cnestis palala stem, Urceola micrantha stem, Marantodes pumilum stem and Microporus xanthopus fruiting bodies) using simplex centroid mixture design (SCMD). After selecting the optimal formulations based on desirability function of antioxidant activity (DPPḢ, ABTS ˙ + and FRAP), they were further examined against the activity of aging-related-enzymes (collagenase, tyrosinase, acetyl- and butyrylcholinesterase). The single extracts of C. palala, U. micrantha and the binary mixture of C. palala and U. micrantha were the optimal formulations with high antioxidant activities. Single extract of U. micrantha showed the highest inhibition towards matrix metalloproteinase-1 (49.44 ± 4.11 %), while C. palala water extract showed highest inhibitions towards tyrosinase (14.06 ± 0.31%), acetylcholinesterase (32.92 ± 2.13%) and butyrylcholinesterase (34.89 ± 2.84%) enzymes. The single extracts of C. palala and U. micrantha displayed better activity as compared to the binary mixture formulation. In conclusion, these findings could be a baseline for further exploration of novel anti-aging agents from natural resources.
Fulltext Secondary Metabolites, Antioxidant, and Antiproliferative Activities of Dioscorea bulbifera Leaf Collected from Endau Rompin, Johor, Malaysia

Mainasara MM, Abu Bakar MF, Md Akim A, Linatoc AC, Abu Bakar FI, Ranneh YKH

Evid Based Complement Alternat Med, 2021;2021:8826986.
PMID: 33505506 DOI: 10.1155/2021/8826986

Breast cancer is among the most commonly diagnosed cancer and the leading cause of cancer-related death among women globally. Malaysia is a country that is rich in medicinal plant species. Hence, this research aims to explore the secondary metabolites, antioxidant, and antiproliferative activities of Dioscorea bulbifera leaf collected from Endau Rompin, Johor, Malaysia. Antioxidant activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assays, while the cytotoxicity of D. bulbifera on MDA-MB-231 and MCF-7 breast cancer cell lines was tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell cycle analysis and apoptosis were assessed using flow cytometry analysis. Phytochemical profiling was conducted using gas chromatography-mass spectrometry (GC-MS). Results showed that methanol extract had the highest antioxidant activity in DPPH, FRAP, and ABTS assays, followed by ethyl acetate and hexane extracts. D. bulbifera tested against MDA-MB-231 and MCF-7 cell lines showed a pronounced cytotoxic effect with IC50 values of 8.96 μg/mL, 6.88 μg/mL, and 3.27 μg/mL in MCF-7 and 14.29 μg/mL, 11.86 μg/mL, and 7.23 μg/mL in MDA-MB-231, respectively. Cell cycle analysis also indicated that D. bulbifera prompted apoptosis at various stages, and a significant decrease in viable cells was detected within 24 h and substantially improved after 48 h and 72 h of treatment. Phytochemical profiling of methanol extract revealed the presence of 39 metabolites such as acetic acid, n-hexadecanoic acid, acetin, hexadecanoate, 7-tetradecenal, phytol, octadecanoic acid, cholesterol, palmitic acid, and linolenate. Hence, these findings concluded that D. bulbifera extract has promising anticancer and natural antioxidant agents. However, further study is needed to isolate the bioactive compounds and validate the effectiveness of this extract in the In in vivo model.
Fulltext Assessment of heat stress contributing factors in the indoor environment among vulnerable populations in Klang Valley using principal component analysis (PCA)

Muhamad SN, How V, Lim FL, Md Akim A, Karuppiah K, Mohd Shabri NSA

Sci Rep, 2024 Jul 15;14(1):16265.
PMID: 39009671 DOI: 10.1038/s41598-024-67110-w

Rising global temperatures can lead to heat waves, which in turn can pose health risks to the community. However, a notable gap remains in highlighting the primary contributing factors that amplify heat-health risk among vulnerable populations. This study aims to evaluate the precedence of heat stress contributing factors in urban and rural vulnerable populations living in hot and humid tropical regions. A comparative cross-sectional study was conducted, involving 108 respondents from urban and rural areas in Klang Valley, Malaysia, using a face-to-face interview and a validated questionnaire. Data was analyzed using the principal component analysis, categorizing factors into exposure, sensitivity, and adaptive capacity indicators. In urban areas, five principal components (PCs) explained 64.3% of variability, with primary factors being sensitivity (health morbidity, medicine intake, increased age), adaptive capacity (outdoor occupation type, lack of ceiling, longer residency duration), and exposure (lower ceiling height, increased building age). In rural, five PCs explained 71.5% of variability, with primary factors being exposure (lack of ceiling, high thermal conductivity roof material, increased building age, shorter residency duration), sensitivity (health morbidity, medicine intake, increased age), and adaptive capacity (female, non-smoking, higher BMI). The order of heat-health vulnerability indicators was sensitivity > adaptive capacity > exposure for urban areas, and exposure > sensitivity > adaptive capacity for rural areas. This study demonstrated a different pattern of leading contributors to heat stress between urban and rural vulnerable populations.
Association between physiological responses and heat shock protein 70 (HSP70) expressions in the vulnerable populations of Kuala Lumpur

Muhamad SN, Lim FL, Md Akim A, Karuppiah K, Mohd Shabri NSA, How V

Int J Environ Health Res, 2024 Apr 14.
PMID: 38616509 DOI: 10.1080/09603123.2024.2340125

Continued heat exposure can cause physiological and cellular responses. This study investigated the association between physiological responses and heat shock protein 70 (HSP70) expressions in Kuala Lumpur's urban vulnerable population. We conducted a cross-sectional study involving 54 participants from four areas classified as experiencing moderate to strong heat stress. Physiological measurements included core body temperature, heart rate, and diastolic and systolic blood pressure. RT-qPCR and ELISA were also performed on blood samples to assess HSP70 gene and protein expressions. Despite indoor heat stress, participants maintained normal physiological parameters while there were significant indications of HSP70 expression at both the gene and protein levels. However, our study found no significant correlation (p > 0.05) between physiological responses and HSP70 expressions. This study shows no interaction between physiological responses and HSP70 expressions in the study population, revealing the complex mechanisms of indoor heat stress in vulnerable individuals.
Adapting to heat-health vulnerability in temperate climates: current adaptation and mitigation responses and future predictions in Aotearoa New Zealand

Muhamad SN, Mohd Shabri NSA, Cotter JD, Bolton A, How V, Lim FL, et al.

Rev Environ Health, 2024 Nov 21.
PMID: 39562285 DOI: 10.1515/reveh-2024-0101

INTRODUCTION: Climate change is raising global temperatures, leading to more extreme heat events, even in temperate climates like Aotearoa|New Zealand (A|NZ). The impact of rising temperatures and the adequacy of planning measures remain underexplored. This paper highlights A|NZ's anticipated heat-health challenges by analyzing vulnerable populations and assessing current response systems, thereby reinforcing the need for system-level redress, mitigation and adaptation.
CONTENT: A scoping review examined the impact of heat and existing mitigation and adaptation responses for vulnerable populations in temperate regions, with a focus on A|NZ. Additionally, temperature trend analysis was conducted for current and projected trends using Climate CHIP for six major heat-affected cities in A|NZ to assess the recognition of heat as a societal concern.
SUMMARY AND OUTLOOK: The review identified mitigation and adaptation strategies for existing vulnerable groups and discovered other potential vulnerable groups in A|NZ, including Indigenous people (Māori), Pacific communities, low-income groups, migrants, and visitors. Temperature trends show an increasing pattern, suggesting heightened future heat-related impacts on these populations. This review reveals A|NZ's growing vulnerability to rising temperatures, particularly among high-risk groups, and calls for stronger mitigation and adaptation strategies to address future heat-health risks.

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