Displaying publications 161 - 180 of 532 in total

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  1. Fulltext Chemically induced breast tumors in rats are detectable in early stages by contrast enhanced magnetic resonance imaging but not by changes in the acute-phase reactants in serum
    Golbabapour S, Pang WW, George J, Pasupati T, Abdul-Rahman PS, Hashim OH
    Int J Mol Sci, 2011;12(2):1030-40.
    PMID: 21541040 DOI: 10.3390/ijms12021030
    The present study was undertaken to develop a rat model for monitoring the early development of breast cancer. Twelve female rats were divided into two groups of six rats that were either treated with N-methyl-N-nitrosourea to induce breast cancer or with bacterial lipopolysaccharide to induce inflammation. Serum samples taken from the rats prior to the treatment were used as controls. By the 14th week, presence of the tumor was detectable by contrast enhanced magnetic resonance imaging and confirmed by histopathology. When the serum proteins of the rats were examined by 2-dimensional electrophoresis (2-DE), no difference could be detected in the profiles of all proteins before and 18 weeks after administration of N-methyl-N-nitrosourea. However, higher expression of alpha-1B glycoprotein was detectable by 2-DE in serum samples of rats at the 18th week post-treatment with lipopolysaccharide.
  2. Fulltext Proteomic analysis of whole human saliva detects enhanced expression of interleukin-1 receptor antagonist, thioredoxin and lipocalin-1 in cigarette smokers compared to non-smokers
    Jessie K, Pang WW, Haji Z, Rahim A, Hashim OH
    Int J Mol Sci, 2010 Nov 09;11(11):4488-505.
    PMID: 21151451 DOI: 10.3390/ijms11114488
    A gel-based proteomics approach was used to screen for proteins of differential abundance between the saliva of smokers and those who had never smoked. Subjecting precipitated proteins from whole human saliva of healthy non-smokers to two-dimensional electrophoresis (2-DE) generated typical profiles comprising more than 50 proteins. While 35 of the proteins were previously established by other researchers, an additional 22 proteins were detected in the 2-DE saliva protein profiles generated in the present study. When the 2-DE profiles were compared to those obtained from subjects considered to be heavy cigarette smokers, three saliva proteins, including interleukin-1 receptor antagonist, thioredoxin and lipocalin-1, showed significant enhanced expression. The distribution patterns of lipocalin-1 isoforms were also different between cigarette smokers and non-smokers. The three saliva proteins have good potential to be used as biomarkers for the adverse effects of smoking and the risk for inflammatory and chronic diseases that are associated with it.
  3. Fulltext Distribution of alpha thalassaemia gene variants in diverse ethnic populations in malaysia: data from the institute for medical research
    Ahmad R, Saleem M, Aloysious NS, Yelumalai P, Mohamed N, Hassan S
    Int J Mol Sci, 2013;14(9):18599-614.
    PMID: 24025420 DOI: 10.3390/ijms140918599
    Alpha thalassaemia is highly prevalent in the plural society of Malaysia and is a public health problem. Haematological and molecular data from 5016 unrelated patients referred from various hospitals to the Institute for Medical Research for α thalassaemia screening from 2007 to 2010 were retrieved. The aims of this retrospective analysis were to describe the distribution of various alpha thalassaemia alleles in different ethnic groups, along with their genotypic interactions, and to illustrate the haematological changes associated with each phenotype. Amongst the patients, 51.2% (n = 2567) were diagnosed with α thalassaemia. Of the 13 α thalassaemia determinants screened, eight different deletions and mutations were demonstrated: three double gene deletions, --(SEA), --(THAI), --(FIL); two single-gene deletions, α-³·⁷ and -α⁴·²; and three non-deletion mutations, Cd59G > A (haemoglobin [Hb] Adana), Cd125T > C (Hb Quong Sze) and Cd142 (Hb Constant Spring). A high incidence of α-³·⁷ deletion was observed in Malays, Indians, Sabahans, Sarawakians and Orang Asli people. However, the --SEA deletion was the most common cause of alpha thalassaemia in Chinese, followed by the α-³·⁷ deletion. As many as 27 genotypic interactions showed 1023 α thalassaemia silent carriers, 196 homozygous α⁺ thalassaemia traits, 973 heterozygous α⁰ thalassaemia carriers and 375 patients with Hb H disease. Statistical analysis showed a significant difference in the distribution of α thalassaemia determinants amongst the various ethnic groups. Hence, the heterogeneous distribution of common determinants indicated that the introduction of an ethnicity-targeted hierarchical α thalassaemia screening approach in this multi-ethnic Malaysian population would be effective.
  4. Fulltext COVID-19 Therapeutic Potential of Natural Products
    Low Z, Lani R, Tiong V, Poh C, AbuBakar S, Hassandarvish P
    Int J Mol Sci, 2023 May 31;24(11).
    PMID: 37298539 DOI: 10.3390/ijms24119589
    Despite the fact that coronavirus disease 2019 (COVID-19) treatment and management are now considerably regulated, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component), have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Their abundant resources and excellent antiviral performance make natural products a relatively cheap and readily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.
  5. Fulltext Recent developments in β-cell differentiation of pluripotent stem cells induced by small and large molecules
    Kumar SS, Alarfaj AA, Munusamy MA, Singh AJ, Peng IC, Priya SP, et al.
    Int J Mol Sci, 2014;15(12):23418-47.
    PMID: 25526563 DOI: 10.3390/ijms151223418
    Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (β)-cells. Small and large molecules play important roles in each stage of β-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs) to differentiate into functional β-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate) and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4), epidermal growth factor (EGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), noggin, transforming growth factor (TGF-α), and WNT3A) are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of β-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for β-cell differentiation.
  6. Fulltext Functional Roles of JNK and p38 MAPK Signaling in Nasopharyngeal Carcinoma
    Pua LJW, Mai CW, Chung FF, Khoo AS, Leong CO, Lim WM, et al.
    Int J Mol Sci, 2022 Jan 20;23(3).
    PMID: 35163030 DOI: 10.3390/ijms23031108
    c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) family members integrate signals that affect proliferation, differentiation, survival, and migration in a cell context- and cell type-specific way. JNK and p38 MAPK activities are found upregulated in nasopharyngeal carcinoma (NPC). Studies have shown that activation of JNK and p38 MAPK signaling can promote NPC oncogenesis by mechanisms within the cancer cells and interactions with the tumor microenvironment. They regulate multiple transcription activities and contribute to tumor-promoting processes, ranging from cell proliferation to apoptosis, inflammation, metastasis, and angiogenesis. Current literature suggests that JNK and p38 MAPK activation may exert pro-tumorigenic functions in NPC, though the underlying mechanisms are not well documented and have yet to be fully explored. Here, we aim to provide a narrative review of JNK and p38 MAPK pathways in human cancers with a primary focus on NPC. We also discuss the potential therapeutic agents that could be used to target JNK and p38 MAPK signaling in NPC, along with perspectives for future works. We aim to inspire future studies further delineating JNK and p38 MAPK signaling in NPC oncogenesis which might offer important insights for better strategies in diagnosis, prognosis, and treatment decision-making in NPC patients.
  7. Fulltext Modulation of Epithelial to Mesenchymal Transition Signaling Pathways by Olea Europaea and Its Active Compounds
    Razali RA, Lokanathan Y, Yazid MD, Ansari AS, Saim AB, Hj Idrus RB
    Int J Mol Sci, 2019 Jul 16;20(14).
    PMID: 31315241 DOI: 10.3390/ijms20143492
    Epithelial-mesenchymal transition (EMT) is a significant dynamic process that causes changes in the phenotype of epithelial cells, changing them from their original phenotype to the mesenchymal cell phenotype. This event can be observed during wound healing process, fibrosis and cancer. EMT-related diseases are usually caused by inflammation that eventually leads to tissue remodeling in the damaged tissue. Prolonged inflammation causes long-term EMT activation that can lead to tissue fibrosis or cancer. Due to activation of EMT by its signaling pathway, therapeutic approaches that modulate that pathway should be explored. Olea europaea (OE) is well-known for its anti-inflammatory effects and abundant beneficial active compounds. These properties are presumed to modulate EMT events. This article reviews recent evidence of the effects of OE and its active compounds on EMT events and EMT-related diseases. Following evidence from the literature, it was shown that OE could modulate TGFβ/SMAD, AKT, ERK, and Wnt/β-catenin pathways in EMT due to a potent active compound that is present therein.
  8. Fulltext Bioactive compounds and biological activities of Jatropha curcas L. kernel meal extract
    Oskoueian E, Abdullah N, Ahmad S, Saad WZ, Omar AR, Ho YW
    Int J Mol Sci, 2011;12(9):5955-70.
    PMID: 22016638 DOI: 10.3390/ijms12095955
    Defatted Jatropha curcas L. (J. curcas) seed kernels contained a high percentage of crude protein (61.8%) and relatively little acid detergent fiber (4.8%) and neutral detergent fiber (9.7%). Spectrophotometric analysis of the methanolic extract showed the presence of phenolics, flavonoids and saponins with values of 3.9, 0.4 and 19.0 mg/g DM, respectively. High performance liquid chromatography (HPLC) analyses showed the presence of gallic acid and pyrogallol (phenolics), rutin and myricetin (flavonoids) and daidzein (isoflavonoid). The amount of phorbol esters in the methanolic extract estimated by HPLC was 3.0 ± 0.1 mg/g DM. Other metabolites detected by GC-MS include: 2-(hydroxymethyl)-2 nitro-1,3-propanediol, β-sitosterol, 2-furancarboxaldehyde, 5-(hydroxymethy) and acetic acid in the methanolic extract; 2-furancarboxaldehyde, 5-(hydroxymethy), acetic acid and furfural (2-furancarboxaldehyde) in the hot water extract. Methanolic and hot water extracts of kernel meal showed antimicrobial activity against both Gram positive and Gram negative pathogenic bacteria (inhibition range: 0-1.63 cm) at the concentrations of 1 and 1.5 mg/disc. Methanolic extract exhibited antioxidant activities that are higher than hot water extract and comparable to β-carotene. The extracts tended to scavenge the free radicals in the reduction of ferric ion (Fe(3+)) to ferrous ion (Fe(2+)). Cytotoxicity assay results indicated the potential of methanolic extract as a source of anticancer therapeutic agents toward breast cancer cells.
  9. Fulltext Thermal Aging Rheological Behavior of Magnetorheological Elastomers Based on Silicone Rubber
    Aziz SAA, Mazlan SA, Ubaidillah U, Mohamad N, Choi SB, Che Aziz MA, et al.
    Int J Mol Sci, 2020 Nov 27;21(23).
    PMID: 33260840 DOI: 10.3390/ijms21239007
    Engineering rubber composites have been widely used as main components in many fields including vehicle engineering and biomedical applications. However, when a rubber composite surface area is exposed to heat or sunlight and over a long-term accelerated exposure and lifecycle of test, the rubber becomes hard, thus influencing the mechanical and rheological behavior of the materials. Therefore, in this study, the deterioration of rheological characteristics particularly the phase shift angle (δ) of silicone rubber (SR) based magnetorheological elastomer (MRE) is investigated under the effect of thermal aging. SR-MRE with 60 wt% of CIPs is fabricated and subjected to a continuous temperature of 100 °C for 72 h. The characterization of SR-MRE before and after thermal aging related to hardness, micrograph, and rheological properties are characterized using low vacuum scanning electron microscopy (LV-SEM) and a rheometer, respectively. The results demonstrated that the morphological analysis has a rough surface and more voids occurred after the thermal aging. The hardness and the weight of the SR-MRE before and after thermal aging were slightly different. Nonetheless, the thermo-rheological results showed that the stress-strain behavior have changed the phase-shift angle (δ) of SR-MRE particularly at a high strain. Moreover, the complex mechanism of SR-MRE before and after thermal aging can be observed through the changes of the 'in-rubber structure' under rheological properties. Finally, the relationship between the phase-shift angle (δ) and the in-rubber structure due to thermal aging are discussed thoroughly which led to a better understanding of the thermo-rheological behavior of SR-MRE.
  10. Fulltext Four novel p.N385K, p.V36A, c.1033-1034insT and c.1417-1418delCT mutations in the sphingomyelin Phosphodiesterase 1 (SMPD1) gene in patients with types A and B Niemann-Pick disease (NPD)
    Manshadi MD, Kamalidehghan B, Keshavarzi F, Aryani O, Dadgar S, Arastehkani A, et al.
    Int J Mol Sci, 2015 Mar 24;16(4):6668-76.
    PMID: 25811928 DOI: 10.3390/ijms16046668
    BACKGROUND: Types A and B Niemann-Pick disease (NPD) are autosomal-recessive lysosomal storage disorders caused by the deficient activity of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene.

    METHODS: In order to determine the prevalence and distribution of SMPD1 gene mutations, the genomic DNA of 15 unrelated Iranian patients with types A and B NPD was examined using PCR, DNA sequencing and bioinformatics analysis.

    RESULTS: Of 8 patients with the p.G508R mutation, 5 patients were homozygous, while the other 3 were heterozygous. One patient was heterozygous for both the p.N385K and p.G508R mutations. Another patient was heterozygous for both the p.A487V and p.G508R mutations. Two patients (one homozygous and one heterozygous) showed the p.V36A mutation. One patient was homozygous for the c.1033-1034insT mutation. One patient was homozygous for the c.573delT mutation, and 1 patient was homozygous for the c.1417-1418delCT mutation. Additionally, bioinformatics analysis indicated that two new p.V36A and p.N385K mutations decreased the acid sphingomyelinase (ASM) protein stability, which might be evidence to suggest the pathogenicity of these mutations.

    CONCLUSION: with detection of these new mutations, the genotypic spectrum of types A and B NPD is extended, facilitating the definition of disease-related mutations. However, more research is essential to confirm the pathogenic effect of these mutations.

  11. Fulltext Fabrication of Hydroxyapatite with Bioglass Nanocomposite for Human Wharton's-Jelly-Derived Mesenchymal Stem Cell Growing Substrate
    Ebrahimi S, Hanim YU, Sipaut CS, Jan NBA, Arshad SE, How SE
    Int J Mol Sci, 2021 Sep 06;22(17).
    PMID: 34502544 DOI: 10.3390/ijms22179637
    Recently, composite scaffolding has found many applications in hard tissue engineering due to a number of desirable features. In this present study, hydroxyapatite/bioglass (HAp/BG) nanocomposite scaffolds were prepared in different ratios using a hydrothermal approach. The aim of this research was to evaluate the adhesion, growth, viability, and osteoblast differentiation behavior of human Wharton's-jelly-derived mesenchymal stem cells (hWJMSCs) on HAp/BG in vitro as a scaffold for application in bone tissue engineering. Particle size and morphology were investigated by TEM and bioactivity was assessed and proven using SEM analysis with hWJMSCs in contact with the HAp/BG nanocomposite. Viability was evaluated using PrestoBlueTM assay and early osteoblast differentiation and mineralization behaviors were investigated by ALP activity and EDX analysis simultaneously. TEM results showed that the prepared HAp/BG nanocomposite had dimensions of less than 40 nm. The morphology of hWJMSCs showed a fibroblast-like shape, with a clear filopodia structure. The viability of hWJMSCs was highest for the HAp/BG nanocomposite with a 70:30 ratio of HAp to BG (HAp70/BG30). The in vitro biological results confirmed that HAp/BG composite was not cytotoxic. It was also observed that the biological performance of HAp70/BG30 was higher than HAp scaffold alone. In summary, HAp/BG scaffold combined with mesenchymal stem cells showed significant potential for bone repair applications in tissue engineering.
  12. Fulltext Isolation and enhancement of a homogenous in vitro human Hertwig's epithelial root sheath cell population
    Farea M, Halim AS, Abdullah NA, Lim CK, Mokhtar KI, Berahim Z, et al.
    Int J Mol Sci, 2013;14(6):11157-70.
    PMID: 23712356 DOI: 10.3390/ijms140611157
    Hertwig's epithelial root sheath (HERS) cells play a pivotal role during root formation of the tooth and are able to form cementum-like tissue. The aim of the present study was to establish a HERS cell line for molecular and biochemical studies using a selective digestion method. Selective digestion was performed by the application of trypsin-EDTA for 2 min, which led to the detachment of fibroblast-like-cells, with the rounded cells attached to the culture plate. The HERS cells displayed a typical cuboidal/squamous-shaped appearance. Characterization of the HERS cells using immunofluorescence staining and flow cytometry analysis showed that these cells expressed pan-cytokeratin, E-cadherin, and p63 as epithelial markers. Moreover, RT-PCR confirmed that these cells expressed epithelial-related genes, such as cytokeratin 14, E-cadherin, and ΔNp63. Additionally, HERS cells showed low expression of CD44 and CD105 with absence of CD34 and amelogenin expressions. In conclusion, HERS cells have been successfully isolated using a selective digestion method, thus enabling future studies on the roles of these cells in the formation of cementum-like tissue in vitro.
  13. Fulltext Microbial-catalyzed biotransformation of multifunctional triterpenoids derived from phytonutrients
    Shah SA, Tan HL, Sultan S, Faridz MA, Shah MA, Nurfazilah S, et al.
    Int J Mol Sci, 2014;15(7):12027-60.
    PMID: 25003642 DOI: 10.3390/ijms150712027
    Microbial-catalyzed biotransformations have considerable potential for the generation of an enormous variety of structurally diversified organic compounds, especially natural products with complex structures like triterpenoids. They offer efficient and economical ways to produce semi-synthetic analogues and novel lead molecules. Microorganisms such as bacteria and fungi could catalyze chemo-, regio- and stereospecific hydroxylations of diverse triterpenoid substrates that are extremely difficult to produce by chemical routes. During recent years, considerable research has been performed on the microbial transformation of bioactive triterpenoids, in order to obtain biologically active molecules with diverse structures features. This article reviews the microbial modifications of tetranortriterpenoids, tetracyclic triterpenoids and pentacyclic triterpenoids.
  14. Fulltext Potential Effects of Sweet Potato (Ipomoea batatas) in Hyperglycemia and Dyslipidemia-A Systematic Review in Diabetic Retinopathy Context
    Naomi R, Bahari H, Yazid MD, Othman F, Zakaria ZA, Hussain MK
    Int J Mol Sci, 2021 Oct 06;22(19).
    PMID: 34639164 DOI: 10.3390/ijms221910816
    Hyperglycemia is a condition with high glucose levels that may result in dyslipidemia. In severe cases, this alteration may lead to diabetic retinopathy. Numerous drugs have been approved by officials to treat these conditions, but usage of any synthetic drugs in the long term will result in unavoidable side effects such as kidney failure. Therefore, more emphasis is being placed on natural ingredients due to their bioavailability and absence of side effects. In regards to this claim, promising results have been witnessed in the usage of Ipomoea batatas (I. batatas) in treating the hyperglycemic and dyslipidemic condition. Thus, the aim of this paper is to conduct an overview of the reported effects of I. batatas focusing on in vitro and in vivo trials in reducing high glucose levels and regulating the dyslipidemic condition. A comprehensive literature search was performed using Scopus, Web of Science, Springer Nature, and PubMed databases to identify the potential articles on particular topics. The search query was accomplished based on the Boolean operators involving keywords such as (1) Beneficial effect OR healing OR intervention AND (2) sweet potato OR Ipomoea batatas OR traditional herb AND (3) blood glucose OR LDL OR lipid OR cholesterol OR dyslipidemia. Only articles published from 2011 onwards were selected for further analysis. This review includes the (1) method of intervention and the outcome (2) signaling mechanism involved (3) underlying mechanism of action, and the possible side effects observed based on the phytoconstiuents isolated. The comprehensive literature search retrieved a total of 2491 articles using the appropriate keywords. However, on the basis of the inclusion and exclusion criteria, only 23 articles were chosen for further review. The results from these articles indicate that I. batatas has proven to be effective in treating the hyperglycemic condition and is able to regulate dyslipidemia. Therefore, this systematic review summarizes the signaling mechanism, mechanism of action, and phytoconstituents responsible for those activities of I. batatas in treating hyperglycemic based on the in vitro and in vivo study.
  15. Fulltext Influence of the polyvinyl pyrrolidone concentration on particle size and dispersion of ZnS nanoparticles sythesized by mcrowave iradiation
    Soltani N, Saion E, Erfani M, Rezaee K, Bahmanrokh G, Drummen GP, et al.
    Int J Mol Sci, 2012;13(10):12412-27.
    PMID: 23202906 DOI: 10.3390/ijms131012412
    Zinc sulfide semiconductor nanoparticles were synthesized in an aqueous solution of polyvinyl pyrrolidone via a simple microwave irradiation method. The effect of the polymer concentration and the type of sulfur source on the particle size and dispersion of the final ZnS nanoparticle product was carefully examined. Microwave heating generally occurs by two main mechanisms: dipolar polarization of water and ionic conduction of precursors. The introduction of the polymer affects the heating rate by restriction of the rotational motion of dipole molecules and immobilization of ions. Consequently, our results show that the presence of the polymer strongly affects the nucleation and growth rates of the ZnS nanoparticles and therefore determines the average particle size and the dispersion. Moreover, we found that PVP adsorbed on the surface of the ZnS nanoparticles by interaction of the C-N and C=O with the nanoparticle's surface, thereby affording protection from agglomeration by steric hindrance. Generally, with increasing PVP concentration, mono-dispersed colloidal solutions were obtained and at the optimal PVP concentration (5%), sufficiently small size and narrow size distributions were obtained from both sodium sulfide and thioacetamide sulfur sources. Finally, the sulfur source directly influences the reaction mechanism and the final particle morphology, as well as the average size.
  16. Fulltext The Impact of Magnesium-Aluminum-Layered Double Hydroxide-Based Polyvinyl Alcohol Coated on Magnetite on the Preparation of Core-Shell Nanoparticles as a Drug Delivery Agent
    Ebadi M, Buskaran K, Saifullah B, Fakurazi S, Hussein MZ
    Int J Mol Sci, 2019 Aug 01;20(15).
    PMID: 31374834 DOI: 10.3390/ijms20153764
    One of the current developments in drug research is the controlled release formulation of drugs, which can be released in a controlled manner at a specific target in the body. Due to the diverse physical and chemical properties of various drugs, a smart drug delivery system is highly sought after. The present study aimed to develop a novel drug delivery system using magnetite nanoparticles as the core and coated with polyvinyl alcohol (PVA), a drug 5-fluorouracil (5FU) and Mg-Al-layered double hydroxide (MLDH) for the formation of FPVA-FU-MLDH nanoparticles. The existence of the coated nanoparticles was supported by various physico-chemical analyses. In addition, the drug content, kinetics, and mechanism of drug release also were studied. 5-fluorouracil (5FU) was found to be released in a controlled manner from the nanoparticles at pH = 4.8 (representing the cancerous cellular environment) and pH = 7.4 (representing the blood environment), governed by pseudo-second-order kinetics. The cytotoxicity study revealed that the anticancer delivery system of FPVA-FU-MLDH nanoparticles showed much better anticancer activity than the free drug, 5FU, against liver cancer and HepG2 cells, and at the same time, it was found to be less toxic to the normal fibroblast 3T3 cells.
  17. Fulltext Toxicity and metabolism of layered double hydroxide intercalated with levodopa in a Parkinson's disease model
    Kura AU, Ain NM, Hussein MZ, Fakurazi S, Hussein-Al-Ali SH
    Int J Mol Sci, 2014;15(4):5916-27.
    PMID: 24722565 DOI: 10.3390/ijms15045916
    Layered hydroxide nanoparticles are generally biocompatible, and less toxic than most inorganic nanoparticles, making them an acceptable alternative drug delivery system. Due to growing concern over animal welfare and the expense of in vivo experiments both the public and the government are interested to find alternatives to animal testing. The toxicity potential of zinc aluminum layered hydroxide (ZAL) nanocomposite containing anti-Parkinsonian agent may be determined using a PC 12 cell model. ZAL nanocomposite demonstrated a decreased cytotoxic effect when compared to levodopa on PC12 cells with more than 80% cell viability at 100 µg/mL compared to less than 20% cell viability in a direct levodopa exposure. Neither levodopa-loaded nanocomposite nor the un-intercalated nanocomposite disturbed the cytoskeletal structure of the neurogenic cells at their IC50 concentration. Levodopa metabolite (HVA) released from the nanocomposite demonstrated the slow sustained and controlled release character of layered hydroxide nanoparticles unlike the burst uptake and release system shown with pure levodopa treatment.
  18. Fulltext Structure prediction, molecular dynamics simulation and docking studies of D-specific dehalogenase from Rhizobium sp. RC1
    Sudi IY, Wong EL, Joyce-Tan KH, Shamsir MS, Jamaluddin H, Huyop F
    Int J Mol Sci, 2012;13(12):15724-54.
    PMID: 23443090 DOI: 10.3390/ijms131215724
    Currently, there is no three-dimensional structure of D-specific dehalogenase (DehD) in the protein database. We modeled DehD using ab initio technique, performed molecular dynamics (MD) simulation and docking of D-2-chloropropionate (D-2CP), D-2-bromopropionate (D-2BP), monochloroacetate (MCA), monobromoacetate (MBA), 2,2-dichloropropionate (2,2-DCP), d,l-2,3-dichloropropionate (d,l-2,3-DCP), and 3-chloropropionate (3-CP) into the DehD active site. The sequences of DehD and D-2-haloacid dehalogenase (HadD) from Pseudomonas putida AJ1 have 15% sequence similarity. The model had 80% of the amino acid residues in the most favored region when compared to the crystal structure of DehI from Pseudomonas putida PP3. Docking analysis revealed that Arg107, Arg134 and Tyr135 interacted with D-2CP, and Glu20 activated the water molecule for hydrolytic dehalogenation. Single residue substitutions at 25-30 °C showed that polar residues of DehD were stable when substituted with nonpolar residues and showed a decrease in activity within the same temperature range. The molecular dynamics simulation of DehD and its variants showed that in R134A variant, Arg107 interacted with D-2CP, while in Y135A, Gln221 and Arg231 interacted with D-2CP. It is our emphatic belief that the new model will be useful for the rational design of DehDs with enhanced potentials.
  19. Fulltext A Review on the Crosstalk between Insulin and Wnt/β-Catenin Signalling for Bone Health
    Wong SK, Mohamad NV, Jayusman PA, Ibrahim N'
    Int J Mol Sci, 2023 Aug 04;24(15).
    PMID: 37569816 DOI: 10.3390/ijms241512441
    A positive association between insulin resistance and osteoporosis has been widely established. However, crosstalk between the signalling molecules in insulin and Wingless (Wnt)/beta-(β-)catenin transduction cascades orchestrating bone homeostasis remains not well understood. The current review aims to collate the existing evidence, reporting (a) the expression of insulin signalling molecules involved in bone-related disorders and (b) the expression of Wnt/β-catenin signalling molecules involved in governing insulin homeostasis. The downstream effector molecule, glycogen synthase kinase-3 beta (GSK3β), has been identified to be a point of convergence linking the two signal transduction networks. This review highlights that GSK3β may be a drug target in the development of novel anabolic agents and the potential use of GSK3β inhibitors to treat bone-related disorders.
  20. Fulltext Extracellular Proteolytic Activity and Amino Acid Production by Lactic Acid Bacteria Isolated from Malaysian Foods
    Toe CJ, Foo HL, Loh TC, Mohamad R, Abdul Rahim R, Idrus Z
    Int J Mol Sci, 2019 Apr 10;20(7).
    PMID: 30974873 DOI: 10.3390/ijms20071777
    Amino acids (AAs) are vital elements for growth, reproduction, and maintenance of organisms. Current technology uses genetically engineered microorganisms for AAs production, which has urged the search for a safer food-grade AA producer strain. The extracellular proteolytic activities of lactic acid bacteria (LAB) can be a vital tool to hydrolyze extracellular protein molecules into free AAs, thereby exhibiting great potential for functional AA production. In this study, eight LAB isolated from Malaysian foods were determined for their extracellular proteolytic activities and their capability of producing AAs. All studied LAB exhibited versatile extracellular proteolytic activities from acidic to alkaline pH conditions. In comparison, Pediococcus pentosaceus UP-2 exhibited the highest ability to produce 15 AAs extracellularly, including aspartate, lysine, methionine, threonine, isoleucine, glutamate, proline, alanine, valine, leucine, tryptophan, tyrosine, serine, glycine, and cystine, followed by Pediococcus pentosaceus UL-2, Pediococcus acidilactici UB-6, and Pediococcus acidilactici UP-1 with 11 to 12 different AAs production detected extracellularly. Pediococcus pentosaceus UL-6 demonstrated the highest increment of proline production at 24 h of incubation. However, Pediococcusacidilactici UL-3 and Lactobacillus plantarum I-UL4 exhibited the greatest requirement for AA. The results of this study showed that different LAB possess different extracellular proteolytic activities and potentials as extracellular AA producers.
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