Displaying publications 41 - 60 of 68 in total

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  1. Comparison of single nucleotide polymorphisms in the human interleukin-10 gene promoter between rheumatoid arthritis patients and normal subjects in Malaysia
    Hee CS, Gun SC, Naidu R, Das Gupta E, Somnath SD, Radhakrishnan AK
    Mod Rheumatol, 2007;17(5):429-35.
    PMID: 17929139 DOI: 10.1007/s10165-007-0612-9
    In this study, three single nucleotide polymorphisms (SNPs) located within the promoter of the human interleukin (IL)-10 gene [rs1800896 (position: -1087G>A), rs1800871 (position: -824C>T) and rs1800872 (position: -597C>A)] were investigated in 84 rheumatoid arthritis (RA) patients and 95 age- and sex-matched healthy subjects using polymerase chain reaction-restriction fragment length polymorphism method. Production of IL-10 by peripheral blood lymphocytes from the RA patients and healthy subjects cultured in the presence of Concanavalin A (Con A) was determined by using enzyme-linked immunosorbent assay. The results show that the distribution of the IL-10 genotypes did not differ significantly between RA patients and healthy subjects (P>0.05). However, a significant difference was observed in allele frequencies of -824CT, -824TT, -597CA, and -597AA between the RA patients and healthy volunteers (P=0.04). The -1087A/-824T/-597A (ATA) haplotype, which comprises all mutant alleles, was associated with lower IL-10 production when compared with the other haplotypes. In contrast, the RA patients who did not display the ATA haplotype produced significantly higher levels of IL-10 when compared with those carrying either one (P=0.012) or two (P=0.005) ATA haplotypes. Our findings suggest that there is an association between SNPs in the promoter of the human IL-10 gene and susceptibility to RA.
    Study site: Hospital Tuanku Ja’afar, (Hospital Seremban), Seremban, Negeri Sembilan, Malaysia
  2. Fulltext Investigation of the curative effects of palm vitamin E tocotrienols on autoimmune arthritis disease in vivo
    Zainal Z, Rahim AA, Radhakrishnan AK, Chang SK, Khaza'ai H
    Sci Rep, 2019 11 14;9(1):16793.
    PMID: 31727971 DOI: 10.1038/s41598-019-53424-7
    The tocotrienol-rich fraction (TRF) from palm oil contains vitamin E, which possesses potent antioxidant and anti-inflammatory activities. Rheumatoid arthritis (RA) is a chronic joint inflammatory disease characterised by severe joint pain, cartilage destruction, and bone erosion owing to the effects of various pro-inflammatory mediators and cytokines. Here, we investigated the therapeutic effects of TRF in a rat model of collagen-induced arthritis (CIA). Arthritis was induced by a single intradermal injection of collagen type II in Dark Agouti (DA) rats. Rats were then treated with or without TRF by oral gavage from day 28 after the first collagen injection. Arthritic rats supplemented with TRF showed decreased articular index scores, ankle circumferences, paw volumes, and radiographic scores when compared with untreated rats. The untreated arthritic rats showed higher plasma C-reactive protein levels (p 
  3. Relationship between various cytokines implicated in asthma
    Ayakannu R, Abdullah NA, Radhakrishnan AK, Lechimi Raj V, Liam CK
    Hum Immunol, 2019 Sep;80(9):755-763.
    PMID: 31054782 DOI: 10.1016/j.humimm.2019.04.018
    Asthma is a complex disorder involving immunologic, environmental, genetic and other factors. Today, asthma is the most common disease encountered in clinical medicine in both children and adults worldwide. Asthma is characterized by increased responsiveness of the tracheobronchial tree resulting in chronic swelling and inflammation of the airways recognized to be controlled by the T-helper 2 (Th2) lymphocytes, which secrete cytokines to increase the production of IgE by B cells. There are many cytokines implicated in the development of the chronic inflammatory processes that are often observed in asthma. Ultimately, these cytokines cause the release of mediators such as histamine and leukotrienes (LT), which in turn promote airway remodeling, bronchial hyperresponsiveness and bronchoconstriction. The CD4+ T-lymphocytes from the airways of asthmatics express a panel of cytokines that represent the Th2 cells. The knowledge derived from numerous experimental and clinical studies have allowed physicians and scientists to understand the normal functions of these cytokines and their roles in the pathogenesis of asthma. The main focus of this review is to accentuate the relationship between various cytokines implicated in human asthma. However, some key findings from animal models will be highlighted to support the discoveries from clinical studies.
  4. Health-promoting effects of red palm oil: evidence from animal and human studies
    Loganathan R, Subramaniam KM, Radhakrishnan AK, Choo YM, Teng KT
    Nutr Rev, 2017 Feb 01;75(2):98-113.
    PMID: 28158744 DOI: 10.1093/nutrit/nuw054
    The fruit of the oil palm tree (Elaeis guineesis) is the source of antioxidant-rich red palm oil. Red palm oil is a rich source of phytonutrients such as tocotrienols, tocopherols, carotenoids, phytosterols, squalene, and coenzyme Q10, all of which exhibit nutritional properties and oxidative stability. Mutagenic, nutritional, and toxicological studies have shown that red palm oil contains highly bioavailable β-carotene and vitamin A and is reasonably stable to heat without any adverse effects. This review provides a comprehensive overview of the nutritional properties of red palm oil. The possible antiatherogenic, antihemorrhagic, antihypertensive, anticancer, and anti-infective properties of red palm oil are examined. Moreover, evidence supporting the potential effectiveness of red palm oil to overcome vitamin A deficiency in children and pregnant women, to improve ocular complications of vitamin A deficiency, to protect against ischemic heart disease, to promote normal reproduction in males and females, to aid in the management of diabetes, to ameliorate the adverse effects of chemotherapy, and to aid in managing hypobaric conditions is presented.
  5. Influence of serum concentration in retinoic acid and phorbol ester induced differentiation of SH-SY5Y human neuroblastoma cell line
    Magalingam KB, Radhakrishnan AK, Somanath SD, Md S, Haleagrahara N
    Mol Biol Rep, 2020 Nov;47(11):8775-8788.
    PMID: 33098048 DOI: 10.1007/s11033-020-05925-2
    Numerous protocols to establish dopaminergic phenotype in SH-SY5Y cells have been reported. In most of these protocols there are variations in concentration of serum used. In this paper, we compared the effects of high (10%), low (3%) and descending (2.5%/1%) serum concentration in differentiation medium containing different proportion of retinoic acid (RA) and 12-O-Tetradecanoylphorbol-13-acetate (TPA) or RA-only on the undifferentiated SH-SY5Y cells with regards to cell morphology, biochemical and gene expression alterations. Cells differentiated in culture medium containing low and descending serum concentrations showed increased number of neurite projections and reduced proliferation rates when compared to undifferentiated cells. The SH-SY5Y cells differentiated in culture medium containing 3% RA and low serum or descending (2.5%/1% RA/TPA) were found to be more susceptible to 6-hydroxydopamine (6-OHDA) induced cytotoxicity. Cells differentiated with RA/TPA or RA differentiated showed increased production of the α-synuclein (SNCA) neuroprotein and dopamine neurotransmitter compared to undifferentiated cells, regardless serum concentrations used. There was no significant difference in the expression of tyrosine hydroxylase (TH) gene between undifferentiated and differentiated SH-SY5Y cells. However, the expression of dopamine receptor D2 (DRD2) gene was markedly increased (p<0.05) in differentiated cells with 3% serum and RA only when compared to undifferentiated cells. In conclusion, to terminally differentiate SH-SY5Y cells to be used as a cell-based model to study Parkinson's disease (PD) to investigate molecular mechanisms and drug discovery, the optimal differentiation medium should contain 3% serum in RA-only.
  6. Lipid based nanocarriers system for topical delivery of photosensitizers
    Md S, Haque S, Madheswaran T, Zeeshan F, Meka VS, Radhakrishnan AK, et al.
    Drug Discov Today, 2017 Aug;22(8):1274-1283.
    PMID: 28456749 DOI: 10.1016/j.drudis.2017.04.010
    Topical photodynamic therapy (PDT) is a non-invasive technique used in the treatment of malignant and non-malignant skin diseases. It offers great promise because of its simplicity, enhanced patient compliance, localisation of the photosensitizer, as well as the use of light and oxygen to achieve photocytotoxicity. Despite progress in photosensitizer-mediated topical PDT, its clinical application is limited by poor penetration of photosensitizers through the skin. Therefore, much effort has been made to develop nanocarriers that can tackle the challenges of conventional photosensitizer-mediated PDT for topical delivery. This review discusses recent data on the use of different types of lipid-based nanocarriers in delivering photosensitizer for topical PDT.
  7. Red palm olein supplementation on cytokines, endothelial function and lipid profile in centrally overweight individuals: a randomised controlled trial
    Loganathan R, Vethakkan SR, Radhakrishnan AK, Razak GA, Kim-Tiu T
    Eur J Clin Nutr, 2019 04;73(4):609-616.
    PMID: 29946115 DOI: 10.1038/s41430-018-0236-5
    BACKGROUND/OBJECTIVES: The consumption of antioxidant-rich cooking oil such as red palm olein may be cardioprotective from the perspective of subclinical inflammation and endothelial function.

    SUBJECTS/METHODS: Using a crossover design, we conducted a randomised controlled trial in 53 free-living high-risk abdominally overweight subjects, comparing the effects of incorporating red palm olein (with palm olein as control) in a supervised isocaloric 2100 kcal diet of 30% en fat, two-thirds (45 g/day) of which were derived from the test oil for a period of 6 weeks each.

    RESULTS: We did not observe a significant change in interleukin-6 (IL-6), in parallel with other pro-inflammatory (tumour necrosis factor-β, interleukin-1β, IL-1β, high sensitivity C-reactive protein, hsCRP) and endothelial function (soluble intercellular adhesion molecules, sICAM, soluble intravascular adhesion molecules, sVCAM) parameters. Interestingly, we observed a significant reduction in oxidised LDL levels (P 

  8. Fulltext The usefulness of osteocalcin measurements in Malaysian patients with rheumatoid arthritis
    Wong TH, Das Gupta E, Radhakrishnan AK, Gun SC, Chembalingam G, Yeap SS
    International e-Journal of Science, Medicine & Education, 2018;12(1):4-10.
    MyJurnal
    Rheumatoid arthritis (RA) is a chronic inflammatory condition that can be associated with abnormal bone turnover and hence osteoporosis. Osteocalcin (OC) levels are increased in conditions with high bone turnover, including high RA disease activity. Thus, OC levels could possibly be used as a marker to assess bone health and disease activity in RA patients. As there have been no previous studies looking at serum OC levels in Malaysian RA patients, this study was performed to examine possible correlations between OC, bone mineral density (BMD) and disease activity in this population. A cross-sectional study of 75 female RA patients and 29 healthy controls was performed. Serum OC was measured using a Quantikine® ELISA kit. Dualenergy x-ray absorptiometry (DXA) was used to assess BMD. Serum OC levels were not significantly different between RA patients (median 14.44 ng/mL, interquartile range [IQR 12.99]) compared to healthy controls (median 11.04 ng/mL IQR 12.29) (p=0.198). Serum OC increased with age (Spearman’s rho r=0.230, p=0.047). There was no significant correlation between serum OC and body mass index (BMI), menopause status, BMD, DAS28, swollen or tender joint counts. Overall, there were 11 (14.7%) patients with osteoporosis and 27 (36.0%) with osteopenia. Menopause status was significantly associated with BMD at all sites (lumbar spine p=0.002, femoral neck p=0.004, total hip p=0.002). Serum OC were similar in RA patients compared to healthy controls. In RA patients, serum OC did not correlate with RA disease activity or BMD. Menopause status remains an important influence on BMD. Thus, measuring serum OC levels in Malaysian RA patients was not useful in identifying those at risk of low BMD.
    Study site: Rheumatology clinic, Hospital Tuanku Jaafar, Seremban, Negeri Sembilan, and Klinik Pakar Puchong, Kuala Lumpur, Malaysia
  9. Effects of 25-hydroxyvitamin D and vitamin D-binding protein on bone mineral density and disease activity in Malaysian patients with rheumatoid arthritis
    Wong TH, Das Gupta E, Radhakrishnan AK, Gun SC, Chembalingam G, Yeap SS
    Int J Rheum Dis, 2018 May;21(5):992-1000.
    PMID: 28217867 DOI: 10.1111/1756-185X.13048
    AIM: Vitamin D3 [25(OH)D] has been shown to be important in bone health and can influence rheumatoid arthritis (RA) disease activity. Vitamin D-binding protein (VDBP) levels vary with race and may modulate 'bioavailable' levels of 25(OH)D. The aim of this study was to explore the relationships between 25(OH)D, VDBP and clinical factors on bone mineral density (BMD) in a group of multi-ethnic Malaysian RA patients and healthy controls.

    METHODS: A cross-sectional study of 77 female RA patients and 29 controls was performed. Serum 25(OH)D was measured using the Elecsys® Vitamin D total assay. Serum VDBP was measured using a Quantikine® enzyme-linked immunosorbent assay kit. BMD was assessed using dual-energy X-ray absorptiometry (DXA).

    RESULTS: Overall, mean 25(OH)D levels were 42.66 ± 21.75 nmol/L with no significant difference between RA patients and controls. 25(OH)D levels were significantly higher in Chinese, compared to Malay/Indian subjects. In RA patients, menopausal status and body mass index (BMI) were significantly associated with BMD but not 25(OH)D or RA Disease Activity Score of 28 joints (DAS28). There was no significant correlation between 25(OH)D and DAS28, even after correction for menopausal status and BMI. VDBP levels were not significantly different between the races and did not significantly correlate with BMD, 25(OH)D overall, or DAS28 in RA patients.

    CONCLUSIONS: In Malaysian RA patients, menopausal status and BMI were more important influences on BMD than 25(OH)D or RA disease activity. The utility of measuring VDBP levels in this population remains uncertain.
    Study site: Rheumatology clinic, Hospital Tuanku Jaafar, Seremban, Negeri Semblance; Klinik Pakar Puchong, Puchong, Kuala Lumpur, Malaysia
  10. Reduced infiltration of regulatory T cells in tumours from mice fed daily with gamma-tocotrienol supplementation
    Subramaniam S, Anandha Rao JS, Ramdas P, Ng MH, Kannan Kutty M, Selvaduray KR, et al.
    Clin Exp Immunol, 2021 Nov;206(2):161-172.
    PMID: 34331768 DOI: 10.1111/cei.13650
    Gamma-tocotrienol (γT3) is an analogue of vitamin E with beneficial effects on the immune system, including immune-modulatory properties. This study reports the immune-modulatory effects of daily supplementation of γT3 on host T helper (Th) and T regulatory cell (Treg ) populations in a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with either γT3 or vehicle (soy oil) for 2 weeks via oral gavage before they were inoculated with syngeneic 4T1 mouse mammary cancer cells (4T1 cells). Supplementation continued until the mice were euthanized. Mice (n = 6) were euthanized at specified time-points for various analysis (blood leucocyte, cytokine production and immunohistochemistry). Tumour volume was measured once every 7 days. Gene expression studies were carried out on tumour-specific T lymphocytes isolated from splenic cultures. Supplementation with γT3 increased CD4+ (p 
  11. Tocotrienols protect differentiated SH-SY5Y human neuroblastoma cells against 6-hydroxydopamine-induced cytotoxicity by ameliorating dopamine biosynthesis and dopamine receptor D2 gene expression
    Magalingam KB, Somanath SD, Md S, Haleagrahara N, Fu JY, Selvaduray KR, et al.
    Nutr Res, 2022 Feb;98:27-40.
    PMID: 35065349 DOI: 10.1016/j.nutres.2021.09.003
    Oxidative stress is a critical factor that triggers a "domino" cascade of events leading to the degeneration of dopaminergic neurons in Parkinson disease. Tocotrienols (T3) have antioxidant effects and can protect neuronal cells against oxidative damage. In the present study, we investigated the neuroprotective effects of different forms of T3 (alpha, delta, gamma) or tocotrienol-rich fraction (TRF) against 6-hydroxydopamine (6-OHDA)-induced oxidative damage in differentiated SH-SY5Y human neural cells. Differentiating the SH-SY5Y cells with retinoic acid and a low-serum culture medium for 6 days allowed development of human dopamine-like neural cells. Subsequently, the differentiated SH-SY5Y neural cells were pretreated with different forms of T3 for 24 hours before these cells were exposed to 6-OHDA. The T3 analogues and TRF displayed neuroprotective effects (P < .05) via restoration of cell viability and activation of antioxidant enzymes (e.g., superoxide dismutase, catalase). Notably, TRF was highly efficient in scavenging reactive oxygen species and upregulating dopamine and tyrosine hydroxylase levels in the differentiated SH-SY5Y cells. Gamma-T3 exhibited the most potent effects in attenuating apoptosis, whereas alpha-T3 was most effective in preventing 6-OHDA-induced leakage of α-Synuclein. Delta-T3 displayed a noticeable effect in upregulating the dopamine receptor D2 gene expression compared with controls. These findings suggest T3 isoforms and TRF demonstrate significant neuroprotective effects in protecting differentiated neural cells against 6-OHDA-mediated oxidative stress.
  12. Fulltext Tocotrienol-Rich Fraction and Levodopa Regulate Proteins Involved in Parkinson's Disease-Associated Pathways in Differentiated Neuroblastoma Cells: Insights from Quantitative Proteomic Analysis
    Magalingam KB, Ramdas P, Somanath SD, Selvaduray KR, Bhuvanendran S, Radhakrishnan AK
    Nutrients, 2022 Nov 03;14(21).
    PMID: 36364894 DOI: 10.3390/nu14214632
    Tocotrienol-rich fraction (TRF), a palm oil-derived vitamin E fraction, is reported to possess potent neuroprotective effects. However, the modulation of proteomes in differentiated human neuroblastoma SH-SY5Y cells (diff-neural cells) by TRF has not yet been reported. This study aims to investigate the proteomic changes implicated by TRF in human neural cells using a label-free liquid-chromatography-double mass spectrometry (LC-MS/MS) approach. Levodopa, a drug used in the treatment of Parkinson's disease (PD), was used as a drug control. The human SH-SY5Y neuroblastoma cells were differentiated for six days and treated with TRF or levodopa for 24 h prior to quantitative proteomic analysis. A total of 81 and 57 proteins were differentially expressed in diff-neural cells following treatment with TRF or levodopa, respectively. Among these proteins, 32 similar proteins were detected in both TRF and levodopa-treated neural cells, with 30 of these proteins showing similar expression pattern. The pathway enrichment analysis revealed that most of the proteins regulated by TRF and levodopa are key players in the ubiquitin-proteasome, calcium signalling, protein processing in the endoplasmic reticulum, mitochondrial pathway and axonal transport system. In conclusion, TRF is an essential functional food that affects differential protein expression in human neuronal cells at the cellular and molecular levels.
  13. Fulltext Clinically Relevant Genes and Proteins Modulated by Tocotrienols in Human Colon Cancer Cell Lines: Systematic Scoping Review
    Khalid AQ, Bhuvanendran S, Magalingam KB, Ramdas P, Kumari M, Radhakrishnan AK
    Nutrients, 2021 Nov 12;13(11).
    PMID: 34836311 DOI: 10.3390/nu13114056
    The last decade has witnessed tremendous growth in tocotrienols (T3s) research, especially in the field of oncology, owing to potent anticancer property. Among the many types of cancers, colorectal cancer (CRC) is growing to become a serious global health threat to humans. Chemoprevention strategies in recent days are open to exploring alternative interventions to inhibit or delay carcinogenesis, especially with the use of bioactive natural compounds, such as tocotrienols. This scoping review aims to distil the large bodies of literature from various databases to identify the genes and their encoded modulations by tocotrienols and to explicate important mechanisms via which T3s combat CRC. For this scoping review, research papers published from 2010 to early 2021 related to T3s and human CRC cells were reviewed in compliance with the PRISMA guidelines. The study included research articles published in English, searchable on four literature databases (Ovid MEDLINE, PubMed, Scopus, and Embase) that reported differential expression of genes and proteins in human CRC cell lines following exposure to T3s. A total of 12 articles that fulfilled the inclusion and exclusion criteria of the study were short-listed for data extraction and analysis. The results from the analysis of these 12 articles showed that T3s, especially its γ and δ analogues, modulated the expression of 16 genes and their encoded proteins that are associated with several important CRC pathways (apoptosis, transcriptional dysregulation in cancer, and cancer progression). Further studies and validation work are required to scrutinize the specific role of T3s on these genes and proteins and to propose the use of T3s to develop adjuvant or multi-targeted therapy for CRC.
  14. Identification of blood-based biomarkers for diagnosis and prognosis of Parkinson's disease: A systematic review of proteomics studies
    Chelliah SS, Bhuvanendran S, Magalingam KB, Kamarudin MNA, Radhakrishnan AK
    Ageing Res Rev, 2022 01;73:101514.
    PMID: 34798300 DOI: 10.1016/j.arr.2021.101514
    Parkinson's Disease (PD), a neurodegenerative disorder, is characterised by the loss of motor function and dopamine neurons. Therapeutic avenues remain a challenge due to lack of accuracy in early diagnosis, monitoring of disease progression and limited therapeutic options. Proteomic platforms have been utilised to discover biomarkers for numerous diseases, a tool that may benefit the diagnosis and monitoring of disease progression in PD patients. Therefore, this systematic review focuses on analysing blood-based candidate biomarkers (CB) identified via proteomics platforms for PD. This study systematically reviewed articles across six databases (EMBASE, Cochrane, Ovid Medline, Scopus, Science Direct and PubMed) published between 2010 and 2020. Of the 504 articles identified, 12 controlled-PD studies were selected for further analysis. A total of 115 candidate biomarkers (CB) were identified across selected 12-controlled studies, of which 23 CB were found to be replicable in more than two cohorts. Using the PANTHER Go-Slim classification system and STRING network, the gene function and protein interactions between biomarkers were analysed. Our analysis highlights Apolipoprotein A-I (ApoA-I), which is essential in lipid metabolism, oxidative stress, and neuroprotection demonstrates high replicability across five cohorts with consistent downregulation across four cohorts. Since ApoA-I was highly replicable across blood fractions, proteomic platforms and continents, its relationship with cholesterol, statin and oxidative stress as PD biomarker, its role in the pathogenesis of PD is discussed in this paper. The present study identified ApoA-I as a potential biomarker via proteomics analysis of PD for the early diagnosis and prediction of disease progression.
  15. Clinical characteristics, cytokine profiles and plasma IgE in adults with asthma
    Ayakannu R, Abdullah NA, Raj VL, Radhakrishnan AK, Liam CK
    Mol Immunol, 2022 Jan 14;143:50-57.
    PMID: 35038659 DOI: 10.1016/j.molimm.2022.01.005
    Asthma is a disease with complicated network of inflammatory responses of cytokines and ImmunoglobulinE (IgE). The aim of this study was to explore the clinical characteristics, cytokine profile and plasma IgE in the Malaysian population. This is a cross-sectional study involving physician-diagnosed asthma patients (n = 287) recruited from the Chest Clinic, University of Malaya Medical Centre (UMMC). Blood (8 mL) was taken after consent was obtained. The peripheral blood leucocytes (PBL) were cultured in presence of a mitogen for 72 h to quantify cytokines [Interleukin-5(IL-5), Interleukin-9 (IL-9), Interleukin-12 Beta (IL-12ꞵ) and granulocyte-macrophage colony-stimulating factor (GM-CSF)] and plasma was used to quantify IgE levels with commercial ELISA kits. Results were compared against the same biomarkers in healthy subjects (n = 203). In addition, the amount of the biomarkers in the asthma patients were compared with their disease severity and clinical characteristics. Statistical tests in the SPSS software (Mann-Whitney U test and the Kruskal Wallis) were used to compare cytokine production and plasma IgE levels. The mean plasma IgE level was markedly higher (p < 0.0001) in asthmatics compared to controls. There were higher levels of IL-5, IL-9, IL-12ꞵ and GM-CSF (p < 0.0001) produced by cultured PBL from asthma patients compared to controls. However, our results did not expose a significant association between these cytokine levels and severity and clinical symptoms of asthma. However, there was a marked association between asthma severity and blood lymphocyte count [ꭓ2(2) = 6.745, p < 0.05]. These findings support the roles played by cytokines and IgE in the airway inflammation in asthma. The findings of this study provide new information about inflammatory cytokines in Malaysian asthma patients.
  16. Fulltext Immune Biomarkers in Blood from Sarcoma Patients: A Pilot Study
    Munisamy S, Radhakrishnan AK, Ramdas P, Samuel PJ, Singh VA
    Curr Oncol, 2022 Aug 05;29(8):5585-5603.
    PMID: 36005179 DOI: 10.3390/curroncol29080441
    The main role of the host immune system is to identify and eliminate cancer cells, which is a complex process, but it is not a fail-safe mechanism. Many sarcoma patients succumb to this disease despite treatments rendered. The aim of this pilot study was to compare the levels of CD4+ T-cells, T-regulatory (Treg) cells, and cytokines such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-17A (IL-17A), and transforming growth factor-beta-1 (TGF-β1) in peripheral blood leukocytes of sarcoma patients and healthy controls. For gene expression studies, total ribonucleic acid (RNA) was extracted from peripheral blood leukocytes and genes that were differentially regulated in peripheral blood leukocytes of sarcoma patients compared with healthy controls were determined using a commercial T-helper cell differentiation quantitative polymerase chain reaction (qPCR) array. Flow cytometer analysis was performed on blood samples from 26 sarcoma patients and 10 healthy controls to identify the levels of CD4+ T-cells and T-reg cells. The level of cytokines in plasma and culture supernatant were quantified using commercial enzyme-linked immunosorbent assay (ELISA) kits. A marked reduction in the percentage of CD4+ T-cells (p = 0.037) and levels of TNF-α (p = 0.004) and IFN-γ (0.010) was observed in sarcoma patients. Gene expression analysis showed five genes (homeobox A10 (HOXA10), GATA binding protein 3 (GATA3), prostaglandin D2 receptor 2 (PTGDR2), thymocyte selection associated high mobility group box (TOX), and C-C motif chemokine receptor 3 (CCR3)) were dysregulated (p < 0.05) in sarcoma patients. This study suggests that T-helper-1 immune responses are reduced in sarcoma patients.
  17. Fulltext Protease-targeting peptide-functionalized porous silicon nanoparticles for cancer fluorescence imaging
    Kanathasan JS, Palanisamy UD, Radhakrishnan AK, Chakravarthi S, Thong TB, Swamy V
    Nanomedicine (Lond), 2022 Sep;17(21):1511-1528.
    PMID: 36382634 DOI: 10.2217/nnm-2022-0017
    Background: Porous silicon (pSi) nanoparticles (NPs) functionalized with suitable targeting ligands are now established cancer bioimaging agents and drug-delivery platforms. With growing interest in peptides as tumor-targeting ligands, much work has focused on the use of various peptides in combination with pSi NPs for cancer theranostics. Here, the authors investigated the targeting potential of pSi NPs functionalized with two types of peptide, a linear 10-mer peptide and its branched (Y-shaped) equivalent, that respond to legumain activity in tumor cells. Results: In vitro experiments established that the linear peptide-pSi NP conjugate had better aqueous stability under tumor conditions and higher binding efficiency (p  0.05) of linear peptide-conjugated pSi NPs in the tumor site within 4 h compared with nonconjugated pSi NPs. These results suggest that the linear peptide-pSi NP formulation is a nontoxic, stable and efficient fluorescence bioimaging agent and potential drug-delivery platform.
  18. Fulltext Poloxamer 188 (P188), A Potential Polymeric Protective Agent for Central Nervous System Disorders: A Systematic Review
    Chen WN, Shaikh MF, Bhuvanendran S, Date A, Ansari MT, Radhakrishnan AK, et al.
    Curr Neuropharmacol, 2022;20(4):799-808.
    PMID: 34077349 DOI: 10.2174/1570159X19666210528155801
    Poloxamer 188 (P188) is an FDA-approved biocompatible block copolymer composed of repeating units of Poly(Ethylene Oxide) (PEO) and poly(propylene oxide) (PPO). Due to its amphiphilic nature and high Hydrophile-Lipophile Balance (HLB) value of 29, P188 is used as a stabilizer/emulsifier in many cosmetics and pharmaceutical preparations. While the applications of P188 as an excipient are widely explored, the data on the pharmacological activity of P188 are scarce. Notably, the neuroprotective potential of P188 has gained a lot of interest. Therefore, this systematic review is aimed at summarizing evidence of neuroprotective potential of P188 in CNS disorders. The PRISMA model was used, and five databases (Google Scholar, Scopus, Wiley Online Library, ScienceDirect, and PubMed) were searched with relevant keywords. The search resulted in 11 articles, which met the inclusion criteria. These articles described the protective effects of P188 on traumatic brain injury or mechanical injury in cells, neurotoxicity, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), and ischemia/ reperfusion injury from stroke. All the articles were original research in experimental or pre-clinical stages using animal models or in vitro systems. The reported activities demonstrated the potential of P188 as a neuroprotective agent in improving CNS conditions such as neurodegeneration.
  19. Fulltext Fabrication, Optimization, and Evaluation of Rotigotine-Loaded Chitosan Nanoparticles for Nose-To-Brain Delivery
    Tzeyung AS, Md S, Bhattamisra SK, Madheswaran T, Alhakamy NA, Aldawsari HM, et al.
    Pharmaceutics, 2019 Jan 10;11(1).
    PMID: 30634665 DOI: 10.3390/pharmaceutics11010026
    The objective of the present study was to develop, optimize, and evaluate rotigotine-loaded chitosan nanoparticles (RNPs) for nose-to-brain delivery. Rotigotine-loaded chitosan nanoparticles were prepared by the ionic gelation method and optimized for various parameters such as the effect of chitosan, sodium tripolyphosphate, rotigotine concentration on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The prepared nanoparticles were characterized using photon correlation spectroscopy, transmission electron microscopy, scanning electron microscopy, atomic force microscopy, fourier-transform infrared spectroscopy, and X-ray diffraction. The developed RNPs showed a small hydrodynamic particle size (75.37 ± 3.37 nm), small PDI (0.368 ± 0.02), satisfactory zeta potential (25.53 ± 0.45 mV), and very high entrapment efficiency (96.08 ± 0.01). The 24-h in vitro release and ex vivo nasal permeation of rotigotine from the nanoparticles were 49.45 ± 2.09% and 92.15 ± 4.74% while rotigotine solution showed corresponding values of 95.96 ± 1.79%and 58.22 ± 1.75%, respectively. The overall improvement ratio for flux and permeability coefficient were found to be 4.88 and 2.67 when compared with rotigotine solution. A histopathological study showed that the nanoparticulate formulation produced no toxicity or structural damage to nasal mucosa. Our results indicated that rotigotine-loaded chitosan nanoparticles provide an efficient carrier for nose-to-brain delivery.
  20. Fulltext Regulation of EMT Markers, Extracellular Matrix, and Associated Signalling Pathways by Long Non-Coding RNAs in Glioblastoma Mesenchymal Transition: A Scoping Review
    Leung DHL, Phon BWS, Sivalingam M, Radhakrishnan AK, Kamarudin MNA
    Biology (Basel), 2023 Jun 04;12(6).
    PMID: 37372103 DOI: 10.3390/biology12060818
    Glioblastoma (GBM) mesenchymal (MES) transition can be regulated by long non-coding RNAs (lncRNAs) via modulation of various factors (Epithelial-to-Mesenchymal (EMT) markers, biological signalling, and the extracellular matrix (ECM)). However, understanding of these mechanisms in terms of lncRNAs is largely sparse. This review systematically analysed the mechanisms by which lncRNAs influence MES transition in GBM from a systematic search of the literature (using PRISMA) performed in five databases (PubMed, MEDLINE, EMBASE, Scopus, and Web of Science). We identified a total of 62 lncRNAs affiliated with GBM MES transition, of which 52 were upregulated and 10 were downregulated in GBM cells, where 55 lncRNAs were identified to regulate classical EMT markers in GBM (E-cadherin, N-cadherin, and vimentin) and 25 lncRNAs were reported to regulate EMT transcription factors (ZEB1, Snai1, Slug, Twist, and Notch); a total of 16 lncRNAs were found to regulate the associated signalling pathways (Wnt/β-catenin, PI3k/Akt/mTOR, TGFβ, and NF-κB) and 14 lncRNAs were reported to regulate ECM components (MMP2/9, fibronectin, CD44, and integrin-β1). A total of 25 lncRNAs were found dysregulated in clinical samples (TCGA vs. GTEx), of which 17 were upregulated and 8 were downregulated. Gene set enrichment analysis predicted the functions of HOXAS3, H19, HOTTIP, MEG3, DGCR5, and XIST at the transcriptional and translational levels based on their interacting target proteins. Our analysis observed that the MES transition is regulated by complex interplays between the signalling pathways and EMT factors. Nevertheless, further empirical studies are required to elucidate the complexity in this process between these EMT factors and the signalling involved in the GBM MES transition.
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