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  1. Fulltext Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis
    Faizal AM, Elias MH, Jin NM, Abu MA, Syafruddin SE, Zainuddin AA, et al.
    Front Endocrinol (Lausanne), 2024;15:1274376.
    PMID: 38524634 DOI: 10.3389/fendo.2024.1274376
    The leading indicator for successful outcomes in in-vitro fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the parameter in assessing these qualities - DNA fragmentation in sperm and oocyte development capacity (ODC) via evaluation of microenvironments involving its maturation process. Regarding oocytes, most evidence reveals the role of cumulus cells as non-invasive methods in assessing their development competency, mainly via gene expression evaluation. Our review aims to consolidate the evidence of GDF-9 derivatives, the HAS2, GREM1, and PTGS2 gene expression in cumulus cells used as ODC markers in relevant publications and tailored to current IVF outcomes. In addition to that, we also added the bioinformatic analysis in our review to strengthen the evidence aiming for a better understanding of the pathways and cluster of the genes of interest - HAS2, GREM1, and PTGS2 in cumulus cell level. Otherwise, the current non-invasive method can be used in exploring various causes of infertility that may affect these gene expressions at the cumulus cell level. Nevertheless, this method can also be used in assessing the ODC in various cohorts of women or as an improvement of markers following targeted tools or procedures by evaluating the advancement of these gene expressions following the targeted intervention.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  2. Fulltext Potential treatment of squamous cell carcinoma by targeting heparin-binding protein 17/fibroblast growth factor-binding protein 1 with vitamin D3 or eldecalcitol
    Shintani T, Higaki M, Rosli SNZ, Okamoto T
    In Vitro Cell Dev Biol Anim, 2024 Jun;60(6):583-589.
    PMID: 38713345 DOI: 10.1007/s11626-024-00913-3
    Heparin-binding protein 17 (HBp17), first purified in 1991 from the conditioned medium of the human A431 squamous cell carcinoma (SCC) cell line, was later renamed fibroblast growth factor-binding protein 1 (FGFBP-1). HBp17/FGFBP-1 is specifically expressed and secreted by epithelial cells, and it reversibly binds to fibroblast growth factor (FGF)-1 and FGF-2, as well as FGFs-7, -10, and -22, indicating a crucial involvement in the transportation and function of these FGFs. Our laboratory has investigated and reported several studies to elucidate the function of HBp17/FGFBP-1 in SCC cells and its potential as a molecular therapeutic target. HBp17/FGFBP-1 transgene exoression in A431-4 cells, a clonal subline of A431 that lacks tumorigenicity and does not express HBp17/FGFBP-1, demonstrated a significantly enhanced proliferation in vitro compared with A431-4 cells, and it acquired tumorigenicity in the subcutis of nude mice. Knockout (KO) of the HBp17/FGFBP-1 by genome editing significantly suppressed tumor growth, cell motility, and tumorigenicity compared with control cells. A comprehensive analysis of expressed molecules in both cell types revealed that molecules that promote epithelial cell differentiation were highly expressed in HBp17/FGFBP-1 KO cells. Additionally, we reported that 1α,25(OH)2D3 or eldecalcitol (ED-71), which is an analog of 1α,25(OH)2D3, suppresses HBp17/FGFBP-1 expression and tumor growth in vitro and in vivo by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Here, we discuss the prospects of molecular targeted therapy targeting HBp17/FGFBP-1 with 1α,25(OH)2D3 or ED71 in SCC and oral SCC.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  3. Brain endothelial cells increase the proliferation of Plasmodium falciparum through production of soluble factors
    Khaw LT, Ball HJ, Mitchell AJ, Grau GE, Stocker R, Golenser J, et al.
    Exp Parasitol, 2014 Oct;145:34-41.
    PMID: 25045850 DOI: 10.1016/j.exppara.2014.07.002
    We here describe the novel finding that brain endothelial cells in vitro can stimulate the growth of Plasmodium falciparum through the production of low molecular weight growth factors. By using a conditioned medium approach, we show that the brain endothelial cells continued to release these factors over time. If this mirrors the in vivo situation, these growth factors potentially would provide an advantage, in terms of enhanced growth, for sequestered parasitised red blood cells in the brain microvasculature. We observed this phenomenon with brain endothelial cells from several sources as well as a second P. falciparum strain. The characteristics of the growth factors included: <3 kDa molecular weight, heat stable, and in part chloroform soluble. Future efforts should be directed at identifying these growth factors, since blocking their production or actions might be of benefit for reducing parasite load and, hence, malaria pathology.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism*
  4. Fulltext Early clearance of Chikungunya virus in children is associated with a strong innate immune response
    Simarmata D, Ng DC, Kam YW, Lee B, Sum MS, Her Z, et al.
    Sci Rep, 2016 05 16;6:26097.
    PMID: 27180811 DOI: 10.1038/srep26097
    Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  5. Microenvironmental factors involved in human amnion mesenchymal stem cells fate decisions
    Syva SH, Ampon K, Lasimbang H, Fatimah SS
    J Tissue Eng Regen Med, 2017 02;11(2):311-320.
    PMID: 26073746 DOI: 10.1002/term.2043
    Human amnion mesenchymal stem cells (HAMCs) show great differentiation and proliferation potential and also other remarkable features that could serve as an outstanding alternative source of stem cells in regenerative medicine. Recent reports have demonstrated various kinds of effective artificial niche that mimic the microenvironment of different types of stem cell to maintain and control their fate and function. The components of the stem cell microenvironment consist mainly of soluble and insoluble factors responsible for regulating stem cell differentiation and self-renewal. Extensive studies have been made on regulating HAMCs differentiation into specific phenotypes; however, the understanding of relevant factors in directing stem cell fate decisions in HAMCs remain underexplored. In this review, we have therefore identified soluble and insoluble factors, including mechanical stimuli and cues from the other supporting cells that are involved in directing HAMCs fate decisions. In order to strengthen the significance of understanding on the relevant factors involved in stem cell fate decisions, recent technologies developed to specifically mimic the microenvironments of specific cell lineages are also reviewed. Copyright © 2015 John Wiley & Sons, Ltd.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  6. Fulltext Prostate Cancer and Bone Metastases: The Underlying Mechanisms
    Wong SK, Mohamad NV, Giaze TR, Chin KY, Mohamed N, Ima-Nirwana S
    Int J Mol Sci, 2019 May 27;20(10).
    PMID: 31137764 DOI: 10.3390/ijms20102587
    Patients with advanced prostate cancer often develop bone metastases, leading to bone pain, skeletal fracture, and increased mortality. Bone provides a hospitable microenvironment to tumor cells. The disease manifestation is driven by the interaction between invading tumor cells, bone-forming osteoblasts, and bone-resorbing osteoclasts. The increased level of osteoclast-activating factor (parathyroid hormone-related peptide, PTHrP) is believed to induce bone resorption by upregulating receptor activator of nuclear factor-kappa B ligand (RANKL) and the release of various growth factors into the bone microenvironment to enhance cancer cell growth. However, the underlying molecular mechanisms remain poorly understood. This review outlines the possible molecular mechanisms involved in governing bone metastases driven by prostate cancer, which further provide the basis in searching for new molecular targets for the development of potential therapy.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  7. Fulltext IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells
    Huat TJ, Khan AA, Pati S, Mustafa Z, Abdullah JM, Jaafar H
    BMC Neurosci, 2014;15:91.
    PMID: 25047045 DOI: 10.1186/1471-2202-15-91
    There has been increasing interest recently in the plasticity of mesenchymal stem cells (MSCs) and their potential to differentiate into neural lineages. To unravel the roles and effects of different growth factors in the differentiation of MSCs into neural lineages, we have differentiated MSCs into neural lineages using different combinations of growth factors. Based on previous studies of the roles of insulin-like growth factor 1 (IGF-1) in neural stem cell isolation in the laboratory, we hypothesized that IGF-1 can enhance proliferation and reduce apoptosis in neural progenitor-like cells (NPCs) during differentiation of MSCs into NCPs.We induced MSCs differentiation under four different combinations of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, (C) EGF + bFGF + LIF, (D) EGF + bFGF + BDNF, and (E) without growth factors, as a negative control. The neurospheres formed were characterized by immunofluorescence staining against nestin, and the expression was measured by flow cytometry. Cell proliferation and apoptosis were also studied by MTS and Annexin V assay, respectively, at three different time intervals (24 hr, 3 days, and 5 days). The neurospheres formed in the four groups were then terminally differentiated into neuron and glial cells.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  8. Topical application of omega-3-, omega-6-, and omega-9-rich oil emulsions for cutaneous wound healing in rats
    Ishak WMW, Katas H, Yuen NP, Abdullah MA, Zulfakar MH
    Drug Deliv Transl Res, 2019 04;9(2):418-433.
    PMID: 29667150 DOI: 10.1007/s13346-018-0522-8
    Wound healing is a physiological event that generates reconstitution and restoration of granulation tissue that ends with scar formation. As omega fatty acids are part of membrane phospholipids and participate in the inflammatory response, we investigated the effects of omega-3, omega-6, and omega-9 fatty acids in the form of oils on wound healing. Linseed (LO), evening primrose (EPO), and olive oils (OO) rich in omega-3, omega-6, and omega-9 fatty acids were formulated into emulsions and were topically applied on rats with excision wounds. All omega-3-, omega-6-, and omega-9-rich oil formulations were found to accelerate wound closure compared to untreated, with significant improvement (p 
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  9. Fulltext Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway
    Kared H, Tan SW, Lau MC, Chevrier M, Tan C, How W, et al.
    Nat Commun, 2020 02 10;11(1):821.
    PMID: 32041953 DOI: 10.1038/s41467-020-14442-6
    The diversity of the naïve T cell repertoire drives the replenishment potential and capacity of memory T cells to respond to immune challenges. Attrition of the immune system is associated with an increased prevalence of pathologies in aged individuals, but whether stem cell memory T lymphocytes (TSCM) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that TSCM heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/β-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/β-catenin pathway. Functional assays support recent thymic emigrants as the precursors of CD4 TSCM. Our data thus hint that reversing TSCM defects by metabolic targeting of the Wnt/β-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  10. Fulltext Lyophilised Platelet-Rich Fibrin: Physical and Biological Characterisation
    Ngah NA, Dias GJ, Tong DC, Mohd Noor SNF, Ratnayake J, Cooper PR, et al.
    Molecules, 2021 Nov 25;26(23).
    PMID: 34885714 DOI: 10.3390/molecules26237131
    BACKGROUND: Platelet-rich fibrin (PRF) has gained popularity in craniofacial surgery, as it provides an excellent reservoir of autologous growth factors (GFs) that are essential for bone regeneration. However, the low elastic modulus, short-term clinical application, poor storage potential and limitations in emergency therapy use restrict its more widespread clinical application. This study fabricates lyophilised PRF (Ly-PRF), evaluates its physical and biological properties, and explores its application for craniofacial tissue engineering purposes.

    MATERIAL AND METHODS: A lyophilisation method was applied, and the outcome was evaluated and compared with traditionally prepared PRF. We investigated how lyophilisation affected PRF's physical characteristics and biological properties by determining: (1) the physical and morphological architecture of Ly-PRF using SEM, and (2) the kinetic release of PDGF-AB using ELISA.

    RESULTS: Ly-PRF exhibited a dense and homogeneous interconnected 3D fibrin network. Moreover, clusters of morphologically consistent cells of platelets and leukocytes were apparent within Ly-PRF, along with evidence of PDGF-AB release in accordance with previously reports.

    CONCLUSIONS: The protocol established in this study for Ly-PRF preparation demonstrated versatility, and provides a biomaterial with growth factor release for potential use as a craniofacial bioscaffold.

    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  11. Fulltext The Effects of Tocotrienol on Bone Peptides in a Rat Model of Osteoporosis Induced by Metabolic Syndrome: The Possible Communication between Bone Cells
    Wong SK, Chin KY, Ima-Nirwana S
    Int J Environ Res Public Health, 2019 09 09;16(18).
    PMID: 31505801 DOI: 10.3390/ijerph16183313
    A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  12. Fulltext Inflammasomes and Pyroptosis as Therapeutic Targets for COVID-19
    Yap JKY, Moriyama M, Iwasaki A
    J Immunol, 2020 Jul 15;205(2):307-312.
    PMID: 32493814 DOI: 10.4049/jimmunol.2000513
    The inflammatory response to severe acute respiratory syndrome-related coronavirus 2 infection has a direct impact on the clinical outcomes of coronavirus disease 2019 patients. Of the many innate immune pathways that are engaged by severe acute respiratory syndrome-related coronavirus 2, we highlight the importance of the inflammasome pathway. We discuss available pharmaceutical agents that target a critical component of inflammasome activation, signaling leading to cellular pyroptosis, and the downstream cytokines as a promising target for the treatment of severe coronavirus disease 2019-associated diseases.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  13. Squamous odontogenic tumor of the mandible: a case report demonstrating immunoexpression of Notch1, 3, 4, Jagged1 and Delta1
    Siar CH, Nakano K, Ng KH, Tomida M, Nagatsuka H, Kawakami T
    Eur J Med Res, 2010 Apr 08;15(4):180-4.
    PMID: 20554499
    BACKGROUND: Squamous odontogenic tumor (SOT) is a rare benign odontogenic epithelial neoplasm. A slow-growing painless expansive swelling is the common presenting symptom. Histopathologically, SOT can be easily misdiagnosed as an acanthomatous ameloblastoma. Although Notch receptors and ligands have been shown to play a role in cell fate decisions in ameloblastomas, the role of these cell signaling molecules in SOT is unknown.

    CASE REPORT: This paper describes a case of SOT affecting the anterior mandible of a 10-year-old Indian female. The patient was treated by local surgical excision and there has been no follow-up clinical record of recurrence 5 years after primary treatment. Histo?pathological examination revealed a solid, locally-infiltrative neoplasm composed of bland-looking squamatoid islands scattered in a mature fibrous connective tissue stroma and the diagnosis was SOT. Immunohistochemical evaluation showed positive reactivity of varying intensity in the neoplastic epithelial cells for Notch1, Notch3, Notch4, and their ligands Jagged1 and Delta1. Expression patterns showed considerable overlap. No immunoreactivity was detected for Notch2 and Jagged2.

    CONCLUSIONS: Present findings suggest that Notch receptors and their ligands play differential roles in the cytodifferentiation of SOT.

    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism*
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