Displaying all 11 publications

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  1. Batool A, Vaithilingam RD, Mohamad Hassan NH, Safii SH, Saub R
    Medicine (Baltimore), 2023 Oct 13;102(41):e35340.
    PMID: 37832126 DOI: 10.1097/MD.0000000000035340
    BACKGROUND: Matrix metalloproteinases (MMPs) play a crucial role in the pathogenesis of several chronic diseases including rheumatoid arthritis (RA) and periodontitis (PD). RA patients with periodontitis (RA-PD) are associated with elevated inflammatory burden due to increased production of proinflammatory cytokines. Controlling upregulated MMPs activity in these patients may have potential therapeutic effects. Therefore, aim of this study is to address the focused question: "Do RA subjects with concurrent PD have different levels of MMPs in comparison to RA alone, PD alone and HC subjects?"

    METHODS: The systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search from 4 electronic databases (EMBASE, Medline, Web of Science, and Cochrane library) and manual search was performed from inception to July 2023. Quality assessment of each article was done using Newcastle-Ottawa Scale. Meta-analyses derived results were summarized as standardized mean difference (SMD) with 95% confidence intervals.

    RESULTS: A total of 879 articles were extracted. Following screening and full text assessment, 9 studies were included. MMP-1, MMP-3, MMP-8, MMP-9, and MMP-13 were consistently elevated in RA-PD subjects. MMP-8 levels were found to be higher in RA-PD subjects compared with RA alone, PD alone, and HC in 3 studies reporting GCF levels (SMD = 1.2; Z = 2.07; P = .04) and 2 studies reporting serum levels (SMD = 0.87; Z = 4.53; P < .00001).

    CONCLUSION: RA-PD group showed significantly higher MMP levels in their serum and GCF compared with HC, RA, and PD alone individuals. MMP-8 may serve as a reliable biomarker in the diagnosis and management of RA-PD subjects.

    Matched MeSH terms: Matrix Metalloproteinase 3
  2. Aminuddin A, Cheong SS, Roos NAC, Ugusman A
    Int J Med Sci, 2023;20(4):482-492.
    PMID: 37057211 DOI: 10.7150/ijms.79889
    Smoking is a risk factor of acute coronary syndrome (ACS) that could increase matrix metalloproteinases (MMPs) levels, leading to unstable coronary artery plaque. The current review aimed to identify the relationship between smoking and MMPs in patients with ACS. Literature search was conducted from inception until March 2022 in three online databases. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was performed, and the odds ratio (OR) together with its 95% confidence interval (CI) were determined. A total of 7,843 articles were identified, and only seven studies were included. Four studies investigated the MMP-3 and MMP-9 related genes and found that smokers with certain MMPs genotypes had high risk of ACS. Smoking also increased the MMPs level in patients with ACS compared with non-smokers. Additionally, a meta-analysis of two studies resulted in an increased odd of ACS in smokers with MMP-3 5A allele versus non-smokers with MMP-3 6A6A allele (OR: 15.94, 95% CI: 10.63-23.92; I2 =55%). In conclusion, the current review highlights the role of MMPs in relation to smoking and ACS. The determination of these roles may help in identifying new ACS markers among smokers and the development of drug-targeted treatment.
    Matched MeSH terms: Matrix Metalloproteinase 3
  3. Loo YC, Hu HC, Yu SY, Tsai YH, Korinek M, Wu YC, et al.
    Phytomedicine, 2023 Feb;110:154643.
    PMID: 36623444 DOI: 10.1016/j.phymed.2023.154643
    BACKGROUND: Skin aging is associated with degradation of collagen by matrix metalloproteinases (MMPs), which leads to loss of skin elasticity and formation of wrinkles. Cosmos caudatus Kunth (CC) has been traditionally claimed as an anti-aging agent in Malaysia. Despite its well-known antioxidant activity, the anti-aging properties of CC was not validated.

    PURPOSE: This study aimed to investigate the anti-aging potential of CC extracts and fractions, particularly their inhibition of collagenase, MMP-1 and MMP-3 activities in human dermal fibroblasts CCD-966SK, followed by isolation, identification and analysis of their bioactive constituents.

    STUDY DESIGN AND METHODS: DPPH assay was firstly used to evaluate the antioxidant activity throughout the bioactivity-guided fractionation. Cell viability was determined using MTS assay. Collagenase activity was examined, while MMP-1 and MMP-3 expression were measured using qRT-PCR and western blotting. Then, chemical identification of pure compounds isolated from CC fractions was done by using ESIMS, 1H and 13C NMR spectroscopies. HPLC analyses were carried out for bioactive fractions to quantify the major components.

    RESULTS: Throughout the antioxidant activity-guided fractionation, fractions CC-E2 and CC-E3 with antioxidant activity and no toxicity towards CCD-966SK cells were obtained from CC 75% ethanol partitioned layer (CC-E). Both fractions inhibited collagenase activity, MMP-1 and MMP-3 mRNA and protein expression, as well as NF-κB activation induced by TNF-α in CCD-966SK cells. 14 compounds, which mainly consists of flavonoids and their glycosides, were isolated. Quercitrin (14.79% w/w) and quercetin (11.20% w/w) were major compounds in CC-E2 and CC-E3, respectively, as quantified by HPLC. Interestingly, both fractions also inhibited the MMP-3 protein expression synergistically, compared with treatment alone.

    CONCLUSION: The quantified CC fractions rich in flavonoid glycosides exhibited skin anti-aging effects via the inhibition of collagenase, MMP-1 and MMP-3 activities, probably through NF-κB pathway. This is the first study reported on MMP-1 and MMP-3 inhibitory activity of CC with its chemical profile, which revealed its potential to be developed as anti-aging products in the future.

    Matched MeSH terms: Matrix Metalloproteinase 3/metabolism
  4. Samah N, Ugusman A, Hamid AA, Sulaiman N, Aminuddin A
    Mediators Inflamm, 2023;2023:9715114.
    PMID: 37457745 DOI: 10.1155/2023/9715114
    Coronary artery disease (CAD) is a caused by atherosclerotic plaque buildup in the coronary arteries that supply blood and oxygen to the heart. Matrix metalloproteinase (MMP) is a family of zinc-dependent endopeptidase that is involved in various stages of atherosclerosis as demonstrated in in vitro and in vivo studies. MMP-2 is associated with both stable and unstable atherosclerotic plaque formation. The current review aimed to identify the role of MMP-2 in atherosclerosis development among CAD patients. Literature search was conducted through four online databases and only studies that were published from 2018 until February 2023 were included. The risk of bias was assessed by using the Newcastle-Ottawa Scale. A total of 10,622 articles were initially identified, and only eight studies that fulfilled the selection criteria were included in this review. The results showed that MMP-2 levels and activity were higher in patients with unstable CAD than those with stable CAD and healthy subjects. There was a significant association between MMP-2 levels and cardiovascular disease with MMP-14 levels, which is a pro-MMP-2 activator. In addition, two single nucleotide polymorphisms of the MMP-2 gene (rs243865 and rs243866) were significantly associated with the development of atherosclerosis. In conclusion, MMP-2 plays a crucial role in the development of atherosclerosis among patients with CAD and could be a potential target for CAD therapy.
    Matched MeSH terms: Matrix Metalloproteinase 3/genetics
  5. Lee KH, Chen YS, Judson JP, Chakravarthi S, Sim YM, Er HM
    Malays J Pathol, 2008 Dec;30(2):95-102.
    PMID: 19291918 MyJurnal
    The effect of water extracts of Euphorbia hirta on the histological features and expressions of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the rat articular cartilage was investigated. Arthritis was induced in rats using Freund's Complete Adjuvant containing heat-killed M. tuberculosis, and treated with water extracts of E. hirta. Paraffin tissue sections of the arthritic joints were evaluated. The extent of cartilage degeneration was found to be greatest in rats treated with the highest dosage of E. hirta, followed by rats in the untreated group. Rats treated with the intermediary and low dosages of Euphorbia hirta showed improved histology. MMP-13 levels were found to be decreased with decreasing dosages of E. hirta. TIMP-1 levels were found to increase with decreasing dosages of E. hirta. MMP-3 levels fluctuated without any appreciable pattern. Low dosages of E. hirta seem to be beneficial in reducing cartilage degeneration in cases of arthritis.
    Matched MeSH terms: Matrix Metalloproteinase 3/drug effects; Matrix Metalloproteinase 3/metabolism
  6. Nga AD, Yap SL, Samsudin A, Abdul-Rahman PS, Hashim OH, Mimiwati Z
    BMC Ophthalmol, 2014;14:33.
    PMID: 24655889 DOI: 10.1186/1471-2415-14-33
    Altered levels of specific matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the aqueous humour of primary open-angle glaucoma (POAG) eyes have been described. In this study, levels of specific MMPs and TIMPs in the aqueous humour of primary angle-closure glaucoma (PACG) eyes were measured and compared with those of POAG as well as non-glaucoma control eyes.
    Matched MeSH terms: Matrix Metalloproteinase 3/metabolism*
  7. Ong MH, Wong HK, Tengku-Muhammad TS, Choo QC, Chew CH
    Mol Biol Rep, 2019 Jun;46(3):2631-2641.
    PMID: 30989556 DOI: 10.1007/s11033-019-04661-6
    The prevalence of atherosclerosis has increased significantly in the recent years due to sedentary lifestyle and high-fat diet. However, the association between saturated fat intake and the increased risk for atherosclerotic cardiovascular diseases remains heavily debated. Lauric acid belongs to the saturated fatty acid group and its unique medium chain fatty acid properties are proven to be beneficial to humans in many ways. Thus, the aim of this project is to investigate the effect of lauric acid on the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes-ADAMTS-1, ADAMTS-4, and ADAMTS-5-in macrophages. These genes encode for proteases that participate in the extracellular matrix remodeling and they play important roles in the vulnerability of atherosclerotic plaque. Here, we show that the treatment of 20 µM of lauric acid successfully reduced both transcriptional and translational expressions of these genes in THP-1 differentiated macrophages after 24-h incubation. Further cell signaling experiments using a panel of kinase inhibitors and phosphorylated antibodies proved that lauric acid down-regulated ADAMTS-1 by reducing the activation of PI3K and JNK at Tyr458 and Tyr185, respectively. Finally, JNK1 siRNA knockdown assay confirmed that ADAMTS-1 was regulated through JNK pathway, and lauric acid interfered with this pathway to down-regulate ADAMTS-1 expression. Although preliminary, this present study indicates that lauric acid has the potential to stabilize atherosclerotic plaque and may prevent thrombosis by interfering with the ADAMTS-1 expression through PI3K/JNK pathways.
    Matched MeSH terms: Matrix Metalloproteinase 3/metabolism
  8. Santhanam RK, Fakurazi S, Ahmad S, Abas F, Ismail IS, Rukayadi Y, et al.
    Phytother Res, 2018 Aug;32(8):1608-1616.
    PMID: 29672974 DOI: 10.1002/ptr.6092
    The antiphoto aging property of Zanthoxylum rhetsa obtained from Pangkor Island, Malaysia, was evaluated. Solvent fractions of different polarity obtained from the methanolic extract of the bark material were initially tested for anticollagenase and antielastase activities. The ethyl acetate fraction showed bioactivity against the protease enzymes. Hence, it was subjected to further purification via column chromatography, to yield a major constituent, hesperidin. Subsequently, the ethyl acetate fraction and hesperidin were tested for their effects against UVB-induced cytotoxicity and expressions of inflammatory cytokines (IL-6, IL-1β, and TNF-α), NF-κB, and MMPs (MMP1, 3, and 9) in human dermal fibroblasts (HDF). Both fraction and pure compound prevented UVB-induced cytotoxicity in HDF cells, in a dose dependent manner. Moreover, the ethyl acetate fraction inhibited the increase of pro-inflammatory cytokines induced by UVB to a level similar to the control (without UV treatment). Additionally, the fraction significantly inhibited the expressions of NF-κB, MMP 1, MMP 3, and MMP 9 in HDF cells treated with UVB. Similar effects were observed with hesperidin. The results obtained suggested that the ethyl acetate fraction of Z. rhetsa and its bioactive constituent, hesperidin, have the potential to be used as active ingredients in sunscreen and antiphoto aging formulations.
    Matched MeSH terms: Matrix Metalloproteinase 3
  9. Chew MM, Gan SY, Khoo AS, Tan EL
    BMC Cancer, 2010;10:574.
    PMID: 20964870 DOI: 10.1186/1471-2407-10-574
    Nasopharyngeal carcinoma (NPC) is a type of neoplasm that is highly prevalent in East Asia and Africa with Epstein-Barr virus (EBV), genetic, and dietary factors implicated as possible aetiologic factors. Previous studies suggested the association of certain cytokines with the invasion and metastatic properties of NPC. The present study examined the roles of EBV latent membrane protein-1 (LMP1), interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-β1) and laminin in the regulation of matrix-metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) in NPC. The effects of these factors on bmi-1, an oncogene, and ngx6, a tumour suppressor gene, were also investigated.
    Matched MeSH terms: Matrix Metalloproteinase 3/metabolism
  10. Ramasamy R, Tong CK, Yip WK, Vellasamy S, Tan BC, Seow HF
    Cell Prolif, 2012 Apr;45(2):132-9.
    PMID: 22309282 DOI: 10.1111/j.1365-2184.2012.00808.x
    BACKGROUND: Mesenchymal stem cells (MSC) have great potential in regenerative medicine, immunotherapy and gene therapy due to their unique properties of self-renewal, high plasticity, immune modulation and ease for genetic modification. However, production of MSC at sufficient clinical scale remains an issue as in vitro generation of MSC inadequately fulfils the demand with respect to patients.

    OBJECTIVES: This study has aimed to establish optimum conditions to generate and characterize MSC from human umbilical cord (UC-MSC).

    MATERIALS AND METHODS: To optimize MSC population growth, basic fibroblast growth factor (bFGF) was utilized in culture media. Effects of bFGF on expansion kinetics, cell cycle, survival of UC-MSC, cytokine secretion, expression of early stem-cell markers and immunomodulation were investigated.

    RESULTS: bFGF supplementation profoundly enhanced UC-MSC proliferation by reducing population doubling time without altering immunophenotype and immunomodulatory function of UC-MSC. However, cell cycle studies revealed that bFGF drove the cells into the cell cycle, as a higher proportion of cells resided in S phase and progressed into M phase. Consistent with this, bFGF was shown to promote expression of cyclin D proteins and their relevant kinases to drive UC-MSC to transverse cell cycle check points, thus, committing the cells to DNA synthesis. Furthermore, supplementation with bFGF changed the cytokine profiles of the cells and reduced their apoptotic level.

    CONCLUSION: Our study showed that bFGF supplementation of UC-MSC culture enhanced the cells' growth kinetics without compromising their nature.

    Matched MeSH terms: Matrix Metalloproteinase 3/metabolism
  11. Madzuki IN, Lau SF, Abdullah R, Mohd Ishak NI, Mohamed S
    Phytother Res, 2019 Jul;33(7):1784-1793.
    PMID: 31033070 DOI: 10.1002/ptr.6366
    Vernonia amygdalina (VA) is a medicinal tropical herb for diabetes and malaria and believed to be beneficial for joint pains. The antiosteorthritis effects of VA leaf in cartilage explant assays and on postmenopausal osteoarthritis (OA) rat model were investigated. The VA reduced the proteoglycan and nitric oxide release from the cartilage explants with interleukin 1β (IL-1β) stimulation. For the preclinical investigation, ovariectomized (OVX) female rats were grouped (n = 8) into nontreated OA, OA + diclofenac (5 mg/kg), OA + VA extract (150 and 300 mg/kg), and healthy sham control. Monosodium iodoacetate was injected into the knee joints to accelerate OA development. After 8 weeks, the macroscopic, microscopic, and histological images showed that the OA rats treated with VA 300 mg/kg and diclofenac had significantly reduced cartilage erosions and osteophytes unlike the control OA rats. The extract significantly down-regulated the inflammatory prostaglandin E2, nuclear factor κβ, IL-1β, ADAMTS-5, collagen type 10α1, and caspase3 in the OVX-OA rats. It up-regulated the anti-inflammatory IL-10 and collagen type 2α1 mRNA expressions, besides reducing serum collagenases (MMP-3 and MMP-13) and collagen type II degradation biomarker (CTX-II) levels in these rats. The VA (containing various caffeoyl-quinic acids, flavanone-O-rutinoside, luteolin, apigenin derivative and vernonioside D) suppressed inflammation, pain, collagenases as well as cartilage degradation, and improved cartilage matrix synthesis to prevent OA.
    Matched MeSH terms: Matrix Metalloproteinase 3
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