Displaying publications 21 - 33 of 33 in total

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  1. Fulltext Anti-Cancer Properties of the Naturally Occurring Aphrodisiacs: Icariin and Its Derivatives
    Tan HL, Chan KG, Pusparajah P, Saokaew S, Duangjai A, Lee LH, et al.
    Front Pharmacol, 2016;7:191.
    PMID: 27445824 DOI: 10.3389/fphar.2016.00191
    Epimedium (family Berberidaceae), commonly known as Horny Goat Weed or Yin Yang Huo, is commonly used as a tonic, aphrodisiac, anti-rheumatic and anti-cancer agent in traditional herbal formulations in Asian countries such as China, Japan, and Korea. The major bioactive compounds present within this plant include icariin, icaritin and icariside II. Although it is best known for its aphrodisiac properties, scientific and pharmacological studies suggest it possesses broad therapeutic capabilities, especially for enhancing reproductive function and osteoprotective, neuroprotective, cardioprotective, anti-inflammatory and immunoprotective effects. In recent years, there has been great interest in scientific investigation of the purported anti-cancer properties of icariin and its derivatives. Data from in vitro and in vivo studies suggests these compounds demonstrate anti-cancer activity against a wide range of cancer cells which occurs through various mechanisms such as apoptosis, cell cycle modulation, anti-angiogenesis, anti-metastasis and immunomodulation. Of note, they are efficient at targeting cancer stem cells and drug-resistant cancer cells. These are highly desirable properties to be emulated in the development of novel anti-cancer drugs in combatting the emergence of drug resistance and overcoming the limited efficacy of current standard treatment. This review aims to summarize the anti-cancer mechanisms of icariin and its derivatives with reference to the published literature. The currently utilized applications of icariin and its derivatives in cancer treatment are explored with reference to existing patents. Based on the data compiled, icariin and its derivatives are shown to be compounds with tremendous potential for the development of new anti-cancer drugs.
    Matched MeSH terms: Immunomodulation
  2. Second regional plasmapheresis conference and workshop for Southeast Asia (SEA) on the immunomodulatory role of plasma exchange in central and peripheral nervous system disorders, Kuala Lumpur, Malaysia, 9th December 2017
    Viswanathan S, Hung SKY, Goyal V, Apiwattanakul M, Thirugnanam UN, Abdullah S, et al.
    J Clin Apher, 2018 Oct;33(5):559-568.
    PMID: 29626354 DOI: 10.1002/jca.21630
    In December 2017, 79 delegates attended the 2nd regional plasmapheresis conference and workshop for Southeast Asia (SEA) on the immunomodulatory role of plasma exchange in central and peripheral nervous system disorders in Kuala Lumpur, Malaysia. This meeting featured 6 plenary lectures, interactive sessions dedicated for experience sharing, case presentations, and a practical session for paramedics. Clinical experts and researchers from 7 SEA countries and India shared experience and challenges in treating autoimmune neurological disorders. While the spectrum of diseases and neurology practice remained largely similar, there was great disparities in accessibility of therapeutic plasma exchange (TPE) within SEA countries and between urban or rural settings. Costs, human resources, and healthcare policies are common challenges in providing sustainable TPE services. Novel techniques and innovative ideas in performing TPE were explored. A working consortium comprising of key opinion leaders was proposed to improve standards of TPE and enhance future research.
    Matched MeSH terms: Immunomodulation
  3. Fulltext Extracellular Vesicles and DAMPs in Cancer: A Mini-Review
    Abu N, Rus Bakarurraini NAA, Nasir SN
    Front Immunol, 2021;12:740548.
    PMID: 34721407 DOI: 10.3389/fimmu.2021.740548
    Certain cancer therapy has been shown to induce immunogenic cell death in cancer cells and may promote tumor progression instead. The external stress or stimuli may induce cell death and contribute toward the secretion of pro inflammatory molecules. The release of damage-associated molecular patterns (DAMPs) upon induction of therapy or cell death has been shown to induce an inflammatory response. Nevertheless, the mechanism as to how the DAMPs are released and engage in such activity needs further in-depth investigation. Interestingly, some studies have shown that DAMPs can be released through extracellular vesicles (EVs) and can bind to receptors such as toll-like receptors (TCRs). Ample pre-clinical studies have shown that cancer-derived EVs are able to modulate immune responses within the tumor microenvironment. However, the information on the presence of such DAMPs within EVs is still elusive. Therefore, this mini-review attempts to summarize and appraise studies that have shown the presence of DAMPs within cancer-EVs and how it affects the downstream cellular process.
    Matched MeSH terms: Immunomodulation
  4. Fulltext In Vivo Immunomodulation and Lipid Peroxidation Activities Contributed to Chemoprevention Effects of Fermented Mung Bean against Breast Cancer
    Yeap SK, Mohd Yusof H, Mohamad NE, Beh BK, Ho WY, Ali NM, et al.
    Evid Based Complement Alternat Med, 2013;2013:708464.
    PMID: 23710232 DOI: 10.1155/2013/708464
    Mung bean has been reported to have antioxidant, cytotoxic, and immunomodulatory effects in vitro. Fermented products are reported to have enhanced immunomodulation and cancer chemopreventive effects. In this study, fermented mung bean treatments in vivo were studied by monitoring tumor development, spleen immunity, serum cytokine (interleukin 2 and interferon gamma) levels, and spleen/tumor antioxidant levels after injection with low and high risk 4T1 breast cancer cells. Pretreatment with fermented mung bean was associated with delayed tumor formation in low risk mice. Furthermore, this treatment was connected with higher serum anticancer cytokine levels, spleen T cell populations, splenocyte cytotoxicity, and spleen/tumor antioxidant levels. Histopathological evaluation of fermented mung bean treated tumor revealed lower event of mitotic division. On the other hand, antioxidant and nitric oxide levels that were significantly increased in the untreated mice were inhibited in the fermented mung bean treated groups. These results suggested that fermented mung bean has potential cancer chemoprevention effects through the stimulation of immunity, lipid peroxidation, and anti-inflammation.
    Matched MeSH terms: Immunomodulation
  5. Fulltext Immunomodulatory effects of 17-O-acetylacuminolide in RAW264.7 cells and HUVECs: involvement of MAPK and NF-κB pathways
    Achoui M, Heyninck K, Looi CY, Mustafa AM, Haegeman G, Mustafa MR
    Drug Des Devel Ther, 2014;8:1993-2007.
    PMID: 25349474 DOI: 10.2147/DDDT.S68659
    The terpenoid 17-O-acetylacuminolide (AA) was shown to inhibit the production of several inflammatory mediators. However, the mechanisms by which this compound elicited its anti-inflammatory activity remain to be elucidated. In this study, we analyzed the effects of AA on inflammatory gene expression in two different cell types with primordial importance in the inflammatory processes - endothelial cells and macrophages. In human umbilical vein endothelial cells, AA inhibited the expression of inflammatory proteins including the adhesion molecules intercellular adhesion molecule 1; vascular cell adhesion molecule 1; and E-selectin, as well as the release of the chemokine interleukin-8. Additionally, AA hindered the formation of capillary-like tubes in an in vitro model of angiogenesis. AA's effects in endothelial cells can be attributed at least in part to AA's inhibition of tumor necrosis factor alpha-induced nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)'s translocation. Also, in lipopolysaccharide-stimulated macrophage-like RAW264.7 cells, AA was able to downregulate the expression of the genes cyclooxygenase 2, inducible nitric oxide synthase, interleukin-6, and chemokine (C-C motif) ligand 2. Moreover, AA inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκBα), IκB kinase (IKK), and the mitogen-activated protein kinases JNK, ERK, and p38. In conclusion, the present results further support the anti-inflammatory potential of AA in different models of inflammation.
    Matched MeSH terms: Immunomodulation/drug effects*
  6. Fulltext Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment
    Looi CK, Chung FF, Leong CO, Wong SF, Rosli R, Mai CW
    J Exp Clin Cancer Res, 2019 Apr 15;38(1):162.
    PMID: 30987642 DOI: 10.1186/s13046-019-1153-8
    BACKGROUND: Pancreatic cancer is one of the most lethal type of cancers, with an overall five-year survival rate of less than 5%. It is usually diagnosed at an advanced stage with limited therapeutic options. To date, no effective treatment options have demonstrated long-term benefits in advanced pancreatic cancer patients. Compared with other cancers, pancreatic cancer exhibits remarkable resistance to conventional therapy and possesses a highly immunosuppressive tumor microenvironment (TME).

    MAIN BODY: In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME.

    CONCLUSIONS: It is imperative for clinicians and scientists to understand tumor immunology, identify novel biomarkers, and optimize the position of immunotherapy in therapeutic sequence, in order to improve pancreatic cancer clinical trial outcomes. Our collaborative efforts in targeting pancreatic TME will be the mainstay of achieving better clinical prognosis among pancreatic cancer patients. Ultimately, pancreatic cancer will be a treatable medical condition instead of a death sentence for a patient.

    Matched MeSH terms: Immunomodulation/drug effects*
  7. Tumor suppression effect of Solanum nigrum polysaccharide fraction on Breast cancer via immunomodulation
    Razali FN, Sinniah SK, Hussin H, Zainal Abidin N, Shuib AS
    Int J Biol Macromol, 2016 Nov;92:185-193.
    PMID: 27365117 DOI: 10.1016/j.ijbiomac.2016.06.079
    A polysaccharide fraction from Solanum nigrum, SN-ppF3 was shown previously to have an immunomodulatory activity where it could possibly be used to enhance the host immune response in fighting cancer. The non-toxic SN-ppF3 was fed orally to breast tumor bearing-mice with concentrations of 250 and 500mg/kg for 10days. During the treatment period, size of the tumor and weight of the mice were monitored. At the end of the treatment, blood, tumor, spleen and thymus were harvested for physiological and immunological analyses. After the treatment, the tumor volume and tumor weight were significantly inhibited by 65% and 40%, respectively. Based on the histological observation, the treatment of SN-ppF3 resulted in the disruption of tumor cells morphology. The increase in infiltrating T cells, NK cells and macrophages were observed in tumor tissues of the treated mice, which partly explained the higher apoptosis tumor cells observed in the treated mice. Moreover, the level of TNF-α, IFN-γ and IL-4 were elevated, while the level of IL-6 was decreased significantly, in serum of the treated mice. These results suggested that tumor suppression mechanisms observed in SN-ppF3-treated mice were most probably due through enhancing the host immune response.
    Matched MeSH terms: Immunomodulation/drug effects*
  8. Inhibitory effects of dynorphin 3-14 on the lipopolysaccharide-induced toll-like receptor 4 signalling pathway
    Rahiman SSF, Morgan M, Gray P, Shaw PN, Cabot PJ
    Peptides, 2017 04;90:48-54.
    PMID: 28219695 DOI: 10.1016/j.peptides.2017.02.004
    Dynorphin 1-17 (DYN 1-17) is biotransformed rapidly to a range of fragments in rodent inflamed tissue with dynorphin 3-14 (DYN 3-14) being the most stable and prevalent. DYN 1-17 has been shown previously to be involved in the regulation of inflammatory response following tissue injury, in which the biotransformation fragments of DYN 1-17 may possess similar features. This study investigated the effects of DYN 3-14 on lipopolysaccharide (LPS)-induced nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of pro-inflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in differentiated THP-1 cells. Treatment with DYN 3-14 (10nM) resulted in 35% inhibition of the LPS-induced nuclear translocation of NF-κB/p65. Furthermore, DYN 3-14 modulated both IL-1β and TNF-α release; inhibiting IL-1β and paradoxically augmenting TNF-α release in a concentration-independent manner. A number of opioids have been implicated in the modulation of the toll-like receptor 4 (TLR4), highlighting the complexity of their immunomodulatory effects. To determine whether DYN 3-14 modulates TLR4, HEK-Blue™-hTLR4 cells were stimulated with LPS in the presence of DYN 3-14. DYN 3-14 (10μM) inhibited TLR4 activation in a concentration-dependent fashion by suppressing the LPS signals around 300-fold lower than LPS-RS, a potent TLR4 antagonist. These findings indicate that DYN 3-14 is a potential TLR4 antagonist that alters cellular signaling in response to LPS and cytokine release, implicating a role for biotransformed endogenous opioid peptides in immunomodulation.
    Matched MeSH terms: Immunomodulation/drug effects
  9. Immunomodulatory Effect of Cytokines in the Differentiation of Mesenchymal Stem Cells: A Review
    Zahari W, Hashim SN, Yusof MF, Osman ZF, Kannan TP, Mokhtar KI, et al.
    Curr Stem Cell Res Ther, 2017;12(3):197-206.
    PMID: 27306400 DOI: 10.2174/1574888X11666160614103404
    Mesenchymal stem cells (MSCs) are stromal origin cells with multilineage differentiation capacity. The immunoregulatory properties of MSCs can be interfered effectively by cytokines. Cytokines, produced by a broad range of cells, act at the systemic level to influence biological phenomena such as inflammation, wound healing, organogenesis and oncogenesis. Cytokines also play vital roles in the differentiation of MSCs into several cell lineages. This review summarizes on how cytokines can affect MSCs differentiation and their relative signaling pathways, which may serve to understand the possible underlying mechanisms. Also, this review reveals the potential clinical use of MSCs as promising therapeutic agents due to their special characteristics such as multipotent differentiation, immunomodulatory properties, and selfrestoration.
    Matched MeSH terms: Immunomodulation
  10. Fulltext Human mesenchymal stem cells inhibit the differentiation and effector functions of monocytes
    Maqbool M, Algraittee SJR, Boroojerdi MH, Sarmadi VH, John CM, Vidyadaran S, et al.
    Innate Immun, 2020 07;26(5):424-434.
    PMID: 32635840 DOI: 10.1177/1753425919899132
    Although monocytes represent an essential part of the host defence system, their accumulation and prolonged stimulation could be detrimental and may aggravate chronic inflammatory diseases. The present study has explored the less-understood immunomodulatory effects of mesenchymal stem cells on monocyte functions. Isolated purified human monocytes were co-cultured with human umbilical cord-derived mesenchymal stem cells under appropriate culture conditions to assess monocytes' vital functions. Based on the surface marker analysis, mesenchymal stem cells halted monocyte differentiation into dendritic cells and macrophages and reduced their phagocytosis functions, which rendered an inability to stimulate T-cell proliferation. The present study confers that mesenchymal stem cells exerted potent immunosuppressive activity on monocyte functions such as differentiation, phagocytosis and Ag presentation; hence, they promise a potential therapeutic role in down-regulating the unwanted monocyte-mediated immune responses in the context of chronic inflammatory diseases.
    Matched MeSH terms: Immunomodulation
  11. The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies
    Khan KM, Mesaik MA, Abdalla OM, Rahim F, Soomro S, Halim SA, et al.
    Bioorg Chem, 2016 Feb;64:21-8.
    PMID: 26637945 DOI: 10.1016/j.bioorg.2015.11.004
    Benzothiazole and its natural or synthetic derivatives have been used as precursors for several pharmacological agents for neuroprotective, anti-bacterial, and anti-allergic activities. The objective of the present study was to evaluate effects of benzothiazole analogs (compounds 1-26) for their immunomodulatory activities. Eight compounds (2, 4, 5, 8-10, 12, and 18) showed potent inhibitory activity on PHA-activated peripheral blood mononuclear cells (PBMCs) with IC50 ranging from 3.7 to 11.9 μM compared to that of the standard drug, prednisolone <1.5 μM. Some compounds (2, 4, 8, and 18) were also found to have potent inhibitory activities on the production of IL-2 on PHA/PMA-stimulated PBMCs with IC50 values ranging between <4.0 and 12.8 μM. The binding interaction of these compounds was performed through silico molecular docking. Compounds 2, 8, 9, and 10 significantly suppressed oxidative burst ROS production in phagocytes with IC50 values between <4.0 and 15.2 μM. The lipopolysaccharide (LPS)-induced nitrites in murine macrophages cell line J774 were found to be inhibited by compounds 4, 8, 9, and 18 at a concentration of 25 μg/mL by 56%, 91%, 58%, and 78%, respectively. Furthermore, compounds 5, 8, 12, and 18 showed significant (P<0.05) suppressive activity on Th-2 cytokine, interleukin 4 (IL-4) with an IC50 range of <4.0 to 40.3 μM. Interestingly compound 4 has shown a selective inhibitory activity on IL-2 and T cell proliferation (naïve T cell proliferation stage) rather than on IL-4 cytokine, while compound 12 displayed an interference with T-cell proliferation and IL-4 generation. Moreover compound 8 and 18 exert non-selective inhibition on both IL-2 and IL-4 cytokines, indicating a better interference with stage leading to humoral immune response and hence possible application in autoimmune diseases.
    Matched MeSH terms: Immunomodulation
  12. Exploring Promising Immunomodulatory Potential of Natural and Synthetic 1,3-Diphenyl-2-propen-1-one Analogs: A Review of Mechanistic Insight
    Safdar MH, Hasan H, Afzal S, Hussain Z
    Mini Rev Med Chem, 2018;18(12):1047-1063.
    PMID: 29173165 DOI: 10.2174/1389557517666171123212039
    The immune system is an intricate and coordinated nexus serving as a natural defense to preclude internal and external pathogenic insults. The deregulation in the natural balance of immunological functions as a consequence of either over expression or under expression of immune cells tends to cause disruption of homeostasis in the body and may lead to development of numerous immune system disorders. Chalcone moieties (1,3-diphenyl-2-propen-1-one) have been well-documented as ideal lead compounds or precursors to design a wide range of pharmacologically active agents to down-regulate various immune disorders. Owing to their unique structural and molecular framework, these α, β-unsaturated carbonyl-based moieties have also gained remarkable recognition due to their other multifarious pharmacological properties including antifungal, anti-inflammatory, anti-malarial, antibacterial, anti-tuberculosis, and anticancer potential. Though a great number of methodologies are currently being employed for their synthesis, this review mainly focuses on the natural and synthetic chalcone derivatives that are exclusively synthesized via Claisen-Schmidt condensation reaction and their immunomodulatory prospects. We have critically reviewed the literature and provided convincing evidence for the promising efficacy of chalcone derivatives to modulate functioning of various innate and adaptive immune players including granulocytes, mast cells, monocytes, macrophages, platelets, dendritic cells, natural killer cells, and T-lymphocytes.
    Matched MeSH terms: Immunomodulation
  13. Fulltext Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases
    Ding SLS, Kumar S, Mok PL
    Int J Mol Sci, 2017 Jul 28;18(8).
    PMID: 28788088 DOI: 10.3390/ijms18081406
    The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action.
    Matched MeSH terms: Immunomodulation
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