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Tyrisonase inhibition and melanin reduction of human melanocytes (HEMn-MP) using Anacardium occidentale L extract

Abdul Gaffar R, Abdul Majid FA, Sarmidi MR

Med J Malaysia, 2008 Jul;63 Suppl A:100-1.
PMID: 19025004

Cashew (Anacardium occindentale L) leaves extract (CLE) has potential as tyrosinase inhibitor that can be used for therapeutic in pigmentation problem. This study investigates the real potential of CLE to inhibit tyrosinase and melanin reduction using human epidermal melanocytes. The extracts were exposed to the human melanocytes for more than 24 hours. The CLE extract exhibited potential as tyrosinase inhibitor, reduced melanin and high in antioxidant activity relative to commercial extract of Emblica sp.
Cinnamtannin B1 activity on adipocytes formation

Taher M, Abdul Majid FA, Sarmidi MR

Med J Malaysia, 2004 May;59 Suppl B:97-8.
PMID: 15468836

In attempt to discover a small active compound that could promote adipogenesis, we investigated the ability of cinnamon (Cinnamomum zeylanicum) extracts to stimulate 3T3-L1 preadipocytes, In this study, we designed an experiment by replacing insulin with cinnamon extracts. The differentiated of 3T3-L1 adipocytes were monitored using oil red O staining method. Induction of adipocyte formation by cinnamtannin B1 or water extract gave the similar effects to insulin activity in adipogenesis.
Molecular docking and dynamics simulations revealed the potential inhibitory activity of honey-iQfood ingredients against GSK-3β and CDK5 protein targets for brain health

Zakaria NH, Mohamed Tap F, Aljohani GF, Abdul Majid FA

J Biomol Struct Dyn, 2024 Jan 02.
PMID: 38165434 DOI: 10.1080/07391102.2023.2298726

Honey-iQfood is an herbal supplement made of a mixture of polyherbal extracts and wild honey. The mixture is traditionally claimed to improve various conditions related to brain cells and functions including dementia and Alzheimer's disease. Glycogen synthase kinase-3 beta (GSK-3β) and cyclin-dependent kinase 5 (CDK5) have been identified as being involved in the pathological hyperphosphorylation of tau proteins, which leads to the formation of neurofibrillary tangles and causes Alzheimer's disease. Therefore, this study was conducted to confirm the traditional claims by detection of active compounds, namely curcumin, gallic acid, catechin, rosmarinic acid, and andrographolide in the raw materials of Honey-iQfood through HPLC analysis, molecular docking, and dynamic simulations. Two potential compounds, andrographolide, and rosmarinic acid, produced the best binding affinities following the molecular docking of the active compounds against the GSK-3β and CDK5 targets. Andrographolide binds with GSK-3β at -8.2 kcal/mol, whereas rosmarinic acid binds to CDK5 targets at -8.6 kcal/mol. Molecular dynamics was further carried out to confirm the docking results and clarify their dynamic properties such as RMSD, RMSF, rGyr, SASA, PSA, and binding free energy. CDK5-andrographolide complexes had the best MM-GBSA score (-83.63 kcal/mol) compared to other complexes, indicating the better interaction profile and stability of the complex. These findings warrant further research into andrographolide and rosmarinic acid as efficient inhibitors of tau protein hyperphosphorylation to verify their therapeutic potential in brain-related illnesses.Communicated by Ramaswamy H. Sarma.
Fulltext Preclinical and clinical effects of mistletoe against breast cancer

Marvibaigi M, Supriyanto E, Amini N, Abdul Majid FA, Jaganathan SK

Biomed Res Int, 2014;2014:785479.
PMID: 25136622 DOI: 10.1155/2014/785479

Breast cancer is among the most frequent types of cancer in women worldwide. Current conventional treatment options are accompanied by side effects. Mistletoe is amongst the important herbal medicines traditionally used as complementary remedies. An increasing number of studies have reported anticancer activity of mistletoe extracts on breast cancer cells and animal models. Some recent evidence suggests that cytotoxic activity of mistletoe may be mediated through different mechanisms. These findings provide a good base for clinical trials. Various studies on mistletoe therapy for breast cancer patients revealed similar findings concerning possible benefits on survival time, health-related quality of life (HRQoL), remission rate, and alleviating adverse reactions to conventional therapy. This review provides an overview of the recent findings on preclinical experiments and clinical trials of mistletoe for its cytotoxic and antitumor activity and its effect on HRQoL in breast cancer patients. Moreover, studies investigating molecular and cellular mechanisms underlying antitumor activity of mistletoe are discussed in this paper. The analyzed trials provided evidence that there might be a combination of pharmacological and motivational aspects mediated by the mistletoe extract application which may contribute to the clinical benefit and positive outcome such as improved HRQoL and self-regulation in breast cancer patients.
Flexible microfluidic cloth-based analytical devices using a low-cost wax patterning technique

Nilghaz A, Wicaksono DH, Gustiono D, Abdul Majid FA, Supriyanto E, Abdul Kadir MR

Lab Chip, 2012 Jan 7;12(1):209-18.
PMID: 22089026 DOI: 10.1039/c1lc20764d

This paper describes the fabrication of microfluidic cloth-based analytical devices (μCADs) using a simple wax patterning method on cotton cloth for performing colorimetric bioassays. Commercial cotton cloth fabric is proposed as a new inexpensive, lightweight, and flexible platform for fabricating two- (2D) and three-dimensional (3D) microfluidic systems. We demonstrated that the wicking property of the cotton microfluidic channel can be improved by scouring in soda ash (Na(2)CO(3)) solution which will remove the natural surface wax and expose the underlying texture of the cellulose fiber. After this treatment, we fabricated narrow hydrophilic channels with hydrophobic barriers made from patterned wax to define the 2D microfluidic devices. The designed pattern is carved on wax-impregnated paper, and subsequently transferred to attached cotton cloth by heat treatment. To further obtain 3D microfluidic devices having multiple layers of pattern, a single layer of wax patterned cloth can be folded along a predefined folding line and subsequently pressed using mechanical force. All the fabrication steps are simple and low cost since no special equipment is required. Diagnostic application of cloth-based devices is shown by the development of simple devices that wick and distribute microvolumes of simulated body fluids along the hydrophilic channels into reaction zones to react with analytical reagents. Colorimetric detection of bovine serum albumin (BSA) in artificial urine is carried out by direct visual observation of bromophenol blue (BPB) colour change in the reaction zones. Finally, we show the flexibility of the novel microfluidic platform by conducting a similar reaction in a bent pinned μCAD.
Effect of temperature and pH on the probiotication of Punica granatum juice using Lactobacillus species

Mustafa SM, Chua LS, El-Enshasy HA, Abd Majid FA, Hanapi SZ, Abdul Malik R

J Food Biochem, 2019 04;43(4):e12805.
PMID: 31353583 DOI: 10.1111/jfbc.12805

This study was focused on the effects of fermentation temperature and pH on the quality of Punica granatum juice probioticated with Lactobacillus species: Lactobacillus plantarum, Lactobacillus casei, Lactobacillus bulgaricus, and Lactobacillus salivarius. The whole fruit juice of P. granatum which is rich with phytonutrients appeared to be a good probiotic carrier. The probiotication was carried out for 24 hr at 30, 35, and 37°C and pH 2.5, 4.0, and 5.5 under microaerophilic conditions. The results found that P. granatum juice cultivated with L. casei had a better growth profile with a higher biomass density at 37°C around pH 3.5-4.0. Probiotication could maintain the scavenging activity of P. granatum juice cultivated with L. casei. The scavenging activity achieved up to 90% inhibition at the concentration of 5 mg/ml. The whole fruit-squeezed P. granatum juice was suitable for the growth of Lactobacillus species even without supplementation during cultivation. PRACTICAL APPLICATIONS: The findings of this study presented the potential of P. granatum juice (whole fruit) to be used as a good probiotic carrier, particularly for Lactobacillus species without supplementation. High nutritious P. granatum juice catered the need of probiotic bacteria during fermentation. Probiotication could maintain the antioxidant capacity of the juice in term of its radical scavenging activity. The antioxidant capacity was mainly attributed to the metabolites such as phenolic acids (romarinic acid and caftaric acid) and flavonoids (quercetin, quercetin 3-glucoside, rutin and kaempferol rutinoside). With the optimized temperature (37°C) and pH (4.00), probiotic bacteria could growth well up to a cell viability of 2.46 × 1010 cfu/ml. This offers P. granatum to be developed into functional food to cater to the needs of the consumers who are lactose intolerant to dairy products.
Drug-eluting coating of ginsenoside Rg1 and Re incorporated poly(lactic-co-glycolic acid) on stainless steel 316L: Physicochemical and drug release analyses

Miswan Z, Lukman SK, Abd Majid FA, Loke MF, Saidin S, Hermawan H

Int J Pharm, 2016 Dec 30;515(1-2):460-466.
PMID: 27793709 DOI: 10.1016/j.ijpharm.2016.10.056

Active ingredients of ginsenoside, Rg1 and Re, are able to inhibit the proliferation of vascular smooth muscle cells and promote the growth of vascular endothelial cells. These capabilities are of interest for developing a novel drug-eluting stent to potentially solve the current problem of late-stent thrombosis and poor endotheliazation. Therefore, this study was aimed to incorporate ginsenoside into degradable coating of poly(lactic-co-glycolic acid) (PLGA). Drug mixture composed of ginseng extract and 10% to 50% of PLGA (xPLGA/g) was coated on electropolished stainless steel 316L substrate by using a dip coating technique. The coating was characterized principally by using attenuated total reflectance-Fourier transform infrared spectroscopy, scanning electron microscopy and contact angle analysis, while the drug release profile of ginsenosides Rg1 and Re was determined by using mass spectrometry at a one month immersion period. Full and homogenous coating coverage with acceptable wettability was found on the 30PLGA/g specimen. All specimens underwent initial burst release dependent on their composition. The 30PLGA/g and 50PLGA/g specimens demonstrated a controlled drug release profile having a combination of diffusion- and swelling-controlled mechanisms of PLGA. The study suggests that the 30PLGA/g coated specimen expresses an optimum composition which is seen as practicable for developing a controlled release drug-eluting stent.
Fulltext Optimization of Ultrasound-Assisted Extraction Conditions Followed by Solid Phase Extraction Fractionation from Orthosiphon stamineus Benth (Lamiace) Leaves for Antiproliferative Effect on Prostate Cancer Cells

Suhaimi SH, Hasham R, Hafiz Idris MK, Ismail HF, Mohd Ariffin NH, Abdul Majid FA

Molecules, 2019 Nov 18;24(22).
PMID: 31752230 DOI: 10.3390/molecules24224183

Primarily, optimization of ultrasonic-assisted extraction (UAE) conditions of Orthospihon stamineus was evaluated and verified using a central composite design (CCD) based on three factors including extraction time (minutes), ultrasound amplitude (A), and solvent concentration (%). The response surface methodology (RSM) was performed to develop an extraction method with maximum yield and high rosmarinic acid content. The optimal UAE conditions were as follows: extraction time 21 min, ultrasound amplitudes 62 A, and solvent composition 70% ethanol in water. The crude extract was further fractionated using solid-phase extraction (SPE), where six sequential fractions that varied in polarity (0-100% Acetonitrile in water) were obtained. Next, the six fractions were evaluated for their antioxidant and anti-cancer properties. This study found that Fraction 2 (F2) contained the highest rosmarinic acid content and showed the strongest antioxidant activity. Additionally, F2 showed an anti-proliferative effect against prostate cancer (DU145) with no harmful effect on normal cells.
Trastuzumab-decorated nanoparticles for in vitro and in vivo tumor-targeting hyperthermia of HER2+ breast cancer

Hamzehalipour Almaki J, Nasiri R, Idris A, Nasiri M, Abdul Majid FA, Losic D

J Mater Chem B, 2017 Sep 21;5(35):7369-7383.
PMID: 32264187 DOI: 10.1039/c7tb01305a

In this study, a magnetic core-shell modified tumor-targeting nanocarrier (MNPs-PEG-TRA) was engineered and demonstrated for the efficient in vitro and in vivo hyperthermia treatment of breast cancer. Magnetic nanoparticles were used as the initial nanocarriers and modified via PEGylation followed by immobilization of Trastuzumab (TRA) with tumor-targeting function towards cancer cells. The hyperthermia performance of the developed targeting drug delivery system was explored using an in vitro study with SK-BR-3 cancer cells and an in vivo study using animal models (mouse) with DMBA-induced breast cancer. The average size of the engineered system was about 100 nm and its zeta potential was about +13 mV, whereby the stability of the system in biological media is enormously enhanced while the possibility of it being removed via the immune system is diminished. The investigation was pursued based on comparing the changes in growth inhibition rates of HSF 1184, MDA-MB-231, MDA-MB-468 and SK-BR-3 cell lines at different temperatures (37 °C, 40 °C, 42 °C, and 45 °C). Compared with bare MNPs and MNPs-PEG, a remarkably enhanced hyperthermia effect using MNPs-PEG-TRA was observed not only in cultured SK-BR-3 cells in vitro but also in an in vivo DMBA tumor bearing mice model. These results are attributed to an about 4 fold higher concentration of MNPs-PEG-TRA carriers in the tumor site compared to the other organs confirming the considerable potential of the magnetic tumor-targeting hyperthermia concept for breast cancer treatment.
The Mechanisms of Inhibition of Advanced Glycation End Products Formation through Polyphenols in Hyperglycemic Condition

Khangholi S, Majid FA, Berwary NJ, Ahmad F, Aziz RB

Planta Med, 2016 Jan;82(1-2):32-45.
PMID: 26550791 DOI: 10.1055/s-0035-1558086

Glycation, the non-enzymatic binding of glucose to free amino groups of an amino acid, yields irreversible heterogeneous compounds known as advanced glycation end products. Those products play a significant role in diabetic complications. In the present article we briefly discuss the contribution of advanced glycation end products to the pathogenesis of diabetic complications, such as atherosclerosis, diabetic retinopathy, nephropathy, neuropathy, and wound healing. Then we mention the various mechanisms by which polyphenols inhibit the formation of advanced glycation end products. Finally, recent supporting documents are presented to clarify the inhibitory effects of polyphenols on the formation of advanced glycation end products. Phytochemicals apply several antiglycation mechanisms, including glucose metabolism, amelioration of oxidative stress, scavenging of dicarbonyl species, and up/down-regulation of gene expression. To utilize polyphenols in order to remedy diabetic complications, we must explore, examine and clarify the action mechanisms of the components of polyphenols.
Fulltext Dual actions of gallic acid and andrographolide trigger AdipoR1 to stimulate insulin secretion in a streptozotocin-induced diabetes rat model

Wong TS, Mohamed Tap F, Hashim Z, Abdul Majid FA, Zakaria NH, Siahaan P, et al.

J Tradit Complement Med, 2023 Jan;13(1):11-19.
PMID: 36685073 DOI: 10.1016/j.jtcme.2022.09.002

Common treatments for the management of diabetes have limitations due to side effects, hence the need for continuous research to discover new remedies with better therapeutic efficacy. Previously, we have reported that the combination treatment of gallic acid (20 mg/kg) and andrographolide (10 mg/kg) for 15 days demonstrated synergistic hypoglycemic activity in the streptozotocin (STZ)-induced insulin-deficient diabetes rat model. Here, we attempt to further elucidate the effect of this combination therapy at the biochemical, histological and molecular levels. Our biochemical analyses showed that the combination treatment significantly increased the serum insulin level and decreased the total cholesterol and triglyceride level of the diabetic animals. Histological examinations of H&E stained pancreas, liver, kidney and adipose tissues of combination-treated diabetic animals showed restoration to the normalcy of the tissues. Besides, the combination treatment significantly enhanced the level of glucose transporter-4 (GLUT4) protein expression in the skeletal muscle of treated diabetic animals compared to single compound treated and untreated diabetic animals. The molecular docking analysis on the interaction of gallic acid and/or andrographolide with the adiponectin receptor 1 (AdipoR1), a key component in the regulation of pancreatic insulin secretion, revealed a greater binding affinity of AdipoR1 to both compounds compared to individual compounds. Taken together, these findings suggest the combination of gallic acid and andrographolide as a potent therapy for the management of diabetes mellitus.
Fulltext Promising roles of Zingiber officinale roscoe, Curcuma longa L., and Momordica charantia L. as immunity modulators against COVID-19: A bibliometric analysis

Sheikh HI, Zakaria NH, Abdul Majid FA, Zamzuri F, Fadhlina A, Hairani MAS

J Agric Food Res, 2023 Dec;14:100680.
PMID: 37346755 DOI: 10.1016/j.jafr.2023.100680

Zingiber officinale, Curcuma longa, and Momordica charantia are medicinal plants that are commonly used in the form of herbal tea, which is formulated to strengthen the immune system, especially against COVID-19 infection. Excellent antioxidant, anti-inflammatory, and immunostimulatory properties have been reported for their bioactive compounds, which have been shown to aid in stimulating immune systems as well as lowering the risk of severe COVID-19 such as lung injury. Yet, no bibliometric study on the subject is available. Hence, the purpose of this study is to quantitatively examine the existing articles related to the therapeutic potential of these three herbs, as well as their mechanisms of action in combating the SARS-CoV-2 virus. A total of 121 papers were retrieved from Scopus database up to 14th March 2023. The bibliometric analysis was conducted using VOSviewer software. Based on the literature search, Z. officinale was the most researched plant. India appeared as the most prolific country, with the highest number of articles contributed by two authors from India (Rathi, R. and Gayatri Devi, R.). In terms of keywords, the plants were associated with immune modulation, management of symptoms, antioxidant, anti-inflammatory and antiviral activities. Several important bioactive compounds were responsible for these effects such as gingerol, paradol, shogaol, curcumin, calebin A, momordicoside, karaviloside and cucurbitadienol. These compounds were hypothesized to prevent and cure COVID-19 by regulating inflammatory response, downregulating oxidative stress and modulating immunostimulatory activity. This review paper therefore supports the potential of Z. officinale, C. longa, and M. charantia to be formulated as a herbal blend for treating and preventing COVID-19 infection.
Antibacterial activity of hexane and methanol fractions of some selected plants against Klebsiella pneumoniae

Andriani Y, Hanifah W, Kholieqoh AH, Abdul Majid FA, Hermansyah H, Amir H, et al.

J Adv Pharm Technol Res, 2023;14(3):220-225.
PMID: 37692002 DOI: 10.4103/JAPTR.JAPTR_183_23

Besides adenovirus, pneumonia can also be caused by bacteria. One of the most common bacteria causing the pneumonia is Klebsiella pneumoniae. Currently, treatment by antibiotics has been widely used. Nevertheless, the increasing failure of existing antibiotics because of antibiotic resistance resulted by bacterial pathogens has become a serious problem to human health. Hence, there is a need for a new antibacterial potential agent against K. pneumoniae as an alternative treatment to the pneumonia to prevent the risk of a severe pneumonia for both healthy people and those already infected with the pneumonia. This study, therefore, investigated the antibacterial activity of some selected plants (Pandanus tectorius, Nypa fruticans, Sonneratia alba, Phaleria macrocarpa, Hibiscus tiliaceus, and Pongamia pinnata) against K. pneumoniae. In this study, samples were extracted successively by cold maceration using hexane and methanol. Antibacterial activity was determined by well and disc diffusion methods. Each fraction was prepared by two-fold dilutions from 20 mg/mL to 0.156 mg/mL. All data were analyzed in triplicate replication and presented as mean values ± standard deviation. Results showed that all methanol fractions of selected plants had antibacterial activity against K. pneumoniae, and well-diffusion method showed better antibacterial results compared to the agar well-diffusion method. The strongest activity was obtained by methanol fraction of S. alba leaf, followed by P. pinnata leaf, Nypa fruticans bark, H. tiliaceus leaf, P. macrocarpa leaf, and P. tectorius leaf with the minimum inhibitory concentrations (MICs) value between 0.625 and 5.0 mg/mL. Phytochemical screening revealed that all methanol fractions were rich in flavonoid content, which could have contributed to their antibacterial activity.
Efficacy of papain-based wound cleanser in promoting wound regeneration

Ajlia SA, Majid FA, Suvik A, Effendy MA, Nouri HS

Pak J Biol Sci, 2010 Jun 15;13(12):596-603.
PMID: 21061910

A new invention, papain-based wound cleanser is formulated by incorporating papain, a proteolytic enzyme extracted from Carica papaya into the formulation. This cleanser is invented to simplify the methods in wound management by combining wound cleansing and wound debridement using a single formulation. This study describes the preparation and preclinical study of papain-based wound cleanser in accelerating wound healing. In this study, papain-based wound cleanser was used to treat wound incision on Sprague-Dawley rats while distilled water and Betadine were used as negative and positive control. Twenty-seven clinically healthy white rats were randomly divided into three groups and treated accordingly until the 21st day post-incision. Wound reduction rates and histological analysis were obtained to asses the healing pattern. Rats treated with papain-based wound cleanser showed a progressive wound healing based on the wound reduction rates and histological analysis when compared with rats treated with distilled water and Betadine. Better collagen deposition and presence of skin organelles in rats treated with papain-based wound cleanser demonstrated its efficacy in promoting wound healing. In addition to its wound healing effect, papain-based wound cleanser is also integrated with antibacterial properties which make it a complete package for wound management. However, further studies should be carried out to ensure its safety for human usage.
Fulltext Potential Health Benefits of Deep Sea Water: A Review

Mohd Nani SZ, Majid FA, Jaafar AB, Mahdzir A, Musa MN

Evid Based Complement Alternat Med, 2016;2016:6520475.
PMID: 28105060 DOI: 10.1155/2016/6520475

Deep sea water (DSW) commonly refers to a body of seawater that is pumped up from a depth of over 200 m. It is usually associated with the following characteristics: low temperature, high purity, and being rich with nutrients, namely, beneficial elements, which include magnesium, calcium, potassium, chromium, selenium, zinc, and vanadium. Less photosynthesis of plant planktons, consumption of nutrients, and organic decomposition have caused lots of nutrients to remain there. Due to this, DSW has potential to become a good source for health. Research has proven that DSW can help overcome health problems especially related to lifestyle-associated diseases such as cardiovascular disease, diabetes, obesity, cancer, and skin problems. This paper reviews the potential health benefits of DSW by referring to the findings from previous researches.
Stress-relieving properties of a polyherbal blend with Syzygium aromaticum L. and Coffea canephora Pierre ex A. Froehner: A review and bibliometric analysis

Zakaria NH, Fadhlina A, Sheikh HI, Hairani MAS, Mohd Fauzi MSH, Abdul Majid FA

World J Biol Psychiatry, 2024 Sep;25(7):353-369.
PMID: 38900601 DOI: 10.1080/15622975.2024.2369329

OBJECTIVE: Syzygium aromaticum and Coffea canephora are acknowledged for their outstanding antioxidant, anti-inflammatory, and nerve-stimulant properties, showcasing potential in brain protection. Therefore, this study aims to quantitatively review existing literature and assess the potential of using it to formulate a herbal tea blend for managing stress and anxiety.
METHODS: Data was retrieved from the Scopus database, and a bibliometric analysis was performed using VOSviewer software.
RESULTS: Following a screening process, a total of 121 articles were identified, with S. aromaticum yielding a higher number compared to C. canephora. A detailed exploration of each plant revealed active components such as eugenol, β-caryophyllene, α-humulene, caffeine, mangiferin, and chlorogenic acids, each exhibiting stimulatory effects alongside antioxidant and anti-inflammatory properties. The neuroprotective effects were attributed to the reduction of oxidative stress and inflammation, coupled with the stimulation of neurotransmitters and hormones like dopamine, serotonin, cortisol, and adrenaline.
CONCLUSIONS: The review showed that these plants positively affect mood and cognition by influencing the brain's pleasure system. This suggests the need for further research to combine these plant extracts for developing 'Tenang tea', a potential herbal blend for managing stress and anxiety.
Synthesis, characterization and in vitro evaluation of exquisite targeting SPIONs-PEG-HER in HER2+ human breast cancer cells

Almaki JH, Nasiri R, Idris A, Majid FA, Salouti M, Wong TS, et al.

Nanotechnology, 2016 Mar 11;27(10):105601.
PMID: 26861770 DOI: 10.1088/0957-4484/27/10/105601

A stable, biocompatible and exquisite SPIONs-PEG-HER targeting complex was developed. Initially synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were silanized using 3-aminopropyltrimethoxysilane (APS) as the coupling agent in order to allow the covalent bonding of polyethylene glycol (PEG) to the SPIONs to improve the biocompatibility of the SPIONs. SPIONs-PEG were then conjugated with herceptin (HER) to permit the SPIONs-PEG-HER to target the specific receptors expressed over the surface of the HER2+ metastatic breast cancer cells. Each preparation step was physico-chemically analyzed and characterized by a number of analytical methods including AAS, FTIR spectroscopy, XRD, FESEM, TEM, DLS and VSM. The biocompatibility of SPIONs-PEG-HER was evaluated in vitro on HSF-1184 (human skin fibroblast cells), SK-BR-3 (human breast cancer cells, HER+), MDA-MB-231 (human breast cancer cells, HER-) and MDA-MB-468 (human breast cancer cells, HER-) cell lines by performing MTT and trypan blue assays. The hemolysis analysis results of the SPIONs-PEG-HER and SPIONs-PEG did not indicate any sign of lysis while in contact with erythrocytes. Additionally, there were no morphological changes seen in RBCs after incubation with SPIONs-PEG-HER and SPIONs-PEG under a light microscope. The qualitative and quantitative in vitro targeting studies confirmed the high level of SPION-PEG-HER binding to SK-BR-3 (HER2+ metastatic breast cancer cells). Thus, the results reflected that the SPIONs-PEG-HER can be chosen as a favorable biomaterial for biomedical applications, chiefly magnetic hyperthermia, in the future.
Modeling of oscillatory bursting activity of pancreatic beta-cells under regulated glucose stimulation

Chew YH, Shia YL, Lee CT, Majid FA, Chua LS, Sarmidi MR, et al.

Mol Cell Endocrinol, 2009 Aug 13;307(1-2):57-67.
PMID: 19524127 DOI: 10.1016/j.mce.2009.03.005

A mathematical model to describe the oscillatory bursting activity of pancreatic beta-cells is combined with a model of glucose regulation system in this work to study the bursting pattern under regulated extracellular glucose stimulation. The bursting electrical activity in beta-cells is crucial for the release of insulin, which acts to regulate the blood glucose level. Different types of bursting pattern have been observed experimentally in glucose-stimulated islets both in vivo and in vitro, and the variations in these patterns have been linked to changes in glucose level. The combined model in this study enables us to have a deeper understanding on the regime change of bursting pattern when glucose level changes due to hormonal regulation, especially in the postprandial state. This is especially important as the oscillatory components of electrical activity play significant physiological roles in insulin secretion and some components have been found to be lost in type 2 diabetic patients.
Modeling of glucose regulation and insulin-signaling pathways

Chew YH, Shia YL, Lee CT, Majid FA, Chua LS, Sarmidi MR, et al.

Mol Cell Endocrinol, 2009 May 6;303(1-2):13-24.
PMID: 19428987 DOI: 10.1016/j.mce.2009.01.018

A model of glucose regulation system was combined with a model of insulin-signaling pathways in this study. A feedback loop was added to link the transportation of glucose into cells (by GLUT4 in the insulin-signaling pathways) and the insulin-dependent glucose uptake in the glucose regulation model using the Michaelis-Menten kinetic model. A value of K(m) for GLUT4 was estimated using Genetic Algorithm. The estimated value was found to be 25.3 mM, which was in the range of K(m) values found experimentally from in vivo and in vitro human studies. Based on the results of this study, the combined model enables us to understand the overall dynamics of glucose at the systemic level, monitor the time profile of components in the insulin-signaling pathways at the cellular level and gives a good estimate of the K(m) value of glucose transportation by GLUT4. In conclusion, metabolic modeling such as displayed in this study provides a good predictive method to study the step-by-step reactions in an organism at different levels and should be used in combination with experimental approach to increase our understanding of metabolic disorders such as type 2 diabetes.
In vitro evaluation of actively targetable superparamagnetic nanoparticles to the folate receptor positive cancer cells

Nasiri R, Hamzehalipour Almaki J, Idris AB, Abdul Majid FA, Nasiri M, Salouti M, et al.

Mater Sci Eng C Mater Biol Appl, 2016 Dec 01;69:1147-58.
PMID: 27612812 DOI: 10.1016/j.msec.2016.07.076

Engineering of a physiologically compatible, stable and targetable SPIONs-CA-FA formulation was reported. Initially fabricated superparamagnetic iron oxide nanoparticles (SPIONs) were coated with citric acid (CA) to hamper agglomeration as well as to ameliorate biocompatibility. Folic acid (FA) as a targeting agent was then conjugated to the citric acid coated SPIONs (SPIONs-CA) for targeting the specific receptors expressed on the FAR+ cancer cells. Physiochemical characterizations were then performed to assure required properties like stability, size, phase purity, surface morphology, chemical integrity and magnetic properties. In vitro evaluations (MTT assay) were performed on HeLa, HSF 1184, MDA-MB-468 and MDA-MB-231cell lines to ensure the biocompatibility of SPIONs-CA-FA. There were no morphological changes and lysis in contact with erythrocytes recorded for SPIONs-CA-FA and SPIONs-CA. High level of SPIONs-CA-FA binding to FAR+ cell lines was assured via qualitative and quantitative in vitro binding studies. Hence, SPIONs-CA-FA was introduced as a promising tool for biomedical applications like magnetic hyperthermia and drug delivery. The in vitro findings presented in this study need to be compared with those of in vivo studies.

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